Evidence Report/Technology Assessment

Number 224

Omega-3 Fatty Acids 

and Maternal and Child 

Health: An Updated 

Systematic Review

Evidence-Based

Practice
Evidence Report/Technology Assessment

Number 224

Omega-3 Fatty Acids and Maternal and Child Health: 

An Updated Systematic Review

Prepared for: 

Agency for Healthcare Research and Quality

U.S. Department of Health and Human Services 

5600 Fishers Lane 

Rockville, MD 20857 

www.ahrq.gov 

Contract No. 290-2012-00006-I 

Prepared by:

Southern California Evidence-based Practice Center

Santa Monica, CA 

Investigators: 

Sydne J. Newberry, M.S., Ph.D. 

Mei Chung, M.P.H., Ph.D. 

Marika Booth, M.S. 

Margaret A. Maglione, M.P.P.

Alice M. Tang, S.C.M., Ph.D. 

Claire E. O’Hanlon, M.P.P. 

Ding Ding Wang, M.P.H. 

Adeyemi Okunogbe, MB.Ch.B, M.S. 

Christina Huang, M.P.H. 

Aneesa Motala, B.A.

Martha Timmer, M.A.

Whitney Dudley, M.A. 

Roberta Shanman, M.L.S. 

Tumaini R. Coker, M.D., M.B.A. 

Paul G. Shekelle, M.D., Ph.D. 

AHRQ Publication No. 16(17)-E003-EF 

October 2016 
This report is based on research conducted by the Southern California Evidence-based Practice 

Center under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, 

MD (Contract No. 290-2012-00006-I). The report is sponsored by the National Institutes of 

Health Office of Dietary Supplements (NIH/ODS). The findings and conclusions in this 

document are those of the authors, who are responsible for its contents; the findings and 

conclusions do not necessarily represent the views of AHRQ or NIH/ODS. Therefore, no 

statement in this report should be construed as an official position of AHRQ, NIH/ODS, or the 

U.S. Department of Health and Human Services. 

None of the investigators have any affiliations or financial involvement that conflicts with the 

material presented in this report. 

The information in this report is intended to help health care decisionmakers—patients and 

clinicians, health system leaders, and policymakers, among others—make well-informed 

decisions and thereby improve the quality of health care services. This report is not intended to 

be a substitute for the application of clinical judgment. Anyone who makes decisions concerning 

the provision of clinical care should consider this report in the same way as any medical 

reference and in conjunction with all other pertinent information, i.e., in the context of available 

resources and circumstances presented by individual patients. 

This report is made available to the public under the terms of a licensing agreement between the 

author and the Agency for Healthcare Research and Quality. This report may be used and 

reprinted without permission except those copyrighted materials that are clearly noted in the 

report. Further reproduction of those copyrighted materials is prohibited without the express 

permission of copyright holders. 

AHRQ or U.S. Department of Health and Human Services endorsement of any derivative 

products that may be developed from this report, such as clinical practice guidelines, other 

quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.

This report may periodically be assessed for the currency of conclusions. If an assessment is 

done, the resulting surveillance report describing the methodology and findings will be found on 

the Effective Health Care Program Web site at www.effectivehealthcare.ahrq.gov. Search on the 

title of the report.

Persons using assistive technology may not be able to fully access information in this report. For 

assistance contact EffectiveHealthCare@ahrq.hhs.gov.

Suggested citation: Newberry SJ, Chung M, Booth M, Maglione MA, Tang AM, O’Hanlon CE, 

Wang DD, Okunogbe A, Huang C, Motala A, Timmer M, Dudley W, Shanman R, Coker TR, 

Shekelle P. Omega-3 Fatty Acids and Maternal and Child Health: An Updated Systematic 

Review. Evidence Report/Technology Assessment No. 224. (Prepared by the RAND Southern 

California Evidence-based Practice Center under Contract No. 290-2012-00006-I.) AHRQ 

Publication No. 16(17)-E003-EF. Rockville, MD: Agency for Healthcare Research and Quality; 

October 2016. www.effectivehealthcare.ahrq.gov/reports/final.cfm. DOI: https://

doi.org/10.23970/AHRQEPCERTA224.

ii
Preface

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based 

Practice Centers (EPCs), sponsors the development of systematic reviews to assist public- and 

private-sector organizations in their efforts to improve the quality of health care in the United 

States. These reviews provide comprehensive, science-based information on common, costly 

medical conditions, and new health care technologies and strategies. 

Systematic reviews are the building blocks underlying evidence-based practice; they focus 

attention on the strength and limits of evidence from research studies about the effectiveness and 

safety of a clinical intervention. In the context of developing recommendations for practice, 

systematic reviews can help clarify whether assertions about the value of the intervention are 

based on strong evidence from clinical studies. For more information about AHRQ EPC 

systematic reviews, see www.effectivehealthcare.ahrq.gov/reference/purpose.cfm.

AHRQ expects that these systematic reviews will be helpful to health plans, providers, 

purchasers, government programs, and the health care system as a whole. Transparency and 

stakeholder input are essential to the Effective Health Care Program. Please visit the Web site 

(www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an 

email list to learn about new program products and opportunities for input. 

If you have comments on this systematic review, they may be sent by mail to the Task Order 

Officer named below at: Agency for Healthcare Research and Quality, 5600 Fishers Lane, 

Rockville, MD 20857, or by email to epc@ahrq.hhs.gov. 

Andrew Bindman, M.D.

Director 

Agency for Healthcare Research and Quality

Stephanie Chang M.D., M.P.H. 

Director

Evidence-based Practice Center Program

Center for Evidence and Practice Improvement

Agency for Healthcare Research and Quality

Arlene S. Bierman, M.D., M.S.

Director

Center for Evidence and Practice Improvement

Agency for Healthcare Research and Quality

Aysegul Gozu, M.D., M.P.H

Task Order Officer

Center for Evidence and Practice Improvement

Agency for Healthcare Research and Quality

iii
Acknowledgments

The authors gratefully acknowledge Patricia Smith for her administrative support to the 

project.

Technical Expert Panel

In designing the study questions and methodology at the outset of this report, the EPC

consulted several technical and content experts. Broad expertise and perspectives were sought. 

Divergent and conflicted opinions are common and perceived as healthy scientific discourse that 

results in a thoughtful, relevant systematic review. Therefore, in the end, study questions, design, 

methodologic approaches, and/or conclusions do not necessarily represent the views of 

individual technical and content experts. 

Technical Experts must disclose any financial conflicts of interest greater than $10,000 and 

any other relevant business or professional conflicts of interest. Because of their unique clinical 

or content expertise, individuals with potential conflicts may be retained. The TOO and the EPC 

work to balance, manage, or mitigate any potential conflicts of interest identified. 

The list of Technical Experts who provided input to this report follows: 

Carlo Agostoni, M.D.*

Professor of Pediatrics

Department of Maternal and Pediatric 

Sciences

University of Milan

Fondazione IRCCS Ca’ Granda – Ospedale 

Maggiore Policlinico

Milan, Italy

Jeanne A. Conry, M.D., Ph.D.*

Assistant Physician in Chief

North Valley Kaiser Permanente

Roseville, CA

Lisa Freund, Ph.D.*

Chief, Child Development and Behavior 

Branch

Eunice Kennedy Shriver National Institute 

of Child Health and Human Development

Health and Human Development

Bethesda, MD

Peter Gillies, Ph.D.

Founding Director of the New Jersey 

Institute for Food, Nutrition, and Health

Rutgers University

New Brunswick, NJ

Ronald E. Kleinman, M.D.*

Chair, Pediatrics Department, Mass General 

Hospital 

Physician-in-Chief, Mass General Hospital 

for Children

Boston, MA

Alice Lichtenstein, Sc.D.

Stanley N. Gershoff Professor of Nutrition 

Science and Policy

Tufts University Friedman School of 

Nutrition Science and Policy

Director, Cardiovascular Nutrition 

Laboratory

USDA Human Nutrition Research Center

Boston, MA

iv
Maria Makrides, Ph.D.*

Theme Leader, Healthy Mothers, Babies, 

and Children

South Australian Health and Medical 

Research Institute

Professor of Human Nutrition

University of Adelaide

North Adelaide, Australia

John Paul SanGiovanni, Sc.D.

Staff Scientist in the Clinical Trials Branch 

at the National Eye Institute

National Institutes of Health

Division of Epidemiology and Clinical 

Applications

Bethesda, MD

*Provided input on Draft Report.

v
Peer Reviewers

Prior to publication of the final evidence report, EPCs sought input from independent Peer 

Reviewers without financial conflicts of interest. However, the conclusions and synthesis of the 

scientific literature presented in this report do not necessarily represent the views of individual 

reviewers. 

Peer Reviewers must disclose any financial conflicts of interest greater than $10,000 and any 

other relevant business or professional conflicts of interest. Because of their unique clinical or 

content expertise, individuals with potential nonfinancial conflicts may be retained. The TOO 

and the EPC work to balance, manage, or mitigate any potential nonfinancial conflicts of interest 

identified.

The list of Peer Reviewers follows: 

Michael H. Bloch, M.S., M.D.

Assistant Professor in the Child Study Center

Yale University School of Medicine

New Haven, CT

Van S. Hubbard, M.D., Ph.D. 

Current: 

Rear Admiral, U.S. Public Health Service (Ret)

At time of review:

National Institutes of Health

Director, Division of Nutrition Research Coordination 

Associate Director for Nutritional Sciences 

National Institute of Diabetes and Digestive and Kidney Diseases 

Washington, DC

vi
Omega-3 Fatty Acids and Maternal and Child Health: 

An Updated Systematic Review

Structured Abstract

Objectives. To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) 

on maternal and child health and to assess the evidence for their effects on, and associations 

with, additional outcomes.

Data sources. MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, 

Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB)

Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant 

systematic reviews.

Review methods. We included randomized controlled trials (RCTs) of any defined dose of n-3 

FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an 

outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or 

term). We also included prospective observational studies that analyzed the association between 

baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began 

within a week of birth for term infants and within a week of beginning enteral or oral feeding for 

preterm infants. Standard methods were used for data abstraction and analysis, according to the 

Evidence-based Practice Center Methods Guide.

Results. We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 

48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs 

and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are 

summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was 

insufficient to draw a conclusion are summarized in Appendix G of the report.)

Maternal Exposures and Outcomes 

Gestational length and risk for preterm birth: Prenatal algal docosahexaenoic acid (DHA) or 

DHA-enriched fish oil supplementation had a small positive effect on length of gestation 

(moderate SoE), but no effect on risk for preterm birth (low SoE). Prenatal EPA

(eicosapentaenoic acid) plus DHA-containing fish oil supplementation has no effect on length of 

gestation (low SoE). Supplementation with DHA, or EPA plus DHA-, or DHA-enriched fish oil

does not decreaserisk for preterm birth (low SoE). 

Birth weight and risk for low birth weight: Changes in maternal n-3 FA biomarkers were 

significantly associated with birth weight. Prenatal algal DHA or DHA-enriched fish oil

supplementation had a positive effect on birth weight among healthy term infants (moderate 

SoE), but prenatal DHA supplementation had no effect on risk for low birth weight (low SoE). 

Prenatal EPA plus DHA or alpha-linolenic acid (ALA) supplementation had no effect on birth 

weight (low SoE). 

Risk for peripartum depression: Maternal n-3 FA biomarkers had no association with risk for

peripartum depression. Maternal DHA, EPA, or DHA-enriched fish oil supplementation had no 

effect on risk for peripartum depression (low SoE). 

Risk for gestational hypertension/preeclampsia: Prenatal DHA supplementation among highrisk pregnant women had no effect on the risk for gestational hypertension or preeclampsia 

vii
(moderate SoE). Prenatal supplementation of any n-3 FA in normal-risk women also had no 

significant effect on risk for gestational hypertension or preeclampsia (low SoE). 

Fetal, Infant, and Child Exposures and Outcomes 

Postnatal growth patterns: Maternal fish oil or DHA plus EPA supplementation had no 

effect on postnatal growth patterns (attainment of weight, length, and head circumference) when 

administered prenatally (moderate SoE) or both pre- and postnatally (low SoE). Fortification of 

infant formulas with DHA plus arachidonic acid (AA, an n-6 FA) had no effect on growth 

patterns of preterm or term infants (low SoE). 

Visual acuity: Prenatal supplementation with DHA had no effect on development of visual 

acuity (low SoE). Supplementing or fortifying preterm infant formula with any n-3 FA had no

significant effect on visual acuity assessed by visual evoked potentials (VEP) at 4 or 6 months 

corrected age (low SoE). Data conflicted on the effectiveness of supplementing infant formula 

for term infants with n-3 FA depending on when and how visual acuity was assessed (i.e. by 

VEP or by behavioral methods) and the type of essential FA provided (low SoE). 

Neurological development: Prenatal or postnatal n-3 FA supplementation had no consistent 

effect on neurological development (low SoE).

Cognitive development: Prenatal DHA supplementation with AA or EPA had no effect on 

cognitive development (moderate SoE). Supplementing breastfeeding women with DHA plus 

EPA also had no effect on cognitive development in infants and children (low SoE). 

Supplementing or fortifying preterm infants’ formula with DHA plus AA had a positive effect on 

infant cognition at some short-term followup times (moderate SoE). Supplementing or fortifying 

infant formula for term infants with any n-3 FA had no effect on cognitive development (low 

SoE). Evidence is insufficient to support any effect of n-3 FA infant supplementation on longterm cognitive outcomes.

Autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), and learning 

disorders: Maternal or infant n-3 FA supplementation had no effect on risk for autism spectrum 

disorders or ADHD (low SoE). No studies on other learning disorders were identified.

Atopic dermatitis (AD), allergies, and respiratory disorders: Pre- and postnatal (maternal 

and infant) n-3 FA supplementation had no consistent effect on the risk for AD/eczema, 

allergies, asthma, and other respiratory illnesses (moderate SoE). Biomarkers and intakes had no 

consistent association with the risk for AD, allergies, and respiratory disorders (low SoE). 

Adverse events: Prenatal and infant supplementation with n-3 FA or fortification of foods

with n-3 FA did not result in any serious or nonserious adverse events (moderate SoE); with the 

exception of an increased risk for mild gastrointestinal symptoms.

Conclusions. Most studies in this report examined the effects of fish oil (or other combinations 

of DHA and EPA) supplements on pregnant or breastfeeding women or the effects of infant 

formula fortified with DHA plus AA. As with the original report, with the exception of small

increases in birth weight and length of gestation,n-3 FA supplementation or fortification has no 

consistent evidence of effects on peripartum maternal or infant health outcomes. No effects of n3 FA were seen on gestational hypertension, peripartum depression, or postnatal growth.

Apparent effects of n-3 FA supplementation were inconsistent across assessment methods and 

followup times for outcomes related to infant visual acuity, cognitive development and 

prevention of allergy and asthma. Future RCTs need to assess standardized preparations of n-3 

and n-6 FA, using a select group of clinically important outcomes, on populations with baseline 

n-3 FA intakes typical of those of most western populations. 

viii
Contents

Executive Summary................................................................................................................ES-1

Introduction................................................................................................................................... 1

Scope and Key Questions........................................................................................................... 2

 Scope of the Review

 Key Questions

 Analytic Frameworks

Methods.......................................................................................................................................... 9

Topic Refinement and Review Protocol..................................................................................... 9

Literature Search......................................................................................................................... 9

Search Strategy

Inclusion and Exclusion Criteria............................................................................................... 10

Study Selection ......................................................................................................................... 14

Data Extraction ......................................................................................................................... 14

Methodological Quality (Risk of Bias) Assessment of Individual Studies .............................. 14

Data Synthesis/Analysis............................................................................................................ 15

Summary of Causality-Related Study Features........................................................................ 15

Grading the Strength of Evidence (SOE) for Major Comparisons and Outcomes................... 16

Assessing Applicability ............................................................................................................ 16

Peer Review and Public Commentary ...................................................................................... 16

Results.......................................................................................................................................... 17

Results of Literature Searches .................................................................................................. 17

Findings..................................................................................................................................... 19

Key Question 1: Maternal Exposures....................................................................................... 19

Key Question 2: Fetal/Childhood Exposures.......................................................................... 103

 Key Question 3: Maternal or Childhood Adverse Events

Discussion................................................................................................................................... 328

Overall Summary of Key Findings......................................................................................... 328

Limitations.............................................................................................................................. 331

Future Research Recommendations........................................................................................ 333

Conclusions............................................................................................................................. 334

 Maternal Exposures

 Infant and Child Outcomes

 Adverse Events

Overall Conclusions................................................................................................................ 335

References.................................................................................................................................. 344

Abbreviations/Acronyms.......................................................................................................... 357

Tables

Table A. Conclusions with strength of evidence for an effect or lack of effect ..................... ES-18

Table 1. RCTs for length of gestation (or gestational age) and preterm birth.............................. 27

Table 2. Observational studies for length of gestation (or gestational age) and preterm birth..... 41

Table 3. RCTs for gestational hypertension preeclampsia eclampsia .......................................... 47

Table 4. Observational studies for gestational hypertension preeclampsia eclampsia ................. 51

Table 5. RCTs that assessed risk for low birth weight ................................................................. 56

ix
Table 6. RCTs for infants born small gestational age and intrauterine growth retardation.......... 64

Table 7. Observational studies for infants born small gestational age ......................................... 69

Table 8. RCTs for birth weight..................................................................................................... 76

Table 9. Observational studies for birth weight............................................................................ 90

Table 10. RCTs for ante postnatal depression .............................................................................. 97

Table 11. Observational studies for ante postnatal depression................................................... 101

Table 12. RCTs for postnatal growth patterns............................................................................ 113

Table 13. Observational studies for postnatal growth patterns................................................... 137

Table 14. RCTs for neurological development........................................................................... 149

Table 15. Observational studies for neurological development.................................................. 172

Table 16. RCTs for visual function............................................................................................. 187

Table 17. RCTs for cognitive development................................................................................ 209

Table 18. Observational studies for cognitive development....................................................... 244

Table 19. RCTs for autism spectrum disorders .......................................................................... 248

Table 20. Observational studies for autism spectrum disorders................................................. 250

Table 21. RCTs for attention deficit hyperactivity disorder....................................................... 252

Table 22. RCTs for atopic dermatitis.......................................................................................... 260

Table 23. Observational studies for atopic dermatitis ................................................................ 270

Table 24. RCTs for allergies....................................................................................................... 280

Table 25. Observational studies for allergies.............................................................................. 288

Table 26. RCTs for respiratory illness........................................................................................ 297

Table 27. Observational studies for respiratory illness............................................................... 309

Table 28. Adverse events............................................................................................................ 318

Table 29. Conclusions with strength of evidence for an effect or lack of effect ........................ 337

Figures

Figure 1. Metabolic pathway of omega-3 fatty acids ..................................................................... 1

Figure 2. Analytic framework for n-3 fatty acids in maternal health ............................................. 7

Figure 3. Analytic framework for n-3 fatty acids in child health ................................................... 8

Figure 4. Literature flow diagram................................................................................................. 18

Figure 5. Length of gestation (weeks): DHA versus placebo, DHA + EPA or fish oil 

versusplacebo................................................................................................................................ 23

Figure 6. Incidence of premature birth: DHA versus placebo, DHA + EPA or fish oil versus

placebo .......................................................................................................................................... 24

Figure 7. Pregnancy induced hypertension/preeclampsia: DHA + EPA versus placebo, DHA 

versus placebo............................................................................................................................... 44

Figure 8. Risk for low birth weight (<2500g) – DHA versus placebo ......................................... 55

Figure 9. Risk for small for gestational age: DHA + EPA or DHA versus placebo..................... 63

Figure 10. Birth weight (g): DHA versus placebo, DHA + EPA versus placebo......................... 73

Figure 11. Weight (kg) at 18 months – DHA versus placebo, given to pregnant women.......... 106

Figure 12. Length (cm) at 18 months – DHA versus placebo, given to pregnant women ......... 106

Figure 13. Head circumference (cm) at 18 months – DHA versus placebo, given to pregnant 

women......................................................................................................................................... 107

Figure 14. Weight (kg) at 4 months – DHA + AA versus placebo, given to preterm infants .... 109

Figure 15. Length (cm) at 4 months – DHA + AA versus placebo, given to preterm infants.... 110

Figure 16. Visual function in preterm infants at 4-months corrected age .................................. 179

x
Figure 17. Visual function in preterm infants at 6-months corrected age .................................. 180

Figure 18. Visual function in term infants at 2-months follow-up, behavior methods............... 182

Figure 19. Visual function in term infants at 4-months follow-up, behavioral methods............ 183

Figure 20. Visual function in term infants at 12-months follow-up, behavioral methods.......... 183

Figure 21. Visual function in term infants at 2-months follow-up, Sweep Visual Evoked Potential

..................................................................................................................................................... 184

Figure 22. Visual function in term infants at 4-months follow-up, Sweep Visual Evoked Potential

..................................................................................................................................................... 184

Figure 23. Visual function in term infants at 12-months follow-up, Sweep Visual Evoked 

Potential ...................................................................................................................................... 185

Figure 24. Preterm cognitive....................................................................................................... 205

Figure 25. Full term cognitive .................................................................................................... 206

Figure 26. Food allergy – Intervention given to pregnant women, 12-month follow-up ........... 276

Figure 27. Wheeze – Intervention given to pregnant women, 12-month follow-up................... 293

Figure 28. Asthma – Intervention given to infants, 18-month follow-up................................... 294

Appendixes

Appendix A. Search Strategy

Appendix B. List of Excluded Studies

Appendix C. Evidence Table for Randomized Controlled Trials

Appendix D. Evidence Table for Observational Studies

Appendix E. Data Abstraction Tools

Appendix F. Quality of Included Studies

Appendix G. Strength of Evidence

Appendix H. List of Included Studies From the Original Report

Appendix I. Causality Table

xi
Executive Summary

Introduction

The n-3 FA (including alpha linolenic acid [ALA], stearidonic acid [SDA], eicosapentaenoic 

acid [EPA], docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) are a group of 

essential long-chain and very-long-chain polyunsaturated fatty acids (PUFA). Along with the n-6 

FA (including linoleic acid [LA] and arachidonic acid [AA]), they are involved in the eicosanoid 

pathway and are incorporated into cell membranes. Eicosanoids (including AA, prostaglandins, 

thromboxanes, and leukotrienes) have wide ranges of physiologic effects and play a key role in 

inflammation regulation. ALA is the simplest n-3 FA from which all other n-3 FA are 

metabolically derived. ALA must come from the diet as it cannot be made by the body. ALA is 

found in plants, such as leafy green vegetables, nuts, and vegetable oils such as canola, soy, and 

flaxseed. SDA can be formed from ALA via Δ-6 desaturase, the rate-limiting enzyme in the 

pathway. When SDA enters the metabolic pathway, it is rapidly converted to EPA. EPA can be 

converted to DPA and vice versa. The conversion rates from ALA to EPA or DHA are highly 

variable. Good sources of EPA and DHA in the diet include fish, other seafood, other marine 

sources (e.g., algae and phytoplankton), and organ meats.

A role for n-3 FAs in prenatal and postnatal growth and development and risk for certain 

chronic diseases has been suggested by a variety of evidence from prospective cohort studies and 

randomized controlled trials (RCTs). In 2002, the Institute of Medicine (IOM) considered the 

evidence inadequate to establish an estimated average requirement (EAR) for n-3 FAs.1 Thus, in 

the absence of sufficient evidence, the IOM set only Adequate Intake values (AIs), based on 

current population intake in the apparent absence of deficiency symptoms.a The IOM set the 

following AIs for n-3 FA (ALA, whose primary dietary sources are plant foods and algae) for 

healthy pregnant women and children:

Pregnant women: 1.4 grams(g)/day (d) of ALA

Infants (≤12 months): 0.5 g/d of n-3 FAs

Children (1 to 3 years): 0.7g/d of ALA

Children (4 to 8 years): 0.9 g/d of ALA

In 2004, at the request of the National Institutes of Health’s (NIH) Office of Dietary 

Supplements (ODS), three Evidence-based Practice Centers (EPCs) conducted 11 systematic 

reviews (SRs) of the evidence for the health effects of n-3 FAs. Included among these SRs was 

one that encompassed outcomes related to the health of pregnant women and their children.2

Maternal outcomes included gestational length, the risk for preterm birth, birth weight, 

intrauterine growth retardation ([IUGR], small-for-gestational age [SGA], and low birth weight

[LBW]); birth length, head circumference, pregnancy hypertension and preeclampsia. Child 

health outcomes included neurological development; visual function in the first year of life; and 

various indices of cognitive development. This review found insufficient evidence to draw 

definitive conclusions about the effects of n-3 FA on maternal or child outcomes. Since the 

original review, many new studies and a number of SRs have examined the role of n -3 FAs in 

these outcomes. In addition, recent studies have suggested a potential role for n-3FAs in some 

a The use of an AI instead of an EAR indicates the need for more research to determine, with confidence, the mean 

and distribution of requirements for that nutrient; AIs are based on much less data and more scientific judgment than 

are EARs.

ES-1

 
related outcomes, e.g., the development of attention and working memory.3 Thus ODS requested 

an update to the original report.

Scope and Key Questions

Scope of the Review

The current systematic review has four aims: 1) to update the original review on the topic of 

the effects of n-3 FAs on maternal and child outcomes,

2 2) to identify the literature for several 

additional outcomes of interest (see below) not included in the original review; 3) to include 

prospective observational studies that were excluded from the original report when two or more 

RCTs were identified for an outcome of interest; and 4) to use this new review to collect 

additional information such as baseline intakes of or exposures to n-3 FAs and associations 

between exposure dose and response that would enhance the usefulness of this report for policy 

and clinical applications. Therefore, it is of interest to systematically compare results across 

different exposure/intervention products and study types (e.g., interventional vs. prospective 

cohort studies), and to account for differences in background n-3 FA intake.

This update includes the addition of seven new outcomes: (maternal) ante- and postnatal 

depression, and pediatric attention deficit hyperactivity disorder (ADHD), autism spectrum 

disorders (ASD), learning disabilities, atopic dermatitis, allergies, and respiratory disorders, 

specifically looking at the risk for (or prevention of) these conditions in otherwise healthy 

individuals and their offspring, rather than the efficacy of n-3 FA in treating affected individuals. 

Key Questions 

The Key Questions address both issues of efficacy (i.e., causal relationships from trials) as 

well as associations (i.e., prospective cohort study results and outcomes or risk factors from 

RCTs for which the randomization may not be applicable). Compared with the Key Questions 

from the 2005 report, they expand the scope of the review to include additional maternal and 

child outcomes, as noted above and described below (shown in bold face). 

Key Question 1: Maternal Exposures

– What is the efficacy of maternal interventions involving—or 

association of maternal exposures to—n-3 FAs (EPA, DHA, 

EPA+DHA, DPA, ALA, SDA, or total n-3 FA) on the following:

• duration of gestation in women with or without a history of preterm 

birth (less than 37 weeks gestation),

• incidence of preeclampsia/eclampsia/gestational hypertension in 

women with or without a history of preeclampsia/ 

eclampsia/gestational hypertension

• Incidence of birth of small-for-gestational age human infants

• Incidence of ante- and/or postnatal depression in women with 

or without a history of major depression or postpartum 

depression

ES-2
– What are the associations of maternal biomarkers of n-3 intake 

during pregnancy and the outcomes identified above?

– What are the effects of potential confounders or interacting factors 

(such as other nutrients or use of other supplements, or smoking 

status)?

– How is the efficacy or association of n-3 FA on the outcomes of 

interest affected by the ratio of different n-3 FAs, as components of 

dietary supplements or biomarkers?

– How does the ratio of n-6 FA to n-3 FA intakes or biomarker 

concentrations affect the efficacy or association of n-3 FA on the 

outcomes of interest?

– Is there a threshold or dose-response relationship between n-3 FA 

exposures and the outcomes of interest or adverse events?

– How does the duration of the intervention or exposure influence 

the effect of n-3 FA on the outcomes of interest?

Key Question 2: Fetal/childhood exposures

– What is the influence of maternal intakes of n-3 fatty acids or the n-3 

fatty acid content of maternal breast milk (with or without knowledge 

of maternal intake of n-3 FA) or n-3 FA-supplemented infant formula 

or intakes of n-3 FA from sources other than maternal breast milk or 

supplemented infant formula on the following outcomes in term or 

preterm human infants? 

• Growth patterns

• Neurological development

• Visual function

• Cognitive development

• Autism

• Learning disorders

• ADHD

• Atopic dermatitis

• Allergies

• Respiratory illness

– What are the associations of the n-3 FA content or the n-6/n-3 FA 

ratio of maternal or fetal or child biomarkers with each of the 

outcomes identified above?

ES-3
Key Question 3: Maternal or childhood adverse events:

– What are the short and long-term risks related to maternal intake of n3 fatty acids during pregnancy or breastfeeding on

• Pregnant women

• Breastfeeding women

• Term or preterm human infants at or after birth

– What are the short and long-term risks associated with intakes of n3s by human infants (as maternal breast milk or infant formula 

supplemented with n-3 FA)?

– Are adverse events associated with specific sources or doses? 

Methods

The present review evaluates the effects of—and the associations between—n-3 FAs intakes

(including EPA, DHA, DPA, ALA, SDA, and n-3 biomarkers) and maternal and child health 

outcomes. The Evidence-based Practice Center (EPC) conducted the review based on a 

systematic review of the published scientific literature using established methods as outlined in 

the Agency for Healthcare Research and Quality (AHRQ)’s Methods Guide for Comparative 

Effectiveness Reviews.4

This review is conducted in parallel with a systematic review of n-3 FA and cardiovascular 

disease, conducted by another EPC. Several aspects of the reviews are being coordinated, 

including eligibility criteria regarding interventions and exposures, search strategies, structure of 

the reviews, and assessments of the studies’ risk of bias, strength of the bodies of evidence, and 

abstraction of study characteristics needed to assess causality. 

We convened a Technical Expert Panel (TEP) to help refine the research questions and 

protocol. We discussed the Key Questions, analytic framework, study eligibility criteria, 

literature search, and analysis plans. The protocol was entered into the PROSPERO register 

(registry number CRD42015020638).

Literature Search Strategy

We modified the existing search strategies from the original report (see Appendix A) to 

include a complete set of terms for the new outcomes of interest based on searches we have 

conducted on these topics for previous reviews and consultation with colleagues. We conducted 

literature searches in Medline (Pubmed), Embase, the Cochrane Collection, Web of Science and 

Centre for Agriculture and Biosciences (CAB). For the topics of depression; ADHD; autism; and 

cognitive, neurological, and visual function development, we searched PsychInfo. We did not 

search for unpublished (grey) literature; however a notice was published in the Federal Register 

requesting unpublished data from manufacturers of omega-3 fatty acid-fortified infant formulae 

and dietary supplements. Searches for all topics began with the year 2000. For the newly added

topics, we “reference mined” articles that we identified to determine whether any studies 

conducted and published prior to 2000 should be obtained and included. Studies in the original 

report deemed eligible for pooling with newly identified studies were included, as were 

ES-4
prospective cohort and nested case control studies excluded from the original report that met 

current inclusion criteria. 

The search was updated upon submission of the draft report for peer and public review. 

Inclusion and Exclusion Criteria

The eligibility criteria applied to the search results were mostly similar to the criteria used in 

the original (2005) review. The populations were expanded to accommodate the expanded 

outcomes of interest. The interventions and exposures remain the same as those in the original 

report, with the addition of two n-3 FA (DPA and SDA). Included study designs have also been 

modified slightly.

The Eligibility Criteria are outlined here according to the PICOT framework, with 

indications of the Key Questions to which they apply.

• Population(s): 

o Key Question (KQ) 1(Maternal exposures and outcomes)

 Healthy pregnant women (for outcomes of birth weight, intrauterine 

growth restriction/small for gestational age, duration of gestation, risk of 

pre-eclampsia, eclampsia, or pregnancy hypertension)

 Pregnant women with a history of pre-eclampsia, eclampsia, or pregnancy 

hypertension (only for outcome of risk of pre-eclampsia, eclampsia, or 

pregnancy hypertension)

 Pregnant women with a history of major depressive disorder or postpartum 

depression (only for the outcome of risk for peripartum depression)

o Key Question 2 (In utero and postnatal (through the first year of life) exposures 

and outcomes)

 Healthy preterm or full term infants of healthy women/mothers whose n-3 

fatty acid exposures were monitored during pregnancy 

 Breastfed infants of healthy mothers whose n-3 fatty acid exposure was 

monitored and/or who participated in an n-3 fatty acid intervention during 

breastfeeding beginning at birth

 Healthy preterm or full term infants with and without family history of 

respiratory conditions (for outcomes related to atopic dermatitis, allergy, 

respiratory conditions) of mothers whose n-3 exposures were monitored 

during pregnancy and/or breastfeeding

 Healthy children or children with a family history of a respiratory 

disorder, a cognitive or visual development disorder, autism spectrum 

disorder, ADHD, or learning disabilities, age 0 to 18 years who 

participated in an n-3 fatty acid-supplemented infant formula intervention 

or an n-3 supplementation trial during infancy 

o Key Question 3 (Adverse events associated with n-3 interventions)

 Healthy pregnant women or pregnant women in the other categories 

described above

 Offspring of women enrolled in an n-3 fatty acid intervention during 

pregnancy 

 Offspring of women whose exposure to n-3 fatty acids was assessed 

during pregnancy

ES-5
 Children whose exposure to n-3 fatty acids (through breast milk, infant 

formula, or supplementation) was monitored during the first year of life 

• Interventions/Exposures: 

o Interventions (KQ1, 2, 3 unless specified): 

 N-3 fatty acid supplements (e.g., EPA, DHA, ALA, singly or in 

combination;

 N-3 fatty acid supplemented foods (e.g., eggs) with quantified n-3 FA

content

 High-dose pharmaceutical grade n-3 fatty acids, e.g., Omacor®, Ropufa®, 

MaxEPA®, Efamed, Res-Q®, Epagis, Almarin, Coromega, Lovaza®, 

Vascepa® (icosapent ethyl)

• Exclude doses of more than 6g/d, except for trials that report 

adverse events

 N-3 fatty acid fortified infant formulae (KQ2,3)

• E.g., Enfamil® Lipil®; Gerber® Good Start DHA & ARA®; 

Similac® Advance®

• N-3 FA fortified follow-up formulae

• Exclude parenterally administered sources 

 Marine oils, including fish oil, cod liver oil, menhaden oil, and algal with 

quantified n-3 FA content

 Algal or other marine sources (e.g., phytoplankton) of omega-3 fatty acids 

with quantified n-3 content

o Exposures (KQ1,2)

 Dietary n-3 fatty acids from foods if concentrations are quantified in food 

frequency questionnaires

 Breast milk n-3 fatty acids (KQ2)

 Biomarkers (EPA, DHA, ALA, DPA, SDA), including but not limited to 

the following:

• Plasma fatty acids

• Erythrocyte fatty acids

• Adipocyte fatty acids. 

• Comparators:

o Inactive comparators:

 Placebo (KQ1, 2, 3)

 Non-fortified infant formula (KQ2)

o Active comparators

 Different n-3 sources 

 Different n-3 concentrations (KQ1, 2, 3)

 Alternative n-3 fortified infant formulae (KQ2)

 Soy-based infant formula (KQ2)

 Diet with different level of Vitamin E exposure 

• Outcomes:

o Maternal outcomes (KQ1)

 Blood pressure control

ES-6
• Incidence of gestational hypertension

• Maternal blood pressure

• Incidence of pre-eclampsia, eclampsia

 Peripartum depression

• Incidence of antepartum depression5

• Incidence of postpartum depression, e.g., 

o Edinburgh Postnatal Depression scale

o Structured Clinical Interview (SCI)

 Gestational length

• Duration of gestation

• Incidence of preterm birth

 Birth weight

• Mean birth weight

• Incidence of low birth weight/small for gestational age

o Pediatric Outcomes (KQ2)

 Neurological/visual/cognitive development

• Visual development, e.g.,

o Visual evoked potential (VEP) acuity

o Behavioral visual acuity testing

 Teller’s Acuity Card test and others

o Electroretinography

• Cognitive development, e.g., 

o Bayley’s Scale of Infant and Toddler Development Mental 

Development Index (MDI)

o Griffith Mental Developmental 

Scale

o Kauffman Assessment Battery for Children

o Neonatal Behavioral Assessment

o Wechsler Scales

o MacArthur Communicative Development Inventory

o Fagan Test of Infant Intelligence

o Ages and Stages Questionnaire

o Stanford-Binet IQ



• Neurological development

o Bayley’s Scale of Infant and Toddler Development 

Psychomotor Development Index (PDI) 

o Electroencephalograms (EEGs) as measure of maturity

o Neurological/movement impairment assessment

o Active sleep, quiet sleep, sleep-wake transition, 

wakefulness

o Nerve conduction test

o Latency Auditory evoked potential

 Risk for ADHD

• Validated evaluation procedures

o E.g., Wechsler Intelligence Scale for Children, 

ES-7
o Behavioral rating scales, e.g., Connors, Vanderbilt, and 

Barkley scales 

 Risk for Autism spectrum disorders

• Validated evaluation procedures

o E.g., Modified Checklist of Autism in Toddlers

 Risk for learning disabilities

• Validated evaluation procedures

 Risk for atopic dermatitis

 Risk for allergies

• Validated allergy assessment procedures, preferably challenge

(skin prick test or validated blood tests accepted)

 Incidence of respiratory disorders

• Spirometry in children 5 and over (peak expiratory flow rate 

[PEFR] and forced expiratory volume in 1 second [FEV1])

o Key Question 3: Adverse effects of intervention(s)

 Incidence of specific adverse events reported in trials by study arm

• Timing:

o Duration of intervention or follow-up

 Key Question 1,3 (maternal interventions/exposures): 

• Interventions implemented anytime during pregnancy but 

preferably during the first or second trimester

• Follow-up duration is anytime during pregnancy (for maternal 

outcomes of pre/eclampsia or maternal hypertension); term (for 

outcomes related to birth weight, duration of pregnancy); or within 

the first 6 months postpartum (for the outcome of postpartum 

depression)

 Key Question 2, 3 (infant exposures):

• Interventions implemented within one month of birth or exposures 

measured within 1 month of birth 

• Follow-up duration is 0 to 18 years 

• Settings: 

o Community-dwelling individuals seen by primary care physicians or obstetricians 

in private or academic medical practices (KQ1, 3) 

o Community dwelling children seen in outpatient health care or educational 

settings (KQ2, 3)

We limited the study designs of interest to RCTs of any size, and to prospective cohort studies 

and nested case control studies of sample size 250 or greater (cross-sectional, retrospective 

cohort, and case study designs were excluded; studies must have measured intake/exposure prior 

to outcome). Only peer-reviewed studies published in English language were included. 

Unpublished studies were not included.

Study Selection

The DistillerSR software package was used to manage the search outputs, screening, and data 

abstraction. Title/abstract screening was conducted in duplicate). All title selections were 

ES-8
accepted without reconciliation for further full-text review. Second-level screening of full text 

articles was conducted by two reviewers and differences reconciled (the project leaders settle 

disagreements, if needed).

Data Extraction

Accepted studies underwent single abstraction of study-level data and risk-of-bias assessment 

in Distiller, with audit by an experienced reviewer. Outcome data were abstracted by a 

biostatistician and audited by an experienced reviewer. We re-extracted data from studies 

included in the original report that are to be included in new pooled analyses as needed.

Methodological Quality (Risk of Bias) Assessment of Individual 

Studies

We assessed the methodological quality of each study based on predefined criteria. Risk of 

bias among RCTs was assessed using the Cochrane Risk of Bias tool,6 which evaluates risk of 

selection bias, performance bias, detection bias, attrition bias, reporting bias, and other potential 

sources of bias. Risk of bias among observational studies was assessed using questions relevant 

for prospective studies from the Newcastle-Ottawa tools.7 Both tools were supplemented with 

nutrition-specific items in consultation with the TEP (e.g., those related to uncertainty of dietary 

assessment measurements and compliance).8-10

Data Synthesis/Analysis

We considered meta-analyses when there were at least three trials with similar intervention 

(i.e. DHA, DHA+EPA, DHA+AA), follow-up time (i.e. birth, 12 months of age), and population 

(i.e. pregnant women, term infants, preterm infants). For trials that had groups with the same 

intervention but with varying doses, we averaged the outcome across doses for the main analysis.

Forest plots were provided for random effects meta-analysis. We used the Hartung-Knapp-SidikJonkman method for our random effects meta-analysis.11-13 It has been shown that the error rates 

from this method are more robust than the previously used DerSimonian and Laird method.14

Heterogeneity was assessed using the I2 statistic.15 All statistical analyses were performed in R 

3.2.0.16

New trial results were added to original meta-analyses, when appropriate, based on similarity 

of participants, interventions (including doses), and outcomes.4

Grading the Strength of Evidence (SOE) for Major Comparisons 

and Outcomes

The strength of evidence was assessed for each outcome and exposure type using the method 

outlined in the AHRQ Methods Guide,4 in which the body of evidence for each outcome is 

assessed based on the following dimensions: study limitations (risk of bias), reporting bias, 

consistency (within and across study designs), directness (of study outcome measures), and 

precision, as well as the number of studies by study design. Based on these assessments, we 

assigned a strength of evidence rating (i.e., insufficient, low, moderate, or high level of 

evidence). The data sources, basic study characteristics, and each strength-of-evidence 

dimensional rating were summarized in a “Summary of Evidence Reviewed” table detailing our 

ES-9
reasoning for arriving at the overall strength of evidence rating. Peer Review and Public 

Commentary

A draft version of this report was reviewed by a panel of expert reviewers, including 

representatives from the American Academy of Pediatrics and the American College of 

Obstetrics and Gynecology, and the general public. The reviewers included experts in prenatal 

and postnatal development and in the clinical effects of n-3FA and representatives of dietary 

supplement trade organizations. These experts were either directly invited by the EPC Program 

or offered comments through a public review process. Revisions of the draft were made, where 

appropriate, based on their comments. The draft and final versions of the report were also 

reviewed by AHRQ. However, the findings and conclusions are those of the authors, who are 

responsible for the contents of the report.

Results

For this systematic review, we identified 95 RCTs and 48 eligible prospective longitudinal 

studies and nested case-control studies that were eligible for inclusion based on the prespecified 

inclusion criteria. Most of the RCTs evaluated the effects of marine oil supplements on weight 

gain during pregnancy (risk for low birth weight) and length of gestation (risk for preterm birth) 

or the effects of DHA with or without arachidonic acid ([AA], an n-6 FA) as supplements or 

added to infant formulas on infant neural, visual, and cognitive development. Most observational 

studies assessed the association between the status of particular n-3 FA and developmental 

outcomes. 

We summarize the results of our review below by the outcomes of interest (maternal 

outcomes, childhood outcomes, adverse events), and within each outcome, by the target 

population for the intervention (e.g., pregnant women, preterm infants, term infants) where 

relevant, and further by the intervention or exposure. Findings included in this summary are 

those for which evidence was determined to be sufficient to draw a conclusion. Findings for all 

interventions/exposures across all outcomes and time points are described in full in the main text 

and the conclusions and strength of evidence are provided in Appendix G.

Maternal Exposures and Outcomes

Length of Gestation and the Risk for Preterm Birth

The original report found inconsistent effects of prenatal maternal n-3 FA supplementation 

on length of gestation or the risk for preterm birth and a consistent finding of no effects of 

prenatal maternal supplementation with EPA+DHA among a large number of RCTs. The current 

report identified a moderate level of evidence that maternal supplementation of DHA or DHAenriched fish oil may increase gestational length, and a low level of evidence that maternal 

supplementation with EPA+DHA-containing fish oils may not have significant effects on 

infants’ gestational length compared with placebo.

For the current report, pooled analysis of 11 RCTs among healthy pregnant women found a 

significant increase in length of gestation among mothers who received algal DHA or DHAenriched fish oil (weighted mean difference [WMD] +0.34 week [95% CI 0.02, 0.67]) compared 

to placebo. Pooled analysis of seven RCTs showed no significant effect of DHA or DHAenriched fish oil on the risk for preterm birth.

Two RCTs in healthy pregnant women showed that maternal fish oil supplementation 

(EPA+DHA) had no significant effects on length of gestation, while one RCT in at-risk pregnant 

ES-10
women found that maternal fish oil supplementation significantly increased the infants’ mean 

gestational age compared with placebo. Pooled analysis of nine RCTs (in four publications) 

found no effects of EPA+DHA supplementation in pregnant women who were at risk for preterm 

birth on the incidence of preterm birth.

Random-effects meta-regression found no significant linear dose-response relationships 

between doses of DHA, EPA, or DHA to EPA ratio (beta coefficient [SE]=-0.04 [0.09], P=0.67, 

n=9) and the effect sizes.

Prospective studies are sparse and found no consistent associations of maternal exposures 

with outcomes related to length of gestation or preterm birth.

Birth Weight and the Risk for Low Birth Weight or Small-forGestational Age Birth

The original report did not find a significant effect of maternal n-3FA supplementation on the 

risk for low birth weight (LBW) or small-for-gestational age (SGA) birth or a clear association 

of any maternal biomarkers with risk for low birth weight or birth weight itself.

For the current report, we found a moderate level of evidence that maternal supplementation 

with DHA may increase birth weight and a low level of evidence that maternal supplementation 

with EPA+DHA may not have significant effects on birth weight compared with placebo. Pooled 

analysis of 12 RCTs showed significantly higher birth weights among infants (mixed term and 

preterm) whose mothers received algal DHA or DHA-enriched fish oil compared with placebo 

(WMD [95% CI]=90.12 [2.62-177.62] grams). Pooled analysis of five RCTs found no 

significant effect of maternal EPA+DHA supplementation on infant birth weight. One RCT that 

assessed the effects of ALA on infant birth weight also showed no effects. These findings are 

consistent with prospective observational studies, which found that higher maternal blood DHA 

concentrations were associated with higher birth weight.

We also found a low level of evidence that maternal supplementation with EPA+DHA may 

not have significant effects on risk for delivering a LBW infant among healthy pregnant women. 

Pooled analysis of five RCTs showed no significant effects of fish or fish oil supplementation 

(doses ranged from 0.49 to 3 g/d) on birth weight compared with placebo or control (WMD

[95% CI]=37.89 [-19.53, 95.31]) grams). Similarly, there is a low level of evidence that maternal 

n-3 FA supplementation may not have significant effects on the incidence of SGA. Two RCTs 

identified in our search found no effect of DHA alone or DHA-enriched fish oil on SGA 

outcomes in healthy pregnant women. Pooled analyses of four RCTs also found no significant 

effects of fish oil supplementation (DHA+EPA) on SGA/IUGR among women at increased risk 

for preterm delivery (OR [95% CI]=1.00, CI[0.70, 1.43]). Pooled analysis of four RCTs 

identified for the current review that assessed the effects of DHA alone or DHA-enriched fish oil 

showed no significant effects on the risk for delivering a LBW infant among women who were 

not at risk. Observational studies were sparse and showed mostly no associations between n-3FA 

intake or biomarkers and these outcomes.

Risk for Antenatal and Postnatal Depression

The outcome of risk for antenatal and postnatal depression was a new one for this review. 

Outcome measures for depression were heterogeneous so meta-analysis is not appropriate. Three 

RCTs that assessed the effects of prenatal supplementation with DHA alone, DHA+AA, or EPAenriched fish oil or postnatal supplementation with DHA alone found no effects on risk of 

developing perinatal depression among healthy pregnant women. One small RCT showed that 

ES-11
women who received prenatal DHA supplementation had significantly fewer symptoms of 

postpartum depression compared to the placebo group. Prospective studies mostly found no 

significant associations of maternal n-3 FA levels and risk of developing postnatal depression. 

Risk for Gestational Hypertension or Preeclampsia

The original report found no consistent effect of maternal supplementation with n-3FA on the 

risk for gestational hypertension or preeclampsia. 

For the current report, pooled analysis of three RCTs (one study identified for the current 

report and two studies from the original report) that randomized women not at high risk for poor 

pregnancy outcomes to DHA supplements or placebo showed no difference in the risk for 

gestational hypertension or preeclampsia among the DHA-treated women compared with the 

placebo-treated women (OR 0.94[0.66, 1.34], I2=0% (n=2,818); pooling studies of high-risk 

women who were randomized to fish oil or placebo also showed no effect (OR 1.04 [0.76 , 1.42], 

I

2= 0%). 

Childhood Outcomes

Postnatal Growth Patterns

The original report found no or inconsistent effects of maternal supplementation or infant 

formula fortification on postnatal growth patterns. The present review identified 24 additional 

RCTs and three observational studies that included pediatric growth pattern outcomes. 

Seven RCTs and two observational studies that evaluated prenatal maternal n-3 FA 

interventions or exposures found no or mixed effects on growth patterns. Four RCTs examined a 

combination of prenatal and postnatal maternal n-3 FA interventions or exposures and found no 

or mixed effects on growth patterns. One RCT examined the effects of a postnatal maternal n-3 

FA intervention and found higher body mass index (BMI) and head circumference in the 

intervention group at 2.5 years, but no effects were observed in an observational study of 

postnatal maternal exposures. Two RCTs examined a mixed set of postnatal maternal and 

postnatal infant n-3 FA interventions or exposures and found inconsistent effects of 

supplementation on growth. Six RCTs that assessed the effects of n-3 FA supplementation in 

infants on growth patterns were conducted among healthy infants or infants born to healthy 

women and found inconsistent associations with supplementation and growth patterns. Four 

RCTs conducted among preterm or LBW infants found inconsistent correlations of n-3 FA 

supplementation with growth pattern outcomes. Pooled analysis of four RCTs of prenatal 

(maternal) supplementation alone with DHA and EPA or fish oil (no postnatal supplementation) 

showed no significant effects on weight, length, or head circumference at 18 months. Pooled 

analysis of three studies of fortification of infant formula with DHA and AA also showed no 

effects on postnatal weight gain and length at 4 months among preterm infants.

Neurological Development

The original report found no consistent effect of maternal or infant supplementation with n-3 

FA on neurological developmental outcomes and inconsistent associations with biomarkers.

Likewise, 17 RCTs identified for the current report found no consistent effects of n-3 FA 

alone or in combination with AA or linoleic acid (LA) on any of these outcomes compared with 

placebo. Two studies reported a positive effect of formula supplemented with DHA and AA on 

ES-12
Bayley’s Psychomotor Development Index (PDI) scores (an index of motor development) in 

preterm infants at 12 and 18 months, and two RCTs reported positive effects on brainstem 

maturation, but the remaining studies reported mixed effects on measures of motor development, 

including the PDI, in term infants supplemented with DHA and similarly mixed effects of DHA 

plus AA on other outcomes. 

Visual Acuity 

The original report found inconsistent effects of maternal and infant supplementation with n3 FA on development of visual acuity, and differences between effects on behavioral measures 

of visual function and effects on electrophysiological measures (visual evoked potentials [VEP]). 

Four RCTs that assessed the effects of prenatal maternal supplementation with DHA found 

no effects on infant visual acuity. 

The current report identified one RCT that found that DHA supplementation of breastfeeding mothers resulted in improvement in one VEP outcome (transient VEP amplitude) at 4 

and 8 months of age but not at 5 years of age; No differences were seen in other VEP measures, 

including sweep VEP and transient VEP latency, and no differences were seen using behavioral 

measures at any age. 

Supplementation of preterm infants with any n-3 FA was assessed in nine RCTs identified 

for the original report and three RCTs identified for the current report. Pooling five studies that 

assessed VEP at 4 and 6 months showed insignificant effects of n-3 FA supplementation on VEP 

at 4 months (WMD -0.06 [-0.12, 0.01]; I2

=1.7%) and 6 months corrected age (WMD -0.04[ -

0.09, 0.01] I2=0%). 

Pooling studies that assessed supplementation of healthy term infants with formula 

containing any n-3 FA showed inconsistent effects on visual acuity. At two months follow-up, 

the pooled effect size for behavioral measurements was significant in favor of n-3 FA (WMD 

0.07 [0.00, 0.14] six RCTs); the pooled effect size for VEP was insignificant (WMD 0.07[-0.03, 

0.17], six RCTs). At 4 months follow-up, the pooled effect size for behavioral measurements was 

significant in favor of placebo treatment (WMD -0.05 [-0.08, -0.01], six RCTs); the pooled effect 

size for VEP was significant in favor of n-3 FA (WMD -0.10[-0.14, -0.07], eight RCTs). At 12 

months follow-up, the pooled effect size for behavioral measures was insignificant (WMD -

0.01[-0.04, 0.01]); the pooled effect size for VEP was significant in favor of n-3 FA (WMD -

0.14 [-0.17, -0.12]).

Supplementation of healthy term infants with formula containing DHA+AA also showed 

inconsistent results. Eight studies identified for the original report showed no differences at 2, 4, 

6, 8 and 9 months; however four studies that assessed VEP at 12 months showed a significant 

pooled effect size in favor of DHA+AA (p=0.01). Two new studies were identified for the 

current report that assessed the effect of supplementation with DHA+AA on VEP at 4 and 12 

months. At 4 months, the pooled effect size for VEP was significant in favor of DHA+AA 

(WMD -0.10 [-0.14, -0.07], five RCTs). At 12 months follow-up, the pooled effect size for VEP 

was also significant in favor of DHA+AA (WMD -0.14 [-0.17, -0.12] six RCTs). None of the 

analyses showed evidence for publication bias.

A small number of trials assessed the association between maternal or infant biomarkers of 

n-3 FA status and subsequent visual acuity, with inconsistent findings. 

ES-13
Cognitive Development 

The original report found inconsistent effects of n-3 FA supplementation on cognitive 

development. follow-up. We identified ten RCTs of pregnant women that reported cognitive 

outcomes in their offspring (including the only RCT identified in the original systematic review); 

only two reported significant results. 

Six RCTs, including two from the original review, reported on supplementation for lactating 

women, including fish oil, cod liver oil, or high-DHA algal oil (two studies each); none reported 

significant results. 

The original review included six RCTs in preterm infants that reported cognitive outcomes, 

while the current one identified an additional six reports on five RCTs. Seven RCTs of preterm 

infants reported the Bayley MDI score at 18 to 24 months of age; the pooled difference between 

the intervention and placebo groups was significant. The other RCTs reported mixed results. 

Regarding healthy infants, the original review reported that six of eight RCTs did not find a 

significant difference between intervention and placebo groups in Bayley MDI scores. The 

current review identified five additional reports on four RCTs that measured cognitive outcomes. 

The pooled difference in MDI scores at 18 months was not significant when 3 RCTs were 

pooled. The RCTs that could not be pooled reported insignificant results regarding cognitive 

outcomes.

Among six observational studies identified for the current report, almost no associations 

between biomarker levels of n-3FAs and cognitive outcomes were noted. In one observational 

study that controlled for 18 potential confounders, low levels of AA in erythrocytes of pregnant 

women were associated with lower performance IQ; high levels of adrenic acid were associated 

with lower verbal IQ; and low levels of DHA were associated with lower verbal and full scale IQ 

at age 8; however, the authors caution that the effect sizes were small.

Risk for Autism, Learning Disorders, and Attention Deficit 

Hyperactivity Disorder

Developmental outcomes newly included for the current report were the risk for Autism 

Spectrum Disorders (ASD), Learning Disorders, and Attention Deficit Hyperactivity Disorder 

(ADHD). Long-term follow-up on one RCT of pregnant women and one RCT of preterm infants 

found no association between n-3 FA and reduced risk of ASD. One large observational study on 

ASD was identified; women with the highest quartile of total PUFA intake while pregnant were 

at lower risk of having a child with ASD than women in the lowest quartile (after controlling for 

many important potential confounders). The authors advised that the results should be interpreted 

with caution, given the small number of cases. Two RCTs of preterm infants and one RCT of 

pregnant women measured attention or reported diagnoses of ADHD at long-term follow-up; no 

association was found with earlier interventions or biomarker levels. No studies of other learning 

disorders were identified.

Allergy, Atopic Dermatitis, and Respiratory Conditions

Additional outcomes newly included in the current report were risks for atopic 

dermatitis/eczema, risks for allergies, and risks for respiratory illnesses, including asthma. A 

number of studies were conducted in mothers or infants at high familial risk for allergies or 

asthma. 

ES-14
Atopic dermatitis/eczema: Four prenatal and three postnatal RCTs showed inconsistent 

effects of maternal n-3 FA supplementation on the risk for atopic dermatitis/eczema: Only one of 

the prenatal studies found a significant reduction in eczema risk. Only one of seven prospective 

observational studies found higher concentrations of breast milk n-3 FA to be significantly 

associated with a lower risk of developing atopic dermatitis; the remaining six studies found no 

associations between n-3 FA exposures (measured through maternal dietary intake or breast milk 

composition) and risk for atopic dermatitis/eczema. Studies that assessed the association of 

biomarkers with this risk observed inconsistent associations of risk for atopic dermatitis with 

plasma levels of DHA, erythrocyte EPA, AA levels, and EPA/AA ratios. One of four prospective 

observational studies of n-3 FA biomarkers (in cord blood or maternal blood sample) found 

decreased risk of eczema and increasing AA levels, with the remaining three studies showing no 

effects. 

Food allergies: Metaanalysis of three RCTs that assessed the effect of maternal 

supplementation with DHA plus EPA showed a reduction in the risk for food allergies that was 

not statistically significant. Use of infant formula fortified with DHA and AA or tuna oil or 

administration of fish oil capsules did not influence the risk for allergies. Prospective 

observational studies showed no consistent associations of maternal or infant n-3 FA exposures 

with risk for allergies. 

Respiratory illness/asthma: Among 8 RCTs and follow-up studies that assessed the effect 

of prenatal n-3 FA supplementation on the risk for respiratory illnesses (including wheeze, 

asthma, persistent cough, inflammation, and respiratory infections), only two reported significant 

effects—decreases in the risk for asthma—but these effects were not consistent over time. A 

metaanalysis of three postnatal interventions that assessed the effects of DHA-supplemented 

formula on risk for wheeze found no significant effect. Prospective observational studies and 

biomarker studies reported inconsistent associations between various postnatal n-3 FA and n-6 

FA exposures and risk for respiratory illnesses, with some studies showing an association 

between lower DHA, EPA, or total n-3 FA exposures or higher n-3 FA to n-6 FA ratios and 

lower risk for respiratory conditions (wheeze or asthma) but some studies of the same exposures 

showing no effects. 

Adverse Events

The original report identified 21 RCTs that reported on adverse events with n-3 FA

supplementation in pregnant women, breastfeeding mothers, and preterm and term infants. 

Overall they found that n-3 FA supplements and fortified formulas were well tolerated. Pregnant 

and breastfeeding women reported no serious adverse events, and adverse events in these groups 

were limited to mild GI symptoms. Among both preterm and term infants, adverse events were 

largely limited to GI symptoms also, with most serious adverse events attributable to morbidities 

associated with prematurity. 

The current report identified 20 RCTs that reported on adverse events. The profile of both 

non-serious and serious adverse events in this report was identical to that of the original report. 

None of the observational studies identified for the current report described adverse events.

ES-15
Discussion 

Overall Summary and Strength of Evidence 

As with the original report, most of the studies identified for the current report assessed the 

effects of n-3 FA interventions (or associations with exposures) on birth weight (or risk for low 

birth weight or intrauterine growth retardation), gestational length (or risk for preterm birth), and 

cognitive outcomes among children. Among studies reporting on the same outcomes, results 

were often inconsistent across studies. 

The current study identified a small but statistically significant effect of DHA 

supplementation of pregnant women on the length of gestation, strengthening a non- statistically 

significant finding in the original report. As in the original report, the current report found no 

effect of DHA- or other n-3 FA supplementation on the risk for preterm birth, and observational 

studies provided inconsistent results. The difference in findings with respect to length of 

gestation (a continuous variable) and the risk for preterm birth (a dichotomous variable) may be 

attributable to any of several factors. Many more studies assessed length of gestation than 

assessed risk for preterm birth. The effect size for the increase in gestational length may not have 

been large enough to translate to an observable decrease in risk for preterm birth. Alternatively, 

the exclusion of preterm infants from some studies that assessed effects of supplementation on 

length of gestation could have skewed the results, or the populations enrolled in studies that 

assessed risk for preterm birth may have had sufficient baseline n-3 FA status. Too few studies 

assessed baseline status to examine this possibility.

The current study also found a significant effect of maternal DHA supplementation on birth

weight in a pooled analysis of twelve studies, in contrast to the original report, which saw no 

effect from pooling two studies. Similar to the original report, a pooled analysis for the current 

report saw no significant effect of supplementation with DHA on the risk for low birth weight 

among women who were not at risk due to a prior low-birth-weight pregnancy. Reasons for the 

difference in these two outcomes may be similar to those posited for length of gestation. In 

addition, a study by Makrides and colleagues included in this review reported that the increase in 

birth weight that resulted from DHA supplementation was largely attributable to the increase in 

gestational age at birth.17

This review also identified no significant effects of n-3 FA supplementation of pregnant 

women on perinatal depression and gestational hypertension/preeclampsia. 

The current report identified effects of supplementing formula with n-3 FA on visual acuity 

of preterm infants at 4 and 6 months corrected age that were not statistically significant but 

approached borderline significance. The report also found small, statistically significant effects 

of supplementing infant formula with n-3 FA, mainly DHA plus AA, on visual acuity 

development in term infants at 4 and 12 months but not at 2 months, when assessed using VEP. 

However, when behavioral measurements were used, an increase in visual acuity was observed 

in supplemented infants only at 2 months but not at 4 or 12 months.Thus the observed effects 

were inconsistent across time and assessment methods. 

The current report identified a significant effect of supplementing infant formula with n-3 FA 

on indices of cognitive development among preterm infants at 18 and 24 months corrected age, 

but no differences were seen on longterm followup (8 to 10 years). No significant effects of 

supplementations were seen on cognitive development among term infants. The findings

regarding the effects of n-3 FA supplementation on other childhood neurodevelopmental 

outcomes (e.g. psychomotor development, autism spectrum disorder, attention deficit 

ES-16
hyperactivity disorder, and learning disorders) and respiratory outcomes (atopic 

dermatitis/eczema, allergy, and respiratory disorders) were either lacking in evidence or too 

inconsistent across studies as well as within studies at different follow-up time points to draw 

any high strength conclusions.

A random-effects meta-regression showed no dose-response effects for n-3 FA and birth 

weight. Too few studies assessed the effects of n-3 FA using similar populations and outcome 

measures to enable dose-response or threshold estimation for other outcomes.

Few studies stratified outcomes according to risk groups, so it was usually not possible to 

assess whether the effectiveness of omega-3 interventions depended on level of risk. In addition, 

no RCTs stratified outcomes by baseline n-3 FA status, so it is not possible to assess whether 

adequacy of n-3 FA status might account for differences in outcomes across (or lack of outcomes 

within) studies. 

Table A summarizes the findings for which we identified a low, moderate, or high strength of 

evidence (SoE) for an effect or no effect of n-3 FA. 

ES-17
Table A. Conclusions with strength of evidence for an effect or lack of effect

Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

Maternal outcomes

Length of gestation Healthy pregnant women:

n-3 FA*d supplementation 

12 RCTs

4 observational studies

Moderate RCTs: Increase in 

gestational length compared 

with placebo

Meta-analysis of 12 RCTs in 

update: 

WMD 0.33 (95% CI 0.04, 

0.62) weeks.

Observational studies: No 

associations.

Original report: mixed 

findings

.

Length of gestation Healthy pregnant women:

Algal DHA or DHA-enriched fish oil 

supplementation 

11 RCTs

4 observational studies

Moderate RCTs: Increase in 

gestational length compared 

with placebo

Meta-analysis of 11 RCTs in 

update: WMD 0.34 (95% CI 

0.02, 0.67) weeks

Observational studies: No 

associations.

Original report: mixed 

findings

Length of gestation Healthy pregnant women:

EPA+DHA fish oil supplementation

7 RCTs

4 observational studies

Low RCTs: No significant effects 

on gestational length

compared with placebo

Observational studies: 3 of 4 

found no association. 

Original report: no effects

founde

Risk for preterm birth Healthy pregnant women:

Algal DHA or DHA-enriched fish oil 

supplementation

7 RCTs Low RCTs: No significant effects 

on the incidence of preterm 

birth compared with placebo

Meta-analysis of 7 RCTs: 

OR 0.87 (95% CI 0.66, 1.15)

Risk for preterm birth At-risk pregnant women:

EPA+DHA fish oil supplementation 

9 RCTs

2 observational studies

Low RCTs:No significant effects 

on the incidence of preterm 

birth compared with placebo

Meta-analysis of 9 RCTs: 

0.86 (95% CI 0.65, 1.15)

ES-18
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

Observational studies 

showed mixed results.

Birth weight Healthy pregnant women:

n-3 FA* supplementation

16 RCTs

10 observational studies

Moderate RCTs: Significant Increase 

in birth weight compared 

with placebo

Meta-analysis of 16 RCTs in 

update: WMD 74.8 (95% CI 

12.4, 137.17) grams.

Observational studies of 

dietary intake, supplement 

use, and biomarkers 

generally showed positive 

associations with birth 

weight.

Original report: Mixed 

findings

Birth weight Healthy pregnant women:

Algal DHA or DHA-enriched fish oil 

supplementation

12 RCTs

3 observational studies

Moderate RCTs: Significant Increase 

in birth weight compared 

with placebo

Meta-analysis of 12 RCTs: 

WMD 90.12 (95% CI 2.62, 

177.62) grams

Observational studies 

showed associations 

between DHA intake and 

biomarkers and birth weight.

Original report: mixed 

findings

Birth weight Healthy pregnant women:

EPA+DHA fish oil supplementation

5 RCTs

4 observational studies

Low RCTs: No significant effects 

on birth weight compared 

with placebo

Meta-analysis of 5 RCTs: 

WMD 37.89 (95% CI -19.53, 

95.31) grams

Observational studies 

showed mixed associations 

with birth weight.

Original report: no effects

Low birth weight Healthy pregnant women:

Algal DHA or DHA-enriched fish oil 

supplementation

4 RCTs Low RCTs: No significant effects 

on risk of low birth weight 

compared with placebo

Meta-analysis of 4 RCTs: 

OR 0.72 (95% CI 0.43, 1.11)

ES-19
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

SGA/IUGR At-risk pregnant women: 

EPA+DHA or fish oil supplementation 

4 RCTs

2 observational studies

Low RCTs: No significant effects 

on SGA/IUGR compared 

with placebo

Observational studies: no 

consistent association with 

SGA

Meta-analysis of 4 RCTs: 

OR 1.00 (95% CI 0.70, 1.43)

Gestational hypertension Normal-risk pregnant women: 

DHA supplementation 

3 RCTs Low RCTs: No significant effect 

on risk for gestational 

hypertension in normal risk 

women

Meta-analysis of 3 RCTs 

OR 0.94 (95% CI 0.66, 1.34)

Gestational hypertension High-risk pregnant women:

Marine oil supplementation 

3 RCTs Moderate RCTs: No significant effect 

on risk for gestational 

hypertension among highrisk women

Meta-analysis of 3 RCTs 

OR 1.04 (95% CI 0.76 , 

1.42)

Peripartum depression Pregnant women:

Prenatal DHA, DHA-rich fish oil,

DHA+AA, EPA+DHA/fish oil, or any n3 FA

4 RCTs

8 observational studies

Low RCTs: Nosignificant effect 

on risk for peripartum 

depression across studies.

Observational studies 

showed no associations with 

risk for depression.e

Infant and child outcomes

Postnatal growth patterns Pregnant women:

Fish oil or DHA+EPA supplementation 

7 RCTs

2 observational studies

Moderate RCTs: No significant effect 

on postnatal growth patterns 

among healthy term infants.

Observational studies: 

Consistent with RCTse

Postnatal growth patterns Breastfeeding women:

Supplementation with any n-3FA

6 RCTs

1 observational study

Low RCTs: No significant effect 

on postnatal growth patterns

Observational study: 

consistent with RCTse

Postnatal growth patterns Preterm or term infants:

Feeding infant formula fortified with 

DHA+AA 

47 RCTs Low RCTs: No significant effect 

on postnatal growth 

patternse

Visual acuity Pregnant women:

Supplementation with DHA-enriched 

fish oil

4 RCTs Low RCTs: No significant effect 

on development of visual 

acuity in infants.e

ES-20
Outcome Intervention/Exposure Study Design

a Strength of Evidenceb Conclusionc

Visual acuityPreterm infants:

Feeding infant formula supplemented 

with any n-3 FA

5 RCTs Low VEP

RCTs: No significant effect 

in preterm infants 4 months

corrected age 

WMD -0.06 (−0.12; 0.01)

Visual acuity Preterm infants:

Feeding infant formula supplemented 

with any n-3 FA

5 RCTs Low VEP

RCTs: No significant effect 

on development of visual 

acuity in preterm infants 6

months corrected age WMD -0.04 (-0.09, 0.01)

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

6 RCTs Low Behavioral measures 

RCTs: Significant effect at 2 

months

WMD 0.07 (0.00, 0.14) six 

RCTs

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

6 RCTs Low VEP

RCTs: No significant effect 

at 2 months

WMD 0.07[-0.03, 0.17], six 

RCTs

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

6 RCTs Low Behavioral measures 

RCTs: Nosignificant effect 

at 4 months

WMD -0.05 (-0.08, 0.01) six 

RCTs

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

6 RCTs Moderate VEP

RCTs: Significant effect at 4 

months

WMD -0.10(-0.14, -0.07), six 

RCTs

Visual acuityTerm infants:

Feeding infant formula supplemented 

with any n-3 FA

8 RCTs Low Behavioral measures

RCTs:No significant effect of n-3 FA at 12 months WMD -

0.10 (-0.14, 

-0.07)

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

8 RCTs Moderate VEP 

RCTs: Significant effect of n-

3 FA at 12 months

WMD -0.14 

(-0.17, -0.12)

Visual acuity Term infants:

Feeding DHA plus AA-fortified infant 

7 RCTs Low VEP

RCTs: Significant effect of 

ES-21
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

formula DHA+AAat 4 months.

WMD -0.10 (-0.14, -0.07)

Visual acuity Term infants:

Feeding DHA plus AA-fortified infant 

formula

6 RCTs Moderate VEP

RCTs: Significant effect of 

DHA+AA at 12 months

WMD -0.14 (-0.17, -0.12)

Neurological development Pregnant women:

Supplementation with any n-3 FA

17 RCTs

5 observational studies

Low RCTs: No significant effects 

on measures of neurological 

development across studies 

(insufficient numbers of 

studies of any outcomes to 

pool) consistent with 

observational studies.e

Cognitive development Pregnant women:

Supplementation with 

DHA+EPA or DHA + AA

10 RCTs Moderate RCTs: No significant effects

on cognitive development

across studiese

Cognitive development Preterm infants:

Supplementation with any n-3 FA

11 RCTs Moderate RCTs: Significant increase in 

cognitive (MDI) scores

WMD 2.24; (95% CI 0.05, 

4.43)

Cognitive development Term infants:

Supplementation with DHA+ AA

12 RCTs Low RCTs: No significant effect 

on cognitive development at 

18-24 months 

WMD 0.75, 95% CI -9.29, 

10.79

Autism Spectrum Disorders

(ASD)

Pregnant women or preterm infants:

Supplementation with DHA

2 RCTs

1 observational study

Low RCTs: No significant effect 

on risk for ASD; association 

shown for intake of n-3 FA in 

observational studye

ADHD Pregnant women or preterm infants:

Supplementation with DHA

3 RCTs Low RCTs: No significant effect 

on risk for ADHDe

Atopic dermatitis/ eczema Pregnant women:

Supplementation with any n-3 FA or 

exposures as assessed by biomarkers

4 RCTs Low RCTs: No significant (and 

inconsistent) effects on risk 

for atopic dermatitis/eczema

Atopic dermatitis/ eczema Breastfeeding women or infants: 

Supplementation of mothers or infants 

through formula fortification with any n3 FA or exposure as assessed with 

biomarkers 

3 RCTs 

7 observational studies

Low RCTs: No significant (and 

inconsistent) effects on risk 

for atopic dermatitis/eczema

across RCTs, consistent 

with observational studiese

Allergies Pregnant women:

Supplementation with any n-3 FA or 

3 RCTs

4 observational studies

Low RCTs: No significant effect 

on the risk for food allergy at 

ES-22
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

exposures as assessed by biomarkers (including 3 biomarker 

studies)

12 months 

OR 0.54 (95% CI 0.05, 6.2); 

Observational studies: no 

consistent association of 

biomarkers and risk for 

allergy 

Allergies Breastfeeding women or infants:

Supplementation of mothers or infants 

through formula fortification with any n3 FA or exposure as assessed by 

biomarkers

3 RCTs

2 observational studies

Low RCTs: No significant effect 

on the risk for food or dust 

mite allergy and no 

association of breastmilk or 

infant biomarkers and risk 

for allergies across 

observational studiese

Asthma and other respiratory 

illnesses

Pregnant women:

Supplementation with any n-3 FA

6 RCTs Moderate RCTs: No significant effect 

on the risk for asthma and 

other respiratory illnesses

Meta-analysis of 3 RCTs OR 

0.95 95% CI 0.77, 1.16

Asthma and other respiratory 

illnesses

Breastfeeding women or infants:

Supplementation of mothers or infants

through formula fortification with any n3 FA

3 RCTs Moderate RCTs: No significant effect 

on the risk for asthma and 

other respiratory illnessese

Asthma and other respiratory 

illnesses

Pregnant women or infants:

Any n-3 FA exposures 

10 observational studies Low Observational Studies: 

Inconsistent associations 

with risk for respiratory 

illnesses across studies.

e

Asthma and other respiratory 

illnesses: Wheeze

Breastfeeding women or infants:

Supplementation of mothers or infants 

through formula fortification with DHA

3 RCTs

5 observational studies

4 biomarkers studies

Low RCTs: No significant effect 

on risk for wheeze at 12 

months; meta-analysis of 3 

RCTs:

OR 1.06 (95% CI 0.73,1.54)

Observational studies:

showed Inconsistent 

associations with risk for 

wheeze across studies

Adverse events

Maternal adverse events

Non-serious

Pregnant or breastfeeding women:

Supplementation with n-3 FA in the 

form of fish oil

9 RCTs Moderate RCTs: Increased risk for 

mild gastrointestinal 

symptoms but no other 

consistent non-serious 

adverse events.

e

Maternal adverse events Pregnant or breastfeeding women: 4 RCTs Moderate RCTs: No significant 

ES-23
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

serious Supplementation with n-3 FA in the 

form of fish oil

difference in risk for serious 

adverse events.

e

Infant adverse events nonseriousHealthy term infants or preterm 

infants:

Supplementation with n-3 FA in the 

form of fish oil alone or added to infant 

formula

13 RCTs Moderate RCTs:Increased risk for mild 

gastrointestinal symptoms 

across studies but no other 

consistent non-serious 

adverse events.

e

Infant adverse events serious Healthy term infants: Supplementation 

with n-3 FA in the form of fish oil

6 RCTs Moderate RCTs:No significant 

difference in risk for serious 

adverse events.

e

Infant adverse events serious Preterm infants:

Supplementation with n-3 FA in the 

form of fish oil

RCTs Low RCTs:No significant 

difference in risk for serious 

events associated with 

preterm birth.

e

a

Figures represent numbers of studies considered as evidence in drawing the conclusion; b

Strength of evidence (SoE) was assessed using a modification of the GRADE method; the assessments for each domain considered in assigning the overall SoE 

grade are provided in Appendix G for each outcome; RCT outcomes were compared with observational study outcomes, when available, to contribute to the 

“consistency” domain; c

Meta-analysis results are shown for all outcomes for which studies were pooled; remaining conclusions are based on trends across studies; d

Any n-3 FA refers to a pooled analysis of studies that employed any or unspecified n-3 FA; e

RCTs determined to be too heterogeneous to permit pooling.

AA = arachidonic acid; ALA = alpha linolenic acid; CI = confidence interval; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; IUGR = intrauterine 

growth retardation; n-3 FA = omega-3 fatty acid; OR odds ratio; RCT = randomized controlled trial; SGA = small for gestational age; VEP = visual evoked 

potentials; WMD = weighted mean difference

ES-24
Limitations 

Within each category of analysis (by outcome, target of intervention, n-3 FA, and study 

design), studies we identified for this review (like the studies included in the original review) 

diverged greatly with respect to the sources, doses, and durations of interventions; definitions or 

tests used to measure outcomes; and follow-up times. For outcomes such as visual, neurological, 

and cognitive development, by necessity, the tests used over time (in studies with multiple 

follow-ups) changed to match maturity level. As a result, it was challenging to identify groups of 

studies that were sufficiently similar to pool, even with studies from the original report. In 

addition, many RCTs employed and reported the results of numerous outcome measures, which 

were often internally inconsistent or showed no apparent pattern over time. The majority of 

studies did not find statistically significant findings. Although one of the charges for the current 

report was to include observational studies that were excluded from the original report when 

sufficient numbers of RCTs reported on similar outcomes, only a small number of observational 

studies that were excluded from the original report met the inclusion criteria for the current 

report, and the observational studies identified for the current report seldom assessed outcomes 

that were similar to those assessed in RCTs.

Overall, both RCTs and observational studies included in this review had numerous quality 

concerns that increased the risk for bias. Across RCTs, the most common risk-of-bias limitation 

was a lack of intention-to-treat analyses (54 percent of the included RCTs). Of included RCTs, 

36 percent failed to describe allocation concealment sufficiently to determine whether it was 

adequate (and many studies failed to describe recruitment methods). Blinding of study 

participants contributed only slightly to potential risk of bias because participants were usually 

infants or children and outcomes were usually clinically apparent or assessed in a clinical 

laboratory. Thirty-seven percent of RCTs were at risk of attrition bias due to overall dropout 

rates greater than 20 percent, although most studies reported similar dropout rates between 

groups. Although 87 percent of the included RCTs reported similar baseline demographic 

characteristics between groups, 57 percent did not report baseline n-3 FA intake or status. This 

omission is a critical concern because baseline n-3 FA status likely affects response to changes in 

n-3 FA intake. 

Across observational studies, the most common risk of bias limitation was the lack of 

representativeness of the cohorts to the population of interest: 35 percent were judged to be 

select populations or only somewhat representative. In most cases, these populations were 

described as having high intakes of fish; in several cases, the populations were at high risk for 

the outcome of interest or another condition. Another reporting inadequacy related to the ranges 

and distribution of n-3 FA exposures. Of included observational studies, most of the n-3 FA 

dietary intake assessments included only dietary sources (not n-3 FA supplements). This issue 

does not affect the quality of biomarker data; however, so many different n-3 FA biomarkers 

were investigated across studies, that it was impossible to make comparisons. Another limitation 

of many of these studies was the inability or failure to control for potentially important 

confounding factors; this issue is magnified for long-term follow up studies.

Few studies reported adverse events, but among the 20 studies that did report adverse events, 

60 percent did not predefine or prespecify adverse events to be queried, and none used a 

recognized categorization system to prespecify or sort categories or levels of intensity of adverse 

events reported. Only 35 percent reported an active mode of collection of adverse event 

information, and of the studies that reported serious adverse events (or lack thereof), most did 

ES-25
not define “serious adverse event.” Of additional concern, studies of preterm infants often 

comingled morbidities associated with prematurity (such as bronchopulmonary dysplasia and 

retinopathy of prematurity) and adverse events that might be associated with the intervention. 

Only one study that met inclusion criteria considered whether mercury exposure could account 

for the findings on the effects of fish oil intake, but the findings were equivocal.

The population profiles differed somewhat between RCTs and observational studies. 

Understandably, a number of the RCTs were conducted in women at risk for premature birth, 

gestational hypertension, a low birth weight infant, or women with a personal or family history 

of allergy or asthma. However, most observational studies examining the associations between 

dietary n-3 FA intake or biomarkers of n-3 FA intake and birth, respiratory, allergy, or 

developmental outcomes were conducted in generally healthy populations. Most RCTs were also 

small in size, although most reported doing power calculations. Observational studies that 

enrolled fewer than 250 were excluded by design. 

Study interventions or measured exposures tended to be highly heterogeneous. Studies that 

labeled themselves as studies of DHA alone often included some amount of EPA as well as n-6 

FA (usually AA). Fish oil studies did not always report the oil’s concentration of n-3 and n-6 FA 

in addition to the one of interest. Few studies assessed the effects of EPA alone and only one 

study assessed the effects of ALA alone. Of most concern was the heterogeneity in the 

description of the n-3 and n-6 FA contents of infant formulas and the systematic lack of 

assessment of formula intake (realizing the difficulty of this measurement in human infants). 

Few trials compared n-3 FA dose, formulation (e.g., ratio of EPA to DHA), or source. No trial 

compared different n-3 to n-6 FA ratios of supplements or intake. None of the observational 

studies attempted to determine a threshold effect of any associations between n-3 FA and the 

outcome of interest. Some observational studies failed to report median or range data of n-3 FA 

levels within quantiles, confidence intervals (or equivalent) of association hazard ratios, or 

conducted only linear analyses across a full range of n-3 FA values. In addition, studies varied in 

the range of n-3 FA status (e.g., intake level) within each study. The applicability of many of the 

observational studies to the U.S. population may also be limited by the higher baseline intakes of 

fish and other n-3 FA-containing foods and supplements among the populations in these studies.

Among studies that assessed associations between biomarkers of n-3 FA status and an 

outcome of interest, so many different n-3 FA biomarkers were investigated, that it was 

impossible to make comparisons across studies.

As mentioned above, another limitation of many of the studies was the inability or failure to 

control for potentially confounding factors. Observational studies often corrected for a large 

number of potential confounders, but many important factors could not be or were not measured;

this issue is magnified for long-term follow up studies of cognitive development, where 

environmental factors were seldom considered. RCTs that reported cognitive outcomes at longterm follow up also rarely controlled for potential confounders, although they did report baseline 

data on characteristics such as SES and parent education, which were usually statistically similar 

among placebo and intervention groups.

For the outcomes related to infant and child development (except for growth patterns), tests 

used to measure most outcomes were numerous and heterogeneous across studies regardless of 

the study designs, and follow-up times varied widely. As a result, studies for a number of 

outcomes of interest could not be pooled, either with studies identified for the original report or 

with newly identified studies. In addition, the multiplicity of measures all but ensured that some 

outcome measure would produce a significant effect. Understandably, studies of cognitive, 

ES-26
neurological, and visual acuity development with multiple follow-up points were required to use 

age/stage-appropriate outcome measures, but they seldom attempted to account for these changes 

in outcome measures.

The RCTs and observational studies also differed in a number of ways regarding 

interventions and exposures, making it difficult to compare outcomes across the two study 

designs. Of note, the doses of n-3 FA supplements in RCTs were often much higher than the 

highest intake reported for observational studies. Furthermore, not all observational studies 

explicitly included n-3 FA supplements in their assessment of intake, and almost none of the 

RCTs attempted to account for background fish or n-3 FA intake as an effect modifier. 

For a very small number of RCTs where no significant differences in outcomes were 

observed between intervention and placebo treatments, posthoc analysis found an association 

between a biomarker of n-3 FA and the outcome of interest. This observation would seem to 

suggest that the apparent lack of effect of the intervention on the outcome of interest might be 

attributable to the participants having had adequate baseline n-3 FA status. However the number 

of studies that conducted these follow-up analyses was too small to draw definitive conclusions. 

Likewise, very few RCTs assessed or reported baseline dietary intakes of n-3 FA or biomarker 

status.

Finally, due to the significant heterogeneity across studies, the interpretation of overall metaanalysis results is limited. Only a small number of RCTs conducted dose response assessments 

(usually with poor results). For those reasons, we did not attempt to do dose-response metaanalysis of observational studies and performed only a small number of meta-regressions on 

dose-response across RCTs. 

Future Research Recommendations

The design of future RCTs should attempt to determine whether particular populations or 

individuals are more likely to benefit from n-3 FA supplements or fortified formulas, e.g., 

individuals with relatively low baseline intakes of n-3 FA. Therefore, studies need to measure—

and match intervention groups according to—baseline n-3 FA biomarker status (although the 

current report has not clearly revealed the most relevant biomarkers). Researchers need to reach 

consensus on standardized formulations and on reporting of concentrations for interventions. The 

results of this review should help guide these decisions.

Studies also need to ascertain whether n-3 FA are more effective in individuals at increased 

risk for particular conditions (such as low birth weight, preterm birth, gestational hypertension, 

or, for infants, risk for delayed visual acuity development or atopy).

Some recent evidence suggests that individuals’ abilities to benefit from dietary 

supplementation with n-3 FA (or breastfeeding) is influenced by polymorphisms within the gene 

encoding FADs2, an enzyme involved in the desaturation of fatty acids to convert precursors to 

LCPUFAs such as DHA. If these findings are confirmed, future studies may need to perform 

genetic profiles on potential participants and to exclude those who are genetically incapable of 

responding to supplementation.

Finally, identifying the most promising and clinically relevant outcome measures will be 

important to expanding the strength of the evidence base for the effectiveness of supplemental n3 FA for maternal and childhood outcomes. The findings of large cohort studies are still needed 

to assess the potential role of n-3 FA status in the risk for conditions such as autism spectrum 

disorder, learning disabilities, and ADHD; however, it may be necessary first to identify clear 

intermediate risk factors for these conditions, because the length of follow-up needed for 

ES-27
diagnosis of the conditions themselves greatly increases the potential interference of other 

confounding factors. 

Conclusions

Most studies identified for this report examined the effects of fish oil (or other combinations 

of DHA and EPA) supplements on pregnant or breastfeeding women or the effects of infant 

formula fortified with DHA plus arachidonic acid. With the exception of small effects on birth 

weight and length of gestation (confirming the findings of the original report), n-3 FA 

supplementation or fortification has no consistent evidence of effects on peripartum maternal or 

infant health outcomes. No effects of n-3 FA were seen on gestational hypertension, peripartum 

depression, or postnatal growth. Apparent effects of n-3 FA supplementation were inconsistent 

across assessment methods and followup times for outcomes related to infant visual acuity and 

cognitive development and prevention of allergy and asthma. No association was seen between 

n-3 FA exposures and the risk for autism spectrum disorders. Evidence was insufficient to draw 

conclusions regarding effects of n-3 FA on or associations of n-3 FA exposures with ADHD and 

learning disabilities. Future RCTs need to assess standardized preparations of n-3 and n-6 FA, 

using a select group of clinically important outcomes, on populations with baseline n-3 FA 

intakes typical of those of most western populations.

ES-28
References

1. Institute of Medicine of the National Academies. 

Dietary reference intakes for energy, carbohydrate, 

fiber, fat, fatty acids, cholesterol, protein, and amino 

acids / Panel on Macronutrients, Panel on the 

Definition of Dietary Fiber, Subcommittee on Upper 

Reference Levels of Nutrients, Subcommittee on 

Interpretation and Uses of Dietary Reference Intakes, 

and the Standing Committee on the Scientific 

Evaluation of Dietary Reference Intakes, Food and 

Nutrition Board. Available at: 

http://www.nal.usda.gov/fnic/. The National 

Academies Press. Washington, DC: 2005.

2. Lewin GA, Schachter HM, Yuen D, et al. Effects 

of omega-3 fatty acids on child and maternal health. 

Evidence report/technology assessment. 2005 

Aug;(2005)(118):1-11.

3. Gould JF, Makrides M, Colombo J, et al. 

Randomized controlled trial of maternal omega-3 

long-chain PUFA supplementation during pregnancy 

and early childhood development of attention, 

working memory, and inhibitory control. Am J Clin 

Nutr. 2014 Apr;99(4):851-9. PMID: 24522442.

4. . Methods Guide for Effectiveness and 

Comparative Effectiveness Reviews. AHRQ 

Publication No. 10(14)-EHC063-EF. Rockville, MD: 

Agency for Healthcare Research and Quality. January 

2014. Chapters available at: 

www.effectivehealthcare.ahrq.gov.

5. American College of Obstetricians, 

Gynecologists. Committee on Obstetric, Practice. 

Committee opinion no. 453: Screening for depression 

during and after pregnancy. Obstet Gynecol. 2010 

Feb;115(2 Pt 1):394-5. PMID: 20093921.

6. Higgins JP, Altman DG, Gotzsche PC, et al. The 

Cochrane Collaboration's tool for assessing risk of 

bias in randomised trials. BMJ. 2011;343:d5928. 

PMID: 22008217.

7. Wells G, Shea B, O'Connell J, et al. The 

Newcastle-Ottawa Scale (NOS) for assessing the 

quality of nonrandomised studies in meta-analysis. 

2010. 

http://www.ohri.ca/programs/clinical_epidemiology/

oxford.asp. Accessed on May 5 2014.

8. Lichtenstein AH, Yetley EA, Lau J. Application 

of systematic review methodology to the field of 

nutrition. J Nutr. 2008 Dec;138(12):2297-306. 

PMID: 19022948.

9. Chung M, Balk EM, Ip S, et al. Reporting of 

systematic reviews of micronutrients and health: a 

critical appraisal. Am J Clin Nutr. 2009 

Apr;89(4):1099-113. PMID: 19244363.

10. Newberry SJ, Chung M, Shekelle PG, et al. 

Vitamin D and Calcium: A Systematic Review of

Health Outcomes (Update). Evidence 

Report/Technology Assessment No. 217. (Prepared 

by the Southern California Evidence-based Practice 

Center under Contract No. 290-2012-00006-I.) 

AHRQ Publication No. 14-E004-EF. Rockville, MD: 

Agency for Healthcare Research and Quality. 

September 2014.

11. Hartung J. An alternative method for metaanalysis. Biometrical Journal. 1999;41(8):901-16. 

PMID: 15206538.

12. Hartung J, Knapp G. A refined method for the 

meta-analysis of controlled clinical trials with binary 

outcome. Stat Med. 2001 Dec 30;20(24):3875-89. 

PMID: 11782040.

13. Sidik K, Jonkman JN. Robust variance 

estimation for random effects meta-analysis. 

Computational Statistics & Data Analysis. 

2006;50(12):3681-701.

14. Sánchez-Meca J, Marín-Martínez F. Confidence 

intervals for the overall effect size in random-effects 

meta-analysis. Psychol Methods. 2008 Mar;13(1):31-

48. PMID: 18331152.

15. Higgins JP, Thompson SG, Deeks JJ, et al. 

Measuring inconsistency in meta-analyses. BMJ. 

2003 Sep 6;327(7414):557-60. PMID: 12958120.

ES-25
16. R Core Team (2015). R: A language and 

environment for statistical computing. Vienna, 

Austria: Computing RFfS. http://www.R-project.org/.

17. Makrides M, Gibson RA, McPhee AJ, et al. 

Effect of DHA supplementation during pregnancy on 

maternal depression and neurodevelopment of young 

children: a randomized controlled trial. JAMA. 2010 

Oct 20;304(15):1675-83. PMID: 20959577.

ES-26
Introduction

The omega-3 fatty acids (n-3 FA) (including alpha-linolenic acid [ALA], stearidonic acid 

[SDA], eicosapentaenoic acid [EPA], docosapentaenoic acid [DPA], and docosahexaenoic acid 

[DHA]) are a group of essential long-chain and very-long-chain polyunsaturated fatty acids (LCPUFA) that are involved in the eicosanoid pathway and are incorporated into cell membranes. 

Eicosanoids (including prostaglandins, thromboxanes, and leukotrienes) have wide ranges of 

physiologic effects and play a key role in inflammation regulation. The metabolic pathway of n-3 

FA is shown in Figure 1. ALA is the simplest n-3 FA, from which all other n-3 FA are 

metabolically derived. ALA must come from the diet, as it cannot be made by the body. ALA is 

found in plant foods, such as leafy green vegetables, nuts, and vegetable oils such as canola, soy, 

and flaxseed. SDA can be formed from ALA via Δ6-desaturase, the rate-limiting enzyme in the 

pathway. When SDA enters the metabolic pathway, it is rapidly converted to EPA. EPA can be 

converted to DPA and vice versa. The rates of conversion from ALA to EPA or DHA are highly 

variable. Good sources of EPA and DHA in the diet include fin fish, other seafood, other marine 

sources, and organ meats.

Figure 1. Metabolic pathway of omega-3 fatty acids

ALA = Alpha (α)-linolenic acid; DHA = Docosahexaenoic acid; DPA = Docosapentaenoic acid; EPA = Eicosapentaenoic acid; 

SDA = Stearidonic acid; n-3 = Omega-3 fatty acids 

A role for n-3 FAs in prenatal and postnatal growth and development and risk for certain 

chronic diseases has been suggested by a variety of evidence from prospective cohort studies and 

randomized controlled trials (RCTs). In 2002, the Institute of Medicine (IOM) considered the 

1
evidence inadequate to establish an estimated average requirement (EAR) for n-3 FAs.1 Thus, in 

the absence of sufficient evidence, the IOM set only Adequate Intake values (AIs), based on 

current population intake in the apparent absence of deficiency symptoms.a The IOM set the 

following AIs for n-3 FA (ALA, whose primary dietary sources are plant foods and algae) for 

healthy pregnant women and children:

Pregnant women: 1.4 grams (g)/day (d) of ALA

Infants (≤12 months): 0.5 g/d of n-3 FAs

Children (1 to 3 years): 0.7g/d of ALA

Children (4 to 8 years): 0.9 g/d of ALA

In 2004, at the request of the National Institutes of Health’s (NIH) Office of Dietary 

Supplements (ODS), three Evidence-based Practice Centers (EPCs) conducted 11 systematic 

reviews (SRs) of the evidence for the health effects of n-3 FAs. Included among these SRs was 

one that encompassed outcomes related to the health of pregnant women and their children.2

Maternal outcomes included the risk for pregnancy hypertension and preeclampsia. Child health 

outcomes included risk for preterm birth, intrauterine growth retardation (IUGR) (small-forgestational age and low birth weight); birth weight, length, and head circumference; neurological 

development; visual function in the first year of life; and various indices of cognitive 

development. This review found insufficient evidence to draw definitive conclusions about the 

effects of n-3 FA on maternal or child outcomes. Since the original review, many new studies 

and a number of SRs have examined the role of n -3 FAs in these outcomes. In addition, recent 

studies have suggested a potential role for n-3s in some related outcomes, e.g., the development 

of attention and working memory.3

Scope and Key Questions

Scope of the Review

The NIH ODS has a long history of commissioning AHRQ-based systematic reviews and 

research methodology reports for nutrient-related topics 

(http://ods.od.nih.gov/Research/Evidence-Based_Review_Program.aspx). The original 2005 

systematic review2 did not reach strong scientific conclusions for many of the outcomes of 

interest, most likely related, at least in part, to the fact that some n-3 FA exposures were from 

fish and other marine sources, some were from dietary supplements, some were indirect (through 

breast milk), and many studies did not assess biomarkers. In addition, for outcomes of interest 

for which RCTs were available, observational studies were not considered, whereas for outcomes 

for which RCTs were unavailable or could not be conducted, the authors relied on observational 

studies of varying design. Studies of different designs each have their own strengths and 

weakness that may result in differences in conclusions. For example, observational studies based 

on self-reported dietary assessments (e.g., food frequency questionnaires) may inaccurately 

estimate n-3 FA intake; RCTs of specific fish or other n-3 FA-rich food may impose an artificial 

dietary pattern that might not be applicable to the general population; RCTs of supplements 

might not fully account for differences in background n-3 FA intake; studies using either study 

a The use of an AI instead of an EAR indicates the need for more research to determine, with confidence, the mean 

and distribution of requirements for that nutrient; AIs are based on much less data and more scientific judgment than 

are EARs.

2

 
design may have subtle differences in eligibility criteria, e.g., length of follow-up period, or 

inclusion of ALA, EPA, and DHA or only EPA and DHA, that significantly impacted the final 

conclusions. 

The current systematic review has four aims: 1) to update the original review on the topic of 

the effects of n-3 FAs on maternal and child outcomes(Lewin, 2005),

2 2) to identify the literature 

for several additional outcomes of interest (see below) not included in the original review; 3) to 

include prospective observational studies that were excluded from the original report when two 

or more RCTs were identified for an outcome of interest; and 4) to use this new review to collect 

additional information that would enhance the usefulness of this report for policy and clinical 

applications. Therefore, it is of interest to systematically compare results across different 

exposure/intervention products and study types (e.g., interventional vs. prospective cohort 

studies), and to account for differences in background n-3 FA intake.

This update includes the addition of seven new outcomes: (maternal) ante- and postnatal 

depression, and pediatric attention deficit hyperactivity disorder (ADHD), autism spectrum 

disorders (ASD), learning disabilities, atopic dermatitis, allergies, and respiratory disorders, 

specifically looking at the risk for (or prevention of) these conditions in otherwise healthy 

individuals and their offspring, rather than the efficacy of n-3 FA in treating affected individuals. 

The additional outcomes may present several challenges: a limited literature base; the need to 

rely largely, if not completely, on population-based cohort studies (RCTs are likely to be rare, 

and case-control studies are inadequate to address these issues); and the need to assess and 

distinguish the effects of potential maternal and postnatal exposures on postnatal outcomes. 

Furthermore, there are ongoing concerns in the scientific community regarding systematic biases 

and random errors in the determination of n-3 FA intakes from dietary and supplement sources, 

using currently available assessment tools. The limitations of the current methods have been 

discussed elsewhere.4, 5 To date, no alternate methods are available. Until “error-free” or “biasfree” methodologies are developed, it is crucial to evaluate the available data with the 

methodological quality and the limitations in mind. Nutrient biomarkers can provide an objective 

measure of dietary status. However, the correspondence between intake and biomarker 

concentration reflects not only recent intake but subsequent metabolism (e.g., elongation, 

desaturation, metabolism to bioactive compounds). Current biomarkers used to estimate n-3 

polyunsaturated fatty acids intakes include ALA, EPA, SDA, and DHA, and are measured in 

adipose tissue, erythrocytes, plasma, or plasma phospholipids, placenta, and umbilical cord.6, 

7

Adipose tissue FAs are thought to reflect long-term intake, erythrocytes FAs are thought to 

reflect the previous 120-day intake, and plasma FAs are thought to reflect more immediate 

intake.7

The 2005 review screened 2,049 abstracts, of which 117 articles (describing 89 studies) were 

included. Of the 89 studies, 63 were RCTs and 26 were observational studies. This current 

systematic review updated the outcomes included in the previous review and expanded the scope 

to include additional maternal (risk for perinatal depression) and childhood (risk for ADHD, 

autism, learning disabilities, allergy, and respiratory conditions) outcomes. Moreover, the current 

review systematically evaluated possible reasons for inconsistencies between observational and 

RCT findings by tabulating causality-related study features such as the Bradford Hill criteria.8

Key Questions 

The Key Questions address both issues of efficacy (i.e., causal relationships from trials) as 

well as associations (i.e., prospective cohort study results and outcomes or risk factors from 

3
RCTs for which the randomization may not be applicable). Compared with the Key Questions 

from the 2005 report, they expand the scope of the review to include additional maternal and 

child outcomes, as noted above and described below (shown in bold face). 

Key Question 1: Maternal Exposures

– What is the efficacy of maternal interventions involving—or 

association of maternal exposures to—n-3 FA (EPA, DHA, EPA+DHA 

[long-chain n-3 FA], DPA, ALA, SDA or total n-3 FA) on the following: 

• duration of gestation in women with or without a history of preterm 

birth (less than 37 weeks gestation), 

• incidence of preeclampsia/eclampsia/gestational hypertension in 

women with or without a history of preeclampsia/ eclampsia/ 

gestational hypertension

• Incidence of birth of small-for-gestational age human infants

• Incidence of ante- and/or postnatal depression in women with 

or without a history of major depression or postpartum 

depression*

– What are the associations of maternal biomarkers of n-3 intake during 

pregnancy and the outcomes identified above?

– What are the effects of potential confounders or interacting factors 

(such as other nutrients or use of other supplements, or smoking 

status)?

– How is the efficacy or association of n-3 FA on the outcomes of 

interest affected by the ratio of different n-3 FAs, as components of 

dietary supplements or biomarkers? 

– How does the ratio of n-6 FA to n-3 FA intakes or biomarker 

concentrations affect the efficacy or association of n-3 FA on the 

outcomes of interest?

– Is there a threshold or dose-response relationship between n-3 FA 

exposures and the outcomes of interest or adverse events?

– How does the duration of the intervention or exposure influence the 

effect of n-3 FA on the outcomes of interest?

4
Key Question 2: Fetal/childhood exposures

– What is the influence of maternal intakes of n-3 fatty acids or the n-3 

fatty acid content of maternal breast milk (with or without knowledge 

of maternal intake of n-3 FA) or n-3 FA-supplemented infant formula 

or intakes of n-3 FA from sources other than maternal breast milk or 

supplemented infant formula on the following outcomes in term or 

preterm human infants? 

• Growth patterns

• Neurological development

• Visual function

• Cognitive development

• Autism

• Learning disorders

• ADHD

• Atopic dermatitis

• Allergies

• Respiratory illness

– What are the associations of the n-3 FA content or the n-6/n-3 FA 

ratio of maternal or fetal or child biomarkers with each of the 

outcomes identified above?

Key Question 3: Maternal or childhood adverse events:

– What are the short and long-term risks related to maternal intake of n3s during pregnancy or breastfeeding on

• Pregnant women

• Breastfeeding women

• Term or preterm human infants at or after birth

– What are the short and long-term risks associated with intakes of n3s by human infants (as maternal breast milk or infant formula 

supplemented with n-3 FA)?

– Are adverse events associated with specific sources or doses? 

Analytic Frameworks

To guide the assessment of studies that examine the association between n-3 FA 

intake/exposure and the maternal and childhood outcomes of interest, we have created two 

analytic frameworks (Figures 2 and 3) that map the specific proposed linkages associating the 

populations of interest, the exposures, modifying factors, and outcomes of interest. The 

framework graphically presents the key components of the study questions presented above and 

further described in the Methods section, below. 

5
1. Who are the participants (i.e., what is the population and setting of interest, including 

the diseases or conditions of interest)? 

2. What are the interventions? 

3. What are the outcomes of interest (intermediate and health outcomes)?

4. What study designs are of value? 

Specifically, this analytic framework depicts the chain of logic that evidence must support to link 

the intervention (exposure to n-3 FA) to improved health outcomes.

6
Figure 2. Analytic framework for n-3 fatty acids in maternal health

Populations of interest, Exposure, Outcomes, and Effect modifiers are described. Solid 

connecting arrows indicate associations and effects reviewed in this report.

POPULATIONS OF INTEREST

“Healthy” pregnant women with or without a history of:

• A previous preterm birth or a birth of an infant small for 

gestational age, or

• Gestational hypertension, preeclampsia, or eclampsia

MATERNAL INTAKE OF OMEGA-3 FATTY ACIDS

• Route of delivery: supplementation and/or diet

• Type (EPA, DHA, ALA), source (e.g., marine, plant) and amount 

(e.g., dose, serving size) of omega-3 fatty acid content

• Length of intervention/exposure

FATTY ACID CONTENT OF BIOMARKERS

• Source: mother’s blood

• Type: e.g., red blood cells (erythrocytes), etc.

• Fatty acid content: EPA, DHA, AA, AA/EPA, AA/DHA, 

AA/EPA+DHA

EFFECT 

MODIFIERS

• E.g., omega-6/

omega-3 fatty 

acid content on 

background 

diet CLINICAL OUTCOMES

• Duration of gestation

• Infants born small for gestational age

• Gestational hypertension, preeclampsia, or 

eclampsia

• Adverse effects

• Ante- and postnatal depression

Note: This framework concerns the effect of n-3 FA exposure (as a supplement or from food sources) on maternal health 

outcomes. Populations of interest, Exposure, Outcomes, and Effect modifiers are described. Solid connecting arrows indicate 

associations and effects reviewed in this report. 

ALA = alpha-linolenic acid, CAD = coronary artery disease, CHF = congestive heart failure, CKD = nondialysis-dependent 

chronic kidney disease, DHA = docosahexaenoic acid, DPA = docosapentaenoic acid, EPA = eicosapentaenoic acid, n-3 FA = 

omega-3 fatty acid(s); SDA = stearidonic acid.

7
Figure 3. Analytic framework for n-3 fatty acids in child health

Populations of interest, Exposure Outcomes, Effect modifiers were listed. Solid connecting 

arrows indicate associations and effects reviewed in this report.

POPULATIONS OF INTERST

“Healthy” term or preterm infants

CHILD INTAKE OF OMEGA-3 FATTY ACIDS

• Timing: during pregnancy vs post-delivery

• Route of delivery: via umbilical cord & placenta, mother’s milk, child’s 

supplementation (e.g., formula) &/or diet

- With vs without mother’s intake via diet &/or supplementation during pregnancy &/

or breastfeeding

• Type (EPA, DHA, ALA), source (e.g., mother’s milk, marine, plant) and amount (e.g., 

dose, serving size) of omega-3 fatty acid content

• Length of intervention/exposure

FATTY ACID CONTENT OF BIOMARKERS

• Source: mother(e.g., venous/umbilical cord, placenta, 

blood), child (e.g., arterial/umbilical cord)

• Type: e.g., ed blood cells (erythrocytes), etc.

• Fatty acid content: EPA, DHA, AA, AA/EPA AA/DHA, 

AA/EPA+DHA

CLINICAL OUTCOMES

• Growth patterns

• Neurological development

• Cognitive development

• Visual function

• Adverse effects

• Autism

• Learning disorders

• ADHD

• Atopic dermatitis

• Allergies

• Respiratory illness

EFFECT MODIFIER

E.g., omega-6/oega3 fatty acid content 

of background diet

Note: This framework concerns the effect of n-3 FA exposure (as a supplement or from food sources) on infant health outcomes. 

Populations of interest, Exposure, Outcomes, and Effect modifiers are described. Solid connecting arrows indicate associations

and effects reviewed in this report. 

ALA = alpha-linolenic acid, CAD = coronary artery disease, CHF = congestive heart failure, CKD = nondialysis-dependent 

chronic kidney disease, DHA = docosahexaenoic acid, DPA = docosapentaenoic acid, EPA = eicosapentaenoic acid, SDA = 

stearidonic acid.

8
Methods

The present review evaluates the effects ofn-3 FAs (including EPA, DHA, DPA, ALA, SDA, 

and n-3 biomarkers) on—and the associations between n-3 FA and—maternal and child health 

outcomes. The Evidence-based Practice Center (EPC) conducted the review of the published 

scientific literature using established methods as outlined in the Agency for Healthcare Research 

and Quality (AHRQ)’s Methods Guide for Comparative Effectiveness Reviews.9

This review was conducted in parallel with a systematic review of n-3 FA and cardiovascular 

disease, conducted by another EPC. Several aspects of the reviews are being coordinated, 

including eligibility criteria regarding interventions and exposures, search strategies, structure of 

the reviews, and assessments of the studies’ risk of bias, strength of the bodies of evidence, and 

abstraction of study characteristics needed to assess causality. 

Topic Refinement and Review Protocol

We convened a Technical Expert Panel (TEP) to help refine the research questions and 

protocol. The TEP included international experts in n-3 FA research, academic pediatricians, an 

obstetrician-gynecologist who represents the American Congress of Obstetricians and 

Gynecologists, and a pediatrician who represents the American Academy of Pediatrics. Also 

included in the discussions with the TEP were the ODS Director of and a Senior Scientist and the 

AHRQ Task Order Officer. We discussed the Key Questions, analytic framework, study 

eligibility criteria, literature searches, and analysis plans. In addition, in separate discussions with 

the ODS representative and our TOO we considered how and whether to assess the concept of 

causality, particularly for the observational studies. After discussion of the Bradford Hill criteria 

and related issues regarding causality,8 we agreed to provide the study-level data for items that 

may be pertinent for users of this report to assess causality (this information is included in the 

Evidence tables in Appendixes C and D).

Furthermore, we had joint discussions with the Brown University EPC—which conducted 

the parallel report on n-3 FA and cardiovascular disease —and our TOO and the ODS 

representative to coordinate our protocols and processes. The protocol was entered into the 

PROSPERO register (registry number CRD42015020638).

Literature Search

Search Strategy

We modified the existing search strategies from the original report (see Appendix A) to 

include a complete set of terms for the new outcomes of interest based on searches we have 

conducted on these topics for previous reviews and consultation with colleagues. We conducted 

literature searches in Medline (Pubmed), Embase, the Cochrane Collection, Web of Science and 

CAB. For the topics of depression; ADHD; autism; and cognitive, neurological, and visual 

function development, we searched PsychInfo. We did not search for unpublished (grey) 

literature; however, a notice was published in the Federal Register requesting unpublished data 

from manufacturers of omega-3 fatty acid-fortified infant formulae and dietary supplements. 

Search dates for all topics were January 1, 2000 to August 24, 2015. For the newly added topics, 

we “reference mined” articles that we identified to determine whether any studies conducted and 

published prior to 2000 should be obtained and included. Search results were crosschecked with 

the list of studies included in the original report (as well as the list of prospective cohort studies 

9
excluded from the original report that must now be included) to ensure that no studies included 

in the original report are inadvertently included in the current report as “new” studies. 

Appendix A displays the current complete search strategy.

Inclusion and Exclusion Criteria

The current eligibility criteria are mostly similar to the criteria used in the original 2005

review. The populations are expanded to accommodate the expanded outcomes of interest. The 

interventions and exposures remain the same as those in the original report, with the addition of 

two n-3 FA (DPA and SDA). Included study designs have been modified slightly.

The Eligibility Criteria are outlined here according to the PICOT framework, with 

indications of the Key Questions to which they apply.

• Population(s): 

o Key Question (KQ) 1(Maternal exposures and outcomes)

 Healthy pregnant women (for outcomes of birth weight, intrauterine 

growth restriction/small for gestational age, duration of gestation, risk of 

pre-eclampsia, eclampsia, or pregnancy hypertension)

 Pregnant women with a history of pre-eclampsia, eclampsia, or pregnancy 

hypertension (only for outcome of risk of pre-eclampsia, eclampsia, or 

pregnancy hypertension)

 Pregnant women with a history of major depressive disorder or postpartum 

depression (only for the outcome of risk for peripartum depression)

o Key Question 2 (In utero and postnatal (through the first year of life) exposures 

and outcomes)

 Healthy preterm or full term infants of healthy women/mothers whose n-3 

fatty acid exposures were monitored during pregnancy 

 Breastfed infants of healthy mothers whose n-3 fatty acid exposure was 

monitored and/or who participated in an n-3 fatty acid intervention during 

breastfeeding beginning at birth

 Healthy preterm or full term infants with and without family history of 

respiratory conditions (for outcomes related to atopic dermatitis, allergy, 

respiratory conditions) of mothers whose n-3 exposures were monitored 

during pregnancy and/or breastfeeding

 Healthy children or children with a family history of a respiratory 

disorder, a cognitive or visual development disorder, autism spectrum 

disorder, ADHD, or learning disabilities, age 0 to 18 years who 

participated in an n-3 fatty acid-supplemented infant formula intervention 

or an n-3 supplementation trial during infancy 

o Key Question 3 (Adverse events associated with n-3 interventions)

 Healthy pregnant women or pregnant women in the other categories 

described above

 Offspring of women enrolled in an n-3 fatty acid intervention during 

pregnancy 

 Offspring of women whose exposure to n 3 fatty acids was assessed 

during pregnancy

 Children whose exposure to n-3 fatty acids (through breast milk, infant 

10
formula, or supplementation) was monitored during the first year of life 

• Interventions/Exposures: 

o Interventions (KQ1, 2, 3 unless specified): 

 N-3 fatty acid supplements (e.g., EPA, DHA, ALA, singly or in 

combination; 

 N-3 fatty acid supplemented foods (e.g., eggs) with quantified n-3 content

 High-dose pharmaceutical grade n-3 fatty acids, e.g., Omacor®, Ropufa®, 

MaxEPA®, Efamed, Res-Q®, Epagis, Almarin, Coromega, Lovaza®, 

Vascepa® (icosapent ethyl)

• Exclude doses of more than 6g/d, except for trials that report 

adverse events

 N-3 fatty acid fortified infant formulae (KQ2,3)

• E.g., Enfamil® Lipil®; Gerber® Good Start DHA & ARA®; 

Similac® Advance®

• N-3 fortified follow-up formulae

• Exclude parenterally administered sources

 Marine oils, including fish oil, cod liver oil, and menhaden oil with 

quantified n-3 content

 Algal or other marine sources of omega-3 fatty acids with quantified n-3 

content

o Exposures (KQ1,2)

 Dietary n-3 fatty acids from foods if concentrations are quantified in food 

frequency questionnaires

 Breast milk n-3 fatty acids (KQ2)

 Biomarkers (EPA, DHA, ALA, DPA, SDA), including but not limited to 

the following:

• Plasma fatty acids

• Erythrocyte fatty acids

• Adipocyte fatty acids. 

• Comparators: 

o Inactive comparators:

 Placebo (KQ1, 2, 3)

 Non-fortified infant formula (KQ2)

o Active comparators

 Different n-3 sources 

 Different n-3 concentrations (KQ1, 2, 3)

 Alternative n-3 fortified infant formulae (KQ2)

 Soy-based infant formula (KQ2)

 Diet with different level of Vitamin E exposure 

• Outcomes:

o Maternal outcomes (KQ1)

 Blood pressure control

• Incidence of gestational hypertension

• Maternal blood pressure

11
• Incidence of pre-eclampsia, eclampsia

 Peripartum depression

• Incidence of antepartum depression10

• Incidence of postpartum depression, e.g., 

o Edinburgh Postnatal Depression scale

o Structured Clinical Interview (SCI)

 Gestational length

• Duration of gestation

• Incidence of preterm birth

 Birth weight

• Mean birth weight

• Incidence of low birth weight/small for gestational age

o Pediatric Outcomes (KQ2)

 Neurological/visual/cognitive development

• Visual development, e.g.,

o Visual evoked potential acuity

o Behavioral visual acuity testing

 Teller’s Acuity Card test and others

o Electroretinography

• Cognitive development, e.g., 

o Bayley’s Scale of Infant and Toddler Development Mental 

Development Index

o Griffith Mental Developmental 

Scale

o Kauffman Assessment Battery for Children

o Neonatal Behavioral Assessment

o Wechsler Scales

o MacArthur Communicative Development Inventory

o Fagan Test of Infant Intelligence

o Ages and Stages Questionnaire

o Stanford-Binet IQ



• Neurological development

o Electroencephalograms (EEGs) as measure of maturity

o Psychomotor developmental index from Bayley’s scales

o Neurological/movement impairment assessment

o Active sleep, quiet sleep, sleep-wake transition, 

wakefulness

o Nerve conduction test

o Latency Auditory evoked potential

 Risk for ADHD

• Validated evaluation procedures

o E.g., Wechsler Intelligence Scale for Children, 

o Behavioral rating scales, e.g., Connors, Vanderbilt, and 

Barkley scales 

 Risk for Autism spectrum disorders

12
• Validated evaluation procedures

o E.g., Modified Checklist of Autism in Toddlers

 Risk for learning disabilities

• Validated evaluation procedures 

 Risk for atopic dermatitis

 Risk for allergies

• Validated allergy assessment procedures, preferably challenge 

(skin prick test or validated blood tests accepted) 

 Incidence of respiratory disorders

• Spirometry in children 5 and over (peak expiratory flow rate 

[PEFR] and forced expiratory volume in 1 second [FEV1])

o Key Question 3: Adverse effects of intervention(s)

 Incidence of specific adverse events reported in trials by study arm

• Timing: 

o Duration of intervention or follow-up

 Key Question 1,3 (maternal interventions/exposures): 

• Interventions implemented anytime during pregnancy but 

preferably during the first or second trimester

• Follow-up duration is anytime during pregnancy (for maternal 

outcomes of pre/eclampsia or maternal hypertension); term (for 

outcomes related to birth weight, duration of pregnancy); or within 

the first 6 months postpartum (for the outcome of postpartum 

depression)

 Key Question 2, 3 (infant exposures): 

• Interventions implemented within one month of birth or exposures 

measured within 1 month of birth 

• Follow-up duration is 0 to 18 years 

• Settings: 

o Community-dwelling individuals seen by primary care physicians or obstetricians 

in private or academic medical practices (KQ1, 3) 

o Community dwelling children seen in outpatient health care or educational 

settings (KQ2, 3) 

We limited the study designs of interest to RCTs, prospective cohort studies, and nested case 

control studies (cross-sectional, retrospective cohort, and case study designs were excluded; 

studies must have measure of intake/exposure prior to outcome). Only peer-reviewed studies 

published in English language were included. Unpublished studies were not included.

To focus on studies of the highest relevance and quality, we also excluded observational 

studies with enrollment sizes of less than 250 unless no other studies were identified for a 

particular outcome; we also excluded studies that reported exposures only as servings of fish 

without calculating n-3 FA intakes, study size, exposure duration, or other similar criteria, if the 

number of studies identified is very large.

13
Study Selection

The DistillerSR software package was used to manage the search outputs, screening, and data 

abstraction. Title/abstract screening was conducted in duplicate (after a training session to ensure 

understanding of the inclusion and exclusion criteria and reasonable inter-rater reliability), using 

a screening form that lists the inclusion and exclusion criteria and allows selection of reasons for 

exclusion. All title selections were accepted without reconciliation for further full-text review. 

Second-level screening of full text articles was conducted by two reviewers and differences 

reconciled (the project leaders settle disagreements, if needed).

Abstracts for a subset of ten percent of titles selected from the EMBASE search were 

reviewed; based on the acceptance rate of the abstracts, it was determined that no additional 

abstracts for publications identified in the EMBASE search would be screened for inclusion. 

Reference lists of existing recent SRs on outcomes of interest were reviewed to ascertain that 

we did not miss relevant studies. 

Studies that were excluded at the full-text screening stage are listed in Appendix B with the 

reasons for exclusion. Publications identified in the searches for this report that were included in 

the original report were excluded at this stage (for purposes of tracking the literature flow) and 

are listed in Appendix B, regardless of whether they were subsequently included in analyses in 

this report.

Data Extraction

Accepted studies underwent single abstraction of study-level data and risk-of-bias assessment 

in Distiller, with audit by an experienced reviewer. Outcome data were abstracted by a 

biostatistician and audited by an experienced reviewer. We re-extracted data from studies 

included in the original report that were included in new pooled analyses as needed.

Data collection forms were designed by the project team in Distiller SR, piloted by the 

reviewers, further modified, and then the final forms piloted with a random selection of included 

studies to ensure agreement of interpretation. Studies based on large prospective cohorts were 

identified in their Distiller records to allow comparison to ensure data were not extracted in 

duplicate. Study-level data included PICOTs, baseline nutritional status/ biomarkers/other 

evidence of initial exposure to n-3 fatty acids as well as status of other nutrients that could 

influence outcomes (e.g., vitamin E), method of exposure assessment and associated margin of 

error, inclusion/exclusion criteria, study design, comorbidities, other potential effect modifiers, 

analytic methods, and characteristics necessary to assess risk of bias, including recruitment, 

blinding, allocation concealment, description of completeness of final dataset, funding source, 

and other potential conflicts of interest. 

Outcome data, including clinical outcomes and intermediate outcomes (concentrations of 

biomarkers), were abstracted in duplicate in Excel files by the biostatistician and one additional 

reviewer. At the end of the project, abstracted data will be uploaded to the Systematic Review 

Data Repository (SRDR) for full public accessibility.

Methodological Quality (Risk of Bias) Assessment of 

Individual Studies

We assessed the methodological quality of each study based on predefined criteria. Risk of 

bias among RCTs was assessed using the Cochrane Risk of Bias tool,11 which evaluates risk of 

selection bias, performance bias, detection bias, attrition bias, reporting bias, and other potential 

14
sources of bias. Risk of bias among observational studies was assessed using questions relevant 

for prospective studies from the Newcastle-Ottawa tools.12 Both tools were supplemented with 

nutrition-specific items in consultation with the TEP (e.g., those related to uncertainty of dietary 

assessment measurements and compliance).13-15 For pooled analyses with significant effect sizes, 

we assessed publication bias using the Egger’s and Begg’s tests. Studies that reported adverse 

events were also assessed for adverse event assessment and reporting using the McMaster 

Quality Assessment Scale of harms (McHarm).16 Any quality issues pertinent to specific 

outcomes within a study were noted and considered when determining the overall strength of 

evidence for conclusions related to those outcomes.

Data Synthesis/Analysis

All included studies were summarized narratively and in summary tables that show the 

important features of the study populations, design, intervention/exposure, outcomes, and results; 

we built off and improved on the tables used in the original review. Separate summary tables 

were used to describe studies that report on a particular outcome of interest.

We analyzed the results of studies of different design separately, combining them if 

appropriate, and we compared and contrasted populations, exposures, and outcomes across study 

designs, examining any differences in outcomes between interventional and observational 

studies. 

Statistical data were extracted from all trials with an outcome of interest. We considered 

meta-analyses when there were at least three trials with similar population (e.g., pregnant 

women, term infants, preterm infants), intervention (e.g., DHA, DHA+EPA, DHA+AA), followup time (e.g. birth, 12 months of age), and outcome measure. For trials that had groups with the 

same intervention but with varying doses, we averaged the outcome across doses for the main 

analysis. Forest plots were provided for random effects meta-analysis. We used the HartungKnapp-Sidik-Jonkman method for our random effects meta-analysis.(Hartung, 1999)

17 (Hartung, 

2001)

18 (Sidik, 2006)19 It has been shown that the error rates from this method are more robust 

than the previously used DerSimonian and Laird method.20 Heterogeneity was assessed using the 

I2 statistic.21 All statistical analyses were performed in R 3.2.0.22

New trial results were added to original meta-analyses, when appropriate, based on similarity 

of participants, interventions (including doses), and outcomes.9 When sufficient data were

available and clinical heterogeneity was minimal, we conducted dose-response meta-analysis 

(for observational studies) or meta-regression on doses (for RCTs) to support our qualitative 

synthesis. When new bodies of observational studies were added, possibility for random-effects 

multivariate dose-response meta-analysis was also assessed (Shekelle, 2014; Ahmadzai, 2013;

Greenland, 1992; Orsini, 2012; Hamling, 2008).23-27 For meta-analysis of data with clear outliers, 

sensitivity analyses were conducted, if appropriate to the question.

Summary of Causality-Related Study Features

Appendix I includes data related to possibility causality criteria for all included studies. The 

list of items in this table was compiled based on discussions between the EPCs and ODS after 

discussion of the Bradford Hill criteria and other issues related to determining causality.8 The 

table lists included studies with their timeframe, country, population category (pregnant, 

breastfeeding, preterm infant, term infant), baseline n-3 FA intake, n-3 FA source, n-3 FA type, 

how n-3 FA intake measured, study design (e.g., randomized controlled trial, prospective or 

15
retrospective longitudinal cohort, or other design), exposure duration, followup time, outcomes 

reported, effect sizes and types, difference in n-3 FA intake (between low and high intake 

groups), and whether outcomes were reported to be primary outcomes (vs. secondary or 

unspecified). The determination of primary outcomes was based on an explicit statement of the 

primary outcomes, the outcome used in reported power calculations, or implied by focus of the 

original article. 

Grading the Strength of Evidence (SOE) for Major 

Comparisons and Outcomes

The strength of evidence was assessed for each outcome and exposure type using the method 

outlined in the AHRQ Methods Guide9, in which the body of evidence for each outcome is 

assessed based on the following dimensions: study limitations (risk of bias), reporting bias, 

consistency (within and across study designs), and precision, as well as the number of studies by 

study design. Based on these assessments, we assigned a strength-of-evidence rating (i.e., 

insufficient, low, moderate, or high level of evidence). The data sources, basic study 

characteristics, and each strength-of-evidence dimensional rating were summarized in “Summary 

of Evidence Reviewed” tables detailing our reasoning for arriving at the overall strength of 

evidence rating (Appendix G). Applicability of studies to the populations and interventions that 

are the focus of the current review was assessed also, as described below.

Assessing Applicability

The primary basis for assessment of applicability was the similarity of average intake of n-3 

fatty acids (as fatty fish or other foods) to that of the U.S. and other healthy western populations

at baseline. Studies of healthy pregnant women and healthy infants were also judged to have

higher applicability than those enrolling women with a prior history of poor pregnancy outcomes 

or children with a family history of the conditions of interest. Studies in which the majority of 

participants were taking n-3 supplements at baseline were also rated as having lower 

applicability.

Peer Review and Public Commentary

A draft version of this report was reviewed by a panel of expert reviewers, including 

representatives from the American Academy of Pediatrics and the American College of 

Obstetrics and Gynecology and the general public. The reviewers included experts in prenatal 

and postnatal development and in the clinical effects of n-3FA and representatives of dietary 

supplement trade organizations. These experts were either directly invited by the EPC or offered 

comments through a public review process. Revisions of the draft were made, where appropriate, 

based on their comments. The draft and final reports are also reviewed by AHRQ. However, the 

findings and conclusions are those of the authors, who are responsible for the contents of the 

report.

16
Results

This section first describes the results of the literature searches, followed by the key findings, 

descriptions of the studies that met inclusion criteria, and detailed descriptions of the findings 

and synthesized outcomes for each of the Key Questions.

Results of Literature Searches

Our searches identified 3,760 titles/abstracts. An additional search of CAB resulted in 480 

titles. Twelve references were suggested by experts and 23 references were rescreened from the 

Ottawa report. This yielded 4,275 titles/abstracts that went out for dual screening, of which 3,617

titles/abstracts were excluded for the following reasons: not human (178), not omega-3 (1,611), 

not in English (1), treatment study that didn’t address prevention/risk (197), study design 

(including editorials, letters, cross sectional study design, and protocols) (178), population not of 

interest (653), omega-3 not orally taken (70), no outcomes of interest (101), does not address the 

KQ (473), only exposure/intervention was total fish intake (33), study only addressed biomarkers 

and no other outcomes of interest (2), duplicate data (3), non-systematic review background (83), 

or no abstract was indexed (34).

We reviewed 658 full text articles, of which 515 were excluded for the following reasons:

study was included in the original report (31: these articles were subsequently included in our 

analyses but that number was subtracted from the number of new articles included from our 

searches in the flow; all studies included in the original report, 117, were included in the current 

report as well, as shown in the flow diagram and in Appendix H), participants were not human 

(4), not omega-3 (53), not in English (1), treatment study only (29), study design (53), population 

not of interest (37), not oral intake (10), no outcomes of interest (75), did not address a Key 

Question (2), fish intake only (14), biomarkers only (39), duplicate data (24), no interventions of 

interest (7), non-systematic review background (58), systematic review (44), observational 

studies with less than a sample size of 250 participants (33), and no numerical data (1). A list of 

references by exclusion reason can be found in Appendix B. 

The Federal Register posting did not yield any additional materials to review for possible 

inclusion. 

We include 143 new articles in our report. Ninety-five of the articles are randomized 

controlled trials (RCTs) and 48 are observational studies. 

We break down the included studies by outcomes, which can be found below in the literature 

flow diagram below (see Figure 4). 

17
Figure 4. Literature flow diagram

AE(s)=Adverse Event(s); KQ=Key Question; RCT(s)=Randomized Controlled Trial(s); SR(s)=Systematic Review(s); TEP = 

Technical expert panel; 

18
Findings

Key Question 1: Maternal Exposures

– What is the efficacy of maternal interventions involving—or 

association of maternal exposures to—n-3 FA (EPA, DHA, EPA+DHA 

[long-chain n-3 FA], DPA, ALA, SDA or total n-3 FA) on the following:

• duration of gestation in women with or without a history of preterm 

birth (less than 37 weeks gestation),

• incidence of preeclampsia/eclampsia/gestational hypertension in 

women with or without a history of preeclampsia/ 

eclampsia/gestational hypertension

• Incidence of birth of small-for-gestational age human infants

• Incidence of ante- and/or postnatal depression in women with 

or without a history of major depression or postpartum 

depression

– What are the associations of maternal biomarkers of n-3 intake during 

pregnancy and the outcomes identified above?

– What are the effects of potential confounders or interacting factors 

(such as other nutrients or use of other supplements, or smoking 

status)?

– How is the efficacy or association of n-3 FA on the outcomes of 

interest affected by the ratio of different n-3 FAs, as components of 

dietary supplements or biomarkers?

– How does the ratio of n-6 FA to n-3 FA intakes or biomarker 

concentrations affect the efficacy or association of n-3 FA on the 

outcomes of interest?

– Is there a threshold or dose-response relationship between n-3 FA 

exposures and the outcomes of interest or adverse events?

– How does the duration of the intervention or exposure influence the 

effect of n-3 FA on the outcomes of interest?

19
Length of Gestation (or Gestational Age) and Preterm Birth

Key Findings and Strength of Evidence for Length of Gestation (or 

Gestational Age) and Preterm Birth

• Overall meta-analysis combining 12 RCTs showed that algal DHA, DHA-rich fish oil, or 

fish oil (EPA+DHA) supplementation during pregnancy significantly increased 

gestational length (Weighted mean difference [WMD] [95% CI] 0.33 [0.04, 0.62] weeks, 

I

2 = 70.6), but there were no significant effects on the incidence of preterm birth 

compared with placebo or control.

o Random-effects meta-regression found no significant linear dose-response

relationships between doses of DHA, EPA, or DHA to EPA ratio (beta coefficient 

[SE]= -0.04 [0.09], P=0.67, n=9) and the effect sizes.

• There is a moderate level of evidence that maternal supplementation with DHA or DHAenriched fish oil may increase gestational length, and a low level of evidence that 

maternal supplementation of EPA+DHA fish oils may not have significant effects on 

infants’ gestational length compared with placebo.

o Pooled analysis of 11 RCTs in healthy pregnant women found a significant 

increase in gestational length among mothers who received algal DHA or DHAenriched fish oil supplements (WMD [95% CI]=+0.34 [95% CI 0.02, 0.67] 

weeks) compared to placebo. 

o Pooled analysis of five RCTs in healthy pregnant women showed that maternal 

fish oil supplementation (EPA+DHA) had no significant effects on gestational 

length, while one RCT in at risk pregnant women found that maternal fish oil 

supplementation significantly increased the infants’ mean gestational length

compared with placebo. 

o One RCT in healthy pregnant women found no significant effects of various doses 

of EPA+DHA supplements on gestational length compared to ALA-supplemented 

controls.

o Three prospective observational studies were heterogeneous and showed mixed 

findings on the associations between maternal n-3 FA intake and birth weight.

• There is a low level of evidence that maternal supplementation of n-3 FA (DHA or 

EPA+DHA) did not have significant effects on the incidence of preterm birth.

o Pooled analysis of seven RCTs showed no significant effect of DHA or DHAenriched fish oil in healthy pregnant women on the incidence of preterm birth.

o Pooled analysis of nine RCTs (in four publications) found no effects of 

EPA+DHA supplementation in pregnant women who were at risk for preterm 

birth on the incidence of preterm birth. 

o Three prospective observational studies found no associations between maternal 

n-3 FA intake and either gestational length or risk of preterm birth.

o One prospective observational study among pregnant women with at least one 

prior spontaneous preterm delivery found no significant difference in odds of 

preterm birth when comparing the lowest quartile of maternal erythrocyte n-3 FA 

biomarker with the upper three quartiles. Only women in quartile two of 

erythrocyte n-3 FA levels had a significantly lower risk for preterm birth 

compared to those in quartile one.

20
Description of Included Studies

The original report included 15 RCTs (in 10 publications – one publication by Olsen et al.28

represented the pooled data of six different RCTs) investigating maternal intake of n-3 FA 

supplementation on infants’ gestational length. Of these studies, eleven RCTs compared fish oil 

capsules (EPA+DHA doses ranging from 0.1 to 5 g/d) with placebo (olive oil and coconut oil), 

two compared high-DHA eggs (DHA 133-184 mg/d) with regular-DHA eggs (DHA 33-35 

mg/d), one compared DHA-rich cod liver oil (1183 mg/d DHA; 803 mg/d EPA; 27.5 mg/d AA) 

with corn oil (8.3 mg/d DHA), and one compared margarine containing different amount of ALA 

and LA (ALA group: 2.82 g/d ALA and 9.02 g/d LA; control group: 0.03 g/d ALA and 10.94 g/d 

LA). Ten of the 15 RCTs did not find a significant effect of maternal n-3 FA supplementation on 

infants’ gestational length. The other five RCTs reported a significant increase in infants’ 

gestational length, comparing maternal n-3 FA supplementation (one study of high-DHA eggs 

with 133 mg/d DHA and four of fish oil supplementation with EPA+DHA ranging from 2.2. to 5 

g/d). Ten of these 15 RCTs also reported incidence of premature delivery outcome. N-3 FA 

supplementation did not have significant effects on the proportion of premature deliveries in 

these studies. Random-effects meta-analyses of eight RCTs (in three publications: again, one 

publication by Olsen et al.28 represented pooled data from six different RCTs) that compared

maternal fish oil supplementation (EPA+DHA) to placebo showed that the odds of premature 

deliveries did not differ significantly between groups (OR 0.88; 95% CI 0.62, 1.25). Similarly, 

meta-analysis of two RCTs comparing maternal intake of high-DHA eggs with regular-DHA 

eggs showed that the odds of premature deliveries did not differ significantly between groups 

(OR 0.53; 95% CI 0.13, 2.29).

The original report included only one prospective cohort study. This cohort study reported a 

positive association between plasma triglyceride AA content and gestation length. However, the 

study did not find a significant association between maternal plasma triglyceride n-3 FA and the 

length of gestation.

Fifteen new RCTs and four observational studies were identified for the current report (see 

Table 1). With the exception of one study (Harper, 2010)

29, the remainder were conducted 

among healthy, pregnant women followed until birth. The one RCT that enrolled pregnant 

women at risk for preterm labor (defined as a documented history of at least one prior singleton 

preterm delivery after spontaneous preterm labor or premature rupture of the membranes) was 

therefore excluded from the meta-analysis. Overall, we found a moderate level of evidence that 

maternal supplementation of DHA or DHA-rich fish oils may increase gestation length, but the 

dose-response relationship between DHA doses and effect sizes is still unclear. However, there is 

a low level of evidence that maternal supplementation of EPA+DHA fish oils may not have any

significant effect on infants’ gestational length compared with placebo in healthy pregnant 

women. 

Furthermore, there is a low level of evidence that maternal supplementation of any n-3 FA 

did not have a significant effect on the risk of preterm birth. 

Limited evidence from one RCT and one cohort study suggested that effects of n-3 FA on 

gestation length and risk of preterm birth may be larger in women with a history of spontaneous 

preterm deliveries.

Randomized Controlled Trials

Fifteen unique RCTs were identified for the current report. Of these, three RCTs (in five

publications) compared algal DHA supplements with placebo,30-34 nine compared DHA-rich fish 

21
oil supplementation (DHA:EPA ratio ≥5:1) with controls,35-43 three compared fish oil 

(EPA+DHA, DHA:EPA ratio <5:1) with placebo,29, 42, 44 and one compared five different doses 

of fish oil supplementation (EPA+DHA 0.1, 0.3, 0.7, 1.4 and 2.8 g/d) with ALA control (ALA 

2.2 g/d).45 Of these, one RCT compared both DHA-rich fish oil supplement and fish oil 

supplement, with placebo.42

All 15 RCTs reported gestation length as an outcome. Among these, seven RCTs also 

reported the incidence of preterm birth.29, 31-35, 37, 43 Overall meta-analysis combining 12 RCTs 

showed that algal DHA, DHA-rich fish oil, or fish oil (EPA+DHA) supplementation during 

pregnancy significantly increased gestational length compared with placebo or controls (WMD 

[95% CI] 0.33 [ 0.04, 0.62] weeks), with high heterogeneity (I2 = 70.6). (Figure 5) Randomeffects meta-regression found no significant linear dose-response relationships between doses of 

DHA (beta coefficient [SE]= 0.12 [0.26], P=0.66, n=12), EPA (beta coefficient [SE]= -0.04

[0.46], P=0.94, n=11), or the ratio of DHA to EPA (beta coefficient [SE]= -0.04 [0.09], P=0.67, 

n=9) and the effect sizes (mean differences in gestational length between n-3 FA and placebo 

groups)

Our update meta-analysis of seven RCTs (two from the original report) did not find a 

significant effect of algal DHA or DHA-rich fish oil supplementation in healthy pregnant women 

on the incidence of preterm birth compared with placebo (OR [95% CI 0.87 [0.66, 1.15]), with 

no heterogeneity (I2 = 0). Similarly, our update meta-analysis of seven RCTs (two from the 

original report) did not show a significant effect of fish oil (EPA+DHA) supplementation in 

pregnant women at risk for preterm birth on the incidence of preterm birth compared with 

placebo (OR=0.86; 95% CI 0.65, 1.15), with no heterogeneity (I2= 0) (Figure 6)

DHA

Four RCTs (in six publications) randomized healthy pregnant women between 8 and 22 

weeks of gestation to an algae-oil source of supplemental DHA (0.2 to 0.6 g/d DHA) or placebo 

(soybean, corn, or olive oil).30-34 Of these, two RCTs reported the outcome of gestational length 

in a total of 302 mothers and their infants living in the US31 and 973 mothers and their infants in 

Mexico (POSGRAD trial),32-34 and one RCT reported the outcome of preterm-premature rupture 

of membranes in a total of 253 pregnant women in Italy.30 It should be noted that, of the three 

publications from the POSGRAD trial, the publication by Ramakrishnan (2010) analyzed the 

largest number of study participants32 while the other two publications analyzed a subset of the 

trial participants.33, 34 Thus, only the results from Ramakrishnan (2010) were included in our 

meta-analysis. The two RCTs that reported a gestational length outcome both found no 

significant effect of DHA (0.4 and 0.6 g/d) supplementation on the length of gestation compared 

with placebo. Furthermore, these two RCTs also showed no significant difference in the 

incidence of preterm birth between groups.31-34 The third RCT found a reduced incidence of 

membrane rupture (0.8% vs. 3.2%, P=0.02) and a longer duration of gestation (data not reported) 

in the DHA supplementation group (n=129) than in the placebo group (n=126).30

Nine RCTs randomized healthy pregnant women between 12 and 24 weeks of gestation to 

DHA-rich fish oil supplementation or controls.35-43 Studies were conducted in the US (n=4), 

Germany (n=2), Australia (n=1), the UK,

43 and the Netherlands (n=1). Of the nine RCTs, three 

compared DHA cereal-based bars (mean DHA 214-240 and EPA 27-30 mg/d; DHA:EPA ratio = 

8) with placebo bars,38-40 five compared DHA-rich fish oil supplements (DHA 200-1020 and 

EPA 100-180 mg/d; DHA:EPA ratio = 5-8),37, 41-43 with controls (vegetable oil, nutritional 

counseling, vitamins and minerals, high oleic acid sunflower oil, or soy oil), and one is a threearm RCT that compared DHA-rich fish oil plus soybean oil (DHA 220 and EPA 36 mg/d plus 

22
ALA 32 mg/d), DHA-rich fish oil plus AA (DHA 220 and EPA 36 mg/d plus AA 220 mg/d) 

with placebo (soybean oil).36 Five of the nine RCTs with lower DHA doses (0.2-0.60 g/d) did not 

find significant differences in the mean gestational length between DHA supplementation and 

placebo in a total of 290 infants,36, 38, 40, 41 but one found an increase in gestational length (+0.9 

[95% CI 0.24, 1.56] weeks) compared DHA cereal-based bars (mean DHA 214-240 and EPA 

27-30 mg/d, n=14) with placebo bars (n=15).39 The other three RCTs with higher DHA doses 

(0.8-1.02 g/d) all found a significantly higher mean gestational length in infants whose mothers 

received DHA-rich fish oil supplement compared with those whose mothers received placebo 

(+0.14 to +1.3 weeks) in a total of 2656 infants.35, 37, 42 In contrast, two of these three RCTs with 

higher DHA doses (0.8 and 1.02 g/d) found no significant difference in the incidence of preterm 

birth between groups (OR 0.75 [95%0.54, 1.04] and OR 0.78 [95% CI 0.17, 3.56].35, 37

Meta-analysis of 11 RCTs showed that mean gestational length was significantly higher in 

infants whose mothers received supplemental algal DHA or DHA-rich fish oil compared with 

those whose mothers received placebo (WMD [95% CI] 0.34 [0.02, 0.67] weeks), with high

heterogeneity (I2 = 75.3) (Figure 5). No evidence of publication bias was seen (Begg’s and 

Egger’s p values were 0.542, 0.188, respectively).

However, our update meta-analysis of seven RCTs (two from the original report) found no 

significant effects of DHA or DHA-rich fish oil supplement on the incidence of preterm birth 

compared with placebo (OR=0.87; 95% CI 0.66, 1.15), with low heterogeneity (I2= 0). (Figure 

6)

Figure 5. Length of gestation (weeks): DHA versus placebo, DHA + EPA or fish oil versus placebo

23
Figure 6. Incidence of premature birth: DHA versus placebo, DHA + EPA or fish oil versus placebo

EPA+DHA

Two RCTs randomized healthy pregnant women between 12 and 20 weeks of gestation, and 

one RCT randomized at-risk pregnant women between 16 and 22 weeks of gestation to fish oil 

supplements (EPA+DHA) or placebo (soybean oil, corn oil, olive oil or inert mineral oil).29, 42, 44

Studies were conducted in the US (n=2) and Australia (n=1). The doses of EPA ranged from 

1.06 to 1.20 g/d, and the doses of DHA ranged from 0.27 to 2.2 g/d. The DHA to EPA ratio 

ranged from 0.25 to 2. The total doses of EPA plus DHA ranged from 1.3 to 3.3 g/d. Two of the 

three studies did not find a significant effect of maternal fish oil supplementation (EPA+DHA 

1.33 and 3.3 g/d) on infants’ gestational length compared with placebo in a total of 152 healthy 

pregnant women,42, 44 while the third study found that maternal fish oil supplementation 

(EPA+DHA 2 g/d) significantly increased the infants’ mean gestational length (+0.30 [95% CI 

0.07, 0.53] weeks, n=852) compared with placebo.29 However, no significant difference was 

observed in the incidence of preterm birth between groups in this study (OR 0.85 [95% CI 0.65, 

1.12]). It should be noted that this study is the only RCT (out of the 14 RCTs that reported 

gestation length outcome) enrolled at risk pregnant women with a history of at least one prior 

singleton preterm delivery.29

24
An insufficient number of RCTs was identified in healthy pregnant women to allow metaanalysis to examine the effect of fish oil supplementation in healthy pregnant women on infants’ 

gestational length. The updated random-effects meta-analysis of nine RCTs (in four publications:

one publication by Olsen et al.28 represented pooled data from six different RCTs) in pregnant 

women who were at risk for preterm delivery found no significant effects of fish oil 

supplementation on the incidence of preterm birth compared with placebo (OR [95% CI] 0.86 

[0.65, 1.15]), with no heterogeneity (I2 = 0).

EPA+DHA Versus ALA

One RCT compared five differences doses of fish oil supplementation (EPA+DHA 0.1, 0.3, 

0.7, 1.4 and 2.8 g/d) with ALA as the control (ALA 2.2 g/d) from week 17–27 of gestation until 

delivery in a total of 3098 healthy pregnant women with low dietary intake of fish (lowest 20% 

of fish consumption).45 There were no significant differences in gestation length between any of 

the fish oil supplementation groups and the control group. Specifically, the mean differences in 

gestational length ranged from -0.7 to +0.3 days between the fish oil and ALA control groups.

Observational Studies

Four prospective cohort studies were identified for the current report (see Table 2). Of these, 

three studies assessed the associations between maternal dietary intake of n-3 FA (from foods or 

supplements) and infants’ gestational length.

46-48 One of the three studies also analyzed the 

relationship between maternal dietary intake of n-3 FA and risk of preterm birth.46 The third 

study examined the relationships between maternal n-3 FA biomarkers and infants’ gestational 

length.

49

n-3 FA Intake

Three studies assessed the associations between maternal n-3 FA intake from supplements 

and infants’ gestational length.

46, 47 Oken46 evaluated the association between quartiles of 

maternal DHA+EPA intake (median 0.27 to 0.38 g/d) at first trimester (median EPA+DHA from 

0.02 to 0.36 g/d, n= 1797), second trimester (median EPA+DHA from 0.02 to 0.38 g/d, n=1663), 

and third trimesters (median EPA+DHA from 0.05 to 0.27 g/d, n=2070) and gestational length. 

No significant associations were found. This study also compared the risk of preterm birth 

between the highest and lowest quartiles of maternal DHA+EPA intake, and found no significant 

association (OR 1.1 [95% CI 0.7, 1.9].46 Badart-Smook (1997)47 reported that "No significant 

correlations were observed between any of the nutrients [including sum of n-3 FA+AA] and birth 

weight or the length of gestation" (data not shown) in 372 healthy pregnant women at the 22nd

week of gestation. Molto-Puigmarti (2014)

48 analyzed the associations between maternal DHA 

or ALA intake at 34 weeks of pregnancy and gestational length in 2006 healthy pregnant women. 

This study found that maternal DHA intake (mg/d) was significantly associated with an increase 

in gestational length (beta coefficient = 0.004 [95% CI 0.001, 0.007], P=0.0016) but maternal 

ALA intake was not associated with gestational length (beta coefficient = 0.001 [95% CI 0.000, 

0.003], P=0.11).

n-3 FA Biomarkers

One study examined the relationships between maternal erythrocyte DHA+EPA biomarkers 

and risk of preterm birth (<37 weeks of GA) in 852 pregnant women with at least one prior 

spontaneous preterm delivery.49 The study showed that the adjusted odds ratio for preterm birth 

among women in the lowest quartile compared with women in the 3 higher quartiles combined 

25
was 1.41 (0.97 – 2.05). When the top 3 quartiles were compared to the lowest quartile 

(erythrocyte DHA+EPA <3.052 % of total FA), only women in quartile 2 (erythrocyte 

DHA+EPA 3.052-3.719 % of total FA), but not quartiles 3 (erythrocyte DHA+EPA 3.723-4.426 

% of total FA) and quartile 4 (erythrocyte DHA+EPA >4.426 % of total FA), had a statistically 

significant reduction in the odds of preterm birth compared with those in quartile 1 (adjusted OR 

0.59 [95% CI 0.37, 0.94]).

26
Table 1. RCTs for length of gestation (or gestational age) and preterm birth

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Carlson et al., 201331

Study name: NR

Study dates: 2006.01-

2011.10

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy pregnant women

Pregnant enrolled 350 

Pregnant withdrawals 49 

Pregnant completers 301

Pregnant age: placebo: 

24.8; DHA: 25.3 (placebo 

4.7; DHA 4.9)

Race of Mother: Black 

(46%;37%) Non-black 

(54%; 63%)

Baseline biomarker 

information: RBCphospholipid-DHA 

(placebo group 4.3 +-

1.3; 4.3 +- 1.1)

Baseline Omega-3 

intake: Voluntary DHA 

intake from supplement 

(placebo group 15%, 

DHA group 9%)

Inclusion Criteria: 

English-speaking, 

between 8 and 20 wk of 

gestation, between 16 

and 35.99 y of age, and 

planning to deliver at a 

hospital in the Kansas 

City metropolitan area

Exclusion Criteria: 

carrying more than one 

fetus, had preexisting 

diabetes mellitus or 

systolic blood pressure 

$140 mm Hg at 

enrollment, or had any 

serious health condition 

likely to affect the 

prenatal or postnatal 

growth and development 

of their offspring, 

including cancer, lupus, 

hepatitis, HIV/AIDS, or a 

diagnosed alcohol or 

chemical dependency. or 

if the initial screening 

based on their selfreported weight and 

height suggested a BMI 

(in kg/m2 >=40).

Start time: Pregnant 99.6/102.9 day

Duration: Pregnant enrollment to birth

Arm 1: Placebo

Description: half soybean and half coin oil

Manufacturer: DSM Nutritional Products)

Active ingredients: a-linolenic acid

Dose: 3 *capsule 200/day

Blinding: both DHA and placebo capsules were 

orange flavored

Arm 2: DHA

Description: marine algae-oil source of DHA

Manufacturer: DHASCO; DSM Nutritional Products, 

formerly Martek Biosciences)

Dose: 200 mg capsule, 3 times a day

DHA: 200mg/capsule * 3

Outcome: gestational age (days) (Primary)

Follow-up time: birth

Arm 1: Sample size 147; mean 272.8; SD 

(17)

Arm 2: Sample size 154; mean 275.7; SD 

(11.2)

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 13/147 (8.8%)

Arm 2: 12/154 (7.8%)

Courville et al., 201138

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Study Population: 

Healthy pregnant women

Pregnant enrolled 47 

Pregnant withdrawals 0 

Pregnant completers 47

Pregnant age: NR (NR) 

NR

Race of Mother: White 

European (8.5) Black 

Inclusion Criteria: 

Healthy pregnant 

women, mid-pregnancy 

(20–24 weeks)

Exclusion Criteria: parity 

.5; history of chronic 

hypertension; 

hyperlipidaemia; renal or 

liver disease; heart 

disease; thyroid disorder; 

multiple gestations; 

Start time: Pregnant 20-24 wk of gestation

Duration: Pregnant until birth

Arm 1: Placebo

Description: placebo bars (

Manufacturer: Nestec Limited (Vevey, Switzerland)

Dose: 5 placebo bars per week

Blinding: NR

Arm 2: DHA-FF

Description: DHA cereal-based bars

Outcome: gestational age (weeks) 

(Unspecified)

Follow-up time: birth

Arm 1: Sample size 25; mean 39.4; SD 

(1.2)

Arm 2: Sample size 22; mean 39.9; SD 

(1.1)

27
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Industry, Government (10.6) Asian (4.3) 

Minority (Puerto 

Rican/Latino 66%; 

African - other 8.5%; 

Other or mixed ethnicity 

= 2%)

Baseline Omega-3 

intake: Dietary DHA 

intake (mg/d), not 

including the intervention 

food, from 24 h dietary 

recalls: DHA-FF 67+-7 

(SD); Placebo 87+-10 

(SD), P=0.059

having been pregnant or 

lactating in the previous 2 

years.

Manufacturer: Nestec Limited (Vevey, Switzerland)

Dose: 5DHA cereal-based bars per week

DHA: 241 mg/d

EPA: 30.1 mg/d

Dunstan et al., 200844

Study name: Dunstan

Study dates: 2000-2003

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Multiple foundations and 

Societies

Original, same study, or 

follow-up studies: 

Dunstan, 200350; 

Meldrum, 201551

Study Population: 

Healthy infants Pregnant 

women with allergies

Pregnant enrolled 98 

Pregnant completers 83

Infants enrolled 83 

Infants withdrawals 11 (7 

FO, 4 control) Infants 

completers 72

Pregnant age: Fish oil: 

30.9 Control: 32.6 (Fish 

oil: 3.7 Control: 3.6)

Infant age: Term (mean 

gestational period 275 

days)

Race of Mother: NR 

Baseline biomarker 

information: Cord blood 

erythrocyte (as % total 

fatty acids) 20:4n-6 14.9 

(1.4) 17.6 (1.0) ,0.001 

20:5n-3 1.3 (0.5) 0.4 

(0.3) ,0.001 22:3n-6 2.8 

(0.5) 3.9 (0.5) ,0.001 

Inclusion Criteria: 

Healthy term infants of 

pregnant women enrolled 

in RCT of gestational 

supplementation

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked, had medical 

problems, a complicated 

pregnancy, seafood 

allergy, or if their normal 

dietary intake exceeded 

two meals of fish per 

week. Children were 

excluded from the study 

if they were born before 

36 weeks’ gestation or 

with major disease (to 

avoid the confounding 

effects on immune 

response) or if cord blood 

was not collected

Start time: Pregnant 20 weeks gestation

Duration: Pregnant to term

Arm 1: Control

Description: olive oil placebo

Blinding: capsules image matched

Maternal conditions

Current smoker 0%

Maternal allergies 100%

Arm 2: Fish oil

Description: same

Manufacturer: Ocean Nutrition, Halifax Nova Scotia

Active ingredients: 3-4mg/g vitamin E

Viability: none reported

Dose: 4 1-gm capsules fish oil per day

Maternal conditions

DHA: 2.2

EPA: 1.1

Other dose 1: fish oil supplying 2,2g/d DHA and 

1.1g/day EPA

Current smoker 0%

Maternal allergies 100%

Outcome: gestational age (days) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 39; mean 274.5; SD (8)

Arm 2: Sample size 33; mean 276.0; SD (8)

28
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

22:4n-6 0.8 (0.2) 1.5 

(0.3) ,0.001 22:5n-3 6.3 

(0.8) 6.0 (0.5) 0.037 

22:6n-3 10.3 (1.1) 7.4 

(0.9) ,0.001 Total n-6 

PUFAs* 25.0 (1.8) 29.6 

(1.1) ,0.001 Total n-3 

PUFAs{ 17.9 (1.9) 13.7 

(1.3) ,0.001 Total n-3 to 

n-6{ 0.8 (0.1) 0.5 (0.1) 

,0.001

Harper et al., 201029

Study name: NR

Study dates: 01. 2005 -

10. 2006

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Klebanoff, 201149

Study Population: At risk 

for preterm labor

Pregnant enrolled 852 

Pregnant withdrawals 0 

Pregnant completers 852

Pregnant age: n3: 28 

placebo 27 n3 23-32; 

placebo 24-32

Race of Mother: White 

European (n3: 56.5; 

placebo 57.7) Black (n3: 

34.1; placebo 34.9) Asian 

(n3: 3, placebo 1.2) 

Hispanic (n3: 14.7; 

placebo 13.6) Other 

race/ethnicity (NR)

Inclusion Criteria: a 

documented history of at 

least one prior singleton 

preterm delivery between 

20 0/7 and 36 6/7 weeks 

of gestation after 

spontaneous preterm 

labor or premature 

rupture of the 

membranes, and a 

current singleton 

pregnancy between 16 

and 21 6/7 weeks of 

gestation

Exclusion Criteria: 

evidence of a major fetal 

anomaly, intake of a fish 

oil supplement in excess 

of 500 mg per week at 

any time during the 

preceding month, allergy 

to fish, anticoagulation 

therapy, hypertension, 

White’s classification D 

or higher diabetes, drug 

or alcohol abuse, seizure 

disorder, uncontrolled 

thyroid disease, clotting 

disorder, current or 

planned cerclage, or a 

plan to deliver either 

elsewhere or before 37 

Start time: Pregnant 16-22 week gestation age

Duration: Pregnant 36 weeks of gestation

Arm 1: placebo

Description: inert mineral oil

Manufacturer: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: four capsules of matching oil containing a 

minute amount of inert mineral oil

Blinding: Boxes containing a woman’s entire supply 

of capsules in blister packs were sequentially 

numbered according to the predetermined 

randomization sequence, and on enrollment a 

woman was assigned the next number in sequence. 

Study group assignment was not known by study 

participants, their health care providers, or the 

research personnel

Arm 2: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: in 4 capsules total 2000 mg of n3

DHA: 800 mg

EPA: 1200 mg

Outcome: gestational age (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 418; mean 37.4; range

Arm 2: Sample size 434; mean 37.7; range

Outcome: incidence of premature birth 

(Primary)

Follow-up time: birth

Arm 1: 174/418 (41.6%)

Arm 2: 164/434 (37.8%)

29
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

weeks of gestation

Hauner et al., 201237

Study name: INFAT

Study dates: July 14 

2006 - may 22 2009

Study design: Trial 

randomized parallel

Location: Germany

Funding source / conflict: 

Industry, Government, 

Multiple foundations and 

Societies

Study Population: 

Healthy pregnant women

Pregnant enrolled 208 

Pregnant withdrawals 38 

Pregnant completers 170

Infants enrolled 188 

Infants withdrawals 18 

Infants completers 170

Pregnant age: 31.9 (4.9) 

18-43

Race of Mother: NR (NR)

Baseline biomarker 

information: Maternal 

fatty acid profile in RBCs 

at 15th wk: EPA, DHA, 

AA, and n-6:n-3 LCPUFA 

ratio (reported in Table 2 

by intervention and 

control groups). No 

significant differences 

between groups.

Baseline Omega-3 

intake: 7-d dietary 

records completed by 

participants at the 15th 

(baseline) and 32nd wk 

of gestation but only 

dietary intake at 32nd we 

of gestation was reported 

(in Table 2). At week 32 

of gestation, the dietary 

n-6:n-3 PUFA ratio was 

.5:1 in the intervention 

group compared with :1 

in the control group, as 

originally intended.

Inclusion Criteria: healthy 

pregnant women before 

the 15th wk of gestation, 

between 18 and 43 y of 

age, prepregnancy BMI 

(in kg/m2) between 18 

and 30, willingness to 

implement the dietary 

recommendations, 

sufficient German 

language skills.

Exclusion Criteria: highrisk pregnancy (multiple 

pregnancy, rhesus 

incompatibility, hepatitis 

B infection, or parity .4); 

hypertension; chronic 

diseases (e.g., diabetes) 

or gastrointestinal 

disorders accompanied 

by maldigestion, 

malabsorption, or 

elevated energy and 

nutritional requirements 

(e.g., gluten 

enteropathy); known 

metabolic defects (e.g., 

phenylketonuria); 

psychiatric diseases; 

hyperemesis gravidarum; 

supplementation with n–3 

LCPUFAs before 

randomization; and 

alcohol abuse and 

smoking.

Start time: Pregnant 15th wk of gestation

Duration: Pregnant to 4 mo postpartum

Arm 1: Control

Description: brief semistructured counseling on a 

healthy balanced diet according to the guidelines of 

the German Nutrition Society and were explicitly 

asked to refrain from taking fish oil or DHA 

supplements

N-6 N-3: 2.80 +- 1.17 (SD) at 32nd wk of gestation

AA: 10.15 +- 3.89 SD) at 32nd wk of gestation

Arm 2: Intervention

Description: Fish-oil supplement + nutritional 

counseling (to normalize the consumption of AA

Brand name: Marinol D-40

Manufacturer: Lipid Nutrition

DHA: 1020 mg

EPA: 180 mg

N-6 N-3: 1.54 +- 0.63 (SD) at 32nd wk of gestation

AA: 8.82 +- 2.84 (SD) at 32nd wk of gestation

Other dose 1: Vit E 9 mg

Outcome: gestational age (days) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 96; mean 275.1; SD 

(11.4)

Arm 2: Sample size 92; mean 279.9; SD 

(8.5)

Judge et al., 200739 Study Population: Inclusion Criteria: women Start time: Pregnant 24 weeks gestation Outcome: gestational age (weeks) 

30
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government, 

None

Healthy pregnant women

Pregnant enrolled 29 

Pregnant completers 29

Pregnant age: 23.75 

years (.4 years) NR

Race of Mother: NR 

(100%)

aged 18 –35 y who were 

at 20 wk of gestation

Exclusion Criteria: 

Women with a history of

drug or alcohol addiction, 

hypertension, smoking, 

hyperlipidemia, renal 

disease, liver disease, 

diabetes, or psychiatric 

disorder

Duration: Pregnant until birth

Arm 1: placebo

Description: cereal based placebo bars

Manufacturer: Nestec

Active ingredients: 18 g carbohydrates, 1.3 grams 

protein, 92 calories, 1.7 g fat

Viability: NR

Dose: 5 bars per week

Blinding: NR

Arm 2: DHA supplemented cereal bars

Manufacturer: Nestec

Active ingredients: 18 g carbohydrates, 1.3 grams 

protein, 92 calories, 1.7 g fat

Viability: NR

Dose: 5 bars per week. DHA-containing cerealbased bars [1.7 g total fat, 300 mg DHA as loweicosapentaenoic oil (EPA) fish oil; EPA:DHA 1:8 

per bar

DHA: mg/d

EPA: .75 mg (calculated based on EPA:DHA ratio)

EPA-DHA: 1:8

(Secondary)

Follow-up time: birth

Arm 1: Sample size 15; mean 39.0; SD (1)

Arm 2: Sample size 14; mean 39.9; SD 

(0.8)

Judge et al., 201240

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Multiple foundations and 

Societies

Study Population: 

Healthy pregnant women

Pregnant enrolled 48

Pregnant age: Treatment 

group: 23.93 Placebo: 

23.86 (Treatment group: 

4.32 Placebo: 4.53)

Race of Mother: White 

European (Treatment: 

11.1%, Placebo: 0%) 

Black (Treatment: 18.5%, 

Placebo: 4.8%) Asian 

(Treatment: 3.7%, 

Placebo: 0%) Hispanic 

(Treatment: 59.3%, 

Placebo: 80.9%) NR 

(Treatment: 7.4%, 3 

(14.3%))

Inclusion Criteria: The 

women were either 

primiparous or had not 

been pregnant for the 

past 2 years.

Exclusion Criteria: parity 

greater than 5, history of 

chronic hypertension, 

hyperlipidemia, renal, 

liver or heart disease, 

thyroid disorder, multiple 

gestations or pregnancy 

induced complications 

including hypertension, 

preeclampsia or preterm 

labor, smoking and 

psychiatric disorders. 

Women who were 

treated during labor with 

analgesics such as 

Start time: Pregnant 24 weeks gestation

Duration: Pregnant until delivery

Arm 1: Placebo

Description: Control group

Manufacturer: Nestec, S.A., Switzerland

Blinding: The total macronutrient content was the 

same in both the DHA and placebo bars with respect 

to carbohydrate, protein and fat, how- ever, the DHA 

bars contained fish oil (300 mg DHA) and the 

placebo bars contained corn oil.

Arm 2: DHA

Description: Intervention group

Manufacturer: Nestec, S.A., Switzerland

Dose: average of 5 bars weekly

DHA: 300 mg

EPA-DHA: 8:1 ratio of DHA to EPA

Outcome: gestational age (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 21; mean 39.19; SD 

(1.17)

Arm 2: Sample size 27; mean 39.72; SD 

(1.2)

31
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Baseline biomarker 

information: Maternal 

plasma phospholipid (PL) 

fatty acids (FA): 2.85 +/-

.87 % in treatment group 

and 2.95 +/- .91% in 

placebo group. Infant 

RBC PL FA: 7.55 +/-

1.61% in treatment group 

and 7.07 +/- 1.25% in 

placebo group.

Stadol (butorphanol 

tartrate), that may cause 

infant respiratory distress 

were also excluded. In 

addition, infants born 

preterm and infants with 

less than 4 h of crib time 

in the first and second 

days postpartum were 

excluded from the 

analyses.

Knudsen et al., 200645

Study name: Danish 

National Birth CohortPregnant Women

Study dates: 2001-

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / conflict: 

Multiple foundations and 

Societies

Study Population: 

Healthy pregnant women

Pregnant enrolled 3098 

Pregnant withdrawals 

1033 Pregnant 

completers 2065

Pregnant age: Group 01: 

28.4 years Group 03: 

28.7 years Group 07: 

28.4 years Group 14: 

28.9 years Group 28: 

28.8 years Group C18: 

28.8 years Group CG: 

28.5 years

Race of Mother: NR

Baseline biomarker 

information: Level of 

EPA, DHA, and AA in 

erythrocyte phospholipids 

assessed in a subsample 

of women in the 6 

treatment groups

Baseline Omega-3 

intake: EPA, DHA, 

EPA+DHA, ALA, AA

Inclusion Criteria: Low 

dietary intake of fish 

(lowest 20% of fish 

consumption), no use of 

fish oil capsules in 

pregnancy, gestational 

age 17-27 weeks.

Exclusion Criteria: NR

Start time: Pregnant 17-27 weeks gestation

Duration: Pregnant until delivery

Arm 1: CG

Description: control group ( flax oi)

Blinding: The women in the control group were 

allocated to any treatment and were not contacted at 

all.

ALA: 2.2 g/d

Arm 2: 01

Description: Treatment Group 1

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, Denmark

Active ingredients: 13.4 mg D-alpha-tocopherol per 

gram

Dose: 1 0.5 g three times per week

DHA: 22%

EPA: 32%

Total N-3: 0.1 g per day

Arm 3: 03

Description: Treatment group 2

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, Denmark

Active ingredients: 13.4 mg D- alpha-tocopherol per

gram

Dose: 1 0.5 g capsule per day

Total N-3: 0.3 g per day

Arm 4: 07

Description: Treatment group 3

Outcome: gestational age (days) (Primary)

Follow-up time: birth

Arm 1: Sample size 748; mean 280.6; SD 

(11.7)

Arm 2: Sample size 229; mean 281.5; SD 

(12.6)

Arm 3: Sample size 224; mean 279.7; SD 

(12)

Arm 4: Sample size 222; mean 280.5; SD 

(12.6)

Arm 5: Sample size 212; mean 280.6; SD 

(12.6)

Arm 6: Sample size 187; mean 279.6; SD 

(14.8)

Arm 7: Sample size 176; mean 280.7; SD 

(12.8)

32
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, Denmark

Active ingredients: 13.4 mg D- alpha-tocopherol per

gram

Dose: 1 1 g capsule per day

DHA: 22%

EPA: 32%

Total N-3: 0.7 g per day

Arm 5: 14

Description: Treatment group 4

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, Denmark

Active ingredients: 13.4 mg D- alpha-tocopherol per

gram

Dose: 2 1g capsules per day

DHA: 22%

EPA: 32%

Total N-3: 1.4 g per day

Arm 6: 28

Description: Treatment group 5

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, Denmark

Active ingredients: 13.4 mg D-alpha-tocopherol per 

gram

Dose: 4 g per day

DHA: 22%

EPA: 32%

Total N-3: 2.8g per day

Arm 7: c18

Description: Treatment group 6 - flax oil

Brand name: Prima FlaxTM

Manufacturer: Bioriginal Food & Science Corp., 

Saskatoon, Canada

Dose: 4 1-g capsules of flax oil

ALA: 2.2g per day

Lucia Bergmann et al., 

200741

Study name: NR

Study dates: 2000-2002

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 144 

Pregnant withdrawals 51 

Pregnant completers 69

Inclusion Criteria: at least 

18 years of age and 

willing to breastfeed for 

at least three months 

were enrolled at 21 

weeks’ gestation during 

the period October 2000 

Start time: Pregnant 21th week

Duration: Pregnant 37th week

Arm 1: Vitamins and minerals

Manufacturer: Nestle ́ (Vevey, Switzerland)

Outcome: gestational age (weeks) 

(Unspecified)

Follow-up time: birth

Arm 1: Sample size 74; mean 39.5; SD 

(1.38)

Arm 3: Sample size 43; mean 39.1; SD 

33
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: Germany

Funding source / conflict: 

NR

Original, same study, or 

follow-up studies: Lucia, 

200752

Pregnant age: 31 (DHA 

4.69; control 4.89)

Infant age: DHA 39.1; 

control 39.5 weeks (DHA 

1.64; control 1.38)

Race of Mother: White 

European (100)

Baseline biomarker 

information: DHA % of all 

identified fatty acid in 

RBC: Vitamin: 5.76 +-

2.45 (47); DHA: 

Prebiotic:5.94+-2.37(48) 

DHA: DHA: 5.69+-

2.40(47) ARA Vitamin: 

14.01+-4.04(47) ARA 

Prebiotic 14.82+-3.60(48) 

ARA DHA: 14.18+-

4.32(47) EPA Vitamin: 

0.72+-0.32(47) EPA 

Prebiotic: 0.78+-0.38(48) 

EPA DHA: 0.79+-

0.41(47)

to August 2002

Exclusion Criteria: 

increased risk of 

premature delivery or 

multiple pregnancy, 

allergy to cow milk 

protein, lactose 

intolerance, diabetes, 

smoking, consumption of 

alcohol ()20 g/week), or 

participation in another 

study. Infants excluded if 

they were premature at 

birth (<37 week 

gestation, or had any 

major malformations or 

hospitalized for more 

than one week.

Arm 2: Prebiotic

Description: basic supplement plus the prebiotic, 

fructooligosaccharide (FOS) (4.5 g)

Manufacturer: Nestle ́ (Vevey, Switzerland)

Active ingredients: fructooligosaccharide (FOS) (4.5 

g)

Arm 3: DHA

Description: basic supplement with FOS and DHA 

(200 mg)

Manufacturer: Nestle ́ (Vevey, Switzerland)

Dose: 200 mg DHA prepared from fish oil (assuming 

that some EPA but dose was not reported)

DHA: 200 mg

EPA: NR

(1.64)

Makrides et al., 201035

Study name: DOMInO

Study dates: 2005-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Study Population: 

Healthy pregnant women

Pregnant enrolled 2399 

Pregnant withdrawals 1

Infants enrolled 605 

Infants withdrawals 32 

Infants completers 726

Pregnant age: 28.9 

(DHA5.7___ control5.6)

Race of Mother: NR (NR)

Inclusion Criteria: with 

singleton pregnancies at 

less than 21 weeks’ 

gestation were 

approached by study 

research assistants while 

attending routine 

antenatal appointments

Exclusion Criteria: 

already taking a prenatal 

supplement with DHA, 

their fetus had a known 

major abnormality, they 

had a bleeding disorder 

in which tuna oil was 

contraindicated, were 

taking anticoagulant 

Start time: Pregnant < 21 week's gestation

Duration: NR

Arm 1: vegetable oil capsules

Description: a blend of 3 nongenetically modified oils 

(rapeseed, sunflower, and palm) in equal 

proportions

Manufacturer: Efamol, Surrey, England.

Dose: 3* 500mg capsule / day

Blinding: All capsules were similar in size, shape, 

and color

Arm 2: DHA

Description: DHA-rich fish oil concentrate

Manufacturer: ; Incromega 500 TG, Croda 

Chemicals, East Yorkshire, England

Dose: 500mg capsule *3/day

Outcome: gestational age (days) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 1202; median 281.0; 

IQR

Arm 2: Sample size 1197; median 282.0; 

IQR

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 88/1202 (7.34%)

Arm 2: 67/1197 (5.6%)

34
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Smithers, 201153; Palmer, 

201254; Zhou, 201255;

Palmer, 201356; 

Makrides, 2014 57

therapy, had a 

documented history of 

drug or alcohol abuse, 

were participating in 

another fatty acid trial, 

were unable to give 

written informed consent, 

or if English was not the 

main language spoken at 

home

DHA: 800mg

EPA: 100mg

Min et al., 201443

Study name: NR

Study dates: Jan 2008 -

Dec 2011

Study design: Trial 

randomized parallel

Location: UK

Funding source / conflict: 

Industry, Government, 

Multiple foundations and 

Societies, Manufacturer 

supplied product

Original, same study, or 

follow-up studies: none

Study Population: 

Healthy pregnant 

women, Pregnant women 

with type 2 diabetes

Pregnant enrolled 85 

Pregnant completers 59

Pregnant age: 29 18-44

Infant age: 11.0-12.1 

weeks gestation 6.0-15.9 

weeks gestation

Race of Mother: White 

European (22.3%) Black 

(28.2%) Asian (40.0%) 

Other race/ethnicity 

(9.4%)

Inclusion Criteria: 

Pregnant women of 17–

45 years old with 

singleton pregnancies 

with either pre-existing 

Type 2 diabetes or 

without any known 

medical condition 

(uncomplicated 

pregnancy group)

Exclusion Criteria: 

Women planning to 

receive tocolytic or 

corticosteroid therapy. 

Note that pregnant 

women with pre-existing 

Type 2 diabetes were 

excluded from this 

systematic review.

Start time: Pregnant average: 9.9-12.1 weeks 

gestation (range: 4.3-15.9 weeks gestation)

Duration: Pregnant until delivery; average: 26.5 

weeks for placebo arm; 28.4 weeks for the fish oil 

arm

Arm 1: Placebo, healthy women

Description: high oleic acid sunflower oil

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: oleic acid, 82.6%; vitamin E (d- a 

tocopherol) NR%

Dose: 2x 750 mg capsules/day

Blinding: identical oblong soft gelatin capsule

Maternal conditions

Current smoker 0%

Arm 2: Fish oil, healthy women

Description: HA-enriched fish oil

Brand name: Mumomega

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: vitamin E (d- a tocopherol) NR%

Dose: 2 750 mg capsules/day

Maternal conditions

DHA: 43.7% (600 mg/d)

EPA: 7.5% (estimated to be 103 mg/d)

Current smoker 13.3%

Arm 3: Placebo, diabetic women

Description: high oleic acid sunflower oil

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: oleic acid, 82.6%; vitamin E (d- a 

tocopherol) NR%

Dose: 2 750 mg capsules/day

Maternal conditions

Outcome: gestational age birth (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 27; median 39.3; range

Arm 2: Sample size 32; median 39.3; range

Outcome: preterm birth (Secondary)

Follow-up time: birth

Arm 1: 3/27 (11.1%)

Arm 2: 3/32 (9.4%)

35
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Current smoker 0%

Other maternal conditions 

1arm_3_maternal_conditions_other1

Other maternal conditions 10 Type 2 diabetes: 100%

Arm 4: Fish oil, diabetic women

Description: HA-enriched fish oil

Brand name: Mumomega

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: vitamin E (d- a tocopherol) NR%

Dose: 2 750 mg capsules/day

Blinding: identical oblong soft gelatin capsule

Maternal conditions

DHA: 43.7%

EPA: 7.5%

Current smoker 4.9%

Other maternal conditions 

1arm_4_maternal_conditions_other1

Other maternal conditions 10 Type 2 diabetes: 100%

Mozurkewich et al., 

201342

Study name: NR

Study dates: Oct 2008 -

May 2011

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy pregnant women

Pregnant enrolled 126 

Pregnant withdrawals 8 

Pregnant completers 118

Pregnant age: EPA 29.9; 

DHA 30.6; placebo 30.4 

(EPA 5.0; DHA 4.5; 

placebo 5.9)

Race of Mother: White 

European (85%; 76%; 

83%) Black (10%; 11%; 

5%) Asian (3%; 3%; 2%) 

Hispanic (0%; 11%; 7%) 

Inuit Eskimo (0%; 0%; 

2%) Pacific Islander (NR)

Baseline biomarker 

information: EPA group: 

EPA 0.29+-0.18; DHA 

4.24+-2.30; total n3 FA: 

22.10+-3.72 DHA group: 

EPA 0.31+-0.24; DHA 

Inclusion Criteria: past 

history of depression, an 

EPDS score 9-19 (at risk 

for depression or mildly 

depressed), singleton 

gestation, a maternal age 

of 18 years or older, and 

a gestational age of 12-

20 weeks

Exclusion Criteria: had a 

history of a bleeding 

disorder, thrombophilia 

requiring anticoagulation, 

multiple gestation, bipolar 

disorder, current major 

depressive disorder, 

current substance abuse,

lifetime substance 

dependence, or 

schizophrenia. Women

were also ineligible if 

they were currently 

taking omega-3 fatty acid 

supplements or 

antidepressant 

Start time: Pregnant 12-20 week gestation

Duration: Pregnant assuming till birth

Arm 1: Control/Placebo

Description: 98% soy oil and 1% each of lemon and 

fish oil

Manufacturer: Nordic Naturals Corporation in 

Watsonville, CA

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large and 4 small placebo capsules

Blinding: The placebos were formulated to be 

identical in appearance to both the EPA- and DHArich supplements

Arm 2: EPA-rich fish oil

Description: an approximate 4:1 ratio of EPA to DHA 

(1060 mg EPA plus 274 mg DHA)

Brand name: ProEPAXtra, Nordic Naturals

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large EPA capsule and 4 small placebo

DHA: 274 mg

EPA: 1060 mg

Outcome: gestational age (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 41; mean 39.1; SD 

(1.5)

Arm 2: Sample size 39; mean 39.1; SD 

(1.5)

Arm 3: Sample size 38; mean 40.4; SD 

(0.9)

36
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

4.66+-2.29; total n3 FA 

36.41+-9.71 placebo: 

EPA .34+-0.22; DHA 

3.85+-1.77; omega3 fa 

322.86+-5.02

medications or eating 

more than 2 fish meals 

per week.

Arm 3: DHA-rich fish oil

Description: DHA and EPA in an approximate 4:1 

ratio o (900 mg DHA plus 180 mg EPA)

Brand name: ProDHA, Nordic Naturals

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large placebo oil and 4 small DHA rich

DHA: 900 mg

EPA: 180 mg

Pietrantoni et al., 201430

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Italy

Funding source / conflict: 

Government

Study Population: 

Healthy pregnant women

Pregnant enrolled 300 

Pregnant completers 255

Pregnant age: DHA 

30.86 +-4.18/placebo 

group 29.92+-4.8

Race of Mother: NR (NR)

Inclusion Criteria:

caucasians 22 to 35 yrs, 

8 week gestational age, 

single pregnancy, BMI 

between 18.5 and 

25.0kg/m2, habitual fish 

consumption (twice a 

week at least), high 

school or university 

degree, average 

socioeconomic status, 

absence of uterine 

abnormalities (fibroids, 

cervical incompetence, 

uterine malformations 

etc.)

Exclusion Criteria: 

smoking, substance 

abuse including alcohol, 

allergy to fish or 

derivates, diabetes, 

hypertension, metabolic, 

cardiovascular, renal, 

psychiatric, neurologic, 

thrombophilic, thyroid or 

autoimmune diseases, 

previous pregnancy 

complications 

(miscarriage, preterm or 

operative delivery), 

previous uterine surgery, 

recurrent genito-urinary 

infections

Start time: Pregnant 8th weeks

Duration: Pregnant 8th week to delivery

Arm 1: Placebo

Description: Olive oil

Arm 2: DHA group

Description: DHA capsule

Dose: 2* 100mg capsule

DHA: 100mg * 2 capsule

Outcome: preterm-premature rupture of 

membranes (Unspecified)

Follow-up time: birth

Arm 1: 4/126 (3.2%)

Arm 2: 1/129 (0.8%)

Ramakrishnan et al., Study Population: Inclusion Criteria: 18-35 Start time: Pregnant at study entry Outcome: gestational age (weeks) 

37
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

201032

Study name: POSGRAD

Study dates: Feb 2005 -

Feb 2007

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, March of 

Dimes

Original, same study, or 

follow-up studies: Stein, 

201233; Imhoff-Kunsch, 

201158; Escamilla-Nunez, 

201459; GonzalezCasanova, 201560; 

Ramakrishnan, 201561; 

Stein, 201134

Healthy pregnant women

Pregnant enrolled 1,094

Pregnant withdrawals 67 

Pregnant completers 973 

(for birth weight)

Pregnant age: 26.2 

(controls) 26.3 (DHA) 

(4.6 (controls) 4.8 (DHA))

Race of Mother: Hispanic 

(NR)

Baseline Omega-3 

intake: mg/day for all: LA: 

17,846 in controls, 

17,645 in DHA AA: 137 

in controls, 140 in DHA 

ALA: 1,488 in controls, 

1,477 in DHA EPA: 18 in 

controls, 18 in DHA: 54 in 

controls, 56 in DHA

yrs. of age, in gestation 

weeks 18-22, planned to 

deliver at the IMSS 

General Hospital in 

Cuernavaca, exclusively 

or predominantly 

breastfeed for at least 3 

months, liver in the area 

for at least 2 years after 

delivery.

Exclusion Criteria: highrisk pregnancy; lipid 

metabolism or absorption 

disorders, regular intake 

of fish oil or DHA 

supplements; chronic use 

of certain medications 

(e.g., medications for 

epilepsy).

Duration: Pregnant mid pregnancy (18-22 weeks 

gestation) until delivery

Arm 1: Controls

Description: Placebo containing olive oil

Manufacturer: Martek Biosciences

Dose: 1 capsule, twice a day

Blinding: Identical tablets

Arm 2: DHA

Description: Intervention

Manufacturer: Martek Biosciences

Dose: 1 capsule twice a day

DHA: 400 mg/d, 200 mg/dl derived from algal source

(Primary)

Follow-up time: birth

Arm 1: Sample size 486; mean 39.1; SD 

(1.7)

Arm 2: Sample size 487; mean 39.0; SD 

(1.9)

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 40/486 (8.3%)

Arm 2: 49/487 (10.1%)

Stein et al., 201134

Study name: POSGRAD

Study dates: 02. 2005-

02.2007

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, Multiple

foundations and 

Societies

Original, same study, or 

follow-up studies: Stein, 

201233; Imhoff-Kunsch, 

201158; Escamilla-Nunez, 

Study Population: 

Healthy infants

Pregnant enrolled 1094 

Pregnant completers 973

Pregnant age: placebo 

26.3; DHA 26.4 (placebo 

4.6; DHA 4.9)

Infant age: 39.1 (placebo 

1.6; DHA 1.8)

Race of Mother: NR

Inclusion Criteria: women 

were 18–35 y, were in 

gestation wk 18–22, and 

planned to deliver at the 

IMSS General Hospital in 

Cuernavaca, exclusively 

or predominantly breastfeed for at least 3 mo, 

and to live in the area for 

at least 2 y after delivery

Exclusion Criteria: NR

Start time: Pregnant 18-22 Gestational week Infants 

birth

Duration: Pregnant birth

Arm 1: Placebo

Description: Olive oil

Manufacturer: Martek Biosciences

Dose: 2 capsules olive oil

Blinding: Similar in appearance and taste to DHA 

capsules

Arm 2: DHA

Description: algal DHA capsules

Manufacturer: Martek Biosciences

Dose: 2 capsules * 200mg

DHA: 400 mg

Outcome: gestational age (weeks) 

(Primary)

Follow-up time: birth

Arm 1: Sample size 368; mean 39.1; SD 

(1.6)

Arm 2: Sample size 369; mean 39.1; SD 

(1.8)

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 30/368 (8.2%)

Arm 2: 33/369 (8.9%)

38
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

201459; GonzalezCasanova, 201560; 

Ramakrishnan, 201561; 

Ramakrishnan, 201132

Stein et al., 201233

Study name: POSGRAD

Study dates: Feb 2005-

Feb 2007

Study design: Trial 

randomized parallel

Location: NR

Funding source / conflict: 

Government

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Imhoff-Kunsch, 201158; 

Escamilla-Nunez, 201459;

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 1094 

Pregnant withdrawals 63 

Pregnant completers 900

Pregnant age: 26.3 (4.6-

4.8)

Infant age: 39.1 (1.7-1.8)

Race of Mother: NR (NR)

Inclusion Criteria: 

Singleton live births 

without congenital 

anomalies

Exclusion Criteria: 3364: 

high risk pregnancy, 

(history and prevalence 

of pregnancy 

complications, including 

abruption placentae,

preeclampsia, 

pregnancy-induced 

hypertension, any 

serious bleeding episode 

in the current pregnancy, 

and physician referral); 

lipid metabolism or 

absorption disorders, 

regular intake of fish oil 

or DHA supplement, or 

chronic use of certain 

medication(e.g. epilepsy 

medications)

Start time: Pregnant 18-22 wk

Duration: Pregnant to birth

Arm 1: Placebo

Description: A mixture of corn and soy oil

Manufacturer: Martek Biosciences

Blinding: "Participants and members of the study 

team were unaware of the treatment scheme 

throughout the intervention period of the study"

Arm 2: DHA

Description: DHA 400 mg/d

Manufacturer: Martek Biosciences

Dose: 2 capsule per day

DHA: 2*200mg

duplicate data of Ramakrishnan, 201132

Outcome: (Primary)

van Goor et al., 201036

Study name: Groningen 

LCPUFA study

Study dates: Enrollment 

from December 2004 

until December 2006

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Industry, Government

Study Population: 

Healthy pregnant women 

Breast-feeding women

Pregnant enrolled 183 

Pregnant completers 125

Infants completers 119

Pregnant age: 32 years 

(5 years)

Infant age: 14 to 20 

weeks gestation

Race of Mother: NR 

Inclusion Criteria: healthy 

women with a first or 

second low-risk singleton 

pregnancy

Exclusion Criteria: 

women with vegetarian 

or vegan diets and 

women with diabetes 

mellitus

Start time: Pregnant 14 to 20 weeks gestation 

Infants 14 to 20 weeks gestation

Duration: Pregnant until 3 months after delivery 

Infants until 3 months of age

Arm 1: placebo

Description: soybean oil capsule

Manufacturer: Wuhan Alking Bioengineering

Active ingredients: standard dose vitamins and 

minerals

Dose: 2 capsules

Maternal conditions

ALA: 60 mg

DHA: 0

EPA: 0

Outcome: gestational age birth (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 36; mean 40.2; SD (1)

Arm 2: Sample size 42; mean 40.2; SD 

(1.1)

Arm 3: Sample size 41; mean 40.2; SD 

(1.1)

39
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 12 

weeks

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; van Goor, 201166

(100) AA: 0

Other dose 1: LA 535 mg

Current smoker 2%

Arm 2: DHA group

Description: DHA fish oil capsule

Manufacturer: Wuhan Alking Bioengineering

Active ingredients: standard dose vitamins and 

minerals

Dose: 2 capsules

Maternal conditions

ALA: 32 mg

DHA: 220 mg

EPA: 34 mg

AA: 15 mg

Other dose 2: LA 274 mg

Current smoker 2%

Arm 3: DHA + AA group

Description: DHA + AA capsule

Brand name: Marinol D40

Manufacturer: Lipid Nutrition B.V., Wormerveer, The 

Netherlands

Active ingredients: standard dose vitamins and 

minerals

Dose: 2 capsules

Maternal conditions

ALA: 7 mg

DHA: 220 mg

EPA: 36 mg

AA: 220 mg

Other dose 2: LA 46 mg

Current smoker 3%

AA = arachidonic acid; ALA = alpha linolenic acid; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; FF = functional food; FOS = fructooligosaccharide; INFAT = impact 

of nutritional fatty acids during pregnancy and lactation on early adipose tissue developmentLCPUFA = long chian polyunsaturated fatty acid; mg = milligram; n-3 FA = omega-3 fatty 

acid; n-6 FA = omega-6 fatty acid; NR = not reported; OR = odds ratio; RBC = red blood cell; RCT = randomized controlled trial; SD = standard deviation

40
Table 2. Observational studies for length of gestation (or gestational age) and preterm birth

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Badart-Smook, et al., 199747

Outcome domain: Duration Gestation

Study dates: NR

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: NR

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 610 Pregnant withdrawals 

240 Pregnant completers 370

Pregnant age: 29 (4)

Race of Mother: White European (100)

Inclusion Criteria: White race, intention to give birth 

to the baby in one of the three hospitals involved in 

the study

Exclusion Criteria: Women with diastolic blood 

pressure of 90mm or higher, women suffering from 

any metabolic, cardiovascular, neurological, or renal 

disorder

Adjustments: 

Maternal(pregnancy) body 

weight, height, age, smoking 

habits, education, parity, and 

sex of the infant were 

included in each multiple 

regression model as possible 

confounding factors; except 

for the regression equation 

with gestational age as a 

dependent variable, 

gestational age at birth was 

also added as a confounder

Klebanoff, et al., 201149

Outcome domain: Duration Gestation

Study dates: Jan 2005- Oct 2006

Study design: Observational prospective

Location: US

Funding source / conflict: Government

Original, same study, or follow-up studies: 

Harper, 201029

Study Population: Healthy pregnant women

Pregnant enrolled 852 Pregnant completers 852

Pregnant age: <1/month, 27.1 (5.6) 0.5-3 per 

week, 28.0 (5.6) >3 per week, 27.3 (5.7) 

(<1/month, 27.1 (5.6) 0.5-3 per week, 28.0 (5.6) 

>3 per week, 27.3 (5.7))

Race of Mother: NR

Inclusion Criteria: at least one prior singleton 

preterm delivery between 20 0/7 and 36 6/7 weeks 

of gestation after spontaneous preterm labor or 

premature rupture of the membranes, and a current 

singleton pregnancy between 16 and 21 6/7 weeks 

of gestation

Exclusion Criteria: evidence of a major fetal 

anomaly, intake of a fish oil supplement in excess of 

500 mg per week at any time during the preceding 

month, allergy to fish, anticoagulation therapy, 

hypertension, White’s classification D or higher 

diabetes, drug or alcohol abuse, seizure disorder, 

uncontrolled thyroid disease, clotting disorder, 

current or planned cerclage, or a plan to deliver 

either elsewhere or before 37 weeks of gestation

Adjustments: Study center, 

number of previous preterm 

births, gestation of earliest 

prior spontaneous preterm 

birth, receipt of omega-3 

versus placebo supplement, 

smoking, age, education, 

body mass index and ethnicity

Molto-Puigmarti, et al., 201448

Outcome domain: Duration Gestation

Study name: KOALA Birth Cohort Study

Study dates: 2000-2002

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Multiple foundations 

and Societies

Study Population: Healthy pregnant women

Pregnant enrolled 2669 Pregnant completers 

1516

Infants enrolled 2669 Infants completers 1515

Pregnant age: years (.7yrs)

Race of Mother: NR (100)

Inclusion Criteria: nr, Described in Ref 37

Exclusion Criteria: nr

Adjustments: Adjusted for 

child gender, study 

recruitment group, maternal 

education, parity, maternal 

smoking status during 

pregnancy, maternal alcohol

use in pregnancy, and 

maternal age at delivery

Oken, et al., 200446 Study Population: Healthy infants Healthy Inclusion Criteria: delivered a live infant, and Adjustments: Enrollment site, 

41
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Outcome domain: Duration Gestation

Study name: Project Viva

Study dates: 1999-2002

Study design: Observational prospective

Location: US

Funding source / conflict: Government, Multiple

foundations and Societies

pregnant women

Pregnant enrolled 2109 Pregnant completers 

2109

Pregnant age: 14-<20, 3% 20-<25, 6% 25-<30, 

21% 30-<35, 42% 35=<40, 23% >=40, 4% (14-

44)

Race of Mother: White European (66) Black 

(16) Asian (6) Hispanic (7) Other race/ethnicity 

(4)

completed at least one dietary questionnaire

Exclusion Criteria: taking cod liver or fish oil 

supplement

infant sex, and maternal age, 

height, intrapartum weight 

gain, prepregnancy BMI, 

race/ethnicity, smoking during 

pregnancy, education, and 

gravidity

42
Gestational Hypertension and Preeclampsia

Because a number of studies identified for this report combined the outcomes of gestational 

hypertension (GHTN), preeclampsia (PE), and eclampsia, we report them together.

Key Findings and Strength of Evidence for Risk for Gestational 

Hypertension/Preeclampsia

• Pooled analysis of three RCTs found no effect of fish oil intake during pregnancy on the 

risk for gestational hypertension or preeclampsia among women at increased risk for poor 

pregnancy outcomes.

• Pooled analysis of three RCTs (n=2,875) assessing the effects of DHA alone or DHAenriched fish oil on the risk for GHTN/PE among women not at increased risk showed no 

effects.

• One study that assessed the effects of EPA alone on women not at risk showed no effect. 

• No studies of ALA supplementation were found.

• Four prospective observational studies that assessed the association between n-3 intake 

and risk for GHTN or PE showed no consistent associations. Of two studies that assessed 

the association of biomarkers for n-3 intake with risk for GHTN/PE, one showed no 

association, whereas one study showed an association between plasma levels and reduced 

risk for GHTN.

Description of Included Studies

Randomized Controlled Trials

The original report identified 8 RCTs that assessed the effects of supplementation of 

pregnant women with n-3s on the outcomes of GHTN and/or PE. Pooling the outcomes of two 

trials on the effects of fish oil on the risk for GHTN among women at increased risk for GHTN 

or other high-risk pregnancy outcomes (N=582) revealed a non-statistically significant increase 

in the risk for GHTN among n-3 supplemented women (OR 1.07 [0.75, 1.51]). 

Four RCTs identified for the current report assessed the effects of n-3s on risk for GHTN 

and/or PE (see Table 3).

29, 31, 42, 55 Three of these RCTs enrolled women with no prior risk of 

poor pregnancy outcomes (N=2,875) (although one of the studies enrolled women at increased 

risk for peripartum depression).31, 42, 55 The fourth RCT, by Harper and colleagues (2012), 

enrolled 852 women with a history of recurrent preterm birth.29

Marine Oil Versus Placebo

Population At Risk For Poor Pregnancy Outcomes.

Meta-analysis of the two RCTs from the original report, which compared the effects of 

marine oil versus placebo on at-risk populations, and the newly identified RCT by Harper and 

colleagues, which compared the effects of a mixture of EPA and DHA derived from fish with 

that of mineral oil among an at-risk population,29 yielded an insignificant summary effect size for 

risk of GHTN or preeclampsia (OR [95% CI]=1.04 [0.76 , 1.42], I2= 0%) (see Figure 7).

43
Figure 7. Pregnancy induced hypertension/preeclampsia: DHA + EPA versus placebo, DHA versus

placebo

The latter study also administered intra-muscular alpha-medroxyprogesterone caproate (the 

primary outcome of interest was prevention of preterm birth) and the fish oil capsules contained 

vitamin E as a preservative. 

The study by Harper and colleagues conducted a subgroup analysis to determine whether the 

outcomes were affected by fish intake. No differences in outcomes were observed between 

women who consumed no fish or less than one serving of fish per month and those who 

consumed more fish.29

Population Not At Risk For Poor Pregnancy Outcomes

No studies were identified that assessed the effects of marine oil compared with placebo on 

the risk for GHTN or PE among women not at risk for poor pregnancy outcomes. 

DHA Versus Placebo

Population At risk For Poor Pregnancy Outcomes 

We identified no studies that compared the effect of supplements containing only DHA to 

that of placebo on the risk for GHTN or PE among women at increased risk for poor pregnancy 

outcomes.

Populations Not At Risk For Poor Pregnancy Outcomes

We identified three RCTs that compared the effect of supplements containing only DHA 

(600 to 900 mg/day) to that of placebo on the risk for GHTN or PE among women not at 

increased risk for poor pregnancy outcomes. The DOMInO trial enrolled 2,399 pregnant 

Australian women (less than 21 weeks gestation) to receive 800 mg/day DHA-enriched fish oil 

or vegetable oil placebo and followed throughout the second half of pregnancy to assess risk for 

gestational diabetes and PE as primary outcomes. No differences were seen in the risk for PE 

(adjusted or unadjusted for clinic and parity).55 The Mothers, Omega-3, and Mental Health Study 

enrolled 126 pregnant U.S. women at risk for depression and randomly assigned them to receive 

44
DHA-enriched fish oil (900 mg DHA:180 mg EPA/day), EPA-enriched fish oil (1,060 mg EPA: 

274mg DHA), or soy bean oil placebo from early gestation through term. No differences were 

seen among groups in risk for development of GHTN or PE.42 Finally, Carlson and coworkers 

randomized 350 pregnant U.S. women at less than 21 weeks gestation to receive 600mg/day 

DHA from marine algal oil or soybean and corn oil through term. No differences were seen 

between groups in the secondary outcome PE.31

Meta-analysis of the three RCTs yielded an insignificant summary effect size for DHA 

supplementation and risk of GHTN or preeclampsia (OR [95% CI]=0.94[0.66, 1.34],

I

2

=0%)(Figure 7).

EPA Versus Placebo

Only one RCT was identified that compared the effects of EPA supplementation with that of 

placebo on the risk for GHTN or PE. This study, described above, found no significant 

difference between EPA-enriched fish oil, DHA-enriched fish oil, and placebo and the risk for 

developing GHTN or PE.42

ALA Versus Placebo

We identified no studies that assessed the effects of ALA supplementation on risk for GHTN 

or PE.

Observational Studies 

Five prospective studies evaluated the association between some measure of n-3 FA exposure 

and risk for GHTN or PE (see Table 4).

67-70 All enrolled populations of healthy pregnant women, 

usually at their first prenatal visit. One study was a nested case-control from a large RCT that 

assessed the association between dietary intakes of n-3 FA and maternal biomarkers and risk for 

GHTN.67 The remainder were prospective cohort studies that assessed the association between 

dietary intakes of n-3 FA and risk for GHTN or PE.68-70 (Table 4) Publications dated from 1995 

to 2007. 

n-3 FA Intake

Four studies evaluated the association between-3 FA intake and risk for GHTN and/or PE.67-

70

A 1995 study assessed the association of n-3 FA intakes with risk for GHTN among a cohort 

of 208 healthy pregnant women in the Netherlands who enrolled in a RCT at less than 16 weeks 

gestation (52 of 208 women developed GHTN).67 Intake of n-3 FA was established based on use 

of FFQ (and dietary history as a double check). No differences were observed in total n-3 FA 

intake between women who subsequently developed GHTN and those who did not, prior to 

delivery. However postpartum levels of serum DHA were significantly higher in women with 

GHTN than in women without GHTN after correction for gestational age. 

A 2001 study of 3,133 healthy Norwegian women who completed a validated FFQ found a 

slight but significant increase in the risk for PE associated with increasing intakes of n-3 FA and 

n-6 FA, adjusted for age, smoking status, BMI, systolic blood pressure, and parity.68 Further 

adjustment for energy intake resulted in these trends no longer being significant.

A 2006 study followed 488 healthy Icelandic women: 30 developed GHTN and 19 developed 

PE. Analysis of responses to a semi-quantitative food and lifestyle questionnaire showed that 

women who consumed cod liver oil early in pregnancy were almost 5 times as likely to develop 

GHTN or PE than women who did not (adjusted OR 4.7, [1.8, 12.6] p=0.002) (findings were 

45
adjusted for weight gain during pregnancy, BMI, weight gain, smoking, parity, and diastolic and 

systolic blood pressure early in pregnancy). Cod liver oil is a source of vitamins A, D, and E as 

well as n-3 FA. A slight U-shaped association was seen between daily intakes of n-3FA and risk 

for GHTN or PE or GHTN alone (p=0.008).70

Project Viva, a U.S. study, followed 1,718 pregnant women, 59 of whom developed PE (3%) 

and 119 who developed GHTN (7%). Multivariate logistic regression analysis of a modified 

validated semi-quantitative FFQ showed a slightly decreased risk for PE with higher intakes of 

DHA + EPA (adjusted OR 0.84 [0.69, 1.03] per 100 mg per day) and DHA+EPA: AA (adjusted 

OR 0.82 [0.66, 1.01]) but not for GHTN (adjusted for maternal age [<20, 20–40, 40+ years], 

prepregnancy body mass index (continuous), first-trimester systolic blood pressure 

[continuous],race/ethnicity (black, Hispanic, white, other), education [college graduate, < college

graduate], and parity [0, 1+]; intakes were adjusted for total energy intake. No association was 

seen for intakes of ALA.69

n-3 FA Biomarkers

One of the studies described above assessed the association between biomarkers for n-3s and 

the risk for GHTN.67 No significant differences were found at any point during pregnancy in any 

of the maternal plasma phospholipid n-3 FA or n-6 FA between women who developed GHTN 

and those who did not. However postnatal plasma phospholipids of women with GHTN showed 

lower levels of ALA and LA than did those of women with normal pregnancies.

A second study identified for this report assessed the association between maternal third 

trimester plasma total n-3 PUFAs and the risk for GHTN.71 The Growing UP in Singapore 

Towards healthy Outcomes (GUSTO) study recruited a cohort of pregnant Chinese, Malay, and 

Indian women residing in Singapore. A total of 28 women out of 722 for whom data were 

available developed GHTN and/or preeclampsia (women with a history of pre-pregnancy HTN 

were excluded from this analysis). A 1 percent increase in plasma total and long-chain n-3 FA 

was significantly inversely associated with the risk for GHTN (adjusted OR 0.76, [0.60, 0.97] 

and 0.77 [0.60, 0.98], respectively). The authors adjusted for age, ethnicity, education, exercise, 

alcohol intake, smoking status, BMI and height at the 26th-28th week of gestation, gestational 

diabetes, heart rate, and fish oil supplementation.

Observational study subgroup analyses

None of the studies reported subgroup analyses. 

46
Table 3. RCTs for gestational hypertension preeclampsia eclampsia

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Carlson et al., 201331

Study name: NR

Study dates: 2006.01-

2011.10

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy pregnant women

Pregnant enrolled 350 

Pregnant withdrawals 49 

Pregnant completers 301

Pregnant age: placebo: 

24.8; DHA: 25.3 (placebo 

4.7; DHA 4.9)

Race of Mother: Black 

(46%;37%) Non-black 

(54%; 63%)

Baseline biomarker 

information: RBCphospholipid-DHA 

(placebo group 4.3 +-

1.3; 4.3 +- 1.1)

Baseline Omega-3 

intake: Voluntary DHA 

intake from supplement 

(placebo group 15%, 

DHA group 9%)

Inclusion Criteria: 

English-speaking, 

between 8 and 20 wk of 

gestation, between 16 

and 35.99 y of age, and 

planning to deliver at a 

hospital in the Kansas

City metropolitan area

Exclusion Criteria: 

carrying more than one 

fetus, had preexisting 

diabetes mellitus or 

systolic blood pressure 

$140 mm Hg at 

enrollment, or had any 

serious health condition 

likely to affect the 

prenatal or postnatal 

growth and development 

of their offspring, 

including cancer, lupus, 

hepatitis, HIV/AIDS, or a 

diagnosed alcohol or 

chemical dependency. or 

if the initial screening 

based on their selfreported weight and 

height suggested a BMI 

(in kg/m2 >=40).

Start time: Pregnant 99.6/102.9 day

Duration: Pregnant enrollment to birth

Arm 1: Placebo

Description: half soybean and half coin oil

Manufacturer: DSM Nutritional Products)

Active ingredients: a-linolenic acid

Dose: 3 *capsule 200/day

Blinding: both DHA and placebo capsules were 

orange flavored

Arm 2: DHA

Description: marine algae-oil source of DHA

Manufacturer: DHASCO; DSM Nutritional Products, 

formerly Martek Biosciences)

Dose: 200 mg capsule, 3 times a day

DHA: 200mg/capsule * 3

Outcome: preeclampsia (Secondary)

Follow-up time: during pregnancy

Arm 1: 2/147 (1.3%)

Arm 2: 2/154 (1.3%)

Harper et al., 201029

Study name: NR

Study dates: 01. 2005 -

10. 2006

Study design: Trial 

randomized parallel

Location: US

Study Population: At risk 

for preterm labor

Pregnant enrolled 852 

Pregnant withdrawals 0 

Pregnant completers 852

Pregnant age: n3: 28 

placebo 27 n3 23-32; 

placebo 24-32

Race of Mother: White 

Inclusion Criteria: a 

documented history of at 

least one prior singleton 

preterm delivery between 

20 0/7 and 36 6/7 weeks 

of gestation after 

spontaneous preterm 

labor or premature 

rupture of the 

membranes, and a 

current singleton 

pregnancy between 16 

Start time: Pregnant 16-22 week gestation age

Duration: Pregnant 36 weeks of gestation

Arm 1: placebo

Description: inert mineral oil

Manufacturer: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: four capsules of matching oil containing a 

minute amount of inert mineral oil

Outcome: preeclampsia or gestational 

hypertension (Secondary)

Follow-up time: during pregnancy

Arm 1: 20/418 (4.8%)

Arm 2: 20/434 (4.6%)

47
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Klebanoff, 201149

European (n3: 56.5; 

placebo 57.7) Black (n3: 

34.1; placebo 34.9) Asian 

(n3: 3, placebo 1.2) 

Hispanic (n3: 14.7; 

placebo 13.6) Other 

race/ethnicity (NR)

and 21 6/7 weeks of 

gestation

Exclusion Criteria: 

evidence of a major fetal 

anomaly, intake of a fish 

oil supplement in excess 

of 500 mg per week at 

any time during the 

preceding month, allergy 

to fish, anticoagulation 

therapy, hypertension, 

White’s classification D 

or higher diabetes, drug 

or alcohol abuse, seizure 

disorder, uncontrolled 

thyroid disease, clotting 

disorder, current or 

planned cerclage, or a 

plan to deliver either 

elsewhere or before 37 

weeks of gestation

Blinding: Boxes containing a woman’s entire supply 

of capsules in blister packs were sequentially 

numbered according to the predetermined 

randomization sequence, and on enrollment a 

woman was assigned the next number in sequence. 

Study group assignment was not known by study 

participants, their health care providers, or the 

research personnel

Arm 2: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: in 4 capsules total 2000 mg of n3

DHA: 800 mg

EPA: 1200 mg

48
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Mozurkewich et al., 

201342

Study name: NR

Study dates: Oct 2008 -

May 2011

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy pregnant women

Pregnant enrolled 126 

Pregnant withdrawals 8 

Pregnant completers 118

Pregnant age: EPA 29.9; 

DHA 30.6; placebo 30.4 

(EPA 5.0; DHA 4.5; 

placebo 5.9)

Race of Mother: White 

European (85%; 76%; 

83%) Black (10%; 11%; 

5%) Asian (3%; 3%; 2%) 

Hispanic (0%; 11%; 7%) 

Inuit Eskimo (0%; 0%; 

2%) Pacific Islander (NR)

Baseline biomarker 

information: EPA group: 

EPA 0.29+-0.18; DHA 

4.24+-2.30; total n3 FA: 

22.10+-3.72 DHA group: 

EPA 0.31+-0.24; DHA 

4.66+-2.29; total n3 FA 

36.41+-9.71 placebo: 

EPA .34+-0.22; DHA 

3.85+-1.77; omega3 FA

322.86+-5.02

Inclusion Criteria: past 

history of depression, an 

EPDS score 9-19 (at risk 

for depression or mildly 

depressed), singleton 

gestation, a maternal age 

of 18 years or older, and 

a gestational age of 12-

20 weeks

Exclusion Criteria: had a 

history of a bleeding 

disorder, thrombophilia 

requiring anticoagulation, 

multiple gestation, bipolar 

disorder, current major 

depressive disorder, 

current substance abuse,

lifetime substance 

dependence, or 

schizophrenia. Women

were also ineligible if 

they were currently 

taking omega-3 fatty acid 

supplements or 

antidepressant 

medications or eating 

more than 2 fish meals 

per week.

Start time: Pregnant 12-20 week gestation

Duration: Pregnant assuming till birth

Arm 1: Control/Placebo

Description: 98% soy oil and 1% each of lemon and 

fish oil

Manufacturer: Nordic Naturals Corporation in

Watsonville, CA

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large and 4 small placebo capsules

Blinding: The placebos were formulated to be 

identical in appearance to both the EPA- and DHArich supplements

Arm 2: EPA-rich fish oil

Description: an approximate 4:1 ratio of EPA to DHA 

(1060 mg EPA plus 274 mg DHA)

Brand name: ProEPAXtra, Nordic Naturals

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large EPA capsule and 4 small placebo

DHA: 274 mg

EPA: 1060 mg

Arm 3: DHA-rich fish oil

Description: DHA and EPA in an approximate 4:1 

ratio o (900 mg DHA plus 180 mg EPA)

Brand name: ProDHA, Nordic Naturals

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large placebo oil and 4 small DHA rich

DHA: 900 mg

EPA: 180 mg

Outcome: gestational hypertension or 

preeclampsia (Secondary)

Follow-up time: during pregnancy

Arm 1: 5/41 (12.0%)

Arm 2: 8/39 (21.0%)

Arm 3: 2/38 (5.0%)

Zhou et al., 201255

Study name: DOMInO

Study dates: 10. 2005 -

01. 2008

Study design: Trial 

randomized parallel

Study Population: 

Healthy pregnant women

Pregnant enrolled 2399

Race of Mother: White 

European (88%;88%) 

Asian (7%;8%) Inuit 

Eskimo (2%;1%) Other 

Inclusion Criteria: NR

Exclusion Criteria: If 

already taking a dietary 

supplement containing 

DHA, their fetus had a 

known major 

abnormality, they had a 

bleeding disorder for 

Start time: Pregnant medium gestational age 19 

weeks

Duration: Pregnant birth

Arm 1: control

Description: 500-mg vegetable oil capsules

Dose: 3*500mg 3 nongenetically modified oils 

(rapeseed, sunflower, and palm) in equal 

Outcome: preeclampsia (Secondary)

Follow-up time: during pregnancy

Arm 1: 58/1202 (4.85%)

Arm 2: 60/1197 (4.97%)

Outcome: pregnancy induced hypertension 

(Secondary)

Follow-up time: during pregnancy

Arm 1: 107/1202 (8.88%)

Arm 2: 98/1197 (8.18%)

49
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Palmer, 

201254; Palmer, 201356; 

Makrides, 2014 57

race/ethnicity (NR) which fish oil was 

contraindicated, they 

were receiving 

anticoagulant therapy, 

they had a documented 

history of drug or alcohol 

abuse, they were 

participating in another 

fatty acid trial, or English 

was not the main

language spoken at 

home

proportions

Blinding: All capsules were similar in size, shape, 

and color

Arm 2: DHA

Description: DHA-rich fish oil

Manufacturer: Incromega 500 TG; Croda Chemicals

Dose: 3*500mg capsule

DHA: 800 mg

EPA: 100 mg

AA = arachidonic acid; ALA = alpha linolenic acid; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; Hg = mercury; LCPUFA = long chian polyunsaturated fatty acid; mg 

= milligram; n-3 FA = omega-3 fatty acid; n-6 FA = omega-6 fatty acid; NR = not reported; RBC = red blood cell; RCT = randomized controlled trial; SD = standard deviation

50
Table 4. Observational studies for gestational hypertension preeclampsia eclampsia

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Clausen, et al., 200168

Outcome domain: Gestational HTN and 

Preeclampsia

Study dates: 12/94-8/96

Study design: Observational prospective

Location: Norway

Funding source / conflict: NR

Study Population: Healthy pregnant women

Pregnant enrolled 3,771 Pregnant completers 

3,133

Pregnant age: 29.8 (4.5)

Race of Mother: White European (100)

Inclusion Criteria: Caucasian women seen at Aker 

University Hospital for prenatal care and who agreed 

to undergo ultrasound at their first prenatal visit and 

who completed a FFQ

Exclusion Criteria: Pregestational diabetes, abortion, 

twin or triplet pregnancies, patients who give birth at 

other hospitals, missing records, loss to followup

Adjustments: Age, smoking 

(yes or no), BMI (<=20, 20-25, 

25-30, >30), systolic blood 

pressure (sBP) before 20 

weeks’ gestation, and 

nullipara (yes or no)

Lim, et al., 201571

Outcome domain: Gestational HTN and 

Preeclampsia

Study dates: 2009-2012

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Study Population: Healthy pregnant women

Pregnant enrolled 1162 Pregnant completers 

751

Infants completers

Pregnant age: 1st tertile 29.9 2nd tertile 30.0 

3rd tertile 31.7 _ (1st tertile 5. 2 2nd tertile 5.2,

3rd tertile 4.8)

Race of Mother: Asian (100)

Inclusion Criteria: Healthy women in early pregnancy 

at one of 3 tertiary care hospitals in Singapore

Exclusion Criteria: receiving chemotherapy, taking 

psychotropic drugs, or having type 1 diabetes

Adjustments: Adjusted for 

age, ethnicity, education, 

exercise, alcohol intake, 

smoking status, BMI, and 

height at the 26th to the 28th 

week of gestation, gestational 

diabetes, and heart rate, fish 

oil supplementation

Oken, et al., 200769

Outcome domain: Gestational HTN and 

Preeclampsia

Study name: Project Viva

Study dates: Recruitment 1999-2002

Study design: Observational prospective

Location: US

Funding source / conflict: Government, Multiple

foundations and Societies

Study Population: Healthy pregnant women

Pregnant enrolled 2,128 Pregnant completers 

1,718

Pregnant age: 93% were 20-40 years

Race of Mother: White European (72%) Black 

(12%) Hispanic (6%) Other race/ethnicity (10%)

Inclusion Criteria: 1st trimester pregnant women 

attending 1st prenatal visit

Exclusion Criteria: Post hoc: no live birth, no medical 

records, failure to complete dietary questionnaires, 

pre-existing chronic hypertension and no 

subsequent preeclampsia

Adjustments: Maternal age, 

prepregnancy BMI, 1st 

trimester sBP, race/ethnicity, 

education, parity; nutrients 

adjusted for total energy 

intake

Olafsdottir, et al., 200670

Outcome domain: Gestational HTN and 

Preeclampsia

Study Population: Healthy pregnant women

Pregnant enrolled 549 Pregnant completers 488

Pregnant age: 28 (5)

Inclusion Criteria: Pregnant women attending first 

prenatal visit at Center of Prenatal Care in Reykjavik 

from 1999-2001, who gave birth to full-term babies 

completed the study.

Adjustments: Weight gain 

during pregnancy, BMI X 

weight gain, smoking, parity 

and diastolic and systolic 

blood pressure early in 

51
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Study dates: 1999-2001

Study design: Observational prospective

Location: NR

Funding source / conflict: Government, Multiple

foundations and Societies

Race of Mother: White European (NR)

Exclusion Criteria: Essential hypertension, 

gestational diabetes, miscarriage/stillbirth, 

twins/triplets, preterm birth, loss of personal data, 

moved, missing data,

pregnancy

BMI = body mass index; HTN = hypertension; NR = not reported; sBP = systolic blood pressure

52
Risk for Low Birth Weight

Key Findings and Strength of Evidence for Risk of Low Birth Weight

• There is a low level of evidence that maternal supplementation of DHA during pregnancy 

may not have significant effects on risk for delivering a low birth weight (LBW) infant. 

o Pooled analysis of 4 RCTs that assessed the effects of DHA alone or DHAenriched fish oil on the risk of delivering a LBW infant among women not at 

increased risk showed no significant effects. 

o One RCT that assessed the effect of DHA+EPA on the risk of delivering a LBW 

infant among women at increased risk showed no significant effects. 

o One prospective observational study that assessed the effect of EPA intake in the 

third trimester of pregnancy on LBW found a significantly increased risk among 

women in the first and second tertiles of EPA intake. No associations were seen 

between tertiles of EPA intake and risk of LBW in the first or second trimesters of 

pregnancy.

Description of Included Studies

The original report included three RCTs that assessed the effects of maternal n-3 FA intake 

on the outcome of intrauterine growth retardation (IUGR) and seven RCTs that assessed the 

effects of maternal n-3 FA intake on the outcome of low birth weight (LBW, defined as less than 

2,500 g or as less than 2,000 g). Two RCTs assessed both IUGR and LBW outcomes. For the 

IUGR outcome, all three RCTs enrolled pregnant women at risk of IUGR, due to a previous 

history of IUGR, twin pregnancy, or history of premature delivery. Meta-analysis of these three 

RCTs found no significant effects of DHA+EPA supplementation (doses ranged from 2.2 to 3 

g/d) on the incidence of IUGR (birth weight < 3rd and 10th percentile, adjusted for gestational 

age [GA]) between DHA+EPA supplementation and control groups (OR: 1.14, 95% Confidence 

Interval [CI] 0.79; 1.64). Of the seven RCTs that assessed LBW outcomes, two compared n-3 

FA-enriched eggs (DHA 0.23 g/d) with control eggs and the other five compared fish oil 

(DHA+EPA) supplements with placebo. Five of the seven RCTs showed that n-3 FA 

supplementation did not influence the incidence of LBW infants among pregnant women with or 

without a history of previous IUGR. The other two RCTs each found a lower incidence of LBW 

infants born to women who received fish oil (DHA+EPA) supplements compared with those 

who received placebo (-26% and -1.9%). 

For the current report, we identified five RCTs (in 9 publications) 29, 31-35, 43, 55, 61 that assessed 

the effects of maternal n-3 FA intake on risk of LBW or small-for-gestational-age (SGA) (see 

Table 5). Three of these RCTs also reported the outcome of risk for very low birth weight 

(VLBW, less than 1500 g).29, 31, 43 Of the five RCTs, three (in four publications)29, 34, 55, 61

assessed the effects of maternal n-3 intake on risk of SGA or IUGR. In addition, we identified 

one observational study72 that assessed the effects of maternal n-3 FA intake on risk of LBW and 

two observational studies 46, 73 that examined the association of maternal n-3 FA exposure 

(dietary intake or plasma concentration) with risk for SGA/IUGR. In all studies, SGA or IUGR 

were both defined as birth weight for gestational age <10th percentile of a reference standard,

and LBW and VLBW were defined as birth weight <2,500 and <1,500 g, respectively. Of the 

studies identified for the current report, all were conducted among healthy pregnant women, 

except for one RCT that enrolled women who were identified as being at risk of having an 

SGA/IUGR outcome due to having at least one prior spontaneous preterm delivery.

29

53
Randomized Controlled Trials

Five RCTs (in eight publications) were identified for the current report that assessed the 

effects of n-3 FA interventions on LBW or VLBW. Three of the publications were from the 

POSGRAD (Prenatal DHA (Omega-3 fatty acid) Supplements on infant GRowth And 

Development) trial, 32-34 and two of the publications were from the Docosahexaenoic Acid to 

Optimise Mother Infant Outcome (DOMInO) trial.

35, 55

DHA

The POSGRAD trial randomized 1,094 pregnant Mexican women (18-22 weeks’ gestation) 

to receive 0.4 g/day DHA or a placebo containing olive oil.34 Data on birth outcomes were 

available for 973 women, of whom 487 were randomized to receive DHA and 486 were 

randomized to receive placebo. Overall, no difference was seen in the percent of women 

delivering LBW infants (percent LBW, 5.5 percent for DHA vs. 5.6 percent for placebo, 

p=0.99). However, when stratified by gravidity, the findings showed a trend towards lower 

percent LBW in the DHA group compared to the placebo group (3.3 percent for DHA vs. 7.4 

percent for placebo, p=0.08) among primigravidae women, but no difference among 

multigravidae women (6.9 percent for DHA vs. 4.4 percent for placebo, p=0.18). The percent of 

LBW infants was not different in the subset of infants with 18-month follow-up data 34 or the 

subset on whom measures of auditory or visual evoked potentials were obtained.33

The DOMInO trial 35, 55 randomized 2,399 healthy pregnant Australian women (<21 weeks’ 

gestation) to receive a DHA-rich fish oil concentrate containing 0.8 g/day DHA and 0.1 g/day 

EPA (n=1197) or a vegetable oil placebo (n=1202). Percent LBW differed significantly between 

the two groups (3.4 percent DHA vs. 5.3 percent placebo, p=0.03).

Two other small RCTs both examined the effects of DHA on the risk for LBW and VLBW in 

a total of 435 healthy pregnant women. 31, 43 Carlson randomized 350 healthy pregnant women in 

the US (8-20 weeks’ gestation) to receive 0.6 g/day DHA or a placebo containing half soybean 

and half corn oil. 31 Of the 301 women with birth outcome data, 154 were randomized to DHA 

and 147 to placebo. The study observed a trend toward lower risk for LBW in the DHA group 

compared to the placebo group (3.9 percent vs. 9.0 percent, p=0.059). A significant difference 

was also observed in the percentage of infants born with VLBW between the two groups (0 

percent for DHA vs. 3.4 percent for placebo, p=0.026). Min randomized 85 healthy pregnant 

women in the UK (11-12 weeks’ gestation) to receive 0.6 g/day DHA or a placebo containing 

high oleic acid sunflower oil. 43 Of the 59 women with birth outcome data, 32 were randomized 

to DHA and 27 to placebo. No significant differences were seen in the risk of LBW (12.5 percent 

for DHA vs. 11.1 percent for placebo, p>0.05) or VLBW (3.1 percent for DHA vs. 0 percent for 

placebo, p>0.05).

Our meta-analysis of four trials in healthy pregnant women showed that maternal DHA 

supplementation had no significant effects on LBW outcome (OR [95% CI]=0.72 [0.43, 1.11], 

I

2

=7%). (Figure 8)

54
Figure 8. Risk for low birth weight (<2500g) – DHA versus placebo

EPA+DHA

Harper et al (2010)29 randomized 852 US women who had at least one prior spontaneous 

preterm delivery to receive marine oils (0.8 g/day DHA plus 1.2 g/day EPA) or a mineral oil 

placebo. Capsules from both groups also contained 10 IU vitamin E per capsule and all women 

received weekly injections of 17α-hydroxyprogesterone caproate. Among the 837 liveborn 

neonates with birth weight data available, 427 were randomized to the n-3 group and 410 were 

randomized to placebo. This study found no significant difference in the percent of LBW infants 

between the two groups (22 percent n-3 vs. 27 percent placebo, p>.05). There was also no 

difference in the percent of VLBW infants between the two groups (6.1 percent n-3 vs. 7.1

percent placebo, p>.05).

Observational Studies

Muthayya (2009) assessed the association between n-3 FA intake in the first, second, and 

third trimesters of pregnancy and LBW among 675 women (ages 17-40 and <20 weeks of 

gestation) receiving medical care at St. John’s Medical College Hospital in Bangalore, India.72

Additionally, erythrocyte membrane phospholipid FA status was measured in a random 

subsample of 150 women in each trimester. No association was observed between tertiles of 

EPA intake and LBW in the first or second trimesters of pregnancy. In the third trimester 

(n=419), women in the first and second tertiles of EPA intake had significantly increased risk of 

LBW compared to the highest tertile after adjusting for confounders (adjusted OR [AOR] 2.75, 

95% CI 1.26-6.02 for tertile 1; AOR 2.54, 95% CI1.17-5.50 for tertile 2). No significant 

association was observed between erythrocyte FA status and risk of LBW in this study.

55
Table 5. RCTs that assessed risk for low birth weight

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Carlson et al., 201331

Study name: NR

Study dates: 2006.01-

2011.10

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population:

Healthy pregnant women

Pregnant enrolled 350 

Pregnant withdrawals 49 

Pregnant completers 301

Pregnant age: placebo: 

24.8; DHA: 25.3 (placebo 

4.7; DHA 4.9)

Race of Mother: Black 

(46%;37%) Non-black 

(54%; 63%)

Baseline biomarker 

information: RBCphospholipid-DHA 

(placebo group 4.3 +-

1.3; 4.3 +- 1.1)

Baseline Omega-3 

intake: Voluntary DHA 

intake from supplement 

(placebo group 15%, 

DHA group 9%)

Inclusion Criteria: 

English-speaking, 

between 8 and 20 wk of 

gestation, between 16 

and 35.99 y of age, and 

planning to deliver at a 

hospital in the Kansas 

City metropolitan area

Exclusion Criteria: 

carrying more than one 

fetus, had preexisting 

diabetes mellitus or 

systolic blood pressure 

$140 mm Hg at 

enrollment, or had any 

serious health condition 

likely to affect the 

prenatal or postnatal 

growth and development 

of their offspring, 

including cancer, lupus, 

hepatitis, HIV/AIDS, or a 

diagnosed alcohol or 

chemical dependency. or 

if the initial screening 

based on their selfreported weight and 

height suggested a BMI 

(in kg/m2 >=40).

Start time: Pregnant 99.6/102.9 day

Duration: Pregnant enrollment to birth

Arm 1: Placebo

Description: half soybean and half coin oil

Manufacturer: DSM Nutritional Products)

Active ingredients: a-linolenic acid

Dose: 3 *capsule 200/day

Blinding: both DHA and placebo capsules were 

orange flavored

Arm 2: DHA

Description: marine algae-oil source of DHA

Manufacturer: DHASCO; DSM Nutritional Products, 

formerly Martek Biosciences)

Dose: 200 mg capsule, 3 times a day

DHA: 200mg/capsule * 3

Outcome: birth weight <1500g (Secondary)

Follow-up time: birth

Arm 1: 5/147 (3.4%)

Arm 2: 0/154 (0.0%)

Outcome: birth weight <2500g (Secondary)

Follow-up time: birth

Arm 1: 13/147 (9.0%)

Arm 2: 6/154 (3 .9%)

Harper et al., 201029

Study name: NR

Study dates: 01. 2005 -

10. 2006

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Study Population: At risk 

for preterm labor

Pregnant enrolled 852 

Pregnant withdrawals 0 

Pregnant completers 852

Pregnant age: n3: 28 

placebo 27 n3 23-32; 

placebo 24-32

Race of Mother: White 

European (n3: 56.5; 

Inclusion Criteria: a 

documented history of at 

least one prior singleton 

preterm delivery between 

20 0/7 and 36 6/7 weeks 

of gestation after 

spontaneous preterm 

labor or premature 

rupture of the 

membranes, and a 

current singleton 

pregnancy between 16 

and 21 6/7 weeks of 

Start time: Pregnant 16-22 week gestation age

Duration: Pregnant 36 weeks of gestation

Arm 1: placebo

Description: inert mineral oil

Manufacturer: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: four capsules of matching oil containing a 

minute amount of inert mineral oil

Blinding: Boxes containing a woman’s entire supply 

Outcome: birth weight <1500g (Secondary)

Follow-up time: birth

Arm 1: 29/410 (7.1%)

Arm 2: 26/427 (6.1%)

Outcome: birth weight <2500g

Follow-up time: birth

Arm 1: 112/410 (27.3%)

Arm 2: 94/427 (22.0%)

56
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Klebanoff, 201149

placebo 57.7) Black (n3: 

34.1; placebo 34.9) Asian 

(n3: 3, placebo 1.2) 

Hispanic (n3: 14.7; 

placebo 13.6) Other 

race/ethnicity (NR)

gestation

Exclusion Criteria: 

evidence of a major fetal 

anomaly, intake of a fish 

oil supplement in excess 

of 500 mg per week at 

any time during the 

preceding month, allergy 

to fish, anticoagulation 

therapy, hypertension, 

White’s classification D 

or higher diabetes, drug 

or alcohol abuse, seizure 

disorder, uncontrolled 

thyroid disease, clotting 

disorder, current or 

planned cerclage, or a 

plan to deliver either 

elsewhere or before 37 

weeks of gestation

of capsules in blister packs were sequentially 

numbered according to the predetermined 

randomization sequence, and on enrollment a 

woman was assigned the next number in sequence. 

Study group assignment was not known by study 

participants, their health care providers, or the 

research personnel

Arm 2: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: in 4 capsules total 2000 mg of n3

DHA: 800 mg

EPA: 1200 mg

Makrides et al., 201035

Study name: DOMInO

Study dates: 2005-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Smithers, 201153; Palmer, 

201254; Zhou, 201255;

Palmer, 201356; 

Makrides, 2014 57

Study Population: 

Healthy pregnant women

Pregnant enrolled 2399 

Pregnant withdrawals 1

Infants enrolled 605 

Infants withdrawals 32 

Infants completers 726

Pregnant age: 28.9 

(DHA5.7___ control5.6)

Race of Mother: NR

Inclusion Criteria: with 

singleton pregnancies at 

less than 21 weeks’ 

gestation were 

approached by study 

research assistants while 

attending routine 

antenatal appointments

Exclusion Criteria: 

already taking a prenatal 

supplement with DHA, 

their fetus had a known 

major abnormality, they 

had a bleeding disorder 

in which tuna oil was 

contraindicated, were 

taking anticoagulant 

therapy, had a 

documented history of 

drug or alcohol abuse, 

were participating in 

another fatty acid trial, 

were unable to give 

Start time: Pregnant < 21 week's gestation

Duration: NR

Arm 1: vegetable oil capsules

Description: a blend of 3 nongenetically modified oils 

(rapeseed, sunflower, and palm) in equal 

proportions

Manufacturer: Efamol, Surrey, England.

Dose: 3* 500mg capsule / day

Blinding: All capsules were similar in size, shape, 

and color

Arm 2: DHA

Description: DHA-rich fish oil concentrate

Manufacturer: ; Incromega 500 TG, Croda 

Chemicals, East Yorkshire, England

Dose: 500mg capsule *3/day

DHA: 800mg

EPA: 100mg

duplicate data of id 4404

57
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

written informed consent, 

or if English was not the 

main language spoken at 

home

Min et al., 201443

Study name: NR

Study dates: Jan 2008 -

Dec 2011

Study design: Trial 

randomized parallel

Location: UK

Funding source / conflict: 

Industry, Government, 

Multiple foundations and 

Societies, Manufacturer 

supplied product

Original, same study, or 

follow-up studies: none

Study Population: 

Healthy pregnant 

women, Pregnant women 

with type 2 diabetes

Pregnant enrolled 85 

Pregnant completers 59

Pregnant age: 29 18-44

Infant age: 11.0-12.1 

weeks gestation 6.0-15.9 

weeks gestation

Race of Mother: White 

European (22.3%) Black 

(28.2%) Asian (40.0%) 

Other race/ethnicity 

(9.4%)

Inclusion Criteria: 

Pregnant women of 17–

45 years old with 

singleton pregnancies 

with either pre-existing 

Type 2 diabetes or 

without any known 

medical condition 

(uncomplicated 

pregnancy group)

Exclusion Criteria: 

Women planning to 

receive tocolytic or 

corticosteroid therapy. 

Note that pregnant 

women with pre-existing 

Type 2 diabetes were 

excluded from this 

systematic review.

Start time: Pregnant average: 9.9-12.1 weeks 

gestation (range: 4.3-15.9 weeks gestation)

Duration: Pregnant until delivery; average: 26.5 

weeks for placebo arm; 28.4 weeks for the fish oil 

arm

Arm 1: Placebo, healthy women

Description: high oleic acid sunflower oil

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: oleic acid, 82.6%; vitamin E (d- a 

tocopherol) NR%

Dose: 2x 750 mg capsules/day

Blinding: identical oblong soft gelatin capsule

Maternal conditions

Current smoker 0%

Arm 2: Fish oil, healthy women

Description: HA-enriched fish oil

Brand name: Mumomega

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: vitamin E (d- a tocopherol) NR%

Dose: 2 750 mg capsules/day

Maternal conditions

DHA: 43.7% (600 mg/d)

EPA: 7.5% (estimated to be 103 mg/d)

Current smoker 13.3%

Arm 3: Placebo, diabetic women

Description: high oleic acid sunflower oil

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: oleic acid, 82.6%; vitamin E (d- a 

tocopherol) NR%

Dose: 2 750 mg capsules/day

Maternal conditions

Current smoker 0%

Other maternal conditions 

1arm_3_maternal_conditions_other1

Other maternal conditions 10 Type 2 diabetes: 100%

Arm 4: Fish oil, diabetic women

Outcome: birth weight <1500g (Secondary)

Follow-up time: birth

Arm 1: 0/27 (0.0%)

Arm 2: 1/32 (3.1%)

Outcome: birth weight <2500g (Secondary)

Follow-up time: birth

Arm 1: 3/27 (11.1%)

Arm 2: 4/32 (12.5%)

58
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Description: HA-enriched fish oil

Brand name: Mumomega

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: vitamin E (d- a tocopherol) NR%

Dose: 2 750 mg capsules/day

Blinding: identical oblong soft gelatin capsule

Maternal conditions

DHA: 43.7%

EPA: 7.5%

Current smoker 4.9%

Other maternal conditions 

1arm_4_maternal_conditions_other1

Other maternal conditions 10 Type 2 diabetes: 10

Ramakrishnan et al., 

201032

Study name: POSGRAD

Study dates: Feb 2005 -

Feb 2007

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, March of 

Dimes

Original, same study, or 

follow-up studies: Stein, 

201233; Imhoff-Kunsch, 

201158; Escamilla-Nunez, 

201459; GonzalezCasanova, 201560; 

Ramakrishnan, 201561; 

Stein, 201134

Study Population: 

Healthy pregnant women

Pregnant enrolled 1,094 

Pregnant withdrawals 67 

Pregnant completers 973 

(for birth weight)

Pregnant age: 26.2 

(controls) 26.3 (DHA) 

(4.6 (controls) 4.8 (DHA))

Race of Mother: Hispanic 

(NR)

Baseline Omega-3 

intake: mg/day for all: LA: 

17,846 in controls, 

17,645 in DHA AA: 137 

in controls, 140 in DHA 

ALA: 1,488 in controls, 

1,477 in DHA EPA: 18 in 

controls, 18 in DHA DHA: 

54 in controls, 56 in DHA

Inclusion Criteria: 18-35 

yrs. of age, in gestation 

weeks 18-22, planned to 

deliver at the IMSS 

General Hospital in 

Cuernavaca, exclusively 

or predominantly 

breastfeed for at least 3 

months, liver in the area 

for at least 2 years after 

delivery.

Exclusion Criteria: highrisk pregnancy; lipid 

metabolism or absorption 

disorders, regular intake 

of fish oil or DHA 

supplements; chronic use 

of certain medications 

(e.g., medications for 

epilepsy).

Start time: Pregnant at study entry

Duration: Pregnant mid pregnancy (18-22 weeks 

gestation) until delivery

Arm 1: Controls

Description: Placebo containing olive oil

Manufacturer: Martek Biosciences

Dose: 1 capsule, twice a day

Blinding: Identical tablets

Arm 2: DHA

Description: Intervention

Manufacturer: Martek Biosciences

Dose: 1 capsule twice a day

DHA: 400 mg/d, 200 mg/dl derived from algal source

Outcome: birth weight <2500g (Secondary)

Follow-up time: birth

Arm 1: 27/486 (5.6%)

Arm 2: 27/487 (5.5%)

Stein et al., 201134

Study name: POSGRAD

Study dates: 02. 2005-

02.2007

Study Population: 

Healthy infants

Pregnant enrolled 1094 

Pregnant completers 973

Pregnant age: placebo 

Inclusion Criteria: women 

were 18–35 y, were in 

gestation wk 18–22, and 

planned to deliver at the 

IMSS General Hospital in 

Cuernavaca, exclusively 

or predominantly breastStart time: Pregnant 18-22 Gestational week Infants 

birth

Duration: Pregnant birth

Arm 1: Placebo

Description: Olive oil

Outcome: birth weight <2500g (Secondary)

Follow-up time: birth

Arm 1: 20/370 (5.4%)

Arm 2: 16/369 (4.3%)

59
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, Multiple

foundations and 

Societies

Original, same study, or 

follow-up studies: Stein, 

201233; Imhoff-Kunsch, 

201158; Escamilla-Nunez, 

201459; GonzalezCasanova, 201560; 

Ramakrishnan, 201561; 

Ramakrishnan, 201132

26.3; DHA 26.4 (placebo 

4.6; DHA 4.9)

Infant age: 39.1 (placebo 

1.6; DHA 1.8)

Race of Mother: NR

feed for at least 3 mo, 

and to live in the area for 

at least 2 y after delivery

Exclusion Criteria: NR

Manufacturer: Martek Biosciences

Dose: 2 capsules olive oil

Blinding: Similar in appearance and taste to DHA 

capsules

Arm 2: DHA

Description: algal DHA capsules

Manufacturer: Martek Biosciences

Dose: 2 capsules * 200mg

DHA: 400 mg

Stein et al., 201233

Study name: POSGRAD

Study dates: Feb 2005-

Feb 2007

Study design: Trial 

randomized parallel

Location: NR

Funding source / conflict: 

Government

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Imhoff-Kunsch, 201158; 

Escamilla-Nunez, 201459;

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 1094 

Pregnant withdrawals 63 

Pregnant completers 900

Pregnant age: 26.3 (4.6-

4.8)

Infant age: 39.1 (1.7-1.8)

Race of Mother: NR (NR)

Inclusion Criteria: 

Singleton live births 

without congenital 

anomalies

Exclusion Criteria: 3364: 

high risk pregnancy, 

(history and prevalence 

of pregnancy 

complications, including 

abruption placentae, 

preeclampsia, 

pregnancy-induced 

hypertension, any 

serious bleeding episode 

in the current pregnancy, 

and physician referral); 

lipid metabolism or 

absorption disorders, 

regular intake of fish oil 

or DHA supplement, or 

chronic use of certain 

medication(e.g. epilepsy 

medications)

Start time: Pregnant 18-22 wk

Duration: Pregnant to birth

Arm 1: Placebo

Description: A mixture of corn and soy oil

Manufacturer: Martek Biosciences

Blinding: "Participants and members of the study 

team were unaware of the treatment scheme 

throughout the intervention period of the study"

Arm 2: DHA

Description: DHA 400 mg/d

Manufacturer: Martek Biosciences

Dose: 2 capsule per day

DHA: 2*200mg

Outcome: birth weight <2500g (Primary)

Follow-up time: birth

Arm 1: 24/452 (5.3%)

Arm 2: 17/448 (3.8%)

Zhou et al., 201255

Study name: DOMInO

Study Population: 

Healthy pregnant women

Inclusion Criteria: NR

Exclusion Criteria: If 

Start time: Pregnant medium gestational age 19 

weeks

Outcome: birth weight <2500g (Secondary)

Follow-up time: birth

Arm 1: 63/1202 (5.27%)

60
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: 10. 2005 -

01. 2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Palmer, 

201254; Palmer, 201356; 

Makrides, 2014 57

Pregnant enrolled 2399

Race of Mother: White 

European (88%;88%) 

Asian (7%;8%) Inuit 

Eskimo (2%;1%) Other 

race/ethnicity (NR)

already taking a dietary 

supplement containing 

DHA, their fetus had a 

known major 

abnormality, they had a 

bleeding disorder for

which fish oil was 

contraindicated, they 

were receiving 

anticoagulant therapy, 

they had a documented 

history of drug or alcohol 

abuse, they were 

participating in another 

fatty acid trial, or English 

was not the main

language spoken at 

home

Duration: Pregnant birth

Arm 1: control

Description: 500-mg vegetable oil capsules

Dose: 3*500mg 3 nongenetically modified oils 

(rapeseed, sunflower, and palm) in equal 

proportions

Blinding: All capsules were similar in size, shape, 

and color

Arm 2: DHA

Description: DHA-rich fish oil

Manufacturer: Incromega 500 TG; Croda Chemicals

Dose: 3*500mg capsule

DHA: 800 mg

EPA: 100 mg

Arm 2: 41/1197 (3.41%)

DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; mg = milligram; n-3 FA = omega-3 fatty acid;; NR = not reported; OR = odds ratio; RBC = red blood cell; RCT = 

randomized controlled trial; UK = United Kingdom

61
Small for Gestational Age (SGA)/Intrauterine Growth Retardation 

(IUGR)

Key Findings and Strength of Evidence for Risk for SGA/IUGR

• There is a low level of evidence that maternal EPA+DHA supplementation may not have 

significant effects on risk for SGA/IUGR among women at increased risk for preterm 

delivery.

o Two RCTs in our update found no effect of DHA alone or DHA-enriched fish oil 

on SGA/IUGR outcomes in healthy pregnant women.

o Pooled analyses of four RCTs that assessed the effects of fish oil supplementation 

(DHA+EPA) on SGA/IUGR among women at increased risk for preterm delivery 

found no significant effects. 

o One prospective observational study found no association between intake of 

DHA+EPA intake and SGA outcome.

o One observational study among multiparous pregnant women found a two-fold 

increase in risk of SGA among women in the lowest quintile of plasma EPA 

concentration in early pregnancy compared to those in the middle quintile. No 

association was seen between plasma DHA concentrations in early pregnancy and 

risk of SGA.

Description of Included Studies

Randomized Controlled Trials

Three RCTs (in four publications) were identified for the current report that examined the 

effects of maternal n-3 supplementation on SGA/IUGR outcomes: one from the POSGRAD 

trial,34, 61 one from the DOMInO trial, 35, 55 and the third by Harper et al.29 Details of these three 

studies have been described above (see Table 6). Overall, our update meta-analysis of six RCTs 

(three from the original report) showed that n-3 supplementation did not have significant effects 

on SGA/IUGR (OR=0.98; 95% CI 0.85, 1.13; I2 = 0).

DHA

In the POSGRAD trial, Ramakrishnan (2015) reported SGA/IUGR outcomes on the subset of 

infants who were followed up at 18 months. Among these, 365 pregnant women were 

randomized to receive 400 mg/day DHA, and 365 received placebo.34, 61 The authors reported no 

significant difference in percent of infants born with IUGR between the two groups (9.9 percent 

DHA vs. 10.7 percent placebo, p=0.91). 

Zhou (2012) reported SGA/IUGR outcomes among women enrolled in the DOMInO trial.55

They found no difference in percent of infants born SGA between the two groups (6.1 percent 

DHA-enriched fish oil vs. 6.8 percent placebo, p=0.49).

EPA+DHA

In the US study by Harper (2010),29 no significant difference was observed in infants born 

SGA between the progesterone group and the progesterone plus marine oils group. Random 

effects meta-analysis of the four RCTs enrolling women at risk of SGA/IUGR (this study plus 

the three from the original report) found no significant effects of DHA+EPA supplementation 

62
(doses ranged from 2.0 to 3 g/d) on the incidence of SGA/IUGR compared with placebo (OR

[95% CI]=1.00, CI[0.70, 1.43], I2=0%) (Figure 9).

Figure 9. Risk for small for gestational age: DHA + EPA or DHA versus placebo

Observational Studies

Two prospective studies evaluated the association between some measure of maternal n-3 FA 

exposure and risk of SGA (see Table 7). One46 measured dietary n-3 FA intake and the other73

measured concentrations of DHA and EPA in the plasma.

n-3 FA Intake

Oken et al.

46 evaluated the association between maternal n-3 FA intake and risk of having an 

SGA birth among 2,109 women enrolled in Project Viva, a prospective, observational cohort 

study of gestational diet, pregnancy outcomes, and offspring health in the US (Massachusetts). 

The investigators reported no association between quartiles of DHA+EPA intake and risk of 

having an SGA birth outcome.

n-3 FA Biomarkers

Smits73 evaluated the role of plasma DHA and EPA concentrations in the relationship 

between interpregnancy interval and adverse pregnancy outcome in a subsample (n=1,659) of the 

Amsterdam Born Children and their Development (ABCD) cohort, a population-based cohort 

study of multiparous pregnant women in the Netherlands. Women in the lowest quintile of EPA 

concentration (<0.33 mg/L) in early pregnancy had a two-fold increased risk (OR=2.09, 95% 

CI1.32-3.30) of having an SGA birth compared to those in the middle quintile (0.46 -0.58 mg/L). 

Concentrations of DHA in early pregnancy showed no association with risk of SGA.

63
Table 6. RCTs for infants born small gestational age and intrauterine growth retardation

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant 

information

Inclusion and Exclusion 

Criteria

Start time,

Duration,

Arms Results

Harper et al., 201029

Study name: NR

Study dates: 01. 2005 - 10. 2006

Study design: Trial randomized 

parallel

Location: US

Funding source / conflict: 

Government, Manufacturer 

supplied product

Original, same study, or follow-up 

studies: Klebanoff, 201149

Study 

Population: At 

risk for preterm 

labor

Pregnant 

enrolled 852 

Pregnant 

withdrawals 0 

Pregnant 

completers 852

Pregnant age: 

n3: 28 placebo 

27 n3 23-32; 

placebo 24-32

Race of Mother: 

White European 

(n3: 56.5; 

placebo 57.7) 

Black (n3: 34.1; 

placebo 34.9) 

Asian (n3: 3, 

placebo 1.2) 

Hispanic (n3: 

14.7; placebo 

13.6) Other 

race/ethnicity 

(NR)

Inclusion Criteria: a 

documented history of at 

least one prior singleton 

preterm delivery between 

20 0/7 and 36 6/7 weeks of 

gestation after 

spontaneous preterm labor 

or premature rupture of the 

membranes, and a current 

singleton pregnancy 

between 16 and 21 6/7 

weeks of gestation

Exclusion Criteria: 

evidence of a major fetal 

anomaly, intake of a fish oil

supplement in excess of 

500 mg per week at any 

time during the preceding 

month, allergy to fish, 

anticoagulation therapy, 

hypertension, White’s 

classification D or higher 

diabetes, drug or alcohol 

abuse, seizure disorder, 

uncontrolled thyroid 

disease, clotting disorder, 

current or planned 

cerclage, or a plan to 

deliver either elsewhere or 

before 37 weeks of 

gestation

Start time: Pregnant 16-22 week gestation age

Duration: Pregnant 36 weeks of gestation

Arm 1: placebo

Description: inert mineral oil

Manufacturer: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: four capsules of matching oil containing a 

minute amount of inert mineral oil

Blinding: Boxes containing a woman’s entire supply 

of capsules in blister packs were sequentially 

numbered according to the predetermined 

randomization sequence, and on enrollment a woman 

was assigned the next number in sequence. Study 

group assignment was not known by study 

participants, their health care providers, or the 

research personnel

Arm 2: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: in 4 capsules total 2000 mg of n3

DHA: 800 mg

EPA: 1200 mg

Outcome: SGA less than 10th percentile 

(Secondary)

Follow-up time: birth

Arm 1: 41/410 (10.0%)

Arm 2: 35/427 (8.2%)

Hauner et al., 201237

Study name: INFAT

Study dates: July 14 2006 - may 

22 2009

Study design: Trial randomized 

parallel

Study 

Population: 

Healthy 

pregnant 

women

Pregnant 

enrolled 208

Pregnant 

withdrawals 38 

Inclusion Criteria: healthy 

pregnant women before 

the 15th wk of gestation, 

between 18 and 43 y of 

age, prepregnancy BMI (in 

kg/m2) between 18 and 30, 

willingness to implement 

the dietary 

recommendations, 

sufficient German 

Start time: Pregnant 15th wk of gestation

Duration: Pregnant to 4 mo postpartum

Arm 1: Control

Description: brief semi structured counseling on a 

healthy balanced diet according to the guidelines of 

the German Nutrition Society and were explicitly 

asked to refrain from taking fish oil or DHA 

supplements

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 4/96 (4.2%)

Arm 2: 3/92 (3.3%)

64
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant 

information

Inclusion and Exclusion 

Criteria

Start time,

Duration,

Arms Results

Location: Germany

Funding source / conflict: Industry, 

Government, Multiple foundations 

and Societies

Pregnant 

completers 170

Infants enrolled 

188 Infants 

withdrawals 18 

Infants 

completers 170

Pregnant age: 

31.9 (4.9) 18-43

Race of Mother: 

NR (NR)

Baseline 

biomarker 

information: 

Maternal fatty 

acid profile in 

RBCs at 15th 

wk: EPA, DHA, 

AA, and n-6:n-3 

LCUFA ratio 

(reported in 

Table 2 by 

intervention and 

control groups). 

No significant 

differences 

between groups.

Baseline 

Omega-3 intake: 

7-d dietary 

records 

completed by 

participants at 

the 15th 

(baseline) and 

32nd wk of 

gestation but 

only dietary 

intake at 32nd 

we of gestation 

language skills.

Exclusion Criteria: high-risk 

pregnancy (multiple 

pregnancy, rhesus 

incompatibility, hepatitis B 

infection, or parity .4); 

hypertension; chronic 

diseases (e.g., diabetes) or 

gastrointestinal disorders 

accompanied by 

maldigestion, 

malabsorption, or elevated 

energy and nutritional 

requirements (e.g., gluten 

enteropathy); known 

metabolic defects (e.g., 

phenylketonuria); 

psychiatric diseases; 

hyperemesis gravidarum; 

supplementation with n–3 

LCPUFAs before 

randomization; and alcohol 

abuse and smoking.

N-6 N-3: 2.80 +- 1.17 (SD) at 32nd wk of gestation

AA: 10.15 +- 3.89 SD) at 32nd wk of gestation

Arm 2: Intervention

Description: Fish-oil supplement + nutritional 

counseling (to normalize the consumption of AA

Brand name: Marinol D-40

Manufacturer: Lipid Nutrition

DHA: 1020 mg

EPA: 180 mg

N-6 N-3: 1.54 +- 0.63 (SD) at 32nd wk of gestation

AA: 8.82 +- 2.84 (SD) at 32nd wk of gestation

Other dose 1: Vit E 9 mg

65
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant 

information

Inclusion and Exclusion 

Criteria

Start time,

Duration,

Arms Results

was reported (in 

Table 2). At 

week 32 of 

gestation, the 

dietary n-6:n-3 

PUFA ratio was 

.5:1 in the 

intervention 

group compared 

with :1 in the 

control group, 

as originally 

intended.

Ramakrishnan et al., 201561

Study name: POSGRAD

Study dates: 2005-2009

Study design: Trial randomized 

parallel

Location: Mexico

Funding source / conflict: 

Government, None, March of 

Dimes

Study follow-up: 18 months

Original, same study, or follow-up 

studies: Ramakrishnan, 201032; 

Stein, 201233; Imhoff-Kunsch, 

201158; Escamilla-Nunez, 201459;

Gonzalez-Casanova, 201560; 

Ramakrishnan, 201561

Study 

Population:

Healthy 

pregnant 

women

Pregnant 

enrolled 1094 

Pregnant 

completers 968

Infants enrolled 

973 Infants 

completers 730

Pregnant age: 

Placebo: 26.3 

Intervention: 

26.5 (Placebo: 

4.6 Intervention: 

4.9)

Infant age: 

Placebo: 20.5 

weeks gestation 

Intervention: 

20.6 weeks 

gestation 

(Placebo: 2.1 

weeks 

Intervention: 2.0 

weeks)

Inclusion Criteria: Women 

who were in gestation 

week 18–22, age 18–35 

years, planned to deliver at 

the IMSS General Hospital 

and to remain in the area 

for the next 2 years, and 

planned predominant 

breastfeeding for at least 3 

months

Exclusion Criteria: High 

risk pregnancy, had any 

lipid metabolism/absorption 

conditions, regularly took 

DHA or fish oil 

supplements, or used 

certain chronic medications 

(such as antiepileptic 

drugs)

Start time: Pregnant 18-22 weeks gestation

Duration: Pregnant 18-22 weeks gestation until 

delivery

Arm 1: Control

Description: Corn and soy oils with no added 

antioxidants

Dose: 2 capsules/day

Blinding: Similar in appearance and taste to the DHA 

capsules

Arm 2: Intervention

Description: Algal-sourced DHA capsule

Manufacturer: Martek Biosciences

Dose: 2 capsules/day

DHA: 200 mg * 2 = 400 mg/d

Outcome: IUGR (Secondary)

Follow-up time: birth

Arm 1: 36/365 (9.9%)

Arm 2: 39/365 (10.7%)

66
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant 

information

Inclusion and Exclusion 

Criteria

Start time,

Duration,

Arms Results

Race of Mother: 

NR (NR)

Baseline 

Omega-3 intake: 

From original 

study ref 3364

mg/day for all: 

LA: 17,846 in 

controls, 17,645 

in DHA AA: 137 

in controls, 140 

in DHA ALA: 

1,488 in 

controls, 1,477 

in DHA EPA: 18 

in controls, 18 in 

DHA DHA: 54 in 

controls, 56 in 

DHA

Stein et al., 201134

Study name: POSGRAD

Study dates: 02. 2005- 02.2007

Study design: Trial randomized 

parallel

Location: Mexico

Funding source / conflict: 

Government, Multiple foundations 

and Societies

Original, same study, or follow-up 

studies: Stein, 201233; ImhoffKunsch, 201158; Escamilla-Nunez, 

201459; Gonzalez-Casanova, 

201560; Ramakrishnan, 201561; 

Ramakrishnan, 201132

Study 

Population: 

Healthy infants

Pregnant 

enrolled 1094 

Pregnant 

completers 973

Pregnant age: 

placebo 26.3; 

DHA 26.4 

(placebo 4.6; 

DHA 4.9)

Infant age: 39.1 

(placebo 1.6; 

DHA 1.8)

Race of Mother: 

NR

Inclusion Criteria: women 

were 18–35 y, were in 

gestation wk 18–22, and 

planned to deliver at the 

IMSS General Hospital in 

Cuernavaca, exclusively or 

predominantly breast-feed 

for at least 3 mo, and to 

live in the area for at least 

2 y after delivery

Exclusion Criteria: NR

Start time: Pregnant 18-22 Gestational week Infants 

birth

Duration: Pregnant birth

Arm 1: Placebo

Description: Olive oil

Manufacturer: Martek Biosciences

Dose: 2 capsules olive oil

Blinding: Similar in appearance and taste to DHA 

capsules

Arm 2: DHA

Description: algal DHA capsules

Manufacturer: Martek Biosciences

Dose: 2 capsules * 200mg

DHA: 400 mg

Outcome: IUGR (intrauterine growth 

retardation); birth weight for gestational 

age < 10th percentile (Secondary)

Follow-up time: birth

Arm 1: 38/368 (10.3%)

Arm 2: 39/369 (10.6%)

Zhou et al., 201255 Study 

Population: 

Inclusion Criteria: NR Start time: Pregnant medium gestational age 19 

weeks

Outcome: SGA for weight (Secondary)

Follow-up time: birth

67
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant 

information

Inclusion and Exclusion 

Criteria

Start time,

Duration,

Arms Results

Study name: DOMInO

Study dates: 10. 2005 - 01. 2008

Study design: Trial randomized 

parallel

Location: Australia

Funding source / conflict: 

Government, Multiple foundations 

and Societies, Manufacturer 

supplied product

Original, same study, or follow-up 

studies: Makrides, 201035; 

Smithers, 201153; Palmer, 201254; 

Palmer, 201356; Makrides, 201457

Healthy 

pregnant 

women

Pregnant 

enrolled 2399

Race of Mother: 

White European 

(88%;88%) 

Asian (7%;8%) 

Inuit Eskimo 

(2%;1%) Other 

race/ethnicity 

(NR)

Exclusion Criteria: If 

already taking a dietary 

supplement containing 

DHA, their fetus had a 

known major abnormality, 

they had a bleeding 

disorder for which fish oil 

was contraindicated, they 

were receiving 

anticoagulant therapy, they 

had a documented history 

of drug or alcohol abuse, 

they were participating in 

another fatty acid trial, or 

English was not the main

language spoken at home

Duration: Pregnant birth

Arm 1: control

Description: 500-mg vegetable oil capsules

Dose: 3*500mg 3 nongenetically modified oils 

(rapeseed, sunflower, and palm) in equal proportions

Blinding: All capsules were similar in size, shape, and 

color

Arm 2: DHA

Description: DHA-rich fish oil

Manufacturer: Incromega 500 TG; Croda Chemicals

Dose: 3*500mg capsule

DHA: 800 mg

EPA: 100 mg

Arm 1: 82/1202 (6.83%)

Arm 2: 73/1197 (6.13%)

68
Table 7. Observational studies for infants born small gestational age

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Smits, et al., 201373

Outcome domain: SGA

Study name: Amsterdam Born Children and 

their Development (ABCD)

Study dates: Jan 2003- Mar 2004

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: None

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 1659 Pregnant completers 

1659

Infants enrolled 1659 Infants completers 1659

Pregnant age: <25 y, 5.7% 25-34 y, 61.2% 

>=35 y, 33.1%

Infant age: 40.0 weeks (1.2)

Race of Mother: White European (88.4)

Inclusion Criteria: NR

Exclusion Criteria: primiparous women or delivered 

preterm

Adjustments: Potential 

confounding factors were 

evaluated but none of them 

was significant confounding 

defined as changing the odds 

ratio by 10%

69
Birth Weight 

Key Findings and Strength of Evidence for Birth Weight

• Overall meta-analysis of 16 RCTs showed that n-3 FA supplementation in healthy 

pregnant women significantly increased birth weight compared with placebo or other 

controls (WMD [95% CI] 74.80 [12.42, 137.17] grams). No evidence of publication bias 

was seen (Begg’s and Egger’s p values were 0.368 and 0.245, respectively)

o Random-effects meta-regression found no significant linear dose-response 

relationships between doses of DHA, EPA, or DHA to EPA ratio and the effect 

sizes.

o No significant difference was seen in the pooled effect sizes between DHA and 

EPA+DHA supplementation subgroups (P=0.52).

• There is a moderate level of evidence that maternal supplementation of DHA or DHArich fish oils may increase birth weight.

o Pooled analysis of 12 RCTs showed significantly higher birth weights among 

infants whose mothers received algal DHA or DHA-enriched fish oil than among 

infants of mothers who received a placebo (WMD [95% CI]=90.12 [2.62, 177.62] 

grams).

o Pooled analysis of five RCTs found no significant effect of maternal EPA+DHA 

supplementation on infant birth weight.

o One RCT that assessed the effects of ALA on infant birth weight showed no 

effects.

o Three prospective observational studies showed that maternal n-3 FA biomarker 

levels were significantly and positively associated with infant birth weight, 

whereas the one other study did not find an association between maternal quartile 

of erythrocyte EPA+DHA and infants’ birth weight.

• There is a low level of evidence that supplementation of EPA+DHA may not have 

significant effects on infants’ birth weight compared with placebo. 

o Pooled analysis of five RCTs showed that fish oil or fish supplementation among 

healthy pregnant women did not have a significant effect on birth weight 

compared with placebo or control.

o Two prospective observational studies showed no association between maternal 

n-3 FA intake from supplements and infant birth weight.

o Four prospective observational studies that assessed the effects of maternal 

dietary n-3 FA intake on infant birth weight showed inconsistent results. Two 

studies found no association between dietary n-3 FA intake and infant birth 

weight. A third study found that infants born to mothers in the lowest quartile of 

DHA+EPA intake had significantly higher birth weights than infants born to 

mothers in the highest quartile of DHA+EPA intake. This association held true for 

DHA+EPA intake measured in all three trimesters of pregnancy. The fourth study 

found that both maternal DHA and ALA intake were significantly and positively 

associated with birth weight.

70
Description of Included Studies

The original report included 12 RCTs (in nine publications) that compared mean birth weight 

values (in grams) between maternal n-3 FA supplemented and control groups. Of these studies, 

pregnant women received DHA-enriched eggs (DHA 0.23 g/d) in two RCTs, fish oil 

supplements (EPA+DHA doses ranged from 0.23 to 5 g/d) in nine RCTs, and dietary 

supplementation with margarine delivering ALA (2.82 g/d) and linoleic acids (9.02 g/d) in one 

RCT. The between-group difference in the mean birth weight was not significant in eight of the 

12 studies, was significantly higher in the n-3 FA supplementation groups compared with 

controls in three studies (1 DHA-enriched eggs, 1 fish oil supplementation, and 1 dietary 

supplementation with ALA and linoleic acids), and was significantly lower in the fish oil 

supplementation (EPA+DHA 2.2 g/d) than in the control group (olive oil) in one study. Only one 

prospective cohort study was included in the original report. This cohort study found that the 

maternal plasma triglyceride AA, but not phospholipid or cholesteryl ester AA, was positively 

related to infant birth weight and length (p<0.01). No other correlations were found between 

maternal plasma n-3 or n-6 FA and these variables.

Eighteen new RCTs and ten observational studies were identified for the current report. All, 

except for one study 29 were conducted among healthy pregnant women and followed up until 

birth. The one RCT that enrolled pregnant women at risk for preterm labor (defined as a 

documented history of at least one prior singleton preterm delivery after spontaneous preterm 

labor or premature rupture of the membranes) was therefore excluded from the meta-analysis. 

Overall we found a moderate level of evidence that maternal supplementation of DHA or DHArich fish oils may increase birth weight but the dose-response relationship between DHA dose 

and the effect size is still unclear. This finding is consistent with findings from the observational 

studies, which found that higher maternal blood DHA concentrations were associated with 

higher birth weight. 

Randomized Controlled Trials

Eighteen unique RCTs were identified for the current report (see Table 8). Of these, four 

RCTs (in six publications) compared algal DHA supplements with placebo controls,31-34, 74, 75, 

eight (in nine publications) compared DHA-rich fish oil supplementation (DHA:EPA ratio ≥5:1) 

with placebo controls,35, 37-42, 55, 66 five compared fish oil supplements (EPA+DHA, DHA:EPA 

ratio <5:1) with placebo,29, 42, 44, 76, 77 one compared a salmon-rich diet with no dietary salmon

(EPA+DHA, DHA:EPA ratio <5:1),78 and one compared black current seed oil (ALA 0.42 g/d; 

0.09 SDA g/d) with placebo.79 One RCT compared both DHA-rich fish oil supplement and more 

balanced (EPA/DHA) fish oil supplement with placebo.42 Overall, meta-analysis combining 16 

RCTs showed that n-3 FA supplementation in healthy pregnant women significantly increased 

birth weight compared with placebo or controls (WMD [95% CI] 74.8 [12.42, 137.17] grams), 

with moderate heterogeneity (I2 = 49.5). (Figure 10) Random-effects meta-regression found no 

significant linear dose-response relationships between doses of DHA (beta coefficient [SE]= 

32.86 [61.32], P=0.60, n=16), EPA (beta coefficient [SE]= -39.64 [51.55], P=0.46, n=15), or 

DHA to EPA ratio (beta coefficient [SE]= 12.0 [13.3], P=0.39, n=11) and the effect sizes (mean 

differences in birth weight between n-3 FA and placebo groups).

DHA

Four RCTs (in six publications) randomized healthy pregnant women between 12 and 20 

weeks of gestation to DHA supplements from algae oil (0.4 or 0.6 g/d DHA) or placebo 

(soybean, corn, or olive oil).31-34, 74 Two RCTs analyzed the birth weight outcome in a total of 

71
353 mothers and their infants living in the US,31, 74 one analyzed 200 mothers and their infants in 

Canada,

75 and one analyzed 973 mothers and their infants in Mexico (POSGRAD trial).32-34 It 

should be noted that, of the three publications from the POSGRAD trial, the Ramakrishnan 

(2010) publication analyzed the largest number of study participants,32 while the other two 

publications analyzed a subset of the trial participants.33, 34 Thus, only results from Ramakrishnan 

(2010) were included in our meta-analysis. Overall, only one of the four RCTs found a 

significantly higher mean birth weight (+172 grams, P=0.004) in infants whose mothers received 

DHA (0.6 g/d) supplementation (n=154) than those whose mothers received placebo (n=147).31

The other three RCTs (DHA 0.4 and 0.6 g/d) did not find significant differences in mean birth 

weight between DHA supplementation and placebo groups.32-34, 74

Eight RCTs randomized healthy pregnant women between 12 and 24 weeks of gestation to 

DHA-rich fish oil supplementation or controls. Studies were conducted in the US (n=4), 

Germany (n=2), Australia (n=1), and the Netherlands (n=1). Of the eight RCTs, three compared 

DHA-containing cereal-based bars (mean DHA 0.214-0.240 and EPA 0.027-0.030 g/d; 

DHA:EPA ratio = 8) with placebo bars;

38-40 four (in five publications) compared DHA-rich fish 

oil supplements (DHA 0.200-1.020 and EPA 0.100-0.180 g/d; DHA:EPA ratio = 5-8), 37, 41, 42

with controls (vegetable oil, nutritional counseling, vitamins and minerals, or soy oil), and one 

three-arm RCT compared DHA-rich fish oil plus soybean oil (DHA 0.220 and EPA 0.036 g/d 

plus ALA 0.032 g/d), DHA-rich fish oil plus AA (DHA 0.220 and EPA 0.036 g/d plus AA 0.220 

g/d) with placebo (soybean oil).66 Five of the eight RCTs with lower DHA doses (0.2-0.22 g/d) 

did not find significant differences in the mean birth weight between DHA supplementation and 

placebo in a total of 316 infants,38-41, 66 whereas the other three RCTs (in four publications) with 

higher DHA doses (0.8-1.02 g/d) all found a significantly higher mean birth weight in infants 

whose mothers received DHA-rich fish oil supplement compared with those whose mothers 

received placebo (+68 to +465 grams) among a total of 2,656 infants.35, 37, 42, 55 The three-arm 

RCT also did not find a significant difference in the mean birth weight between DHA-rich fish 

oil plus AA (DHA 0.220 and EPA 0.036 g/d plus AA 0.220 g/d, n=39) and placebo (soybean oil, 

n=34).66

Our random-effects meta-analysis of 12 RCTs showed that the mean birth weight was 

significantly higher in infants whose mothers received algal DHA or DHA-rich fish oil 

supplement than in those whose mothers received placebo (WMD [95% CI]=90.12 [2.62 177.62] 

grams high heterogeneity (I2 = 63.2). (Figure 10)

72
Figure 10. Birth weight (g): DHA versus Placebo, DHA + EPA versus placebo

EPA+DHA

Four RCTs randomized healthy pregnant women between 12 and 25 weeks of gestation to 

fish oil supplements (EPA+DHA) or placebo (soybean oil, corn oil, olive oil or inert mineral 

oil).42, 44, 76, 77 In addition, one other single-blind trial randomized healthy pregnant women at 

week 20 of gestation to oily fish (farmed salmon) or no oily fish added to their habitual diet.78

Studies were conducted in the US (n=2), U.K. (n=1), Norway (n=1), and Bangladesh (n=1). The 

doses of EPA ranged from 0.16 to 1.8 g/d, and the doses of DHA ranged from 0.27 to 2.2 g/d. 

The DHA to EPA ratio ranged from 0.26 to 2. The total doses of EPA plus DHA ranged from 

0.49 to 3.3 g/d. None of these studies found a significant difference in mean birth weight 

between groups.

Our random-effects meta-analysis of five RCTs showed that maternal fish oil or fish 

supplementation (EPA+DHA doses ranged from 0.49 to 3.3 g/d) did not have a significant effect 

on birth weight compared with placebo or control (WMD [95% CI]=37.89 [-19.53, 95.31] 

grams; no heterogeneity [I

2 = 0%]). 

73
One additional RCT that enrolled 852 pregnant US women at risk for preterm labor (defined as a 

documented history of at least one prior singleton preterm delivery after spontaneous preterm 

labor or premature rupture of membranes) also did not find a significant effect of fish oil 

supplementation (EPA+DHA 2 g/d) on birth weight (Figure 10).

29

ALA

One RCT randomized healthy pregnant women (<16 weeks of gestation) to either black 

current seed oil (ALA 0.42 g/d; SDA 0.09 g/d) or placebo (olive oil). The results did not show a 

significant difference in birth weight between groups in a total of 241 infants.79

Observational Studies

Ten prospective cohort studies that assessed the association between n-3 FA intakes or status 

and birth weight were identified for the current report (see Table 9). Of these, six studies 

assessed the associations between maternal dietary intake of n-3 FA (from foods or supplements) 

and birth weight.46, 47, 80-82 The other four studies examined the relationships between maternal n3 FA biomarkers and birth weight.73, 83, 84

n-3 FA Intake

Two studies assessed the associations between maternal n-3 FA intake from supplements and

birth weight.81, 82 The Norwegian Mother and Child Cohort Study (MoBa), which enrolled a 

nation-wide pregnancy cohort, did not find significant associations between maternal 

supplementary n-3 FA intake (g/d) at 28 weeks of gestation and infants’ birth weight (n=61,387).

In contrast, a small cohort study in Iceland found that infants born to mothers who reported 

taking liquid cod liver oil in first trimester had higher birth weight (132 [95% CI 18, 246] grams) 

than did those born to mothers who did not take liquid cod liver oil in first trimester (n=350)

Four studies assessed the associations between maternal dietary n-3 FA intake and birth 

weight.46-48, 80 Two of the four studies, enrolling a total of 1816 mother-infant pairs, did not find 

a significant association between maternal dietary n-3 FA intake and birth weight.47, 80 The third 

study, by Oken et al.,

46 evaluated the association between quartiles of maternal DHA+EPA 

intake (median 0.02 g/d) and birth weight: They found that infants born to mothers in the lowest 

quartile of DHA+EPA intake had higher birth weight than those born to mothers in the highest 

quartile of DHA+EPA intake (median 0.27 to 0.38 g/d) during the first (94 [95%CI 23, 166] 

grams, n=1797), second (50 [95%CI -19, 119] grams, n=1663), and third (90 [95%CI 33, 147] 

grams, n=2070) trimesters. The fourth study, by Molto-Puigmarti,

48 found that maternal DHA 

intake (mg/d) was significantly associated with birth weight in a fully adjusted model (beta 

coefficient=0.16; 95% CI 0.008, 0.313, n=2606). Similarly, a significant association was 

observed between maternal ALA intake (mg/d) and birth weight (beta coefficient=0.106; 95% CI 

0.026, 0.186, n=2606).

n-3 FA Biomarkers

Four prospective cohort studies examined the relationships between maternal n-3 FA 

biomarkers and birth weight.73, 83-85 Three studies assessed blood DHA measures (one red blood 

cell [RBC]; two plasma phospholipids). All three studies found that higher maternal blood DHA 

concentrations were associated with higher birth weight in a total of 2,491 mother-and-infant 

pairs. One study each also assessed RBC total n-3 FA83, RBC EPA+DHA (% total FA),85 and 

plasma EPA.73 Similar findings were reported for the associations between plasma EPA or RBC 

74
total n-3 FA concentrations and birth weight, but no associations was found between RBC 

EPA+DHA concentrations and birth weight. Individual study findings are described below.

The INFAT study,83 conducted in Germany, enrolled healthy pregnant women at the 14th

week of gestation and examined the associations between maternal RBC DHA and total n-3 FA 

at 32 weeks of gestation and birth weight. They found that per unit increase in percent maternal 

RBC DHA or percent total n-3 FA of total FA was significantly associated with an average of 24 

(95% CI 0.42, 48) and 20 (95% CI 2.78, 38) grams increase in birth weight (n=187).

Dirix (2009)

84 enrolled healthy pregnant women less than 16 weeks of gestation and 

measured their plasma DHA (%, w/w plasma phospholipids) at 16, 22, and 32 weeks of 

gestation. This study found that per unit increase in maternal plasma DHA content (%, w/w 

plasma phospholipids) at 16 weeks of gestation was significantly associated with an average of 

52 (95% CI 20, 84) grams increase in infants’ birth weight (n=665). Per unit increase in maternal 

plasma DHA content (%, w/w plasma phospholipids) at 22 weeks (n=623) and 32 weeks (n=644) 

of gestation were marginally associated with an average of 31 (95% CI -4.3, 67) and 33 (95% CI 

-5.7, 72) grams increase in infants’ birth weight, respectively.

Smits et al.73 analyzed the associations between plasma DHA and EPA concentrations and 

infants’ birth weight in a subsample (n=1,659) of the Amsterdam Born Children and their 

Development (ABCD) cohort, a population-based cohort study of multiparous pregnant women 

in the Netherlands. Infants born to mothers in the lowest quintile of EPA concentration (<0.33 

mg/L) or DHA concentration (<3.74 mg/L) in early pregnancy had significantly lower birth 

weight (-182.5 [39 SE] or -118.2 [39 SE] grams, respectively) compared with those born to 

mothers in the middle quintile (EPA 0.46 -0.58 mg/L or DHA 4.35 -4.86 mg/L). 

Mohanty (2015)85 analyzed a subset of 534 (60%) healthy pregnant women at 16 weeks 

gestation who participated in the Omega study and were randomly selected for the analysis of 

erythrocyte membrane EPA and DHA. Their analysis did not find an association between 

maternal quartile of erythrocyte EPA + DHA (ranging from 2.28 to 9.55 percent of total fatty 

acids) and infants’ birth weight after adjusting for potential confounders.

75
Table 8. RCTs for birth weight

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Carlson et al., 201331

Study name: NR

Study dates: 2006.01-

2011.10

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy pregnant women

Pregnant enrolled 350 

Pregnant withdrawals 49 

Pregnant completers 301

Pregnant age: placebo: 

24.8; DHA: 25.3 (placebo 

4.7; DHA 4.9)

Race of Mother: Black 

(46%;37%) Non-black 

(54%; 63%)

Baseline biomarker 

information: RBCphospholipid-DHA 

(placebo group 4.3 +-

1.3; 4.3 +- 1.1)

Baseline Omega-3 

intake: Voluntary DHA 

intake from supplement 

(placebo group 15%, 

DHA group 9%)

Inclusion Criteria: 

English-speaking, 

between 8 and 20 wk of 

gestation, between 16 

and 35.99 y of age, and 

planning to deliver at a 

hospital in the Kansas 

City metropolitan area

Exclusion Criteria: 

carrying more than one 

fetus, had preexisting 

diabetes mellitus or 

systolic blood pressure 

$140 mm Hg at 

enrollment, or had any 

serious health condition 

likely to affect the 

prenatal or postnatal 

growth and development 

of their offspring, 

including cancer, lupus, 

hepatitis, HIV/AIDS, or a 

diagnosed alcohol or 

chemical dependency. or 

if the initial screening 

based on their selfreported weight and 

height suggested a BMI 

(in kg/m2 >=40).

Start time: Pregnant 99.6/102.9 day

Duration: Pregnant enrollment to birth

Arm 1: Placebo

Description: half soybean and half coin oil

Manufacturer: DSM Nutritional Products)

Active ingredients: a-linolenic acid

Dose: 3 *capsule 200/day

Blinding: both DHA and placebo capsules were 

orange flavored

Arm 2: DHA

Description: marine algae-oil source of DHA

Manufacturer: DHASCO; DSM Nutritional Products, 

formerly Martek Biosciences)

Dose: 200 mg capsule, 3 times a day

DHA: 200mg/capsule * 3

Outcome: birth weight (g) (Primary)

Follow-up time: birth

Arm 1: Sample size 147; mean 3187.0; SD 

(602)

Arm 2: Sample size 154; mean 3359.0; SD 

(524)

Courville et al., 201138

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Study Population: 

Healthy pregnant women

Pregnant enrolled 47 

Pregnant withdrawals 0 

Pregnant completers 47

Pregnant age: NR (NR) 

NR

Race of Mother: White 

European (8.5) Black 

Inclusion Criteria: 

Healthy pregnant 

women, mid-pregnancy 

(20–24 weeks)

Exclusion Criteria: parity 

.5; history of chronic 

hypertension; 

hyperlipidaemia; renal or 

liver disease; heart 

disease; thyroid disorder; 

multiple gestations; 

Start time: Pregnant 20-24 wk of gestation

Duration: Pregnant until birth

Arm 1: Placebo

Description: placebo bars (

Manufacturer: Nestec Limited (Vevey, Switzerland)

Dose: 5 placebo bars per week

Blinding: NR

Arm 2: DHA-FF

Description: DHA cereal-based bars

Outcome: birth weight (kg) (Unspecified)

Follow-up time: birth

Arm 1: Sample size 25; mean 3.19; SD 

(0.44)

Arm 2: Sample size 22; mean 3.33; SD 

(0.46)

76
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Industry, Government (10.6) Asian (4.3) 

Minority (Puerto 

Rican/Latino 66%; 

African - other 8.5%; 

Other or mixed ethnicity 

= 2%)

Baseline Omega-3 

intake: Dietary DHA 

intake (mg/d), not 

including the intervention 

food, from 24 h dietary 

recalls: DHA-FF 67+-7 

(SD); Placebo 87+-10 

(SD), P=0.059

having been pregnant or 

lactating in the previous 2 

years.

Manufacturer: Nestec Limited (Vevey, Switzerland)

Dose: 5DHA cereal-based bars per week

DHA: 241 mg/d

EPA: 30.1 mg/d

Dunstan et al., 200844

Study name: Dunstan

Study dates: 2000-2003

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Multiple foundations and 

Societies

Original, same study, or 

follow-up studies: 

Dunstan, 200350; 

Meldrum, 201551

Study Population: 

Healthy infants Pregnant 

women with allergies

Pregnant enrolled 98 

Pregnant completers 83

Infants enrolled 83 

Infants withdrawals 11 (7 

FO, 4 control) Infants 

completers 72

Pregnant age: Fish oil: 

30.9 Control: 32.6 (Fish 

oil: 3.7 Control: 3.6)

Infant age: Term (mean 

gestational period 275 

days)

Race of Mother: NR (NR)

Baseline biomarker 

information: Cord blood 

erythrocyte (as % total 

fatty acids) 20:4n-6 14.9 

(1.4) 17.6 (1.0) ,0.001 

20:5n-3 1.3 (0.5) 0.4 

(0.3) ,0.001 22:3n-6 2.8 

(0.5) 3.9 (0.5) ,0.001 

Inclusion Criteria: 

Healthy term infants of 

pregnant women enrolled 

in RCT of gestational 

supplementation

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked, had medical 

problems, a complicated 

pregnancy, seafood 

allergy, or if their normal 

dietary intake exceeded 

two meals of fish per 

week. Children were 

excluded from the study 

if they were born before 

36 weeks’ gestation or 

with major disease (to 

avoid the confounding 

effects on immune 

response) or if cord blood 

was not collected

Start time: Pregnant 20 weeks gestation

Duration: Pregnant to term

Arm 1: Control

Description: olive oil placebo

Blinding: capsules image matched

Maternal conditions

Current smoker 0%

Maternal allergies 100%

Arm 2: Fish oil

Description: same

Manufacturer: Ocean Nutrition, Halifax Nova Scotia

Active ingredients: 3-4mg/g vitamin E

Viability: none reported

Dose: 4 1-gm capsules fish oil per day

Maternal conditions

DHA: 2.2

EPA: 1.1

Other dose 1: fish oil supplying 2,2g/d DHA and 

1.1g/day EPA

Current smoker 0%

Maternal allergies 100%

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 39; mean 3434.0; SD 

(377)

Arm 2: Sample size 33; mean 3508.0; SD 

(353)

77
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

22:4n-6 0.8 (0.2) 1.5 

(0.3) ,0.001 22:5n-3 6.3 

(0.8) 6.0 (0.5) 0.037 

22:6n-3 10.3 (1.1) 7.4 

(0.9) ,0.001 Total n-6 

PUFAs* 25.0 (1.8) 29.6 

(1.1) ,0.001 Total n-3 

PUFAs{ 17.9 (1.9) 13.7 

(1.3) ,0.001 Total n-3 to 

n-6{ 0.8 (0.1) 0.5 (0.1) 

,0.001

van Goor et al., 201166

Study name: Groningen 

LCPUFA study

Study dates: 2004-2009

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Industry

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; van Goor, 201036

Study Population: 

Healthy infants

Pregnant enrolled 119

Infants enrolled 119 

Infants completers 114

Pregnant age: Placebo: 

32.7 DHA: 32.5

DHA+AA: 32.9 (Placebo: 

5.1 DHA: 4.4 DHA+AA: 

4.8)

Infant age: 18 months

Race of Mother: NR 

(100)

Inclusion Criteria: women 

with a first or second lowrisk singleton pregnancy, 

between the 14th and 

20th weeks of pregnancy

Exclusion Criteria: 

women with vegetarian 

or vegan diets; women 

with diabetes mellitus; 

birth complications

Start time: Pregnant 14th-20th week pregnancy 

Lactating 3 months after delivery Mothers 3 months 

after delivery Infants NR

Duration: Pregnant NR Lactating 33-39 weeks 

Mothers 33-39 weeks Infants NR

Arm 1: placebo

Description: Soy bean oil

Brand name: none

Arm 2: DHA

Description: DHA plus soy bean oil

Brand name: Marinol D40

Manufacturer: Lipid Nutrition B.V., Wormerveer, The 

Netherlands; AA:

Dose: 1 capsule DHA and 1 capsule soy bean oil 

once a day

ALA: 32 mg/d

DHA: 220 mg/d

EPA: 34 mg/d

Arm 3: DHA+AA

Description: DHA plus AA

Brand name: AA: no brand name

Manufacturer: Wuhan Alking Bioengeneering Co. 

Ltd., Wuhan, China

Dose: 2 capsules once a day

ALA: 7 mg/d

DHA: 220 mg/d

EPA: 36 mg/d

AA: 220 mg per capsule

Outcome: birth weight (g) (Unspecified)

Follow-up time: birth

Arm 1: Sample size 34; mean 3576.0; SD 

(551)

Arm 2: Sample size 41; mean 3592.0; SD 

(465)

Arm 3: Sample size 39; mean 3652.0; SD 

(377)

Gustafson et al., 201374 Study Population: Inclusion Criteria: Start time: Pregnant 12-20 week gestation Infants Outcome: birth weight (g) (Secondary)

78
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: NR

Study dates: May 2009 -

July 2011

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Healthy infants Healthy 

pregnant women

Pregnant enrolled 67 

Pregnant withdrawals 12 

Pregnant completers 52

Infants enrolled 44 

Infants completers 41

Pregnant age: placebo 

25.6+; DHA 25.5 

(placebo 4.8; DHA 4.3)

Race of Mother: White 

European (46.3) Black 

(37.3) Asian (3) Hispanic 

(13.4)

Baseline biomarker 

information: plasma DHA 

(wt% TFA) placebo 

group: 3.91 (3.15-4.21); 

DHA group: 3.94(3.39-

4.72) RBC DHA (wt%

TFA) placebo group 

4.30(3.99-5.03); DHA 

group 4.50 (3.73-5.44)

between 16–35.9 years 

of age and carrying a 

singleton pregnancy 

between the 12th and 

20th week of gestation

Exclusion Criteria: any 

serious health condition 

likely to affect the growth 

and development of the 

fetus or health of the 

mother including cancer, 

lupus, hepatitis, diabetes 

mellitus (Type1, Type 2 

or gestational) or 

HIV/AIDS at baseline or 

fetal cardiac structural or 

conduction defects. 

Women who selfreported illicit drug use or 

alcohol use during 

pregnancy and those 

with hypertension or BMI 

Z40 were excluded. 

Women who were taking 

more than 200 mg/day 

DHA in prenatal vitamins 

or over the counter 

supplements were 

excluded from

participation

birth

Duration: Pregnant till birth

Arm 1: Placebo

Description: g 50% soy and 50% corn oil

Manufacturer: Martek Biosciences, now DSM 

Nutritional Products

Dose: 3 capsule a day each 500 mg

Blinding: Only members of the investigational 

pharmacy knew the subject allocation. Participants 

and all members of the investigational team were 

blinded to the intervention assignment. Participants

were allocated to either group based on the simple 

randomization procedure using random numbers 

generated by SAS. All capsules were the same 

color, size, weight and the oils were orange-flavored 

to prevent investigator or subject bias.

Arm 2: algal oil as a source of DHA (200 mg of DHA 

per capsule for a total of 600 mg DHA/day)

Dose: 3 capsule of 200mg DHA total 600 mg

DHA: 200 mg * 3

Follow-up time: birth

Arm 1: Sample size 24; mean 3435.5; SD 

(404.8)

Arm 2: Sample size 22; mean 3416.8; SD 

(552.9)

Harper et al., 201029

Study name: NR

Study dates: 01. 2005 -

10. 2006

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Study Population: At risk 

for preterm labor

Pregnant enrolled 852 

Pregnant withdrawals 0 

Pregnant completers 852

Pregnant age: n3: 28 

placebo 27 n3 23-32; 

placebo 24-32

Race of Mother: White 

European (n3: 56.5; 

placebo 57.7) Black (n3: 

Inclusion Criteria: a 

documented history of at 

least one prior singleton 

preterm delivery between 

20 0/7 and 36 6/7 weeks 

of gestation after 

spontaneous preterm 

labor or premature 

rupture of the 

membranes, and a 

current singleton 

pregnancy between 16 

and 21 6/7 weeks of 

gestation

Start time: Pregnant 16-22 week gestation age

Duration: Pregnant 36 weeks of gestation

Arm 1: placebo

Description: inert mineral oil

Manufacturer: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: four capsules of matching oil containing a 

minute amount of inert mineral oil

Blinding: Boxes containing a woman’s entire supply 

of capsules in blister packs were sequentially 

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 418; median 2923.0; 

IQR

Arm 2: Sample size 434; median 2990.0; 

IQR

79
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Klebanoff, 201149

34.1; placebo 34.9) Asian 

(n3: 3, placebo 1.2) 

Hispanic (n3: 14.7; 

placebo 13.6) Other 

race/ethnicity (NR)

Exclusion Criteria: 

evidence of a major fetal 

anomaly, intake of a fish 

oil supplement in excess 

of 500 mg per week at 

any time during the 

preceding month, allergy 

to fish, anticoagulation 

therapy, hypertension, 

White’s classification D 

or higher diabetes, drug 

or alcohol abuse, seizure 

disorder, uncontrolled 

thyroid disease, clotting 

disorder, current or 

planned cerclage, or a 

plan to deliver either 

elsewhere or before 37 

weeks of gestation

numbered according to the predetermined 

randomization sequence, and on enrollment a 

woman was assigned the next number in sequence. 

Study group assignment was not known by study 

participants, their health care providers, or the 

research personnel

Arm 2: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: in 4 capsules total 2000 mg of n3

DHA: 800 mg

EPA: 1200 mg

Hauner et al., 201237

Study name: INFAT

Study dates: July 14 

2006 - may 22 2009

Study design: Trial 

randomized parallel

Location: Germany

Funding source / conflict: 

Industry, Government, 

Multiple foundations and 

Societies

Study Population: 

Healthy pregnant women

Pregnant enrolled 208 

Pregnant withdrawals 38 

Pregnant completers 170

Infants enrolled 188 

Infants withdrawals 18 

Infants completers 170

Pregnant age: 31.9 (4.9) 

18-43

Race of Mother: NR (NR)

Baseline biomarker 

information: Maternal 

fatty acid profile in RBCs 

at 15th wk: EPA, DHA, 

AA, and n-6:n-3 LCUFA 

ratio (reported in Table 2 

by intervention and 

control groups). No 

significant differences 

Inclusion Criteria: healthy 

pregnant women before 

the 15th wk of gestation, 

between 18 and 43 y of 

age, prepregnancy BMI 

(in kg/m2) between 18 

and 30, willingness to 

implement the dietary 

recommendations, 

sufficient German 

language skills.

Exclusion Criteria: highrisk pregnancy (multiple 

pregnancy, rhesus 

incompatibility, hepatitis 

B infection, or parity .4); 

hypertension; chronic 

diseases (e.g., diabetes) 

or gastrointestinal 

disorders accompanied 

by maldigestion, 

malabsorption, or 

elevated energy and 

nutritional requirements 

Start time: Pregnant 15th wk of gestation

Duration: Pregnant to 4 mo postpartum

Arm 1: Control

Description: brief semistructured counseling on a 

healthy balanced diet according to the guidelines of 

the German Nutrition Society and were explicitly 

asked to refrain from taking fish oil or DHA 

supplements

N-6 N-3: 2.80 +- 1.17 (SD) at 32nd wk of gestation

AA: 10.15 +- 3.89 SD) at 32nd wk of gestation

Arm 2: Intervention

Description: Fish-oil supplement + nutritional 

counseling (to normalize the consumption of AA

Brand name: Marinol D-40

Manufacturer: Lipid Nutrition

DHA: 1020 mg

EPA: 180 mg

N-6 N-3: 1.54 +- 0.63 (SD) at 32nd wk of gestation

AA: 8.82 +- 2.84 (SD) at 32nd wk of gestation

Other dose 1: Vit E 9 mg

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 96; mean 3357.0; SD 

(557)

Arm 2: Sample size 92; mean 3534.0; SD 

(465)

80
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

between groups.

Baseline Omega-3 

intake: 7-d dietary 

records completed by 

participants at the 15th 

(baseline) and 32nd wk 

of gestation but only 

dietary intake at 32nd we 

of gestation was reported 

(in Table 2). At week 32 

of gestation, the dietary 

n-6:n-3 PUFA ratio was 

.5:1 in the intervention 

group compared with :1 

in the control group, as 

originally intended.

(e.g., gluten 

enteropathy); known 

metabolic defects (e.g., 

phenylketonuria); 

psychiatric diseases; 

hyperemesis gravidarum; 

supplementation with n–3 

LCPUFAs before 

randomization; and 

alcohol abuse and 

smoking.

Helland et al., 200876

Study name: NR

Study dates: 1994-2003

Study design: Trial 

randomized parallel

Location: Norway

Funding source / conflict: 

Industry, Government, 

Multiple foundations and 

Societies

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Helland, 200186 and 

Helland, 200387 and

which are both included 

in the original report

Study Population: 

Healthy infants Healthy 

pregnant women Breastfeeding women

Infants enrolled 262 

Infants completers 143

Pregnant age: cod oil 

28.6 n=175 corn oil 27.6 

n=166 (cod oil 3.4; corn 

oil 3.2)

Race of Mother: NR 

(100)

Baseline biomarker 

information: from id 

10331 cod(n148) corn 

(n137) n-3 cod: 73.7 

(30.0) corn 52.0 (14.9)*** 

20:5n-3 cod: 10.8 (7.6) 

corn: 2.5 (1.8)*** 22:5n-3 

cod: 5.0 (2.6) corn: 2.9 

(1.3)*** 22:6n-3 cod: 55.8 

(20.6) corn: 45.3 

(12.8)***

Inclusion Criteria: 

Healthy nulliparous or 

primiparous women, 

aged 19-35 with single 

pregnancies

Exclusion Criteria: 

Unhealthy neonates

Start time: Pregnant week 18 of pregnancy

Duration: NR

Arm 1: Cod oil

Manufacturer: NR

Active ingredients: Vit 1: 117 ug/mL, Vit D3: 1 

ug/mL, vit E: 1.4 mg/mL

Viability: frozen at _x0003_ 70 ° C under nitrogen. 

Before storage, the samples were sonicated and 

ethylenediaminetetraacetic acid and butylated 

hydroxytoluene were added to a final concentration

of 1.85 mg/mL and 75 _x0003_ g/mL, respectively

DHA: 1183mg/10 mL

EPA: 803 mg/10mL

Total N-3: 2494 mg/10mL

Arm 2: corn oil

Active ingredients: Vit 1: 117 ug/mL, Vit D3: 1 

ug/mL, vit E: 1.4 mg/mL

Viability: frozen at _x0003_ 70 ° C under nitrogen. 

Before storage, the samples were sonicated and 

ethylenediaminetetraacetic acid and butylated 

hydroxytoluene were added to a final concentration

of 1.85 mg/mL and 75 _x0003_ g/mL, respectively

ALA: 92 mg/10mL

Outcome: birth weight (g) (Primary)

Follow-up time: birth

Arm 1: Sample size 61; mean 3518.0; SD 

(560)

Arm 2: Sample size 82; mean 3613.0; SD 

(458)

81
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Baseline Omega-3 

intake: from 10331 cod 

n147 corn n159 18:3 n-3: 

cod: 1.3 (0.5) corn: 1.2 

(0.5) 20:5 n-3 cod: 0.2 

(0.2) corn:0.2 (0.2) 22:5 

n-3 cod: 0.05 (0.03) corn: 

0.05 (0.03) 22:6 n-3 cod: 

0.3 (0.3) corn: 0.3 (0.3)

Judge et al., 200739

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government, 

None

Study Population: 

Healthy pregnant women

Pregnant enrolled 29 

Pregnant completers 29

Pregnant age: 23.75 

years (.4 years) NR

Race of Mother: NR 

(100%)

Inclusion Criteria: women 

aged 18 –35 y who were 

at 20 wk of gestation

Exclusion Criteria: 

Women with a history of

drug or alcohol addiction, 

hypertension, smoking, 

hyperlipidemia, renal 

disease, liver disease, 

diabetes, or psychiatric 

disorder

Start time: Pregnant 24 weeks gestation

Duration: Pregnant until birth

Arm 1: placebo

Description: cereal based placebo bars

Manufacturer: Nestec

Active ingredients: 18 g carbohydrates, 1.3 grams 

protein, 92 calories, 1.7 g fat

Viability: NR

Dose: 5 bars per week

Blinding: NR

Arm 2: DHA supplemented cereal bars

Manufacturer: Nestec

Active ingredients: 18 g carbohydrates, 1.3 grams 

protein, 92 calories, 1.7 g fat

Viability: NR

Dose: 5 bars per week. DHA-containing cerealbased bars [1.7 g total fat, 300 mg DHA as loweicosapentaenoic oil (EPA) fish oil; EPA:DHA 1:8 

per bar

DHA: mg/d

EPA: .75 mg (calculated based on EPA:DHA ratio)

EPA-DHA: 1:8

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 15; mean 3222.0; SD 

(363)

Arm 2: Sample size 14; mean 3465.0; SD 

(406)

Judge et al., 201240

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Study Population: 

Healthy pregnant women

Pregnant enrolled 48

Pregnant age: Treatment 

group: 23.93 Placebo: 

23.86 (Treatment group: 

4.32 Placebo: 4.53)

Inclusion Criteria: The 

women were either 

primiparous or had not 

been pregnant for the 

past 2 years.

Exclusion Criteria: parity 

greater than 5, history of 

chronic hypertension, 

hyperlipidemia, renal, 

Start time: Pregnant 24 weeks gestation

Duration: Pregnant until delivery

Arm 1: Placebo

Description: Control group

Manufacturer: Nestec, S.A., Switzerland

Blinding: The total macronutrient content was the 

same in both the DHA and placebo bars with respect 

to carbohydrate, protein and fat, how- ever, the DHA 

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 21; mean 3224.62; SD 

(431.25)

Arm 2: Sample size 27; mean 3394.7; SD 

(430)

82
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / conflict: 

Multiple foundations and 

Societies

Race of Mother: White 

European (Treatment: 

11.1%, Placebo: 0%) 

Black (Treatment: 18.5%, 

Placebo: 4.8%) Asian 

(Treatment: 3.7%, 

Placebo: 0%) Hispanic 

(Treatment: 59.3%, 

Placebo: 80.9%) NR 

(Treatment: 7.4%, 3 

(14.3%))

Baseline biomarker 

information: Maternal 

plasma phospholipid (PL) 

fatty acids (FA): 2.85 +/-

.87 % in treatment group 

and 2.95 +/- .91% in 

placebo group. Infant 

RBC PL FA: 7.55 +/-

1.61% in treatment group 

and 7.07 +/- 1.25% in 

placebo group.

liver or heart disease, 

thyroid disorder, multiple 

gestations or pregnancy 

induced complications 

including hypertension, 

preeclampsia or preterm 

labor, smoking and 

psychiatric disorders. 

Women who were

treated during labor with 

analgesics such as 

Stadol (butorphanol 

tartrate), that may cause 

infant respiratory distress 

were also excluded. In 

addition, infants born 

preterm and infants with 

less than 4 h of crib time 

in the first and second 

days postpartum were 

excluded from the 

analyses.

bars contained fish oil (300 mg DHA) and the 

placebo bars contained corn oil.

Arm 2: DHA

Description: Intervention group

Manufacturer: Nestec, S.A., Switzerland

Dose: average of 5 bars weekly

DHA: 300 mg

EPA-DHA: 8:1 ratio of DHA to EPA

Linnamaa et al., 201079

Study name: NR

Study dates: 2004-2008

Study design: Trial 

randomized parallel

Location: Finland

Funding source / conflict: 

Government, Multiple

foundations and

Societies

Study Population: 

Healthy infants Healthy 

pregnant women

Infants enrolled 314 

Infants withdrawals 137 

Infants completers 177

Mother age: NR (NR) NR

Race of Mother: NR (NR)

Inclusion Criteria: All 

pregnant mothers <16 

weeks of gestation

Exclusion Criteria: Sick 

children and those born 

prematurely who required 

more intensive care 

(n=8)

Start time: Pregnant 8th to 16th weeks of pregnancy 

and then continued Infants when exclusive 

breastfeeding ended

Duration: Pregnant until the end of the exclusive 

breastfeeding period Infants until 2 years of age

Arm 1: Controls

Description: Olive oil

Manufacturer: Santagata Luigi s.r.l., Genova, Italia

Dose: 3 g/day for mothers, 1 mL/day for infants

Blinding: NR "double-blind"

ALA: 0

DHA: 0

EPA: 0

EPA-DHA: 0

AA: 0

Total N-3: 0

Other dose 1: LA (18:2n-6): 9 weight% of total

Arm 2: Intervention

Description: Blackcurrant seed oil

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 129; mean 3599.0; SD 

(468)

Arm 2: Sample size 112; mean 3595.0; SD 

(461)

83
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Manufacturer: Aromtech Ltd, Tornio, Finland

Dose: 3 g/day for mothers, 1 mL/day for infants

ALA: 14 weight% of total

DHA: 0

EPA: 0

EPA-DHA: 0

AA: 0

Total N-3: 17 weight% of total

Other dose 1: SDA: 3 weight% of total

Lucia Bergmann et al., 

200741

Study name: NR

Study dates: 2000-2002

Study design: Trial 

randomized parallel

Location: Germany

Funding source / conflict: 

NR

Original, same study, or 

follow-up studies: Lucia, 

200752

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 144 

Pregnant withdrawals 51 

Pregnant completers 69

Pregnant age: 31 (DHA 

4.69; control 4.89)

Infant age: DHA 39.1; 

control 39.5 weeks (DHA 

1.64; control 1.38)

Race of Mother: White 

European (100)

Baseline biomarker 

information: DHA % of all 

identified fatty acid in 

RBC: Vitamin: 5.76 +-

2.45 (47); DHA: 

Prebiotic:5.94+-2.37(48) 

DHA: DHA: 5.69+-

2.40(47) ARA Vitamin: 

14.01+-4.04(47) ARA 

Prebiotic 14.82+-3.60(48) 

ARA DHA: 14.18+-

4.32(47) EPA Vitamin: 

0.72+-0.32(47) EPA 

Prebiotic: 0.78+-0.38(48) 

EPA DHA: 0.79+-

0.41(47)

Inclusion Criteria: at least 

18 years of age and 

willing to breastfeed for 

at least three months 

were enrolled at 21 

weeks’ gestation during 

the period October 2000 

to August 2002

Exclusion Criteria: 

increased risk of 

premature delivery or 

multiple pregnancy, 

allergy to cow milk 

protein, lactose 

intolerance, diabetes, 

smoking, consumption of 

alcohol (20 g/week), or 

participation in another 

study. Infants excluded if 

they were premature at 

birth (<37 week 

gestation, or had any 

major malformations or 

hospitalized for more 

than one week.

Start time: Pregnant 21th week

Duration: Pregnant 37th week

Arm 1: Vitamins and minerals

Manufacturer: Nestle ́ (Vevey, Switzerland)

Arm 2: Prebiotic

Description: basic supplement plus the prebiotic, 

fructooligosaccharide (FOS) (4.5 g)

Manufacturer: Nestle ́ (Vevey, Switzerland)

Active ingredients: fructooligosaccharide (FOS) (4.5 

g)

Arm 3: DHA

Description: basic supplement with FOS and DHA 

(200 mg)

Manufacturer: Nestle ́ (Vevey, Switzerland)

Dose: 200 mg DHA prepared from fish oil (assuming 

that some EPA but dose was not reported)

DHA: 200 mg

EPA: NR

Outcome: birth weight (g) (Unspecified)

Follow-up time: birth

Arm 1: Sample size 74; mean 3548.0; SD 

(469.3)

Arm 3: Sample size 43; mean 3427.0; SD 

(493.6)

Makrides et al., 201035 Study Population: Inclusion Criteria: with Start time: Pregnant < 21 week's gestation duplicate data of id 4404

84
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: DOMInO

Study dates: 2005-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Smithers, 201153; Palmer, 

201254; Zhou, 201255;

Palmer, 201356; 

Makrides, 2014 57

Healthy pregnant women

Pregnant enrolled 2399 

Pregnant withdrawals 1

Infants enrolled 605 

Infants withdrawals 32 

Infants completers 726

Pregnant age: 28.9 

(DHA5.7___ control5.6)

Race of Mother: NR (NR)

singleton pregnancies at 

less than 21 weeks’ 

gestation were 

approached by study 

research assistants while 

attending routine 

antenatal appointments

Exclusion Criteria: 

already taking a prenatal 

supplement with DHA, 

their fetus had a known 

major abnormality, they 

had a bleeding disorder 

in which tuna oil was 

contraindicated, were 

taking anticoagulant 

therapy, had a 

documented history of 

drug or alcohol abuse, 

were participating in 

another fatty acid trial, 

were unable to give 

written informed consent, 

or if English was not the 

main language spoken at 

home

Duration: NR

Arm 1: vegetable oil capsules

Description: a blend of 3 nongenetically modified oils 

(rapeseed, sunflower, and palm) in equal 

proportions

Manufacturer: Efamol, Surrey, England.

Dose: 3* 500mg capsule / day

Blinding: All capsules were similar in size, shape, 

and color

Arm 2: DHA

Description: DHA-rich fish oil concentrate

Manufacturer: ; Incromega 500 TG, Croda 

Chemicals, East Yorkshire, England

Dose: 500mg capsule *3/day

DHA: 800mg

EPA: 100mg

Outcome: (Secondary)

Miles et al., 201178

Study name: SiPS

Study dates: NR

Study design: Trial 

randomized parallel

Location: UK

Funding source / conflict: 

Government, Some 

authors employed by 

industry (companies that 

make the supplements)

Original, same study, or 

Study Population: 

Healthy pregnant women

Pregnant enrolled 123 

Pregnant completers 101

Pregnant age: Salmon: 

29.5 Control: 28.4 

(Salmon 0.5 Control: 0.6)

Race of Mother: NR 

(100%)

Inclusion Criteria: age 

18–40 y; ,19 wk 

gestation; healthy, 

uncomplicated singleton 

pregnancy; infant at risk 

of atopy (one or more 

first-degree relatives of 

the baby affected by 

atopy, asthma, or allergy 

by self-report); 

consuming <2 portions of 

oily fish/mo (excluding 

canned tuna); not using 

fish-oil supplements 

currently or in the 

previous 3 mo

Exclusion Criteria: age 

Start time: Pregnant Week 20

Duration: Pregnant Week 20 until Term (delivery)

Arm 1: Control

Description: No added fish

DHA: 16 mg/d in diet

EPA: 10 mg/d in diet

EPA-DHA: 24 mg/d in diet

Arm 2: Salmon

Description: 2 portions salmon per week

DHA: 326 mg/d

EPA: 162 mg/d

EPA-DHA: 491 mg/d

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 54; mean 3425.0; SE 

(82)

Arm 2: Sample size 53; mean 3449.0; SE 

(72)

85
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

follow-up studies: 

Noakes, 201288

<18 or >40 y; .19 wk 

gestation; no first-degree 

relatives of the infant 

affected by atopy, 

asthma, or allergy; 

consuming >2 portions of 

oily fish/mo (excluding 

canned tuna); use of fishoil supplements within 

previous 3 mo;

participation in another 

research study; known 

diabetic; or presence of 

any autoimmune 

disease, learning 

disability, terminal illness, 

or mental health 

problems

Mozurkewich et al., 

201342

Study name: NR

Study dates: Oct 2008 -

May 2011

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy pregnant women

Pregnant enrolled 126 

Pregnant withdrawals 8 

Pregnant completers 118

Pregnant age: EPA 29.9; 

DHA 30.6; placebo 30.4 

(EPA 5.0; DHA 4.5; 

placebo 5.9)

Race of Mother: White 

European (85%; 76%; 

83%) Black (10%; 11%; 

5%) Asian (3%; 3%; 2%) 

Hispanic (0%; 11%; 7%) 

Inuit Eskimo (0%; 0%; 

2%) Pacific Islander (NR)

Baseline biomarker 

information: EPA group: 

EPA 0.29+-0.18; DHA 

4.24+-2.30; total n3 FA: 

22.10+-3.72 DHA group: 

EPA 0.31+-0.24; DHA 

4.66+-2.29; total n3 FA 

Inclusion Criteria: past 

history of depression, an 

EPDS score 9-19 (at risk 

for depression or mildly 

depressed), singleton 

gestation, a maternal age 

of 18 years or older, and 

a gestational age of 12-

20 weeks

Exclusion Criteria: had a 

history of a bleeding 

disorder, thrombophilia 

requiring anticoagulation, 

multiple gestation, bipolar 

disorder, current major 

depressive disorder, 

current substance abuse, 

lifetime substance 

dependence, or 

schizophrenia. Women

were also ineligible if 

they were currently 

taking omega-3 fatty acid 

supplements or 

antidepressant 

medications or eating 

Start time: Pregnant 12-20 week gestation

Duration: Pregnant assuming till birth

Arm 1: Control/Placebo

Description: 98% soy oil and 1% each of lemon and 

fish oil

Manufacturer: Nordic Naturals Corporation in 

Watsonville, CA

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large and 4 small placebo capsules

Blinding: The placebos were formulated to be 

identical in appearance to both the EPA- and DHArich supplements

Arm 2: EPA-rich fish oil

Description: an approximate 4:1 ratio of EPA to DHA 

(1060 mg EPA plus 274 mg DHA)

Brand name: ProEPAXtra, Nordic Naturals

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large EPA capsule and 4 small placebo

DHA: 274 mg

EPA: 1060 mg

Arm 3: DHA-rich fish oil

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 40; mean 3309.0; SD 

(555)

Arm 2: Sample size 40; mean 3402.0; SD 

(550)

Arm 3: Sample size 38; mean 3774.0; SD 

(438)

86
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

36.41+-9.71 placebo: 

EPA .34+-0.22; DHA 

3.85+-1.77; omega3 fa 

322.86+-5.02

more than 2 fish meals 

per week.

Description: DHA and EPA in an approximate 4:1 

ratio o (900 mg DHA plus 180 mg EPA)

Brand name: ProDHA, Nordic Naturals

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large placebo oil and 4 small DHA rich

DHA: 900 mg

EPA: 180 mg

Mulder et al., 201475

Study name: NR

Study dates: 2004 to 

2008

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Government

Study follow-up: 18 

months

Study Population: 

Healthy pregnant women

Pregnant enrolled 271 

Pregnant completers 200

Pregnant age: 33 years 

(4 years) NR

Race of Mother: White 

European (73%) Other 

race/ethnicity (27%)

Baseline biomarker 

information: maternal 

RBC 

Phusphatidylethanolamin

e DHA: placebo group 

6.25 (1.60) g/ 100g DHA 

group 6.36 (1.62) g/ 100g

Baseline Omega-3 

intake: median (2.5 to 

97.5th percentile range) 

intake: placebo group

80.0 (0.00-334) mg/day, 

DHA group 90.0 (6.00-

472) mg/d

Inclusion Criteria: at least 

16 wk gestation, not 

taking any lipid or fatty 

acid supplement, and 

were expected to deliver 

one infant at full-term 

gestation, with no 

maternal or fetal 

complications

Exclusion Criteria: NR

Start time: Pregnant 16 weeks gestation

Duration: Pregnant Until birth

Arm 1: placebo

Description: corn and soybean oil supplement

Manufacturer: Martek Biosciences

Blinding: supplements were identical in appearance, 

contained an orange flavor mask

Arm 2: DHA supplement

Description: algal oil DHA supplement

Manufacturer: Martek Biosciences

DHA: 400 mg

Outcome: birth weight (g) (Unspecified)

Follow-up time: birth

Arm 1: Sample size 111; mean 3497.0; SD 

(479)

Arm 2: Sample size 104; mean 3494.0; SD 

(400)

Ramakrishnan et al., 

201032

Study name: POSGRAD

Study dates: Feb 2005 -

Feb 2007

Study Population: 

Healthy pregnant women

Pregnant enrolled 1,094 

Pregnant withdrawals 67 

Pregnant completers 973 

(for birth weight)

Inclusion Criteria: 18-35 

yrs. of age, in gestation 

weeks 18-22, planned to 

deliver at the IMSS 

General Hospital in 

Cuernavaca, exclusively 

or predominantly 

breastfeed for at least 3 

Start time: Pregnant at study entry

Duration: Pregnant mid pregnancy (18-22 weeks 

gestation) until delivery

Arm 1: Controls

Description: Placebo containing olive oil

Manufacturer: Martek Biosciences

Outcome: birth weight (g) (Primary)

Follow-up time: birth

Arm 1: Sample size 486; mean 3202.0; SD 

(472)

Arm 2: Sample size 487; mean 3207.2; SD 

(449.4)

87
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, March of 

Dimes

Original, same study, or 

follow-up studies: Stein, 

201233; Imhoff-Kunsch, 

201158; Escamilla-Nunez, 

201459; GonzalezCasanova, 201560; 

Ramakrishnan, 201561; 

Stein, 201134

Pregnant age: 26.2 

(controls) 26.3 (DHA) 

(4.6 (controls) 4.8 (DHA))

Race of Mother: Hispanic 

(NR)

Baseline Omega-3 

intake: mg/day for all: LA: 

17,846 in controls, 

17,645 in DHA AA: 137 

in controls, 140 in DHA 

ALA: 1,488 in controls, 

1,477 in DHA EPA: 18 in 

controls, 18 in DHA DHA: 

54 in controls, 56 in DHA

months, liver in the area 

for at least 2 years after 

delivery.

Exclusion Criteria: highrisk pregnancy; lipid 

metabolism or absorption 

disorders, regular intake 

of fish oil or DHA 

supplements; chronic use 

of certain medications 

(e.g., medications for 

epilepsy).

Dose: 1 capsule, twice a day

Blinding: Identical tablets

Arm 2: DHA

Description: Intervention

Manufacturer: Martek Biosciences

Dose: 1 capsule twice a day

DHA: 400 mg/d, 200 mg/dl derived from algal source

Stein et al., 201134

Study name: POSGRAD

Study dates: 02. 2005-

02.2007

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, Multiple

foundations and 

Societies

Original, same study, or 

follow-up studies: Stein, 

201233; Imhoff-Kunsch, 

201158; Escamilla-Nunez, 

201459; GonzalezCasanova, 201560; 

Ramakrishnan, 201561; 

Ramakrishnan, 201132

Study Population: 

Healthy infants

Pregnant enrolled 1094 

Pregnant completers 973

Pregnant age: placebo 

26.3; DHA 26.4 (placebo 

4.6; DHA 4.9)

Infant age: 39.1 (placebo 

1.6; DHA 1.8)

Race of Mother: NR

Inclusion Criteria: women 

were 18–35 y, were in 

gestation wk 18–22, and 

planned to deliver at the 

IMSS General Hospital in 

Cuernavaca, exclusively 

or predominantly breastfeed for at least 3 mo, 

and to live in the area for 

at least 2 y after delivery

Exclusion Criteria: NR

Start time: Pregnant 18-22 Gestational week Infants 

birth

Duration: Pregnant birth

Arm 1: Placebo

Description: Olive oil

Manufacturer: Martek Biosciences

Dose: 2 capsules olive oil

Blinding: Similar in appearance and taste to DHA 

capsules

Arm 2: DHA

Description: algal DHA capsules

Manufacturer: Martek Biosciences

Dose: 2 capsules * 200mg

DHA: 400 mg

Outcome: birth weight (g) (Primary)

Follow-up time: birth

Arm 1: Sample size 370; mean 3220.0; SD 

(475)

Arm 2: Sample size 369; mean 3242.0; SD 

(441)

88
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Tofail et al., 200677

Study name: NR

Study dates: Enrollment 

January to March 2000

Study design: Trial 

randomized parallel

Location: Bangladesh

Funding source / conflict: 

Government

Study follow-up: 10 

months

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 400 

Pregnant completers 151

Pregnant age: 22.7 years 

(4.35 years) NR

Race of Mother: Asian 

(100%)

Inclusion Criteria: seems 

as if all pregnant women 

at 25 weeks gestation 

were enrolled, no 

inclusion criteria 

specified

Exclusion Criteria: NR

Start time: Pregnant 25 weeks gestation

Duration: Pregnant until birth

Arm 1: placebo

Description: soy oil capsule

Dose: 4 one gram capsules per day

Blinding: capsules were identical in appearance

Other dose 1: LNA 0.27 g

Other dose 2: linoleic acid 2.25 g

Arm 2: DHA supplement

Description: fish oil capsules

Dose: 4 one gram capsules per day

DHA: 1.2 g

EPA: 1.8 g

Outcome: birth weight (kg) (Unspecified)

Follow-up time: birth

Arm 1: Sample size 124; mean 2.7; SD 

(0.4)

Arm 2: Sample size 125; mean 2.7; SD 

(0.4)

Zhou et al., 201255

Study name: DOMInO

Study dates: 10. 2005 -

01. 2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Palmer, 

201254; Palmer, 201356; 

Makrides, 2014 57

Study Population: 

Healthy pregnant women

Pregnant enrolled 2399

Race of Mother: White 

European (88%;88%) 

Asian (7%;8%) Inuit 

Eskimo (2%;1%) Other 

race/ethnicity (NR)

Inclusion Criteria: NR

Exclusion Criteria: If 

already taking a dietary 

supplement containing 

DHA, their fetus had a 

known major 

abnormality, they had a 

bleeding disorder for 

which fish oil was 

contraindicated, they 

were receiving 

anticoagulant therapy, 

they had a documented 

history of drug or alcohol 

abuse, they were 

participating in another 

fatty acid trial, or English 

was not the main

language spoken at 

home

Start time: Pregnant medium gestational age 19 

weeks

Duration: Pregnant birth

Arm 1: control

Description: 500-mg vegetable oil capsules

Dose: 3*500mg 3 nongenetically modified oils 

(rapeseed, sunflower, and palm) in equal 

proportions

Blinding: All capsules were similar in size, shape, 

and color

Arm 2: DHA

Description: DHA-rich fish oil

Manufacturer: Incromega 500 TG; Croda Chemicals

Dose: 3*500mg capsule

DHA: 800 mg

EPA: 100 mg

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 1202; mean 3407.0; 

SD (576)

Arm 2: Sample size 1197; mean 3475.0; 

SD (564)

89
Table 9. Observational studies for birth weight

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Badart-Smook, et al., 199747

Outcome domain: Birth Weight

Study dates: NR

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: NR

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 610 Pregnant withdrawals 

240 Pregnant completers 370

Pregnant age: 29 (4)

Race of Mother: White European (100)

Inclusion Criteria: White race, intention to give birth

to the baby in one of the three hospitals involved in 

the study

Exclusion Criteria: Women with diastolic blood 

pressure of 90mm or higher, women suffering from 

any metabolic, cardiovascular, neurological, or renal 

disorder

Adjustments: 

Maternal(pregnancy) body 

weight, height, age, smoking 

habits, education, parity, and 

sex of the infant were 

included in each multiple 

regression model as possible 

confounding factors; except 

for the regression equation 

with gestational age as a 

dependent variable, 

gestational age at birth was 

also added as a confounder

Brantsaeter, et al., 201281

Outcome domain: Birth Weight

Study name: Norwegian Mother and Child 

Cohort Study (MoBa)

Study dates: 2002-2009

Study design: Observational prospective

Location: Norway

Funding source / conflict: Government

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 76218 Pregnant completers 

62099

Race of Mother: NR

Inclusion Criteria: first participation for women with 

multiple participation in MoBa and women with

singleton births.

Exclusion Criteria: participants with a pregnancy

duration <28 weeks or >42 weeks (n=628), if the 

birth weight of the baby had not been recorded or if

the birth weight was, <600 g ( n = 35). We also 

excluded participants who had not given birth to a

live baby ( n 153). Lastly, we excluded women 

having improbable energy intakes, i.e. energy intake 

, >4·5 MJ or .<20 MJ ( n 1063)

Adjustments: Adjusted for 

maternal age, height, prepregnant BMI, parity, 

pregnancy duration, maternal 

education, smoking status, 

mother tongue other than 

Norwegian and total energy 

intake, and with intakes of 

seafood/seafood items and 

supplementary n-3 mutually 

adjusted

Dirix, et al., 200984

Outcome domain: Birth Weight

Study name: Maastricht Essential Fatty Acid 

Birth (MEFAB) Cohort

Study dates: 1990-1997

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Government

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 1238 Pregnant completers 

782

Infants enrolled 1238 Infants completers 782

Pregnant age: 29.0 26.2-31.7

Infant age: 40.1 wk 39.3-41.0

Race of Mother: White European (100)

Inclusion Criteria: gestational age of <16 weeks at

study entry, singleton pregnancy, Caucasian race, 

diastolic blood pressure, 90 mmHg and the absence 

of any metabolic, cardiovascular, neurological or

renal disorder at the time of recruitment

Exclusion Criteria: excluded if infants were born 

preterm (gestational age < 37 weeks,), mothers had 

diabetes or developed pregnancy-induced 

hypertension, mothers had reported specific health

problems in the past (e.g. diabetes mellitus,

hypertension and heart, kidney, liver, gall bladder or

thyroid gland disorders, one or both parents were

non-Caucasians or values for any of the aforementioned exclusion criteria were missing. The

mother – infant pairs were also excluded if fatty acid

Adjustments: Infant sex, 

gestational age, maternal 

height

90
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

analyses were not reported or values were missing

for birth weight, birth length and head circumference

Drouillet, et al., 200980

Outcome domain: Birth Weight

Study name: EDEN

Study dates: February 2003 - September 2003

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government, 

Multiple foundations and Societies

Original, same study, or follow-up studies: 

Bernard, 201389

Study Population: Healthy pregnant women

Pregnant enrolled 2002 Pregnant completers 

1446

Pregnant age: 29.2 (4.8)

Race of Mother: NR

Inclusion Criteria: NR

Exclusion Criteria: twin pregnancies, known diabetes

before pregnancy, not being able to speak and read 

French, and planned moving away from the region

Adjustments: Centre, mother's 

age and height, smoking 

habits, parity, gestational age, 

newborn's sex, delay between 

birth and anthropometric 

measures, and BMI

Mohanty, et al., 201585

Outcome domain: Birth Weight

Study dates: 1996-2008

Study design: Observational prospective

Location: US

Funding source / conflict: Government

Study Population: Healthy infants Healthy 

pregnant women

Pregnant completers 534

Race of Mother: White European (88)

Inclusion Criteria: initiated prenatal care at or before 

20 weeks gestation, were aged = 18 years, able to 

speak and read English, planned to carry the 

pregnancy to term, and to deliver at either of the two 

hospitals

Exclusion Criteria: multi-fetal pregnancies, 

implausible total energy intake of <500 or >3500 

kcal/day, pregnancies complicated by fetal demise 

(after 20 weeks of gestation), missing labor and 

delivery information, missing information on fetal 

growth indices, missing seafood intake information

Adjustments: Adjusted for 

maternal age (years), nonHispanic white race, post 

high-school education, 

unmarried marital status, prepregnancy body mass index 

(indicator variables: 18.5-

24.9, 25-29.9, =30 kg/m2), 

total energy (kcal/day), 

current recreational physical 

activity, current smoking, 

current alcohol intake, 

nulliparity, intake of 

red/processed meats 

(servings/day), male infant 

sex.

Molto-Puigmarti, et al., 201448

Outcome domain: Birth Weight

Study name: KOALA Birth Cohort Study

Study dates: 2000-2002

Study design: Observational prospective

Location: Netherlands

Study Population: Healthy pregnant women

Pregnant enrolled 2669 Pregnant completers 

1516

Infants enrolled 2669 Infants completers 1515

Pregnant age: years (.7yrs)

Race of Mother: NR (100)

Inclusion Criteria: nr, Described in Ref 37

Exclusion Criteria: nr

Adjustments: Adjusted for 

child gender, study 

recruitment group, maternal 

education, parity, maternal 

smoking status during 

pregnancy, maternal alcohol 

use in pregnancy, and 

maternal age at delivery

91
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Funding source / conflict: Multiple foundations 

and Societies

Much, et al., 201383

Outcome domain: Birth Weight

Study name: INFAT

Study dates: >2009-<2013

Study design: Observational prospective

Location: Germany

Funding source / conflict: Industry, Government, 

Some authors employed by industry (companies 

that make the supplements), Multiple

foundations and Societies, None

Study Population: Healthy infants Breastfeeding women

Pregnant enrolled 208

Infants completers 187

Race of Mother: NR (NR)

Inclusion Criteria: Healthy pregnant women at 14th 

week of gestation

Exclusion Criteria: None reported

Adjustments: Pregnancy 

duration, group, parity, and 

sex

Muthayya, et al., 200972

Outcome domain: Birth Weight

Study dates: Jan 2002- Mar 2006

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Study Population: Healthy pregnant women

Pregnant enrolled 829 Pregnant completers 676

Pregnant age: group 1, 23 group 2, 23 group 3, 

23 total, 24 group 1, 21-26 group 2, 21-27 group 

3, 23-29 total: 21-27

Race of Mother: Asian (Indian, 100%)

Inclusion Criteria: pregnant women aged 17–40 

years and at <20 weeks of gestation, registered for 

antenatal screening at the Department of Obstetrics 

and Gynecology at St John’s Medical College 

Hospital,

Exclusion Criteria: Women with multiple 

pregnancies, those with a clinical diagnosis of 

chronic illness such as diabetes mellitus, 

hypertension, heart disease and thyroid disease, 

those who tested positive for HbSAg/HIV/VDRL 

infection or who anticipated moving out of the city 

before delivery were excluded

Adjustments: Adjusted for 

maternal age, maternal 

education, parity, maternal 

weight/maternal weight gain 

per week and gestational age

Oken, et al., 200446

Outcome domain: Birth Weight

Study name: Project Viva

Study dates: 1999-2002

Study design: Observational prospective

Location: US

Funding source / conflict: Government, Multiple

foundations and Societies

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 2109 Pregnant completers 

2109

Pregnant age: 14-<20, 3% 20-<25, 6% 25-<30, 

21% 30-<35, 42% 35=<40, 23% >=40, 4% (14-

44)

Race of Mother: White European (66) Black 

(16) Asian (6) Hispanic (7) Other race/ethnicity 

(4)

Inclusion Criteria: delivered a live infant, and 

completed at least one dietary questionnaire

Exclusion Criteria: taking cod liver or fish oil 

supplement

Adjustments: Enrollment site, 

infant sex, and maternal age, 

height, intrapartum weight 

gain, prepregnancy BMI, 

race/ethnicity, smoking during 

pregnancy, education, and 

gravidity

92
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Olafsdottir, et al., 200582

Outcome domain: Birth Weight

Study dates: 1999-2001

Study design: Observational prospective

Location: NR

Funding source / conflict: Government, Multiple

foundations and Societies

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 436 Pregnant completers 436

Pregnant age: No 27.8; Yes 29.6 (no 4.9; yes 

4.6)

Race of Mother: NR

Inclusion Criteria: absence of pre-eclampsia, 

hypertension or diabetes mellitus

Exclusion Criteria: women whose personal data 

could not be found or who moved abroad before 

giving birth ( n 8), had a miscarriage or stillbirth ( n 

17), twins or triplets ( n 5), a preterm birth 

hypertension/pre-eclampsia (n 62) or gestational 

diabetes mellitus (n=4)

Adjustments: Gender, 

gestational age, mother's 

height, BMI, haemoglobin, 

alcohol consumption in first 

trimester, parity, smoking 

during pregnancy, weight gain 

during pregnancy

Smits, et al., 201373

Outcome domain: Birth Weight

Study name: Amsterdam Born Children and 

their Development (ABCD)

Study dates: Jan 2003- Mar 2004

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: None

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 1659 Pregnant completers 

1659

Infants enrolled 1659 Infants completers 1659

Pregnant age: <25 y, 5.7% 25-34 y, 61.2% 

>=35 y, 33.1%

Infant age: 40.0 weeks (1.2)

Race of Mother: White European (88.4)

Inclusion Criteria: NR

Exclusion Criteria: primiparous women or delivered 

preterm

Adjustments: Potential 

confounding factors were 

evaluated but none of them 

was significant confounding 

defined as changing the odds 

ratio by 10%

93
Antenatal and Postnatal Depression

Key Findings and Strength of Evidence for Antenatal and/or Postnatal 

Depression Outcome

• Three RCTs that assessed the effects of prenatal supplementation with DHA alone, 

DHA+AA, or EPA-enriched fish oil found no effects on either antenatal or postnatal 

depression among healthy pregnant women.

• One small RCT showed that women who received prenatal DHA supplementation had 

significantly fewer symptoms of postpartum depression compared to the placebo group.

• Two prospective observational studies found no associations between prenatal dietary or 

supplemental n-3 FA intake and antenatal or postnatal depression. 

• Three prospective observational studies found no significant associations between n-3 FA 

biomarkers and postnatal depression.

• One RCT that assessed the effects of postnatal supplementation with DHA alone found 

no effects on postnatal depression. 

This outcome is an additional outcome of interest that was not included in the original 

review. A total of five eligible RCTs and six observational studies were identified. Of these 11 

studies, four RCTs and all of the observational studies evaluated the effects of prenatal maternal 

n-3 FA interventions or exposures, while the fifth RCT examined the effects of postnatal 

maternal n-3 FA interventions. All studies that assessed the effects of n-3 FA on antenatal or 

postnatal depression were conducted among healthy pregnant or lactating women.

Description of Included Studies

Prenatal Maternal n-3 FA Interventions/Exposures

Randomized Controlled Trials

Four RCTs assessed the effects of prenatal maternal supplementation on the risk for antenatal 

and/or postnatal depression (See Table 10).

35, 42, 90, 91 While all of the studies compared the 

effects of DHA (200 to 900 mg/day) to that of placebo, two studies also included a third study 

arm. One included a third arm with supplements containing DHA+AA 90, and the other included 

a third arm with supplements containing EPA-rich fish oil. 42 Two studies examined the effects 

of n-3 FAs on postnatal depression only 35, 91, while the other two RCTs examined the effects on 

both antenatal and postnatal depression.

42, 90 Three of the four studies found no significant effects 

of marine oils on ante- or postnatal depression outcomes compared with placebo. Only one small 

pilot study showed that women who received prenatal DHA supplementation had significantly 

fewer symptoms of postpartum depression compared to the placebo group.91

The DOMInO trial randomized 2,399 pregnant Australian women (<21 week’s gestation) to 

receive fish oil containing 0.80 g/day DHA and 0.10 g/day EPA (n=1197) or vegetable oil 

placebo (n=1202) and followed women up to six months postpartum to assess for depressive 

symptoms using the Edinburgh Postnatal Depression Scale (EPDS).

35 The duration of 

intervention was not reported. No differences were found between the groups in percentage of 

women reporting high levels of depressive symptoms (EPDS score >12) at either 6 weeks or 6 

months postpartum.

94
Doornbos (2009) enrolled 182 pregnant Dutch women (14-20 weeks gestation) into a threearm trial (0.220 g/day DHA+ 0.220 g/day AA vs. 0.220 g/day DHA vs. soybean oil placebo)90. 

Sixty three women dropped out prior to 36 weeks gestation, leaving data from 119 women 

available for analysis. No differences were found in median EPDS scores among the groups at 

either week 36 of pregnancy or 6 months postpartum. 

Mozurkewich (2013) enrolled 126 pregnant women in the US (12-20 weeks gestation) into a 

three arm trial (0.900 g/d DHA+0.180 g/d EPA vs. 1.060 g/d EPA+274 g/d DHA vs. soy oil 

placebo). After adjusting for baseline Beck Depression Inventory (BDI) scores, no differences 

were found in mean BDI score between groups at either 34-36 weeks’ gestation or 6-8 weeks 

postpartum. However, a trend was observed toward significance at 26-28 weeks’ gestation 

(p=0.05). 

Judge (2015) enrolled 42 healthy pregnant women in the US at 24 weeks of gestation into a 

pilot trial comparing the effect of prenatal supplementation of 300 mg/d DHA to that of placebo 

(corn oil) on postpartum depression. After adjusting for baseline Center for Epidemiological 

Studies –Depression (CES-D) score, age, dietary DHA outside of intervention, and ethnicity, 

women who received prenatal DHA supplementation had significantly lower Postpartum 

Depression Screening Scale (PDSS) scores from 2 weeks to 6 months postpartum compared with 

those who received placebo (P=0.016).

Observational Studies

Six prospective studies were identified that assessed the effects of prenatal maternal n-3 FA 

intake or status on antenatal, perinatal, or postnatal depression (see Table 11). Two studies 

measured dietary n-3 FA intake,

92, 93 one study measured n-3 supplement intake,94 one study 

measured plasma total n-3 FA,95 and two studies measured the percent of total RBC 

phospholipid FAs.

96, 97

Dietary n-3 FA intake

Strom (2009) analyzed data from 54,202 women enrolled in the Danish National Birth 

Cohort.

92 They examined the association between deciles of n-3 FA intake estimated from a food 

frequency questionnaire administered mid-pregnancy and either admittance to a psychiatric 

hospital due to postpartum depression (PPD-admission) or purchase of antidepressants in a 

pharmacy with a prescription (PPD-prescription). No association was seen between any decile of 

intake of n-3 FAs and risk of either PPD-admission or PPD-prescription after adjusting for 

confounders. 

Miyake (2006) assessed the association of n-3 FA intake with risk of postpartum depression 

among 865 Japanese women enrolled in the Osaka Maternal and Child Health Study 

(OMCHS).

93 The authors observed no significant dose-response relationship between intakes of 

total n-3 FAs, EPA, DHA, or n-3/n-6 FA ratio and postpartum depression (as measured by the 

EPDS), even after adjusting for confounders. 

Supplementary n-3 FA intake

Leung (2013) analyzed data from 475 Canadian women enrolled in the Alberta Pregnancy 

Outcomes and Nutrition (APrON) study who completed the EPDS questionnaire at least twice 

during pregnancy and at 12 weeks postpartum.

94 Mean supplementary intake of n-3 FA differed 

significantly between women with a postpartum EPDS score <10 (n=416) and those with a 

postpartum EPDS score≥10 (n=59) (180 vs. 90 mg, p=0.01); however, the association did not 

95
persist in multivariate analyses. No association was observed between supplementary n-3 FA 

intake and prenatal EPDS scores measured in the second and third trimesters.

n-3 FA Biomarkers

Sallis (2014) reported results from 3,397 women enrolled in the Avon Longitudinal Study of 

Parents and Children (ALSPAC) cohort in England.

96 The authors examined the association 

between percent of total RBC phospholipid FAs measured from antenatal blood samples and 

ante-, peri-, and postnatal depression as measured by the EPDS. EPDS score >12 was the cutoff 

used to define depression. A weak association between prenatal EPA levels and perinatal onset 

depression was observed after adjusting for social class and maternal age (OR 1.07, 95% CI

0.99, 1.15). Levels of n-3 FAs were not associated with antenatal or postnatal depression in

multivariate models. 

Parker (2015) analyzed 895 women at 36 weeks of pregnancy for whom PUFA data were 

available.97 Postpartum depression status was measured by the Mini International 

Neuropsychiatric Interview (MINI) and EPDS scores. No associations were observed between 

any of the maternal PUFA measures and the MINI outcome after adjusting for other non-PUFA 

variables. When PUFA variables were added individually, only lower n-3 (OR=1.1, P<0.05), 

lower EPA (OR=2.7, P<0.05), and higher n-6 (OR=1.1, P<0.05) remained significant associated 

with postnatal depression measured by EPDS after adjusting for non-PUFA variables.

Chong et al (2015) analyzed the associations between prenatal plasma n-3 FAs and 

postpartum depression in 698 women from the Growing Up in Singapore Toward healthy 

Outcomes (GUSTO) study.95 The results showed no significant associations in either univariate 

or adjusted multivariate analyses between total plasma n-3 FAs or plasma AA:DHA ratio and 

risk of postpartum depression measured by EPDS at 3 months.

Postnatal maternal n-3 FA interventions/exposures

Randomized Controlled Trials

One RCT conducted in the U. that assessed the effects of a postnatal intervention on risk for 

PPD was identified.

98 Llorente (2003) enrolled 138 pregnant women who planned to breast feed 

for at least 4 months to receive an algae-derived triglyceride capsule containing 0.200 g/day of 

DHA or placebo, beginning within a week of delivery for four months. Eighty nine (64%) 

lactating women, mean age 31.5 years, completed four months of the study (44 in the DHA 

group and 45 in the placebo group) and were assessed for depressive symptoms using the BDI. 

Sixty three (46%) women were followed up to 18 months (31 in the DHA group and 32 in the 

placebo group) and were assessed for depressive symptoms using the EPDS. No significant 

differences in depressive symptom scores were found between groups at any of the time points 

(3 weeks, 2 months, 4 months, or 18 months postpartum).

96
Table 10. RCTs for ante postnatal depression

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Doornbos et al., 200990

Study name: NR

Study dates: Not reported

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Industry

Study follow-up: 3 

months/12 weeks 

postpartum

Study Population: 

Healthy pregnant women

Pregnant enrolled 182 

Pregnant withdrawals 63 

Pregnant completers 119

Pregnant age: NR (NR) 

NR

Race of Mother: NR 

(100)

Baseline biomarker 

information: Placebo 

group: DHA- 4.44 (3.00–

6.92); AA-12.91 (9.95–

14.95) DHA group: DHA5.51 (3.98–8.20); AA12.13 (9.63–15.22) 

DHA+AA group: DHA5.57 (2.48–8.32); AA13.60 (11.17–15.52)

Inclusion Criteria: women 

with first or second, 

singleton pregnancies

Exclusion Criteria: 

women with a vegetarian 

or vegan diet or 

gestational diabetes and 

preterm delivery (<37 

weeks)

Start time: Pregnant 16.5 (14-20) week of pregnancy

Duration: Pregnant till 3 months after delivery

Arm 1: Control group

Description: Placebo-soybean oil

Arm 2: DHA group

Brand name: NR

Manufacturer: NR

DHA: 220mg

Arm 3: DHA + AA group

Brand name: NR

Manufacturer: NR

DHA: 220 mg

AA: 220mg

Outcome: Edinburgh Postnatal Depression 

Scale (EPDS) (Secondary)

Follow-up time: 36 weeks pregnant

Arm 1: Sample size 34; median 4.0; IQR

Arm 2: Sample size 40; median 4.0; IQR

Arm 3: Sample size 37; median 6.0; IQR

Follow-up time: 6 weeks post-partum

Arm 1: Sample size 32; median 5.0; IQR

Arm 2: Sample size 38; median 4.0; IQR

Arm 3: Sample size 30; median 5.0; IQR

Judge et al., 201491

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Multiple foundations and 

Societies, None

Original, same study, or 

follow-up studies: none

Study Population: 

Healthy pregnant women

Pregnant enrolled 73 

Pregnant completers 42

Pregnant age: 18-35

Race of Mother: NR 

(100)

Inclusion Criteria: No 

other births in the 

previous two years; 20 

weeks pregnant; and 18-

35 years of age.

Exclusion Criteria: with a 

self-reported significant 

medical history (i.e., 

currently being treated 

for depression/psychiatric 

illness, addiction 

problems, 

hyperlipidemia, 

hypertension, renal 

disease, liver disease, or 

diabetes).

Start time: Pregnant 24 weeks gestation

Duration: Pregnant 24 weeks gestation until delivery

Arm 1: Placebo

Description: corn oil capsule

Dose: 1 capsule, 5 days/week

Blinding: Identical package and only ID information

Arm 2: DHA group

Description: 300mg DHA fish oil capsule

Dose: 1 capsule, 5 days/week

DHA: 300mg

Outcome: Postpartum Depression 

Screening Scale (PDSS) total score 

(Primary)

Follow-up time: 2 weeks

Arm 1: Sample size 22; mean 53.86; SD 

(15.25)

Arm 2: Sample size 20; mean 47.65; SD 

(12.96)

Follow-up time: 3 months

Arm 1: Sample size 22; mean 42.63; SD 

(9.52)

Arm 2: Sample size 20; mean 45.28; SD 

(12.25)

Follow-up time: 6 months

Arm 1: Sample size 22; mean 48.42; SD 

(17.18)

Arm 2: Sample size 20; mean 45.55; SD 

(13.5)

97
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 6 weeks

Arm 1: Sample size 22; mean 47.4; SD 

(12.42)

Arm 2: Sample size 20; mean 47.61; SD 

(14.31)

Llorente et al., 200398

Study name: Unnamed 

Trial A

Study dates: <2002

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: Isaacs, 

201199

Study Population: Breastfeeding women

Lactating enrolled 138 

Lactating completers 101

Lactating enrolled 138 

Lactating completers 101

Lactating age: 31.5 years 

(4.5 years) 18 - 42

Race of Mother: White 

European (82%) Black 

(14%) Hispanic (2.3%) 

Other race/ethnicity 

(1.6%)

Baseline biomarker

information: Placebo 

group Total saturated 

49.7 ± 2.3 Total 

monounsaturated 12.2 ± 

1.9 Total __6 33.7 ± 2.2

Total __3 4.37 ± 0.91

Intervention group Total 

saturated 49.3 ± 2.7 

Total monounsaturated

12.3 ± 1.3 Total __6 34.2 

± 2.0 Total __3 4.14 ± 

0.89

Inclusion Criteria: 

pregnant women who 

were 18 to 42 years old 

and planned to breast 

feed for at least 4 months

Exclusion Criteria: those 

with chronic medical 

conditions, or taking 

dietary supplements 

other than vitamins, or 

smokers, or who had 

been pregnant >5 times

Start time: Lactating birth

Duration: Lactating 4 months

Arm 1: placebo

Description: placebo capsule

Manufacturer: Martek Biosciences Corporation, 

Columbia, MD

Dose: 1 capsule

Blinding: capsules were identical in appearance

Arm 2: omega 3 capsule

Description: algae-derived triglyceride capsule

Brand name: DHASCO

Manufacturer: Martek Biosciences Corporation, 

Columbia, MD

Dose: 1 capsule

DHA: 200 mg

Outcome: Beck Depression Inventory (BDI) 

(Unspecified)

Follow-up time: 2 months

Arm 1: Sample size 45; mean 4.4; SD (4.2)

Arm 2: Sample size 44; mean 5.5; SD (4.3)

Follow-up time: 3 weeks

Arm 1: Sample size 45; mean 6.3; SD (4.7)

Arm 2: Sample size 44; mean 7.1; SD (5.7)

Follow-up time: 4 months

Arm 1: Sample size 45; mean 4.8; SD (5.9)

Arm 2: Sample size 44; mean 5.8; SD (5.2)

Outcome: Edinburgh Postnatal Depression 

Scale (EPDS) (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 32; mean 6.3; SD (4.1)

Arm 2: Sample size 31; mean 6.3; SD (5.2)

Outcome: responder: BDI<10 (Unspecified)

Follow-up time: at either 2, 4 or 18 months

Arm 1: 36/45 (79.0%)

Arm 2: 33/44 (76.0%)

Outcome: responder: BDI<20 (Unspecified)

Follow-up time: at either 2, 4 or 18 months

Arm 1: 43/45 (95.5%)

Arm 2: 40/44 (91.1%)

98
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Makrides et al., 201035

Study name: DOMInO

Study dates: 2005-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Smithers, 201153; Palmer, 

201254; Zhou, 201255;

Palmer, 201356; 

Makrides, 2014 57

Study Population: 

Healthy pregnant women

Pregnant enrolled 2399 

Pregnant withdrawals 1

Infants enrolled 605 

Infants withdrawals 32 

Infants completers 726

Pregnant age: 28.9 

(DHA5.7___ control5.6)

Race of Mother: NR (NR)

Inclusion Criteria: with 

singleton pregnancies at 

less than 21 weeks’ 

gestation were 

approached by study 

research assistants while 

attending routine 

antenatal appointments

Exclusion Criteria: 

already taking a prenatal 

supplement with DHA, 

their fetus had a known 

major abnormality, they 

had a bleeding disorder 

in which tuna oil was 

contraindicated, were 

taking anticoagulant 

therapy, had a 

documented history of 

drug or alcohol abuse, 

were participating in 

another fatty acid trial, 

were unable to give 

written informed consent, 

or if English was not the 

main language spoken at 

home

Start time: Pregnant < 21 week's gestation

Duration: NR

Arm 1: vegetable oil capsules

Description: a blend of 3 nongenetically modified oils 

(rapeseed, sunflower, and palm) in equal 

proportions

Manufacturer: Efamol, Surrey, England.

Dose: 3* 500mg capsule / day

Blinding: All capsules were similar in size, shape, 

and color

Arm 2: DHA

Description: DHA-rich fish oil concentrate

Manufacturer: ; Incromega 500 TG, Croda 

Chemicals, East Yorkshire, England

Dose: 500mg capsule *3/day

DHA: 800mg

EPA: 100mg

Outcome: % with Edinburgh Postnatal 

Depression Scale (EPDS) > 12 (Primary)

Follow-up time: 6 months

Arm 1: 138/1202 (11.5%)

Arm 2: 117/1197 (9.74%)

Follow-up time: 6 weeks

Arm 1: 131/1202 (10.88%)

Arm 2: 115/1197 (9.61%)

Mozurkewich et al., 

201342

Study name: NR

Study dates: Oct 2008 -

May 2011

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Study Population: 

Healthy pregnant women

Pregnant enrolled 126 

Pregnant withdrawals 8 

Pregnant completers 118

Pregnant age: EPA 29.9; 

DHA 30.6; placebo 30.4 

(EPA 5.0; DHA 4.5; 

placebo 5.9)

Race of Mother: White 

European (85%; 76%; 

83%) Black (10%; 11%; 

Inclusion Criteria: past 

history of depression, an 

EPDS score 9-19 (at risk 

for depression or mildly 

depressed), singleton 

gestation, a maternal age 

of 18 years or older, and 

a gestational age of 12-

20 weeks

Exclusion Criteria: had a 

history of a bleeding 

disorder, thrombophilia 

requiring anticoagulation, 

multiple gestation, bipolar 

Start time: Pregnant 12-20 week gestation

Duration: Pregnant assuming till birth

Arm 1: Control/Placebo

Description: 98% soy oil and 1% each of lemon and 

fish oil

Manufacturer: Nordic Naturals Corporation in 

Watsonville, CA

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large and 4 small placebo capsules

Blinding: The placebos were formulated to be 

identical in appearance to both the EPA- and DHArich supplements

Outcome: Beck Depression Inventory (BDI) 

(Primary)

Follow-up time: 26-28 weeks

Arm 1: Sample size 41; mean 6.3; SD (3.9)

Arm 2: Sample size 39; mean 8.7; SD (4.2)

Arm 3: Sample size 38; mean 7.0; SD (4.6)

Follow-up time: 34-36 weeks

Arm 1: Sample size 41; mean 7.4; SD (5.5)

Arm 2: Sample size 39; mean 8.2; SD (5.7)

Arm 3: Sample size 38; mean 6.9; SD (6.3)

Follow-up time: 6-8 weeks post-partum

Arm 1: Sample size 41; mean 5.9; SD (6.1)

Arm 2: Sample size 39; mean 6.6; SD (5.2)

Arm 3: Sample size 38; mean 5.7; SD (4.8)

99
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Manufacturer supplied 

product

5%) Asian (3%; 3%; 2%) 

Hispanic (0%; 11%; 7%) 

Inuit Eskimo (0%; 0%; 

2%) Pacific Islander (NR)

Baseline biomarker 

information: EPA group: 

EPA 0.29+-0.18; DHA 

4.24+-2.30; total n3 FA: 

22.10+-3.72 DHA group: 

EPA 0.31+-0.24; DHA 

4.66+-2.29; total n3 FA 

36.41+-9.71 placebo: 

EPA .34+-0.22; DHA 

3.85+-1.77; omega3 fa 

322.86+-5.02

disorder, current major 

depressive disorder, 

current substance abuse, 

lifetime substance 

dependence, or 

schizophrenia. Women

were also ineligible if 

they were currently 

taking omega-3 fatty acid 

supplements or 

antidepressant 

medications or eating 

more than 2 fish meals 

per week.

Arm 2: EPA-rich fish oil

Description: an approximate 4:1 ratio of EPA to DHA 

(1060 mg EPA plus 274 mg DHA)

Brand name: ProEPAXtra, Nordic Naturals

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large EPA capsule and 4 small placebo

DHA: 274 mg

EPA: 1060 mg

Arm 3: DHA-rich fish oil

Description: DHA and EPA in an approximate 4:1 

ratio o (900 mg DHA plus 180 mg EPA)

Brand name: ProDHA, Nordic Naturals

Viability: centrifuged before separation into the 6 

aliquots and were stored at 70 degrees C.

Dose: 2 large placebo oil and 4 small DHA rich

DHA: 900 mg

EPA: 180 mg

100
Table 11. Observational studies for ante postnatal depression

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Chong, et al., 201595

Outcome domain: Depression

Study dates: 2009-2010

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Follow-up: 3 months postpartum

Study Population: Healthy pregnant women 

Postpartum women

Pregnant enrolled 997 Pregnant completers 698

Pregnant age: NR (NR)

Race of Mother: Asian (100)

Inclusion Criteria: Within range of 18-50 years, 

recruited from 2 major public maternity units in NUH 

and KKH. Were Singaporean citizens or permanent

resident of Chinese, Malay, Indian ethnicity with 

parents of homogeneous ethnic background, with 

the intention to deliver in the two hospitals and 

residing in Singapore for next 5 years and willing to 

donate birth tissues including cord, placenta, cord 

blood at delivery

Exclusion Criteria: pre-existing health conditions 

such as type 1 diabetes, depression, or mental 

health related disorders self-reported during 

recruitment

Adjustments: Adjusted for 

ethnicity, parity, education 

level, marital status, maternal 

body mass index at 26-28

week's gestation, maternal 

age, employment status, 

obstetric and neonatal 

complications, smoking status 

and smoke exposure before 

and during pregnancy, alcohol 

consumption before and 

during pregnancy, history of 

abortion, miscarriage, 

stillbirth, exercise frequency, 

and reported fish oil 

supplementation

Leung, et al., 201394

Outcome domain: Depression

Study name: Alberta Pregnancy Outcomes and 

Nutrition (APrON) study

Study dates: %n

Study design: Observational prospective

Location: Canada

Funding source / conflict: NR

Study Population: Healthy pregnant women

Pregnant enrolled 600 Pregnant withdrawals 

125 Pregnant completers 475

Pregnant age: 31.2 not depressed 31.6 

depressed (4.16 not depressed 4.7 depressed) 

not reported

Race of Mother: White European (87%) Other 

race/ethnicity (13%)

Inclusion Criteria: at least 16 years old with 

gestational age =27 weeks. Women must be in the 

first (T1) or second (T2) trimester

Exclusion Criteria: Any woman who was 28 weeks 

or beyond, Non-English speakers, known drug and 

alcohol abusers, and those planning to move out of 

the region within 6 months

Adjustments: Born in Canada, 

prenatal and postnatal social 

support, prenatal EPDS, 

selenium

Parker, et al., 201597

Outcome domain: Depression

Study dates: NR

Study design: Observational prospective

Location: Australia

Funding source / conflict: Government

Study Population: Healthy pregnant women 

Postpartum women

Pregnant enrolled 1232 Pregnant completers 

831

Pregnant age: 31.0 (5.7)

Race of Mother: NR (100)

Inclusion Criteria: Women between 34 and37 weeks

of pregnancy and attending an obstetric service. 

Participants had to be more than 18 years of age, be 

proficient in English and able to provide informed 

consent

Exclusion Criteria: nr

Adjustments: Age, education 

level, income level, marital 

status, number of children, 

neuroticism scores, the 

presence or absence of a 

lifetime mood disorder, coffee 

drinking, cigarette smoking 

and alcohol intake, as well as 

stress levels during 

pregnancy

Sallis, et al., 201496

Outcome domain: Depression

Study Population: Healthy pregnant women

Pregnant enrolled 14,541 Pregnant withdrawals 

Inclusion Criteria: All women with an expected due 

date between April 1991 and December 1992 were 

eligible for the study. Only women with data 

Adjustments: Social class (I/II, 

III or IV/V) and maternal age

101
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Study name: Avon Longitudinal Study of 

Parents and Children (ALSPAC)

Study dates: 1991-1992

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

11,144 Pregnant completers 3,397

Pregnant age: 28.9 (4.5) not reported

Race of Mother: White European (100%)

available on genotype, FA levels and depressive 

symptoms during pregnancy or at 8 weeks 

postnatally and women with a self-reported ethnicity 

of White European were included in this analysis.

Exclusion Criteria: Mothers who lost a child during 

the neonatal period and those with a still birth; 

mothers with multiple births.

Strom, et al., 200992

Outcome domain: Depression

Study name: Danish National Birth Cohort

Study dates: 1996-2002

Study design: Observational prospective

Location: Denmark

Funding source / conflict: Government, Multiple

foundations and Societies, Funding Affiliations 

trade group, March of Dimes

Study Population: Healthy pregnant women

Pregnant enrolled 86,453 Pregnant withdrawals 

32,251 Pregnant completers 54,202

Pregnant age: not reported (not reported) not 

reported

Race of Mother: NR (100%)

Inclusion Criteria: All pregnant women living in 

Denmark between 1996 and 2002, who were fluent 

in Danish

Exclusion Criteria: NR

Adjustments: Total energy 

intake, prepregnant BMI, 

maternal age, parity, alcohol 

intake, smoking, occupation, 

education, homeownership, 

marital status, social support, 

and history of previous 

depression

Yoshihiro Miyake, et al., 200693

Outcome domain: Depression

Study name: Osaka maternal and child health 

study

Study dates: 2001-2003

Study design: Observational prospective

Location: Japan

Funding source / conflict: Government, Multiple

foundations and Societies, None

Study Population: Healthy pregnant women

Pregnant enrolled 1002 Pregnant withdrawals 

137 Pregnant completers 865

Pregnant age: age reported in categories

Race of Mother: Asian (100%)

Inclusion Criteria: women who became pregnant in 

Neyagawa City, Osaka Prefecture, Japan

Exclusion Criteria: NR

Adjustments: Age, gestation, 

parity, cigarette smoking, 

family structure, family 

income, education, changes 

in diet in the previous month, 

season when data at baseline 

were collected, body mass 

index, time of delivery before 

the second survey, medical 

problems in pregnancy, 

baby’s sex and baby’s birth

weight

102
Key Question 2: Fetal/Childhood Exposures

What is the influence of maternal intakes of n-3 fatty acids or the n-3 fatty 

acid content of maternal breast milk (with or without knowledge of maternal 

intake of n-3 FA) or n-3 FA-supplemented infant formula or intakes of n-3 

FA from sources other than maternal breast milk or supplemented infant 

formula on the following outcomes in term or preterm human infants?

• Postnatal Growth patterns

• Neurological development

• Visual function

• Cognitive development

• Autism

• Learning disorders

• ADHD

• Atopic dermatitis

• Allergies

• Respiratory illness

What are the associations of the n-3 FA content or the n-6/n-3 FA ratio of 

maternal or fetal or child biomarkers with each of the outcomes identified 

above?

Postnatal Growth Patterns

Key Findings and Strength of Evidence

• There is moderate evidence that prenatal maternal supplementation of fish oil or 

DHA+EPA supplements has no effect on weight, length, or head circumference at 18 

months. Pooled analysis of 5 RCTs shows null effects for weight (0.22, 95% CI [-0.62, 

0.19]), length (0.01 [-0.52, 0.54]), and head circumference (-0.01 [-0.28, 0.27]).

• There is low evidence that prenatal maternal supplementation of fish oil or DHA+EPA 

supplements continuing postpartum has no effect on growth outcomes.

• There is low evidence that supplementation of DHA+AA formula in preterm infants has 

no effect on overall weight and length. Pooled analysis of three studies showed null 

effects for weight at 4 months (-0.01 [-0.48, 0.47]) and length at 4 months (-0.03 [-0.91, 

0.85]).

• There is low evidence that supplementation of DHA+AA formula in term infants has no 

effect on growth outcomes.

• There is low evidence from three observational studies that biomarkers associated with n3s in infant red blood cells are consistently associated with increased weight gain, length 

gain, and BMI at 7 years.

• There is insufficient evidence to determine whether prenatal and postnatal maternal 

supplementation with DHA+AA has an effect on growth outcomes.

103
• There is insufficient evidence to determine whether postnatal maternal supplementation 

with DHA+EPA has an effect on growth outcomes.

• There is insufficient evidence to determine whether prenatal maternal supplementation in 

combination with postnatal infant supplementation with DHA+EPA has an effect on 

growth outcomes.

• There is insufficient evidence to determine whether supplementation of preterm infants 

with DHA+AA+EPA has an effect on growth outcomes.

Description of Included Studies

The original review included 42 RCTs and two observational studies for the outcomes of 

postnatal growth patterns, including one RCT that assessed the effects of prenatal maternal 

intake of n-3 FAs during pregnancy in term and preterm infants; one RCT and one cohort study 

on n-3 FA content of breast milk with or without known maternal intake in term infants only (no 

studies assessed the effects of n-3 FA intake by breastfeeding mothers on growth patterns of 

preterm infants); 20 RCTs on postnatal n-3 FA supplementation in preterm infants; 18 RCTs on 

postnatal n-3 FA supplementation in term infants; five RCTs that also assessed associations of n3 FA biomarkers with growth patterns of preterm infants; five RCTs and a prospective cohort 

study that assessed associations of n-3 FA biomarkers with postnatal growth patterns in term 

infants; and one RCT that assessed the associations of n-3 FA biomarkers with postnatal growth 

patterns in very low birth weight (VLBW) term and preterm infants.

The present review identified 24 additional RCTs and three observational studies that 

included pediatric growth pattern outcomes. Three of the RCTs also included associations of 

growth patterns with biomarkers of n-3 FA. Of these, seven RCTs and two observational studies 

evaluated prenatal maternal n-3 FA interventions or exposures, four RCTs examined a 

combination of prenatal and postnatal maternal n-3 FA interventions or exposures, and one RCT 

and one observational study examined postnatal maternal n-3 FA interventions or exposures. 

Nine RCTs examined postnatal infant n-3 FA interventions or exposures, and two RCTs 

examined a mixed set of postnatal maternal and postnatal infant n-3 FA interventions or 

exposures. Six RCTs that assessed the effects of n-3 FA supplementation in infants on growth 

patterns were conducted among healthy infants or infants born to healthy women, while four

RCTs were conducted among preterm or low birth weight infants.

Prenatal Maternal Interventions/Exposures

In the original review, one good quality RCT found no difference in weight, length, and head 

circumference from birth to 12 months between infants (590 enrolled, 341 completers) born to 

mothers who used n-3 FA and n-6 FA supplements or predominantly n-6 FA supplements during 

pregnancy.

Randomized Controlled Trials

DHA+EPA

The present review identified seven studies of prenatal maternal DHA, DHA+EPA, fish oil, 

or algal oil supplementation34, 41, 44, 60, 75, 77, 100 and four studies of prenatal and postnatal maternal 

DHA, DHA+EPA, or fish oil supplementation (see Table 12).

37, 52, 66, 76

104
Dunstan (2008) assessed the effects of prenatal supplementation with 4 g fish oil capsules 

daily compared to olive oil in 72 pregnant Australian women with allergies starting at 20 weeks 

of gestation until delivery, but found no differences in infant weight, length, or head 

circumference at 30 months.

44

Bergmann and coworkers (2007) compared the effects of a vitamin and mineral supplement, 

the supplement plus a prebiotic, and the supplement plus prebiotic and DHA (0.200 g/d) on the 

offspring of 144 healthy pregnant women in Germany, supplemented from the 21st to 37th 

weeks of pregnancy. The authors report that mothers whose supplements included DHA had 

infants that were not significantly different from the control infants at 1 or 3 months for BMI, 

weight, length, or head circumference, but BMI (-0.76, 955 CI -1.46, -0.07) and weight (kg) (-

0.601, 95% CI -1.46, -0.07) for infants taking DHA were actually less than in control infants at 

21 months, although length and head circumference were not significantly different.41

Stein and coworkers (2011) randomized 1,094 pregnant Mexican women in weeks 18-22 of 

gestation to daily olive oil capsules or 0.200 g/d DHA through term.34 Data from the 739 infants 

followed up at 18 months indicated no overall effects on weight, length, BMI, or head 

circumference, although infants born to primigravid women (women pregnant for the first time) 

supplemented with DHA were significantly longer by 0.7 cm (95% CI 0.1, 1.3; P = 0.02).

Another study in Mexico by Gonzalez-Casanova et al. (2015) randomized 1,040 pregnant 

women to daily supplementation of 400 mg DHA from an algal source or soy/corn placebo from 

18-22 weeks gestation until delivery. No effect on attained size (weight, height, BMI, or any of 

the “for-age” z-scores for these metrics) was observed at five years.60

Similarly, Malcolm and coworkers (2003) randomized 100 pregnant women from 15 weeks 

gestation until birth to receive either sunflower oil or fish oil (DHA 0.200 g/d) and found no 

differences in weight, length, or head circumference between the groups at 50 or 66 weeks.

100

Tofail et al. (2006) compared supplementation of 249 pregnant women in Bangladesh with 

DHA (1.2 g) and EPA (1.8 g) daily from 25 weeks until delivery with that of soy oil alone, and 

found no differences in head circumference at 10 months.

77

A recent study by Mulder et al. (2014) compared 270 subjects supplemented with 400 

mg/day DHA or placebo capsules from less than 16 weeks gestation until delivery. No 

significant differences in weight-for-length, length-for-age, or weight-for-age Z-scores were 

observed at 2, 6, 9, 12, or 18 months by ANOVA (P≥0.05).75

Van Goor and colleagues (2011) randomized pregnant Dutch women in the 14th-20th weeks 

of pregnancy to soybean oil capsules with (n=41) or without (n=34) DHA (0.220 g/d) until 3 

months after delivery; again, no significant differences with regard to weight, length, or head 

circumference were found at 18 months.

66

Bergmann et al. (2012) enrolled 144 pregnant women in a study comparing a basic 

supplement (vitamins and minerals only) to a basic supplement with fructooligosaccharide

prebiotic, to the basic prebiotic supplement with fish oil (200 mg DHA and 60 mg EPA) from 21 

weeks gestation until 3 months after delivery. While the weight, length, BMI, head 

circumference, and skin-fold thickness at 6 years were similar among the DHA+EPAsupplemented and control groups at 6 years, the BMI z-scores increased at a later age in the 

DHA+EPA group. There was a negative correlation between height at 6 years and the increase in 

red blood cell DHA concentration of mothers from 22 to 37 weeks of pregnancy (p=0.007).52

We identified a long-term (7-year) follow-up of a study conducted in Norway that was

discussed in the original report. In this study, pregnant women were randomized at 18 weeks 

gestation to receive 10 mL cod liver oil daily (1.183 g/10 mL DHA, 0.803 g/10 mL EPA, and a 

105
total of 2.494 g/10 mL n-3 PUFAs) or 10 mL corn oil (4.747 g/10 mL LA and 0.092 g/10 mL 

ALA) through 3 months postpartum. This study found no significant differences in weight, 

height, or BMI at 7 years.

76

A study by Hauner et al. (2012) compared the effect of fish oil supplements (DHA 1.020 g/d

and EPA 0.180 g/d) and nutritional counseling to that of nutritional counseling alone in German 

women from 15 weeks gestation to four months postpartum.

37 No differences were seen between 

treatments in weight, length, BMI, or head circumference at 6 weeks, 4 months, or 12 months.

Pooling the results of four RCTs,34, 41, 66, 100 on the effects of DHA given to pregnant women 

compared to placebo on weight, length, and head circumference at 18 months showed no 

statistically significant effects ( WMD [95% CI] in weight (kg): -0.22, [-0.62, 0.19], I2=52%; 

WMD [95% CI]in length (cm): 0.01 [ -0.52, 0.54] ], I2=0%; WMD [95% CI]in head 

circumference (cm): -0.01, [ -0.28, 0.27], I2=0%. These studies are further summarized in Table 

11 and the forest plots are shown in Figures 11, 12, and 13.

Figure 11. Weight (kg) at 18 months – DHA versus placebo, given to pregnant women

Figure 12. Length (cm) at 18 months – DHA versus placebo, given to pregnant women

106
Figure 13. Head circumference (cm) at 18 months – DHA vs. placebo, given to pregnant women

DHA+AA

Only one study was identified that compared the effects on postnatal growth patterns of 

administering supplemental DHA+AA to pregnant women with that of placebo. Van Goor 

(2011) randomized pregnant Dutch women in the 14th-20th weeks of pregnancy to soybean oil 

capsules with (n=39) or without DHA+AA (0.220 g/d) (n=34) until 3 months after delivery. 

Again, no significant differences with regard to weight, length, or head circumference were 

found at 18 months.66

Observational Studies

The outcomes of the INFAT study101 were used to assess the association of n-3 FAs in breast 

milk (in 208 women who had been following their usual diet or supplementing their usual diet 

with 1.200 g/d LCPUFAs) Negative associations were observed between length at one year and 

both DHA and n-3 LCPUFA in breast milk (p<0.05); no other significant associations were 

observed between breast milk FA concentrations and weight, length, BMI, or head 

circumference outcomes. 

Another analysis of data from the INFAT study83 found no significant growth outcome 

associations of LCPUFA content of maternal red blood cells at 32 weeks gestation with weight, 

length, BMI, or head circumference at 6 weeks, 4 months, or one year (see Table 13).

Postnatal Maternal Interventions/Exposures

The original review identified one good quality RCT, one poor quality RCT, and an 

observational study on the effect of maternal supplementation of n-3 FA after delivery on 

postnatal growth patterns. Neither RCT showed effects of maternal intake of n-3 FA or n-6 FA 

on growth patterns at any time point. The observational study showed a positive correlation 

between the breast milk AA/DHA content and the infant’s rate of increase in head circumference 

at 1 and 3 months. 

Randomized Controlled Trials

DHA+EPA

Only one RCT on the effect of postnatal maternal interventions on growth patterns was 

identified for the current report. Lauritzen and colleagues (2005) randomized Danish 

breastfeeding women less than 2 weeks postpartum to olive oil or fish oil in the form of capsules, 

musli bars, and/or cookies, providing either 0.62 g/d EPA and 0.79 g/d DHA or 0.36 g/d EPA 

107
and 0.99 g/d DHA daily, depending on the dosage form. Of the 100 children completing the trial, 

72 were followed up to 2.5 years. While growth in weight, length, and head circumference did 

not differ between the randomized groups up to 9 months, children in the fish oil group had 

larger BMI (p = 0.022), and head circumference (p = 0.028) than those in the olive oil group at 

2.5 years (102).

Observational studies

The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study 

enrolled 244 mothers in the Netherlands. Concentrations by weight of total LCPUFAs, DHA, 

EPA, or ALA in breast milk samples provided by the mothers showed no significant associations 

with mean gain in weight, length, or BMI in the first year of life.103

Combination of Postnatal Maternal and Preterm Infant Interventions/Exposures

The original review did not describe any interventions that combined both maternal and 

infant exposures.

Randomized Controlled Trials

DHA+EPA

The DINO study was an Australian RCT104, 105 that investigated the effect of both n-3 FA 

tuna oil supplements for lactating mothers of preterm (<33 weeks gestation) infants and formula 

supplemented with and without DHA from 2-5 days after delivery through the estimated due date 

(n=657). DHA supplementation had no observable effects on weight or head circumference at 

4,12, and 17 months, but DHA-supplemented infants were 0.7 cm (95% CI 0.1, 1.4 cm; P=0·02) 

longer in length at 18 months corrected age. An interaction effect was observed between DHA 

supplementation and birth weight strata for weight (P=0.01) and length (P=0.04). Infants who 

weighed ≥1250 g at birth and received supplemental DHA had greater length at 4 months 

corrected age and greater weight and length at 12 and 18 months corrected age. 

Observational Studies

No observational studies were identified with both maternal and preterm infant exposures. 

Preterm Infant Interventions/Exposures

The original review identified 20 RCTs, all of poor quality, that studied the effects of n-3 FA 

supplementation of preterm infants on postnatal growth patterns. Eighteen of the 20 studies 

found no effect on growth parameters at any time point. Two trials found that the n-3 FAsupplemented group actually had significantly lower weight at 6-18 months than the placebosupplemented group. A meta-analysis in the original review of studies comparing formula with 

DHA+AA and control formula on mean weight and length at 4 months showed no significant 

effect (MWD for weight: -0.01, 95% CI -0.48, 0.47; MWD for length: -0.03, 95% CI -0.91, 

0.86).

Randomized Controlled Trials

DHA+AA

Three studies examined differences in growth outcomes among preterm or VLBW infants 

supplemented with DHA and AA compared with controls.

108
Groh-Wargo compared 60 preterm infants in the U.S. given n-3 FA supplements (0.15%-

0.24% DHA and 0.41% AA) to those given a placebo until one year corrected age. No 

significant differences were observed at any time point in weight, length, or head circumference. 

However, at 12 months corrected age, DHA+AA supplemented infants had significantly greater 

lean body mass (p < 0.05) and significantly less fat mass (p < 0.05) than the control infants.106

A study of 141 VLBW preterm infants in Norway supplemented with human milk with 

added oils containing DHA (6.9%) and AA (6.7%) from birth until discharge from the hospital 

(9 weeks on average) found no differences in growth outcomes between the groups at 6 

months.107

A study by Clandinin and colleagues (2005) of 361 preterm infants in the U.S. also compared 

the effects of administering two different kinds of DHA sources (algal sources and fish oil, both 

0.32-0.33%) with AA (0.64-0.67%) from fungal sources with that of a placebo until 92 weeks 

postmenstrual age. Since the results were shown only on a graph, they were not abstracted into 

the evidence tables. However, the algal-DHA group was significantly greater than the control 

group in terms of weight (66 to 118 weeks) and length (48, 79, and 92 weeks). The algal-DHA 

group also exceeded the fish-DHA group in weight at 118 weeks PMA and in length at 57, 79, 

and 92 weeks PMA. Mean head circumference did not differ between the DHA groups and 

control groups at any follow-up time.108

Results for the effects of DHA+AA compared to placebo on weight and length of preterm 

infants at 4 months were pooled106 with the outcomes of two studies from the original report, but 

the pooled effect sizes were not statistically significant (WMD [95% CI] in weight (kg): -0.01[-

0.48, 0.47] I2=33.5%; WMD [95% CI]in length (cm): -0.03[-0.91, 0.85] I2=0%. The summary if 

this study and the results are shown in Table 12 and Figures 14 and 15.

Figure 14. Weight (kg) at 4 months – DHA + AA versus placebo, given to preterm infants

109
Figure 15. Length (cm) at 4 months – DHA + AA versus placebo, given to preterm infants

DHA+AA+EPA

Groh-Wargo compared the effects of n-3 FA supplements (0.16%-0.27% DHA, 0.43% AA, 

and 0.08% EPA) and placebo given to 60 U.S. preterm infants until one year corrected age. No 

significant differences were observed at any time point in weight, length, or head circumference 

(although at 12 months corrected age, DHA+AA+EPA-supplemented infants had significantly 

greater lean body mass (p < 0.05) and significantly less fat mass (p < 0.05) than the control 

infants).106

A study of 139 preterm infants in the Netherlands supplemented with either preterm formula 

(0.14% DHA, 0.14% AA, and 0.039% EPA), term formula (0.07% DHA and 0.07% AA), or 

human milk found no significant differences in weight, length, or head circumference at 3 and 6 

months corrected age.109

Observational studies

No observational studies were identified for preterm infant exposures.

Term infant interventions/exposures

The original review identified 18 RCTs, all of good quality, that assessed the effect of n-3 FA 

supplementation in term infants on growth patterns. While the effects on growth patterns were 

not significantly different between study arms overall, certain time points and subgroups showed 

inconsistent differences. The meta-analysis showed a non-statistically significant overall effect 

of formulas containing DHA+AA at 4 months (MWD for weight: -0.06, 95% CI -0.45, 0.34; 

MWD for length: -0.33, 95% CI -1.07; 0.40) and 12 months (MWD for weight: -0.33, 95% CI -

0.87, 0.21; mean weight difference for length: 0.37, 95% CI -1.26, 0.51; MWD for head 

circumference 0.14, 95% CI -0.83, 1.12). Similarly, formulas containing DHA showed a nonstatistically significant overall effect at 4 months (MWD for weight: -0.12, 95% CI -0.44, 0.20,

MWD for length: -0.43, 95% CI -1.20, 0.34; MWD for head circumference: 0.04, 95% CI -0.37, 

0.46) and 12 months (MWD for weight: -0.33, 95% CI -0.87, 0.21; MWD for length: : -0.71, 

95% CI -2.18, 0.76; MWD for head circumference -0.04, 95% CI -0.45, 0.38). Four trials 

adjusted results for confounders, but failed to find any difference in the results. 

110
Randomized Controlled Trials

DHA+AA

The current review identified six RCTs that studied the effect of DHA+AA supplementation 

in term infants.

Sala-Vila et al. (2004) compared growth outcomes in 35 term infants in Spain supplemented 

with human milk (0.4 and 0.3 g/100 g total FA as AA and DHA) to growth outcomes of infants 

supplemented with n-3 FA from eggs and to growth outcomes of infants supplemented with n-3 

FA from fungi and algae (both 0.4 and 0.1 g/100 g total FA as AA and DHA). After three 

months supplementation, no differences in weight, length, or head circumference were 

observed.110

Birch and colleagues (2005) randomized 103 term infants in the United States to DHA and 

AA (0.36% and 0.72% of total FA) from five days to 52 weeks. They observed no significant 

differences in weight, length, and head circumference at 6, 17, 39, or 52 weeks.111 Since results 

were shown only graphically, they were not pooled. 

Another study compared 30 term infants supplemented with term infant formula or a high 

DHA (0.20%) and AA (0.34%) formula for an unknown duration, commencing less than 14 days 

after birth. No significant differences were seen among either group at age 6 weeks or 2 years.112

The BeMIM (Belgrade-Munch Infant Milk) Trial 113 recruited and randomized 213 infants to 

term infant formula or to a high DHA (7.2g/100mL) and AA (7.2g/100mL) formula from 

younger than 1 month to 4 months of life. While the rates of change of head circumference and 

weight gain were not statistically different between formula groups (high DHA+AA formula: 

30.2 ± 6.3 vs. control formula: 28.3 ± 6.5 g/day, mean ± SD, P = 0.06), rates of length gain were 

higher in the high DHA+AA group than in the term infant formula group (0.11 ± 0.02 vs. 0.10 ± 

0.02 cm/day, P = 0.02).114

Currie and coauthors (2015) compared 54 healthy term infants in a trial of infant formula that 

combined three arms of DHA+AA (0.32% DHA and 0.64% AA, 0.64% DHA and 0.64% AA, 

and 0.64% DHA and 0.32% AA) and to a placebo group of 15 infants up to 6 years. DHA+AA 

supplementation in infancy predicted higher length from birth to 18 months (p=0.033) and higher 

weight (p=0.02) and stature-for-age (p=0.0007) percentiles from 2 to 6 years. No differences in 

BMI (p=0.38) or BMI-for-age (p=0.20) percentile from infancy to age six were observed.115

Observational studies

No observational studies were identified for term infant exposures.

Maternal and Infant Biomarkers

The original report included eleven studies on the relationship between n-3 FA biomarkers in 

children and growth patterns. Five were RCTs in preterm infants, five were RCTs in term 

infants, and one was a prospective cohort study of term infants. A negative correlation was seen 

between weight and the plasma or red blood cell content of DHA, and a positive correlation 

between weight and the content of AA in plasma or red blood cells was seen in some but not all 

studies. As biomarkers, n-6 FA (AA) may be related to infant weight gain, whereas DHA seems 

to be inversely related, but no significant clinical outcomes were detected.

The current report identified three additional studies with biomarker results related to growth 

patterns. A follow-up of studies on maternal n-3 FA supplementation during pregnancy and 

breastfeeding reviewed in the original report found no significant correlations between umbilical 

plasma phospholipid concentrations of LA, AA, ALA, DHA, or the ratio of n-3/n-6 fatty acids 

111
and the children’s BMI at 7 years.76 In addition, no significant correlations between umbilical 

plasma phospholipid concentrations of LA, AA, ALA, DHA, or the ratio of n-3/n-6 fatty acids at 

4 weeks or 3 months and BMI at 7 years were found. 

The DINO study104) in preterm (<33 weeks gestation) infants in Australia (n=657) found no 

consistent relations between erythrocyte phospholipid polyunsaturated fatty acids and weight, 

length, and head circumference at 4 months corrected age. Changes in RBC-DHA were 

positively associated with gain in weight (p<0.001) and length (p<0.001) and negatively 

associated with gain in head circumference (p<0.05) between term and 6 months corrected age. 

A study of 139 preterm infants in the Netherlands supplemented with preterm formula, term 

formula, or human milk found that changes in RBC-AA were positively associated with gain in 

head circumference (p<0.001) and negatively associated with gain in weight (p<0.001) and 

length (p<0.05), while changes in RBC-DHA/AA ratios were positively associated with weight 

gain (p<0.001) and length gain (p<0.001) but negatively associated with increases in head 

circumference (p<0.001) between term and six months corrected age. Changes in RBC-EPA 

showed no associations with gain in weight, length, or head circumference between term and six 

months corrected age.109

112
Table 12. RCTs for postnatal growth patterns

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Bergmann et al., 201252

Study name: NR

Study dates: 2000-2009

Study design: Trial 

randomized parallel

Location: Germany

Funding source / conflict: 

NR, None, Manufacturer 

supplied product

Study follow-up: 6 years

Original, same study, or 

follow-up studies: 

Bergmann, 201241

Study Population: 

Healthy infants

Pregnant enrolled 144 

Pregnant completers 115

Infants enrolled 123 

Infants completers 115

Pregnant age: 30.9 years 

(4.89)

Infant age: 21 weeks 

gestation

Race of Mother: White 

European (100)

Baseline biomarker 

information: In previous 

study, see Bergmann, 

2012 41

Inclusion Criteria: 

Healthy pregnant 

Caucasian women who 

were at least 18 years 

and willing to breastfeed 

for at least 3 months 

were enrolled at 21 

weeks of gestation

Exclusion Criteria: 

Mothers: increased risk 

of premature delivery or 

multiple pregnancy, 

allergy to cow milk 

protein, lactose 

intolerance, diabetes, 

smoking, consumption of 

alcohol (>20 g/week), or 

participation in another 

study Infants: Premature 

at birth (<37 weeks’ 

gestation), had any major 

malformations, or were 

hospitalized for more 

than one week

Start time: Pregnant 21 weeks gestation

Duration: Pregnant 21 weeks until 3 months after 

delivery

Arm 1: Vitamins and minerals ("basic")

Description: Control 1

Manufacturer: Nestle

Arm 2: Basic supplements plus a prebiotic

fructooligosaccharide (FOS)

Description: Control 2

Manufacturer: Nestle

Arm 3: Basic supplements, FOS, and fish oil

Description: Intervention

Manufacturer: Nestle

DHA: 200 mg

EPA: 60 mg

Outcome: BMI (kg/m2) (Secondary)

Follow-up time: 6 yrs

Arm 1: Sample size 74; mean 15.5; SD 

(1.3)

Arm 2: Sample size 41; mean 15.7; SD 

(1.5)

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 6 yrs

Arm 1: Sample size 74; mean 52.7; SD 

(1.3)

Arm 2: Sample size 41; mean 52.5; SD 

(1.6)

Outcome: height (cm) (Secondary)

Follow-up time: 6 yrs

Arm 1: Sample size 74; mean 119.6; SD 

(4.6)

Arm 2: Sample size 41; mean 119.2; SD 

(5.3)

Outcome: weight (kg) (Secondary)

Follow-up time: 6 yrs

Arm 1: Sample size 74; mean 22.3; SD 

(2.9)

Arm 2: Sample size 41; mean 22.4; SD 

(3.1)

Birch et al., 2005111

Study name: NR

Study dates: Not reported

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy infants

Infants enrolled 103 

Infants completers 86

Pregnant age: 31 years 

(4 years)

Infant age: 3.6 

_x0004_days (1.3 days) 

1-5 days

Race of Mother: NR

Inclusion Criteria: All 

were born at 37– 40 wk 

after conception. Only 

singleton births with birth 

weight appropriate for 

gestational age

Exclusion Criteria: Family 

history of milk protein 

allergy, genetic or familial 

eye disease, vegetarian 

or vegan maternal dietary 

patterns, maternal 

metabolic disease or 

infection, jaundice, 

perinatal asphyxia, 

Start time: Infants 1-5 days

Duration: Infants 52 wks

Arm 1: Control

Description: Commercial infant formula

Brand name: Enfamil with Iron

Manufacturer: Mead Johnson Nutritionals, 

Evansville, IN

Active ingredients: Linoleic acid-8.48g/L (14.6%); 

14.7 g protein/L, 37.5 g fat/L, 69.0 g carbohydrate/L

Blinding: Each diet was masked by 2 color and 2 

number codes, for a total of 4 possible diet 

assignments. The randomization schedule had 

random-length blocks (block length varied from 6 to 

12) and was provided in individual sealed envelopes 

data only reported on graph

Outcome: (Secondary)

113
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

meconium aspiration, or 

any perinatal event that 

resulted in placement of 

the infant in the neonatal 

intensive care unit.

to the study site.

ALA: 1.5% of total fatty acids

Arm 2: LCPUFA-supplemented formula

Description: Commercial formula supplemented with 

LCPUFA

Brand name: Enfamil with Iron plus DHASCO and 

ARASCO

Manufacturer: Formula: Mead Johnson; DHA+ARA: 

Martek Biosciences

Active ingredients: 15% linoleic acid,14.7 g /L 

protein, 37.5 g /L fat, 69.0 g /L carbohydrate

ALA: 1.5% of total fatty acids

DHA: 0.36% of total fatty acids

AA: 0.72% of total fatty acids

Clandinin et al., 2005108

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Industry

Study Population: 

Preterm infants

Infants enrolled 361 

preterm+105 term 

breastfed Infants 

completers 179 preterm 

and 76/105 term 

breastfed

Infant age: 30.6 weeks 

postmenstrual age 24-36 

weeks postmenstrual age

Race of Mother: NR 

(100)

Inclusion Criteria: Phase 

I: gestational age <35 

weeks PMA and received 

<10 total days of enteral 

feedings of >30 mL/kg 

per day. Infants initially 

fed human milk were not 

enrolled unless formula 

was started within 10 

days after completing the 

first day of human milk 

feeding Phase II: 

completion of phase I 

and >=80% enteral 

intake from study formula 

during hospitalization and 

100% of caloric intake 

from study formula at 

completion of phase 1.

Birth weight<1500g

Exclusion Criteria: 

congenital abnormalities 

of the gastrointestinal 

tract, hepatitis, hepatic or 

biliary pathology, 

necrotizing enterocolitis 

confirmed before 

Start time: Infants 10 days of age

Duration: Infants 118 weeks

Arm 1: Control

Description: Non-supplemented premature, 

discharge, and term formula

Dose: Ad lib

Blinding: Not reported

Infant conditions

Pre-term birth 119 (100%)

Arm 2: Algal-DHA

Description: supplemented premature infant formula 

supplemented with DHA from algal oil

Manufacturer: Martek Biosciences

Dose: ad lib

DHA: 17mg/100kcal (0.33% by weight)

EPA: 0.1% by weight

AA: 34mg/100kcal (0.67% by weight)

Arm 3: Fish-DHA

Description: Premature infant formula supplemented 

with DHA from tuna fish oil

Manufacturer: Martek Biosciences

Dose: ad lib

DHA: 17mg DHA/100 kcal

AA: 34mg/100 kcal

data only reported on graph

Outcome: (Unspecified)

114
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

enrollment, or history of 

underlying disease or 

congenital malformation 

likely to interfere with 

evaluation

Arm 4: Reference

Description: Breast fed term infants

Collins et al., 2011105

Study name: DINO

Study dates: 2001-2007

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Atwell, 

2013119; Collins, 2015120

Study Population: 

Preterm infants 

Postpartum women 

Breast-feeding women

Pregnant enrolled 545

Infants enrolled 657 

Infants completers 598

Pregnant age: high DHA 

group 29.9; standard 

DHA group 30.2 (high 

DHA group 5.8; standard 

DHA group 5.4)

Infant age: 4 day high 

DHA 3-6; standard 2-5

Race of Mother: NR 

(100)

Inclusion Criteria: infant 

born <33 weeks 

gestation

Exclusion Criteria: Infants 

were excluded if they had 

major congenital or 

chromosomal 

abnormalities; were a 

multiple birth where not 

all live births were 

eligible; were in other 

trials of fatty acid 

supplementation or had a 

lactating mother where 

tuna oil was 

contraindicated (bleeding 

disorders, 

anticoagulants).

Start time: Infants birth

Duration: NR

Arm 1: standard DHA

Description: placebo soya oil capsules for lactating 

women and/or standard pre-term formula

Manufacturer: Capsule: Clover Corporation; 

Formula: Mead Johnson Nutritionals and Nutricia 

Australasia

Dose: 6*500mg placebo soya oil capsules

Blinding: All capsules were similar in size, shape 

and color. Formula was packaged by color code. 

Parents, clinicians and all research personnel were 

blinded to the participant’s study group

Arm 2: High DHA

Description: tuna oil capsules or DHA pre-term 

formula

Manufacturer: Capsule: Clover Corporation; 

Formula: Mead Johnson Nutritionals and Nutricia 

Australasia

Dose: six 500 mg DHA-rich tuna oil capsules per 

day

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 12 months

Arm 1: Sample size 231; mean 46.2; SD 

(1.8)

Arm 2: Sample size 225; mean 46.1; SD 

(1.8)

Follow-up time: 18 months

Arm 1: Sample size 305; mean 47.8; SD 

(1.7)

Arm 2: Sample size 282; mean 47.8; SD 

(1.8)

Follow-up time: 4 months

Arm 1: Sample size 312; mean 41.8; SD 

(1.7)

Arm 2: Sample size 289; mean 41.6; SD 

(1.7)

Outcome: length (cm) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 239; mean 74.1; SD 

(3.7)

Arm 2: Sample size 226; mean 74.3; SD 

(3.6)

Follow-up time: 18 months

Arm 1: Sample size 306; mean 81.2; SD 

(3.9)

Arm 2: Sample size 286; mean 81.9; SD (4)

Follow-up time: 4 months

Arm 1: Sample size 311; mean 61.2; SD 

(3.4)

Arm 2: Sample size 294; mean 61.3; SD 

(3.2)

Outcome: weight (g) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 240; mean 9195.0; SD 

(1410)

Arm 2: Sample size 231; mean 9317.0; SD 

(1455)

115
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 18 months

Arm 1: Sample size 306; mean 10775.; SD 

(1520)

Arm 2: Sample size 292; mean 11029.; SD 

(1764)

Follow-up time: 4 months

Arm 1: Sample size 316; mean 6203.0; SD 

(1059)

Arm 2: Sample size 299; mean 6218.0; SD 

(1013)

Currie et al., 2015115

Study name: Diamond

Study dates: 2003-2011

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government, 

Manufacturer supplied 

product

Study follow-up: 6 years

Original, same study, or 

follow-up studies: Birch, 

2010121; Drover, 2011122; 

Drover. 2012123; 

Colombo, 2013124

Study Population: 

Healthy infants

Infants enrolled 159 

Infants completers 92

Mother age: 22.9 y (4.1 

y)

Race of Mother: White 

European (NR) Black 

(59-87%) Asian (NR) 

Hispanic (0-9%) Inuit 

Eskimo (NR) Other 

race/ethnicity (NR) Nonblack (13-41%)

Inclusion Criteria: 

Healthy, singleton, term 

(37–42 weeks gestation), 

formula-fed infants were 

eligible for the study if 

they weighed between 

2490 and 4550 g at birth. 

All were born between 

September 2003 and 

October 2005. Only one 

child per family could 

participate.

Exclusion Criteria: Infants 

were excluded if they 

were older than 9 days, 

had received human 

breast milk within 24 h of 

randomization or if there 

were newborn health 

conditions known to 

interfere with normal 

growth and development 

or cognitive function 

(e.g., intrauterine growth 

restriction, congenital 

anomalies or established 

genetic disorders 

associated with 

intellectual disability). 

Infants were also 

excluded if they 

previously demonstrated 

Start time: Infants birth

Duration: Infants 12 months

Arm 1: Placebo

Manufacturer: Mead Johnson Nutrition

Blinding: eight colored labeling scheme and 

provided to participants by courier

Arm 2: DHA < ARA

Description: 0.32% DHA 0.64% ARA

Manufacturer: Mead Johnson Nutrition

DHA: 0.32%

AA: 0.64%

Arm 3: DHA = ARA

Description: 0.64% DHA 0.64% ARA

Manufacturer: Mead Johnson Nutrition

DHA: 0.64%

AA: 0.64%

Arm 4: DHA > ARA

Description: 0.96% DHA 0.64% ARA

Manufacturer: Mead Johnson Nutrition

DHA: 0.96%

AA: 0.64%

Outcome: BMI (Secondary)

Follow-up time: 2-6 years

Arm 1: Sample size 15; mean 16.6; SE 

(0.4)

Arm 2: Sample size 54; mean 16.9; SE 

(0.4)

Outcome: BMI-for-age percentile 

(Secondary)

Follow-up time: 2-6 years

Arm 1: Sample size 15; mean 61.2; SE 

(4.8)

Arm 2: Sample size 54; mean 67.8; SE 

(3.2)

Outcome: Length-for-age percentile 

(Secondary)

Follow-up time: 2-6 years

Arm 1: Sample size 15; mean 46.5; SE 

(4.6)

Arm 2: Sample size 54; mean 59.1; SE 

(3.5)

Follow-up time: birth-18 months

Arm 1: Sample size 15; mean 53.1; SE 

(3.7)

Arm 2: Sample size 54; mean 61.8; SE 

(2.4)

Outcome: Weight-for-age percentile 

(Secondary)

Follow-up time: 2-6 years

Arm 1: Sample size 15; mean 49.8; SE (12)

Arm 2: Sample size 54; mean 68.0; SE 

(10.8)

Follow-up time: birth-18 months

Arm 1: Sample size 15; mean 50.0; SE 

116
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

any evidence of cows' 

milk formula intolerance 

or if born to mothers with 

physician-documented 

chronic illness (e.g., HIV, 

renal or hepatic disease, 

type 1 or 2 diabetes, 

alcoholism or other 

substance abuse).

(3.8)

Arm 2: Sample size 54; mean 54.5; SE 

(2.6)

Dunstan et al., 200844

Study name: Dunstan

Study dates: 2000-2003

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Multiple foundations and 

Societies

Original, same study, or 

follow-up studies: 

Dunstan, 200350; 

Meldrum, 201551

Study Population: 

Healthy infants Pregnant 

women with allergies

Pregnant enrolled 98 

Pregnant completers 83

Infants enrolled 83 

Infants withdrawals 11 (7 

FO, 4 control) Infants 

completers 72

Pregnant age: Fish oil: 

30.9 Control: 32.6 (Fish 

oil: 3.7 Control: 3.6)

Infant age: Term (mean 

gestational period 275 

days)

Race of Mother: NR (NR)

Baseline biomarker 

information: Cord blood 

erythrocyte (as % total 

fatty acids) 20:4n-6 14.9 

(1.4) 17.6 (1.0) ,0.001 

20:5n-3 1.3 (0.5) 0.4 

(0.3) ,0.001 22:3n-6 2.8 

(0.5) 3.9 (0.5) ,0.001 

22:4n-6 0.8 (0.2) 1.5 

(0.3) ,0.001 22:5n-3 6.3 

(0.8) 6.0 (0.5) 0.037 

22:6n-3 10.3 (1.1) 7.4 

Inclusion Criteria: 

Healthy term infants of 

pregnant women enrolled 

in RCT of gestational 

supplementation

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked, had medical 

problems, a complicated 

pregnancy, seafood 

allergy, or if their normal 

dietary intake exceeded 

two meals of fish per 

week. Children were 

excluded from the study 

if they were born before 

36 weeks’ gestation or 

with major disease (to 

avoid the confounding 

effects on immune 

response) or if cord blood 

was not collected

Start time: Pregnant 20 weeks gestation

Duration: Pregnant to term

Arm 1: Control

Description: olive oil placebo

Blinding: capsules image matched

Maternal conditions

Current smoker 0%

Maternal allergies 100%

Arm 2: Fish oil

Description: same

Manufacturer: Ocean Nutrition, Halifax Nova Scotia

Active ingredients: 3-4mg/g vitamin E

Viability: none reported

Dose: 4 1-gm capsules fish oil per day

Maternal conditions

DHA: 2.2

EPA: 1.1

Other dose 1: fish oil supplying 2,2g/d DHA and 

1.1g/day EPA

Current smoker 0%

Maternal allergies 100%

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 30 months

Arm 1: Sample size 36; mean 49.8; SD 

(1.7)

Arm 2: Sample size 28; mean 49.4; SD 

(1.6)

Outcome: length (cm) (Secondary)

Follow-up time: 30 months

Arm 1: Sample size 36; mean 93.3; SD 

(4.6)

Arm 2: Sample size 28; mean 93.8; SD 

(3.8)

Outcome: weight (kg) (Secondary)

Follow-up time: 30 months

Arm 1: Sample size 36; mean 14.1; SD (2)

Arm 2: Sample size 28; mean 14.5; SD (2)

117
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(0.9) ,0.001 Total n-6 

PUFAs* 25.0 (1.8) 29.6 

(1.1) ,0.001 Total n-3 

PUFAs{ 17.9 (1.9) 13.7 

(1.3) ,0.001 Total n-3 to 

n-6{ 0.8 (0.1) 0.5 (0.1) 

,0.001

Field et al., 2008112

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Industry

Study Population: 

Healthy infants

Infants enrolled 30 

Infants completers 30

Infant age: 2 weeks 7 to 

14 days

Race of Mother: NR 

(100)

Inclusion Criteria: 

Inclusion criteria for all 

infants stipulated that by 

age 14 d infants were 

receiving 100 % of their 

intake by mouth from 

human milk or 

commercial infant 

formula and that infants 

were healthy with birth 

weight, length and head 

circumference between 

the 10th and 90th 

percentile for gestational 

age, according to the 

National Center for 

Health Statistics growth 

charts14.

Exclusion Criteria: Infants 

with major congenital 

malformations, 

documented systemic or 

congenital infection, 

significant neonatal 

morbidity, diagnosed 

maternal autoimmune 

disorders, acute illness 

precluding oral feedings, 

or conditions requiring 

infant feedings other than 

standard formula or 

human milk were 

excluded from the study. 

None of the infants had 

received corticosteroids, 

Start time: Infants no later than 14 days

Duration: NR

Arm 1: Formula (unsuppl)

Description: Placebo/control formula

Brand name: S-26

Manufacturer: Wyeth Nutrition

ALA: 2.3% by weight

Arm 2: Formula + LCP

Description: LCP supplemented formula

Brand name: S-26 Gold

Manufacturer: Wyeth Nutrition

Active ingredients: arachidonic acid - see below

ALA: 1.9%

DHA: 0.20%

AA: 0.34%

Arm 3: Breastfed comparison

Description: Breastfed group, not randomized

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 6 wk

Arm 1: Sample size 14; mean 38.6; SD 

(1.1)

Arm 2: Sample size 16; mean 38.4; SD 

(1.4)

Arm 3: Sample size 16; mean 38.9; SD 

(1.2)

Outcome: length (cm) (Secondary)

Follow-up time: 6 wk

Arm 1: Sample size 14; mean 56.0; SD (2)

Arm 2: Sample size 16; mean 56.0; SD (2)

Arm 3: Sample size 16; mean 58.0; SD (3)

Outcome: weight (g) (Secondary)

Follow-up time: 6 wk

Arm 1: Sample size 14; mean 4901.0; SD 

(590)

Arm 2: Sample size 16; mean 5076.0; SD 

(646)

Arm 3: Sample size 16; mean 5045.0; SD 

(516)

118
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

erythrocyte or plasma 

transfusions, or 

intravenous lipid 

emulsions before 

entering the study

Fleddermann et al., 

2014113

Study name: BeMIM 

(Belgrade-Munch Infant 

Milk Trial)

Study dates: Jan 2010 to 

May 2011

Study design: Trial 

randomized parallel

Location: Serbia

Funding source / conflict: 

Industry

Study Population: 

Healthy infants

Infants enrolled 207 

Infants completers 164

Mother age: Control: 30.6 

Intervention: 30.7 

Breastfed: 30.1 (Control: 

5.5 Intervention: 5.5 

Breastfed: 4.7)

Infant age: Gestation 

(weeks) Control: 39.2 

Intervention: 39.2 

Breastfed: 39.2 

(Gestation (weeks) 

Control: 1.1 Intervention: 

1.0 Breastfed: 1.1) until 

28 days

Race of Mother: NR 

(100%)

Inclusion Criteria: Eligible 

infants had to be born 

apparently healthy from 

singleton pregnancies 

after 37-41 weeks of 

gestation, with a birth 

weight between the 3rd 

and 97th weight-for-age 

percentile according to 

the EURO-Growth 

charts.

Exclusion Criteria: Infants 

with malformations, 

congenital heart defects, 

congenital vascular 

diseases, severe 

diseases of 

gastrointestinal tract, 

kidney, liver, central 

nervous system, or 

metabolic disease.

Start time: Infants within 28 days

Duration: Infants until 120 days

Arm 1: Control Formula (CF)

Description: Placebo/control formula

Manufacturer: HiPP GmbH & Co. Vertrieb KG 

(Pfaffenhofen, Germany)

Blinding: 600g cartons and labeled by random 

numbers. The products were packed in identical 

white boxes and labeled with the same product 

name.

ALA: 0.1g/100mL

Arm 2: Intervention Formula (IF)

Manufacturer: HiPP GmbH & Co. Vertrieb KG 

(Pfaffenhofen, Germany)

ALA: 0.1g/100mL

DHA: 7.2g/100mL

AA: 7.2g/100mL

Arm 3: Breastfed

Description: Breastfeeding reference group

Outcome: head circumference gain (g/day) 

(Secondary)

Follow-up time: about 92 days

Arm 1: Sample size 82; mean 0.05; SD 

(0.01)

Arm 2: Sample size 82; mean 0.05; SD 

(0.01)

Outcome: length gain (g/day) (Secondary)

Follow-up time: about 92 days

Arm 1: Sample size 82; mean 0.1; SD 

(0.02)

Arm 2: Sample size 82; mean 0.11; SD 

(0.02)

Outcome: weight gain (g/day) (Primary)

Follow-up time: about 92 days

Arm 1: Sample size 82; mean 28.3; SD 

(6.5)

Arm 2: Sample size 82; mean 30.2; SD 

(6.3)

Gonzalez-Casanova et 

al., 201560

Study name: POSGRAD

Study dates: 2005-2012

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, None

Study Population: 

Healthy infants Preterm 

infants

Pregnant enrolled 1040 

Pregnant completers 968

Infants enrolled 973 

Infants completers 802

Pregnant age: 26.3 y (4.7 

y)

Infant age: 20.5 weeks 

gestation (2.0)

Inclusion Criteria: 

Pregnant women 18–35 

y of age, in week 18–22 

of gestation, and planned 

to deliver at the hospital, 

breastfeed for >3 mo, 

and reside in the area for 

>2 y after delivery

Exclusion Criteria: NR

Start time: Pregnant 18-22 weeks gestation

Duration: Pregnant 18-22 weeks gestation until 

delivery

Arm 1: Placebo

Description: Soy and corn placebo

Dose: 2 200 mg capsules/day

Blinding: Soy-corn placebo of similar taste and 

appearance

Arm 2: DHA (algal)

Dose: 2 200 mg capsules/day

DHA: 400mg

Outcome: BMI-for-age z score (Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean 0.1; SD 

(1.1)

Arm 2: Sample size 403; mean 0.1; SD 

(1.1)

Outcome: height (cm) (Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean 108.4; SD 

(4.5)

Arm 2: Sample size 403; mean 108.3; SD 

(4.4)

Outcome: height-for-age z-score (Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean -0.4; SD 

119
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 60 

months

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Stein, 201233; ImhoffKunsch, 201158; 

Escamilla-Nunez, 201459; 

Ramakrishnan, 201561

Race of Mother: NR 

(100)

(0.9)

Arm 2: Sample size 403; mean -0.4; SD 

(0.9)

Outcome: weight (kg) (Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean 18.4; SD (3)

Arm 2: Sample size 403; mean 18.3; SD (3)

Outcome: weight-for-age z-score (Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean -0.1; SD 

(1.1)

Arm 2: Sample size 403; mean -0.2; SD 

(1.1)

van Goor et al., 201166

Study name: Groningen 

LCPUFA study

Study dates: 2004-2009

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Industry

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; van Goor, 201036

Study Population: 

Healthy infants

Pregnant enrolled 119

Infants enrolled 119 

Infants completers 114

Pregnant age: Placebo: 

32.7 DHA: 32.5

DHA+AA: 32.9 (Placebo: 

5.1 DHA: 4.4 DHA+AA: 

4.8)

Infant age: 18 months

Race of Mother: NR 

(100)

Inclusion Criteria: women 

with a first or second lowrisk singleton pregnancy, 

between the 14th and 

20th weeks of pregnancy

Exclusion Criteria: 

women with vegetarian 

or vegan diets; women 

with diabetes mellitus; 

birth complications

Start time: Pregnant 14th-20th week pregnancy 

Lactating 3 months after delivery Mothers 3 months 

after delivery Infants NR

Duration: Pregnant NR Lactating 33-39 weeks 

Mothers 33-39 weeks Infants NR

Arm 1: placebo

Description: Soy bean oil

Brand name: none

Arm 2: DHA

Description: DHA plus soy bean oil

Brand name: Marinol D40

Manufacturer: Lipid Nutrition B.V., Wormerveer, The 

Netherlands; AA:

Dose: 1 capsule DHA and 1 capsule soy bean oil 

once a day

ALA: 32 mg/d

DHA: 220 mg/d

EPA: 34 mg/d

Arm 3: DHA+AA

Description: DHA plus AA

Brand name: AA: no brand name

Manufacturer: Wuhan Alking Bioengeneering Co. 

Ltd., Wuhan, China

Dose: 2 capsules once a day

ALA: 7 mg/d

DHA: 220 mg/d

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 47.8; SD 

(1.5)

Arm 2: Sample size 41; mean 47.6; SD 

(1.1)

Arm 3: Sample size 39; mean 47.5; SD 

(1.4)

Outcome: length (cm) (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 84.0; SD 

(3.8)

Arm 2: Sample size 41; mean 82.8; SD 

(4.7)

Arm 3: Sample size 39; mean 83.6; SD 

(2.9)

Outcome: weight (kg) (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 11.5; SD 

(1.1)

Arm 2: Sample size 41; mean 11.3; SD 

(1.4)

Arm 3: Sample size 39; mean 11.5; SD 

(1.3)

120
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

EPA: 36 mg/d

AA: 220 mg per capsule

Groh-Wargo et al., 

2005106

Study name: NR

Study dates: Sept 1997 -

Sept 1998

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government

Study Population: 

Preterm infants

Infants enrolled 60 

Infants withdrawals 3 

Infants completers 57

Infant age: GA= 30 

weeks (0.5) NR

Race of Mother: NR

Inclusion Criteria: 

Preterm infants with birth 

weights from 750 to 1800 

g and GA at birth <33 wk 

were recruited between 

September 1997 and 

September 1998 from the 

neonatal intensive care 

unit. No restrictions on 

the type of feeding before 

study entry.

Exclusion Criteria: 

Congenital abnormalities 

that could affect growth 

or development, major 

surgery, periventricular 

hemorrhage greater than 

grade II (Papile 

classification), asphyxia 

resulting in severe and 

permanent neurologic 

damage, treatment with 

extracorporeal 

membrane oxygenation,

maternal incapacity 

(including substance 

abuse), or uncontrolled 

systemic infection at the 

time of enrollment.

Start time: Infants first enteral formula feeding

Duration: Infants 24 kcal/fl oz formula until 40 wk 

corrected age; 22 kcal/fl oz formula from 40 wk CA 

to 1 year CA

Arm 1: Control

Description: Control formula without DHA or ARA

Brand name: Similac Special Care to 40 wk GA; and 

NeoSure until 1 year

ALA: 2.4 g/100 g (to 40 wk GA); 2.4 g/100 g (to 1 

year)

DHA: 0

EPA: 0

AA: 0

Arm 2: DHA+ARA (FF)

Description: DHA or ARA from fish/fungal oil

Brand name: Similac Special Care to 40 wk GA; and 

NeoSure until 1 year

ALA: 2.6 g/100 g (to 40 wk GA); 2.4 g/100 g (to 1 

year)

DHA: 0.27 g/100 g (to 40 wk GA); 0.16 g/100 g (to 1 

yr)

EPA: 0.08 g/100 g (to 40 wk GA); 0 (to 1 yr)

AA: 0.43 g/100 g (to 40 wk GA); 0 (to 1 yr)

Arm 3: DHA+ARA (EF)

Description: DHA or ARA from egg-derived 

triglyceride and fish oil

Brand name: Similac Special Care to 40 wk GA; and 

NeoSure until 1 year

ALA: 2.5 g/100 g (to 40 wk GA); 2.4 g/100 g (to 1 

year)

DHA: 0.24 g/100 g (to 40 wk GA); 0.15 g/100 g (to 1 

yr)

EPA: 0

AA: 0.41 g/100 g

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 12 months (corrected age)

Arm 1: Sample size 14; mean 46.2; SE 

(0.4)

Arm 2: Sample size 14; mean 46.0; SE 

(0.4)

Arm 3: Sample size 13; mean 46.2; SE 

(0.4)

Follow-up time: 35 weeks (corrected age)

Arm 1: Sample size 18; mean 30.8; SE 

(0.2)

Arm 2: Sample size 17; mean 30.6; SE 

(0.5)

Arm 3: Sample size 18; mean 30.3; SE 

(0.4)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 14; mean 41.9; SE 

(0.4)

Arm 2: Sample size 16; mean 41.1; SE 

(0.6)

Arm 3: Sample size 14; mean 42.0; SE 

(0.3)

Follow-up time: 40 weeks (corrected age)

Arm 1: Sample size 18; mean 25.4; SE 

(0.3)

Arm 2: Sample size 18; mean 34.5; SE 

(0.5)

Arm 3: Sample size 17; mean 35.0; SE 

(0.3)

Outcome: length (cm) (Secondary)

Follow-up time: 12 months (corrected age)

Arm 1: Sample size 14; mean 73.9; SE 

(0.9)

Arm 2: Sample size 14; mean 75.2; SE 

(0.9)

Arm 3: Sample size 13; mean 76.3; SE 

(0.8)

Follow-up time: 35 weeks (corrected age)

Arm 1: Sample size 18; mean 42.5; SE 

(0.5)

121
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 17; mean 42.7; SE 

(0.7)

Arm 3: Sample size 18; mean 42.7; SE 

(0.5)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 14; mean 61.8; SE 

(0.7)

Arm 2: Sample size 16; mean 60.9; SE 

(0.6)

Arm 3: Sample size 14; mean 62.8; SE 

(0.7)

Follow-up time: 40 weeks (corrected age)

Arm 1: Sample size 18; mean 48.0; SE 

(0.7)

Arm 2: Sample size 18; mean 48.2; SE 

(0.7)

Arm 3: Sample size 17; mean 48.1; SE 

(0.5)

Outcome: weight (g) (Secondary)

Follow-up time: 12 months (corrected age)

Arm 1: Sample size 14; mean 9343.0; SE 

(307)

Arm 2: Sample size 14; mean 8977.0; SE 

(293)

Arm 3: Sample size 13; mean 9505.0; SE 

(243)

Follow-up time: 35 weeks (corrected age)

Arm 1: Sample size 18; mean 1916.0; SE 

(73)

Arm 2: Sample size 17; mean 1871.0; SE 

(118)

Arm 3: Sample size 18; mean 1874.0; SE 

(85)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 14; mean 6524.0; SE 

(220)

Arm 2: Sample size 16; mean 6454.0; SE 

(212)

Arm 3: Sample size 14; mean 6432.0; SE 

(217)

Follow-up time: 40 weeks (corrected age)

Arm 1: Sample size 18; mean 3280.0; SE 

(135)

Arm 2: Sample size 18; mean 3147.0; SE 

122
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(149)

Arm 3: Sample size 17; mean 3136.0; SE 

(105)

Hauner et al., 201237

Study name: INFAT

Study dates: July 14 

2006 - may 22 2009

Study design: Trial 

randomized parallel

Location: Germany

Funding source / conflict: 

Industry, Government, 

Multiple foundations and 

Societies

Study Population: 

Healthy pregnant women

Pregnant enrolled 208 

Pregnant withdrawals 38 

Pregnant completers 170

Infants enrolled 188 

Infants withdrawals 18 

Infants completers 170

Pregnant age: 31.9 (4.9) 

18-43

Race of Mother: NR (NR)

Baseline biomarker 

information: Maternal 

fatty acid profile in RBCs 

at 15th wk: EPA, DHA, 

AA, and n-6:n-3 LCUFA 

ratio (reported in Table 2 

by intervention and 

control groups). No 

significant differences 

between groups.

Baseline Omega-3 

intake: 7-d dietary 

records completed by 

participants at the 15th 

(baseline) and 32nd wk 

of gestation but only 

dietary intake at 32nd we 

of gestation was reported 

(in Table 2). At week 32 

of gestation, the dietary 

n-6:n-3 PUFA ratio was 

.5:1 in the intervention 

group compared with :1 

Inclusion Criteria: healthy 

pregnant women before 

the 15th wk of gestation, 

between 18 and 43 y of 

age, prepregnancy BMI 

(in kg/m2) between 18 

and 30, willingness to 

implement the dietary 

recommendations, 

sufficient German 

language skills.

Exclusion Criteria: highrisk pregnancy (multiple 

pregnancy, rhesus 

incompatibility, hepatitis 

B infection, or parity .4); 

hypertension; chronic 

diseases (e.g., diabetes) 

or gastrointestinal 

disorders accompanied 

by maldigestion, 

malabsorption, or 

elevated energy and 

nutritional requirements 

(e.g., gluten 

enteropathy); known 

metabolic defects (e.g., 

phenylketonuria); 

psychiatric diseases; 

hyperemesis gravidarum; 

supplementation with n–3 

LCPUFAs before 

randomization; and 

alcohol abuse and 

smoking.

Start time: Pregnant 15th wk of gestation

Duration: Pregnant to 4 mo postpartum

Arm 1: Control

Description: brief semistructured counseling on a 

healthy balanced diet according to the guidelines of 

the German Nutrition Society and were explicitly 

asked to refrain from taking fish oil or DHA 

supplements

N-6 N-3: 2.80 +- 1.17 (SD) at 32nd wk of gestation

AA: 10.15 +- 3.89 SD) at 32nd wk of gestation

Arm 2: Intervention

Description: Fish-oil supplement + nutritional 

counseling (to normalize the consumption of AA

Brand name: Marinol D-40

Manufacturer: Lipid Nutrition

DHA: 1020 mg

EPA: 180 mg

N-6 N-3: 1.54 +- 0.63 (SD) at 32nd wk of gestation

AA: 8.82 +- 2.84 (SD) at 32nd wk of gestation

Other dose 1: Vit E 9 mg

Outcome: BMI (kg/m2) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 83; mean 16.7; SD 

(1.4)

Arm 2: Sample size 87; mean 16.9; SD 

(1.5)

Follow-up time: 4 months

Arm 1: Sample size 87; mean 16.2; SD 

(1.3)

Arm 2: Sample size 87; mean 16.5; SD 

(1.4)

Follow-up time: 6 weeks

Arm 1: Sample size 91; mean 15.3; SD 

(1.2)

Arm 2: Sample size 89; mean 15.2; SD 

(1.4)

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 12 months

Arm 1: Sample size 83; mean 46.1; SD 

(1.5)

Arm 2: Sample size 87; mean 46.5; SD 

(1.6)

Follow-up time: 4 months

Arm 1: Sample size 87; mean 41.0; SD 

(1.3)

Arm 2: Sample size 87; mean 41.2; SD 

(1.3)

Follow-up time: 6 weeks

Arm 1: Sample size 90; mean 38.8; SD 

(1.2)

Arm 2: Sample size 89; mean 38.4; SD 

(1.1)

Outcome: length (cm) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 83; mean 74.9; SD 

(2.8)

Arm 2: Sample size 87; mean 75.5; SD 

(2.4)

Follow-up time: 4 months

123
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

in the control group, as 

originally intended.

Arm 1: Sample size 87; mean 62.4; SD 

(2.2)

Arm 2: Sample size 88; mean 62.6; SD (2)

Follow-up time: 6 weeks

Arm 1: Sample size 91; mean 55.6; SD 

(2.6)

Arm 2: Sample size 89; mean 56.0; SD (2)

Outcome: weight (g) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 83; mean 9379.0; SD 

(1035)

Arm 2: Sample size 87; mean 9650.0; SD 

(1025)

Follow-up time: 4 months

Arm 1: Sample size 87; mean 6303.0; SD 

(724)

Arm 2: Sample size 87; mean 6476.0; SD 

(679)

Follow-up time: 6 weeks

Arm 1: Sample size 91; mean 4736.0; SD 

(625)

Arm 2: Sample size 89; mean 4793.0; SD 

(606)

Helland et al., 200876

Study name: NR

Study dates: 1994-2003

Study design: Trial 

randomized parallel

Location: Norway

Funding source / conflict: 

Industry, Government, 

Multiple foundations and 

Societies

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Study Population: 

Healthy infants Healthy 

pregnant women Breastfeeding women

Infants enrolled 262 

Infants completers 143

Pregnant age: cod oil 

28.6 n=175 corn oil 27.6 

n=166 (cod oil 3.4; corn 

oil 3.2)

Race of Mother: NR 

(100)

Baseline biomarker 

information: from id 

10331 cod(n148) corn 

(n137) n-3 cod: 73.7 

Inclusion Criteria: 

Healthy nulliparous or 

primiparous women, 

aged 19-35 with single 

pregnancies

Exclusion Criteria: 

Unhealthy neonates

Start time: Pregnant week 18 of pregnancy

Duration: NR

Arm 1: Cod oil

Manufacturer: NR

Active ingredients: Vit 1: 117 ug/mL, Vit D3: 1 

ug/mL, vit E: 1.4 mg/mL

Viability: frozen at _x0003_ 70 ° C under nitrogen. 

Before storage, the samples were sonicated and 

ethylenediaminetetraacetic acid and butylated 

hydroxytoluene were added to a final concentration

of 1.85 mg/mL and 75 _x0003_ g/mL, respectively

DHA: 1183mg/10 mL

EPA: 803 mg/10mL

Total N-3: 2494 mg/10mL

Arm 2: corn oil

Active ingredients: Vit 1: 117 ug/mL, Vit D3: 1 

ug/mL, vit E: 1.4 mg/mL

Outcome: BMI (kg/m2) (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 61; mean 16.3; SD 

(1.7)

Arm 2: Sample size 82; mean 16.4; SD 

(1.7)

Outcome: length (cm) (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 61; mean 128.6; SD (5)

Arm 2: Sample size 82; mean 127.5; SD 

(5.5)

Outcome: weight (kg) (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 61; mean 27.0; SD 

(4.1)

Arm 2: Sample size 82; mean 26.8; SD 

(4.1)

124
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Helland, 200186 and 

Helland, 200387 and

which are both included 

in the original report

(30.0) corn 52.0 (14.9)*** 

20:5n-3 cod: 10.8 (7.6) 

corn: 2.5 (1.8)*** 22:5n-3 

cod: 5.0 (2.6) corn: 2.9 

(1.3)*** 22:6n-3 cod: 55.8 

(20.6) corn: 45.3 

(12.8)***

Baseline Omega-3 

intake: from 10331 cod 

n147 corn n159 18:3 n-3: 

cod: 1.3 (0.5) corn: 1.2 

(0.5) 20:5 n-3 cod: 0.2 

(0.2) corn:0.2 (0.2) 22:5 

n-3 cod: 0.05 (0.03) corn: 

0.05 (0.03) 22:6 n-3 cod: 

0.3 (0.3) corn: 0.3 (0.3)

Viability: frozen at _x0003_ 70 ° C under nitrogen. 

Before storage, the samples were sonicated and 

ethylenediaminetetraacetic acid and butylated 

hydroxytoluene were added to a final concentration

of 1.85 mg/mL and 75 _x0003_ g/mL, respectively

ALA: 92 mg/10mL

Henriksen et al., 2008107

Study name: Unnamed 

Trial D

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: Norway

Funding source / conflict: 

Multiple foundations and 

Societies, Manufacturer 

supplied product

Study follow-up: 6 

months

Original, same study, or 

follow-up studies: 

Westerberg, 2011125; 

Almaas, 2015126

Study Population: 

Preterm infants

Infants enrolled 141 

Infants completers 129

Mother age: Median: 

Intervention: 31 years 

Control: 32 years 28-35 

years

Infant age: Median 

Gestational age: Control: 

28.9 weeks Intervention: 

28.4 weeks Gestational 

age: 26.6-30.9 weeks

Race of Mother: White 

European (Intervention: 

79%; Control 84%)

Inclusion Criteria: All 

VLBW infants (<1500g) 

born between December 

2003 and November 

2005 at RikshospitaletRadiumhospitalet 

Medical Center, 

Akershus University 

Hospital, Buskerud 

Hospital, and Vestfold 

Hospital in Norway

Exclusion Criteria: Major 

congenital abnormalities 

or cerebral hemorrhage 

(grade 3 or 4, as 

determined through 

ultrasonography)

Start time: Infants (intervention began when the 

infant received most of his nutrients enterally: 

>100ml human milk/kg body weight/day

Duration: Infants Until discharge or bottle of study oil 

was empty (average 63 days of age)

Arm 1: Control

Description: Study oil: soy oil and medium chain 

triglycerides

Active ingredients: 127mg linolenic acid/100 ml 

milk(27.1% total fatty acids)

Dose: 0.5 ml study oil/100 ml human milk

Blinding: Study oils packed in numbered bottles in 

hospital pharmacy

ALA: 16mg/100 ml milk; 3.4% total fatty acids

Arm 2: Intervention

Description: DHA and AA-containing oil

Manufacturer: Martek Biosciences

Active ingredients: 88mg/100 ml linoleic acid per 100 

ml milk (18.8%)

Dose: 0.5 ml study oil per 100 ml milk, ad lib

Maternal conditions

Infant conditions

DHA: 32mg/100ml milk (6.9%)

Outcome: head circumference (mm/day) 

(Secondary)

Follow-up time: day 65

Arm 1: Sample size 50; mean 1.0; SD (0.4)

Arm 2: Sample size 50; mean 1.2; SD (0.7)

125
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

AA: 31 mg/100 ml milk (6.7% total fatty acids

Current smoker 22% during pregnancy

Low birth weight 100% (median 1090 g)

Hoffman et al., 2008114

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Manufacturer 

supplied product

Study Population: 

Healthy infants

Infants enrolled 244 

Infants withdrawals 3 

Infants completers 241

Infant age: 14 days

Race of Mother: NR

Inclusion Criteria: 12–16 

days of age, had a 

minimum birth weight of 

2,500 g, and solely 

received formula at least 

24 h prior to 

randomization

Exclusion Criteria: history 

of underlying disease or 

malformation that could 

interfere with growth and 

development; large-forgestational-age infants 

whose mothers were 

diabetic; breastfeeding 

within 24 h prior to 

randomization; evidence 

of formula intolerance or 

poor intake at time of 

randomization; weight at 

randomization less than 

98% of birth weight; 

enlarged liver or spleen; 

or plans to move outside 

of the study area within 

the study time frame (120 

days)

Start time: Infants 14 day

Duration: NR

Arm 1: Control

Description: soy formula without supplementation

Brand name: Enfamil ProSobee1, Mead Johnson & 

Company, Evansville, IN

Blinding: Aside from the addition of DHA and ARA, 

the formulas were identical in all other respects.

Arm 2: DHA + ARA

Description: soy formula supplemented with a 

minimum 17 mg DHA/100kcal from algal oil and 34 

mg ARA/100kcal from fungal oil

Brand name: Enfamil ProSobee1 LIPIL1, Mead 

Johnson & Company, Evansville, IN)

DHA: 0.3%

AA: 0.6%

Outcome: head circumference (cm/day) 

(Secondary)

Follow-up time: 14-120d

Arm 1: Sample size 86; mean gain 0.05; SE 

(0.001)

Arm 2: Sample size 93; mean gain 0.05; SE 

(0.001)

Outcome: length (cm/day) (Secondary)

Follow-up time: 14-120d

Arm 1: Sample size 86; mean change 0.1; 

SE (0.002)

Arm 2: Sample size 93; mean change 0.1; 

SE (0.002)

Outcome: weight (g/day) (Secondary)

Follow-up time: 14-120d

Arm 1: Sample size 86; mean change 27.8; 

SE (0.8)

Arm 2: Sample size 93; mean change 27.3; 

SE (0.7)

Lagemaat et al., 2011109

Study name: NR

Study dates: 2003 - 2006

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Study Population: 

Preterm infants Low birth 

weight infants

Infants enrolled 152 

Infants completers 139

Infant age: Gestational 

age (week) PDF: 30.5 

TF: 30.5 HM: 30.0 (PDF: 

1.4 TF: 1.4 HM: 1.6)

Inclusion Criteria: infants 

born at gestational ages 

of 32 weeks or less 

and/or with birth weights 

of 1500 g or less

Exclusion Criteria: NR

Start time: Infants at term

Duration: Infants 6 months

Arm 1: Term Formula (TF)

Description: Placebo/control formula

Brand name: Friso 1 normaal

Manufacturer: FrieslandCampina, Leeuwarden, The 

Netherlands

Blinding: NR

ALA: 63mg / 100ml

DHA: 7mg / 100ml

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: term age

Arm 1: Sample size 41; mean 35.8; SD 

(1.5)

Arm 2: Sample size 52; mean 35.9; SD 

(1.2)

Arm 3: Sample size 46; mean 35.6; SD 

(1.5)

Outcome: length (cm) (Unspecified)

Follow-up time: term age

Arm 1: Sample size 41; mean 48.7; SD 

126
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Industry Race of Mother: NR 

(100)

Baseline biomarker 

information: Baseline (at 

term) Mean(SD) AA PDF: 

13.74 (0.89) TF: 13.86 

(0.93) HM: 14.06 (1.17)

DHA PDF: 4.71 (0.70) 

TF: 4.59 (0.76) HM: 4.08 

(0.55) EPA PDF: 0.34 

(0.05) TF: 0.32 (0.06) 

HM: 0.33 (0.13) DHA/AA 

ratio PDF: 0.34 (0.05)

TF: 0.33 (0.06) HM: 0.29 

(0.04)

AA: 7mg/ 100ml

Arm 2: PDF

Description: Post-discharge formula (LCPUFA 

enriched)

Brand name: Friso 1 premature

Manufacturer: Friesland Foods

ALA: 59mg/ 100ml

DHA: 14mg/ 100ml

EPA: 3.9mg/ 100ml

AA: 14mg/ 100ml

Arm 3: HM

Description: Human milk

(2.1)

Arm 2: Sample size 52; mean 48.7; SD 

(2.3)

Arm 3: Sample size 46; mean 48.2; SD 

(2.5)

Outcome: weight (g) (Unspecified)

Follow-up time: term age

Arm 1: Sample size 41; mean 3193.0; SD 

(489)

Arm 2: Sample size 52; mean 3137.0; SD 

(511)

Arm 3: Sample size 46; mean 3138.0; SD 

(513)

Lauritzen et al., 2005102

Study name: Danish 

National Birth CohortLactating Women

Study dates: 

Recruitment: April 1999-

February 2000 Follow-up 

2.5 years

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / conflict: 

Industry, Government

Study follow-up: 2.5 

years

Original, same study, or 

follow-up studies: 

Lauritzen, 2004127; 

Lauritzen, 2005128; 

Cheatham, 2011129;

Study Population: Breastfeeding women

Infants enrolled 100 

Infants completers 72

Mother age: High fish: 

31.9 Fish oil: 29.6 Olive 

oil: 30.2 (High fish: 4.1 

Fish oil: 4.3 Olive oil: 4.1)

Race of Mother: NR 

(100%)

Inclusion Criteria: 

Pregnant women who 

were recruited for the 

Danish National Birth 

Cohort (DNBC) (16), all 

from the greater 

Copenhagen area, who 

were in their eighth 

month of gestation and 

had a fish intake below 

the median (0.40 g/d n3LCPUFA) (554 women 

with a fish intake in the 

upper quartile (0.82 g/d 

n-3LCPUFA) were invited 

to participate in the study 

as a high fish intake 

reference group); 

uncomplicated 

pregnancy; body mass 

index (BMI) <30 kg/m2; 

no metabolic disorders;

intention to breastfeed for 

at least 4 mo.; 

willingness to begin 

supplement within 2 

weeks of birth. Newborns 

Start time: Lactating within 2 weeks of delivery

Duration: Lactating 4 months

Arm 1: Olive oil

Description: Control group receiving olive oil 

supplement

Dose: 2 müsli bars daily; or 4 1000-mg capsules

Blinding: Investigators and families were blinded to 

the randomization throughout the first year of life of 

the infants. Fish oil as well as olive oil supplements 

were given as microencapsulated oils concealed in 

two müsli bars (produced by Halo Foods Ltd., Tywyn 

Gwynedd, Wales, UK) daily for the first 4 mo of 

lactation.

Arm 2: Fish oil

Description: Intervention group receiving fish oil 

supplement

Manufacturer: BASF Health and Nutrition A/S, 

Ballerup, Denmark

Dose: 2 müsli bars providing 0.62g EPA and 0.79g 

DHA; or fish oil capsules providing 0.36g EPA and 

0.99g DHA

DHA: 0.79g/d

EPA: 0.62g/d

Total N-3: 1.5g/d

Outcome: BMI (kg/m2) (Secondary)

Follow-up time: 2 months

Arm 1: Sample size 51; mean 15.93; SD 

(1.37)

Arm 2: Sample size 52; mean 15.74; SD 

(1.24)

Arm 3: Sample size 50; mean 15.63; SD 

(1.36)

Follow-up time: 2.5 years

Arm 1: Sample size 28; mean 15.86; SD 

(1.21)

Arm 2: Sample size 42; mean 16.51; SD 

(1.08)

Arm 3: Sample size 29; mean 16.11; SD 

(1.08)

Follow-up time: 4 months

Arm 1: Sample size 46; mean 17.04; SD 

(1.7)

Arm 2: Sample size 52; mean 16.93; SD 

(1.23)

Arm 3: Sample size 49; mean 16.57; SD 

(1.66)

Follow-up time: 9 months

Arm 1: Sample size 47; mean 17.64; SD 

(1.52)

Arm 2: Sample size 53; mean 17.91; SD 

(1.24)

127
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

had to be healthy (no 

admission to a neonatal 

department), term (37–

43 wk of gestation), 

singleton infants with 

normal weight for 

gestation (17) and an 

Apgar score 7 at 5 min 

after delivery.

Exclusion Criteria: NR

Arm 3: High fish

Description: Group with high fish intake as reference 

group

Arm 3: Sample size 48; mean 17.27; SD 

(1.39)

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 1 week

Arm 1: Sample size 56; mean 35.72; SD 

(1.53)

Arm 2: Sample size 54; mean 36.11; SD 

(1.25)

Arm 3: Sample size 51; mean 36.18; SD 

(1.59)

Follow-up time: 2 months

Arm 1: Sample size 50; mean 39.28; SD 

(1.16)

Arm 2: Sample size 50; mean 39.7; SD 

(1.22)

Arm 3: Sample size 47; mean 39.68; SD 

(1.27)

Follow-up time: 2.5 years

Arm 1: Sample size 30; mean 49.74; SD 

(1.34)

Arm 2: Sample size 41; mean 50.42; SD 

(1.2)

Arm 3: Sample size 29; mean 50.62; SD 

(1.23)

Follow-up time: 4 months

Arm 1: Sample size 46; mean 41.84; SD 

(1.12)

Arm 2: Sample size 45; mean 42.17; SD 

(1.16)

Arm 3: Sample size 45; mean 42.4; SD 

(1.38)

Follow-up time: 9 months

Arm 1: Sample size 45; mean 45.29; SD 

(1.4)

Arm 2: Sample size 52; mean 45.85; SD 

(1.53)

Arm 3: Sample size 42; mean 45.81; SD 

(1.36)

Outcome: length (cm) (Secondary)

Follow-up time: 2 months

Arm 1: Sample size 51; median 58.7; 10th, 

90th percentile

Arm 2: Sample size 52; median 58.8; 10th, 

128
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

90th percentile

Arm 3: Sample size 50; median 59.1; 10th, 

90th percentile

Follow-up time: 2.5 years

Arm 1: Sample size 28; mean 92.65; SD 

(3.04)

Arm 2: Sample size 42; mean 92.58; SD 

(3.14)

Arm 3: Sample size 29; mean 93.74; SD 

(2.93)

Follow-up time: 4 months

Arm 1: Sample size 46; mean 64.02; SD 

(2.16)

Arm 2: Sample size 52; mean 64.21; SD 

(2.08)

Arm 3: Sample size 50; mean 64.7; SD 

(1.71)

Follow-up time: 9 months

Arm 1: Sample size 47; mean 72.15; SD 

(2.04)

Arm 2: Sample size 53; mean 72.66; SD 

(2.35)

Arm 3: Sample size 48; mean 72.75; SD 

(2.01)

Outcome: weight (kg) (Secondary)

Follow-up time: 2 months

Arm 1: Sample size 51; mean 5.4; 10th, 

90th percentile

Arm 2: Sample size 53; median 5.5; 10th, 

90th percentile

Arm 3: Sample size 50; median 5.3; 10th, 

90th percentile

Follow-up time: 2.5 years

Arm 1: Sample size 30; mean 13.71; SD 

(1.26)

Arm 2: Sample size 42; mean 14.16; SD 

(1.26)

Arm 3: Sample size 29; mean 14.18; SD 

(1.43)

Follow-up time: 4 months

Arm 1: Sample size 47; mean 7.0; SD 

(0.85)

Arm 2: Sample size 53; mean 7.0; SD 

(0.73)

129
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 3: Sample size 49; mean 6.93; SD 

(0.67)

Follow-up time: 9 months

Arm 1: Sample size 47; mean 9.19; SD 

(0.94)

Arm 2: Sample size 53; mean 9.47; SD 

(0.94)

Arm 3: Sample size 48; mean 9.15; SD 

(0.9)

Lucia Bergmann et al., 

200741

Study name: NR

Study dates: 2000-2002

Study design: Trial 

randomized parallel

Location: Germany

Funding source / conflict: 

NR

Original, same study, or 

follow-up studies: Lucia, 

200752

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 144 

Pregnant withdrawals 51 

Pregnant completers 69

Pregnant age: 31 (DHA 

4.69; control 4.89)

Infant age: DHA 39.1; 

control 39.5 weeks (DHA 

1.64; control 1.38)

Race of Mother: White 

European (100)

Baseline biomarker 

information: DHA % of all 

identified fatty acid in 

RBC: Vitamin: 5.76 +-

2.45 (47); DHA: 

Prebiotic:5.94+-2.37(48) 

DHA: DHA: 5.69+-

2.40(47) ARA Vitamin: 

14.01+-4.04(47) ARA 

Prebiotic 14.82+-3.60(48) 

ARA DHA: 14.18+-

4.32(47) EPA Vitamin: 

0.72+-0.32(47) EPA 

Prebiotic: 0.78+-0.38(48) 

EPA DHA: 0.79+-

0.41(47)

Inclusion Criteria: at least 

18 years of age and 

willing to breastfeed for 

at least three months 

were enrolled at 21 

weeks’ gestation during 

the period October 2000 

to August 2002

Exclusion Criteria: 

increased risk of 

premature delivery or 

multiple pregnancy, 

allergy to cow milk 

protein, lactose 

intolerance, diabetes, 

smoking, consumption of 

alcohol ()20 g/week), or 

participation in another 

study. Infants excluded if 

they were premature at 

birth (<37 week 

gestation, or had any 

major malformations or 

hospitalized for more 

than one week.

Start time: Pregnant 21th week

Duration: Pregnant 37th week

Arm 1: Vitamins and minerals

Manufacturer: Nestle ́ (Vevey, Switzerland)

Arm 2: Prebiotic

Description: basic supplement plus the prebiotic, 

fructooligosaccharide (FOS) (4.5 g)

Manufacturer: Nestle ́ (Vevey, Switzerland)

Active ingredients: fructooligosaccharide (FOS) (4.5 

g)

Arm 3: DHA

Description: basic supplement with FOS and DHA 

(200 mg)

Manufacturer: Nestle ́ (Vevey, Switzerland)

Dose: 200 mg DHA prepared from fish oil (assuming 

that some EPA but dose was not reported)

DHA: 200 mg

EPA: NR

Outcome: BMI (kg/m2) (Unspecified)

Follow-up time: 1 month

Arm 1: Sample size 74; mean 14.2; SE 

(0.37)

Arm 3: Sample size 43; mean 14.06; SE 

(0.4)

Follow-up time: 21 months

Arm 1: Sample size 74; mean 15.46; SE 

(0.32)

Arm 3: Sample size 43; mean 14.7; SE 

(0.36)

Follow-up time: 3 months

Arm 1: Sample size 74; mean 15.58; SE 

(0.38)

Arm 3: Sample size 43; mean 16.14; SE 

(0.44)

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: 1 month

Arm 1: Sample size 74; mean 37.4; SE 

(0.41)

Arm 3: Sample size 43; mean 37.1; SE 

(0.44)

Follow-up time: 21 months

Arm 1: Sample size 74; mean 47.7; SE 

(0.36)

Arm 3: Sample size 43; mean 48.4; SE 

(0.4)

Follow-up time: 3 months

Arm 1: Sample size 74; mean 40.6; SE 

(0.43)

Arm 3: Sample size 43; mean 40.6; SE 

(0.5)

Outcome: length (cm) (Unspecified)

130
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 1 month

Arm 1: Sample size 74; mean 55.6; SE 

(0.64)

Arm 3: Sample size 43; mean 56.3; SE 

(0.69)

Follow-up time: 21 months

Arm 1: Sample size 74; mean 85.4; SE 

(0.56)

Arm 3: Sample size 43; mean 85.5; SE 

(0.62)

Follow-up time: 3 months

Arm 1: Sample size 74; mean 61.9; SE 

(0.65)

Arm 3: Sample size 43; mean 61.7; SE 

(0.76)

Outcome: weight (kg) (Unspecified)

Follow-up time: 1 month

Arm 1: Sample size 74; mean 4.45; SE 

(0.226)

Arm 3: Sample size 43; mean 4.52; SE 

(0.244)

Follow-up time: 21 months

Arm 1: Sample size 74; mean 11.35; SE 

(0.197)

Arm 3: Sample size 43; mean 10.75; SE 

(0.22)

Follow-up time: 3 months

Arm 1: Sample size 74; mean 6.03; SE 

(0.23)

Arm 3: Sample size 43; mean 6.19; SE 

(0.269)

Malcolm et al., 2003100

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: NR

Funding source / conflict: 

Study Population: NR

Pregnant enrolled 100 

Pregnant withdrawals 37 

Pregnant completers 63

Infants enrolled 60 

Infants withdrawals 5 

Infants completers 55

Infant age: 279.6 (8.5)

Inclusion Criteria: d 

women who were 

expected to deliver their 

infants at term and 

planned to feed them on 

breast and/or formula 

milk

Exclusion Criteria: 

diabetes, twin 

pregnancies, preeclamptic toxaemia, a 

Start time: Pregnant week 15 Infants birth

Duration: Pregnant birth

Arm 1: Placebo

Description: contained 323 mg sunflower oil with 

high levels of oleic acid and was free of any 

significant amounts of LCPUFAs or their precursors

Manufacturer: R P Scherer Limited (Swindon, 

Wiltshire, UK)

Dose: 323 mg per capsule * 2

Blinding: e identical in appearance and could not be 

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 50 weeks PCA 

(postconceptional age)

Arm 1: Sample size 27; mean 40.1; SD 

(2.3)

Arm 2: Sample size 28; mean 39.9; SD 

(1.5)

Follow-up time: 66 weeks (post 

conceptional age)

Arm 1: Sample size 27; mean 44.1; SD 

(1.7)

131
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

NR Race of Mother: NR (NR)

Baseline biomarker 

information: Only 

reported: "The fish oil 

and placebo groups did 

not differ in maternal 

RBC and plasma fatty 

acid composition at 

enrollment"

past history of abruption 

or postpartum 

haemorrhage, allergy to 

fish products, a 

thrombophilic tendency, 

or who were receiving 

drugs that affect 

thrombocyte function 

(non-steroidal antiinflammatories)

identified on the basis of scent or taste

Total N-3: 0

Arm 2: DHA

Description: f a blended fish oil, Marinol D40, and 

contained 100 mg DHA in 323 mg oil per capsule

Manufacturer: R P Scherer Limited (Swindon, 

Wiltshire, UK)

Dose: 323 mg capsule * 2

DHA: 200 mg

EPA: .64 mg (estimated based on the FA 

composition)

Arm 2: Sample size 28; mean 43.8; SD 

(2.4)

Outcome: length (cm) (Secondary)

Follow-up time: 50 weeks PCA 

(postconceptional age)

Arm 1: Sample size 27; mean 60.5; SD 

(2.9)

Arm 2: Sample size 28; mean 60.0; SD 

(2.6)

Follow-up time: 66 weeks (post 

conceptional age)

Arm 1: Sample size 27; mean 69.1; SD 

(3.2)

Arm 2: Sample size 28; mean 68.5; SD 

(2.6)

Outcome: weight (g) (Secondary)

Follow-up time: 50 weeks PCA 

(postconceptional age)

Arm 1: Sample size 27; mean 5995.7; SD 

(827.9)

Arm 2: Sample size 28; mean 5894.4; SD 

(662.3)

Follow-up time: 66 weeks (post 

conceptional age)

Arm 1: Sample size 27; mean 8626.7; SD 

(208.2)

Arm 2: Sample size 28; mean 8263.7; SD 

(999.4)

Mulder et al., 201475

Study name: NR

Study dates: 2004 to 

2008

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Government

Study Population: 

Healthy pregnant women

Pregnant enrolled 271 

Pregnant completers 200

Pregnant age: 33 years 

(4 years) NR

Race of Mother: White 

European (73%) Other 

race/ethnicity (27%)

Baseline biomarker 

information: maternal 

Inclusion Criteria: at least 

16 wk gestation, not 

taking any lipid or fatty 

acid supplement, and 

were expected to deliver 

one infant at full-term 

gestation, with no 

maternal or fetal 

complications

Exclusion Criteria: NR

Start time: Pregnant 16 weeks gestation

Duration: Pregnant Until birth

Arm 1: placebo

Description: corn and soybean oil supplement

Manufacturer: Martek Biosciences

Blinding: supplements were identical in appearance, 

contained an orange flavor mask

Arm 2: DHA supplement

Description: algal oil DHA supplement

Manufacturer: Martek Biosciences

DHA: 400 mg

Outcome: length-for-age z score 

(Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 94; mean 0.44; SD 

(1.11)

Arm 2: Sample size 84; mean 0.11; SD 

(1.06)

Follow-up time: 18 months

Arm 1: Sample size 82; mean 0.41; SD 

(1.14)

Arm 2: Sample size 76; mean 0.16; SD 

(1.11)

Follow-up time: 2 months

Arm 1: Sample size 102; mean 0.29; SD 

(1.08)

132
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 18 

months

RBC 

Phusphatidylethanolamin

e DHA: placebo group 

6.25 (1.60) g/ 100g DHA 

group 6.36 (1.62) g/ 100g

Baseline Omega-3 

intake: median (2.5 to 

97.5th percentile range) 

intake: placebo group

80.0 (0.00-334) mg/day, 

DHA group 90.0 (6.00-

472) mg/d

Arm 2: Sample size 92; mean 0.17; SD 

(1.04)

Follow-up time: 6 months

Arm 1: Sample size 101; mean 0.25; SD 

(1.06)

Arm 2: Sample size 95; mean 0.17; SD 

(1.04)

Follow-up time: 9 months

Arm 1: Sample size 95; mean 0.22; SD 

(1.08)

Arm 2: Sample size 88; mean -0.06; SD 

(1.05)

Outcome: weight-for-age z score 

(Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 94; mean 0.15; SD 

(1.02)

Arm 2: Sample size 81; mean 0.12; SD 

(1.05)

Follow-up time: 18 months

Arm 1: Sample size 70; mean 0.27; SD 

(0.99)

Arm 2: Sample size 74; mean 0.21; SD 

(1.04)

Follow-up time: 2 months

Arm 1: Sample size 101; mean 0.06; SD 

(1.08)

Arm 2: Sample size 90; mean -0.19; SD 

(1.08)

Follow-up time: 6 months

Arm 1: Sample size 101; mean 0.1; SD 

(1.01)

Arm 2: Sample size 95; mean -0.06; SD 

(1.11)

Follow-up time: 9 months

Arm 1: Sample size 94; mean 0.03; SD 

(0.99)

Arm 2: Sample size 87; mean 0.04; SD 

(1.11)

Outcome: weight-for-length z score 

(Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 93; mean -0.04; SD 

(0.99)

133
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 81; mean 0.14; SD 

(1.09)

Follow-up time: 18 months

Arm 1: Sample size 70; mean 0.14; SD 

(1.05)

Arm 2: Sample size 74; mean 0.14; SD 

(1.05)

Follow-up time: 2 months

Arm 1: Sample size 101; mean -0.16; SD 

(1.08)

Arm 2: Sample size 90; mean -0.42; SD 

(1.2)

Follow-up time: 6 months

Arm 1: Sample size 101; mean 0.04; SD 

(1.04)

Arm 2: Sample size 95; mean -0.11; SD 

(1.02)

Follow-up time: 9 months

Arm 1: Sample size 94; mean -0.04; SD 

(0.99)

Arm 2: Sample size 87; mean 0.17; SD 

(1.05)

Sala-Vila et al., 2004110

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Spain

Funding source / conflict: 

Multiple foundations and 

Societies, Manufacturer 

supplied product

Study Population: 

Healthy infants

Infants enrolled 35 

Infants completers 35

Pregnant age: 28.3

Infant age: NR

Race of Mother: NR 

(100)

Inclusion Criteria: fullterm infants (37–42 wk 

gestation), of appropriate 

weight-for-gestation-age

Exclusion Criteria: NR

Start time: Infants birth

Duration: Infants 3 mo

Arm 1: Human Milk (HM)

Description: breast milk with composition of protein 

carbohydrate fat ash

Arm 2: E-PL formula

Description: E-PL formula provided 10% of its fat 

from egg PLs

Brand name: Ovotin 120, Lucas Meyer

DHA: 1.25%

AA: 1.9%

Arm 3: S-TG formula

Description: single-cell (SC)-TG formula provided 

_x0004_0.3 and 0.5% of its fat from TGs 

synthesized by single cells of algal and fungal 

microorganisms

Manufacturer: Martek Biosciences

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: 3 months

Arm 1: Sample size 11; mean 41.86; SE 

(1.78)

Arm 2: Sample size 12; mean 42.01; SE 

(1.46)

Arm 3: Sample size 12; mean 43.98; SE 

(1.38)

Outcome: length (cm) (Unspecified)

Follow-up time: 3 months

Arm 1: Sample size 11; mean 60.5; SE 

(6.31)

Arm 2: Sample size 12; mean 61.08; SE 

(5.31)

Arm 3: Sample size 12; mean 60.98; SE 

(3.98)

Outcome: weight (g) (Unspecified)

Follow-up time: 3 months

Arm 1: Sample size 11; mean 6460.1; SE 

(630.6)

134
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

DHA: 0.1g/100g; 0.3% of 40-45% DHASCO

AA: 0.4g/100g, 0.5% of 38-44% ARASCO

Arm 2: Sample size 12; mean 6640.8; SE 

(741)

Arm 3: Sample size 12; mean 6491.9; SE 

(906.1)

Smithers et al., 2008104

Study name: DINO

Study dates: 2001-2004

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Manufacturer supplied 

product

Study follow-up: 2

months, 4 months

Original, same study, or 

follow-up studies: 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Study Population: 

Preterm infants

Lactating enrolled 

unclear

Infants enrolled 143 

Infants completers 125

Lactating enrolled 

unclear

Mother age: Control: 31 

Treatment: 29 (Control: 6 

Treatment: 6)

Infant age: 5 days 

(control) (mean 

gestational age at birth 

29.4 weeks) 6 days 

(Treatment) (3)

Race of Mother: NR (NR)

Baseline Omega-3 

intake: Intervention 

begun at birth: see below

Inclusion Criteria: infants 

born_x0001_33 wk 

gestation at the Women’s 

and Children’s Hospital 

of the Child, Youth, and 

Women’s Health Service, 

Adelaide, Australia, 

between April 2001 and 

September 2003

Exclusion Criteria: Infants 

with major congenital or 

chromosomal 

abnormalities, lactating 

mothers for whom tuna 

oil was contraindicated 

(women with bloodthinning disorders or 

currently taking 

anticoagulants)

Start time: Lactating approximately 5 days after birth 

Infants approximately 5 days after birth

Duration: Lactating to estimated due date Infants to 

estimated due date

Arm 1: Control group

Description: Placebo capsules and/or formula

Active ingredients: Linoleic acid 53.4% of fatty acids

Dose: 6 500-mg capsules per day to mothers

Blinding: The soy and tuna oil capsules were 

identical in size, color, and shape

ALA: 5.9% of total fatty acids

Arm 2: Treatment

Description: DHA supplemented breastfeeding 

mothers and/or formula

Active ingredients: Linoleic acid 2.7% of fatty acids

Dose: 6 capsules or formula ad lib

ALA: 0.4% total FA

DHA: 29.5% total FA

EPA: 6.5% total FA

AA: 1.8% total FA

duplicate data of id 8885

Outcome: (Secondary)

135
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Stein et al., 201134

Study name: POSGRAD

Study dates: 02. 2005-

02.2007

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, Multiple

foundations and 

Societies

Original, same study, or 

follow-up studies: Stein, 

201233; Imhoff-Kunsch, 

201158; Escamilla-Nunez, 

201459; GonzalezCasanova, 201560

; 

Ramakrishnan, 201561; 

Ramakrishnan, 201132

Study Population: 

Healthy infants

Pregnant enrolled 1094 

Pregnant completers 973

Pregnant age: placebo 

26.3; DHA 26.4 (placebo 

4.6; DHA 4.9)

Infant age: 39.1 (placebo 

1.6; DHA 1.8)

Race of Mother: NR

Inclusion Criteria: women 

were 18–35 y, were in 

gestation wk 18–22, and 

planned to deliver at the 

IMSS General Hospital in 

Cuernavaca, exclusively 

or predominantly breastfeed for at least 3 mo, 

and to live in the area for 

at least 2 y after delivery

Exclusion Criteria: NR

Start time: Pregnant 18-22 Gestational week Infants 

birth

Duration: Pregnant birth

Arm 1: Placebo

Description: Olive oil

Manufacturer: Martek Biosciences

Dose: 2 capsules olive oil

Blinding: Similar in appearance and taste to DHA 

capsules

Arm 2: DHA

Description: algal DHA capsules

Manufacturer: Martek Biosciences

Dose: 2 capsules * 200mg

DHA: 400 mg

Outcome: head circumference (cm) 

(Primary)

Follow-up time: 18 months

Arm 1: Sample size 370; mean 47.0; SD 

(1.4)

Arm 2: Sample size 369; mean 47.0; SD 

(1.5)

Outcome: length (cm) (Primary)

Follow-up time: 18 months

Arm 1: Sample size 370; mean 79.5; SD 

(2.8)

Arm 2: Sample size 369; mean 79.6; SD 

(2.8)

Outcome: weight (kg) (Primary)

Follow-up time: 18 months

Arm 1: Sample size 370; mean 10.4; SD 

(1.2)

Arm 2: Sample size 369; mean 10.4; SD 

(1.1)

Tofail et al., 200677

Study name: NR

Study dates: Enrollment 

January to March 2000

Study design: Trial 

randomized parallel

Location: Bangladesh

Funding source / conflict: 

Government

Study follow-up: 10 

months

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 400 

Pregnant completers 151

Pregnant age: 22.7 years 

(4.35 years) NR

Race of Mother: Asian 

(100%)

Inclusion Criteria: seems 

as if all pregnant women 

at 25 weeks gestation 

were enrolled, no 

inclusion criteria 

specified

Exclusion Criteria: NR

Start time: Pregnant 25 weeks gestation

Duration: Pregnant until birth

Arm 1: placebo

Description: soy oil capsule

Dose: 4 one gram capsules per day

Blinding: capsules were identical in appearance

Other dose 1: LNA 0.27 g

Other dose 2: linoleic acid 2.25 g

Arm 2: DHA supplement

Description: fish oil capsules

Dose: 4 one gram capsules per day

DHA: 1.2 g

EPA: 1.8 g

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: 10 months

Arm 1: Sample size 124; mean 43.2; SD 

(1.4)

Arm 2: Sample size 125; mean 43.0; SD 

(1.4)

136
Table 13. Observational studies for postnatal growth patterns

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Mohanty, et al., 201585

Outcome domain: Growth

Study dates: 1996-2008

Study design: Observational prospective

Location: US

Funding source / conflict: Government

Study Population: Healthy infants Healthy 

pregnant women

Pregnant completers 534

Race of Mother: White European (88)

Inclusion Criteria: initiated prenatal care at or before 

20 weeks gestation, were aged = 18 years, able to 

speak and read English, planned to carry the 

pregnancy to term, and to deliver at either of the two 

hospitals

Exclusion Criteria: multi-fetal pregnancies, 

implausible total energy intake of <500 or >3500 

kcal/day, pregnancies complicated by fetal demise 

(after 20 weeks of gestation), missing labor and 

delivery information, missing information on fetal 

growth indices, missing seafood intake information

Adjustments: Adjusted for 

maternal age (years), nonHispanic white race, post 

high-school education, 

unmarried marital status, prepregnancy body mass index 

(indicator variables: 18.5-

24.9, 25-29.9, =30 kg/m2), 

total energy (kcal/day), 

current recreational physical 

activity, current smoking, 

current alcohol intake, 

nulliparity, intake of 

red/processed meats 

(servings/day), male infant 

sex.

Much, et al., 2013101

Outcome domain: Growth

Study name: INFAT

Study dates: Recruitment: 2006-2009 Followup: 

1 year

Study design: Observational prospective

Location: Germany

Funding source / conflict: Industry, Government, 

Some authors employed by industry (companies 

that make the supplements)

Follow-up: 1 year

Original, same study, or follow-up studies: 

Hauner, 201237

Study Population: Healthy infants Breastfeeding women

Pregnant enrolled 208

Lactating enrolled 152 at 6 weeks/120 at 4 

months

Infants enrolled 56 at 4 months/31 at 12 months

Lactating enrolled 152 at 6 weeks/120 at 4 

months

Pregnant age: Intervention: 31.9 Control: 31.6 

(Intervention: 4.9 Control: 4.5)

Race of Mother: NR (NR)

Inclusion Criteria: Gestational age =15th wk of 

gestation, between 18 and 43 y of age, 

prepregnancy BMI (in kg/m2) between 18 and 30, 

willingness to implement the dietary 

recommendations, sufficient German language 

skills, and written informed consent

Exclusion Criteria: High-risk pregnancy (multiple 

pregnancy, rhesus incompatibility, hepatitis B 

infection, or parity >4); hypertension; chronic 

diseases (e.g., diabetes) or gastrointestinal 

disorders accompanied by maldigestion, 

malabsorption, or elevated energy and nutritional 

requirements (e.g., gluten enteropathy); known 

metabolic defects (e.g., phenylketonuria); psychiatric 

diseases; hyperemesis gravidarum; supplementation 

with n–3 LCPUFAs before randomization; and 

alcohol abuse and smoking

Adjustments: Gestational age, 

parity, infant sex, group, 

ponderal index at birth, 

breastfeeding status of infants 

at 6 wk, 4 mo, and 1 yr.

137
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Much, et al., 201383

Outcome domain: Growth

Study name: INFAT

Study dates: >2009-<2013

Study design: Observational prospective

Location: Germany

Funding source / conflict: Industry, Government, 

Some authors employed by industry (companies 

that make the supplements), Multiple

foundations and Societies, None

Study Population: Healthy infants Breastfeeding women

Pregnant enrolled 208

Infants completers 187

Race of Mother: NR (NR)

Inclusion Criteria: Healthy pregnant women at 14th 

week of gestation

Exclusion Criteria: None reported

Adjustments: Pregnancy 

duration, group, parity, and 

sex

Scholtens, et al., 2009103

Outcome domain: Growth

Study name: The Prevention and Incidence of 

Asthma and Mite Allergy (PIAMA) birth cohort 

study

Study dates: Recruitment: 1996-1997 Followup: 

1 year

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government, 

Multiple foundations and Societies, None

Follow-up: 1 year

Original, same study, or follow-up studies: Study 

described in Brunekreef, 2002

Study Population: NR

Pregnant enrolled 4146

Infants enrolled 276 Infants completers 244

Infant age: Birth

Race of Mother: NR (NR)

Inclusion Criteria: Children of mothers recruited from 

the general population during pregnancy

Exclusion Criteria: None reported

Adjustments: Age of child at 

breast-milk collection and 

total breast-feeding duration

138
Neurological Development

Key Findings and Strength of Evidence 

Antepartum supplementation: 

• The original report identified one study that supplemented pregnant women with fish oil 

and found no effects on infant EEG.

• The current report identified four RCTs that reported on the effects of prenatal DHA 

supplementation on indices of neurological development infants or children. One large 

RCT reported no effects on brain auditory evoked potentials despite low baseline intakes; 

one small RCT on sleep patterns reported significant effect on arousal at days 1 and 2 but 

no other findings among any of the many other measures; one RCT reported no effects on 

Bayley Infant Development Motor Subscale scores at 18 months; and another reported no 

change in the Bayley Psychomotor Development Index at 18 months. 

• Among four RCTs that reported on the effects of prenatal supplementation with fish oil, 

two large RCTs found no differences in motor development at 10 or 18 months, and two 

reported no differences in neurological optimality scores at 4 or 5.5 years or the 

Developmental Test of Visual-Motor Integration at 12 years. 

• The current report identified two prospective cohort studies and four biomarker studies 

that assessed the association between prenatal exposures or biomarkers and 

neurodevelopmental outcomes. One prospective cohort study found an association 

between the lowest quintile of n-3FA and risk for epilepsy; one prospective cohort study 

found no association of n-3, n-6, or n-6/n-3 FA with a measure of fine motor 

development. One biomarker study found no association of any maternal n-3 or n-6 FA 

biomarkers and the Bailey psychomotor development index (PDI). A second study found 

an inverse association of videographically assessed (mildly abnormal) movement at 3 

months with arterial but not venous cord blood biomarkers; at 18 months, the same 

cohort showed an association of umbilical vein DHA with NOS but not PDI; umbilical 

arterial LC-PUFA were no longer associated with any neurodevelopmental indices. A 

third study found no significant association of cord blood DHA with NOS at 4 years but 

did identify an association at 5.5 years. The fourth study found no association between 

umbilical DHA or AA and Maastricht motor scores at 7 years of age. 

Pre and postpartum maternal supplementation

• One RCT that compared DHA vs DA+AA vs placebo had inconsistent effects on mildly 

abnormal movement and PDI at 0.5, 3, and 18 months. Maternal biomarkers showed 

inconsistent associations with infant movement.

Postpartum maternal supplementation and infant outcomes:

• Healthy term infants breastfed by mothers who received supplemental DHA showed 

significantly improved adjusted PDI scores at 30 months but not at12 months. At 5 years 

a different battery of age-appropriate motor tests showed no difference between groups.

Postpartum supplementation of preterm infants 

139
• The original report identified six RCTs that could not be pooled and reported mixed 

findings with respect to neurological developmental outcomes. The current report 

identified three RCTs that could not be pooled due to different interventions, outcome 

measures, and follow-up times; supplementation showed mixed effects.

Postpartum infant supplementation healthy term

• The original report identified seven RCTs with mixed interventions, durations, and 

outcome measures; pooling three RCTs of DHA+AA showed no effect on PDI at 12 

months compared with placebo. The current report identified five additional RCTS. In a 

small Turkish study, DHA-supplemented formula improved brainstem maturation at 4 

months. In a large Italian study, DHA affected only one out of four measures of gross 

motor development at 12 months. One larger Dutch study showed significant impact of 

DHA+AA on mildly abnormal movement at 2 months compared with placebo; at 18 

months, intervention, placebo, and breastfed children had similar PDI scores; at 9 years, 

the fine motor control of both supplemented and placebo children was similar but poorer 

than that of breastfed. A large US study that randomized infants to one of four different 

levels of DHA-supplemented formula found no differences in PDI scores from placebo 

among any of the supplemented groups. An Australian study that supplemented infant 

formula with DHA-enriched fish oil also found no differences in the BSID Composite 

motor score, the Categorical Child Behavior Checklist, or several indices of sleep.

Description of Included Studies

We identified 17 RCTs and five large observational studies that assessed the effects of n-3 

FA interventions on, or the associations of n-3 FA exposures with, neurodevelopment in the 

developing infant and child, as distinct from cognitive development. Outcomes varied and 

included the Bailey’s Psychomotor Development Index (PDI), brainstem auditory evoked 

potentials, neurological optimality scores, general movement assessment, and the Touwen 

Neurological Assessment, among others.

This section reports the findings of studies that assessed the effects of prenatal, postnatal 

maternal (breast milk), or postnatal infant PUFA supplementation or exposure on these 

outcomes. Studies identified for this report are summarized in Table 13 and briefly summarized 

below. 

Antepartum Maternal Supplementation with or Exposure to n-3 Fatty Acids and 

Infant Neurodevelopmental Outcomes

Randomized Controlled Trials

The original report identified one RCT that assessed the effects of an n-3 intervention (cod 

liver oil) with pregnant women on neurodevelopmental outcomes; the outcome was brain 

maturity as assessed by infant electroencephalogram (EEG) recordings at 1 day and again at 6 

months of age; this study found no effect of maternal supplementation at either time point. No 

studies were identified for the current report that assessed effects of maternal supplementation on 

infant EEG patterns.

For the current report, we identified nine RCTs that assessed the effects of antepartum 

maternal supplementation with n-3 FA on neurodevelopmental outcomes (see Table 14). We also 

identified five articles that reported the results of three prospective cohort studies that assessed

the association between antepartum maternal n-3 FA exposures and infant neurodevelopment 

140
(two of these articles were post hoc assessments of the association between maternal n-3 FA 

status and subsequent neurodevelopmental outcomes in RCTs).

DHA Versus Placebo 

Brainstem Auditory Evoked Potentials. For the current report, we identified one 2012 RCT that 

randomized 1,094 pregnant women in Mexico to 0.4g/d algal DHA or corn and soy bean oil from 

approximately 17 weeks of gestation through term and assessed the effect of supplementation on 

brainstem auditory evoked potentials (a measure of brainstem maturation).33 The women had low 

baseline intakes of DHA. No differences were seen in any comparisons (latency and interpeak 

latency at 1, 3, and 5 milliseconds) between infants of placebo and DHA-supplemented women 

at either time point.

Sleep/Wakefulness. A 2013 RCT randomized 48 U.S. women to consume five cereal bars per 

week from 24 weeks of gestation until delivery; 27 of the women received bars that contained 

0.3g DHA each (for an average of 0.21g/d DHA and a trace amount [0.023 g/d] EPA) and the 

remaining women received bars without DHA.40 Early infant sleep patterns, a predictor of 

subsequent neurological development, were measured at 1 and 2 postnatal days using a pressure 

sensitive mattress. On both days 1 and 2, infants of DHA-supplemented mothers showed fewer 

arousals in both quiet (adjusted p=0.006 for day 1, adjusted p=0.011 for day 2) and active 

(adjusted p=0.012 for day 1) sleep than did infants of control mothers. No differences were 

observed between groups in arousal from active sleep on day 2, quiet sleep, sleep transitions, 

active sleep, wakefulness, sleep bout lengths, mean sleep period, and longest sleep period.

Neonatal Behavioral Assessment Scale (Motor and Autonomic Clusters). Carlson and colleagues 

(Gustafson et al., 2013) randomized 46 pregnant women (average 14 weeks gestation) to receive 

600 mg per day of DHA or placebo.74 At one week of age, 27 infants (15 from mothers given 

DHA and 12 from mothers given placebo capsules) completed the Neonatal Behavioral 

Assessment scale (NBAS). Infants from women randomized to the DHA intervention during 

showed significantly higher (better) scores on the Motor (t25=1.87, P=0.038) and Autonomic

clusters(t25=1.99, P=0.029).

Bayley PDI. Ramakrishnan and colleagues (in the POSGRAD study) examined the effects of 

prenatal maternal algal DHA supplementation (400 mg daily) on neurodevelopmental outcomes 

of 730 Mexican infants at 18 months.61 The effects of supplementation on birth outcomes were 

reported previously.32 Toddlers of supplemented mothers did not differ from toddlers of placebotreated mothers in adjusted (-0.46; -1.80, 0.88) or unadjusted PDI scores (-0.26; -1.63, 1.10).

Bayley Scales of Infant Development Motor Subscales. Innes and colleagues (Mulder et al., 

2014) developed a risk-reduction model to examine whether the DHA-status in some pregnant 

women, and therefore their fetuses, is sufficiently low as to increase the risk for neurological and 

cognitive developmental delay. The study, conducted in Canada, randomized pregnant women at 

16 weeks gestation or less to 400mg DHA daily in the form of algal oil or to a corn and soy oil 

placebo.75 This amount of DHA was chosen as it is the equivalent of about two weekly servings 

of fish. At 18 months, toddlers of placebo mothers did not differ from those of DHA-fed mothers 

in the likelihood of scoring in the highest quartile for fine (P=0.33) and gross (P=0.40) motor 

141
skills (outcomes for the cognitive subscales and visual acuity are described elsewhere in this 

report).

Fish Oil Versus Placebo

Bayley’s PDI or Motor Standardized Score. For the current report, we identified three studies 

that assessed the effects of supplementing pregnant women with fish oil on infant psychomotor 

development, compared with those of placebo.35, 77

In one 2006 study, four hundred healthy pregnant women in Dhaka Bangladesh were

randomized to receive fish oil (1.2g/d DHA and 1.8g/d EPA) or placebo (soy oil) from the 25th

week of gestation through term. No differences were seen in PDI scores between the two groups 

of infants (n=249) at 10 months of age (effect size -2.1±1.1[-4.3, 0.1]).

A 2010 study, the DOMInO Study,35 randomized 2,399 women seen at five hospitals in 

Australia to a daily DHA-rich fish oil supplement (0.8g/d DHA; 0.1g/d EPA) or placebo 

beginning at 21 weeks of gestation or earlier through term. The primary outcome of the study 

was risk for depression; however infant neuro- and cognitive development were assessed as 

secondary outcomes in 726 infants at 18 months of age. No differences were seen in unadjusted 

or adjusted effect sizes among boys or girls between treatment group offspring (-0.69[-2.31, 

0.93]p=0.40) for girls; (0.85[-1.00, 2.70] p=0.37)).

Beery-Buktenica Developmental Test of Visual-Motor Integration. Meldrum and coworkers51

reported on a group of 50 children at 12 years’ follow-up whose mothers were randomized 

prenatally to receive fish oil or placebo capsules.44 Secondary outcomes included the BeeryBuktenica Developmental Test of Visual-Motor Integration (TVMI). No differences were 

observed between the groups on TVMI scores, and no association was observed between these 

scores and blood levels of DHA at 12 years of age.

Neurological Optimality Score. Koletzko’s group (Escolano-Margarit et al, 2011) randomized 

315 healthy pregnant women at 20 weeks gestation to receive a milk-based supplement 

containing fish oil that delivered 500mg DHA and 50mg EPA daily or a placebo oil, with or 

without 400 micrograms 5-methylline tetrahydrofolate (5-MTHF) through term.130 Infants whose 

mothers had received fish oil and were not breastfed received infant formula that contained fish 

oil. Children were examined at the age of 4 years with the Hempel assessment and also received 

a neurological optimality score (NOS). At 5.5 years, they were reassessed using the Touwen 

assessment. No differences were seen in any of the assessments between children who received 

fish oil pre- and postnatally and those who were exposed to placebo only. Associations between 

cord blood n-3 FA levels and outcomes are described below.

Observational Studies 

We identified two prospective cohort studies that assessed the association between maternal 

intakes of n-3 FA during pregnancy and infant neurodevelopmental outcomes (see Table 15).

89, 

131 We also identified four studies (reported in five publications) that assessed the association 

between umbilical venous LC-PUFA and these outcomes (one of these studies was a follow-up

to a study described in the original report, and another was a follow-up to a study described 

below).

142
Prospective Cohort Studies

A 2010 study used data from the Danish National Birth Cohort, which estimated n-3 FA 

intake from self-administered FFQ around 25 weeks gestation.131 The authors followed 65,754 

live-born infants up to 11 years of age to determine their risk for a diagnosis of epilepsy 

(according to ICD-10 criteria) associated with quintiles of total n-3 FA intake. Based on the 

middle quintile as the reference (0.31±0.07g/d, adjusted for energy intake), infants born to 

women with the lowest quintile of pregnancy n-3 FA intake (0.12±0.04g/d) were at a slightly but 

not significantly increased risk for epilepsy (adjusted incidence rate ratio, 1.28[0.98, 1.67]) and 

infants born to women with the highest quintile (0.0.82 ±0.35g/d) of intake were at a 

significantly increased risk for epilepsy (IRR 1.33[1.02, 1.74]). Restricting the analyses to 

children for whom information on breastfeeding was actually available, the risk increase 

remained insignificant for the lowest quintile of n-3FA intake (IRR 1.35[0.99, 1.83]), and the 

risk for infants of mothers with the highest quintile of intake was no longer significant (IRR 

1.24[0.90, 1.69]). 

A 2013 study assessed the association between n-3 FA/ n-6 FA intake during pregnancy 

among 1,335 French women enrolled in the EDEN cohort study and performance of their 

children at 2 years of age on tests of cognitive and motor development, included the Peg 

Movement Task (PMT)-5.89 Neither breastfed nor never-breastfed children showed any 

association between performance on the PMT-5 and maternal intake of n-6 FA, n-3 FA or the n6/n-3 ratio.

Biomarker Studies

A 2013 study whose primary outcome of interest was the association between prenatal 

mercury exposure, LC-PUFA, and infant neurodevelopment assessed the association between 

maternal serum n-3 and n-6 FA and Bailey Scale of Infant Development composite motor scores 

at 18 months of age among a population-based cohort of 606 mother-child pairs in Italy.132 No 

significant association was found between motor scores and maternal EPA, DHA, ALA, DPA, or 

AA status or n-6:n-3 ratio.

Bouwstra and colleagues utilized a cohort of children enrolled in a RCT to assess the effect 

of DHA and AA-supplemented infant formula (compared with standard formula and breast milk) 

on neurological development to assess the associations between umbilical venous and arterial n3FA status and neurological development at 3 months133 (the RCT is described below). 

Neurological development was assessed by videographically recording and analyzing general 

movement quality: Movements were classified as normal optimal, normal suboptimal (both 

normal optimal and normal suboptimal are considered clinically normal), mildly abnormal or 

definitely abnormal. At 3 months, the quality of general movements among 269 infants was not 

associated with the DHA or AA concentration of venous cord blood. However movement quality 

was associated with the FA content of arterial cord blood. An increase in mildly abnormal 

movements was associated with adjusted lower arterial cord blood levels of total 

monounsaturated FA; several n-6 FA, including AA; n-9 FA; and total n-3 and n-6 FA. 

Bouwstra and colleagues reassessed neurologic development of the same cohort at 18 months 

(n=317), this time using the Hempel neurological exam to obtain a neurologic optimality score 

(NOS) and the Bailey PDI. Children whose umbilical vein DHA concentrations were in the 

lowest quartile had significantly lower adjusted NOS but no difference in PDI scores compared 

with children whose umbilical vein DHA concentrations were higher (β=0.17; p=0.003). 

Umbilical venous AA concentrations were not associated with NOS or PDI scores in 

143
multivariate analysis, and umbilical arterial LC-PUFA concentrations were not associated with 

neurodevelopmental indices.

In a follow-up to a 2003 cohort study described in the original report (but not originally 

including neurological outcomes), Bakker and colleagues also assessed the association between 

umbilical venous LC-PUFA and neurological development, as indicated by motor development, 

in another Dutch cohort.134 The cohort comprised 750 white children born between 1990 and 

1994 and seen at the University Hospital Maastricht, for whom umbilical blood LC-PUFA had 

been assessed. At 7 years of age, 306 children were given the Maastricht Motor Test (MMT) by 

a blinded tester. The composite (total) score comprises a quantity score (whether the participant 

can perform the movement) and a quality score (how well the participant performs the 

movement). MMT total score and quality score were significantly positively associated with 

umbilical plasma DHA in multivariate models (β=0.13, p=0.01; β=0.14, p=0.10, respectively). 

Umbilical DHA was not significantly associated with MMT quantity score. Umbilical AA was 

not significantly associated with MMT scores ((β=-0.10, p=0.069; β=-0.11, p=0.052, for total 

and quality scores, respectively).

Koletzko’s group assessed the association between maternal cord blood DHA and AA status 

and NOS in their trial of fish oil and 5-MTHF supplementation.130 At 4 and 5.5 years of age, the 

risk for MND was not associated with maternal plasma or erythrocyte DHA, AA or AA:DHA or 

with cord blood DHA, AA or AA:DHA. At 4 years of age, children’s NOS were not associated 

with plasma or erythrocyte DHA or AA levels or the AA:DHA ratio. However, at 5.5 years, 

NOS was significantly associated with cord blood DHA, such that the odds of achieving the 

maximal NOS score increased with every unit increase in cord blood plasma phospholipid DHA 

(95% CI 1.094, 2.262) and in erythrocyte phosphatidyl ethanolamine (95% CI 1.091, 2.417) and 

phosphatidyl choline DHA (95% CI 1.003, 2.643). Term maternal erythrocyte DHA was 

positively associated and the AA:DHA ratio was negatively associated with NOS.

Ante- and Postpartum Maternal Supplementation with n-3 FA and Infant 

Neurodevelopment

For the current report, we identified one study that examined the effects of both prenatal and 

postnatal maternal supplementation with LCPUFA on infant neurological development. 

DHA or DHA plus AA Versus Placebo

For the current report, we identified one study, reported in two publications, that examined 

the effects of both prenatal and postnatal maternal supplementation with DHA or DHA plus AA 

on infant neurological development compared with those of placebo. 

One study, reported in two publications, enrolled 183 healthy pregnant women between 14 

and 20 weeks of pregnancy (80% between 15.6 and 17.4 weeks) in the Netherlands and 

randomized them to receive a daily supplement of vitamins and minerals alone, vitamins and 

minerals along with DHA (0.22 g/d), or vitamins and minerals along with DHA (0.22g/d from 

fish oil) and AA (0.22g/d) from enrollment to 3 weeks after delivery.36 Infant neurological 

development was assessed at 0.5 months, 3 months,36 and 18 months66 of age using two 

instruments. At 0.5 months and 18 months, a standard neurological assessment was conducted, 

resulting in a NOS. At all time points, general movement quality was assessed videographically 

as described above. And at 18 months, infants were assessed using the PDI. No significant 

differences in NOS were seen among the three groups of infants at 0.5 months of age (n=183). 

At 0.5 months of age, infants of mothers supplemented only with DHA showed significantly 

more mildly abnormal movements than the infants of control mothers (adjusted β 3.867, 

144
p=0.021); no significant difference was seen between infants of DHA-supplemented mothers and 

those of mothers who received DHA plus AA (adjusted β, p=0.19), and controls did not differ 

from the DHA plus AA group (p=0.29). At 3 months (n=96), the adjusted differences attained 

significance for DHA vs. controls (p=0.014), and for DHA vs. DHA plus AA (p=0.017). At 18 

months (n=114), no difference in PDI scores was observed among the three groups of infants.66

Maternal Biomarkers

The study by van Goor that assessed the effects of maternal pre- and postnatal 

supplementation with DHA or DHA plus AA on neurological development also assessed the 

association between maternal36 biomarkers of n-3 FA status and infant neurological 

development. They reported no correlations between prenatal (3 weeks gestation) maternal 

erythrocyte n-3, n-6 FA, or the DHA:AA ratio and the NOS. Mildly abnormal infant general 

movements at 2 weeks were correlated with lower maternal erythrocyte AA compared with 

normal general movements (median 12.25 vs. 13.03, p=0.02). No associations were found at 3 

months.36

Postpartum Maternal Supplementation with n-3 FA and Infant Neurodevelopment

For the current report, we identified one new RCT, reported in two publications, that 

examined the effects of supplementing lactating mothers with n-3 FA on infant neurological 

development. 

DHA Versus Placebo

We identified two new articles reporting on one RCT that examined the effects of postpartum 

maternal DHA supplementation on infant neurological development.135, 136

Jensen and colleagues randomly assigned 227 pregnant U.S. women who planned to 

breastfeed for at least 4 months to either algal DHA (approximately 0.2g/d) or placebo, to begin 

at 5 days postpartum and continue for 4 months.135 Mothers of preterm or low birth weight 

infants were excluded. Compliance with the supplement was 95 percent to 100 percent. The 

Bailey PDI and the Gesell Developmental Inventory were used to assess motor development at 

12 and 30 months of age in the 230 infants (including 3 twin pairs). At 12 months, no differences 

were seen between groups in either of the tests. At 30 months, infants of DHA-supplemented 

mothers had significantly higher adjusted PDI scores than infants of placebo-supplemented 

mothers (p=0.0008), although no difference was seen using the Gesell Inventory.136

A subsequent article reported on psychomotor development as measured by the K-ABC 

Hand movement scale; McCarthy Leg Coordination component; Purdue Peg board Test; and the 

Developmental Test of Visual Motor Integration Motor component at 5 years of age in the same 

population (n=60 children of DHA-supplemented mothers and 57 children of placebo 

mothers).135 No differences were seen between the two groups of infants in performance on any 

of the tests. 

Maternal and Infant Biomarkers

Jensen and colleagues assessed the association between infant plasma phospholipid DHA and 

psychomotor development and found no association (data not reported).136

145
Infant Formula Supplementation with n-3 FA and Neurodevelopment in Preterm 

Infants

The original report identified six RCTs that examined the effects of supplementing formula 

with n-3 FA with or without breast feeding on neurological development among preterm infants; 

the studies dated from 1999 to 2004. Duration of supplementation varied. Follow-ups ranged 

from 1 month to 24 months: in some studies, the intervention ended several months before 

follow-up assessment. Three RCTs assessed the use of formula supplemented with DHA plus 

AA, two RCTs assessed the use of formula supplemented with DHA plus EPA plus AA, and one 

used DHA plus gamma-linoleic acid. Across the studies, outcomes were mixed: two studies 

reported a positive effect of DHA plus AA on PDI scores, whereas four reported no or negative 

effects. No studies were pooled because of differences in intervention duration and follow-up.

DHA, DHA plus AA, or DHA plus EPA Versus Placebo

Three RCTs were identified for the current report that assessed the effects of providing infant 

formula supplemented with DHA with or without EPA and AA on PDI scores of preterm infants. 

The outcomes could not be pooled because of differences in the interventions and follow-up

times. 

A 2005 RCT randomized 27 preterm infants in Taiwan (born at 30 to 37 weeks gestation and 

over 2kg body weight) to oral formula supplemented with DHA (0.05%) and AA (0.1%) or a 

control formula for 6 months.137 PDI scores in the supplemented group were not significantly 

different from the unsupplemented group at 6 months (102.2±10.5 vs. 95.4±13.2) but 

significantly higher in this group at 12 months (98.0±5.8 vs. 86.7±11.1, p=0.008) compared to 

the unsupplemented group.

Another 2005 RCT randomized 361 preterm U.S. infants (≤35 weeks gestation) to one of 

three groups: oral formula supplemented with algal DHA (0.017g/100kcal) plus algal AA

(0.034g/100kcal); oral formula supplemented with fish DHA and algal AA in the same 

concentrations; or standard formula for approximately 18 months (until 118 weeks postmenstrual 

age [PMA]).108 At 118 weeks PMA, both supplemented groups had significantly higher PDI 

scores than the unsupplemented group but significantly lower than a group of term breastfed 

infants of similar ages.

The DINO trial, a 2009 RCT, randomized 657 preterm infants (≤33 weeks gestation) to 

receive “high DHA” (1% of total fatty acids) or “standard DHA” (0.3% of total fatty acids) 

enteral formula from day 2 to 4 until term-corrected age (expected date of delivery) and assessed 

the effects of the two supplements at 18 months corrected age on a number of outcomes, 

including neurological development. In an intention to treat analysis, the authors reported no 

differences between groups in PDI scores.116

Infant Formula Supplementation with n-3 FA and Neurodevelopment in Term 

Infants

The original report identified seven RCTs that examined the effects of supplementing infant 

formula with various combinations of n-3 and n-6 FA on neurodevelopmental outcomes of term 

infants. Across these RCTs, effects of supplementation on neurodevelopment, usually assessed 

using the Bailey PDI, were mixed. 

For the current report we identified five new studies reported in seven publications that 

assessed the effects of n-3 FA with or without other LCPUFA on neurodevelopmental outcomes. 

None of these studies could be pooled with studies in the original report.

146
DHA Versus Placebo 

We identified two RCTs that assessed the effects of DHA supplementation alone on 

neurodevelopmental outcomes. 

A 2004 RCT randomized 54 healthy term infants in Turkey within the first week of life to 4 

months of Farleys First Milk (a DHA-supplemented infant formula [0.5% DHA]), or Nutrilon, a 

control formula.138 A group of 23 infants breastfed from birth served as a reference. At 4 months, 

brainstem maturation was assessed in the remaining 44 infants by measuring the decrease in 

brainstem auditory evoked potentials: All six measures (three absolute wave and three interpeak 

latencies) showed significantly greater maturation in the infants given the DHA-supplemented 

formula (p=0.038-0.001) and the breast fed infants (P=P=0.04-0.001), compared with the infants 

fed non-supplemented formula. 

A 2011 RCT randomized 1,160 healthy term newborns in Italy to a daily supplement of oil 

containing DHA and vitamin D (0.4g/d DHA and 400IU, respectively) or vitamin D alone for 12 

months to assess the effect on four measures of gross motor development.139 At 12 months, 

among the remaining 1,091 infants, only one of the outcome measures, time to sitting without 

support, was achieved significantly faster in the DHA-supplemented infants. The remaining three 

outcome measures did not differ between intervention groups. 

Fish Oil Versus Placebo

The Infant Fish Oil Supplementation Study (IFOS) randomized 420 healthy term infants at 

high family risk for allergy to receive DHA-enriched fish oil (250-280mg DHA daily and 110 

mg EPA) or olive oil placebo from birth to 6 months of age.140 At 18 months of age, toddlers 

were given a battery of cognitive and neurodevelopmental tests, including the Bayley Scales of 

Infant and Toddler Development (BSID, 287 toddlers) and Categorical Child Behavior Checklist 

(269 toddlers). Composite motor scores on the BSID were not significantly different between the 

fish oil treated and placebo-treated infants (P=0.097). Sleep problems also did not differ between 

the groups (P=0.453). Cognitive and respiratory outcomes are described elsewhere in this report. 

DHA Plus AA Versus Placebo

The original report pooled the results of three RCTs (n=184) that assessed the effects of 

supplementing term infants with DHA plus AA on PDI scores at 12 months: the pooled weighted 

mean difference was -2.80 (95% CI -7.43, 1.82; I2 36%), thus showing no significant effect of 

the supplemented formula. 

For the current report, we identified two RCTs that assessed the effects of supplementing 

infant formula with DHA plus AA, but could not be pooled with the earlier studies. 

The DIAMOND Study randomized healthy term U.S. infants born at one of 7 hospitals at 

two study sites to one of four intervention groups within 9 days of birth (study sites differed 

significantly by race, ethnicity, parental education, and gestational length). Children who had 

received breast milk were excluded. Three of the intervention groups received a standard formula 

fortified with 0.32% DHA (0.017g/100kcal), 0.64% DHA (0.034g/100 kcal), or 0.96% DHA; all 

intervention formulae also included 0.64% fatty acids as AA (0.034 g/100kcal). The control 

group received the standard formula with no DHA or AA. The intervention was continued for 12 

months and no other foods were introduced prior to 4 months of age. A subset of participants at 

one of the two sites received neurodevelopmental assessments at 18 months and a series of 

cognitive developmental assessments through 6 years of age (described elsewhere in this 

report).121-124 PDI scores at 18 months did not differ significantly among the four groups of 

147
infants (statistics not reported); scores for the placebo group actually slightly exceeded those of 

the three active treatment groups combined.

A 2003 multisite study conducted around Groningen in the Netherlands randomized 312 

healthy term infants to one of two infant formulas: Nutricia Nutrilon formula supplemented with 

0.30% DHA from egg yolk and tuna oil and 0.45% AA from egg yolk and fungal oil or the same 

formula without DHA and AA. The fatty acid patterns of the fortified formula were similar to 

those of breast milk. A third group of 160 breastfed infants was also included. The intervention 

was continued for 2 months. Videographed general movements were analyzed at 3 months and 

quality was classified as described above.62 The occurrence of mildly abnormal movements was 

significantly less frequent in the supplemented formula group than in the control group (adjusted 

OR 0.49[0.26, 0.92]p=0.032) and not significantly different from the breastfed group (p=0.87). 

At 18 months’ follow-up, toddlers were re-assessed with the PDI, the Hempel Test (to assess 

minor neurological dysfunction [MND]), and assessment of NOS (attrition was 5.5% and not 

selective).63 In both univariate and multivariate analysis, the rate of MND, the NOS, and the PDI 

scores did not differ among the three groups (supplemented formula, control formula, and breast 

fed). 

At 9 years of age, the children were re-assessed (attrition was 28% and boys with lower MDI 

scores were more heavily represented among the dropouts).64 The primary outcome was the 

NOS, based on the Touwen Neurological assessment of neurological dysfunction, and the MND. 

No differences were seen between the supplemented formula-fed group and the control group in 

the NOS or the ratios of neurologically normal, simple MND, and complex MND children. 

However, breastfed children were less likely to show fine manipulative dysfunction than either 

group of formula-fed children.

148
Table 14. RCTs for neurological development

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Agostoni et al., 2009139

Study name: NR

Study dates: Enrollment 

occurred May and June 

2005; 1-year followup

Study design: Trial

randomized parallel

Location: Italy

Funding source / conflict: 

Manufacturer supplied 

product

Study Population: 

Healthy infants

Infants enrolled 1160 

Infants withdrawals 69 

Infants completers 1091

Mother age: 32 years 

(4.5 years) NR

Infant age: intervention 

began 1 day after 

discharge (NA) NA

Race of Mother: White 

European (100%)

Inclusion Criteria: weight 

at birth 2500 g or more, 

gestational age between 

37 and 42 completed 

weeks, single birth, 

absence of neonatal or 

birth abnormalities, 

Apgar score 7 or higher 

at 5 min, and white 

parents.

Exclusion Criteria: 

presence of neonatal 

diseases requiring 

hospitalization for 7 days 

or more; involvement of 

neonate in another 

clinical study; unknown 

father; and parents 

unable to understand the 

protocol requirements, to 

fill out the infant’s diary, 

or to understand and 

speak the Italian 

language adequately.

Start time: Infants 1 day after discharge from birth 

hospital

Duration: Infants 1 year

Arm 1: placebo

Description: oral liquid

Manufacturer: Humana Italia SpA

Active ingredients: 400 IU vitamin D3

Viability: Parents were advised to store the bottles in 

a dry and fresh environment.

Dose: 1 mL once per day

Blinding: Intervention and placebo preparations were 

identical in aroma, taste, and texture

Total N-3: 0

Arm 2: Human Italia SpA

Active ingredients: 400 IU vitamin D3

Viability: Parents were advised to store the bottles in 

a dry and fresh environment.

Dose: 1 mL once per day

DHA: 20 mg DHA/ml

Outcome: age achieving gross motor: 

hands-and-knees crawling (weeks) 

(Primary)

Follow-up time: varies

Arm 1: Sample size 476; mean 39.4; SD 

(6.2)

Arm 2: Sample size 482; mean 38.9; SD 

(6.4)

Outcome: age achieving gross motor: 

sitting without support (weeks) (Primary)

Follow-up time: varies

Arm 1: Sample size 542; mean 28.3; SD 

(4.2)

Arm 2: Sample size 551; mean 26.8; SD 

(4.2)

Outcome: age achieving gross motor: 

standing alone (weeks) (Primary)

Follow-up time: varies

Arm 1: Sample size 542; mean 50.1; SD 

(8.1)

Arm 2: Sample size 549; mean 49.2; SD 

(7.6)

Outcome: age achieving gross motor: 

walking alone (weeks) (Primary)

Follow-up time: varies

Arm 1: Sample size 542; mean 55.8; SD 

(6.7)

Arm 2: Sample size 549; mean 54.9; SD 

(6.8)

Bouwstra et al., 200362

Study name: Groningen 

LCPUFA study

Study dates: 1997-1999

Study design: Trial 

randomized parallel

Location: Netherlands

Study Population: 

Healthy infants

Infants enrolled 472 

Infants completers 397

Mother age: 31 (5) NR

Infant age: Gestational 

age 39.6 wk (1.3) NR

Race of Mother: White 

Inclusion Criteria: healthy 

term infants

Exclusion Criteria: infants 

who had a congenital 

disorder that interfered 

with adequate functioning 

in daily life, infants from 

multiple births, infants 

whose mothers did not 

have mastery of the 

Dutch language or 

Start time: Infants Birth

Duration: Infants 2 months

Arm 1: Control formula

Description: Standard formula with no supplemental 

LCPUFA

Brand name: Nutrilon premium

Manufacturer: Zoetermeer, Netherlands

Active ingredients: linoleic acid (11mol%); ALA 1.27 

mol%

Dose: ad lib

Outcome: mildly abnormal general 

movements (Primary)

Follow-up time: 3 months

Arm 1: 41/131 (31.0%)

Arm 2: 23/119 (19.0%)

Outcome: normal-optimal general 

movements (Primary)

Follow-up time: 3 months

Arm 1: 28/131 (21.0%)

Arm 2: 21/119 (18.0%)

149
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / conflict: 

Industry

Study follow-up: 3 

months

Original, same study, or 

follow-up studies: 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; van Goor, 201036; 

van Goor, 201166

European (100) suffered from significant 

illness or disability, 

adopted and foster 

infants, and formula-fed 

infants who had received 

human milk for >5 d.

Blinding: not reported

Maternal conditions

Current smoker 32% during pregnancy

Maternal abuse of alcohol/psychotropic drugs 

Alcohol USE during pregnancy 10%

Arm 2: LCPUFA formula

Description: LCPUFA formula fortified with n-3s and 

n-6s

Brand name: NR

Maternal conditions

DHA: 0.30% (by wt)

AA: h 0.45% (by wt)

Current smoker 32% smoked during pregnancy

Maternal abuse of alcohol/psychotropic drugs 13% 

used alcohol during pregnancy

Arm 3: breastfed group

Description: breastfed, no formula, not randomized 

here - used as reference group

Maternal conditions

Current smoker 28% smoked during pregnancy

Maternal abuse of alcohol/psychotropic drugs 38% 

consumed alcohol during pregnancy

Bouwstra et al., 200563

Study name: Groningen 

LCPUFA study

Study dates: 1997-2002

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Industry

Study follow-up: 18 

months

Original, same study, or 

Study Population: 

Healthy infants

Infants enrolled 472 

Infants completers 446

Mother age: 31 years (5 

years) NR

Infant age: birth

Race of Mother: White 

European (100%)

Inclusion Criteria: healthy 

term infants

Exclusion Criteria: infants 

who had a congenital 

disorder that interfered 

with adequate functioning 

in daily life, infants from 

multiple births, infants 

whose mothers did not 

have mastery of the 

Dutch language or 

suffered from significant 

illness or disability, 

adopted and foster 

infants, and formula-fed 

infants who had received 

human milk for >5 d.

Start time: Infants Birth

Duration: Infants 2 months

Arm 1: Control group

Description: Standard formula

Brand name: Nutrilon premium

Manufacturer: Zoetermeer, Netherlands

Active ingredients: linoleic acid (11mol%); ALA 1.27 

mol%

Dose: ad lib

Maternal conditions

Current smoker 31% during pregnancy

Maternal abuse of alcohol/psychotropic drugs 

Alcohol USE during pregnancy 8%

Arm 2: LCPUFA formula

Description: LCPUFA formula

Dose: ad lib

Outcome: Bayley PDI (Secondary)

Follow-up time: 18 months

Arm 1: Sample size 169; mean 100.9; SD 

(13.6)

Arm 2: Sample size 146; mean 99.4; SD 

(13.4)

Outcome: neurological optimality score 

(Secondary)

Follow-up time: 18 months

Arm 1: Sample size 169; median 52.0; 5, 

95 percentile

Arm 2: Sample size 146; median 52.0; 5, 

95 percentile

Outcome: number of children with minor 

neurological dysfunction (Secondary)

Follow-up time: 18 months

Arm 1: 8/169 (5.0%)

Arm 2: 10/146 (7.0%)

150
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

follow-up studies: 

Bouwstra, 200362; de 

Jong, 201064; de Jong, 

201265; van Goor, 201036; 

van Goor, 201166

Maternal conditions

DHA: 0.30% DHA

AA: 0.45% AA

Current smoker 31% during pregnancy

Maternal abuse of alcohol/psychotropic drugs 9% 

used alcohol during pregnancy

Arm 3: breast feeding group

Description: breast fed, no formula

Maternal conditions

Current smoker 19% smoked during pregnancy

Maternal abuse of alcohol/psychotropic drugs 24% 

used alcohol during pregnancy

Clandinin et al., 2005108

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Industry

Study Population: 

Preterm infants

Infants enrolled 361 

preterm+105 term 

breastfed Infants 

completers 179 preterm 

and 76/105 term 

breastfed

Infant age: 30.6 weeks 

postmenstrual age 24-36 

weeks postmenstrual age

Race of Mother: NR 

(100)

Inclusion Criteria: Phase 

I: gestational age <35 

weeks PMA and received 

<10 total days of enteral 

feedings of >30 mL/kg 

per day. Infants initially 

fed human milk were not 

enrolled unless formula 

was started within 10 

days after completing the 

first day of human milk 

feeding Phase II: 

completion of phase I 

and >=80% enteral 

intake from study formula 

during hospitalization and 

100% of caloric intake 

from study formula at 

completion of phase 1.

Birth weight<1500g

Exclusion Criteria: 

congenital abnormalities 

of the gastrointestinal 

tract, hepatitis, hepatic or 

biliary pathology, 

necrotizing enterocolitis 

confirmed before 

enrollment, or history of 

underlying disease or 

Start time: Infants 10 days of age

Duration: Infants 118 weeks

Arm 1: Control

Description: Non-supplemented premature, 

discharge, and term formula

Dose: Ad lib

Blinding: Not reported

Infant conditions

Pre-term birth 119 (100%)

Arm 2: Algal-DHA

Description: supplemented premature infant formula 

supplemented with DHA from algal oil

Manufacturer: Martek Biosciences

Dose: ad lib

DHA: 17mg/100kcal (0.33% by weight)

EPA: 0.1% by weight

AA: 34mg/100kcal (0.67% by weight)

Arm 3: Fish-DHA

Description: Premature infant formula supplemented 

with DHA from tuna fish oil

Manufacturer: Martek Biosciences

Dose: ad lib

DHA: 17mg DHA/100 kcal

AA: 34mg/100 kcal

Arm 4: Reference

Outcome: Bayley Scale of Infant 

Development II (Physical developmental 

index) (Unspecified)

Follow-up time: 118 weeks

Arm 1: Sample size 54; mean 83.0; SE (2)

Arm 2: Sample size 46; mean 88.0; SE (2)

Arm 3: Sample size 59; mean 88.0; SE (2)

Arm 4: Sample size 59; mean 98.0; SE (2)

151
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

congenital malformation 

likely to interfere with 

evaluation

Description: Breast fed term infants

Collins et al., 2015120

Study name: DINO

Study dates: 2001-2013

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Study Population: 

Preterm infants

Infants enrolled 657 

Infants completers 604

Infant age: median 30 

weeks gestational age 

28-31 weeks

Race of Mother: NR 

(100)

Inclusion Criteria: infants 

born at <33 weeks’ 

gestation from five 

Australian tertiary 

hospitals between 2001 

and 2005

Exclusion Criteria: a 

major congenital or 

chromosomal 

abnormality, multiple 

birth in which not all liveborn infants were eligible, 

enrollment in other trials 

of fatty acid 

supplementation, or if 

fish oil was 

contraindicated in the 

lactating mother

Start time: Infants within 5 days of 1st enteral 

feeding

Duration: Infants to expected due date

Arm 1: standard DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentrations of term formula fed infants

DHA: ___20 mg/kg/ day of DHA

Arm 2: High DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentration of breastmilk

DHA: ___50 mg/kg/ day of DHA

Outcome: Rey Auditory Verbal Learning 

Test: Delayed recall raw score (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 7.2; SD (3)

Arm 2: Sample size 291; mean 7.3; SD 

(3.5)

Outcome: Rey Auditory Verbal Learning 

Test: Delayed recognition correct words 

(Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 13.1; SD (3)

Arm 2: Sample size 291; mean 13.3; SD 

(2.6)

Outcome: Rey Auditory Verbal Learning 

Test: Total (trials 1-5) correct words 

(Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 34.8; SD 

(10.8)

Arm 2: Sample size 291; mean 34.4; SD 

(12.1)

Outcome: Rey Auditory Verbal Learning 

Test: Total intrusions (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 2.5; SD (4)

Arm 2: Sample size 291; mean 2.1; SD 

(3.5)

Outcome: Rey Auditory Verbal Learning 

Test: Total repetitions (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 3.7; SD 

(4.1)

Arm 2: Sample size 291; mean 4.0; SD 

(4.5)

Outcome: Rey Auditory Verbal Learning 

Test: Trial 1 correct words (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 4.3; SD (2)

Arm 2: Sample size 291; mean 4.4; SD (2)

Colombo et al., 2013124 Study Population: Inclusion Criteria: Start time: Infants Birth Outcome: Bayley PDI (Secondary)

152
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: Diamond

Study dates: 09/03/03-

09/25/05

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government, 

Manufacturer supplied 

product

Study follow-up: 18 

months-6 years

Original, same study, or 

follow-up studies: Birch, 

2010121; Drover, 2011122; 

Drover. 2012123; Currie, 

2015115

Healthy infants

Infants enrolled 159 

Infants completers 81

Pregnant age: 24.1 (5.1)

Race of Mother: White 

European (34.9) Black 

(63.9) Other 

race/ethnicity (1.2)

Healthy, full term 

formula-fed singleton 

infants, 37-42 weeks 

gestation, 2490-4200 g 

birth weight, born in 

Kansas City between 

9/3/03 and 9/25/05

Exclusion Criteria: 

Receipt of human milk 

within 24 h of 

randomization; maternal 

and newborn health 

conditions known to 

interfere with normal 

growth and development 

(e.g., intrauterine growth 

restriction) or with normal 

cognitive function (e.g., 

congenital anomalies or 

established genetic 

diagnoses associated 

with intellectual 

disability), poor formula 

intake, or intolerance to 

cow milk infant formula; 

mothers with physiciandocumented chronic 

illness (e.g., HIV, renal or 

hepatic disease, type 1 

or type 2 diabetes, 

alcoholism, or substance 

abuse)

Duration: Infants 12 months

Arm 1: 0.00%

Description: Control, no DHA or AA

Blinding: NR

Arm 2: 0.32%

Description: 0.32% DHA

DHA: 17mg/100 kcal

AA: 34 mg/100 kcal

Arm 3: 0.64%

DHA: 34mg/100 kcal

AA: 34 mg/100 kcal

Arm 4: 0.96%

DHA: 51mg/100 kcal

AA: 34 mg/100 kcal

Follow-up time: 18 months

Arm 1: Sample size 18; mean 99.0; SEM 

(5)

Arm 2: Sample size 21; mean 97.0; SEM 

(5)

Arm 3: Sample size 18; mean 97.0; SEM 

(5)

Arm 4: Sample size 24; mean 98.0; SEM 

(5)

Escolano-Margarit et al., 

2011130

Study name: NUHEAL

Study dates: 2001-2008

Study design: Trial 

randomized parallel

Study Population: 

Healthy pregnant women

Pregnant enrolled 315 

Pregnant completers 157

Infants enrolled 315 

Infants completers 148

Pregnant age: 31 (NR) 

Inclusion Criteria: 

singleton pregnancy, 

gestation 20 week at 

enrollment, and intention 

to deliver in one of the 

obstetrical centers

Exclusion Criteria: 

serious chronic illness 

(e.g., diabetes, hepatitis, 

Start time: Pregnant week 22 of pregnancy Infants 

NA

Duration: Pregnant until birth

Arm 1: placebo

Description: milk-based supplement

Brand name: Blemil Plus

Manufacturer: Ordesa Laboratorios, Barcelona, 

Spain)

Outcome: number considered normal on 

Hempel exam (Secondary)

Follow-up time: 5.5 years

Arm 1: 81/87 (93.0%)

Arm 2: 74/80 (93.0%)

Outcome: number considered normal on 

Towen exam (Secondary)

Follow-up time: 5.5 years

Arm 1: 48/69 (70.0%)

Arm 2: 55/79 (70.0%)

153
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: Germany, 

Spain, Hungary

Funding source / conflict: 

Manufacturer supplied 

product

Study follow-up: 5.5 

years

Original, same study, or 

follow-up studies: 

Campoy, 2011141.

18 to 41

Race of Mother: NR 

(100)

Baseline biomarker 

information: For 

newborns mean plasma 

DHA Placebo group

_x0007_6.9 Fish oil 

group 7.8 5-MHTF (folic 

acid) group 6.2 

_x0007_Fish oil + 5-

MHTF group _x0007_7.0

mean plasma AA

Placebo group 17.6 Fish 

oil group 16.8 5-MHTF 

(folic acid) group 17.3 

_x0007_Fish oil + 5-

MHTF group 16.4

or chronic enteric 

disease), use of FO 

supplements since the 

beginning of pregnancy 

or folate or vitamin B-12 

supplements after 

gestation week 16

Active ingredients: vitamins and minerals in amounts 

meeting the recommended intakes during the 

second half of pregnancy for European women

Dose: one daily dose of 15 g

Blinding: supplements were not distinguishable with 

respect to the appearance of the sachets or to their 

contents

Arm 2: fish oil

Description: fish oil in milk-based supplement

Manufacturer: Pronova Biocare, Lysaker, Norway

Active ingredients: vitamins and minerals in amounts 

meeting the recommended intakes during the 

second half of pregnancy for European women

Dose: one daily dose of 15 g

DHA: 500 mg

EPA: 100 mg

Arm 3: folic acid

Description: 400 _x0001_g 5-MTHF

Manufacturer: BASF, Ludwigshafen, Germany

Active ingredients: vitamins and minerals in amounts 

meeting the recommended intakes during the 

second half of pregnancy for European women

Dose: one dose of 15 g

Arm 4: folic acid + fish oil

Description: fish oil + 400 _x0001_g 5-MTHF

Manufacturer: BASF, Ludwigshafen, Germany

Active ingredients: vitamins and minerals in amounts 

meeting the recommended intakes during the 

second half of pregnancy for European women

Dose: one dose of 15 g

DHA: 500 mg

EPA: 100 mg

Fang et al., 2005137

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Study Population: 

Preterm infants

Infants enrolled 28 

Infants withdrawals 1 

Infants completers 27

Infant age: 1 week (mean 

Inclusion Criteria: (1) A 

gestational age at birth 

between 30 and 37 

weeks; (2) Normal 

fundus oculi; (3) 

Recruitment prior to 

commencement of 

feeding

Start time: Infants 1 week after birth

Duration: Infants 24 weeks

Arm 1: placebo

Description: infant formula based on the composition 

of human milk

Brand name: Neoangelac

Outcome: Bayley psychomotor 

development index (Primary)

Follow-up time: 12 months

Arm 1: Sample size 11; mean 86.7; SD 

(11.1)

Arm 2: Sample size 16; mean 98.0; SD 

(5.8)

Follow-up time: 6 months

154
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: Taiwan

Funding source / conflict: 

Manufacturer supplied 

product

gestation age 33 weeks) 

(0.5 week) NA

Race of Mother: NR 

(100)

Exclusion Criteria: (1) 

Breast feeding; (2) A 

maternal history of 

infection, diabetes 

mellitus, gestational 

diabetes mellitus, 

cocaine or alcohol abuse, 

systemic diseases or if 

intrauterine growth 

retardation had been 

diagnosed during 

pregnancy; (3) Major 

congenital abnormality; 

(4) Severe 

intraventricular 

hemorrhage > grade 2; 

(5) Cystic periventricular 

leukomalacia; (6) 

Retinopathy of 

prematurity stage 2; (7) 

Bronchopulmonary

dysplasia on radiographs 

or oxygen usage 28 

days; (8) Body weight 

less than the third 

percentile; (9) Surgical 

intervention for 

necrotizing enterocolitis 

(10) Mechanical 

ventilation after achieving 

enteral intake > 110 

kcal/kg per day; (11) A 5-

min Apgar score < 7; (12) 

Administration of blood 

transfusion, blood 

products, or parenteral 

lipids with DHA or AA.

Manufacturer: Multipower Enterprise Corporation

Dose: Babies were given more than 110 kcal/kg per 

day during the first 4 months and more than 70 

kcal/kg per day from 4 to 6 months

N-6 N-3: 10:1 linoleic:linolenic

Arm 2: Neoangelac Plus

Description: Neoangelac supplemented with Omega 

3

Brand name: Neoangelac Plus

Manufacturer: Multipower Enterprise Corporation

Dose: Babies were given more than 110 kcal/kg per 

day during the first 4 months and more than 70 

kcal/kg per day from 4 to 6 months

DHA: 0.05%

AA: 0.10%

Arm 1: Sample size 11; mean 95.4; SD 

(13.2)

Arm 2: Sample size 16; mean 102.2; SD 

(10.5)

van Goor et al., 201166

Study name: Groningen 

LCPUFA study

Study Population: 

Healthy infants

Pregnant enrolled 119

Inclusion Criteria: women 

with a first or second lowrisk singleton pregnancy, 

between the 14th and 

20th weeks of pregnancy

Start time: Pregnant 14th-20th week pregnancy 

Lactating 3 months after delivery Mothers 3 months 

after delivery Infants NR

Duration: Pregnant NR Lactating 33-39 weeks 

Outcome: Bayley psychomotor 

development index (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 91.7; SD 

(8.3)

155
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: 2004-2009

Study design: Trial

randomized parallel

Location: Netherlands

Funding source / conflict: 

Industry

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; van Goor, 201036

Infants enrolled 119 

Infants completers 114

Pregnant age: Placebo: 

32.7 DHA: 32.5

DHA+AA: 32.9 (Placebo: 

5.1 DHA: 4.4 DHA+AA: 

4.8)

Infant age: 18 months

Race of Mother: NR 

(100)

Exclusion Criteria: 

women with vegetarian 

or vegan diets; women 

with diabetes mellitus; 

birth complications

Mothers 33-39 weeks Infants NR

Arm 1: placebo

Description: Soy bean oil

Brand name: none

Arm 2: DHA

Description: DHA plus soy bean oil

Brand name: Marinol D40

Manufacturer: Lipid Nutrition B.V., Wormerveer, The 

Netherlands; AA:

Dose: 1 capsule DHA and 1 capsule soy bean oil 

once a day

ALA: 32 mg/d

DHA: 220 mg/d

EPA: 34 mg/d

Arm 3: DHA+AA

Description: DHA plus AA

Brand name: AA: no brand name

Manufacturer: Wuhan Alking Bioengeneering Co. 

Ltd., Wuhan, China

Dose: 2 capsules once a day

ALA: 7 mg/d

DHA: 220 mg/d

EPA: 36 mg/d

AA: 220 mg per capsule

Arm 2: Sample size 41; mean 95.8; SD 

(11.4)

Arm 3: Sample size 39; mean 92.4; SD 

(8.8)

Outcome: fluency score (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; median 10.0; range

Arm 2: Sample size 41; median 9.0; range

Arm 3: Sample size 39; median 10.0; range

Outcome: neurological optimality score 

(Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; median 47.5; range

Arm 2: Sample size 41; median 46.0; range

Arm 3: Sample size 39; median 48.0; range

Outcome: prevalence of complex minor 

neurological dysfunction (Unspecified)

Follow-up time: 18 months

Arm 1: 5/34 (14.7%)

Arm 2: 3/41 (7.3%)

Arm 3: 5/39 (12.8%)

Outcome: prevalence of normal 

neurological condition (Unspecified)

Follow-up time: 18 months

Arm 1: 20/34 (58.8%)

Arm 2: 24/41 (58.5%)

Arm 3: 28/39 (71.8%)

Outcome: prevalence of simple minor 

neurological dysfunction (Unspecified)

Follow-up time: 18 months

Arm 1: 9/34 (26.5%)

Arm 2: 14/41 (34.1%)

Arm 3: 6/39 (15.4%)

Gustafson et al., 201374

Study name: NR

Study dates: May 2009 -

July 2011

Study design: Trial 

randomized parallel

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 67 

Pregnant withdrawals 12 

Pregnant completers 52

Infants enrolled 44 

Infants completers 41

Inclusion Criteria: 

between 16–35.9 years 

of age and carrying a 

singleton pregnancy 

between the 12th and 

20th week of gestation

Exclusion Criteria: any 

serious health condition 

likely to affect the growth 

Start time: Pregnant 12-20 week gestation Infants 

birth

Duration: Pregnancy to birth

Arm 1: Placebo

Description: g 50% soy and 50% corn oil

Manufacturer: Martek Biosciences, now DSM 

Nutritional Products

Dose: 3 capsule a day each 500 mg

Outcome: Neonatal Behavior Assessment: 

autonomic (Primary)

Follow-up time: 7 days post-partum

Arm 1: Sample size 12; mean 14.83; SD 

(16.9)

Arm 2: Sample size 15; mean 18.13; SD 

(14.48)

t25=1.99, P=0.029

Outcome: Neonatal Behavior Assessment: 

156
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Pregnant age: placebo 

25.6+; DHA 25.5 

(placebo 4.8; DHA 4.3)

Race of Mother: White 

European (46.3) Black 

(37.3) Asian (3) Hispanic 

(13.4)

Baseline biomarker 

information: plasma DHA 

(wt% TFA) placebo 

group: 3.91 (3.15-4.21); 

DHA group: 3.94(3.39-

4.72) RBC DHA (wt%

TFA) placebo group 

4.30(3.99-5.03); DHA 

group 4.50 (3.73-5.44)

and development of the 

fetus or health of the 

mother including cancer, 

lupus, hepatitis, diabetes 

mellitus (Type1, Type 2 

or gestational) or 

HIV/AIDS at baseline or 

fetal cardiac structural or 

conduction defects. 

Women who selfreported illicit drug use or 

alcohol use during 

pregnancy and those 

with hypertension or BMI 

Z40 were excluded. 

Women who were taking 

more than 200 mg/day 

DHA in prenatal vitamins 

or over the counter 

supplements were 

excluded from

participation

Blinding: Only members of the investigational 

pharmacy knew the subject allocation. Participants 

and all members of the investigational team were 

blinded to the intervention assignment. Participants

were allocated to either group based on the simple 

randomization procedure using random numbers 

generated by SAS. All capsules were the same 

color, size, weight and the oils were orange-flavored 

to prevent investigator or subject bias.

Arm 2: algal oil as a source of DHA (200 mg of DHA 

per capsule for a total of 600 mg DHA/day)

Dose: 3 capsule of 200mg DHA total 600 mg

DHA: 200 mg * 3

motor (Primary)

Follow-up time: 7 days post-partum

Arm 1: Sample size 12; mean 23.08; SD 

(11.4)

Arm 2: Sample size 15; mean 26.07; SD 

(18.13)

t25=1.87, P=0.038)

Jensen et al., 2005136

Study name: Unnamed 

Trial B

Study dates: <2004

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government

Original, same study, or 

follow-up studies: 

Jensen, 2010135

Study Population: Breastfeeding women

Lactating enrolled 227 

Lactating completers 174

Infants enrolled 230 

Infants completers 177

Lactating enrolled 227 

Lactating completers 174

Lactating age: 31.5 years 

(5 years) 18-40

Infant age: birth (NA) NA

Race of Mother: NR

Inclusion Criteria: 

maternal age between 18 

and 40 y, infant 

gestational age >=37 wk, 

infant birth weight 

between 2500 and 4200 

g

Exclusion Criteria: 

chronic maternal 

disorders, major 

congenital anomalies, 

obvious gastrointestinal 

or metabolic disorders of 

the infant

Start time: Lactating 5 days after delivery Infants 5 

days after birth

Duration: Lactating 4 months Infants 4 months

Arm 1: placebo

Description: capsule containing corn & soy oil

Manufacturer: Martek Biosciences

Purity Data: 15% saturated fatty acids, 23.5% 

monounsaturated fatty acids, 56.3% linoleic acid 

(18: 2n_x0001_6), and 3.9% _x0001_-linolenic acid 

(18:3n_x0001_3)

Dose: 1 capsule

Blinding: identical capsules

ALA: 56.3% linoleic acid (18: 2n_x0001_6), 3.9% 

_x0001_-linolenic acid (18:3n_x0001_3)

Total N-3: 57.2%

Arm 2: DHA algal triacylglycerol (DHASCO)

Description: DHA capsule

Brand name: DHASCO

Outcome: Bayley Physical Developmental 

Index (Primary)

Follow-up time: 30 months

Arm 1: Sample size 65; mean 108.4; SD 

(13.8)

Arm 2: Sample size 68; mean 116.8; SD 

(15.2)

Outcome: Clinical Linguistic and Auditory 

Milestone Scale (CLAMS) (Secondary)

Follow-up time: 30 months

Arm 1: Sample size 72; mean 106.6; SD 

(14.9)

Arm 2: Sample size 75; mean 106.8; SD 

(15.2)

Follow-up time: 12 months

Arm 1: Sample size 76; mean 102.5; SD 

(13.2)

Arm 2: Sample size 86; mean 100.6; SD 

(14.6)

Outcome: Clinical adaptive test 

development quotient (CAT DQ) 

157
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Manufacturer: Martek Biosciences

Purity Data: 44%saturatedfattyacids, 13.6% 

monounsaturated fatty acids, 0.8% linoleic acid 

(18:2n _x0001_ 6), and 41.7% DHA (22:6n-3) by 

weight

Dose: 1 capsule

ALA: 0.8% (18:2n-6)

DHA: 200 mg, 41.7% (22:6n-3)

Total N-3: 42.5%

(Secondary)

Follow-up time: 30 months

Arm 1: Sample size 72; mean 98.3; SD 

(8.7)

Arm 2: Sample size 75; mean 98.1; SD (9)

Follow-up time: 12 months

Arm 1: Sample size 76; mean 110.0; SD 

(10.8)

Arm 2: Sample size 86; mean 109.0; SD 

(10)

Outcome: Gesell Gross Motor development 

quotient (DQ) (Secondary)

Follow-up time: 30 months

Arm 1: Sample size 72; mean 102.4; SD 

(10.2)

Arm 2: Sample size 75; mean 100.8; SD 

(11.4)

Follow-up time: 12 months

Arm 1: Sample size 76; mean 99.5; SD 

(13.3)

Arm 2: Sample size 86; mean 101.8; SD 

(13.8)

Jensen et al., 2010135

Study name: Unnamed 

Trial B

Study dates: NR (<2010)

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government

Study follow-up: 5 years

Original, same study, or 

follow-up studies: 

Jensen, 2005136

Study Population: Breastfeeding women

Lactating enrolled 227

Infants enrolled 230 

Infants completers 119

Lactating enrolled 227

Lactating age: 31.5 years 

(5 years) 18 to 40

Infant age: birth (NA) NA

Race of Mother: NR (NR)

Inclusion Criteria: 

maternal age between 18 

and 40 y, infant 

gestational age >=37 wk, 

infant birth weight 

between 2500 and 4200 

g

Exclusion Criteria: 

chronic maternal 

disorders, major 

congenital anomalies, 

obvious gastrointestinal 

or metabolic disorders of 

the infant

Start time: Infants birth

Duration: Infants 4 months

Arm 1: placebo

Description: capsule containing corn & soy oil

Manufacturer: Martek Biosciences

Purity Data: 50:50 mixture of soy and corn oils 

consisting, by weight, of 15% saturated fatty acids, 

23.5% monounsaturated fatty acids, 56.3% linoleic 

acid (18:2 n-6) and 3.9% a-linolenic acid (18:3 n-3)

Dose: 1 capsule

Blinding: capsules were identical

ALA: 3.9%

Arm 2: omega 3 capsule

Description: high-DHA algal triglyceride capsule

Brand name: DHASCO

Manufacturer: Martek

Purity Data: by weight, 44% saturated fatty acids, 

13.6% monounsaturated fatty acids, 0.8% linoleic 

Outcome: Development test of Visual-Motor 

Integration (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 11.8; SD 

(1.8)

Arm 2: Sample size 57; mean 11.6; SD 

(1.9)

Outcome: Kaufman Assessment Battery for 

Children: hand movement (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 9.02; SD 

(2.84)

Arm 2: Sample size 59; mean 8.39; SD 

(2.55)

Outcome: McCarthy (leg coordination) 

(Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 10.7; SD 

(1.9)

Arm 2: Sample size 59; mean 10.6; SD 

(1.5)

158
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

acid (18:2n-6) and 41.7% DHA (22:6n-3)

Dose: 1 capsule

DHA: 200 mg

Outcome: Purdue pegboard test (dominant 

hand) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 9.8; SD (2.7)

Arm 2: Sample size 59; mean 9.6; SD (1.7)

Outcome: Purdue pegboard test (nondominant hand) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 8.9; SD (2.7)

Arm 2: Sample size 59; mean 8.9; SD (1.6)

Judge et al., 201240

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Multiple foundations and 

Societies

Study Population: 

Healthy pregnant women

Pregnant enrolled 48

Pregnant age: Treatment 

group: 23.93 Placebo: 

23.86 (Treatment group: 

4.32 Placebo: 4.53)

Race of Mother: White 

European (Treatment: 

11.1%, Placebo: 0%) 

Black (Treatment: 18.5%, 

Placebo: 4.8%) Asian 

(Treatment: 3.7%, 

Placebo: 0%) Hispanic 

(Treatment: 59.3%, 

Placebo: 80.9%) NR 

(Treatment: 7.4%, 3 

(14.3%))

Baseline biomarker 

information: Maternal 

plasma phospholipid (PL) 

fatty acids (FA): 2.85 +/-

.87 % in treatment group 

and 2.95 +/- .91% in 

placebo group. Infant 

RBC PL FA: 7.55 +/-

1.61% in treatment group 

and 7.07 +/- 1.25% in 

placebo group.

Inclusion Criteria: The 

women were either 

primiparous or had not 

been pregnant for the 

past 2 years.

Exclusion Criteria: parity 

greater than 5, history of 

chronic hypertension, 

hyperlipidemia, renal, 

liver or heart disease, 

thyroid disorder, multiple 

gestations or pregnancy 

induced complications 

including hypertension, 

preeclampsia or preterm 

labor, smoking and 

psychiatric disorders. 

Women who were 

treated during labor with 

analgesics such as 

Stadol (butorphanol 

tartrate), that may cause 

infant respiratory distress 

were also excluded. In 

addition, infants born 

preterm and infants with 

less than 4 h of crib time 

in the first and second 

days postpartum were 

excluded from the 

analyses.

Start time: Pregnant 24 weeks gestation

Duration: Pregnant until delivery

Arm 1: Placebo

Description: Control group

Manufacturer: Nestec, S.A., Switzerland

Blinding: The total macronutrient content was the 

same in both the DHA and placebo bars with respect 

to carbohydrate, protein and fat, how- ever, the DHA 

bars contained fish oil (300 mg DHA) and the 

placebo bars contained corn oil.

Arm 2: DHA

Description: Intervention group

Manufacturer: Nestec, S.A., Switzerland

Dose: average of 5 bars weekly

DHA: 300 mg

EPA-DHA: 8:1 ratio of DHA to EPA

Outcome: Infant sleep: Active Sleep (AS, 

%) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 51.81; SD 

(10.43)

Arm 2: Sample size 27; mean 49.39; SD 

(10.32)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 51.7; SD 

(11.13)

Arm 2: Sample size 24; mean 51.57; SD 

(14.54)

Outcome: Infant sleep: Active–Quiet Sleep 

Transition (AQST, %) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 0.53; SD 

(0.23)

Arm 2: Sample size 27; mean 0.59; SD 

(0.37)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 0.41; SD 

(0.27)

Arm 2: Sample size 24; mean 0.47; SD 

(0.3)

Outcome: Infant sleep: Arousals in AS 

(Ar/AS) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 20.41; SD 

(4.39)

Arm 2: Sample size 27; mean 17.41; SD 

(4.71)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 24.67; SD 

159
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(6.82)

Arm 2: Sample size 24; mean 24.04; SD 

(7.04)

Outcome: Infant sleep: Arousals in QS 

(Ar/QS) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 5.89; SD 

(6.01)

Arm 2: Sample size 27; mean 2.7; SD 

(2.65)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 5.44; SD 

(4.07)

Arm 2: Sample size 24; mean 3.55; SD 

(3.98)

Outcome: Infant sleep: Mean Sleep Period 

(LSP, min) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 185.95; SD 

(79.75)

Arm 2: Sample size 27; mean 228.19; SD 

(104.89)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 202.6; SD 

(123.18)

Arm 2: Sample size 24; mean 190.75; SD 

(102.75)

Outcome: Infant sleep: Mean Sleep Period 

(MSP, min) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 46.09; SD 

(17.6)

Arm 2: Sample size 27; mean 48.03; SD 

(17.55)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 48.85; SD 

(29.99)

Arm 2: Sample size 24; mean 48.67; SD 

(21.18)

Outcome: Infant sleep: Wakefulness (W, %) 

(Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 27.59; SD 

(11.54)

160
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 27; mean 29.57; SD 

(13.56)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 28.95; SD 

(12.14)

Arm 2: Sample size 24; mean 30.71; SD 

(18.92)

Outcome: Infant sleep: quiet sleep (QS,%) 

(Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 15.14; SD 

(4.26)

Arm 2: Sample size 27; mean 15.88; SD 

(5.1)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 13.7; SD 

(4.76)

Arm 2: Sample size 24; mean 12.7; SD 

(5.85)

Outcome: Infant sleep: Active sleep bout 

length (ASBL, min) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 28.93; SD 

(9.67)

Arm 2: Sample size 27; mean 29.0; SD 

(7.07)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 29.81; SD 

(12.5)

Arm 2: Sample size 24; mean 30.48; SD 

(9.14)

Outcome: Infant sleep: Active/Quiet Sleep 

Ratio(AS:QS) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 3.83; SD 

(2.15)

Arm 2: Sample size 27; mean 3.38; SD 

(1.1)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 4.56; SD 

(3.13)

Arm 2: Sample size 24; mean 4.46; SD 

(2.14)

Outcome: Infant sleep: Quiet sleep bout 

161
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

length (QSBL, min) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 21.81; SD 

(4.93)

Arm 2: Sample size 27; mean 22.74; SD 

(5.73)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 20.59; SD 

(4.98)

Arm 2: Sample size 24; mean 18.75; SD 

(6.86)

Outcome: Infant sleep: Sleep–Wake 

Transition (T, %) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 4.92; SD 

(1.48)

Arm 2: Sample size 27; mean 4.57; SD 

(1.33)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 5.23; SD 

(1.88)

Arm 2: Sample size 24; mean 4.5; SD 

(1.39)

Outcome: Infant sleep: Sleep–Wake 

Transition (T, %) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 4.92; SD 

(1.48)

Arm 2: Sample size 27; mean 4.57; SD 

(1.33)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 5.23; SD 

(1.88)

Arm 2: Sample size 24; mean 4.5; SD 

(1.39)

Makrides et al., 2009116

Study name: DINO

Study dates: Enrollment 

April 2001 to October 

2005

Study Population: 

Preterm infants Breastfeeding women

Pregnant enrolled 545

Infants enrolled 657 

Infants completers 614

Inclusion Criteria: infants 

born at < 33 wk of 

gestation

Exclusion Criteria: Infants 

born with major 

congenital or 

chromosomal 

Start time: Infants 4 days after birth

Duration: Infants until infants reached their 

"expected" date of delivery

Arm 1: Placebo

Description: Soy oil capsules or regular preterm 

formula

Outcome: Bayley psychomotor 

development index (Secondary)

Follow-up time: 18 months

Arm 1: Sample size 335; mean 92.1; SD 

(16.3)

Arm 2: Sample size 322; mean 93.1; SD 

(16.1)

162
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer

supplied product, Some 

authors serve on 

scientific advisory boards 

for corporations, Some 

authors have received 

research funding from 

infant formula 

manufacturers

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Lactating age: 30 years 

(5.5 years) NR

Infant age: 4 days after 

birth (29 weeks 

gestation) 2 to 6 days 

after birth

Race of Mother: White 

European (90%)

abnormalities, lactating 

women for whom tuna oil 

was 

contraindicated(women 

with bleeding disorders 

or taking anticoagulants)

Manufacturer: Clover Corporation

Dose: six 500-mg soy oil capsules

Blinding: all capsules were similar in size, shape, 

and color

Maternal conditions

Infant conditions

Current smoker 25.1% during pregnancy

Pre-term birth 100%

Low birth weight 44.5%

Other conditions 1 SGA 18.6%

Arm 2: tuna oil capsules

Description: DHA-rich tuna oil capsules or high-DHA 

formula

Manufacturer: Clover Corporation

Dose: 6 500 mg capsules

Maternal conditions

Infant conditions

DHA: Capsules: Intended to achieve breast milk 

concentration of 1.0%.Formula: 1.0%

AA: Capsules: not intended to alter AA levels. 

Formula: 0.6%

Current smoker 25.6% during pregnancy

Pre-term birth 100%

Low birth weight 45.7%

Other conditions 1 SGA 18.9%

Meldrum et al., 2012140

Study name: Infant 

FishOil Supplementation 

Study (IFOS)

Study dates: Recruitment 

from June 2005 through 

October 2008

Study design: Trial 

randomized parallel

Location: Australia

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 420

Infants enrolled 420 

Infants completers 287

Mother age: NR (NR) NR

Infant age: Birth (NA) NA

Race of Mother: NR

Inclusion Criteria: allergic 

pregnant women were 

recruited as their infants 

are at a higher risk of 

developing allergic 

disease. Maternal atopy 

was defined by at least 

one positive skin prick 

test to at least one of a 

defined panel of 

allergens.

Exclusion Criteria: 

maternal smoking, a preexisting medical 

Start time: Infants birth

Duration: Infants 6 months

Arm 1: placebo

Description: olive oil capsule

Manufacturer: Ocean Nutrition, Canada

Active ingredients: 66·6 % n-9 oleic acid

Viability: he composition was regularly tested by an 

independent laboratory during the trial

Dose: one 650 mg capsule

Blinding: image and scent matched

Arm 2: fish oil capsule

Manufacturer: Ocean Nutrition, Canada

Outcome: Categorical Child Behavior 

Checklist: Sleep problems - number with tscore>59 (Primary)

Follow-up time: 18 months

Arm 1: 56/144 (39.0%)

Arm 2: 54/125 (43.5%)

163
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / conflict: 

Government, None, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: D'Vaz, 

2012142

Baseline biomarker 

information: Cord blood 

data Fish oil group LA, 

linoleic acid 3.71 ALA, alinolenic acid 0·496 EPA

0·334 DHA 7·36 DPA 

0·700 AA, arachidonic 

acid 15·76 Olive oil group 

LA, linoleic acid 3.81 

ALA, a-linolenic acid 

0·513 EPA 0·308 DHA 

7·44 DPA 0·673 AA, 

arachidonic acid 15·54

Baseline Omega-3 

intake: From maternal 

food questionnaire, while 

pregnant Fish oil group 

LA, linoleic acid 10·59 

ALA, a-linolenic acid 0·87 

EPA 0·07 DHA 0·09 AA, 

arachidonic acid 0·87

Olive oil group LA, 

linoleic acid 9·90 ALA, alinolenic acid 0·89 EPA

0.06 DHA 0·08 AA, 

arachidonic acid 0·84

condition or high-risk 

pregnancy, more than 

three fish meals 

consumed per week or 

fish oil intake during 

pregnancy in excess of 

1000 mg/d, preterm 

delivery, and infants with 

significant congenital 

abnormalities or medical 

conditions.

Viability: he composition was regularly tested by an 

independent laboratory during the trial.

Dose: one 650 mg capsule

DHA: 280 mg

EPA: 110 mg

Meldrum et al., 201551

Study name: Dunstan

Study dates: 10/2012-

12/2013 for 12-year 

followup

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Multiple foundations and 

Societies, None

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 98 

Pregnant completers 82

Infants enrolled 82 

Infants completers 50

Pregnant age: Fish oil 

30.9 Control 32.6 (Fish 

oil: 3.7 Control: 3.6)

Infant age: NR (NR)

Inclusion Criteria: 

Pregnant women with 

allergies

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked, had medical 

problems, a complicated 

pregnancy, seafood 

allergy, or if their normal 

dietary intake exceeded 

two meals of fish per 

week. Children were 

excluded from the study 

if they were born before 

Start time: Pregnant 20 weeks gestation

Duration: Pregnant to birth

Arm 1: Placebo

Description: Olive oil capsules

Manufacturer: Pan Laboratories

Dose: 4 1g capsules per day

Blinding: Randomization and allocation of capsules 

was carried out in a blinded manner, and capsules in 

the two groups were image matched

Arm 2: Fish oil

Manufacturer: Ocean Nutrition

Active ingredients: 3–4 mg/g oil a-tocopherol 

(vitamin E)

Outcome: Beery-Buktenica Development 

Test of Visual-Motor Integration (TVMI) 

(Secondary)

Follow-up time: 12 years

Arm 1: Sample size 23; mean 103.2; SD 

(9.9)

Arm 2: Sample size 24; mean 104.4; SD (9)

164
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 12 years

Original, same study, or 

follow-up studies: 

Dunstan, 200350; 

Dunstan, 200844;

Race of Mother: NR 

(100)

36 weeks’ gestation or 

with major disease (to 

avoid the confounding 

effects on immune 

response) or if cord blood 

was not collected

Dose: 4 1g capsules per day

DHA: 2.2g

EPA: 1.1g

Mulder et al., 201475

Study name: NR

Study dates: 2004 to 

2008

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Government

Study follow-up: 18 

months

Study Population: 

Healthy pregnant women

Pregnant enrolled 271 

Pregnant completers 200

Pregnant age: 33 years 

(4 years) NR

Race of Mother: White 

European (73%) Other 

race/ethnicity (27%)

Baseline biomarker 

information: maternal 

RBC 

Phusphatidylethanolamin

e DHA: placebo group 

6.25 (1.60) g/ 100g DHA 

group 6.36 (1.62) g/ 100g

Baseline Omega-3 

intake: median (2.5 to 

97.5th percentile range) 

intake: placebo group

80.0 (0.00-334) mg/day, 

DHA group 90.0 (6.00-

472) mg/d

Inclusion Criteria: at least 

16 wk gestation, not 

taking any lipid or fatty 

acid supplement, and 

were expected to deliver 

one infant at full-term 

gestation, with no 

maternal or fetal 

complications

Exclusion Criteria: NR

Start time: Pregnant 16 weeks gestation

Duration: Pregnant Until birth

Arm 1: placebo

Description: corn and soybean oil supplement

Manufacturer: Martek Biosciences

Blinding: supplements were identical in appearance, 

contained an orange flavor mask

Arm 2: DHA supplement

Description: algal oil DHA supplement

Manufacturer: Martek Biosciences

DHA: 400 mg

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

fine motor (Unspecified)

Follow-up time: 18 months

Arm 1: 20/80 (25.6%)

Arm 2: 22/74 (30.1%)

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

gross motor (Unspecified)

Follow-up time: 18 months

Arm 1: 21/80 (26.6%)

Arm 2: 22/74 (29.7%)

Ramakrishnan et al., 

201561

Study name: POSGRAD

Study dates: 2005-2009

Study design: Trial 

Study Population: 

Healthy pregnant women

Pregnant enrolled 1094 

Pregnant completers 968

Infants enrolled 973 

Infants completers 730

Inclusion Criteria: 

Women who were in 

gestation week 18–22, 

age 18–35 years, 

planned to deliver at the 

IMSS General Hospital 

and to remain in the area 

for the next 2 years, and 

Start time: Pregnant 18-22 weeks gestation

Duration: Pregnant 18-22 weeks gestation until 

delivery

Arm 1: Control

Description: Corn and soy oils with no added 

antioxidants

Outcome: Bayley PDI (Primary)

Follow-up time: 18 months

Arm 1: Sample size 365; mean 93.3; SD 

(9.8)

Arm 2: Sample size 365; mean 93.0; SD 

(8.9)

165
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, None, 

March of Dimes

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Stein, 201233; ImhoffKunsch, 201158; 

Escamilla-Nunez, 201459;

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561

Pregnant age: Placebo: 

26.3 Intervention: 26.5 

(Placebo: 4.6 

Intervention: 4.9)

Infant age: Placebo: 20.5 

weeks gestation 

Intervention: 20.6 weeks 

gestation (Placebo: 2.1 

weeks Intervention: 2.0 

weeks)

Race of Mother: NR (NR)

Baseline Omega-3 

intake: From original 

study ref 3364 mg/day for 

all: LA: 17,846 in 

controls, 17,645 in DHA 

AA: 137 in controls, 140 

in DHA ALA: 1,488 in 

controls, 1,477 in DHA 

EPA: 18 in controls, 18 in 

DHA DHA: 54 in controls, 

56 in DHA

planned predominant 

breastfeeding for at least 

3 months

Exclusion Criteria: High 

risk pregnancy, had any 

lipid 

metabolism/absorption 

conditions, regularly took 

DHA or fish oil 

supplements, or used 

certain chronic 

medications (such as 

antiepileptic drugs)

Dose: 2 capsules/day

Blinding: Similar in appearance and taste to the DHA 

capsules

Arm 2: Intervention

Description: Algal-sourced DHA capsule

Manufacturer: Martek Biosciences

Dose: 2 capsules/day

DHA: 200 mg * 2 = 400 mg/d

Stein et al., 201233

Study name: POSGRAD

Study dates: Feb 2005-

Feb 2007

Study design: Trial 

randomized parallel

Location: NR

Funding source / conflict: 

Government

Original, same study, or 

follow-up studies: 

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 1094 

Pregnant withdrawals 63 

Pregnant completers 900

Pregnant age: 26.3 (4.6-

4.8)

Infant age: 39.1 (1.7-1.8)

Race of Mother: NR (NR)

Inclusion Criteria: 

Singleton live births 

without congenital 

anomalies

Exclusion Criteria: 3364: 

high risk pregnancy, 

(history and prevalence 

of pregnancy 

complications, including 

abruption placentae, 

preeclampsia, 

pregnancy-induced 

hypertension, any 

serious bleeding episode 

in the current pregnancy, 

and physician referral); 

Start time: Pregnant 18-22 wk

Duration: Pregnant to birth

Arm 1: Placebo

Description: A mixture of corn and soy oil

Manufacturer: Martek Biosciences

Blinding: "Participants and members of the study 

team were unaware of the treatment scheme 

throughout the intervention period of the study"

Arm 2: DHA

Description: DHA 400 mg/d

Manufacturer: Martek Biosciences

Dose: 2 capsule per day

DHA: 2*200mg

Outcome: auditory evoked responses: 

latency 1 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 1.63; SD 

(0.14)

Arm 2: Sample size 372; mean 1.62; SD 

(0.16)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 1.58; SD 

(0.15)

Arm 2: Sample size 330; mean 1.58; SD 

(0.15)

Outcome: auditory evoked responses: 

latency 1-3 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 2.57; SD 

(0.36)

166
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Ramakrishnan, 201032; 

Imhoff-Kunsch, 201158; 

Escamilla-Nunez, 201459;

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561

lipid metabolism or 

absorption disorders, regular intake of fish oil 

or DHA supplement, or 

chronic use of certain 

medication(e.g. epilepsy 

medications)

Arm 2: Sample size 372; mean 2.56; SD 

(0.27)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 2.44; SD 

(0.28)

Arm 2: Sample size 330; mean 2.45; SD 

(0.28)

Outcome: auditory evoked responses: 

latency 1-5 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 4.93; SD 

(0.36)

Arm 2: Sample size 372; mean 4.91; SD 

(0.39)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 4.75; SD 

(0.39)

Arm 2: Sample size 330; mean 4.72; SD 

(0.39)

Outcome: auditory evoked responses: 

latency 3 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 4.19; SD 

(0.33)

Arm 2: Sample size 372; mean 4.18; SD 

(0.32)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 4.02; SD 

(0.32)

Arm 2: Sample size 330; mean 4.03; SD 

(0.33)

Outcome: auditory evoked responses: 

latency 3-5 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 2.37; SD 

(0.3)

Arm 2: Sample size 372; mean 2.37; SD 

(0.34)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 2.31; SD 

(0.35)

Arm 2: Sample size 330; mean 2.28; SD 

(0.33)

Outcome: auditory evoked responses: 

167
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

latency 5 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 6.55; SD 

(0.42)

Arm 2: Sample size 372; mean 6.52; SD 

(0.48)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 6.33; SD 

(0.4)

Arm 2: Sample size 330; mean 6.29; SD 

(0.42)

Tofail et al., 200677

Study name: NR

Study dates: Enrollment 

January to March 2000

Study design: Trial 

randomized parallel

Location: Bangladesh

Funding source / conflict: 

Government

Study follow-up: 10 

months

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 400 

Pregnant completers 151

Pregnant age: 22.7 years 

(4.35 years) NR

Race of Mother: Asian 

(100%)

Inclusion Criteria: seems 

as if all pregnant women 

at 25 weeks gestation 

were enrolled, no 

inclusion criteria 

specified

Exclusion Criteria: NR

Start time: Pregnant 25 weeks gestation

Duration: Pregnant until birth

Arm 1: placebo

Description: soy oil capsule

Dose: 4 one gram capsules per day

Blinding: capsules were identical in appearance

Other dose 1: LNA 0.27 g

Other dose 2: linoleic acid 2.25 g

Arm 2: DHA supplement

Description: fish oil capsules

Dose: 4 one gram capsules per day

DHA: 1.2 g

EPA: 1.8 g

Outcome: Bayley Scale of Infant 

Development (Psychomotor developmental 

index) (Unspecified)

Follow-up time: 10 months

Arm 1: Sample size 124; mean 100.5; SD 

(10.1)

Arm 2: Sample size 125; mean 101.7; SD 

(10.9)

Unay et al., 2004138

Study name: NR

Study dates: 2000-2001

Study design: Trial 

randomized parallel

Location: Turkey

Funding source / conflict: 

NR

Study Population: 

Healthy infants

Infants enrolled 54 

Infants completers 44

Infant age: NR (term)

Race of Mother: NR (NR)

Inclusion Criteria: 

healthy, full term 

newborns of appropriate 

size for gestational age, 

who were not going to be 

breast fed because that 

was the mother’s wish or 

because of maternal 

illness or medication 

incompatible with breast 

feeding just after birth

Exclusion Criteria: 

Perinatal asphyxia, 

central nervous system 

Start time: Infants week 1

Duration: Infants 16 weeks

Arm 1: Formula B

Description: Infant formula without added DHA

Brand name: Nutrilon I

Manufacturer: NV Nutricia Netherlands

Active ingredients: Linoleic acid 11.2gm/100gm fat

ALA: 2.2g/100g fat

AA: Trace

Arm 2: Formula A

Description: DHA-containing formula

Brand name: Farley's First Milk

Outcome: brainstem auditory evoked 

potentials: interpeak latency I-III 

(Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.25; SD (0.14)

Arm 2: Sample size 22; mean decrease 

0.34; SD (0.16)

Outcome: brainstem auditory evoked 

potentials: interpeak latency I-V 

(Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.33; SD (0.16)

Arm 2: Sample size 22; mean decrease 

168
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

infection, congenital 

malformation, or 

significant 

hyperbilirubinaemia

Manufacturer: HJ Heinz UK

Blinding: not reported

ALA: 1.2g/100gm

DHA: 0.5g/100gm

AA: Trace

Arm 3: Human milk

Description: Breast milk

Active ingredients: Linoleic acid: 10.85 gm/100gm 

fat

ALA: 1.03gm/100g fat

DHA: 0.25 gm/100gm fat

AA: 0.46 gm/100g fat

0.47; SD (0.2)

Outcome: brainstem auditory evoked 

potentials: interpeak latency III-V 

(Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.08; SD (0.07)

Arm 2: Sample size 22; mean decrease 

0.14; SD (0.1)

Outcome: brainstem auditory evoked 

potentials: wave I (Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.27; SD (0.14)

Arm 2: Sample size 22; mean decrease 

0.35; SD (0.13)

Outcome: brainstem auditory evoked 

potentials: wave III (Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.52; SD (0.15)

Arm 2: Sample size 22; mean decrease 

0.69; SD (0.16)

Outcome: brainstem auditory evoked 

potentials: wave V (Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.6; SD (0.11)

Arm 2: Sample size 22; mean decrease 

0.83; SD (0.18)

169
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

de Jong et al., 201064

Study name: Groningen 

LCPUFA study

Study dates: 1997-2008

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Government

Study follow-up: 9 years

Original, same study, or

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201265; van Goor, 

201036; van Goor, 201166

Study Population: 

Healthy infants

Infants enrolled 474 

Infants completers 341

Infant age: Gestational 

age 39.6 wk (1.3 weeks) 

NR

Race of Mother: White 

European (100)

Inclusion Criteria: healthy 

term infants

Exclusion Criteria: Infants 

who had a congenital 

disorder that interfered 

with adequate functioning 

in daily life, infants from 

multiple births, infants 

whose mothers did not 

have mastery of the 

Dutch language or 

suffered from significant 

illness or disability, 

adopted and foster 

infants, and formula-fed 

infants who had received 

human milk for >5 d.

Start time: Infants birth

Duration: NR

Arm 1: control group

Description: standard formula

Manufacturer: Zoetermeer, Netherlands

Active ingredients: linoleic acid (11mol%); ALA 1.27 

mol%

Blinding: NR

Arm 2: Omega 3 group

Description: LCPUFA formula

Brand name: Nutrilon Premium

Manufacturer: Nutricia, Zoetermeer, The 

Netherlands

Dose: NR

DHA: 0·30 % (by weight)

AA: 0·45 % (by weight)

Arm 3: Breast fed group

Description: Breast feeding only - no formula

Outcome: Touwen examination: 

neurologically normal (Unspecified)

Follow-up time: 9 years

Arm 1: 56/123 (46.0%)

Arm 2: 44/91 (48.0%)

van Goor et al., 201036

Study name: Groningen 

LCPUFA study

Study dates: Enrollment 

from December 2004 

until December 2006

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Industry, Government

Study follow-up: 12 

weeks

Study Population: 

Healthy pregnant women 

Breast-feeding women

Pregnant enrolled 183 

Pregnant completers 125

Infants completers 119

Pregnant age: 32 years 

(5 years)

Infant age: 14 to 20 

weeks gestation

Race of Mother: NR 

(100)

Inclusion Criteria: healthy 

women with a first or 

second low-risk singleton 

pregnancy

Exclusion Criteria: 

women with vegetarian 

or vegan diets and 

women with diabetes 

mellitus

Start time: Pregnant 14 to 20 weeks gestation 

Infants 14 to 20 weeks gestation

Duration: Pregnant until 3 months after delivery 

Infants until 3 months of age

Arm 1: placebo

Description: soybean oil capsule

Manufacturer: Wuhan Alking Bioengineering

Active ingredients: standard dose vitamins and 

minerals

Dose: 2 capsules

Maternal conditions

ALA: 60 mg

DHA: 0

EPA: 0

AA: 0

Other dose 1: LA 535 mg

Current smoker 2%

Outcome: general movements: number 

definitely abnormal (Secondary)

Follow-up time: 12 weeks

Arm 1: 0/36 (0.0%)

Arm 2: 1/42 (2.38%)

Arm 3: 0/41 (0.0%)

Follow-up time: 2 weeks

Arm 1: 1/36 (2.78%)

Arm 2: 0/42 (0.0%)

Arm 3: 0/41 (0.0%)

Outcome: general movements: number 

mildly abnormal (Secondary)

Follow-up time: 12 weeks

Arm 1: 11/36 (30.56%)

Arm 2: 25/42 (59.52%)

Arm 3: 14/41 (34.15%)

Follow-up time: 2 weeks

Arm 1: 11/36 (30.56%)

Arm 2: 20/42 (47.62%)

Arm 3: 15/41 (36.59%)

170
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; van Goor, 201166

Arm 2: DHA group

Description: DHA fish oil capsule

Manufacturer: Wuhan Alking Bioengineering

Active ingredients: standard dose vitamins and 

minerals

Dose: 2 capsules

Maternal conditions

ALA: 32 mg

DHA: 220 mg

EPA: 34 mg

AA: 15 mg

Other dose 2: LA 274 mg

Current smoker 2%

Arm 3: DHA + AA group

Description: DHA + AA capsule

Brand name: Marinol D40

Manufacturer: Lipid Nutrition B.V., Wormerveer, The 

Netherlands

Active ingredients: standard dose vitamins and 

minerals

Dose: 2 capsules

Maternal conditions

ALA: 7 mg

DHA: 220 mg

EPA: 36 mg

AA: 220 mg

Other dose 2: LA 46 mg

Current smoker 3%

Outcome: general movements: number 

normal optimal (Secondary)

Follow-up time: 12 weeks

Arm 1: 2/36 (5.56%)

Arm 2: 0/42 (0.0%)

Arm 3: 1/41 (2.44%)

Follow-up time: 2 weeks

Arm 1: 1/36 (2.78%)

Arm 2: 0/42 (0.0%)

Arm 3: 1/41 (2.44%)

Outcome: general movements: number 

normal suboptimal (Secondary)

Follow-up time: 12 weeks

Arm 1: 23/36 (63.89%)

Arm 2: 16/42 (38.1%)

Arm 3: 26/41 (63.41%)

Follow-up time: 2 weeks

Arm 1: 19/36 (52.78%)

Arm 2: 17/42 (40.48%)

Arm 3: 22/41 (53.66%)

Outcome: neonatal neurological 

classification: number definitely abnormal 

(Secondary)

Follow-up time: 2 weeks

Arm 1: 0/36 (0.0%)

Arm 2: 0/42 (0.0%)

Arm 3: 0/41 (0.0%)

Outcome: neonatal neurological 

classification: number mildly abnormal 

(Secondary)

Follow-up time: 2 weeks

Arm 1: 7/36 (19.44%)

Arm 2: 6/42 (14.29%)

Arm 3: 8/41 (19.51%)

Outcome: neonatal neurological 

classification: number normal (Secondary)

Follow-up time: 2 weeks

Arm 1: 28/36 (77.78%)

Arm 2: 35/42 (83.33%)

Arm 3: 33/41 (80.49%)

171
Table 15. Observational studies for neurological development

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Bakker, et al., 2009134

Outcome domain: Neurological

Study dates: 12/90-1/94

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Government

Follow-up: 7 years

Original, same study, or follow-up studies: 

Bakker, 200380 and two articles in original 

report: Ghys, 2002 and Al, 1995

Study Population: Healthy infants

Infants enrolled 750 Infants withdrawals 444 

Infants completers 306

Pregnant age: 29.8 (4.1)

Infant age: gestational age: boys: 39.8; girls 

40.0 (boys 1.7; girls 1.4)

Race of Mother: White European (100)

Inclusion Criteria: 750 Caucasian children of 7 y old, 

born between December 1990 and January 1994 in 

the course of an earlier study on maternal and 

neonatal LCPUFA status and pregnancy outcome

Exclusion Criteria: Not reported

Adjustments: Gender, 

cognitive function, gestational 

age, age at measurement

Bernard, et al., 201389

Outcome domain: Neurological

Study name: EDEN

Study dates: Recruitment 2003 to 2005

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Follow-up: 2 and 3 years

Original, same study, or follow-up studies: 

Drouillet, 200980

Study Population: Healthy pregnant women

Pregnant enrolled 2,002 Pregnant completers 

1,882

Infants enrolled 1.882 Infants completers 1,510

Pregnant age: 29.2 years (at conception) (4.8 

years) NR

Infant age: < 24 weeks gestation (NR) NR

Race of Mother: NR (100)

Inclusion Criteria: < 24 weeks amenorrhea

Exclusion Criteria: multiple pregnancies, known 

diabetes before pregnancy, illiteracy, and intention 

to move outside the region in the next 3 years

Adjustments: Center, child 

gender & age, gestational 

age, maternal age, obesity, 

energy intake, tobacco & 

alcohol consumption, parental 

education & income, first 

born, main daytime caregiver, 

and frequency of maternal 

stimulations

Bouwstra, et al., 2006133

Outcome domain: Neurological

Study dates: 1997-1999

Study Population: Healthy infants

Infants enrolled 317 Infants completers 269

Pregnant age: 30 (4.3)

Inclusion Criteria: All infants were born at 37–42 wk 

of gestation, had a native West European origin, and 

were born between February 1997 and October 

1999.

Exclusion Criteria: children with a congenital 

Adjustments: Type of 

postnatal feeding and 

potential confounders such as 

the postnatal age of the infant 

at GM assessment, paternal 

smoking, and the total 

172
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Study design: NR

Location: Netherlands

Funding source / conflict: Industry

Follow-up: 3 months

Original, same study, or follow-up studies: 

Bouwstra, 200362

Infant age: 3 months (NR)

Race of Mother: White European (100)

disorder interfering with adequate functioning in daily 

life, children from multiple births, children whose 

mother did not master the Dutch language or had 

significant illness or disability, and adopted and 

fostered children

Obstetric Optimality Score

Jordi Julvez, et al., 2014143

Outcome domain: Neurological

Study name: INMA

Study dates: Enrollment conducted July 2004 to 

July 2006 Followup: 4 years

Study design: Observational prospective

Location: Spain

Funding source / conflict: Government, Multiple

foundations and Societies

Follow-up: 4 years

Original, same study, or follow-up studies: 

Guxens, 2011144

Study Population: Breast-feeding women

Pregnant enrolled 657 Pregnant completers 622

Lactating enrolled 622 Lactating completers 582

Infants enrolled 622 Infants completers 434

Lactating enrolled 622 Lactating completers 582

Lactating age: 31.6 years (4.2 years)

Infant age: 2 to 5 days after birth

Race of Mother: NR (NR)

Inclusion Criteria: age older than 16 years, intent to 

deliver at the reference hospital, singleton 

pregnancy

Exclusion Criteria: no problems with communication,

no assisted conception

Adjustments: Test conditions, 

child age & sex, parental age, 

parity, alcohol consumption 

and smoking during 

pregnancy, day care 

attendance, country of birth, 

maternal education, social 

class, mental health, 

attachment to child, and 

perceptive performance IQ at 

14 months, maternal psych

symptoms, verbal IQ at 4 

years, pollutant exposure 

during pregnancy.

173
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Sun, et al., 2010131

Outcome domain: Neurological

Study name: Danish National Birth Cohort

Study dates: Recruitment March 1996 to 

November 2002

Study design: Observational prospective

Location: Denmark

Funding source / conflict: Government

Follow-up: 10.8 years (median 7.8 years)

Study Population: Healthy infants

Infants enrolled 65,754 Infants completers 

65754

Infant age: birth

Race of Mother: NR (NR)

Inclusion Criteria: live-born singletons whose 

mothers provided information on fish intake from 

food frequency questionnaire

Exclusion Criteria: children with missing information 

on maternal smoking and parity, children who died 

during the neonatal period, and children born to 

mothers with an unlikely high (>16,700 kJ/day) or 

low (<4200 kJ/day) intake of energy during 

pregnancy

Adjustments: Energy intake, 

sex, gestational age, parity, 

time breastfeeding, maternal 

age, SES, pre-pregnancy 

BMI, smoking status at 

recruitment, maternal history 

of epilepsy

Valent, et al., 2013132

Outcome domain: Neurological

Study dates: 2007-2011

Study design: Observational prospective

Location: Italy

Funding source / conflict: Government

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 900 Pregnant completers 767

Infants enrolled 767 Infants completers 632

Pregnant age: 33.3 (4.3)

Infant age: Birth

Race of Mother: NR (100)

Inclusion Criteria: Permanent residents of the study 

areas for at least 2 years, at least 18 years of age, 

and had no absence from the study area for more 

than 6 weeks during pregnancy, no history of drug 

abuse, no serious health problems or complications 

of pregnancy, and no twin gestation

Exclusion Criteria: Preterm births (<37 weeks of 

gestational age), babies with congenital 

malformations or severe perinatal problems, and 

those with severe health problems that presented 

postnatally and potentially compromised their 

neurological development

Adjustments: Fish intake, fatty 

acids in maternal serum and 

proportion of PUFAs, sex, 

birth weight, maternal IQ, 

weight gain during pregnancy, 

marital status at delivery, SES 

index, number of children 

living in home, alcohol intake 

during pregnancy, 

breastfeeding history, child 

intake of fish until age 18 

months, and daycare 

attendance at age 18 months

174
Development of Visual Function (Acuity)

Key Points

• Prenatal Supplementation: Four RCTs found no effects of prenatal supplemental DHA on 

infant visual acuity, measured behaviorally or using VEP, at follow-up times ranging 

from 1 week to 6 months. (Studies were too dissimilar to pool).

o Assessment of the associations between maternal and infant biomarkers following 

prenatal supplementation and visual acuity showed no association with maternal red 

blood cell DHA levels or maternal breast milk DHA but a significant association of 

earlier VEP development with cord blood DHA (p=0.003) . 

o No prospective cohort studies were identified that assessed associations with visual 

function.

• Postpartum maternal supplementation: Four RCTs (two described in the original report) 

found no effect of postpartum maternal supplementation (of mothers with healthy term 

infants) with DHA on any measure of infant visual acuity among breastfed infants at 4 or 

8 months, except for one study (n=230) that found a significant improvement in transient 

VEP amplitude at both time points, favoring DHA (p<0.03); this improvement was not 

seen at 5 years (n=117). 

o No association of infant plasma biomarkers with visual acuity was seen in one study 

but an association between visual acuity at 4 months and infant RBC DHA was 

reported in another study. No studies assessed the association of maternal biomarkers. 

o No observational studies were identified that assessed associations of postpartum 

maternal exposures with infant visual function.

• Supplementation of preterm infants with any n-3 FA and its effects on infant visual acuity 

was assessed in 9 studies in the original report and three studies identified for the current 

report. Pooling five studies that assessed visual acuity using visually-evoked potentials 

(VEP) at 4 and 6 months of age showed an insignificant effect of n-3 FA supplementation 

on VEP compared with placebo.

• Supplementation of preterm infants with DHA and its effect on visual acuity was 

assessed in four RCTs (two in the original report and two identified for the current report; 

the intervention formula in two of the studies actually included small amounts of EPA). 

No differences were seen between groups at 2 months, but one study found a significant 

improvement in adjusted sweep VEP in boys (but not girls) at 4 months of age (p=0.017). 

. 

• Supplementation of healthy term infants with any n-3 FA showed inconsistent effects on 

visual acuity. At two months’ follow-up, the pooled effect size for behavioral 

measurements showed an insignificant effect of n-3 FA (WMD 0.07 [0.00, 0.14] six 

RCTs); the pooled effect size for VEP was insignificant (WMD 0.07[-0.03, 0.17], six 

RCTs). At 4 months’ follow-up, the pooled effect size for behavioral measurements was 

significant in favor of placebo treatment (WMD -0.05 [-0.08, -0.01], six RCTs); the 

pooled effect size for VEP was significant in favor of n-3 FA (WMD 0.10[0.07, 0.13], 

eight RCTs). At 12 months follow-up, the pooled effect size for behavioral measures was 

insignificant (WMD -0.01[-0.04, 0.01]); the pooled effect size for VEP was significant in 

favor of n-3 FA (WMD 0.14 [0.11, 0.16]).

175
• Supplementation of healthy term infants with DHA+AA also showed inconsistent results. 

Eight studies identified for the original report showed no differences at 2, 4, 6, 8 and 9 

months; however four studies that assessed VEP at 12 months showed a significant 

pooled effect size in favor of DHA+AA (p=0.01). Two new studies were identified for 

the current report that assessed VEP at 4 and 12 months. At 4 months, the pooled effect 

size for VEP was significant in favor of DHA+AA (WMD -0.10 [-0.14, -0.07], five 

RCTs). At 12 months follow-up, the pooled effect size for VEP was significant in favor 

of DHA+AA (WMD -0.14 [-0.17, -0.12] six RCTs).

• Only one study assessed the association between infant biomarkers and visual acuity: 

This study found mixed associations between term infant red blood cell DHA, and 

subsequent visual acuity; however better visual acuity was associated with lower n-6 FA 

to n-3 FA ratios at 4, 9, and 12 months of age. 

• No prospective observational studies assessed the association of infant n-3FA exposures 

and visual acuity development. 

Description of Included Studies

Visual acuity in the developing infant and child is assessed using two types of methods. 

Behavioral methods assess eye movement and head turning in response to the presentation of 

infants’ preferred visual stimuli (patterns); visual acuity is defined as the highest spatial 

frequency that is distinguishable by the infant (according to the examiner). Electrophysiological 

methods include the measurement of visual evoked potentials (VEPs), which are physiological 

responses to these stimuli.

This section reports the findings of studies that assessed the effects of prenatal, postnatal 

maternal (breast milk), or postnatal infant PUFA supplementation or exposure on visual acuity 

development. Studies identified for this report are summarized in Table 16 and briefly 

summarized below. 

Antepartum Maternal Supplementation with n-3 Fatty Acids and Infant Visual 

Acuity

The original report identified one RCT that assessed the effects of administering fish oil to 

pregnant women on infant photoreceptor function (by electroretinogram) at 1 week of age; this 

study found no effect. 

DHA Versus Placebo 

For the current report, we identified four articles reporting on four RCTs that assessed the 

effect of supplementation of pregnant women with n-3 FA on infant visual acuity:33, 53, 100, 145 one 

article100 reported on the same study in the original report that found no effect of DHA 

supplementation on photoreceptor function at 1 week. Enrollments ranged from 100 100 to 900.33

Studies were conducted in the UK, Canada, Australia, and Mexico.

All four studies administered supplemental DHA, two in the form of DHA-enriched fish 

oil,53, 100 and two from algal sources33, 145 Concentrations ranged from 0.2g/d to 1 gm/d. One 

study commenced supplementation at 15 weeks,100 one began at 16 weeks,145 and the two 

remaining studies began at midterm: all four continued supplementation until term.

176
Behavioral Measures

One study employed a BM, Teller visual acuity cards, to assess visual acuity in term infants 

at 60 days of age.145

This study was not powered or designed to assess the effects of maternal DHA 

supplementation on infant visual acuity but to establish a range of visual acuity scores for infants 

born to women whose DHA intake was considered to be above requirements.145 Visual acuity 

scores did not differ significantly between groups (p=0.3), however, in multivariate analysis, 

visual acuity scores were related only to sex and DHA intervention group.

Electrophysiological Measures

The remaining three studies employed various VEP measures to assess visual acuity at 0.25, 

2.5, and 4 months,

100 4 months,53 and 3 and 6 months.33 The study by Malcolm and colleagues 

(2003) found no difference between intervention groups in any VEP measure at birth or at 2.5 

months and 4 months.

100 The study by Smithers and colleagues (2011) found no difference 

between intervention groups in mean sweep VEP acuity at 4 months in healthy full-term 

infants.53 The study by Stein and colleagues (2012) found no difference between intervention 

groups in any measure of VEPs at 3 and 6 months.33

Maternal and Infant Biomarkers

Two of the four RCTs that assessed the effects of antepartum maternal supplementation with 

n-3 FA on children’s visual acuity also assessed the association between biomarkers of exposure 

and visual acuity outcomes. 

Innis and Friesen assessed the association between maternal red blood cell (RBC) 

ethanolamine phosphoglyceride (EPG) concentrations of DHA and infant visual acuity at 2 

months of age. No difference was seen in Spearman rank correlation coefficients for either the 

DHA-supplemented or placebo groups, for girls (ρ =0.18, 0.10) or boys (ρ=-0.06, 0.07).145

Malcolm and colleagues assessed the association between cord RBC DHA maternal breast 

milk DHA, and VEP. They found a significant association between higher cord blood DHA at 

birth and earlier VEP development (pattern reversal peak latencies) (p=0.03 for absolute levels 

and 0.004 for RBC DHA as a percent of total fatty acids). They observed no association between 

maternal breast milk DHA levels and VEPs.100

No prospective cohort studies that assessed the association between maternal or infant 

biomarkers of n-3 FA status and visual acuity met our inclusion criteria.

Postpartum Maternal Supplementation with n-3 FA and Infant Visual Acuity

The original report identified two RCTs (one reported in an abstract) that examined the 

effects of postpartum maternal supplementation with increasing doses of n-3 FA (DHA) on the 

visual acuity of healthy term infants who were breastfed for at least 4 months (follow-up time). 

Doses ranged from 0.2g/d to 1.3g/d. Neither study showed a significant effect of DHA.

For the current report, we identified two new RCTs that examined the effects of 

supplementing lactating mothers with n-3 FA on infant visual acuity. 

Fish Oil Versus Placebo

We identified one 2004 RCT not included in the original report that examined the effects of 

postpartum maternal fish oil supplementation on visual acuity in 97 healthy term infants using 

sweep VEP at 2 and 4 months of age.127 Mothers in the Danish National Birth Cohort with low 

habitual fish intake were supplemented beginning within one week of birth to microencapsulated 

177
FO (1.3g per day) or olive oil. Supplementation resulted in significant increases in the n-3 FA 

content of breastmilk and infant erythrocytes at 4 months. No difference was seen in mean visual 

acuity measures between the infants of women who received FO (0.62±0.08), those of mothers 

who received olive oil 0.64±0.09), and those of mothers with high fish intake (0.63±0.09). 

Bivariate analysis showed that across treatment groups, visual acuity was not significantly 

associated with infant erythrocyte n-3 FA (p=0.117); however, multivariate analysis that 

controlled for gestational age and parity showed that infant RBC DHA was significantly 

associated with visual acuity at 4 months (p=0.008).

DHA Versus Placebo

We identified two new articles reporting on one RCT that examined the effects of postpartum 

maternal DHA supplementation on infant visual acuity.135, 136

Jensen and colleagues (the authors of the abstract summarized in the original report) 

randomly assigned 227 pregnant U.S. women who planned to breastfeed for at least 4 months to 

either algal DHA (approximately 0.2g/d) or placebo, to begin at 5 days postpartum and continue 

for 4 months.136 Mothers of preterm or low birth weight infants were excluded. Compliance with 

the supplement was 95 percent to 100 percent. Visual acuity was assessed at 4 and 8 months of 

age in the 230 infants (including 3 twin pairs) as a secondary variable, using both BM and VEP. 

No significant differences were seen in visual acuity as assessed by BM at 4 (5.6±0.71 vs. 

5.3±0.56 cycles/degree) or 8 months of age (12.3±0.53 vs. 13.5±0.57 cycles/degree) or sweep 

VEP at 4 months (9.4±0.23 vs. 9.4±0.21 cycles/degree). Transient VEP latency also did not 

differ between groups at 4 (124.8±11.7 vs. 123.9±0.10.6 milliseconds) or 8 months (115.1±8.1 

vs. 115.3±10.5 milliseconds). Transient VEP amplitude was significantly lower in the infants of 

DHA-treated mothers than in the infants of placebo-treated mothers at both 4 (28.9±12.1 vs. 

33.3±12.4 μVolts, p<0.03) and 8 months (24.3±8.9 vs. 27.9±11.0 μV, p<0.03).

A subsequent article reported on visual acuity at 5 years of age in the same population (n=60 

children of DHA-supplemented mothers and 57 children of placebo mothers).135 No differences 

were seen in visual acuity as measured by BM (Bailey Lovie visual acuity for both right and left 

eyes) between the groups (52.6±4.6 vs. 51.6 ±5.6 letters correct and 53.1±4.7 vs. 52.1± 4.9, 

respectively). VEP latency, amplitude, and sweep VEP acuity also showed no significant 

differences between treatment groups (110.3±8.1 vs. 108.0 ±6.5 msec; 39.6 ±13.7 vs. 45.3 ±18.0 

μVolts; 11.9 cycles/degree ±0.3 octaves vs. 11.8 ±0.3 octaves, respectively).

Maternal and Infant Biomarkers

Jensen and colleagues assessed the association between infant plasma phospholipid DHA and 

visual acuity and found no association (data not reported).136

As described above, in an RCT by Lauritzen and colleagues, bivariate analysis showed that 

across treatment groups, visual acuity was not significantly associated with infant erythrocyte n3 FA (p=0.117); however, multivariate analysis that controlled for gestational age and parity 

showed that infant RBC DHA was significantly associated with visual acuity at 4 months 

(p=0.008).127

Infant Formula Supplementation with n-3 FA and Visual Acuity in Preterm Infants

The original report identified nine RCTs that examined the effects of supplementing preterm 

or term formula with n-3 FA with or without breast feeding on visual acuity in preterm infants; 

the studies dated from 1992 to 2002. Duration of supplementation ranged from 3⁄4 month to 12 

months. Follow-ups ranged from 2 months to 12 months: in some studies, the intervention ended 

178
several months before follow-up assessment. Two RCTs assessed the use of formula 

supplemented with DHA alone, 5 RCTs assessed the use of formula supplemented with DHA 

plus AA (or DHA plus AA plus a very small quantity of EPA), and the remainder used some 

combination of DHA, EPA, and ALA. Seven of the RCTs assessed visual acuity using BM, five 

employed VEP or flash VEP, and three RCTs employed both. Across the nine studies, outcomes 

were mixed: five studies reported a positive effect of some combination of n-3 FA on a visual 

acuity outcome, whereas four reported no effects (the intervention in three of these four studies 

was 2 months or less).

The searches for the current report identified three new studies on the effects of 

supplementing preterm infants with n-3 FA on visual acuity. One study supplemented infant 

formula given to large preterm infants with DHA and AA for 6 months and assessed visual 

acuity at 4 and 6 months using BM and VEP.137 A second study supplemented breastfeeding 

mothers of preterm infants or formula fed infants from birth with DHA and assessed visual 

acuity using sweep VEP (primary) and VEP latency (secondary) at 2 and 4 months 

(supplementation duration was until expected due date).104 The third study, DINO, also 

supplemented breastfeeding mothers of preterm infants or supplemented the formula of formulafed infants from birth with DHA and conducted tests of visual perception skills at 7 years of 

age.120. 121, 146

Any Omega-3 Fatty Acid vs. Placebo

We were able to pool one of the studies identified for the current report137 with three studies 

identified for the original report,147-149 all measuring visual acuity using VEP at 4 months and 6 

months corrected age (one of the studies in the original report stratified participant responses by 

diagnosis of bronchopulmonary dysplasia)(Figures 16 and 17). At 4 months, the pooled analysis 

showed an insignificant effect of the intervention on VEP (WMD -0.06 [−0.12; 0.01]; I2

=1.7%). 

At 6 months corrected age, the pooled analysis showed a similarly insignificant effect (WMD -

0.04[-0.09, 0.01] I2

=0%).

Figure 16. Visual function in preterm infants at 4-months corrected age

179
Figure 17. Visual function in preterm infants at 6-months corrected age

DHA Versus Placebo 

The original report identified two RCTs that compared the effects of supplementing preterm 

or term infant formula with DHA vs. placebo on visual acuity outcomes of healthy preterm 

infants, as assessed using BM. One RCT assessed acuity at 0, 2, 4, 6, and 9 months, and the other 

at 2 and 4 months. The formula employed in one of the two RCTs actually contained more EPA 

than DHA and the intervention duration was 9 months; the formula employed in the other 

intervention appears to have contained only DHA, but the intervention duration was only 1 

month. No differences in visual acuity between treatment groups were observed at any time 

(effect sizes were pooled at 2 and 4 months).

One RCT identified for the current report randomized 143 preterm Australian infants (born at 

less than 33 weeks gestation) and their mothers to a supplement that contained DHA (29.5 

percent of total fatty acids), EPA (6.5 percent), and a small amount of AA (1.8%) in the form of 

tuna fish oil or to a preterm formula that contained soy oil; the concentration of DHA was 

intended to mimic that provided in utero.104 Breastfeeding mothers consumed the oil for the 

group to which they were assigned (the proportion of infants who received some breastmilk did 

not differ significantly between groups). The intervention duration was from birth to the 

expected delivery data. Visual acuity was assessed by sweep VEP at 4 months corrected age (the 

primary outcome) and VEP latency at 2 and 4 months corrected age. Adjusted sweep VEP was 

significantly higher at 4 months in the group that received the fish oil-supplemented formula (-

1.4[-2.6,-0.2] p=0.017). The effect was significant in boys (-2.1[-3.4, -0.9]) but it was not 

significant in girls (-0.8[-1.9, 0.4). No differences were observed in visual acuity latency at 2 or 4 

months. Use of n-3 FA supplements prenatally was similar across both groups.

A second RCT identified for the current report, the DINO Trial, randomized 657 preterm 

infants to receive high-dose DHA (or lactating mothers of preterm infants to receive DHA-rich 

tuna oil capsules) or standard-DHA infant formula (lactating mothers received soy oil 

capsules).116, 120 At 7 years corrected age, 604 children were tested on a battery of 

neurodevelopmental tests, including the Test of Visual Perception Skills. No difference was seen 

between treatment groups in any of the standard scores.

180
DHA plus AA Versus Placebo

The original report identified five RCTs that compared the effects of infant formula 

supplemented with DHA and AA to a control formula. Pooled analysis of studies that measured 

visual acuity using BM found no differences between groups at 0, 2, 3, 4, or 6 months. Two 

studies employed VEP to measure visual acuity: One of the studies reported significantly 

improved visual acuity at 6 months, and pooled assessment of the outcomes of the two studies at 

4 months showed no difference.

One RCT identified for the current report randomized 27 preterm infants (30 to 37 weeks 

gestation, >2000g birth weight) in Taiwan to a DHA (0.05%)- and AA(0.1%)-supplemented 

infant formula or the same formula without LC-PUFA.137 The intervention duration was 6 

months. No significant differences were observed in visual acuity between the intervention and 

control groups, measured by VEP or BM, at 4 or 6 months. The VEP outcomes were included in 

the pooled analyses described above. 

Infant Formula Supplementation with n-3 FA and Visual Acuity in Term Infants

The original report identified 13 RCTs that examined the effects of supplementing infant 

formula with various combinations of n-3 and n-6 FA on visual acuity of term infants. Across the 

13 RCTs, effects of supplementation on visual acuity were mixed. For the current report, we 

identified two new RCTs that examined the effect of supplementing infant formula with n-3 FA 

on visual acuity in term infants. We were able to pool the results of these studies with those of 

studies identified for the original report for both BM and VEP at follow-up times of 2, 4, and 12 

months of age. At 2 months follow-up time, the pooled effect size for BM of acuity was 

significant in favor of n-3 FA (WMD 0.07 [0.00, 0.14] I2

=20.2%). The pooled effect size for 

sweep VEP/VEP was not significant and studies were highly heterogeneous (WMD 0.07 [-0.03, 

0.17] I2=88.3%). At 4 months follow-up time, the pooled effect size for BM of acuity was 

significant in favor of the placebo (WMD -0.05 [-0.08, -0.01] I2=0%), whereas the pooled effect 

size for sweep VEP/VEP was significant in favor of n-3 FA supplementation (WMD 0.10 [0.07, 

0.13] I2

=9.1%). No evidence of publication bias was seen (Begg’s and Egger’s p values were 

0.652 and 0.663, respectively) At 12 months follow-up time, the pooled effect size for BM of 

acuity showed no difference (WMD -0.01 [-0.04, -0.01] I2

=0%), whereas the pooled effect size 

for sweep VEP/VEP was significant in favor of n-3 FA supplementation (WMD -0.14 [-0.16, -

0.11] I2

=18.1%). Again, no evidence of publication bias was seen (Begg’s and Egger’s p values 

were 0.188, 0.189, respectively)

DHA Versus Placebo 

The original report conducted a pooled analysis of two studies that compared infant formula 

supplemented with DHA on BM of visual acuity and found no significant benefit at 2, 4, 6, 9, or 

12 months. Pooled analysis of three RCTs that used VEP to assess visual acuity also showed no 

effects at 2, 4, 6, 8, 9, or 12 months.

We identified one RCT121 that was not included in the original report.146 A 2007 article 

reported on a 4-year follow-up to a 1993-1995 RCT that randomized 79 healthy term U.S. 

infants within the first 5 days of life to 4 months of microalgal DHA, DHA plus microfungal 

AA, or a control formula.150 At 1.5, 4 and 12 months of age follow-up, infants supplemented 

with DHA had shown significantly better visual acuity than the control group (as measured by 

sweep VEP), but not at 6 months.150 Of the 79, 52 were available for follow-up visual acuity 

assessment at 4 years using a BM. At 4 years, the DHA group showed significantly better righteye visual acuity than did the controls; the DHA group did not differ significantly from the DHA 

181
plus AA group or from a breast fed reference standard group. Left-eye visual acuity did not 

differ significantly among the groups. This follow-up could not be pooled with those of any other 

studies.

DHA plus AA Versus Placebo

The original report pooled the results of three RCTs, which showed a significant 

improvement in visual acuity with DHA plus AA supplementation at 2 months, as measured 

using BM (p<0.01) but not at 4 months or older (outcomes at 6, 9, and12 months were reported 

in only one or two studies each). The original report also pooled eight RCTs that assessed visual 

acuity using VEP and found no effects of n-3 FA and AA at 2, 4, 6, 8, and 9 months; however 

pooling four studies that reported VEP outcomes at 12 months showed significant improvement 

(p=0.01). Three new RCTs were identified for the current report. These studies are described 

briefly below. One of the studies identified for the current report121 was pooled with three studies 

from the original report150-152 that assessed the effects of supplementation with DHA+AA on 

sweep VEP/VEP at 2 months of age; the pooled effect size showed no significant difference 

(WMD -0.06 [−0.22; 0.10] I

2

=92%).(Figure 18) Two of the studies identified for the current 

report111, 121 were pooled with three studies from the original report150-152 that assessed the effects 

of supplementation with DHA+AA on sweep VEP/VEP at 4 months of age. The pooled effect 

size was significant in favor of DHA+AA (WMD -0.10 [-0.14, -0.07] I2=31.8%)(Figure 19). The 

two new studies were also pooled with four studies from the original report150-153 that assessed 

the effects of supplementation with DHA+AA on sweep/VEP at 12 months (Figure 20); the 

pooled effect size was significant in favor of DHA+AA (WMD -0.14 [-0.17, -

0.12]I2=6.9%)%)(Figures 21-23).

Figure 18. Visual function in term infants at 2-months follow-up, behavior methods

182
Figure 19. Visual function in term infants at 4-months follow-up, behavioral methods

Figure 20. Visual function in term infants at 12-months follow-up, behavioral methods

183
Figure 21. Visual function in term Infants at 2-months follow-up, Sweep Visual Evoked Potential

Figure 22. Visual function in term infants at 4-months follow-up, Sweep Visual Evoked Potential

184
Figure 23. Visual function in term infants at 12-months follow-up, Sweep Visual Evoked Potential

The 2005 RCT by Birch and colleagues randomized103 healthy term U.S. infants in the first 

5 days of life to a standard infant formula or a formula fortified with DHA (0.36% of total fatty 

acids) and AA (0.72% of total fatty acids).111 The experimental diets were given through 12 

months and solid foods were not introduced before 4 months. Visual function was assessed by 

sweep VEP, random dot stereoacuity, and electroretinography at 1.5 months, 4 months, 9 

months, and 12 months. VEP acuity was significantly greater in the intervention group at all 

time-points, with the overall differences corresponding to slightly more than a one-line 

difference in reading a standard eye chart.

A 2010 RCT by the same researchers, the DIAMOND Study, randomized healthy term U.S. 

infants born at one of 7 hospitals at two study sites to one of four intervention groups within 9 

days of birth (study sites differed significantly by race, ethnicity, parental education, and 

gestational length).121 Children who had received breast milk were excluded. Three of the 

intervention groups received a standard formula fortified with 0.32% DHA (0.017g/100kcal), 

0.64% DHA (0.034g/100 kcal), or 0.96% DHA; all intervention formulae also included 0.64% 

fatty acids as AA (0.034 g/100kcal). The control group received the standard formula with no 

DHA or AA. As in the 2005 study, the intervention was continued for 12 months and no other 

foods were introduced prior to 4 months of age. Visual acuity was assessed by sweep VEP at 1.5, 

4, 6, 9 and 12 months. Control infants had poorer visual acuity than the intervention groups at all 

time-points; visual acuity did not differ among the active intervention groups at any time, 

demonstrating no dose-response effect. Significant differences in acuity and response to the 

interventions were noted between study sites, with the control group at one site showing 

significantly worse visual acuity than the control group at the other site but the interventions 

groups at the first site showing significantly better response to the interventions than the 

intervention groups at the second site.

185
The 2007 4-year follow-up RCT described in the previous subsection on DHA-only 

interventions found that right-eye visual acuity in the children who received formula with DHA 

plus AA was better, but not significantly better, than that of the children who had received the 

control formula. Left-eye visual acuity did not differ significantly among the groups.146 Infants 

treated with formula containing DHA plus AA had shown significantly better visual acuity than 

the control group (as measured by sweep VEP), at 1.5, 4 and 12 months of age but not at 6 

months.

150

Infant biomarkers

One RCT identified for the current study assessed the association between infant red blood 

cell lipids and sweep VEP acuity.111 This study, which compared visual acuity over 12 months 

between infants who received a formula containing DHA plus AA and those receiving a control 

formula, found that at 4 months, better visual acuity was associated with higher DHA 

concentrations but not with AA, ALA, or LA concentrations. At 9 months, better visual acuity 

was associated with higher DHA and AA levels at both 4 months and 9 months. At 1 year, better 

visual acuity was associated with higher DHA at 4 months and 9 months and with higher AA at 9 

months. At all time-points, better visual acuity was also associated with a lower n-6 to n-3 ratio 

and higher DHA to n-6 DPA. 

186
Table 16. RCTs for visual function

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Birch et al., 2005111

Study name: NR

Study dates: Not reported

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy infants

Infants enrolled 103 

Infants completers 86

Pregnant age: 31 years 

(4 years)

Infant age: 3.6 

_x0004_days (1.3 days) 

1-5 days

Race of Mother: NR

Inclusion Criteria: All 

were born at 37– 40 wk 

after conception. Only 

singleton births with birth 

weight appropriate for 

gestational age

Exclusion Criteria: Family 

history of milk protein 

allergy, genetic or familial 

eye disease, vegetarian 

or vegan maternal dietary 

patterns, maternal 

metabolic disease or 

infection, jaundice, 

perinatal asphyxia, 

meconium aspiration, or 

any perinatal event that 

resulted in placement of 

the infant in the neonatal 

intensive care unit.

Start time: Infants 1-5 days

Duration: Infants 52 wks

Arm 1: Control

Description: Commercial infant formula

Brand name: Enfamil with Iron

Manufacturer: Mead Johnson Nutritionals, 

Evansville, IN

Active ingredients: Linoleic acid-8.48g/L (14.6%); 

14.7 g protein/L, 37.5 g fat/L, 69.0 g carbohydrate/L

Blinding: Each diet was masked by 2 color and 2 

number codes, for a total of 4 possible diet 

assignments. The randomization schedule had

random-length blocks (block length varied from 6 to 

12) and was provided in individual sealed envelopes 

to the study site.

ALA: 1.5% of total fatty acids

Arm 2: LCPUFA-supplemented formula

Description: Commercial formula supplemented with 

LCPUFA

Brand name: Enfamil with Iron plus DHASCO and 

ARASCO

Manufacturer: Formula: Mead Johnson; DHA+ARA: 

Martek Biosciences

Active ingredients: 15% linoleic acid,14.7 g /L 

protein, 37.5 g /L fat, 69.0 g /L carbohydrate

ALA: 1.5% of total fatty acids

DHA: 0.36% of total fatty acids

AA: 0.72% of total fatty acids

data only reported on graph

Outcome: (Primary)

Birch et al., 2007146

Study name: Birch

Study dates: 1993-1999

Study design: Trial 

randomized parallel

Location: US

Study Population: 

Healthy infants, Pregnant 

women whose unborn 

children were at high risk 

of developing asthma

Infants enrolled 79+40BF 

Infants completers 

52+32BF

Inclusion Criteria: All 

participants were born at 

37 to 40 weeks 

postmenstrual age. Only 

singleton births with birth

weights appropriate for 

gestational age

Exclusion Criteria: family 

history of milk-protein 

Start time: Infants birth (0-5 days)

Duration: Infants 17 weeks

Arm 1: Control

Description: standard infant formula without added 

n-3 FA

Brand name: Enfamil with Iron

Manufacturer: Mead Johnson Nutritionals

Active ingredients: linoleic acid: 15% of total fats

Outcome: Visual acuity Left Eye (log 

minimum angle of resolution in minutes of 

arc) (Primary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 0.05; SE 

(0.016)

Arm 2: Sample size 16; mean 0.02; SE 

(0.018)

Arm 3: Sample size 17; mean 0.03; SE 

(0.017)

187
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study follow-up: 4 years

Infant age: birth (0-5 

days)

Race of Mother: NR

allergy, genetic or familial 

eye disease (e.g. 

hereditary retinal 

disease, strabismus), 

vegetarian or vegan 

maternal dietary patterns, 

maternal metabolic 

disease, anemia, or 

infection, presence of a

congenital malformation 

or infection, jaundice, 

perinatal asphyxia, 

meconium aspiration, 

and any perinatal event 

which resulted in 

placement of the infant in 

the neonatal intensive 

care unit

ALA: 1.5% of total fats

Arm 2: DHA

Description: infant formula fortified with DHA

Brand name: Enfamil with Iron, supplemented with 

DHASCO

Manufacturer: Formula: Mead Johnson; DHA: 

Martek Biosciences

Active ingredients: linoleic acid: 15% of total fats

ALA: 1.5%

DHA: 0.36%

Arm 3: DHA+ARA

Description: infant formula fortified with DHA and 

ARA

Brand name: Enfamil with Iron, fortified with 

DHASCO and ARASCO

Manufacturer: Formula: Mead-Johnson; DHA, ARA: 

Martek Biosciences

Active ingredients: linoleic acid 15%

ALA: 1.5%

DHA: 0.36%

AA: 0.72%

Outcome: Visual acuity Right Eye (log 

minimum angle of resolution in minutes of 

arc) (Primary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 0.08; SE 

(0.022)

Arm 2: Sample size 16; mean 0.02; SE 

(0.019)

Arm 3: Sample size 17; mean 0.03; SE 

(0.017)

Birch et al., 2010121

Study name: Diamond

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Some authors 

employed by industry 

(companies that make 

the supplements)

Original, same study, or 

follow-up studies: Drover, 

2011122; Drover. 2012123; 

Study Population: 

Healthy infants

Infants enrolled 343 

Infants completers 244

Pregnant age: NR

Mother age: NR

Infant age: 1-9 days

Race of Mother: NR

Inclusion Criteria: 

Healthy term formula-fed, 

singleton-birth infants 

born in any of 5 hospitals

Exclusion Criteria: Infants 

who had received human 

milk within 24 h of 

randomization or who 

had diseases or 

congenital abnormalities 

likely to interfere with 

normal growth and 

development or with the 

normal maturation of 

visual or cognitive 

function, poor formula 

intake, or known or 

suspected intolerance to 

cow milk infant formula 

Start time: Infants 4-9 days of age

Duration: Infants 12 months

Arm 1: Control

Brand name: Enfamil with Iron

Manufacturer: Mead-Johnson Nutrition, Evansville 

IN

Arm 2: 0.32% DHA

Brand name: Enfamil LIPIL

Manufacturer: Mead-Johnson; DHA and ARA from 

algal and fungal oils manufactured by Martek 

Biosciences

Dose: not specified

Blinding: not specified

DHA: 0.32% or 17mg/100kcal

AA: 0.64% FA or 34mg/100kcal

Arm 3: 0.64% DHA

data only reported on graph

Outcome: (Primary)

188
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Colombo, 2013124; Currie, 

2015115

were excluded from the 

study. Also excluded 

were infants born to 

mothers with chronic 

illness, such as HIV 

disease, renal or hepatic 

disease, type 1 or type 2 

diabetes, alcoholism, or 

substance abuse

Brand name: not specified

Manufacturer: not specified

DHA: 34mg/100kg

AA: 0.64% FA or 34mg/100kcal

Arm 4: 0.96% DHA

Brand name: not specified

Manufacturer: not specified

DHA: 51mg/100kg

AA: 0.64% FA or 34mg/100kcal

Collins et al., 2015120

Study name: DINO

Study dates: 2001-2013

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Study Population: 

Preterm infants

Infants enrolled 657 

Infants completers 604

Infant age: median 30 

weeks gestational age 

28-31 weeks

Race of Mother: NR 

(100)

Inclusion Criteria: infants 

born at <33 weeks’ 

gestation from five 

Australian tertiary 

hospitals between 2001 

and 2005

Exclusion Criteria: a 

major congenital or 

chromosomal 

abnormality, multiple 

birth in which not all liveborn infants were eligible,

enrollment in other trials 

of fatty acid 

supplementation, or if 

fish oil was 

contraindicated in the 

lactating mother

Start time: Infants within 5 days of 1st enteral 

feeding

Duration: Infants to expected due date

Arm 1: standard DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentrations of term formula fed infants

DHA: ___20 mg/kg/ day of DHA

Arm 2: High DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentration of breastmilk

DHA: ___50 mg/kg/ day of DHA

Outcome: Test of visual perception skills: 

figure ground standard score (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 9.6; SD 

(4.3)

Arm 2: Sample size 291; mean 9.4; SD 

(3.8)

Outcome: Test of visual perception skills: 

visual closure standard score (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 8.0; SD 

(3.7)

Arm 2: Sample size 291; mean 7.6; SD 

(3.6)

Outcome: Test of visual perception skills: 

visual discrimination standard score 

(Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 8.1; SD 

(3.6)

Arm 2: Sample size 291; mean 8.1; SD 

(3.1)

Fang et al., 2005137

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Study Population: 

Preterm infants

Infants enrolled 28 

Infants withdrawals 1 

Infants completers 27

Infant age: 1 week (mean 

gestation age 33 weeks) 

Inclusion Criteria: (1) A 

gestational age at birth 

between 30 and 37 

weeks; (2) Normal 

fundus oculi; (3) 

Recruitment prior to 

commencement of 

feeding

Start time: Infants 1 week after birth

Duration: Infants 24 weeks

Arm 1: placebo

Description: infant formula based on the composition 

of human milk

Brand name: Neoangelac

Manufacturer: Multipower Enterprise Corporation

Outcome: Hiding Heidi Analysis <100% 

(Primary)

Follow-up time: 4 months

Arm 1: 2/11 (18.0%)

Arm 2: 5/16 (31.0%)

Follow-up time: 6 months

Arm 1: 10/11 (91.0%)

Arm 2: 16/16 (100.0%)

Outcome: Lea grating acuity card 1 or 2 

189
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: Taiwan

Funding source / conflict: 

Manufacturer supplied 

product

(0.5 week) NA

Race of Mother: NR 

(100)

Exclusion Criteria: (1) 

Breast feeding; (2) A 

maternal history of 

infection, diabetes 

mellitus, gestational 

diabetes mellitus, 

cocaine or alcohol abuse, 

systemic diseases or if 

intrauterine growth 

retardation had been 

diagnosed during 

pregnancy; (3) Major 

congenital abnormality; 

(4) Severe 

intraventricular 

hemorrhage > grade 2; 

(5) Cystic periventricular 

leukomalacia; (6) 

Retinopathy of 

prematurity stage 2; (7) 

Bronchopulmonary 

dysplasia on radiographs 

or oxygen usage 28 

days; (8) Body weight 

less than the third 

percentile; (9) Surgical 

intervention for 

necrotizing enterocolitis 

(10) Mechanical 

ventilation after achieving 

enteral intake > 110 

kcal/kg per day; (11) A 5-

min Apgar score < 7; (12) 

Administration of blood 

transfusion, blood 

products, or parenteral 

lipids with DHA or AA.

Dose: Babies were given more than 110 kcal/kg per 

day during the first 4 months and more than 70 

kcal/kg per day from 4 to 6 months

N-6 N-3: 10:1 linoleic:linolenic

Arm 2: Neoangelac Plus

Description: Neoangelac supplemented with Omega 

3

Brand name: Neoangelac Plus

Manufacturer: Multipower Enterprise Corporation

Dose: Babies were given more than 110 kcal/kg per 

day during the first 4 months and more than 70 

kcal/kg per day from 4 to 6 months

DHA: 0.05%

AA: 0.10%

cycles per degree (Primary)

Follow-up time: 4 months

Arm 1: 8/11 (72.0%)

Arm 2: 16/16 (100.0%)

Outcome: Lea grating acuity card 2 or4 

cycles per degree (Primary)

Follow-up time: 6 months

Arm 1: 8/11 (73.0%)

Arm 2: 15/16 (94.0%)

Outcome: Visual evoked potential (log 

minimum angle of resolution in minutes of 

arc) (Primary)

Follow-up time: 4 months

Arm 1: Sample size 10; mean 0.36; SD 

(0.34)

Arm 2: Sample size 14; mean 0.19; SD 

(0.27)

Follow-up time: 6 months

Arm 1: Sample size 10; mean 0.13; SD 

(0.22)

Arm 2: Sample size 13; mean 0.1; SD 

(0.17)

Innis et al., 2008145

Study name: NR

Study dates: NR, <2008

Study Population: 

Healthy pregnant women

Pregnant enrolled NR 

Pregnant completers 135

Inclusion Criteria: 14 –16 

wk gestation, not taking 

any lipid supplement, no 

complications likely to 

affect maternal or fetal 

metabolism or fetal 

Start time: Pregnant 16 weeks gestation Infants 16 

weeks gestation

Duration: Pregnant to birth Infants to birth

Arm 1: placebo

Outcome: Teller Acuity Card procedure 

(visual acuity) (cyc/deg) (Secondary)

Follow-up time: 60 days

Arm 1: Sample size 68; mean 2.42; SD 

(0.63)

Arm 2: Sample size 67; mean 2.6; SD (0.5)

190
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Government, None, 

Manufacturer supplied 

product

Study follow-up: 60 days

Infants enrolled 135 

Infants completers 134

Pregnant age: 33 years 

(0. 4 years)

Infant age: 14 to 16 

weeks gestation

Race of Mother: White 

European (72%)

Baseline biomarker 

information: 16 week 

gestation baseline values 

for both groups similar. 

Reported graphically, so 

approximations. 22:6n-3: 

7 %wt of total FA 22:5n3: 4 %wt of total FA 

20:5n-3: 1 %wt of total 

FA 18:3n-3: 0.4 %wt of 

total FA

Baseline Omega-3 

intake: For mothers, at 

assignment: Linoleic acid 

(g) median 13.5 range 

2.52–43 Alpha Linolenic 

acid (g) median 1.48 

range 0.46–9.21

Arachidonic acid (mg) 

median 90 range 20–360 

EPA (mg) median 70 

range 10–280 DHA (mg)

median 110 range 10–

760

development, expected 

to deliver one full-term 

infant

Exclusion Criteria: NR

Description: corn oil / soybean oil capsule

Manufacturer: Martek Biosciences, Columbia, MD)

Dose: 2 capsules

Blinding: identical capsules, containing an orange 

flavor to assist in further blinding

Maternal conditions

ALA: 40 mg

Other dose 1: LA 265 mg

Current smoker 2/67

Arm 2: DHA supplement

Description: capsule containing 200 mg DHA

Manufacturer: Martek Biosciences, Columbia, MD)

Dose: 2 capsules

Maternal conditions

DHA: 200 mg/g

Current smoker 0/68

Jensen et al., 2005136

Study name: Unnamed 

Trial B

Study dates: <2004

Study Population: Breastfeeding women

Lactating enrolled 227 

Lactating completers 174

Inclusion Criteria: 

maternal age between 18 

and 40 y, infant 

gestational age >=37 wk, 

infant birth weight 

between 2500 and 4200 

Start time: Lactating 5 days after delivery Infants 5 

days after birth

Duration: Lactating 4 months Infants 4 months

Arm 1: placebo

Outcome: Sweep VEP (cyc/deg) 

(Secondary)

Follow-up time: 4 months

Arm 1: Sample size 79; mean 9.4; SD 

(0.21)

Arm 2: Sample size 81; mean 9.4; SD 

191
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government

Original, same study, or 

follow-up studies: 

Jensen, 2010135

Infants enrolled 230 

Infants completers 177

Lactating enrolled 227 

Lactating completers 174

Lactating age: 31.5 years 

(5 years) 18-40

Infant age: birth (NA) NA

Race of Mother: NR

g

Exclusion Criteria: 

chronic maternal 

disorders, major 

congenital anomalies, 

obvious gastrointestinal 

or metabolic disorders of 

the infant

Description: capsule containing corn & soy oil

Manufacturer: Martek Biosciences

Purity Data: 15% saturated fatty acids, 23.5% 

monounsaturated fatty acids, 56.3% linoleic acid 

(18: 2n_x0001_6), and 3.9% _x0001_-linolenic acid 

(18:3n_x0001_3)

Dose: 1 capsule

Blinding: identical capsules

ALA: 56.3% linoleic acid (18: 2n_x0001_6), 3.9% 

_x0001_-linolenic acid (18:3n_x0001_3)

Total N-3: 57.2%

Arm 2: DHA algal triacylglycerol (DHASCO)

Description: DHA capsule

Brand name: DHASCO

Manufacturer: Martek Biosciences

Purity Data: 44%saturatedfattyacids, 13.6% 

monounsaturated fatty acids, 0.8% linoleic acid 

(18:2n _x0001_ 6), and 41.7% DHA (22:6n-3) by 

weight

Dose: 1 capsule

ALA: 0.8% (18:2n-6)

DHA: 200 mg, 41.7% (22:6n-3)

Total N-3: 42.5%

(0.23)

Outcome: Teller Acuity Card procedure 

(cyc/deg) (Secondary)

Follow-up time: 4 months

Arm 1: Sample size 77; mean 5.3; SD 

(0.56)

Arm 2: Sample size 70; mean 5.6; SD 

(0.71)

Follow-up time: 8 months

Arm 1: Sample size 73; mean 13.5; SD 

(0.57)

Arm 2: Sample size 74; mean 12.3; SD 

(0.53)

Outcome: Visual evoked potential 

amplitude (mV) (Secondary)

Follow-up time: 4 months

Arm 1: Sample size 82; mean 33.3; SD 

(12.4)

Arm 2: Sample size 86; mean 28.9; SD 

(12.1)

Follow-up time: 8 months

Arm 1: Sample size 74; mean 27.9; SD (11)

Arm 2: Sample size 79; mean 24.3; SD 

(8.9)

Outcome: Visual evoked potential latency 

(ms) (Secondary)

Follow-up time: 4 months

Arm 1: Sample size 82; mean 123.9; SD 

(10.6)

Arm 2: Sample size 86; mean 124.8; SD 

(11.7)

Follow-up time: 8 months

Arm 1: Sample size 74; mean 115.3; SD 

(10.5)

Arm 2: Sample size 79; mean 115.1; SD 

(8.1)

Jensen et al., 2010135

Study name: Unnamed 

Trial B

Study dates: NR (<2010)

Study Population: Breastfeeding women

Lactating enrolled 227

Infants enrolled 230 

Infants completers 119

Inclusion Criteria: 

maternal age between 18 

and 40 y, infant 

gestational age >=37 wk, 

infant birth weight 

between 2500 and 4200 

g

Start time: Infants birth

Duration: Infants 4 months

Arm 1: placebo

Description: capsule containing corn & soy oil

Manufacturer: Martek Biosciences

intervention first 4 months; same trial as 

3433 (later followup)

Outcome: Bailey Lovie Acuity - left eye 

(number of letters correct) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 52.1; SD 

(4.9)

192
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government

Study follow-up: 5 years

Original, same study, or 

follow-up studies: 

Jensen, 2005136

Lactating enrolled 227

Lactating age: 31.5 years 

(5 years) 18 to 40

Infant age: birth (NA) NA

Race of Mother: NR (NR)

Exclusion Criteria: 

chronic maternal 

disorders, major 

congenital anomalies, 

obvious gastrointestinal 

or metabolic disorders of 

the infant

Purity Data: 50:50 mixture of soy and corn oils 

consisting, by weight, of 15% saturated fatty acids, 

23.5% monounsaturated fatty acids, 56.3% linoleic 

acid (18:2 n-6) and 3.9% a-linolenic acid (18:3 n-3)

Dose: 1 capsule

Blinding: capsules were identical

ALA: 3.9%

Arm 2: omega 3 capsule

Description: high-DHA algal triglyceride capsule

Brand name: DHASCO

Manufacturer: Martek

Purity Data: by weight, 44% saturated fatty acids, 

13.6% monounsaturated fatty acids, 0.8% linoleic 

acid (18:2n-6) and 41.7% DHA (22:6n-3)

Dose: 1 capsule

DHA: 200 mg

Arm 2: Sample size 60; mean 53.1; SD 

(4.7)

Outcome: Bailey Lovie Acuity - right eye 

(number of letters correct) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 58; mean 51.6; SD 

(5.6)

Arm 2: Sample size 60; mean 52.6; SD 

(4.6)

Outcome: Sweep VEP acuity (cyc/deg) 

(Secondary)

Follow-up time: 5 years

Arm 1: Sample size 55; mean 11.8; SD 

(0.3)

Arm 2: Sample size 56; mean 11.9; SD 

(0.3)

Outcome: VEP Amplitude (mV) 

(Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 45.3; SD (18)

Arm 2: Sample size 60; mean 39.6; SD 

(13.7)

Outcome: VEP Latency (30' check sizes) 

(ms) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 108.0; SD 

(6.5)

Lauritzen et al., 2004127

Study name: Danish 

National Birth CohortLactating Women

Study dates: December 

1998 to November 1999

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / conflict: 

Industry, Government

Study Population: Breastfeeding mothers with 

lower than average fish 

intake

Infants enrolled 175 

Infants completers 149

Pregnant age: Olive oil 

30.2 Fish oil 29.6 High 

fish 31.9 (Olive oil ± 4.1

Fish oil ± 4.3 High fish ± 

4.1)

Infant age: 40.1 weeks 

gestation (birth) (1.2 

Inclusion Criteria: 

pregnant Danish women 

living in the greater 

Copenhagen area who 

had a fish intake below 

the 50th percentile of the 

DNBC population; an 

uncomplicated 

pregnancy, prepregnancy 

body mass index (BMI) < 

30 kg/m2 , and an 

absence of metabolic 

disorders; intention to 

breast-feed for at least 4 

mon at the time of 

recruiting; newborns had 

Start time: NR

Duration: NR

Arm 1: Placebo

Blinding: Intervention fish oil was deodorized

Arm 2: FO Intervention

Description: Fish oil powder baked into cookies

Other dose 1: 17 g/d of deodorized 

microencapsulated FO powder, containing 4.5 g of 

FO and 1.5 g of n-3 LCPUF

Outcome: swept visual evoked potential 

(SWEEP-VEP) (Primary)

Follow-up time: 2 months

Arm 1: Sample size 46; mean 0.84; SD 

(0.08)

Arm 2: Sample size 42; mean 0.84; SD 

(0.09)

Follow-up time: 4 months

Arm 1: Sample size 45; mean 0.64; SD 

(0.09)

Arm 2: Sample size 52; mean 0.62; SD 

(0.08)

193
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 2 and 4 

months

Original, same study, or 

follow-up studies: 

Lauritzen, 2005102; 

Lauritzen, 2005128; 

Cheatham, 2011129;

weeks)

Race of Mother: NR 

(100)

Baseline Omega-3 

intake: Habitual n-3 

LCPUFA intake (g/d)

Olive oil: 0.3 ± 0.3 Fish 

oil: 0.3 ± 0.3 High fish: 

1.1 ± 0.6

to be healthy (no 

admission to a neonatal 

department), term (37–43 

wks of gestation), 

singleton infants with 

normal weight for 

gestation (20) and an 

Apgar score >7 at 5 min 

after delivery. Willingness 

to start on the 

supplements within 2 wks 

after birth; no use of 

other types of oil 

supplements

Exclusion Criteria: BMI 

>= 30 kg/m2

Malcolm et al., 2003100

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: NR

Funding source / conflict: 

NR

Study Population: NR

Pregnant enrolled 100 

Pregnant withdrawals 37 

Pregnant completers 63

Infants enrolled 60 

Infants withdrawals 5 

Infants completers 55

Infant age: 279.6 (8.5)

Race of Mother: NR (NR)

Baseline biomarker 

information: Only 

reported: "The fish oil 

and placebo groups did 

not differ in maternal 

RBC and plasma fatty 

acid composition at 

enrollment"

Inclusion Criteria: d 

women who were 

expected to deliver their 

infants at term and 

planned to feed them on 

breast and/or formula 

milk

Exclusion Criteria: 

diabetes, twin 

pregnancies, preeclamptic toxaemia, a 

past history of abruption 

or postpartum 

haemorrhage, allergy to 

fish products, a 

thrombophilic tendency, 

or who were receiving 

drugs that affect 

thrombocyte function 

(non-steroidal antiinflammatories)

Start time: Pregnant week 15 Infants birth

Duration: Pregnant birth

Arm 1: Placebo

Description: contained 323 mg sunflower oil with 

high levels of oleic acid and was free of any 

significant amounts of LCPUFAs or their precursors

Manufacturer: R P Scherer Limited (Swindon, 

Wiltshire, UK)

Dose: 323 mg per capsule * 2

Blinding: e identical in appearance and could not be 

identified on the basis of scent or taste

Total N-3: 0

Arm 2: DHA

Description: f a blended fish oil, Marinol D40, and 

contained 100 mg DHA in 323 mg oil per capsule

Manufacturer: R P Scherer Limited (Swindon, 

Wiltshire, UK)

Dose: 323 mg capsule * 2

DHA: 200 mg

EPA: .64 mg (estimated based on the FA 

composition)

Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: N1 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 18; mean 58.1; SD 

(21.4)

Arm 2: Sample size 19; mean 54.7; SD 

(16.2)

Follow-up time: 66 weeks (corrected age)

Arm 1: Sample size 24; mean 57.3; SD 

(10.7)

Arm 2: Sample size 23; mean 61.5; SD 

(5.4)

Follow-up time: birth

Arm 1: Sample size 4; mean 74.8; SD 

(16.8)

Arm 2: Sample size 5; mean 62.2; SD (3.8)

Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: N2 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 28; mean 112.8; SD 

(46.5)

Arm 2: Sample size 24; mean 128.9; SD 

(47.9)

Follow-up time: 66 weeks (corrected age)

194
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 26; mean 122.1; SD 

(33.7)

Arm 2: Sample size 25; mean 128.5; SD 

(30.3)

Follow-up time: birth

Arm 1: Sample size 22; mean 149.9; SD 

(28)

Arm 2: Sample size 27; mean 153.5; SD 

(28.9)

Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: N3 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 20; mean 277.3; SD 

(49.4)

Arm 2: Sample size 14; mean 241.8; SD 

(49.8)

Follow-up time: 66 weeks (corrected age)

Arm 1: Sample size 15; mean 209.2; SD 

(38.2)

Arm 2: Sample size 11; mean 228.9; SD 

(55.9)

Follow-up time: birth

Arm 1: Sample size 27; mean 298.4; SD 

(52.8)

Arm 2: Sample size 26; mean 292.2; SD 

(58.2)

Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: P1 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 22; mean 84.2; SD

(22.5)

Arm 2: Sample size 23; mean 80.3; SD 

(21.1)

Follow-up time: 66 weeks (corrected age)

Arm 1: Sample size 26; mean 76.5; SD 

(19.5)

Arm 2: Sample size 25; mean 80.1; SD 

(15.8)

Follow-up time: birth

Arm 1: Sample size 5; mean 107.8; SD 

(11.8)

Arm 2: Sample size 9; mean 101.0; SD 

195
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(13.6)

Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: P2 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 26; mean 162.5; SD 

(26.5)

Arm 2: Sample size 21; mean 164.2; SD 

(29.9)

Follow-up time: 66 weeks (corrected age)

Arm 1: Sample size 19; mean 152.5; SD 

(43.6)

Arm 2: Sample size 12; mean 150.6; SD 

(33)

Follow-up time: birth

Arm 1: Sample size 27; mean 201.8; SD 

(33.3)

Arm 2: Sample size 28; mean 201.9; SD 

(28.4)

Mulder et al., 201475

Study name: NR

Study dates: 2004 to 

2008

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Government

Study follow-up: 18 

months

Study Population: 

Healthy pregnant women

Pregnant enrolled 271 

Pregnant completers 200

Pregnant age: 33 years 

(4 years) NR

Race of Mother: White 

European (73%) Other 

race/ethnicity (27%)

Baseline biomarker 

information: maternal 

RBC 

Phusphatidylethanolamin

e DHA: placebo group 

6.25 (1.60) g/ 100g DHA 

group 6.36 (1.62) g/ 100g

Baseline Omega-3 

intake: median (2.5 to 

97.5th percentile range) 

Inclusion Criteria: at least 

16 wk gestation, not 

taking any lipid or fatty 

acid supplement, and 

were expected to deliver 

one infant at full-term 

gestation, with no 

maternal or fetal 

complications

Exclusion Criteria: NR

Start time: Pregnant 16 weeks gestation

Duration: Pregnant Until birth

Arm 1: placebo

Description: corn and soybean oil supplement

Manufacturer: Martek Biosciences

Blinding: supplements were identical in appearance, 

contained an orange flavor mask

Arm 2: DHA supplement

Description: algal oil DHA supplement

Manufacturer: Martek Biosciences

DHA: 400 mg

Outcome: number with visual acuity>==13 

cycles/degree (Unspecified)

Follow-up time: 12 months

Arm 1: 20/95 (21.1%)

Arm 2: 20/81 (24.7%)

Outcome: number with visual acuity>==3.3 

cycles/degree (Unspecified)

Follow-up time: 2 months

Arm 1: 8/94 (8.51%)

Arm 2: 17/90 (18.9%)

196
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

intake: placebo group

80.0 (0.00-334) mg/day, 

DHA group 90.0 (6.00-

472) mg/d

Smithers et al., 2008104

Study name: DINO

Study dates: 2001-2004

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Manufacturer supplied 

product

Study follow-up: 2 

months, 4 months

Original, same study, or 

follow-up studies: 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Study Population: 

Preterm infants

Lactating enrolled 

unclear

Infants enrolled 143 

Infants completers 125

Lactating enrolled 

unclear

Mother age: Control: 31 

Treatment: 29 (Control: 6 

Treatment: 6)

Infant age: 5 days 

(control) (mean 

gestational age at birth 

29.4 weeks) 6 days 

(Treatment) (3)

Race of Mother: NR (NR)

Baseline Omega-3 

intake: Intervention 

begun at birth: see below

Inclusion Criteria: infants 

born_x0001_33 wk 

gestation at the Women’s 

and Children’s Hospital 

of the Child, Youth, and 

Women’s Health Service, 

Adelaide, Australia, 

between April 2001 and 

September 2003

Exclusion Criteria: Infants 

with major congenital or 

chromosomal 

abnormalities, lactating 

mothers for whom tuna 

oil was contraindicated 

(women with bloodthinning disorders or 

currently taking 

anticoagulants)

Start time: Lactating approximately 5 days after birth 

Infants approximately 5 days after birth

Duration: Lactating to estimated due date Infants to 

estimated due date

Arm 1: Control group

Description: Placebo capsules and/or formula

Active ingredients: Linoleic acid 53.4% of fatty acids

Dose: 6 500-mg capsules per day to mothers

Blinding: The soy and tuna oil capsules were 

identical in size, color, and shape

ALA: 5.9% of total fatty acids

Arm 2: Treatment

Description: DHA supplemented breastfeeding 

mothers and/or formula

Active ingredients: Linoleic acid 2.7% of fatty acids

Dose: 6 capsules or formula ad lib

ALA: 0.4% total FA

DHA: 29.5% total FA

EPA: 6.5% total FA

AA: 1.8% total FA

Outcome: Visual evoked potential acuity 

(cyc/deg) (Primary)

Follow-up time: 2 months (corrected age)

Arm 1: Sample size 61; mean 5.6; SD (2.4)

Arm 2: Sample size 54; mean 5.6; SD (2.4)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 51; mean 8.2; SD (1.8)

Arm 2: Sample size 44; mean 9.6; SD (3.7)

Outcome: Visual evoked potential latency: 

48 min of arc (ms) (Secondary)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 67; mean 138.0; SD 

(23)

Arm 2: Sample size 58; mean 135.0; SD 

(23)

Outcome: Visual evoked potential latency: 

69 min of arc (ms) (Secondary)

Follow-up time: 2 months (corrected age)

Arm 1: Sample size 66; mean 200.0; SD 

(29)

Arm 2: Sample size 58; mean 193.0; SD 

(27)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 67; mean 131.0; SD 

(21)

Arm 2: Sample size 58; mean 129.0; SD 

(20)

Outcome: Visual evoked potential latency: 

96 min of arc (ms) (Secondary)

Follow-up time: 2 months (corrected age)

Arm 1: Sample size 66; mean 188.0; SD 

(27)

Arm 2: Sample size 58; mean 182.0; SD 

(24)

Smithers et al., 201153

Study name: DOMInO

Study dates: Enrollment 

Study Population: 

Healthy infants Healthy 

pregnant women

Infants enrolled 185 

Inclusion Criteria: 

singleton pregnancies at 

less than 21 weeks’ 

gestation

Start time: Pregnant 18 to 21 weeks gestation

Duration: Pregnant until birth

Arm 1: placebo

Outcome: VEP Latency: 20 min of arc (ms) 

(Secondary)

Follow-up time: 4 months

Arm 1: Sample size 93; mean 133.0; SD 

(14)

197
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

from June 2007 to 

August 2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product, Some authors 

serve on scientific 

advisory boards for 

corporations, Some 

authors have received 

research funding from 

infant formula 

manufacturers

Study follow-up: 4 

months

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Palmer, 201254; Zhou, 

201255; Palmer, 201356; 

Makrides, 2014 57

Infants completers 182

Pregnant age: Tx = 29.5 

years, Placebo = 28.7 

years (Tx = 5.5 years, 

Placebo = 5.4 years) NR

Infant age: (NA) NA

Race of Mother: NR (NR)

Exclusion Criteria: 

already taking a prenatal 

supplement with DHA,

fetus had a known major 

abnormality, mother had 

a bleeding disorder in 

which tuna oil was 

contraindicated, taking 

anticoagulant therapy, 

history of drug or alcohol 

abuse, participating in 

another fatty acid trial,

unable to give written 

informed consent, or

English was not the main 

language spoken at 

home

Description: vegetable oil capsule

Manufacturer: Efamol

Dose: 3 500 mg capsules

Blinding: similar in size, shape, and color

Arm 2: Omega 3 supplement

Description: fish oil capsule

Brand name: Incromega

Manufacturer: Croda Chemicals

Dose: 3 500 mg capsules

DHA: 800/3 mg

EPA: 100/3 mg

Arm 2: Sample size 89; mean 133.0; SD 

(15)

Outcome: VEP Latency: 48 min of arc (ms) 

(Secondary)

Follow-up time: 4 months

Arm 1: Sample size 93; mean 121.0; SD 

(12)

Arm 2: Sample size 89; mean 121.0; SD 

(10)

Outcome: VEP Latency: 69 min of arc (ms) 

(Secondary)

Follow-up time: 4 months

Arm 1: Sample size 93; mean 116.0; SD (9)

Arm 2: Sample size 89; mean 115.0; SD (8)

Outcome: VEP acuity (adjusted) (cyc/deg) 

(Primary)

Follow-up time: 4 months

Arm 1: Sample size 93; mean 8.55; SD 

(1.97)

Arm 2: Sample size 89; mean 8.37; SD 

(1.97)

Outcome: VEP acuity (unadjusted) 

(cyc/deg) (Primary)

Follow-up time: 4 months

Arm 1: Sample size 93; mean 8.55; SD 

(1.86)

Arm 2: Sample size 89; mean 8.37; SD 

(2.11)

198
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Stein et al., 201233

Study name: POSGRAD

Study dates: Feb 2005-

Feb 2007

Study design: Trial 

randomized parallel

Location: NR

Funding source / conflict: 

Government

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Imhoff-Kunsch, 201158; 

Escamilla-Nunez, 201459;

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 1094 

Pregnant withdrawals 63 

Pregnant completers 900

Pregnant age: 26.3 (4.6-

4.8)

Infant age: 39.1 (1.7-1.8)

Race of Mother: NR (NR)

Inclusion Criteria: 

Singleton live births 

without congenital 

anomalies

Exclusion Criteria: 3364: 

high risk pregnancy, 

(history and prevalence 

of pregnancy 

complications, including 

abruption placentae, 

preeclampsia, 

pregnancy-induced 

hypertension, any 

serious bleeding episode 

in the current pregnancy, 

and physician referral); 

lipid metabolism or 

absorption disorders, 

regular intake of fish oil 

or DHA supplement, or 

chronic use of certain 

medication(e.g. epilepsy 

medications)

Start time: Pregnant 18-22 wk

Duration: Pregnant to birth

Arm 1: Placebo

Description: A mixture of corn and soy oil

Manufacturer: Martek Biosciences

Blinding: "Participants and members of the study 

team were unaware of the treatment scheme 

throughout the intervention period of the study"

Arm 2: DHA

Description: DHA 400 mg/d

Manufacturer: Martek Biosciences

Dose: 2 capsule per day

DHA: 2*200mg

Outcome: Visual evoked potential: 

Amplitude P (mV) (Primary)

Follow-up time: 3 months

Arm 1: Sample size 342; mean 8.14; SD 

(6.04)

Arm 2: Sample size 337; mean 7.75; SD 

(5.97)

Follow-up time: 6 months

Arm 1: Sample size 342; mean 11.3; SD 

(6.9)

Arm 2: Sample size 337; mean 11.2; SD 

(7.2)

Outcome: Visual evoked potential: Latency 

N1 (ms) (Primary)

Follow-up time: 3 months

Arm 1: Sample size 342; mean 93.9; SD 

(17.1)

Arm 2: Sample size 337; mean 94.2; SD 

(16.3)

Follow-up time: 6 months

Arm 1: Sample size 342; mean 91.9; SD 

(15.1)

Arm 2: Sample size 337; mean 90.5; SD 

(14.6)

Outcome: Visual evoked potential: Latency 

N3 (ms) (Primary)

Follow-up time: 3 months

Arm 1: Sample size 342; mean 157.1; SD 

(24.1)

Arm 2: Sample size 337; mean 154.8; SD 

(23.8)

Follow-up time: 6 months

Arm 1: Sample size 342; mean 154.9; SD 

(20.2)

Arm 2: Sample size 337; mean 154.2; SD 

(19.9)

Outcome: Visual evoked potential: Latency 

P1 (ms) (Primary)

Follow-up time: 3 months

Arm 1: Sample size 342; mean 126.3; SD 

(18.3)

Arm 2: Sample size 337; mean 125.8; SD 

(17.5)

Follow-up time: 6 months

199
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 342; mean 123.5; SD 

(14.3)

Arm 2: Sample size 337; mean 122.7; SD 

(14.6)

Werkman et al., 1996154

Study name: NR

Study dates: 1987-1990

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study follow-up: 12 

months

Study Population: 

Preterm infants

Infants enrolled 67 

Infants completers 64

Mother age: 23 y (6 y)

Infant age: Born at 29 

wks gestation (2 wks)

Race of Mother: NR 

(100)

Inclusion Criteria: 

Preterm infants weighing 

between 748 and 1398 g 

at birth. They were 

eligible for this study 

when they had tolerated 

enteral intakes > 462 

kJ/kg body weight/day for 

5-7 days

Exclusion Criteria: Need 

for mechanical ventilation 

at that time, 

intraventricular 

hemorrhage > grade 2, 

retinopathy of prematurity 

> stage 2, surgery for 

necrotizing enterocolitis, 

a weight less than the 

fifth percentile for 

gestational age, and a 

history of maternal 

substance abuse

Start time: Infants 25 days

Duration: Infants 25 days - 9 months

Arm 1: Placebo term and pre-term infant formulas

Active ingredients: n-6: 19.1-33.2% of total FA

Dose: Formula remained the infants' major source of 

nutrients and energy through at least 9 mo past 

expected term, but other foods were gradually 

added to the diet beginning at -4 mon past term

Blinding: NR

Total N-3: Preterm: 3% of total FA; term: 4.8% of 

total FA

Arm 2: DHA-supplemented term and pre-term infant 

formulas

Description: Marine oil replaced fat blend in 

commercial formulas

Brand name: Similac

Manufacturer: Ross Products Division

Active ingredients: 18.7-32.6% of total FA

Dose: Formula remained the infants' major source of 

nutrients and energy through at least 9 mo past 

expected term, but other foods were gradually 

added to the diet beginning at -4 mon past term

ALA: Preterm: 3.1% of total FA; Term: 4.9% of total 

FA

DHA: 0.2% of total FA

EPA: 0.3% of total FA

Other dose 1: Preterm: 3.6% of total FA; term: 5.4% 

of total FA

Outcome: number of total looks 

(Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 38.4; SD 

(1.6)

Arm 2: Sample size 33; mean 38.9; SD 

(1.7)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 52.6; SD 

(2.1)

Arm 2: Sample size 33; mean 56.3; SD (2)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 39.1; SD 

(1.8)

Arm 2: Sample size 33; mean 42.0; SD 

(1.8)

Outcome: time/total looks (seconds) 

(Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 1.39; SD 

(0.06)

Arm 2: Sample size 33; mean 1.34; SD 

(0.06)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 2.01; SD 

(0.08)

Arm 2: Sample size 33; mean 1.84; SD 

(0.07)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 1.49; SD 

(0.07)

Arm 2: Sample size 33; mean 1.4; SD 

(0.06)

200
Cognitive Development

Key Points

• Pregnant women. One RCT on supplementation of pregnant women was included in the 

previous AHRQ systematic review; we identified nine additional RCTs. Due to 

heterogeneity of n-3 FA content and outcomes reported, meta-analysis was not possible. 

One study that assessed infants at 14 days reported significant associations between DHA 

supplementation and higher scores on two scales of the Neonatal Behavior Assessment in 

offspring. Another RCT reported that infants of mothers who received placebo were 

significantly less likely than those of mothers who received DHA to score in the highest 

quartile on the receptive language scale of the Bayley Scales of Infant Development 

(BSID) and words understood on the McArthur Communicative Developmental 

Inventory CDI at 18 months. All other RCTs reported insignificant results.

• Breastfeeding women. Six RCTs, including two from the previous AHRQ review, 

reported on supplementation for lactating women. Due to heterogeneity of n-3FA content 

and outcomes measured, meta-analysis was not possible. Associations between 

supplementation and cognitive outcomes in offspring were not significant in these 

studies.

• Pre-term infants. The previous AHRQ systematic review included six RCTs in preterm 

infants that reported cognitive outcomes, while the current one identified an additional 

six reports on five RCTs. Seven of these RCTs (identified by either the new or prior 

systematic review) reported the Bayley MDI score at 18 to 24 months of age; the pooled 

difference between the intervention and placebo groups was significant (WMD 2.24; 95% 

CI 0.05, 4.43). The other RCTs reported mixed results.

• Full term infants. The previous AHRQ systematic review reported that six of eight 

RCTs did not find a significant difference between intervention and placebo groups in 

Bayley MDI scores. The current review identified five additional reports on four RCTs 

that measured cognitive outcomes. One of the RCTs identified in the prior AHRQ review 

and two identified in the current systematic review reported Bayley MDI at 18 to 24 

months of age; the pooled difference in MDI scores between the intervention and placebo 

groups was not significant (WMD 0.75, 95% CI -9.29, 10.79). The two new RCTs that 

could not be pooled reported insignificant results regarding cognitive outcomes.

• Observational studies. Seven reports on six observational studies investigated potential 

association of maternal or infant n-3 FA intake with childhood cognitive outcomes. 

Several assessed infant cognitive development using the BSID, whereas others conducted 

follow up at seven, eight, and eleven years of age. Only one study reported a significant 

association between n-3 FA intake and cognitive outcomes. Although that study was high 

quality in that in controlled for 18 important potential confounders, the authors caution 

that the effect sizes were small (approximately one-tenth of a standard deviation).

201
Description of Included Studies

Randomized Controlled Trials

Interventions with pregnant women

The prior AHRQ-funded systematic review included one RCT on maternal supplementation 

during pregnancy; no differences were observed between groups in the Fagan Test of Infant 

Intelligence at 6 and 9 months of age.86

For the current systematic review, nine additional RCTs of pregnant women that reported 

cognitive outcomes were identified (see Table 17).

35, 44, 66, 74, 76, 77, 141 Follow-up times were 

diverse; children ranged in age from 14 days to 7 years. Due to the heterogeneity of 

interventions, populations, outcome measures, and timing, meta-analysis was not conducted. 

Results are summarized below.

DHA Alone

In the US, Gustafson et al., 201374 randomized healthy pregnant women to capsules 

containing either vegetable oil or algal oil as a source of DHA (total of 0.600 g/d). The majority 

of enrollees were non-White (37.3% African American, 3.0% Asian, and 13.4% Hispanic). This 

study had a significantly lower rate of completion (78%) than other studies of pregnant women. 

Of 67 pregnant women enrolled, 52 completed the study through childbirth. Forty-one infants 

participated in the Neonatal Behavior Assessment at 14 days of age. Infants in the DHA group 

scored significantly higher on the autonomic and motor skills scales.

Mulder, 201475 enrolled 271 pregnant women in an RCT of supplements containing 400 mg 

DHA versus placebo conducted in Canada. At 18 months of age, 200 of their infants were 

assessed using the BSID (Version 3) and the McArthur Communicative Developmental 

Inventory (CDI). Infants in the placebo group were significantly less likely than those in the 

DHA group to score in the highest quartile on the receptive language scale of the BSID and 

words understood on the CDI.

Ramakrishnan, 201561 reported on the POSGRAD study conducted in Mexico. Over 1,000 

pregnant women at 18 to 22 weeks gestation were randomized to placebo or capsule containing 

200 mg DHA. There was no difference between groups in Bayley MDI score at 18 months; 730 

children completed this follow-up. 

DHA Plus EPA

Makrides, 201035 reported on the DOMInO trial conducted in Australia which randomized 

pregnant women to either capsules containing vegetable oil or fish oil (0.800 g DHA and 0.100 

g/d EPA). The authors reported no difference in mean score on the cognitive component of the 

BSID (Version 3) at 18 months of age. Makrides, 201457 reported results of this study at four 

years. There were no significant differences between groups in any scales of the Behavior Rating 

Inventory of Executive Function (Preschool). 

Dunstan et al., 200844 also conducted an RCT in Australia. Pregnant women with a history of 

allergy were randomized to olive oil capsule or fish oil capsule containing 2.2 g DHA and 1.1 g 

EPA. Children in the fish oil group scored significantly higher on the hand eye coordination 

component of the Griffith Mental Development Scale scores at 2.5 years of age. Differences 

were not statistically significant for the six other Griffith components.

Campoy et al., 2011141 reported on the NUHEAL study conducted in Germany, Spain, and 

Hungary. Pregnant women in the second half of pregnancy were randomized to three groups who 

202
all received a milk based supplement containing vitamins and minerals in amounts meeting the 

recommended intakes for European women. One of the groups received the supplement 

containing additional n-3 FA (DHA 0.500 g, EPA 0.100 g), while another received a supplement 

containing additional folic acid. Children were followed up at 6.5 years of age; differences in the 

Kauffman Assessment Battery for Children (K-ABC) were insignificant for all scales.

Tofail et al., 200677 randomized pregnant women in Bangladesh to either soy oil capsules 

containing 0.27 g ALA and 2.25 g linoleic acid or fish oil capsules containing 1.2 g DHA and 1.8 

g EPA. Only 151 of the 400 women enrolled (38%) completed the study. There were no 

significant differences in BSID II Mental Development Index (MDI) scores when infants were 

10 months of age. 

Helland et al., 200876 randomized pregnant women in Norway to 10 mL of either corn oil or 

cod liver oil (n-3 FA content not reported) from week 18 of pregnancy until 3 months after 

delivery. At 7 years of age, no significant differences were observed in scores on the Kaufman 

Assessment Battery for Children (K-ABC) test.

DHA Plus AA

Van Goor et al., 201166 reported on the Groningen LCPUFA study conducted in the 

Netherlands. One hundred and nineteen pregnant women were randomized to three groups who 

received soy oil capsules containing either no n-3 FA, DHA (0.220 g/d), or DHA (0.220 g) +AA 

(0.220 g). There were no differences between groups in the BSID MDI at 18 months of age.

Postpartum Maternal Supplementation

Two RCTs86, 155 and one prospective cohort study156 on maternal supplementation during 

breastfeeding were identified in the prior AHRQ systematic review. In these studies, 

supplementation with n-3 FA had no effect on cognition in offspring.

The current systematic review identified four new RCTs of lactating women that reported 

cognitive outcomes.76, 116, 128, 135 All were conducted in Western countries; most primarily 

enrolled white women. Sample sizes ranged from 89 to 545 women. Enrollment took place 

between 1995 and 2012. Follow up timing ranged from 9 months of age to 7 years. Due to 

heterogeneity of interventions, populations, outcome measures, and timing, meta-analysis was 

not conducted. Results are summarized below.

DHA Plus EPA

Makrides et al., 2009116 reported on the DINO trial, conducted in Australia. Breast-feeding 

mothers of pre-term children were randomized to soy capsules or tuna oil capsules (0.500 g/d 

DHA) and instructed to take them daily until the infant reached "expected" date of delivery. 

When children were 18 months old, no difference was observed between groups in mean BSID 

MDI scores. However, for infants born weighing less than 1250g, the MDI in the high-DHA 

group was higher than with standard DHA in the unadjusted comparison (mean difference, 4.7; 

95% CI, 0.2-9.2) but did not reach statistical significance following adjustment for gestational 

age, sex, maternal education, and birth order (mean difference, 3.8; 95% CI, −0.5 to 8.0). 

Lauritzen et al., 2005128 randomized pregnant Danish women with a fish intake below the 

population median (< 0.4 g n-3 LCPUFA·d–1) and an intention to breastfeed for at least four 

months to muesli bars containing either olive oil or 4.5 g fish oil (DHA 60%). At one year of 

age, infants were assessed with the MacArthur CDI Linguistic Development instrument. No 

significant differences were seen between groups. 

203
In the U.S., Jensen et al., 2010135 randomized breast feeding women to receive either 

vegetable oil capsule or high-DHA (0.200 g/d) algal triglyceride capsules for the first four 

months of lactation. At five years of age, children were assessed with the Wechsler Primary and 

Preschool Scale of Intelligence – Revised. No significant differences were observed between 

groups. The results for Helland et al., 2008,76which randomized pregnant and breastfeeding 

women to cod liver oil or vegetable oil, are described above in the section on pregnant women. 

This trial included supplementation during both pregnancy and lactation. No significant results 

were found for cognitive outcomes.

Infant Formula Supplementation with n-3 FA and Cognitive Function in Preterm infants

The previous AHRQ systematic review identified six RCTs in pre-term infants. Four of the 

five trials that reported the Bayley MDI score at various follow-up times found no significant 

difference between the placebo and intervention groups.149, 157-159Two studies154, 160found a 

significant difference between the supplementation group and the placebo group on some scales 

of the Fagan Test of Infant Intelligence. One RCT that reported Bayley scores also found no 

significant differences between groups in the Infant version of the MacArthur Communicative 

Development Inventories (MCDI).157

Five RCTs identified for the current report (described in six publications) assessed the effects 

of supplementing pre-term infants with n-3 FA on cognitive outcomes.99, 107, 108, 116, 125, 137 Studies 

were conducted in Taiwan, the UK, Norway, Canada, and Australia. Follow up timing ranged 

from 6 months to 10 years. Using studies from both the prior and current systematic reviews, we 

were able to pool seven studies of n-3 supplemented formulas that reported the Bayley’s MDI at 

18 to 24 months of age. Four of these studies were reported in the previous AHRQ systematic 

review,157, 159 158 149 while three were newly identified in the current review.108, 116, 125 All 

supplements were categorized as DHA plus AA. Three of the formulas included some EPA; 

however, the proportion was too small to have clinical significance. The pooled difference in 

MDI scores between the intervention and placebo groups was significant (WMD 2.24; 95% CI 

0.05, 4.43), as displayed in Figure 24. There was low heterogeneity (I2 = 23.2%) and no evidence 

of publication bias (Begg’s p=0.293; Egger’s p=0.388). 

Results of new studies that could not be pooled, due to heterogeneity of intervention, 

outcome, or follow-up, are described below.

DHA Plus AA

We identified two studies of supplements containing DHA plus AA for pre-term infants not 

included in the prior systematic review that we did not pool due to follow-up timing. We also 

identified one long-term follow-up of a study included in the pooled analysis. 

Fang (2005)

137 conducted an RCT in Taiwan that randomized preterm infants to either 

standard formula or formula supplemented with DHA (0.05%) and AA (0.10%) for 24 weeks. 

Infants were assessed at 6 months and 1 year of age using the Bayley MDI. Infants who received 

supplemented formula scored significantly higher at both time points. 

Isaacs (2011)

99 randomized preterm infants in the UK to nine months of either standard 

formula or formula supplemented with DHA (0.5 g /100g fat), EPA (0.1 g/100g fat) and AA 

(0.04 g /100g fat). At 10 years of age, children were assessed with the Wechsler Abbreviated 

Scale of Intelligence, Wechsler Individual Achievement Test, and the CMS Word Pairs 

instrument. Differences between groups were not statistically significant.

Almaas, 2015126 reported on a long term follow-up of an RCT that was included in the metaanalysis described above.125 At 8 years, children completed the Wechsler Abbreviated Scale of 

204
Intelligence, Wechsler Intelligence Scale for Children III Digit Span, and the California Verbal 

Learning Test II. No significant differences were observed between the intervention group and 

the control group on any of these outcomes.

DHA Plus EPA Plus AA

One study identified for the current report that administered formula supplemented with 

DHA+EPA+AA could not be pooled with the other studies. Isaacs et al., 201199 randomized 

preterm infants in the UK to nine months of either standard formula or formula supplemented 

with DHA (0.5 g /100g fat), EPA (0.1 g/100g fat) and AA (0.04 g /100g fat). At 10 years of age, 

children were assessed with the Wechsler Abbreviated Scale of Intelligence, Wechsler Individual 

Achievement Test, and the CMS Word Pairs instrument. Differences between groups were not 

statistically significant.

Figure 24. Preterm cognitive

Infant Formula Supplementation with n-3 FA and Cognitive Function in Full Term infants

The original report identified eight RCTs that assessed the effect of supplementing term 

infants with n-3 FA on cognitive outcomes; six of the eight studies found no significant 

difference between intervention and placebo groups in the Bayley MDI score at any follow-up 

point. A meta-analysis of 3 RCTs reporting the Bayley MDI score at 12 months showed no 

significant difference between intervention and placebo groups. 

The current review identified five additional reports on four RCTs of full term infants that 

measured cognitive outcomes.63, 65, 122, 140, 146 With the exception of a study conducted in 

Bangladesh, the studies were conducted in Western countries with primarily Caucasian samples. 

Follow-up timing ranged from 10 months to 9 years. One of the RCTs161 identified in the prior 

AHRQ review and two identified in the current systematic review63, 122 reported Bayley’s MDI at 

18 to 24 months of age, and used supplements containing DHA + AA; thus we pooled these 

three studies. The pooled difference in MDI scores between the intervention and placebo groups 

was not significant (WMD 0.75, 95% CI -9.29, 10.79), as displayed in Figure 25. Considerable 

heterogeneity was detected (I2 = 70.3%).

Results of the two new studies that could not be pooled, due to heterogeneity of intervention, 

outcome, or follow-up timing, are described below.

205
DHA Plus AA

Birch et al., 2007146randomized healthy full term infants in the US to 17 weeks of either 

standard formula, formula supplemented with DHA (0.36%), or formula supplemented with 

DHA (0.36%) plus AA (0.72%). A breast fed group served as an additional comparison. At four 

years of age, the control and DHA-supplemented groups had significantly lower verbal IQ scores 

than the breast fed group (the group that received DHA plus AA had an insignificantly lower 

score than the breastfed group). However, no differences were observed between any of the 

formula-fed groups and the breast-fed group in performance IQ or full scale IQ.

DHA Plus EPA

A newly identified study, Meldrum et al., 2012140 was not pooled due to heterogeneity of 

population and intervention. Researchers randomized healthy Australian full term infants of 

women with allergies to six months of either olive oil or fish oil (0.250 g/d DHA, 0.060 g/d 

EPA) supplements. At 18 months of age, infants were assessed using the cognitive component of 

the BSID (Version 3); differences between the groups were not significant.

Figure 25. Full term cognitive

Observational Studies

Seven reports on six observational studies that investigated potential associations of maternal 

or infant n-3 FA intake with childhood cognitive outcomes were identified for the current report

(see Table 18).

89, 132, 143, 144, 162-164 All were conducted in the U.S. or Europe. Two studies 

collected diet information via food frequency questionnaires (FFQ) and five collected biomarker 

data. Several assessed infant cognitive development using the Bayley Scales of Infant 

Development (BSID), while others conducted follow up at seven, eight, and eleven years of age.

Valent, et al.132 recruited pregnant women at 20 to 22 weeks gestation from a hospital in 

northern Italy. The primary purpose of the study was to assess the potential association between 

maternal mercury exposure and neurodevelopment outcomes in offspring. Information on 

maternal fish intake was collected by FFQ and levels of PUFAs were measured via maternal 

serum at week 32 of gestation. (Mercury levels were obtained from cord blood; it is unclear why 

PUFAs were not measured in the cord blood samples.) Of 900 women recruited, 767 (85%) 

completed the study through childbirth. At 18 months, 632 children were assessed using the 

BSID III. Mothers of children lost to follow-up were of lower socio-economic status and had 

lower median IQ than those who participated. The authors developed a model that adjusted for 

206
maternal factors (concentration of mercury in hair during pregnancy, fish intake, weight gain 

during pregnancy, marital status, SES, number of children living at home, alcohol intake during 

pregnancy, breastfeeding history) and child factors (sex, birth weight, intake of fish, day care 

attendance) to assess whether concentration of ALA, EPA, DHA, LA, or ARA (mg/ml) were 

associated with BSID III scores. No statistically significant associations were found. However, 

child duration of fresh fish intake was associated with increased score on the cognitive 

component of the BSID III.

Keim, et al.162 analyzed data from the Pregnancy, Infection, and Nutrition Study. This 

prospective cohort study enrolled pregnant women from North Carolina hospitals; 1,169 were 

eligible for post-partum follow-up. At four months post-partum, the study analyzed n-3 FA 

content of mothers’ breast milk samples and also collected data on n-3 FA content of any infant 

formula utilized. At 12 months of age, offspring cognition was assessed using the Mullen Scales 

of Early Learning. When controlling for infant sex, pre-term status, race/ethnicity, mother’s 

education, and parity, no statistically significant associations between scores and AA, DHA, or 

total LCPUFA were identified.

Julvez et al.143 and Guxens, et al.144 reported on the INMA (Infancia Y Medio Ambiete) 

prospective cohort study conducted in Catalonia, Spain. Pregnant women (N = 657) were 

recruited from a public health center. Colostrum was collected two to four days after childbirth to 

measure LCPUFA content for a sub-sample of women (N = 277). Breastfeeding information was 

collected by questionnaire from all women when the offspring were 6 and 14 months of age. At 

14 months of age, 504 infants were assessed using the BSID; in a model adjusted for child’s age, 

maternal and paternal factors (education, social class, attachment to the child, IQ, mental health) 

and maternal smoking and alcohol use, PUFA levels in colostrum were not associated with 

scores. At four years of age, cognition was assessed in 434 children using the McCarthy Scales 

of Children’s Abilities (MSCA). No association was seen between n-3 FA intake during infancy 

and MSCA scores143 when adjusting for child (age, sex, day care attendance) and parental (age, 

parity, alcohol and smoking during pregnancy, education, social class, mental health, attachment 

with child) characteristics.

Bernard et al.89 reported on the EDEN prospective cohort study conducted in France. Using 

data on diet during last trimester of pregnancy collected via FFQ and a booklet displaying 

portion sizes, the researchers estimated intake of LA, AA, ALA, EPA, DHA, total n-6, total n-3, 

and total LCPUFAs for 1,585 women. At two years of age, 1,215 of their children were assessed 

using the Communicative Development Inventory (CDI). At three years of age 1,185 children 

were assessed using the Ages and Stages Questionnaire (ASQ), and Peg Moving Task Version 5. 

Among never breastfed children, a significant inverse relationship between maternal n6:n3 ratio 

and CDI and ASQ scores was reported. No significant associations were seen among scores of 

breastfed children and maternal intakes. Models were adjusted for child factors (gender, age, 

gestational age, firstborn, and main daytime caregiver) and parental factors (maternal age, 

obesity, energy intake, smoking and alcohol consumption during pregnancy, education, income, 

and maternal attachment).

Bakker, et al.163 conducted a prospective cohort study that enrolled 750 pregnant women in

the Netherlands. At childbirth, cord plasma was collected and analyzed for LCPUFA content. At 

7 years of age, 306 children were assessed using the Kaufman Assessment Battery for Children 

(K-ABC). Baseline characteristics of participating and non-participating children were not 

significantly different. Backward stepwise multiple linear regression analyses found no 

association between cord plasma AA or DHA and K-ABC scores. 

207
Finally, Steer, et al.164 analyzed data from the Avon Longitudinal Study Of Parents in 

Children, conducted in the UK. Blood samples from 5,222 pregnant women were analyzed for 

LCPUFA content. At 8 years of age, 2,839 of their children were assessed using the Wechsler 

Intelligence Scale for Children (WISC). In a model that controlled for 18 potential confounders, 

low levels of AA were associated with lower performance IQ, high levels of adrenic acid were 

associated with lower verbal IQ, and low levels of DHA were associated with lower verbal and 

full scale IQ scores. The authors caution that the effect sizes were small (approximately onetenth of a standard deviation.

208
Table 17. RCTs for cognitive development

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Almaas et al., 2015126

Study name: Unnamed 

Trial D

Study dates: 2003-2014

Study design: Trial 

randomized parallel

Location: Norway

Funding source / conflict: 

Government, None

Study follow-up: 8 years

Original, same study, or 

follow-up studies: 

Henriksen, 20008107; 

Westerberg, 2011125

Study Population: 

Preterm infants Low birth 

weight infants

Infants enrolled 129 

Infants completers 98

Mother age: Median: 

Intervention: 31 years 

Control: 32 years 28-35 

years

Infant age: Median 

Gestational age: Control: 

28.9 weeks Intervention: 

28.4 weeks Gestational 

age: 26.6-30.9 weeks

Race of Mother: NR

Inclusion Criteria: Very 

low birth weight infants 

(birth weight <1500 g)

Exclusion Criteria: Major 

congenital abnormalities 

and cerebral hemorrhage

Start time: Infants (intervention began when the 

infant received most of his nutrients enterally: 

>100ml human milk/kg body weight/day

Duration: Infants Until discharge or bottle of study oil 

was empty (average 63 days of age)

Arm 1: Control

Description: Study oil: soy oil and medium chain 

triglycerides

Active ingredients: 127mg linolenic acid/100 ml 

milk(27.1% total fatty acids)

Dose: 0.5 ml study oil/100 ml human milk

Blinding: Study oils packed in numbered bottles in 

hospital pharmacy

Maternal conditions

Infant conditions

ALA: 16mg/100 ml milk; 3.4% total fatty acids

Current smoker 15%

Low birth weight 100%

Other conditions 1 Small for gestational age: 30%

Arm 2: Intervention

Description: DHA and AA-containing oil

Manufacturer: Martek Biosciences

Active ingredients: 88mg/100 ml linoleic acid per 100 

ml milk (18.8%)

Dose: 0.5 ml study oil per 100 ml milk, ad lib

Maternal conditions

Infant conditions

DHA: 32mg/100ml milk (6.9%)

AA: 31 mg/100 ml milk (6.7% total fatty acids

Current smoker 19%

Low birth weight 100%

Other conditions 1 Small for gestational age: 29%

Outcome: Wechsler Abbreviated Scale of 

Intelligence: Full Scale IQ (Secondary)

Follow-up time: 8 years

Arm 1: Sample size 52; mean 93.9; SD (10)

Arm 2: Sample size 45; mean 92.7; SD 

(8.8)

Outcome: Wechsler Abbreviated Scale of 

Intelligence: Verbal IQ (Secondary)

Follow-up time: 8 years

Arm 1: Sample size 52; mean 90.3; SD 

(12.5)

Arm 2: Sample size 45; mean 88.8; SD 

(10.3)

Outcome: Wechsler Abbreviated Scale of 

Intelligence: performance IQ (Secondary)

Follow-up time: 8 years

Arm 1: Sample size 52; mean 95.9; SD 

(14.4)

Arm 2: Sample size 45; mean 95.0; SD 

(12.6)

Westerberg et al., 2011125

Study name: Unnamed 

Trial D

Study dates: Enrollment:

Study Population: 

Preterm infants

Infants enrolled 141 

Infants completers 92

Inclusion Criteria: All 

VLBW infants (<1500g) 

born between December 

2003 and November 

2005 at RikshospitaletRadiumhospitalet 

Start time: Infants at start of enteral feeding

Duration: Infants until discharge or until the study oil 

bottle was empty (mean duration of supplementation 

was 63 days)

Outcome: Bayley Mental Development 

Index (MDI) (Secondary)

Follow-up time: 20 months

Arm 1: Sample size 42; mean 82.9; SD 

(13.3)

Arm 2: Sample size 40; mean 83.5; SD 

209
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

December 2003 and 

October 2005

Study design: Trial 

randomized parallel

Location: Norway

Funding source / conflict: 

Multiple foundations and 

Societies, Manufacturer 

supplied product

Study follow-up: 20 

months

Mother age: Intervention: 

30.8 years Control: 31.7 

years (Intervention: 4.9 

years Control: 5.0 years) 

28-35 years

Infant age: Mean 

Gestational age: 

Intervention: 28.7 weeks 

Control: 28.9 weeks 

(Intervention: 2.9 weeks 

Control: 2.7 weeks) 

Gestational age: 26.6-

30.9 weeks

Race of Mother: NR

Baseline biomarker 

information: DHA: 

intervention[64.2 (23.5) 

mg/mL] and control 

group [61.3 (18.7)mg / 

mL], AA:

intervention[205.6 (52.8) 

mg/mL] and control 

group [199.6 (48.7)mg / 

mL],

Medical Center, 

Akershus University 

Hospital, Buskerud 

Hospital, and Vestfold 

Hospital in Norway

Exclusion Criteria: Major 

congenital abnormalities 

or cerebral hemorrhage 

(grade 3 or 4) as

determined through 

ultrasonography

Arm 1: Placebo

Description: Soy oil

Active ingredients: 127mg linolenic acid/100 ml 

milk(27.1% total fatty acids)

Dose: 0.5 ml study oil/100 ml human milk

Blinding: Study oils packed in numbered bottles in 

hospital pharmacy

ALA: 16mg/100 ml milk; 3.4% total fatty acids

Arm 2: DHA + AA group

Description: DHA and AA-containing oil

Manufacturer: Martek

Active ingredients: 88mg/100 ml linoleic acid per 100 

ml milk (18.8%)

Dose: 0.5 ml study oil per 100 ml milk, ad lib

Maternal conditions

ALA: 11mg/100 ml milk; 3.4% total fatty acids

DHA: 32mg/100ml milk (6.9%)

AA: 31 mg/100 ml milk (6.7% total fatty acids

Current smoker 22% during pregnancy

(10.5)

Birch et al., 2007146

Study name: Birch

Study dates: 1993-1999

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy infants, Pregnant 

women whose unborn 

children were at high risk 

of developing asthma

Infants enrolled 79+40BF 

Infants completers 

52+32BF

Infant age: birth (0-5 

days)

Race of Mother: NR

Inclusion Criteria: All 

participants were born at 

37 to 40 weeks 

postmenstrual age. Only 

singleton births with birth

weights appropriate for 

gestational age

Exclusion Criteria: family 

history of milk-protein 

allergy, genetic or familial 

eye disease (e.g. 

hereditary retinal 

disease, strabismus), 

vegetarian or vegan 

maternal dietary patterns, 

Start time: Infants birth (0-5 days)

Duration: Infants 17 weeks

Arm 1: Control

Description: standard infant formula without added 

n-3 FA

Brand name: Enfamil with Iron

Manufacturer: Mead Johnson Nutritionals

Active ingredients: linoleic acid: 15% of total fats

ALA: 1.5% of total fats

Arm 2: DHA

Description: infant formula fortified with DHA

Brand name: Enfamil with Iron, supplemented with 

DHASCO

Outcome: Wechsler Preschool and Primary 

Scale of Intelligence: Full-Scale IQ 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 101.0; SE 

(2.6)

Arm 2: Sample size 16; mean 105.9; SE 

(3.9)

Arm 3: Sample size 32; mean 107.5; SE 

(3.1)

Outcome: Wechsler Preschool and Primary 

Scale of Intelligence: Performance IQ 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 104.2; SE 

(2.7)

210
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 4 years maternal metabolic 

disease, anemia, or 

infection, presence of a 

congenital malformation 

or infection, jaundice, 

perinatal asphyxia, 

meconium aspiration, 

and any perinatal event 

which resulted in 

placement of the infant in 

the neonatal intensive 

care unit

Manufacturer: Formula: Mead Johnson; DHA: 

Martek Biosciences

Active ingredients: linoleic acid: 15% of total fats

ALA: 1.5%

DHA: 0.36%

Arm 3: DHA+ARA

Description: infant formula fortified with DHA and 

ARA

Brand name: Enfamil with Iron, fortified with 

DHASCO and ARASCO

Manufacturer: Formula: Mead-Johnson; DHA, ARA: 

Martek Biosciences

Active ingredients: linoleic acid 15%

ALA: 1.5%

DHA: 0.36%

AA: 0.72%

Arm 2: Sample size 16; mean 108.1; SE 

(3.8)

Arm 3: Sample size 32; mean 108.6; SE 

(3.3)

Outcome: Wechsler Preschool and Primary 

Scale of Intelligence: Verbal IQ 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 98.8; SE 

(2.6)

Arm 2: Sample size 16; mean 102.7; SE 

(4.1)

Arm 3: Sample size 32; mean 104.5; SE 

(2.9)

Bouwstra et al., 200563

Study name: Groningen 

LCPUFA study

Study dates: 1997-2002

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Industry

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; de 

Jong, 201064; de Jong, 

201265; van Goor, 201036; 

van Goor, 201166

Study Population: 

Healthy infants

Infants enrolled 472 

Infants completers 446

Mother age: 31 years (5 

years) NR

Infant age: birth

Race of Mother: White 

European (100%)

Inclusion Criteria: healthy 

term infants

Exclusion Criteria: infants 

who had a congenital 

disorder that interfered 

with adequate functioning 

in daily life, infants from 

multiple births, infants 

whose mothers did not 

have mastery of the 

Dutch language or 

suffered from significant 

illness or disability, 

adopted and foster 

infants, and formula-fed 

infants who had received 

human milk for >5 d.

Start time: Infants Birth

Duration: Infants 2 months

Arm 1: Control group

Description: Standard formula

Brand name: Nutrilon premium

Manufacturer: Zoetermeer, Netherlands

Active ingredients: linoleic acid (11mol%); ALA 1.27 

mol%

Dose: ad lib

Maternal conditions

Current smoker 31% during pregnancy

Maternal abuse of alcohol/psychotropic drugs 

Alcohol USE during pregnancy 8%

Arm 2: LCPUFA formula

Description: LCPUFA formula

Dose: ad lib

Maternal conditions

DHA: 0.30% DHA

AA: 0.45% AA

Current smoker 31% during pregnancy

Maternal abuse of alcohol/psychotropic drugs 9% 

used alcohol during pregnancy

Outcome: Bayley Scales of Infant 

Development (Mental Development Index) 

(Secondary)

Follow-up time: 18 months

Arm 1: Sample size 155; mean 105.4; SD 

(15)

Arm 2: Sample size 135; mean 102.7; SD 

(15.4)

211
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 3: breast feeding group

Description: breast fed, no formula

Maternal conditions

Current smoker 19% smoked during pregnancy

Maternal abuse of alcohol/psychotropic drugs 24% 

used alcohol during pregnancy

Brew et al., 2015165

Study name: CAPS

Study dates: September 

1997 to 1999-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government

Study follow-up: 3, 5, 7, 

and 9 years of school

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; 

Toelle, 2010169

Study Population: 

Healthy infants

Infants enrolled 616 

Infants completers 239

Pregnant age: 29.8 

(4.90)

Infant age: NR

Race of Mother: NR (NR)

Baseline biomarker 

information: Total n-3 

PUFA 

(DHA+EPA+DPA+ALA) 

as % of total fatty acids 

at 4 ages (on a bar 

chart): 18 months: 

Intervention 72% 

Controls: 48% 3 years 

Intervention 64% 

Controls: 46% 5 years 

Intervention 62% 

Controls: 50% 8 years: 

Intervention 50% 

Controls: 45%

Baseline Omega-3 

intake: 500 mg of tuna 

fish oil, daily, which 

comprised 37% LCPUFA 

(including 135 mg of 

DHA and 32 mg of EPA 

per capsule) and 6% 

omega-6 PUFA (linoleic 

Inclusion Criteria: parent 

or an older sibling had a 

history of asthma or 

recurrent wheezing, and 

that the child was born at 

436 weeks of gestation

Exclusion Criteria: NR

Start time: Infants Birth

Duration: Infants 8 years

Arm 1: Intervention

Description: d 500 mg of tuna fish oil 37% LCPUFA

Manufacturer: Nu-Mega Industries Pty Ltd, Brisbane, 

Australia

DHA: 135 mg

EPA: 32 mg

AA: 6% of omega 3PUFA (linoleic acid, arachidonic 

acid, docosapentaenoic acid)

Arm 2: Control

Description: a daily Sunola oil capsule

Manufacturer: Nu-Mega Industries

ALA: 0.3%

Outcome: National Assessment Program 

Literacy and Numeracy (NAPLAN): 

numeracy score (difference in NAPLAN 

units) (Secondary)

Follow-up time: 10-11 years

239; difference in means -13.7; 95% CI

Follow-up time: 12-13 years

239; difference in means -11.7; 95% CI

Follow-up time: 14-15 years

239; difference in means -24.1; 95% CI

Follow-up time: 8-9 years

239; difference in means -25.4; 95% CI

Outcome: National Assessment Program 

Literacy and Numeracy (NAPLAN): reading 

score (difference in NAPLAN units) 

(Secondary)

Follow-up time: 10-11 years

239; difference in means -3.2; 95% CI

Follow-up time: 12-13 years

239; difference in means -7.0; 95% CI

Follow-up time: 14-15 years

239; difference in means -19.9; 95% CI

Follow-up time: 8-9 years

239; difference in means -27.03; 95% CI

212
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

acid, arachidonic acid 

and docosapentaenoic 

acid)

Campoy et al., 2011141

Study name: NR

Study dates: NR, <2011

Study design: Trial 

randomized factorial 

design

Location: Germany, 

Spain, Hungary

Funding source / conflict: 

Government, None

Study follow-up: 6.5 

years

Original, same study, or 

follow-up studies: 

Escolano-Margarit, 

2011130

Study Population: 

Healthy pregnant women

Pregnant enrolled 315 

Pregnant completers 154

Pregnant age: 31 years 

(NR)

Race of Mother: White 

European (99%)

Baseline biomarker 

information: From 

Krauss, 2007 mean DHA 

Placebo group 5.95 Fish 

oil group 5.75 5-MHTF 

(folic acid) group 5.68 

Fish oil + 5-MHTF group 

5.89 mean EPA Placebo 

group 0.28 Fish oil group 

0.18 5-MHTF (folic acid) 

group 0.17 Fish oil + 5-

MHTF group 0.22

Inclusion Criteria: health 

pregnant women, 

singleton pregnancy, 

gestation 20 week at 

enrollment, body weight 

between 50 and 92 kg at 

study entry, and intention 

to deliver in one of the 

obstetrical centers

Exclusion Criteria: 

serious chronic illness 

(e.g., diabetes, hepatitis, 

or chronic enteric 

disease), use of FO 

supplements since the 

beginning of pregnancy 

or folate or vitamin B-12 

supplements after 

gestation week 16

Start time: Pregnant 22 weeks gestation Infants 22 

weeks gestation

Duration: Pregnant until birth Infants until birth

Arm 1: placebo

Description: milk-based supplement

Brand name: Blemil Plus

Manufacturer: Ordesa Laboratorios, Barcelona, 

Spain)

Active ingredients: vitamins and minerals in amounts 

meeting the recommended intakes during the 

second half of pregnancy for European women

Dose: one daily dose of 15 g

Blinding: supplements were not distinguishable with 

respect to the appearance of the sachets or to their 

contents

Maternal conditions

Current smoker during pregnancy 8.9%

Arm 2: fish oil

Description: fish oil in milk-based supplement

Manufacturer: Pronova Biocare, Lysaker, Norway

Active ingredients: vitamins and minerals in amounts 

meeting the recommended intakes during the 

second half of pregnancy for European women

Dose: one 15 g dose

Maternal conditions

DHA: 500 mg

EPA: 100 mg

Current smoker during pregnancy 18.9%

Arm 3: folic acid

Description: 400 ug 5-MTHF

Manufacturer: BASF, Ludwigshafen, Germany

Active ingredients: vitamins and minerals in amounts 

meeting the recommended intakes during the 

second half of pregnancy for European women

Dose: one 15 g dose

Maternal conditions

Outcome: Kauffman Assessment Battery 

for Children: Mental Processing Composite 

(Secondary)

Follow-up time: 6.5 years

Arm 1: Sample size 45; median 110.0; IQR 

(14.5)

Arm 2: Sample size 37; median 110.0; IQR 

(11)

Arm 3: Sample size 35; median 108.0; IQR 

(12)

Arm 4: Sample size 37; median 108.0; IQR 

(10.5)

Outcome: Kauffman Assessment Battery 

for Children: Sequential Processing Scale 

(Secondary)

Follow-up time: 6.5 years

Arm 1: Sample size 45; median 106.0; IQR 

(19)

Arm 2: Sample size 37; median 108.0; IQR 

(12)

Arm 3: Sample size 35; median 104.0; IQR 

(14)

Arm 4: Sample size 37; median 104.0; IQR 

(17)

Outcome: Kauffman Assessment Battery 

for Children: Simultaneous Processing 

Scale (Secondary)

Follow-up time: 6.5 years

Arm 1: Sample size 45; median 112.0; IQR 

(11.5)

Arm 2: Sample size 37; median 112.0; IQR 

(10.5)

Arm 3: Sample size 35; median 109.0; IQR 

(14)

Arm 4: Sample size 37; median 110.0; IQR 

(10.5)

213
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Current smoker during pregnancy 17.1%

Arm 4: folic acid + fish oil

Description: 400 _x0001_g 5-MTHF +fish oil

Manufacturer: BASF, Ludwigshafen, Germany

Active ingredients: vitamins and minerals in amounts 

meeting the recommended intakes during the 

second half of pregnancy for European women

Dose: one 15 g dose

Maternal conditions

DHA: 500 mg

EPA: 100 mg

Current smoker during pregnancy 18.9%

Carlson et al., 1996160

Study name: NR

Study dates: NR (<1995)

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study follow-up: 12 

months

Study Population: 

Preterm infants

Infants enrolled 59 

Infants completers 27

Infant age: 3 days (NR) 2 

to 5 days

Race of Mother: NR 

(100)

Inclusion Criteria: infants 

weighing between 747 

and 1275 g at birth who 

achieved full enteral 

feeding of 418 kJ (100 

kcal)/kg/d by 6 wk of age 

and tolerated enteral 

feeding thereafter

Exclusion Criteria: 

intraventricular or 

periventricular 

hemorrhage > grade 2, a 

history of maternal 

cocaine or alcohol abuse, 

congenital anomalies 

likely to affect long-term 

growth and development, 

or intrauterine growth 

retardation defined as a 

weight for gestational 

age below the 5th 

percentile

Start time: Infants 3 days after birth

Duration: Infants 2 months

Arm 1: Placebo

Description: standard formula

Brand name: Similac Special Care

Manufacturer: Ross Products Division, Abbott 

Laboratories

Infant conditions

ALA: 2.4 g / 100 g

Other dose 1: linolenic acid 21.2 g/ 100 g

Pre-term birth 100%

Other conditions 1 bronchopulmonary dysplasia

(BPD) or chronic lung disease of %

Arm 2: DHA supplement

Description: formula supplemented with DHA from 

marine oil

Brand name: Similac Special Care (plus marine oil)

Manufacturer: Ross Products Division, Abbott 

Laboratories

Infant conditions

ALA: 2.4 g / 100 g

DHA: 0.20 g / 100g

EPA: 0.06 g / 100 g

Other dose 1: linolenic acid 21.2 g/ 100 g

Pre-term birth 100%

Other conditions 1 bronchopulmonary dysplasia

(BPD) or chronic lung disease of- %

Outcome: Fagan Test of Intelligence:

time/look (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 1.3; SD (0.1)

Arm 2: Sample size 15; mean 1.13; SD 

(0.07)

Outcome: Fagan Test of Intelligence: looks 

to familiar (number) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 17.5; SD 

(1.4)

Arm 2: Sample size 15; mean 21.5; SD 

(1.3)

Outcome: Fagan Test of Intelligence: looks 

to novel (number) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 22.9; SD 

(1.5)

Arm 2: Sample size 15; mean 25.3; SD 

(1.6)

Outcome: Fagan Test of Intelligence: novel 

time (% of total) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 64.0; SD 

(1.9)

Arm 2: Sample size 15; mean 59.7; SD 

(1.7)

Outcome: Fagan Test of Intelligence: time 

to familiar (seconds) (Secondary)

Follow-up time: 12 months

214
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 12; mean 16.9; SD (1)

Arm 2: Sample size 15; mean 19.3; SD 

(0.9)

Outcome: Fagan Test of Intelligence: time 

to novel (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 33.1; SD 

(1.4)

Arm 2: Sample size 15; mean 31.5; SD 

(1.5)

Outcome: Fagan Test of Intelligence: 

time/familiar look (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 1.04; SD 

(0.11)

Arm 2: Sample size 15; mean 0.95; SD 

(0.08)

Outcome: Fagan Test of Intelligence: 

time/novel look (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 1.49; SD 

(0.09)

Arm 2: Sample size 15; mean 1.28; SD 

(0.06)

Outcome: Fagan Test of Intelligence: total 

looks (number) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 40.4; SD 

(2.7)

Arm 2: Sample size 15; mean 46.8; SD 

(2.7)

Outcome: Fagan Test of Intelligence: total 

time (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 50.0; SD 

(1.6)

Arm 2: Sample size 15; mean 50.8; SD 

(1.7)

Cheatham et al., 2011129

Study name: Danish 

National Birth CohortLactating Women

Study Population: 

Healthy infants

Pregnant enrolled 150 

Pregnant completers 98

Inclusion Criteria: 

Described in Ref. 26 All 

the children who 

participated in the 9 

month followup visit (n = 

Start time: Pregnant birth

Duration: Pregnant 9 months

Arm 1: Fish oil

Outcome: Stroop scores (Secondary)

Follow-up time: 7.5 years

Arm 1: Sample size 28; mean -0.21; SD 

(0.1)

Arm 2: Sample size 35; mean -0.23; SD 

215
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: 1998-2007

Study design: 

Observational 

prospective

Location: Denmark

Funding source / conflict: 

Government

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Lauritzen, 2004127; 

Lauritzen, 2005102; 

Lauritzen, 2005128

Infants enrolled 98 

Infants completers 92

Infant age: 7.5

Race of Mother: NR 

(100)

149) were invited to 

participate in the 7 year 

follow-up study.

Exclusion Criteria: Living 

outside Zealand

Manufacturer: m BASF Health and Nutrition A/S, 

Ballerup, Denmark

DHA: 0.62 g

EPA: 0.79 g

Total N-3: 1.5 g/d LCPUFA

Arm 2: Olive oil

Manufacturer: m BASF Health and Nutrition A/S, 

Ballerup, Denmark

(0.14)

Outcome: Woodcock Johnson Test: 

Standardized speed of processing 

(Secondary)

Follow-up time: 7.5 years

Arm 1: Sample size 27; mean 1.02; SD 

(0.26)

Arm 2: Sample size 36; mean 0.96; SD 

(0.26)

Clandinin et al., 2005108

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Industry

Study Population: 

Preterm infants

Infants enrolled 361 

preterm+105 term 

breastfed Infants 

completers 179 preterm 

and 76/105 term 

breastfed

Infant age: 30.6 weeks 

postmenstrual age 24-36 

weeks postmenstrual age

Race of Mother: NR 

(100)

Inclusion Criteria: Phase 

I: gestational age <35 

weeks PMA and received 

<10 total days of enteral 

feedings of >30 mL/kg 

per day. Infants initially 

fed human milk were not 

enrolled unless formula

was started within 10 

days after completing the 

first day of human milk 

feeding Phase II: 

completion of phase I 

and >=80% enteral 

intake from study formula 

during hospitalization and 

100% of caloric intake 

from study formula at 

completion of phase 1.

Birth weight<1500g

Exclusion Criteria: 

congenital abnormalities 

of the gastrointestinal 

Start time: Infants 10 days of age

Duration: Infants 118 weeks

Arm 1: Control

Description: Non-supplemented premature, 

discharge, and term formula

Dose: Ad lib

Blinding: Not reported

Infant conditions

Pre-term birth 119 (100%)

Arm 2: Algal-DHA

Description: supplemented premature infant formula 

supplemented with DHA from algal oil

Manufacturer: Martek Biosciences

Dose: ad lib

DHA: 17mg/100kcal (0.33% by weight)

EPA: 0.1% by weight

AA: 34mg/100kcal (0.67% by weight)

Arm 3: Fish-DHA

Description: Premature infant formula supplemented 

with DHA from tuna fish oil

Outcome: Bayley Scale of Infant 

Development II (Mental developmental 

index) (Unspecified)

Follow-up time: 118 weeks

Arm 1: Sample size 54; mean 77.0; SE (2)

Arm 2: Sample size 44; mean 83.0; SE (2)

Arm 3: Sample size 60; mean 87.0; SE (2)

Arm 4: Sample size 58; mean 98.0; SE (2)

216
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

tract, hepatitis, hepatic or 

biliary pathology, 

necrotizing enterocolitis 

confirmed before 

enrollment, or history of 

underlying disease or 

congenital malformation 

likely to interfere with 

evaluation

Manufacturer: Martek Biosciences

Dose: ad lib

DHA: 17mg DHA/100 kcal

AA: 34mg/100 kcal

Arm 4: Reference

Description: Breast fed term infants

Collins et al., 2015120

Study name: DINO

Study dates: 2001-2013

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Study Population: 

Preterm infants

Infants enrolled 657 

Infants completers 604

Infant age: median 30 

weeks gestational age 

28-31 weeks

Race of Mother: NR 

(100)

Inclusion Criteria: infants 

born at <33 weeks’ 

gestation from five 

Australian tertiary 

hospitals between 2001 

and 2005

Exclusion Criteria: a 

major congenital or 

chromosomal 

abnormality, multiple 

birth in which not all liveborn infants were eligible, 

enrollment in other trials 

of fatty acid 

supplementation, or if 

fish oil was 

contraindicated in the 

lactating mother

Start time: Infants within 5 days of 1st enteral 

feeding

Duration: Infants to expected due date

Arm 1: standard DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentrations of term formula fed infants

DHA: ___20 mg/kg/ day of DHA

Arm 2: High DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentration of breastmilk

DHA: ___50 mg/kg/ day of DHA

Outcome: Wechsler Abbreviated Scale of 

Intelligence: Full Scale IQ (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 98.5; SD 

(14.9)

Arm 2: Sample size 291; mean 98.3; SD 

(14)

Outcome: Wechsler Abbreviated Scale of 

Intelligence: Performance IQ (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 98.5; SD 

(13.6)

Arm 2: Sample size 291; mean 98.5; SD 

(14.5)

Outcome: Wechsler Abbreviated Scale of 

Intelligence: Verbal IQ (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 98.8; SD 

(15.8)

Arm 2: Sample size 291; mean 98.0; SD 

(14.2)

Colombo et al., 2013124

Study name: Diamond

Study dates: 09/03/03-

09/25/05

Study design: Trial 

randomized parallel

Study Population: 

Healthy infants

Infants enrolled 159 

Infants completers 81

Pregnant age: 24.1 (5.1)

Race of Mother: White 

European (34.9) Black 

Inclusion Criteria: 

Healthy, full term 

formula-fed singleton 

infants, 37-42 weeks 

gestation, 2490-4200 g 

birth weight, born in 

Kansas City between 

9/3/03 and 9/25/05

Exclusion Criteria: 

Start time: Infants Birth

Duration: Infants 12 months

Arm 1: 0.00%

Description: Control, no DHA or AA

Blinding: NR

Arm 2: 0.32%

Description: 0.32% DHA

Outcome: Macarthur-Bates Communicative 

Development Inventory

Follow-up time: 18 months

Arm 1: Sample size 18; mean 71.0; SEM

(20)

Arm 2: Sample size 21; mean 55.0; SEM 

(15)

Arm 3: Sample size 18; mean 97.0; SEM 

(20)

Arm 4: Sample size 24; mean 73.0; SEM 

217
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: US

Funding source / conflict: 

Industry, Government, 

Manufacturer supplied 

product

Study follow-up: 18 

months-6 years

Original, same study, or 

follow-up studies: Birch, 

2010121; Drover, 2011122; 

Drover. 2012123; Currie, 

2015115

(63.9) Other 

race/ethnicity (1.2)

Receipt of human milk 

within 24 h of 

randomization; maternal 

and newborn health 

conditions known to 

interfere with normal 

growth and development 

(e.g., intrauterine growth 

restriction) or with normal 

cognitive function (e.g., 

congenital anomalies or 

established genetic 

diagnoses associated 

with intellectual 

disability), poor formula 

intake, or intolerance to 

cow milk infant formula; 

mothers with physiciandocumented chronic 

illness (e.g., HIV, renal or 

hepatic disease, type 1 

or type 2 diabetes, 

alcoholism, or substance 

abuse)

DHA: 17mg/100 kcal

AA: 34 mg/100 kcal

Arm 3: 0.64%

DHA: 34mg/100 kcal

AA: 34 mg/100 kcal

Arm 4: 0.96%

DHA: 51mg/100 kcal

AA: 34 mg/100 kcal

(15)

Outcome: Wechsler Primary Preschool 

Test of Intelligence: Full Scale IQ 

(Secondary)

Follow-up time: 6 year

66; mean 96.2; SE (2)

Arm 1: Sample size 18; mean 90.5; SE (3)

Drover et al., 2011122

Study name: Diamond

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: Birch, 

Study Population: 

Healthy infants

Infants enrolled 181 

Infants withdrawals 64 

Infants completers 117

Infant age: 18.1 month 

(0.2)

Race of Mother: White 

European (70%) Minority 

(30%)

Inclusion Criteria: 

Children who had 

enrolled in the initial 

phase of the DIAMOND 

study at the Dallas site, 

and had completed the 

12-month feeding 

protocol and the 12-

month primary outcome 

visit (141 children)

Exclusion Criteria: Infants 

who had diseases or 

congenital abnormalities 

known to affect growth, 

development, visual or 

cognitive maturation, or 

who had poor formula 

intake did not participate 

Start time: Infants birth (1 9 days)

Duration: Infants 1 year

Arm 1: No DHA (Control)

Description: Cow's milk-based infant formula without 

DHA or ARA

Brand name: Enfamil® with iron

Manufacturer: Mead Johnson & Co, Evansville, IN

Blinding: After obtaining signed assent from a 

parent, the study coordinator opened the next 

sequentially-numbered opaque sealed envelope to 

determine the code of the study formula to be 

assigned to that infant. All recruiting personnel, 

parents or guardians, study monitors, researchers, 

and pediatricians were masked to the infant's 

assigned formula.

Arm 2: 0.32% DHA

Outcome: Bayley Scale of Infant 

Development II (Mental developmental 

index) (Secondary)

Follow-up time: 18 months

Arm 1: Sample size 28; mean 98.4; SD 

(13.1)

Arm 2: Sample size 29; mean 105.2; SD 

(10.7)

Arm 3: Sample size 32; mean 104.2; SD 

(9.8)

Arm 4: Sample size 28; mean 102.6; SD 

(11.9)

218
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

2010121; Drover. 2012123; 

Colombo, 2013124; Currie, 

2015115

in the study. Infants were 

also excluded if they had 

received human milk 

within 24 h of 

randomization, or if they 

were born to mothers 

with chronic illness such 

as HIV disease, renal or 

hepatic disease, type 1 

or type 2 diabetes, 

alcoholism, or substance 

abuse

Description: 0.32% fatty acids from DHA & 0.64% 

ARA

Brand name: Enfamil LIPIL®)

Manufacturer: Enfamil LIPIL®

DHA: 17mg/100 kcal, 0.32% DHA with 0.32% fatty 

acids from DHA

AA: 34mg/100 kcal, 0.64% ARA

Arm 3: 0.64% DHA

Description: 0.64% DHA & 0.64% ARA

Brand name: Enfamil LIPIL

Manufacturer: Mead Johnson Nutrition

DHA: 34 mg/100 kcal

AA: 34mg/100 kcal, 0.64% ARA

Arm 4: 0.96% DHA

Description: 0.96% DHA & 0.64% ARA

Brand name: Enfamil LIPIL

Manufacturer: Mead Johnson Nutrition

DHA: 54 mg/100 kcal; 0.96% DHA

AA: 34 mg/100 kcal; 0.64% ARA

Drover et al., 2012123

Study name: Diamond

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry

Study follow-up: 3.5 

years

Original, same study, or 

follow-up studies: Birch, 

2010121; Drover, 2011122; 

Colombo, 2013124; Currie, 

2015115

Study Population: 

Healthy infants

Infants enrolled 343 

Infants completers 88

Pregnant age: 31 years 

(4 years)

Infant age: <= 9 days 1 to 

9 days

Race of Mother: NR 

(100)

Inclusion Criteria: 

Healthy term singletonbirth infants born in any 

of 5 hospitals

Exclusion Criteria: Infants 

who had diseases or 

congenital abnormalities 

known to affect growth, 

development, visual or 

cognitive maturation, 

Infants were also 

excluded if they had 

received human milk

within 24 h of 

randomization, or if they 

were born to mothers 

with chronic illness such 

as HIV disease, renal or 

hepatic disease, type 1 

or type 2 diabetes, 

alcoholism, or substance 

Start time: Infants <=9 days after birth

Duration: Infants 12 months

Arm 1: Control group

Description: Standard infant formula

Brand name: Enfamil with Iron

Manufacturer: Mead-Johnson Nutrition, Evansville 

IN

Arm 2: 0.32% DHA formula

Brand name: Enfamil LIPIL®

Manufacturer: Mead-Johnson; DHA and ARA from 

algal and fungal oils manufactured by Martek 

Biosciences

DHA: 0.32% or 17mg/100kcal

AA: 0.64% FA or 34mg/100kcal

Arm 3: 0.64% DHA formula

Brand name: NR

Manufacturer: NR

DHA: 34mg/100kg

Outcome: School Readiness Composite 

(SRC) (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 19; mean 9.79; SD 

(2.42)

Arm 2: Sample size 23; mean 10.3; SD 

(1.92)

Arm 3: Sample size 27; mean 10.63; SD 

(2.75)

Arm 4: Sample size 24; mean 10.79; SD 

(2.62)

219
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

abuse AA: 0.64% FA or 34mg/100kcal

Arm 4: 0.96% DHA formula

Brand name: NR

Manufacturer: NR

DHA: 51mg/100kg

AA: 0.64% FA or 34mg/100kcal

Dunstan et al., 200844

Study name: Dunstan

Study dates: 2000-2003

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Multiple foundations and 

Societies

Original, same study, or 

follow-up studies: 

Dunstan, 200350; 

Meldrum, 201551

Study Population: 

Healthy infants Pregnant 

women with allergies

Pregnant enrolled 98 

Pregnant completers 83

Infants enrolled 83 

Infants withdrawals 11 (7 

FO, 4 control) Infants 

completers 72

Pregnant age: Fish oil: 

30.9 Control: 32.6 (Fish 

oil: 3.7 Control: 3.6)

Infant age: Term (mean 

gestational period 275 

days)

Race of Mother: NR (NR)

Baseline biomarker 

information: Cord blood 

erythrocyte (as % total 

fatty acids) 20:4n-6 14.9 

(1.4) 17.6 (1.0) ,0.001 

20:5n-3 1.3 (0.5) 0.4 

(0.3) ,0.001 22:3n-6 2.8 

(0.5) 3.9 (0.5) ,0.001 

22:4n-6 0.8 (0.2) 1.5 

(0.3) ,0.001 22:5n-3 6.3 

(0.8) 6.0 (0.5) 0.037 

22:6n-3 10.3 (1.1) 7.4 

(0.9) ,0.001 Total n-6 

PUFAs* 25.0 (1.8) 29.6 

Inclusion Criteria: 

Healthy term infants of 

pregnant women enrolled 

in RCT of gestational 

supplementation

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked, had medical 

problems, a complicated 

pregnancy, seafood 

allergy, or if their normal 

dietary intake exceeded 

two meals of fish per 

week. Children were 

excluded from the study 

if they were born before 

36 weeks’ gestation or 

with major disease (to 

avoid the confounding 

effects on immune 

response) or if cord blood 

was not collected

Start time: Pregnant 20 weeks gestation

Duration: Pregnant to term

Arm 1: Control

Description: olive oil placebo

Blinding: capsules image matched

Maternal conditions

Current smoker 0%

Maternal allergies 100%

Arm 2: Fish oil

Description: same

Manufacturer: Ocean Nutrition, Halifax Nova Scotia

Active ingredients: 3-4mg/g vitamin E

Viability: none reported

Dose: 4 1-gm capsules fish oil per day

Maternal conditions

DHA: 2.2

EPA: 1.1

Other dose 1: fish oil supplying 2,2g/d DHA and 

1.1g/day EPA

Current smoker 0%

Maternal allergies 100%

Outcome: Griffith Mental Development 

Scales: Eye and hand coordination 

(Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 108.0; SD 

(11.3)

Arm 2: Sample size 33; mean 114.0; SD 

(10.2)

Outcome: Griffith Mental Development 

Scales: Performance (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 115.8; SD 

(13.7)

Arm 2: Sample size 33; mean 120.9; SD 

(12.7)

Outcome: Griffith Mental Development 

Scales: Practical reasoning (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 113.6; SD 

(15)

Arm 2: Sample size 33; mean 114.3; SD 

(14.5)

Outcome: Griffith Mental Development 

Scales: Speech and hearing (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 109.6; SD 

(14.9)

Arm 2: Sample size 33; mean 112.0; SD 

(15)

Outcome: Griffith Mental Development 

Scales: General quotient score (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 110.5; SD 

(10.6)

Arm 2: Sample size 33; mean 114.2; SD 

(9.8)

220
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(1.1) ,0.001 Total n-3 

PUFAs{ 17.9 (1.9) 13.7 

(1.3) ,0.001 Total n-3 to 

n-6{ 0.8 (0.1) 0.5 (0.1) 

,0.001

Outcome: Griffith Mental Development 

Scales: Personal social (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 109.4; SD 

(11.5)

Arm 2: Sample size 33; mean 112.4; SD 

(11.9)

Outcome: Griffith Mental Development 

Scales: Locomotor (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 107.9; SD 

(12.6)

Arm 2: Sample size 33; mean 112.5; SD 

(12.2)

Fang et al., 2005137

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Taiwan

Funding source / conflict: 

Manufacturer supplied 

product

Study Population: 

Preterm infants

Infants enrolled 28 

Infants withdrawals 1 

Infants completers 27

Infant age: 1 week (mean 

gestation age 33 weeks) 

(0.5 week) NA

Race of Mother: NR 

(100)

Inclusion Criteria: (1) A 

gestational age at birth 

between 30 and 37 

weeks; (2) Normal 

fundus oculi; (3) 

Recruitment prior to 

commencement of 

feeding

Exclusion Criteria: (1) 

Breast feeding; (2) A 

maternal history of 

infection, diabetes 

mellitus, gestational 

diabetes mellitus, 

cocaine or alcohol abuse, 

systemic diseases or if 

intrauterine growth 

retardation had been 

diagnosed during 

pregnancy; (3) Major 

congenital abnormality; 

(4) Severe 

intraventricular 

hemorrhage > grade 2; 

(5) Cystic periventricular 

leukomalacia; (6) 

Retinopathy of 

prematurity stage 2; (7) 

Start time: Infants 1 week after birth

Duration: Infants 24 weeks

Arm 1: placebo

Description: infant formula based on the composition 

of human milk

Brand name: Neoangelac

Manufacturer: Multipower Enterprise Corporation

Dose: Babies were given more than 110 kcal/kg per 

day during the first 4 months and more than 70 

kcal/kg per day from 4 to 6 months

N-6 N-3: 10:1 linoleic:linolenic

Arm 2: Neoangelac Plus

Description: Neoangelac supplemented with Omega 

3

Brand name: Neoangelac Plus

Manufacturer: Multipower Enterprise Corporation

Dose: Babies were given more than 110 kcal/kg per 

day during the first 4 months and more than 70 

kcal/kg per day from 4 to 6 months

DHA: 0.05%

AA: 0.10%

Outcome: Bayley Mental Development 

Index (Primary)

Follow-up time: 1 year

Arm 1: Sample size 11; mean 90.5; SD 

(6.9)

Arm 2: Sample size 16; mean 98.7; SD (8)

Follow-up time: 6 months

Arm 1: Sample size 11; mean 91.7; SD 

(10.4)

Arm 2: Sample size 16; mean 96.1; SD 

(8.6)

221
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Bronchopulmonary 

dysplasia on radiographs 

or oxygen usage 28 

days; (8) Body weight 

less than the third 

percentile; (9) Surgical 

intervention for 

necrotizing enterocolitis 

(10) Mechanical 

ventilation after achieving 

enteral intake > 110 

kcal/kg per day; (11) A 5-

min Apgar score < 7; (12) 

Administration of blood 

transfusion, blood 

products, or parenteral 

lipids with DHA or AA.

van Goor et al., 201166

Study name: Groningen 

LCPUFA study

Study dates: 2004-2009

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / conflict: 

Industry

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; van Goor, 201036

Study Population: 

Healthy infants

Pregnant enrolled 119

Infants enrolled 119 

Infants completers 114

Pregnant age: Placebo: 

32.7 DHA: 32.5

DHA+AA: 32.9 (Placebo: 

5.1 DHA: 4.4 DHA+AA: 

4.8)

Infant age: 18 months

Race of Mother: NR 

(100)

Inclusion Criteria: women 

with a first or second lowrisk singleton pregnancy, 

between the 14th and 

20th weeks of pregnancy

Exclusion Criteria: 

women with vegetarian 

or vegan diets; women 

with diabetes mellitus; 

birth complications

Start time: Pregnant 14th-20th week pregnancy 

Lactating 3 months after delivery Mothers 3 months 

after delivery Infants NR

Duration: Pregnant NR Lactating 33-39 weeks 

Mothers 33-39 weeks Infants NR

Arm 1: placebo

Description: Soy bean oil

Brand name: none

Arm 2: DHA

Description: DHA plus soy bean oil

Brand name: Marinol D40

Manufacturer: Lipid Nutrition B.V., Wormerveer, The 

Netherlands; AA:

Dose: 1 capsule DHA and 1 capsule soy bean oil 

once a day

ALA: 32 mg/d

DHA: 220 mg/d

EPA: 34 mg/d

Arm 3: DHA+AA

Description: DHA plus AA

Brand name: AA: no brand name

Manufacturer: Wuhan Alking Bioengeneering Co. 

Outcome: Bayley Scale of Infant 

Development (Mental developmental index) 

(Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 115.2; SD 

(11.6)

Arm 2: Sample size 41; mean 113.7; SD 

(13)

222
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Ltd., Wuhan, China

Dose: 2 capsules once a day

ALA: 7 mg/d

DHA: 220 mg/d

EPA: 36 mg/d

AA: 220 mg per capsule

Gustafson et al., 201374

Study name: NR

Study dates: May 2009 -

July 2011

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 67 

Pregnant withdrawals 12 

Pregnant completers 52

Infants enrolled 44 

Infants completers 41

Pregnant age: placebo 

25.6+; DHA 25.5 

(placebo 4.8; DHA 4.3)

Race of Mother: White 

European (46.3) Black 

(37.3) Asian (3) Hispanic 

(13.4)

Baseline biomarker 

information: plasma DHA 

(wt% TFA) placebo 

group: 3.91 (3.15-4.21); 

DHA group: 3.94(3.39-

4.72) RBC DHA (wt%

TFA) placebo group 

4.30(3.99-5.03); DHA 

group 4.50 (3.73-5.44)

Inclusion Criteria: 

between 16–35.9 years 

of age and carrying a 

singleton pregnancy 

between the 12th and 

20th week of gestation

Exclusion Criteria: any 

serious health condition 

likely to affect the growth 

and development of the 

fetus or health of the 

mother including cancer, 

lupus, hepatitis, diabetes 

mellitus (Type1, Type 2 

or gestational) or 

HIV/AIDS at baseline or 

fetal cardiac structural or 

conduction defects. 

Women who selfreported illicit drug use or 

alcohol use during 

pregnancy and those 

with hypertension or BMI 

Z40 were excluded. 

Women who were taking 

more than 200 mg/day 

DHA in prenatal vitamins 

or over the counter 

supplements were 

excluded from

participation

Start time: Pregnant 12-20 week gestation Infants 

birth

Duration: Pregnant till birth

Arm 1: Placebo

Description: g 50% soy and 50% corn oil

Manufacturer: Martek Biosciences, now DSM 

Nutritional Products

Dose: 3 capsule a day each 500 mg

Blinding: Only members of the investigational 

pharmacy knew the subject allocation. Participants 

and all members of the investigational team were 

blinded to the intervention assignment. Participants

were allocated to either group based on the simple 

randomization procedure using random numbers 

generated by SAS. All capsules were the same 

color, size, weight and the oils were orange-flavored 

to prevent investigator or subject bias.

Arm 2: algal oil as a source of DHA (200 mg of DHA 

per capsule for a total of 600 mg DHA/day)

Dose: 3 capsule of 200mg DHA total 600 mg

DHA: 200 mg * 3

Outcome: Neonatal Behavior Assessment:

state organization (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 13.5; SD 

(13.89)

Arm 2: Sample size 15; mean 15.13; SD 

(8.02)

Outcome: Neonatal Behavior Assessment: 

autonomic (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 14.83; SD 

(16.9)

Arm 2: Sample size 15; mean 18.13; SD 

(14.48)

Outcome: Neonatal Behavior Assessment: 

reflexes (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 21.92; SD 

(14.45)

Arm 2: Sample size 15; mean 22.6; SD 

(14.33)

Outcome: Neonatal Behavior Assessment: 

state regulation (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 16.42; SD 

(20.02)

Arm 2: Sample size 15; mean 16.93; SD 

(20.06)

Outcome: Neonatal Behavior Assessment: 

habituation (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 9.92; SD 

(9.28)

Arm 2: Sample size 15; mean 8.47; SD 

(9.26)

Outcome: Neonatal Behavior Assessment: 

orienting (Primary)

223
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 19.75; SD 

(15.45)

Arm 2: Sample size 15; mean 23.4; SD 

(18.32)

Helland et al., 200876

Study name: NR

Study dates: 1994-2003

Study design: Trial 

randomized parallel

Location: Norway

Funding source / conflict: 

Industry, Government, 

Multiple foundations and 

Societies

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Helland, 200186 and 

Helland, 200387 and

which are both included 

in the original report

Study Population: 

Healthy infants Healthy 

pregnant women Breastfeeding women

Infants enrolled 262 

Infants completers 143

Pregnant age: cod oil 

28.6 n=175 corn oil 27.6 

n=166 (cod oil 3.4; corn 

oil 3.2)

Race of Mother: NR 

(100)

Baseline biomarker 

information: from id 

10331 cod(n148) corn 

(n137) n-3 cod: 73.7 

(30.0) corn 52.0 (14.9)*** 

20:5n-3 cod: 10.8 (7.6) 

corn: 2.5 (1.8)*** 22:5n-3 

cod: 5.0 (2.6) corn: 2.9 

(1.3)*** 22:6n-3 cod: 55.8 

(20.6) corn: 45.3 

(12.8)***

Baseline Omega-3 

intake: from 10331 cod 

n147 corn n159 18:3 n-3: 

cod: 1.3 (0.5) corn: 1.2 

(0.5) 20:5 n-3 cod: 0.2 

(0.2) corn:0.2 (0.2) 22:5 

n-3 cod: 0.05 (0.03) corn: 

0.05 (0.03) 22:6 n-3 cod: 

0.3 (0.3) corn: 0.3 (0.3)

Inclusion Criteria: 

Healthy nulliparous or 

primiparous women, 

aged 19-35 with single 

pregnancies

Exclusion Criteria: 

Unhealthy neonates

Start time: Pregnant week 18 of pregnancy

Duration: NR

Arm 1: Cod oil

Manufacturer: NRActive ingredients: Vit 1: 117 

ug/mL, Vit D3: 1 ug/mL, vit E: 1.4 mg/mL

Viability: frozen at _x0003_ 70 ° C under nitrogen. 

Before storage, the samples were sonicated and 

ethylenediaminetetraacetic acid and butylated 

hydroxytoluene were added to a final concentration

of 1.85 mg/mL and 75 _x0003_ g/mL, respectively

DHA: 1183mg/10 mL

EPA: 803 mg/10mL

Total N-3: 2494 mg/10mL

Arm 2: corn oil

Active ingredients: Vit 1: 117 ug/mL, Vit D3: 1 

ug/mL, vit E: 1.4 mg/mL

Viability: frozen at _x0003_ 70 ° C under nitrogen. 

Before storage, the samples were sonicated and 

ethylenediaminetetraacetic acid and butylated 

hydroxytoluene were added to a final concentration

of 1.85 mg/mL and 75 _x0003_ g/mL, respectively

ALA: 92 mg/10mL

Outcome: Kaufman Assessment Battery for 

Children (K-ABC): mental processing 

composite (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 28; mean 102.0

Arm 2: Sample size 30; mean 107.0

Follow-up time: 7 years

Arm 1: Sample size 28; mean 108.0

Arm 2: Sample size 30; mean 110.0

Outcome: Kaufman Assessment Battery for 

Children (K-ABC): non-verbal abilities 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 28; mean 102.0

Arm 2: Sample size 30; mean 107.0

Follow-up time: 7 years

Arm 1: Sample size 28; mean 112.0

Arm 2: Sample size 30; mean 112.0

Outcome: Kaufman Assessment Battery for 

Children (K-ABC): sequential processing 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 28; mean 107.0

Arm 2: Sample size 30; mean 109.0

Follow-up time: 7 years

Arm 1: Sample size 28; mean 105.0

Arm 2: Sample size 30; mean 107.0

Outcome: Kaufman Assessment Battery for 

Children (K-ABC): simultaneous processing 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 28; mean 98.0

Arm 2: Sample size 30; mean 102.0

Follow-up time: 7 years

Arm 1: Sample size 28; mean 110.0

Arm 2: Sample size 30; mean 110.0

Henriksen et al., 2008107 Study Population: Inclusion Criteria: All Start time: Infants (intervention began when the Outcome: Ages and Stages: 

224
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: Unnamed 

Trial D

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: Norway

Funding source / conflict: 

Multiple foundations and 

Societies, Manufacturer 

supplied product

Study follow-up: 6 

months

Original, same study, or 

follow-up studies: 

Westerberg, 2011125; 

Almaas, 2015126

Preterm infants

Infants enrolled 141 

Infants completers 129

Mother age: Median: 

Intervention: 31 years 

Control: 32 years 28-35 

years

Infant age: Median 

Gestational age: Control: 

28.9 weeks Intervention: 

28.4 weeks Gestational 

age: 26.6-30.9 weeks

Race of Mother: White 

European (Intervention: 

79%; Control 84%)

VLBW infants (<1500g) 

born between December 

2003 and November 

2005 at RikshospitaletRadiumhospitalet 

Medical Center, 

Akershus University 

Hospital, Buskerud 

Hospital, and Vestfold 

Hospital in Norway

Exclusion Criteria: Major 

congenital abnormalities 

or cerebral hemorrhage 

(grade 3 or 4, as 

determined through 

ultrasonography)

infant received most of his nutrients enterally: 

>100ml human milk/kg body weight/day

Duration: Infants Until discharge or bottle of study oil 

was empty (average 63 days of age)

Arm 1: Control

Description: Study oil: soy oil and medium chain 

triglycerides

Active ingredients: 127mg linolenic acid/100 ml 

milk(27.1% total fatty acids)

Dose: 0.5 ml study oil/100 ml human milk

Blinding: Study oils packed in numbered bottles in 

hospital pharmacy

ALA: 16mg/100 ml milk; 3.4% total fatty acids

Arm 2: Intervention

Description: DHA and AA-containing oil

Manufacturer: Martek Biosciences

Active ingredients: 88mg/100 ml linoleic acid per 100 

ml milk (18.8%)

Dose: 0.5 ml study oil per 100 ml milk, ad lib

Maternal conditions

Infant conditions

DHA: 32mg/100ml milk (6.9%)

AA: 31 mg/100 ml milk (6.7% total fatty acids

Current smoker 22% during pregnancy

Low birth weight 100% (median 1090 g)

Communication

Follow-up time: 6 months

Arm 1: Sample size 55; mean 46.6; SD 

(9.1)

Arm 2: Sample size 50; mean 45.4; SD 

(7.9)

Outcome: Ages and Stages: Fine motor

Follow-up time: 6 months

Arm 1: Sample size 55; mean 45.8; SD 

(14.3)

Arm 2: Sample size 50; mean 45.2; SD 

(10.7)

Outcome: Ages and Stages: Gross motor

Follow-up time: 6 months

Arm 1: Sample size 55; mean 30.9; SD 

(11.1)

Arm 2: Sample size 50; mean 33.3; SD 

(11.5)

Outcome: Ages and Stages: Personalsocial

Follow-up time: 6 months

Arm 1: Sample size 55; mean 42.2; SD 

(12.3)

Arm 2: Sample size 50; mean 43.2; SD 

(12.8)

Outcome: Ages and Stages: Problemsolving

Follow-up time: 6 months

Arm 1: Sample size 55; mean 49.5; SD 

(9.5)

Arm 2: Sample size 50; mean 53.4; SD (7)

Outcome: Ages and Stages: Total

Follow-up time: 6 months

Arm 1: Sample size 55; mean 215.0; SD 

(39)

Arm 2: Sample size 50; mean 221.0; SD 

(32)

Isaacs et al., 201199

Study name: Unnamed 

Trial A

Study dates: Recruitment 

Study Population: 

Preterm infants

Infants enrolled 238 

Infants completers 107

Inclusion Criteria: birth 

weight of < 2000 g, and 

gestational age of < 35 

weeks

Exclusion Criteria: 

Start time: Infants at hospital discharge

Duration: Infants 9 months

Arm 1: control

Description: control formula

Outcome: Wechsler Abbreviated Scale of 

Intelligence: FSIQ (Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 92.7; SD 

(12.3)

Arm 2: Sample size 50; mean 95.1; SD 

225
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

of infants from 1995 

through 1997 with 10-

year followup

Study design: Trial 

randomized parallel

Location: UK

Funding source / conflict: 

Industry, Government, 

Some authors have 

received research 

funding from infant 

formula manufacturers

Study follow-up: 10 years

Original, same study, or 

follow-up studies: 

Fewtrell, 2002158 is the 

original study; Llorente, 

200398 reports postpartum depression

Infant age: birth (at < 35 

weeks gestation) NA

Race of Mother: NR (NR)

congenital malformations Active ingredients: protein, minerals, vitamins A, E, 

K, D

DHA: 0

EPA: 0

AA: 0

Other dose 1: C18:2, n-6, linoleic acid 11.5 g / 100g 

fat

Other dose 2: C18:3, n-3, alpha_x0004_-linolenic 

acid 1.6 g / 100g fat

Arm 2: Omega 3 supplemented formula

Description: LCPUFA-Supplemented Formula

Active ingredients: protein, minerals, vitamins A, E, 

K, D

Infant conditions

DHA: 0.5 g / 100g fat

EPA: 0.1 g/ 100g fat

AA: 0.04 g / 100g fat

Other dose 1: C18:2, n-6, linoleic acid 12.3 g / 100g 

fat

Other dose 2: C18:3, n-6, gamma-linoleic acid 0.9 g 

/ 100g fat

Other dose 3: C18:3, n-3, _x0004_alpha-linolenic 

acid 1.5 g / 100g fat

Pre-term birth 100%

Low birth weight 100%

(13.2)

Outcome: Wechsler Abbreviated Scale of 

Intelligence: Performance IQ (Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 94.5; SD 

(14.1)

Arm 2: Sample size 50; mean 94.2; SD 

(12.7)

Outcome: Wechsler Abbreviated Scale of 

Intelligence: VIQ (Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 92.6; SD 

(12.6)

Arm 2: Sample size 50; mean 96.7; SD 

(13.2)

Jensen et al., 2010135

Study name: Unnamed 

Trial B

Study dates: NR (<2010)

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Industry, Government

Study follow-up: 5 years

Study Population: Breastfeeding women

Lactating enrolled 227

Infants enrolled 230 

Infants completers 119

Lactating enrolled 227

Lactating age: 31.5 years 

(5 years) 18 to 40

Infant age: birth (NA) NA

Race of Mother: NR (NR)

Inclusion Criteria: 

maternal age between 18 

and 40 y, infant 

gestational age >=37 wk, 

infant birth weight 

between 2500 and 4200 

g

Exclusion Criteria: 

chronic maternal 

disorders, major 

congenital anomalies, 

obvious gastrointestinal 

or metabolic disorders of 

the infant

Start time: Infants birth

Duration: Infants 4 months

Arm 1: placebo

Description: capsule containing corn & soy oil

Manufacturer: Martek Biosciences

Purity Data: 50:50 mixture of soy and corn oils 

consisting, by weight, of 15% saturated fatty acids, 

23.5% monounsaturated fatty acids, 56.3% linoleic 

acid (18:2 n-6) and 3.9% a-linolenic acid (18:3 n-3)

Dose: 1 capsule

Blinding: capsules were identical

ALA: 3.9%

Arm 2: omega 3 capsule

Description: high-DHA algal triglyceride capsule

Outcome: Wechsler Primary and Preschool 

Scale of Intelligence - Revised : Vocabulary 

Subset (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 12.9; SD 

(2.4)

Arm 2: Sample size 60; mean 12.3; SD 

(2.8)

Outcome: Wechsler Primary and Preschool 

Scale of Intelligence - Revised : Animal 

Pegs Subset (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 12.2; SD 

(1.8)

Arm 2: Sample size 60; mean 12.1; SD 

(2.4)

Outcome: Wechsler Primary and Preschool 

226
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Original, same study, or 

follow-up studies: 

Jensen, 2005136

Brand name: DHASCO

Manufacturer: Martek

Purity Data: by weight, 44% saturated fatty acids, 

13.6% monounsaturated fatty acids, 0.8% linoleic 

acid (18:2n-6) and 41.7% DHA (22:6n-3)

Dose: 1 capsule

DHA: 200 mg

Scale of Intelligence - Revised : Block 

Design Subset (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 11.1; SD 

(2.2)

Arm 2: Sample size 60; mean 11.3; SD 

(2.1)

Outcome: Wechsler Primary and Preschool 

Scale of Intelligence - Revised : Information 

Subset (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 11.2; SD 

(2.6)

Arm 2: Sample size 60; mean 10.8; SD 

(2.6)

Lauritzen et al., 2005128

Study name: Danish 

National Birth CohortLactating Women

Study dates: Enrolled in 

1999

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / conflict: 

Industry, Government

Study follow-up: 9 

months, 1 year, 2 years

Original, same study, or 

follow-up studies: 

Lauritzen, 2004127; 

Lauritzen, 2005102; 

Cheatham, 2011129;

Study Population: 

Healthy infants Breastfeeding women

Lactating enrolled 122 

Lactating completers 89

Infants enrolled 122 

Infants completers 89

Lactating enrolled 122 

Lactating completers 89

Pregnant age: NR (NR) 

NR

Infant age: 9 days (3 

days) NA

Race of Mother: NR 

(100%)

Baseline Omega-3 

intake: < 0.4 g n-3 

LCPUFA/d

Inclusion Criteria: 

pregnant women with a 

fish intake below the 

population median (< 0.4 

g n-3 LCPUFA·d–1), 

uncomplicated 

pregnancy, a normal 

prepregnancy body mass 

index (< 30 kg·m–2), no 

metabolic disorders, an 

intention to breastfeed for 

at least four months. 

Newborns had to be 

healthy, singleton, term 

infants with normal 

weight for gestation [33] 

and an Apgar score > 7 

five minutes after 

delivery.

Exclusion Criteria: NR

Start time: Lactating 9 days after birth Infants 9 days 

after birth

Duration: Lactating 4 months Infants 4 months

Arm 1: placebo group

Description: olive oil in musli bars, cookies, or 

capsules

Manufacturer: BASF

Dose: one bar/cookie/capsule containing 4.5 g olive 

oil

Blinding: identical bars/cookies/capsules

Arm 2: fish oil

Description: fish oil in musli bars, cookies, or 

capsules

Manufacturer: BASF

Dose: one bar/cookie/capsule containing 4.5 g fish 

oil

DHA: 0.9 g

Total N-3: Other FA (not DHA): 0.6 g

Arm 3: high n-3 reference group

Description: top quartile fish intake at baseline

Dose: no supplementation, high fish intake

Total N-3: > 0.8 n-3 LCPUFA/d

Outcome: Infant Planning Test (problem 

solving) (Secondary)

Follow-up time: 9 months

Arm 1: Sample size 38; mean 4.3; SD (3.6)

Arm 2: Sample size 48; mean 4.5; SD (3.1)

Arm 3: Sample size 42; mean 4.5; SD (3.3)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: late gestures (Secondary)

Follow-up time: 1 year

Arm 1: Sample size 37; mean 15.0; SD (7)

Arm 2: Sample size 52; mean 14.0; SD (6)

Arm 3: Sample size 42; mean 16.0; SD (7)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: number of irregular words 

(Secondary)

Follow-up time: 2 years

Arm 1: Sample size 31; median 3.0; IQR

Arm 2: Sample size 40; median 3.0; IQR

Arm 3: Sample size 40; median 4.0; IQR

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: number of over regularized 

words (Secondary)

Follow-up time: 2 years

Arm 1: Sample size 31; median 1.0; IQR

Arm 2: Sample size 40; median 1.0; IQR

227
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 3: Sample size 40; median 1.0; IQR

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: early gestures (Secondary)

Follow-up time: 1 year

Arm 1: Sample size 37; median 11.0; IQR

Arm 2: Sample size 52; median 11.0; IQR

Arm 3: Sample size 42; median 12.0; IQR

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: percent starting to talk 

(Secondary)

Follow-up time: 1 year

Arm 1: 6/37 (16.0%)

Arm 2: 6/52 (12.0%)

Arm 3: 7/42 (17.0%) Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: phrases understood 

(Secondary)

Follow-up time: 1 year

Arm 1: Sample size 37; mean 11.0; SD (6)

Arm 2: Sample size 52; mean 11.0; SD (5)

Arm 3: Sample size 42; mean 11.0; SD (5) Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: talk about abstract 

(Secondary)

Follow-up time: 2 years

Arm 1: 29/31 (94.0%)

Arm 2: 30/40 (75.0%)

Arm 3: 38/40 (95.0%)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: use grammar (Secondary)

Follow-up time: 2 years

Arm 1: 10/31 (32.0%)

Arm 2: 10/40 (25.0%)

Arm 3: 16/40 (40.0%)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: vocabulary comprehension 

(Secondary)

Follow-up time: 1 year

228
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 37; mean 71.0; SD (45)

Arm 2: Sample size 52; mean 54.0; SD (37)

Arm 3: Sample size 42; mean 65.0; SD (40)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: vocabulary production 

(Secondary)

Follow-up time: 1 year

Arm 1: Sample size 37; median 5.0; IQR

Arm 2: Sample size 52; median 3.0; IQR

Arm 3: Sample size 42; median 5.0; IQR

Follow-up time: 2 years

Arm 1: Sample size 31; mean 297.0; SD 

(147)

Arm 2: Sample size 40; mean 242.0; SD 

(170)

Arm 3: Sample size 40; mean 312.0; SD 

(146)

Makrides et al., 2009116

Study name: DINO

Study dates: Enrollment 

April 2001 to October 

2005

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product, Some 

authors serve on 

scientific advisory boards 

for corporations, Some 

authors have received 

research funding from 

infant formula 

manufacturers

Study Population: 

Preterm infants Breastfeeding women

Pregnant enrolled 545

Infants enrolled 657 

Infants completers 614

Lactating age: 30 years 

(5.5 years) NR

Infant age: 4 days after 

birth (29 weeks 

gestation) 2 to 6 days 

after birth

Race of Mother: White 

European (90%)

Inclusion Criteria: infants 

born at < 33 wk of 

gestation

Exclusion Criteria: Infants 

born with major 

congenital or 

chromosomal 

abnormalities, lactating 

women for whom tuna oil 

was 

contraindicated(women 

with bleeding disorders 

or taking anticoagulants)

Start time: Infants 4 days after birth

Duration: Infants until infants reached their 

"expected" date of delivery

Arm 1: Placebo

Description: Soy oil capsules or regular preterm 

formula

Manufacturer: Clover Corporation

Dose: six 500-mg soy oil capsules

Blinding: all capsules were similar in size, shape, 

and color

Maternal conditions

Infant conditions

Current smoker 25.1% during pregnancy

Pre-term birth 100%

Low birth weight 44.5%

Other conditions 1 SGA 18.6%

Arm 2: tuna oil capsules

Description: DHA-rich tuna oil capsules or high-DHA 

formula

Manufacturer: Clover Corporation

Dose: 6 500 mg capsules

Maternal conditions

Outcome: Bayley Scale of Infant 

Development (Mental developmental index) 

(Primary)

Follow-up time: 18 months

Arm 1: Sample size 335; mean 93.0; SD 

(17.3)

Arm 2: Sample size 322; mean 94.9; SD 

(14.5)

229
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Infant conditions

DHA: Capsules: Intended to achieve breast milk 

concentration of 1.0%.Formula: 1.0%

AA: Capsules: not intended to alter AA levels. 

Formula: 0.6%

Current smoker 25.6% during pregnancy

Pre-term birth 100%

Low birth weight 45.7%

Other conditions 1 SGA 18.9%

Makrides et al., 201035

Study name: DOMInO

Study dates: 2005-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Smithers, 201153; Palmer, 

201254; Zhou, 201255;

Palmer, 201356; 

Makrides, 2014 57

Study Population: 

Healthy pregnant women

Pregnant enrolled 2399 

Pregnant withdrawals 1

Infants enrolled 605 

Infants withdrawals 32 

Infants completers 726

Pregnant age: 28.9 

(DHA5.7___ control5.6)

Race of Mother: NR (NR)

Inclusion Criteria: with 

singleton pregnancies at 

less than 21 weeks’ 

gestation were 

approached by study 

research assistants while 

attending routine 

antenatal appointments

Exclusion Criteria: 

already taking a prenatal 

supplement with DHA, 

their fetus had a known 

major abnormality, they 

had a bleeding disorder 

in which tuna oil was 

contraindicated, were 

taking anticoagulant 

therapy, had a 

documented history of 

drug or alcohol abuse, 

were participating in 

another fatty acid trial, 

were unable to give 

written informed consent, 

or if English was not the 

main language spoken at 

home

Start time: Pregnant < 21 week's gestation

Duration: NR

Arm 1: vegetable oil capsules

Description: a blend of 3 nongenetically modified oils 

(rapeseed, sunflower, and palm) in equal 

proportions

Manufacturer: Efamol, Surrey, England.

Dose: 3* 500mg capsule / day

Blinding: All capsules were similar in size, shape, 

and color

Arm 2: DHA

Description: DHA-rich fish oil concentrate

Manufacturer: ; Incromega 500 TG, Croda 

Chemicals, East Yorkshire, England

Dose: 500mg capsule *3/day

DHA: 800mg

EPA: 100mg

Outcome: Bayley Scale of Infant 

Development III (Cognitive Component) 

(Primary)

Follow-up time: 18 months

Arm 1: Sample size 375; weighted mean 

101.75; SD (12.56)

Arm 2: Sample size 351; weighted mean 

101.81; SD (11.05)

Makrides et al., 201457

Study name: DOMInO

Study Population:

Healthy pregnant women

Infants enrolled 726 

Inclusion Criteria: 

Women with singleton 

pregnancies at less than 

21 weeks' gestation

Start time: Pregnant <21 weeks gestation

Duration: Pregnant <21 weeks gestation until birth

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Emergent 

Meta-Cognition Index (Secondary)

Follow-up time: 4 years

230
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: October 31, 

2005 to September 25, 

2012

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product, Some authors 

have received research 

funding from infant 

formula manufacturers

Original, same study, or 

follow-up studies: 

Makrides, 2010 35

Smithers, 201153; Palmer, 

201254; Zhou, 201255;

Palmer, 201356

Infants completers 646

Race of Mother: NR 

(100)

Exclusion Criteria: 

Already taking a prenatal 

supplement with DHA, 

fetus had a known major 

abnormality, had a 

bleeding disorder in 

which tuna oil was 

contraindicated, were 

taking anticoagulant 

therapy, had a 

documented history of 

drug or alcohol abuse, 

were participating in 

another fatty acid trial, 

were unable to give 

written informed consent, 

or if English was not the 

main language spoken at 

home

Arm 1: Placebo

Description: rapeseed, sunflower, and palm oil 

capsules

Manufacturer: Enfamol

Dose: 3 500mg capsules/day

Blinding: similar in size, shape, and color

Arm 2: DHA supplement

Description: DHA-rich fish oil capsules

Manufacturer: Enfamol

Dose: 3 500mg capsules/day

DHA: 800 mg/d

EPA: 100 mg/day

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Emotional 

Control Scale (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Flexibility

Index (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Global 

Executive Composite score (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Inhibition 

Scale (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Inhibitory 

Self-Control Index (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: 

Plan/Organize Scale (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Shift Scale 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

231
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Working 

Memory Scale (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: CELF-P2 Core Language Score 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Day-night Stroop (measure of 

efficiency) (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Differential Ability Scales, second 

edition (DAS II) score: General Conceptual 

Ability Score (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Differential Ability Scales, second 

edition (DAS II) score: General Conceptual 

Ability Score (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Meldrum et al., 2012140

Study name: Infant 

FishOil Supplementation 

Study (IFOS)

Study dates: Recruitment 

from June 2005 through 

October 2008

Study design: Trial 

randomized parallel

Location: Australia

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 420

Infants enrolled 420 

Infants completers 287

Mother age: NR (NR) NR

Infant age: Birth (NA) NA

Race of Mother: NR

Inclusion Criteria: allergic 

pregnant women were 

recruited as their infants 

are at a higher risk of 

developing allergic 

disease. Maternal atopy 

was defined by at least 

one positive skin prick 

test to at least one of a 

defined panel of 

allergens.

Exclusion Criteria: 

maternal smoking, a preexisting medical 

Start time: Infants birth

Duration: Infants 6 months

Arm 1: placebo

Description: olive oil capsule

Manufacturer: Ocean Nutrition, Canada

Active ingredients: 66·6 % n-9 oleic acid

Viability: he composition was regularly tested by an 

independent laboratory during the trial

Dose: one 650 mg capsule

Blinding: image and scent matched

Arm 2: fish oil capsule

Manufacturer: Ocean Nutrition, Canada

Outcome: Bayley Scales of Infant and 

Toddler Development (BSID-III) Composite 

Scores Cognitive (Primary)

Follow-up time: 18 months

Arm 1: Sample size 149; mean 105.28; SD 

(19.9)

Arm 2: Sample size 138; mean 107.65; SD 

(11.6)

Outcome: Bayley Scales of Infant and 

Toddler Development (BSID-III) Standard 

Scores Cognitive (Primary)

Follow-up time: 18 months

Arm 1: Sample size 149; mean 11.43; SD 

(2.3)

Arm 2: Sample size 138; mean 11.55; SD 

232
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / conflict: 

Government, None, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: D'Vaz, 

2012142

Baseline biomarker 

information: Cord blood 

data Fish oil group LA, 

linoleic acid 3.71 ALA, alinolenic acid 0·496 EPA

0·334 DHA 7·36 DPA 

0·700 AA, arachidonic 

acid 15·76 Olive oil group 

LA, linoleic acid 3.81 

ALA, a-linolenic acid 

0·513 EPA 0·308 DHA 

7·44 DPA 0·673 AA, 

arachidonic acid 15·54

Baseline Omega-3 

intake: From maternal 

food questionnaire, while 

pregnant Fish oil group 

LA, linoleic acid 10·59 

ALA, a-linolenic acid 0·87 

EPA 0·07 DHA 0·09 AA, 

arachidonic acid 0·87

Olive oil group LA, 

linoleic acid 9·90 ALA, alinolenic acid 0·89 EPA

0.06 DHA 0·08 AA, 

arachidonic acid 0·84

condition or high-risk 

pregnancy, more than 

three fish meals 

consumed per week or 

fish oil intake during 

pregnancy in excess of 

1000 mg/d, preterm 

delivery, and infants with 

significant congenital 

abnormalities or medical 

conditions.

Viability: he composition was regularly tested by an 

independent laboratory during the trial.

Dose: one 650 mg capsule

DHA: 280 mg

EPA: 110 mg

(2.2)

Outcome: Macarthur-Bates Communicative 

Development Inventory raw score: early 

gestures (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 9.56; SD 

(3.14)

Arm 2: Sample size 62; mean 10.29; SD 

(3.5)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 13.62; SD 

(7.7)

Arm 2: Sample size 77; mean 14.09; SD 

(2.3)

Outcome: Macarthur-Bates Communicative 

Development Inventory raw score: later 

gestures (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 11.26; SD 

(7.5)

Arm 2: Sample size 62; mean 15.16; SD 

(8.3)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 28.08; SD 

(7.7)

Arm 2: Sample size 77; mean 30.81; SD 

(7.6)

Outcome: Macarthur-Bates Communicative 

Development Inventory raw score: phrases 

understood (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 13.6; SD 

(5.8)

Arm 2: Sample size 62; mean 13.34; SD 

(6.7)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 23.5; SD 

(5.1)

Arm 2: Sample size 77; mean 24.06; SD 

(4.7)

Outcome: Macarthur-Bates Communicative 

Development Inventory raw score: total 

gestures (Primary)

Follow-up time: 12 months

233
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 66; mean 20.76; SD 

(10.1)

Arm 2: Sample size 62; mean 25.47; SD 

(10.9)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 41.48; SD 

(9.3)

Arm 2: Sample size 77; mean 44.75; SD (9)

Outcome: Macarthur-Bates Communicative 

Development Inventory raw score: words 

spoken (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 5.52; SD 

(8.7)

Arm 2: Sample size 62; mean 6.11; SD 

(7.5)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 58.5; SD 

(63.5)

Arm 2: Sample size 77; mean 49.16; SD 

(55.8)

Outcome: Macarthur-Bates Communicative 

Development Inventory raw score: words 

understood (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 61.42; SD 

(52.2)

Arm 2: Sample size 62; mean 68.3; SD 

(47.6)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 190.43; SD 

(94.5)

Arm 2: Sample size 77; mean 199.09; SD 

(83.7)

Meldrum et al., 201551

Study name: Dunstan

Study dates: 10/2012-

12/2013 for 12-year 

followup

Study design: Trial 

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 98 

Pregnant completers 82

Infants enrolled 82 

Infants completers 50

Inclusion Criteria: 

Pregnant women with 

allergies

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked, had medical 

problems, a complicated 

Start time: Pregnant 20 weeks gestation

Duration: Pregnant to birth

Arm 1: Placebo

Description: Olive oil capsules

Manufacturer: Pan Laboratories

Dose: 4 1g capsules per day

Blinding: Randomization and allocation of capsules 

Outcome: Wechsler Intelligence Scale for 

Children IV (Secondary)

Follow-up time: 12 years

Arm 1: Sample size 25; mean 107.6; SD 

(9.9)

Arm 2: Sample size 25; mean 108.6; SD 

(12.2)

234
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

randomized parallel

Location: Australia

Funding source / conflict: 

Multiple foundations and 

Societies, None

Study follow-up: 12 years

Original, same study, or 

follow-up studies: 

Dunstan, 200350; 

Dunstan, 200844;

Pregnant age: Fish oil 

30.9 Control 32.6 (Fish 

oil: 3.7 Control: 3.6)

Infant age: NR (NR)

Race of Mother: NR 

(100)

pregnancy, seafood 

allergy, or if their normal 

dietary intake exceeded 

two meals of fish per 

week. Children were 

excluded from the study 

if they were born before 

36 weeks’ gestation or 

with major disease (to 

avoid the confounding 

effects on immune 

response) or if cord blood 

was not collected

was carried out in a blinded manner, and capsules in 

the two groups were image matched

Arm 2: Fish oil

Manufacturer: Ocean Nutrition

Active ingredients: 3–4 mg/g oil a-tocopherol 

(vitamin E)

Dose: 4 1g capsules per day

DHA: 2.2g

EPA: 1.1g

Mulder et al., 201475

Study name: NR

Study dates: 2004 to 

2008

Study design: Trial 

randomized parallel

Location: Canada

Funding source / conflict: 

Government

Study follow-up: 18 

months

Study Population: 

Healthy pregnant women

Pregnant enrolled 271 

Pregnant completers 200

Pregnant age: 33 years 

(4 years) NR

Race of Mother: White 

European (73%) Other 

race/ethnicity (27%)

Baseline biomarker 

information: maternal 

RBC 

Phusphatidylethanolamin

e DHA: placebo group 

6.25 (1.60) g/ 100g DHA 

group 6.36 (1.62) g/ 100g

Baseline Omega-3 

intake: median (2.5 to 

97.5th percentile range) 

intake: placebo group

80.0 (0.00-334) mg/day, 

DHA group 90.0 (6.00-

472) mg/d

Inclusion Criteria: at least 

16 wk gestation, not 

taking any lipid or fatty 

acid supplement, and 

were expected to deliver 

one infant at full-term 

gestation, with no 

maternal or fetal 

complications

Exclusion Criteria: NR

Start time: Pregnant 16 weeks gestation

Duration: Pregnant Until birth

Arm 1: placebo

Description: corn and soybean oil supplement

Manufacturer: Martek Biosciences

Blinding: supplements were identical in appearance, 

contained an orange flavor mask

Arm 2: DHA supplement

Description: algal oil DHA supplement

Manufacturer: Martek Biosciences

DHA: 400 mg

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

cognitive (Unspecified)

Follow-up time: 18 months

Arm 1: 18/80 (23.1%)

Arm 2: 15/74 (20.0%)

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

expressive language (Unspecified)

Follow-up time: 18 months

Arm 1: 19/80 (24.1%)

Arm 2: 28/74 (37.5%)

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

receptive language (Unspecified)

Follow-up time: 18 months

Arm 1: 16/80 (20.5%)

Arm 2: 27/74 (36.5%)

Outcome: Number in highest quartile of 

Infant MacArthur Communicative 

Development Inventory: words produced 

(Unspecified)

Follow-up time: 14 months

Arm 1: 13/81 (16.0%)

Arm 2: 26/78 (33.3%)

Follow-up time: 18 months

Arm 1: 12/61 (19.1%)

Arm 2: 27/73 (37.3%)

Outcome: Number in highest quartile of 

235
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Infant MacArthur Communicative 

Development Inventory: words understood 

(Unspecified)

Follow-up time: 14 months

Arm 1: 12/81 (14.8%)

Arm 2: 28/78 (35.9%)

Follow-up time: 18 months

Arm 1: 11/61 (18.8%)

Arm 2: 27/73 (37.3%)

Outcome: Number in highest quartile of 

Toddler MacArthur Communicative 

Development Inventory: words produced 

(Unspecified)

Follow-up time: 18 months

Arm 1: 10/61 (17.1%)

Arm 2: 26/73 (35.0%)

Ramakrishnan et al., 

201561

Study name: POSGRAD

Study dates: 2005-2009

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, None, 

March of Dimes

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Stein, 201233; ImhoffKunsch, 201158; 

Escamilla-Nunez, 201459;

Gonzalez-Casanova, 

201560; Ramakrishnan, 

Study Population: 

Healthy pregnant women

Pregnant enrolled 1094 

Pregnant completers 968

Infants enrolled 973 

Infants completers 730

Pregnant age: Placebo: 

26.3 Intervention: 26.5 

(Placebo: 4.6 

Intervention: 4.9)

Infant age: Placebo: 20.5 

weeks gestation 

Intervention: 20.6 weeks 

gestation (Placebo: 2.1 

weeks Intervention: 2.0 

weeks)

Race of Mother: NR (NR)

Baseline Omega-3 

intake: From original 

study ref 3364 mg/day for 

all: LA: 17,846 in 

Inclusion Criteria: 

Women who were in 

gestation week 18–22, 

age 18–35 years, 

planned to deliver at the 

IMSS General Hospital 

and to remain in the area 

for the next 2 years, and 

planned predominant 

breastfeeding for at least 

3 months

Exclusion Criteria: High 

risk pregnancy, had any 

lipid 

metabolism/absorption 

conditions, regularly took 

DHA or fish oil 

supplements, or used 

certain chronic 

medications (such as 

antiepileptic drugs)

Start time: Pregnant 18-22 weeks gestation

Duration: Pregnant 18-22 weeks gestation until 

delivery

Arm 1: Control

Description: Corn and soy oils with no added 

antioxidants

Dose: 2 capsules/day

Blinding: Similar in appearance and taste to the DHA 

capsules

Arm 2: Intervention

Description: Algal-sourced DHA capsule

Manufacturer: Martek Biosciences

Dose: 2 capsules/day

DHA: 200 mg * 2 = 400 mg/d

Outcome: Bayley Mental Development 

Index (Primary)

Follow-up time: 18 months

Arm 1: Sample size 365; mean 95.2; SD 

(9.3)

Arm 2: Sample size 365; mean 94.3; SD 

(10.7)

236
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

201561 controls, 17,645 in DHA 

AA: 137 in controls, 140 

in DHA ALA: 1,488 in 

controls, 1,477 in DHA 

EPA: 18 in controls, 18 in 

DHA DHA: 54 in controls, 

56 in DHA

Smithers et al., 2010117

Study name: DINO

Study dates: April 2001 

through September 2003

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product, Some 

authors serve on 

scientific advisory boards 

for corporations, Some 

authors have received 

research funding from 

infant formula 

manufacturers

Study follow-up: 3-5 

years

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Study Population: 

Preterm infants

Lactating enrolled 545

Infants enrolled 657 

Infants completers 614

Lactating enrolled 545

Lactating age: 30 years 

(5.5 years) NR

Infant age: 4 days after 

birth (29 weeks 

gestation) 2 to 6 days 

after birth

Race of Mother: White 

European (90%)

Inclusion Criteria: infants 

born at < 33 wk of 

gestation

Exclusion Criteria: Infants 

born with major 

congenital or 

chromosomal 

abnormalities or born to 

lactating women for 

whom tuna oil was 

contraindicated (women 

with bleeding disorders 

or taking anticoagulants)

Start time: Lactating 4 days after birth Infants 4 days 

after birth

Duration: Lactating until infants reached their 

"expected" date of delivery. Infants until infants 

reached their "expected" date of delivery

Arm 1: Placebo

Description: Soy oil capsules or standard preterm 

formula if not breastfeeding

Manufacturer: Clover Corporation

Dose: six 500-mg soy oil capsules

Blinding: all capsules were similar in size, shape, 

and color

DHA: Formula: 0.35%

AA: Formula: 0.6%

Total N-3: Capsules: did not change FA content of 

breastmilk

Arm 2: DHA

Description: DHA-rich tuna oil capsules or high-DHA 

formula

Manufacturer: Clover Corporation

Dose: six 500 mg capsules per day

DHA: Capsules: Achieved breast milk concentration 

of 1.0%. Formula: 1.0%

AA: Capsules: Did not change AA in breast-milk. 

Formula 0.6%

Other dose 1: DHA-rich tuna oil capsules to achieve 

a breast milk DHA concentration that was 

approximately 1% of total fatty acids without altering 

the naturally occurring concentration of arachidonic 

acid (AA) in breast milk

Outcome: MacArthur Communicative 

Development Inventory (MCDI) vocabulary 

production score (Secondary)

Follow-up time: 26 months CA

Arm 1: Sample size 67; mean 316.0; SD 

(192)

Arm 2: Sample size 60; mean 308.0; SD 

(179)

Tofail et al., 200677 Study Population: Inclusion Criteria: seems Start time: Pregnant 25 weeks gestation Outcome: Bayley Scale of Infant 

237
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: NR

Study dates: Enrollment 

January to March 2000

Study design: Trial 

randomized parallel

Location: Bangladesh

Funding source / conflict: 

Government

Study follow-up: 10 

months

Healthy infants Healthy 

pregnant women

Pregnant enrolled 400 

Pregnant completers 151

Pregnant age: 22.7 years 

(4.35 years) NR

Race of Mother: Asian 

(100%)

as if all pregnant women 

at 25 weeks gestation 

were enrolled, no 

inclusion criteria 

specified

Exclusion Criteria: NR

Duration: Pregnant until birth

Arm 1: placebo

Description: soy oil capsule

Dose: 4 one gram capsules per day

Blinding: capsules were identical in appearance

Other dose 1: LNA 0.27 g

Other dose 2: linoleic acid 2.25 g

Arm 2: DHA supplement

Description: fish oil capsules

Dose: 4 one gram capsules per day

DHA: 1.2 g

EPA: 1.8 g

Development (Mental developmental index) 

(Unspecified)

Follow-up time: 10 months

Arm 1: Sample size 124; mean 101.5; SD 

(7.8)

Arm 2: Sample size 125; mean 102.5; SD 

(8)

Werkman et al., 1996154

Study name: NR

Study dates: 1987-1990

Study design: Trial 

randomized parallel

Location: US

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study follow-up: 12 

months

Study Population: 

Preterm infants

Infants enrolled 67 

Infants completers 64

Mother age: 23 y (6 y)

Infant age: Born at 29 

wks gestation (2 wks)

Race of Mother: NR 

(100)

Inclusion Criteria: 

Preterm infants weighing 

between 748 and 1398 g 

at birth. They were 

eligible for this study 

when they had tolerated 

enteral intakes > 462 

kJ/kg body weight/day for 

5-7 days

Exclusion Criteria: Need 

for mechanical ventilation 

at that time, 

intraventricular 

hemorrhage > grade 2, 

retinopathy of prematurity 

> stage 2, surgery for 

necrotizing enterocolitis, 

a weight less than the 

fifth percentile for 

gestational age, and a 

history of maternal 

substance abuse

Start time: Infants 25 days

Duration: Infants 25 days - 9 months

Arm 1: Placebo term and pre-term infant formulas

Active ingredients: n-6: 19.1-33.2% of total FA

Dose: Formula remained the infants' major source of 

nutrients and energy through at least 9 mo past 

expected term, but other foods were gradually 

added to the diet beginning at -4 mon past term

Blinding: NR

Total N-3: Preterm: 3% of total FA; term: 4.8% of 

total FA

Arm 2: DHA-supplemented term and pre-term infant 

formulas

Description: Marine oil replaced fat blend in 

commercial formulas

Brand name: Similac

Manufacturer: Ross Products Division

Active ingredients: 18.7-32.6% of total FA

Dose: Formula remained the infants' major source of 

nutrients and energy through at least 9 mo past 

expected term, but other foods were gradually 

added to the diet beginning at -4 mon past term

ALA: Preterm: 3.1% of total FA; Term: 4.9% of total 

FA

Outcome: Fagan Test of Intelligence: 

average time/look (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 1.18; SD 

(0.05)

Arm 2: Sample size 33; mean 1.11; SD 

(0.05)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 1.75; SD 

(0.06)

Arm 2: Sample size 33; mean 1.62; SD 

(0.06)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 1.3; SD 

(0.06)

Arm 2: Sample size 33; mean 1.13; SD 

(0.05)

Outcome: Fagan Test of Intelligence: looks 

to familiar (number) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 18.8; SD 

(0.8)

Arm 2: Sample size 33; mean 21.7; SD 

(0.8)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 18.8; SD (1)

Arm 2: Sample size 33; mean 22.1; SD (1)

238
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

DHA: 0.2% of total FA

EPA: 0.3% of total FA

Other dose 1: Preterm: 3.6% of total FA; term: 5.4% 

of total FA

Follow-up time: 9 months

Arm 1: Sample size 34; mean 18.2; SD 

(0.9)

Arm 2: Sample size 33; mean 21.4; SD 

(0.9)

Outcome: Fagan Test of Intelligence: looks 

to novel (number) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 23.6; SD 

(0.8)

Arm 2: Sample size 33; mean 26.0; SD 

(0.8)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 22.2; SD (1)

Arm 2: Sample size 33; mean 26.0; SD (1)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 22.1; SD 

(0.9)

Arm 2: Sample size 33; mean 25.2; SD 

(0.8)

Outcome: Fagan Test of Intelligence: novel 

time (% of total) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 64.6; SD 

(1.2)

Arm 2: Sample size 33; mean 60.5; SD 

(1.3)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 60.4; SD 

(1.4)

Arm 2: Sample size 33; mean 59.8; SD 

(1.3)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 62.2; SD 

(1.2)

Arm 2: Sample size 33; mean 62.2; SD 

(1.2)

Outcome: Fagan Test of Intelligence: time 

to familiar (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 16.3; SD 

(0.8)

Arm 2: Sample size 33; mean 19.3; SD 

(0.9)

239
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 26.6; SD 

(1.1)

Arm 2: Sample size 33; mean 26.6; SD 

(1.1)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 18.2; SD (1)

Arm 2: Sample size 33; mean 18.3; SD 

(0.9)

Outcome: Fagan Test of Intelligence: time 

to novel (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 32.6; SD 

(1.2)

Arm 2: Sample size 33; mean 31.9; SD 

(1.2)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 45.3; SD 

(1.5)

Arm 2: Sample size 33; mean 45.9; SD 

(1.5)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 32.9; SD 

(1.3)

Arm 2: Sample size 33; mean 32.6; SD 

(1.3)

Outcome: Fagan Test of Intelligence: 

time/familiar look (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 0.85; SD 

(0.05)

Arm 2: Sample size 33; mean 0.91; SD 

(0.05)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 1.42; SD 

(0.06)

Arm 2: Sample size 33; mean 1.31; SD 

(0.06)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 1.04; SD 

(0.06)

Arm 2: Sample size 33; mean 0.91; SD 

(0.05)

Outcome: Fagan Test of Intelligence: 

240
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

time/novel look (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 1.43; SD 

(0.07)

Arm 2: Sample size 33; mean 1.27; SD 

(0.07)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 2.03; SD 

(0.09)

Arm 2: Sample size 33; mean 1.88; SD 

(0.08)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 1.51; SD 

(0.08)

Arm 2: Sample size 33; mean 1.33; SD 

(0.07)

Outcome: Fagan Test of Intelligence: total 

looks (number) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 42.4; SD 

(1.3)

Arm 2: Sample size 33; mean 47.7; SD 

(1.4)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 41.0; SD 

(1.7)

Arm 2: Sample size 33; mean 48.2; SD 

(1.7)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 40.3; SD 

(1.5)

Arm 2: Sample size 33; mean 47.0; SD 

(1.5)

Outcome: Fagan Test of Intelligence: total 

time (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 48.9; SD 

(1.4)

Arm 2: Sample size 33; mean 51.2; SD 

(1.4)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 72.0; SD 

(1.8)

Arm 2: Sample size 33; mean 72.6; SD 

241
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(1.7)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 51.1; SD 

(1.6)

Arm 2: Sample size 33; mean 50.9; SD 

(1.5)

Willatts et al., 2013170

Study name: NR

Study dates: 1992

Study design: Trial 

randomized parallel

Location: Italy, UK, 

Belgium

Funding source / conflict: 

Industry

Study follow-up: 6 years

Study Population: 

Healthy infants

Infants enrolled 237 

Infants completers 147

Infant age: birth

Race of Mother: NR 

(100)

Inclusion Criteria: 

Healthy term singletons, 

37-42 weeks gestation, 

2500-4000g birth weight

Exclusion Criteria: NR

Start time: Infants Birth to 1 week

Duration: Infants 4 months

Arm 1: Non-LC-PUFA

Description: Control formula lacking LCPUFA

Manufacturer: Milupa GmbH

Viability: g/100 g fat

Dose: NR

Blinding: NR

ALA: 0.7

DHA: 0

AA: <0.10

Arm 2: LC-PUFA formula

Manufacturer: Milupa GmbH

Dose: NR

ALA: 0.62 g/100g fat

DHA: 0.21 g/100g fat

AA: 0.35 g/100g fat

Outcome: Wechsler Preschool and Primary 

Scale of Intelligence: Full-Scale IQ 

(Secondary)

Follow-up time: 6 year

Arm 1: Sample size 76; mean 100.9; SD 

(16.2)

Arm 2: Sample size 71; mean 98.0; SD 

(14.8)

Outcome: Wechsler Preschool and Primary 

Scale of Intelligence: Performance IQ 

(Secondary)

Follow-up time: 6 year

Arm 1: Sample size 76; mean 101.3; SD 

(15.5)

Arm 2: Sample size 71; mean 99.6; SD 

(13.6)

Outcome: Wechsler Preschool and Primary 

Scale of Intelligence: Verbal IQ 

(Secondary)

Follow-up time: 6 year

Arm 1: Sample size 76; mean 100.2; SD 

(16.4)

Arm 2: Sample size 71; mean 97.3; SD 

(17.5)

de Jong et al., 201265

Study name: Groningen 

LCPUFA study

Study dates: Enrollment 

from February 1997 

through October 1999, 

follow-up 9 years later

Study design: Trial 

randomized parallel

Study Population: 

Healthy infants

Infants enrolled 314 

Infants completers 214

Mother age: 31 years (5 

years) NR

Infant age: birth (NA) NA

Race of Mother: White 

Inclusion Criteria: healthy 

infants

Exclusion Criteria: infants 

who had a congenital 

disorder that interfered 

with adequate functioning 

in daily life, infants from 

multiple births, infants 

whose mothers did not 

have mastery of the 

Dutch language or 

suffered from significant 

Start time: Infants birth

Duration: Infants 2 months

Arm 1: Control formula

Description: Standard formula with no supplemental 

LCPUFA

Brand name: Nutrilon premium

Manufacturer: Nutricia, Zoetermeer, Netherlands

Active ingredients: linoleic acid (11mol%); ALA 1.27 

mol%

Blinding: NR

Maternal conditions

No usable data.

Outcome: (Secondary)

242
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: Netherlands

Funding source / conflict: 

Industry, Government, 

Some authors have 

received research 

funding from infant 

formula manufacturers

Study follow-up: 9 years

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; van Goor, 

201036; van Goor, 201166

European (100%) illness or disability, 

adopted and foster 

infants, and formula-fed 

infants who had received 

human milk for >5 d.

Current smoker 23% during pregnancy

Other maternal conditions 

1arm_1_maternal_conditions_other1

Other maternal conditions 10 maternal hypertension 

17%

Arm 2: Omega 3 supplemented formula

Description: LCPUFA formula

Manufacturer: Nutricia, Zoetermeer, Netherlands

Active ingredients: linoleic acid (11mol%); ALA 1.30 

mol%

Maternal conditions

DHA: 0.30% by weight

AA: 0.45% by weight

Current smoker 32% during pregnancy

Other maternal conditions 

1arm_2_maternal_conditions_other1

Other maternal conditions 10 maternal hypertension

12%

Arm 3: breastfeeding comparison group

Maternal conditions

Current smoker 10% during pregnancy

Other maternal conditions 

1arm_3_maternal_conditions_other1

Other maternal conditions 10 maternal hypertension 

9%

243
Table 18. Observational studies for cognitive development

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Bakker, et al., 2003163

Outcome domain: Cognitive

Study name: Maastricht Essential Fatty Acid 

Birth (MEFAB) Cohort

Study dates: Recruitment December 1990 to 

January 1994

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Government

Follow-up: 7 years

Original, same study, or follow-up studies: 

Bakker, 2009134 and two articles in original 

report: Ghys, 2002 and Al, 1995

Study Population: Healthy infants

Infants enrolled 750 Infants withdrawals 444 

Infants completers 306

Pregnant age: 29.8 (4.1)

Infant age: birth

Race of Mother: White European (100)

Inclusion Criteria: 750 Caucasian children, 7 y old, 

born between December 1990 and January 1994 in 

the course of an earlier study on maternal and 

neonatal LCPUFA status and pregnancy outcome

Exclusion Criteria: Not reported

Adjustments: Social class, 

maternal intelligence, 

parenting skills, maternal 

smoking and drinking habits 

during pregnancy, 

breastfeeding duration, and 

the child’s sex, birth order and 

birth weight

Bernard, et al., 201389

Outcome domain: Cognitive

Study name: EDEN

Study dates: Recruitment 2003 to 2005

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Follow-up: 2 and 3 years

Original, same study, or follow-up studies: 

Drouillet, 200980

Study Population: Healthy pregnant women

Pregnant enrolled 2,002 Pregnant completers 

1,882

Infants enrolled 1.882 Infants completers 1,510

Pregnant age: 29.2 years (at conception) (4.8 

years) NR

Infant age: < 24 weeks gestation (NR) NR

Race of Mother: NR (100)

Inclusion Criteria: < 24 weeks amenorrhea

Exclusion Criteria: multiple pregnancies, known 

diabetes before pregnancy, illiteracy, and intention 

to move outside the region in the next 3 years

Adjustments: Center, child 

gender & age, gestational 

age, maternal age, obesity, 

energy intake, tobacco & 

alcohol consumption, parental 

education & income, first 

born, main daytime caregiver, 

and frequency of maternal 

stimulations

Guxens, et al., 2011144

Outcome domain: Cognitive

Study Population: Healthy infants Breastfeeding women

Pregnant enrolled 657 Pregnant completers 622

Inclusion Criteria: age older than 16 years, intent to 

deliver at the reference hospital, singleton 

pregnancy

Adjustments: Child's age, 

maternal and paternal: 

education, social class, 

attachment to child, mental 

244
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Study name: INMA

Study dates: Recruitment: July 2004 to July 

2006 Followup: 14 months

Study design: Observational prospective

Location: Spain

Funding source / conflict: Government, Multiple

foundations and Societies

Follow-up: 14 months

Original, same study, or follow-up studies: 

Julvez, 2014143

Lactating enrolled 622 Lactating completers 582

Infants enrolled 622 Infants completers 582 

(319 with LCPUFA data)

Lactating enrolled 622 Lactating completers 582

Lactating age: 31.6 years (4.2 years)

Infant age: 2 to 5 days postpartum

Race of Mother: NR (NR)

Exclusion Criteria: no problems of communication,

no assisted conception

health; maternal age, 

maternal alcohol use during 

pregnancy, use of gas stove, 

child age of food introduction

Keim, et al., 2012162

Outcome domain: Cognitive

Study name: Pregnancy, Infection and Nutrition 

Study

Study dates: Recruitment between January 

2001 and June 2005 Followup: 1 year

Study design: Observational prospective

Location: US

Funding source / conflict: Government

Follow-up: 12 months

Study Population: Healthy infants Breastfeeding women

Pregnant enrolled 1,169 Pregnant completers 

689

Infants enrolled 408 Infants completers 358

Pregnant age: NR

Infant age: 20 weeks gestation NA

Race of Mother: White European (79.1%) Other 

race/ethnicity (21.0)

Inclusion Criteria: health women at less than 20 

weeks of pregnancy

Exclusion Criteria: pregnant with multiple fetuses, 

unable to communicate in English, under age 16 

years, no access to a telephone, intention to go 

elsewhere for future care or delivery

Adjustments: Laboratory, 

infant sex, race, parity, 

maternal smoking, education, 

breastfeeding status and 

preterm status

245
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Steer, et al., 2013164

Outcome domain: Cognitive

Study name: Avon Longitudinal Study of 

Parents and Children (ALSPAC)

Study dates: 1991-2000

Study design: Observational prospective

Location: UK

Funding source / conflict: Government

Follow-up: 8 years

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 14,541

Infants completers 2,839

Mother age: 29.33 (4.48)

Infant age: birth

Race of Mother: White European (98.8) Black 

(0.6) Asian (0.6)

Inclusion Criteria: pregnant women with expected 

delivery date between 4/91 and 12/92 in Bristol UK

Exclusion Criteria: Not reported

Adjustments: Maternal age, 

education, ethnicity, alcohol 

consumption and smoking; 

partner status, housing 

tenure, crowding index, parity, 

preterm gestation (37 wk), low 

birth weight (,2500 g), multiple 

births, sex, breastfeeding, and 

measures of adversity (in 

pregnancy and during the first 

2 y after birth) and child 

stimulation (both from the 

home environment and 

maternal interaction with the 

child)

Valent, et al., 2013132

Outcome domain: Cognitive

Study dates: 2007-2011

Study design: Observational prospective

Location: Italy

Funding source / conflict: Government

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 900 Pregnant completers 767

Infants enrolled 767 Infants completers 632

Pregnant age: 33.3 (4.3)

Infant age: Birth

Race of Mother: NR (100)

Inclusion Criteria: Permanent residents of the study 

areas for at least 2 years, at least 18 years of age, 

and had no absence from the study area for more 

than 6 weeks during pregnancy, no history of drug 

abuse, no serious health problems or complications 

of pregnancy, and no twin gestation

Exclusion Criteria: Preterm births (<37 weeks of 

gestational age), babies with congenital 

malformations or severe perinatal problems, and 

those with severe health problems that presented 

postnatally and potentially compromised their 

neurological development

Adjustments: Fish intake, fatty 

acids in maternal serum and 

proportion of PUFAs, sex, 

birth weight, maternal IQ, 

weight gain during pregnancy, 

marital status at delivery, SES 

index, number of children 

living in home, alcohol intake 

during pregnancy, 

breastfeeding history, child 

intake of fish until age 18 

months, and daycare 

attendance at age 18 months

246
Autism Spectrum Disorders (ASD)

Description of Included Studies

Randomized Controlled Trials

The original report did not include ASD as an outcome of interest. Two RCTs reported autism 

outcomes at long-term follow-up (Table 19). One trial that randomized pregnant women to either 

high DHA supplement or placebo57 reported that diagnoses of ASD among offspring at age four 

did not differ between groups (two cases in the DHA group and four cases in the control group). 

Another RCT that randomized pre-term infants to either high-DHA or standard DHA enteral 

feeds from two to four days after birth until term corrected age; parent reports of ASD diagnosis 

at seven years did not differ significantly between the groups.120

Observational Studies

One observational study investigated whether n-3 FA intake before and during pregnancy 

was associated with risk of ASD in offspring (Table 20).

171 Lyall et al (2013) conducted an 

analysis of data from the Nurses’ Health Study II. They compared dietary intake between 317 

mothers of children with ASD and 17,728 comparison mothers. Children were born from 1991 

through 2007. Prepregnancy and pregnancy dietary information was reported via food frequency 

questionnaire (FFQ) and ASD diagnosis was self-reported by mothers. The authors found that 

women with the highest quartile of total PUFA intake were at lower risk of having a child with 

ASD than women in the lowest quartile (RR 0.67; 95% CI 0.49, 0.92). This model adjusted for 

maternal age, income level, race, BMI, total energy intake, pre-pregnancy smoking status, and 

child’s year of birth. Using the same model and adjustments, the researchers also found that 

women whose intake of linoleic acid was in the highest quartile had a lower risk of having a 

child with ASD than those in the lowest quartile (RR 0.66 95% CI 0.48, 0.92). The authors 

advised that the results should be interpreted with caution, given the small number of cases.

247
Table 19. RCTs for autism spectrum disorders

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Collins et al., 2015120

Study name: DINO

Study dates: 2001-2013

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Study Population: 

Preterm infants

Infants enrolled 657 

Infants completers 604

Infant age: median 30 

weeks gestational age 

28-31 weeks

Race of Mother: NR 

(100)

Inclusion Criteria: infants 

born at <33 weeks’ 

gestation from five 

Australian tertiary 

hospitals between 2001 

and 2005

Exclusion Criteria: a 

major congenital or 

chromosomal 

abnormality, multiple 

birth in which not all liveborn infants were eligible, 

enrollment in other trials 

of fatty acid 

supplementation, or if 

fish oil was 

contraindicated in the 

lactating mother

Start time: Infants within 5 days of 1st enteral 

feeding

Duration: Infants to expected due date

Arm 1: standard DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentrations of term formula fed infants

DHA: ___20 mg/kg/ day of DHA

Arm 2: High DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentration of breastmilk

DHA: ___50 mg/kg/ day of DHA

Outcome: number with autism spectrum 

disorder

Follow-up time: 7 years

Arm 1: 9/298 (3.0%)

Arm 2: 10/285 (3.5%)

Makrides et al., 201457

Study name: DOMInO

Study dates: October 31, 

2005 to September 25, 

2012

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product, Some authors 

Study Population: 

Healthy pregnant women

Infants enrolled 726 

Infants completers 646

Race of Mother: NR 

(100)

Inclusion Criteria: 

Women with singleton 

pregnancies at less than 

21 weeks' gestation

Exclusion Criteria: 

Already taking a prenatal 

supplement with DHA, 

fetus had a known major 

abnormality, had a 

bleeding disorder in 

which tuna oil was 

contraindicated, were 

taking anticoagulant 

therapy, had a 

documented history of 

drug or alcohol abuse, 

Start time: Pregnant <21 weeks gestation

Duration: Pregnant <21 weeks gestation until birth

Arm 1: Placebo

Description: rapeseed, sunflower, and palm oil 

capsules

Manufacturer: Enfamol

Dose: 3 500mg capsules/day

Blinding: similar in size, shape, and color

Arm 2: DHA supplement

Description: DHA-rich fish oil capsules

Manufacturer: Enfamol

Dose: 3 500mg capsules/day

DHA: 800 mg/d

EPA: 100 mg/day

Outcome: diagnosis of autism

Follow-up time: 4 years

Arm 1: 4/333 (1.2%)

Arm 2: 2/313 (0.64%)

248
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

have received research 

funding from infant 

formula manufacturers

Original, same study, or 

follow-up studies: 

Makrides, 2010 35

Smithers, 201153; Palmer, 

201254; Zhou, 201255;

Palmer, 201356

were participating in 

another fatty acid trial, 

were unable to give 

written informed consent, 

or if English was not the 

main language spoken at 

home

249
Table 20. Observational studies for autism spectrum disorders

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Lyall, et al., 2013171

Outcome domain: Autism

Study name: Nurses’ Health Study

Study dates: Births 1991 to 2007

Study design: NR

Location: US

Funding source / conflict: Government

Study Population: Healthy pregnant women

Pregnant enrolled 18,045 Pregnant completers 

5,884

Pregnant age: Q1 34.7y Q4 33.7 y NR

Infant age: birth

Race of Mother: White European (Q1: 96%; Q4: 

98%) Other race/ethnicity (Q1 4%; Q4 2%)

Inclusion Criteria: female nurses who were 25–42 

years of age in 1989, with index births between 1991 

(the year of first collection of dietary information) and 

2007; women reported a child with ASD either in 

2005 or 2009 not both, if 1) the reason for 

nonreporting on the other questionnaire was on 

participation in that questionnaire year; 2) the nurse 

confirmed the diagnosis in a previous substudy; or 

3) for women reporting on the 2009 questionnaire 

only, the child was born after 2000 (in which case, 

the child might have been too young for report of 

diagnosis by the 2005 questionnaire mailing)

Exclusion Criteria: Women reporting competing 

diagnoses (fragile X syndrome, Ret syndrome, 

tuberous sclerosis, Down syndrome, trisomy 18; in a 

previous sub-study were not included. Women 

without food frequency questionnaire data or without 

autism diagnosis info on child

Adjustments: Adjusted for 

total energy intake, maternal 

age, child’s year of birth, 

income level, race, body 

mass index, and 

prepregnancy smoking status. 

Removal of adjustment for 

smoking did not affect results. 

Additional adjustment for child 

birth order, maternal physical 

activity level, spouse’s 

education level, or 

multivitamin use, or for transfat in PUFA model, did not 

materially alter estimates

250
Attention Deficit Hyperactivity Disorder (ADHD)

Description of Included Studies

Randomized Controlled Trials

The original report did not include ADHD as an outcome of interest. We identified three 

RCTs that reported on ADHD or attention outcomes (see Table 21). The first, Isaacs et al., 

201199, randomized pre-term infants in the UK to either control formula or LCPUFA 

supplemented formula containing DHA, EPA, and AA. At ten year follow-up there were no 

significant differences between groups on the any of the scales of the Test of Everyday Attention 

for Children. Another identified study was a seven year follow-up of the DINO trial conducted in 

Australia.120 Pre-term infants were randomized to either standard (20 mg/kg/ day of DHA) or 

high-dose DHA (50 mg/kg/ day) formula. There were no significant differences between groups 

on the any of the scales of the Test of Everyday Attention for Children or the Conners ADHD 

score. Finally, there was no difference in the rate of “hyperactivity disorder” at four years among 

offspring of mothers receiving DHA supplementation or placebo during pregnancy in the 

DOMINO study, an Australian RCT.57

Observational Studies

No observational studies on ADHD or attention were identified.

251
Table 21. RCTs for attention deficit hyperactivity disorder

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Collins et al., 2015120

Study name: DINO

Study dates: 2001-2013

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Study Population: 

Preterm infants

Infants enrolled 657 

Infants completers 604

Infant age: median 30 

weeks gestational age 

28-31 weeks

Race of Mother: NR 

(100)

Inclusion Criteria: infants 

born at <33 weeks’ 

gestation from five 

Australian tertiary 

hospitals between 2001 

and 2005

Exclusion Criteria: a 

major congenital or 

chromosomal 

abnormality, multiple 

birth in which not all liveborn infants were eligible, 

enrollment in other trials 

of fatty acid 

supplementation, or if 

fish oil was 

contraindicated in the 

lactating mother

Start time: Infants within 5 days of 1st enteral 

feeding

Duration: Infants to expected due date

Arm 1: standard DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentrations of term formula fed infants

DHA: ___20 mg/kg/ day of DHA

Arm 2: High DHA

Description: DHA supplementation of infant formula 

or breastfeeding mothers to achieve DHA 

concentration of breastmilk

DHA: ___50 mg/kg/ day of DHA

Outcome: ADHD Conners 3 Al-parent: 

ADHD t score (total score) (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 64.4; SD 

(18.7)

Arm 2: Sample size 291; mean 65.6; SD 

(18.5)

Outcome: number with ADHD (parent 

reported) (Secondary)

Follow-up time: 7 years

Arm 1: 7/298 (2.3%)

Arm 2: 9/285 (3.16%)

252
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Isaacs et al., 201199

Study name: Unnamed 

Trial A

Study dates: Recruitment 

of infants from 1995 

through 1997 with 10-

year followup

Study design: Trial 

randomized parallel

Location: UK

Funding source / conflict: 

Industry, Government, 

Some authors have 

received research 

funding from infant 

formula manufacturers

Study follow-up: 10 years

Original, same study, or 

follow-up studies: 

Fewtrell, 2002158 is the 

original study; Llorente, 

200398 reports postpartum depression

Study Population: 

Preterm infants

Infants enrolled 238 

Infants completers 107

Infant age: birth (at < 35 

weeks gestation) NA

Race of Mother: NR (NR)

Inclusion Criteria: birth 

weight of < 2000 g, and 

gestational age of < 35 

weeks

Exclusion Criteria: 

congenital malformations

Start time: Infants at hospital discharge

Duration: Infants 9 months

Arm 1: control

Description: control formula

Active ingredients: protein, minerals, vitamins A, E, 

K, D

DHA: 0

EPA: 0

AA: 0

Other dose 1: C18:2, n-6, linoleic acid 11.5 g / 100g 

fat

Other dose 2: C18:3, n-3, alpha_x0004_-linolenic 

acid 1.6 g / 100g fat

Arm 2: Omega 3 supplemented formula

Description: LCPUFA-Supplemented Formula

Active ingredients: protein, minerals, vitamins A, E, 

K, D

Infant conditions

DHA: 0.5 g / 100g fat

EPA: 0.1 g/ 100g fat

AA: 0.04 g / 100g fat

Other dose 1: C18:2, n-6, linoleic acid 12.3 g / 100g 

fat

Other dose 2: C18:3, n-6, gamma-linoleic acid 0.9 g 

/ 100g fat

Other dose 3: C18:3, n-3, _x0004_alpha-linolenic 

acid 1.5 g / 100g fat

Pre-term birth 100%

Low birth weight 100%

Outcome: Test of Everyday Attention for 

Children: Attention scaled score 

(Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 8.3; SD (2.6)

Arm 2: Sample size 50; mean 8.2; SD (2.5)

Outcome: Test of Everyday Attention for 

Children: Creature counting scale score 

(Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 9.6; SD (2.1)

Arm 2: Sample size 50; mean 10.0; SD 

(2.7)

Outcome: Test of Everyday Attention for 

Children: Dual-task decrement scaled score 

(Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 7.3; SD (2.8)

Arm 2: Sample size 50; mean 7.6; SD (2.5)

Outcome: Test of Everyday Attention for 

Children: Opposite Worlds different scaled 

score (Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 8.4; SD (2.8)

Arm 2: Sample size 50; mean 8.9; SD (3.5)

Outcome: Test of Everyday Attention for 

Children: Score! Scale scored (Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 7.8; SD (3.4)

Arm 2: Sample size 50; mean 7.7; SD (3.4)

Makrides et al., 201457

Study name: DOMInO

Study dates: October 31, 

2005 to September 25, 

2012

Study design: Trial 

randomized parallel

Study Population: 

Healthy pregnant women

Infants enrolled 726 

Infants completers 646

Race of Mother: NR 

(100)

Inclusion Criteria: 

Women with singleton 

pregnancies at less than 

21 weeks' gestation

Exclusion Criteria: 

Already taking a prenatal 

supplement with DHA, 

fetus had a known major 

abnormality, had a 

bleeding disorder in 

Start time: Pregnant <21 weeks gestation

Duration: Pregnant <21 weeks gestation until birth

Arm 1: Placebo

Description: rapeseed, sunflower, and palm oil 

capsules

Manufacturer: Enfamol

Dose: 3 500mg capsules/day

Blinding: similar in size, shape, and color

Outcome: hyperactivity disorder

Follow-up time: 4 years

Arm 1: 0/333 (0.0%)

Arm 2: 0/313 (0.0%)

253
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product, Some authors 

have received research 

funding from infant 

formula manufacturers

Original, same study, or 

follow-up studies: 

Makrides, 2010 35

Smithers, 201153; Palmer, 

201254; Zhou, 201255;

Palmer, 201356

which tuna oil was 

contraindicated, were 

taking anticoagulant 

therapy, had a 

documented history of 

drug or alcohol abuse, 

were participating in 

another fatty acid trial, 

were unable to give 

written informed consent, 

or if English was not the 

main language spoken at 

home

Arm 2: DHA supplement

Description: DHA-rich fish oil capsules

Manufacturer: Enfamol

Dose: 3 500mg capsules/day

DHA: 800 mg/d

EPA: 100 mg/day

254
Atopic Dermatitis and Eczema

Key Points

• Of four interventions and two follow-up studies that examined the effects of prenatal n-3 

FA on the risk for developing eczema (DHA + EPA, varying doses), one of the studies 

found a significant association between n-3 FA supplementation and decreasing risk of 

eczema, whereas the other studies found no effects. A single trial that investigated ALA 

supplementation found no significant association with eczema risk. 

• Three postnatal n-3 interventions and three follow-up studies found no effect of 

supplementation of infant formula with n-3 FA (DHA or DHA+EPA, varying doses) and 

eczema prevalence up to8 years of age. 

• One biomarker study found associations between higher infant plasma DHA, erythrocyte 

EPA, and EPA/AA ratio and lower risk of eczema as well as increased symptoms of 

eczema with higher levels of AA and total n-6 PUFA.

• Six of seven prospective observational studies found no associations between n-3 FA 

exposure (measured through maternal dietary intake or breast milk composition) and 

eczema. One of four prospective observational studies of n-3 FA biomarkers (in cord

blood or maternal blood sample) found decreased risk of eczema and increasing AA 

levels, with null findings for the remaining three studies. 

This outcome is an additional outcome of interest that was not included in the original 

review. A total of 13 eligible studies (8 original RCTs and 5 follow-up studies) and 11 

observational studies were identified for this report. The study population included healthy 

pregnant women and infants with history of allergy as well as preterm infants.

Description of Included Studies

Randomized Controlled Trials

Prenatal Maternal Interventions/Exposures

We identified seven studies (five RCTs and two follow-up studies) that evaluated n-3 FA 

interventions given to the mothers during the prenatal period (see Table 22). 50, 54, 56, 79, 88, 172, 173

Among these studies, five studies assessed interventions with duration from pregnancy until 

birth.50, 54, 56, 88, 174 Three studies with maternal supplementation started during pregnancy and 

continued into breastfeeding, 79, 172, 173 with one of those trials also adding infant supplementation 

following breastfeeding.

79 All of these trials except for one 79 recruited pregnant women whose 

infants were at risk of atopy (i.e., one or more first-degree relatives of the infant affected by 

atopy, asthma, or allergy). 

DHA Plus EPA Versus Placebo

Four RCTs and two follow-up studies compared EPA plus DHA versus placebo.50, 54, 56, 88, 172, 

173

Dunstan (2003) randomized 98 pregnant, atopic Australian women to fish oil (3.7g n-3 

PUFA, 56.0% DHA, 27.7% EPA) or placebo (olive oil [4g]) daily from 20 weeks gestation until 

255
delivery.50 A total of 83 mothers and their children completed the 12-month follow-up. The 

authors report that infants in the fish oil group had higher odds of eczema, although this increase 

in risk is not statistically significant (OR1.88, 95% CI 0.77, 4.65; p=0.167). In addition, of the 

infants with eczema, those in the fish oil group were less likely to have severe disease, defined as 

a modified SCORAD index>25, than those in the placebo group (OR=0.09; 95% CI 0.01, 0.94; 

p=0.045).50

In the Salmon in Pregnancy Study (SiPS), 123 pregnant women in the UK were randomized 

to the salmon group (300g salmon / week) or control group (no changes in diet) from 20 weeks 

gestation until delivery.88 Clinical outcomes were available for 86 infants at 6 months. No 

differences in the incidence or severity (using the SCORAD index) of atopic dermatitis were 

observed between the salmon and control groups.88

In a subset of the Docosahexaenoic Acid (DHA) to Optimise Mother Infant Outcome 

(DOMInO) trial, 706 pregnant Australian women whose child was at high risk for genetic allergy 

were randomized to an n-3 LCPUFA group (800 g/d DHA + 100 g/d EPA) or placebo group 

(vegetable oil) from 21 weeks gestation until delivery.54, 56 In a 1-year follow-up study, the n-3 

LCPUFA group showed an unadjusted decrease in the risk for eczema with sensitization, 

however, once adjusted for study center, parity, maternal history, and sex, this difference was 

only marginal (RR 0.64; 95% CI 0.40, 1.03; p=0.06).54 In a longer follow-up, medical 

assessments were completed for 638 children (90.4%) at 3 years of age: No differences were 

seen between treatment groups for eczema with sensitization during the first 3 years of life 

(RR=0.75; 95% CI 0.53, 1.05) or at age 3 (RR=0.86, 95% CI 0.58, 1.27) in analyses adjusted and 

unadjusted for study center, parity, maternal history, and sex.56

One RCT randomized 145 pregnant women in Sweden to daily n-3 FA (1.6g EPA + 1.1g 

DHA) or placebo (soy oil) supplementation from the 25th gestational week through the exclusive 

breastfeeding period (average 3-4 months). Period prevalence for the first 12 months of life was 

lower in infants of n-3 FA supplemented mothers in adjusted analyses for IgE-associated 

eczema, defined as clinical diagnosis of eczema and positive SPT/IgE to egg, milk, and/or wheat 

(OR 0.22, 95% CI 0.06-0.81).173 In another follow-up study with 143 infants, no differences 

were observed in cumulative eczema through 24 months or current eczema at 24 months between 

the treatment groups. A significant difference in IgE-associated eczema was seen, favoring the 

EPA+DHA intervention (9% vs 24%, p=0.04); however this difference became marginal in an 

adjusted multiple regression model (OR 0.33; 95% CI 0.1, 1.1, p=0.06).172

ALA Versus Placebo

We identified a single trial that examined ALA supplementation during pregnancy, 

breastfeeding, and infancy. 79 Linnamaa (2010) randomized 313 pregnant Finnish women (<16 

weeks gestation) to blackcurrant seed oil (14% ALA by weight of 3g/d) or olive oil (placebo). 

The first dose was administered between the 8th and 16th week of pregnancy and continued 

during breastfeeding. Once the exclusive breastfeeding period was over, infants received 1 

mL/day of supplemental oil until age 2 years. Of the 313 mother-infant pairs, 241 were analyzed 

at 3 months, 210 at 12 months, and 177 at 24 months. No differences were seen in prevalence of 

atopic dermatitis at 3 months or 24 months. However, at 12 months, fewer cases of atopic 

dermatitis were noted (33.0% vs 47.3%, p=0.035) and severity of symptoms was lower

(p=0.035) in the ALA group compared to the placebo. 

256
Postnatal Maternal or Infant Interventions/Exposures

Three RCTs and three follow-up studies evaluated maternal n-3 FA interventions during the 

postnatal period.

118, 142, 166-169 One of the RCTs evaluated preterm infants 118 while the remaining 

two assessed term infants who were at genetic risk for allergy. All RCTs evaluated DHA or 

DHA+EPA.

DHA, DHA Plus EPA Versus Placebo

One RCT began the n-3 FA intervention during the postnatal period.118 The DINO trial 

randomized 657 preterm Australian infants (<33 weeks gestation) to receive a high-DHA diet 

(~1% DHA and 0.6% AA) or standard DHA diet ( ~0.35% DHA and 0.6% AA) through breast 

milk or formula until their expected delivery date. Eczema data were available for 232 infants at 

12 months and 292 infants at 18 months. No differences were seen in the risk for eczema 

(adjusted or unadjusted for gestational age at delivery and gender).118

In the Infant Fish Oil Supplementation Study (IFOS), 420 infants at high risk for atopy were 

randomized to daily fish oil capsules (280 mg DHA + 110 mg EPA) or placebo capsules (olive 

oil) from birth to 6 months. At 12 months, no significant overall difference in eczema was seen

between the fish oil and placebo groups; however when infants were stratified by adherence, 

among those in the highest adherence quartile, the fish oil group had a lower prevalence of 

eczema (p=0.041).

142

In the Childhood Asthma Prevention Study (CAPS), 616 pregnant women (<36 weeks 

gestation) whose child was at high risk for developing asthma were randomized into four groups, 

including two groups with a dietary component (500 mg tuna fish oil supplement + canola-based 

oils and spreads or placebo supplement + polyunsaturated oils and margarines) from 6 months. 

In an 18-month follow-up with 543 infants (88% of the total sample size), no significant 

difference in prevalence of eczema or dermatitis was seen by parental report or nurse 

examination between the diet intervention and control groups.166 In a 3-year follow-up with 526 

infants, no difference was observed between the diet and control groups for prevalence of 

eczema.167 In a 5-year follow-up with 516 children (84%), the diet intervention and control 

groups did not differ significantly in risk for current eczema (RR=0.85; 95% CI 0.61, 1.17).168 In 

an 8-year follow-up with 450 children (73%), no significant differences were seen between the 

diet intervention and control groups for eczema (ARR= 21.1, 95% CI 27.8, 5.6). 169

Biomarker Studies

Biomarker associations were also captured in the previously mentioned IFOS trial.142

The study found that infants with higher erythrocyte EPA composition (P = .033) and higher 

EPA/AA ratio (P = .022) as well as higher plasma DHA levels (P = .047) at 6 months of age 

were significantly less likely to develop eczema by 12 months. Also, higher levels of AA (P 

= .004) and total n-6 PUFA (P = .005) levels at 6 months were associated with increased 

symptoms of eczema at 6 months of age.

142

Observational Studies

Eleven observational studies were identified that evaluated the association between some 

measure of n-3 FA exposure and risk of atopic dermatitis/eczema (see Table 23).

175-185

All studies enrolled populations of healthy infants except one180 that enrolled infants with

human leucocyte antigen (HLA)-conferred susceptibility to type I diabetes. All the studies were 

prospective cohort studies. The range of exposures included maternal dietary intake of n-3 FA,

257
180-183 breast milk n-3 FA, 175, 178, 184 and maternal biomarkers.176, 177, 179,185 Publications dated 

from 2004 to 2015.

Maternal n-3 FA Intake and Risk for Atopic Dermatitis/Eczema

Four studies evaluated the association between maternal dietary n-3 FA intake and risk of 

atopic dermatitis.180-183

In a 2009 study of 763 healthy mother-infant pairs from the Osaka Maternal and Child 

Health Study in Japan, no significant association was detected between maternal intake of n-3 

fatty acids during pregnancy and risk of eczema in the offspring.

182 Maternal dietary intake was 

assessed with a validated diet history questionnaire during pregnancy, whereas eczema was 

assessed by maternal report based on the International Study of Asthma and Allergies in 

Childhood for offspring at 16-24 months postpartum.

A 2010 study of 771 healthy Japanese infants aged 3-4 months found no relationship between 

maternal intake of n-3 FAs during pregnancy (calculated based on a validated diet history 

questionnaire) and risk of atopic eczema.

181

A 2012 study assessed the association between maternal n-3 FA intake in a cohort of 2,441 

newborn infants born between 1997 and 2004 in Finland and atopic dermatitis after 5 years of 

follow-up. Enrolled infants had a history of human leucocyte antigen (HLA)-conferred 

susceptibility to type I diabetes. No significant difference was observed in total maternal n-3 FA 

intake or n-3/n-6 FA ratio (assessed using a validated FFQ) between offspring who developed 

atopic eczema and those who did not.

180

Also, in a 2013 study of 1,354 healthy mother-infant pairs from the Kyushu Okinawa 

Maternal and Child Health Study (KOMCHS) in Japan, no significant association was detected 

between maternal intake of n-3 fatty acids during pregnancy and risk of eczema in the 

offspring.

183 Maternal dietary intake was assessed with a dietary history questionnaire during 

pregnancy, whereas infantile eczema was assessed by parental report based on the International 

Study of Asthma and Allergies in Childhood for offspring at 23-29 months postpartum.

Breastmilk n-3 FAs and Risk for Atopic Dermatitis/Eczema 

Three studies assessed the association of breast milk fatty acids with risk for atopic 

eczema.

175, 178, 184

A 2006 study of 265 mother-infant pairs in the Netherlands found no relationship between 

breast milk n-3 fatty acid concentration (measured at 3 months postpartum) and risk of atopic 

eczema in children at 1 year and 4 years of age. Similar results were found in children of mothers 

both with and without allergy.175

However, in a 2011 study of 310 mother-infant pairs in the Netherlands, higher 

concentrations of breast milk n-3 fatty acid (EPA+DHA+DPA) were significantly associated 

with lower risk of developing atopic dermatitis (using the UK Working Party criteria [p for 

trend=0.024]) and parent-reported eczema (p for trend=0.040) at 2 years of age, adjusted for 

recruitment group, maternal age, maternal education, infant’s gender, number of older siblings 

and their atopic history, parental atopic history, maternal smoking during pregnancy and/or 

smoking in presence of the infant, place of birth, season of breast milk collection and other 

potential confounders.

178

A 2012 study of 580 infants in Spain found no significant association between colostrum n-3 

LC-PUFA and risk of atopic eczema during the first 14 months of life.

184 Only random samples 

of colostrum were collected for analysis (n=352), with n-3 LC-PUFA values imputed for the rest 

258
of the sample; however no differences were observed in analyses with the colostrum subsample 

only. 

Blood n-3 FA Biomarkers and Risk for Atopy/Eczema

Four studies examined the association between n-3 FA biomarkers and risk of atopic 

dermatitis.176, 177, 179, 185

A 2004 study of 1238 mother-infant pairs conducted in the UK found a positive association 

between the ratio of AA: EPA in cord blood and risk of eczema at 18 to 30 months (adjusted 

odds ratio [OR] per doubling, 1.14; 95% CI, 1.00-1.31; P = .044). However, the association was 

no longer significant after adjusting for multiple comparisons. No significant associations were 

observed for late pregnancy maternal plasma phospholipid n-3 fatty acid exposures (n=2945).

176

In a 2011 study of 1,275 children from the KOALA Birth Cohort Study who were followed 

for 6-7 years, lower risk of eczema was associated with a higher ratio of maternal plasma 

phospholipid n-6 to n-3 LCPUFAs, measured at 34–36 weeks of pregnancy (p for trend = 0.012). 

In addition, a decreased risk of eczema in the first 7 months of life was observed with increasing 

AA levels (p for trend = 0.013).

179

A 2014 study of 436 infants from the Munich LISA plus birth cohort study in Germany 

found no significant association between n-3 LC-PUFA or n-6/n-3 ratio in cord blood serum and 

eczema at 2, 6, and 10 years follow-up.177

In a 2010 study of 1162 children from the Growing Up in Singapore Towards healthy 

Outcomes (GUSTO) birth cohort study who were followed for 18 months, no significant 

associations were found between maternal plasma phospholipid DHA, EPA, ALA, total n-3 LCPUFA or n-6/n-3 ratio measured at 26-28 weeks and risk for developing eczema.185

Observational study subgroup analyses

None of the studies reported subgroup analyses. 

259
Table 22. RCTs for atopic dermatitis

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

D'Vaz et al., 2012142

Study name: IFOS

Study dates: 2005-2009

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, None, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Meldrum, 2012140

Study Population: 

Pregnant women with 

allergies

Infants enrolled 420 

Infants completers 323

Pregnant age: Placebo: 

33.2 Fish Oil: 32.5

(Placebo: 4.2 Fish Oil: 

4.8)

Infant age: Term (39.3 

weeks gestation)

Race of Mother: NR 

(100)

Inclusion Criteria: 

Maternal: Pregnant 

History of doctor 

diagnosed asthma or 

allergic rhinitis Skin prick 

positive to at least one 

allergen

Exclusion Criteria: 

Maternal: Smoking Autoimmune disease Preexisting medical 

conditions other than 

asthma High-risk 

pregnancy Seafood 

allergy Fish eaten more 

than three times per 

week Fish oil 

supplementation already 

taken (in excess of 1000 

mg per day) Exclusion 

from data analysis 

criteria due to protocol 

deviations: Pre-term 

delivery (gestation <36 

weeks) Infant with 

congenital abnormalities 

or significant disease not 

related to intervention

Start time: Infants Birth

Duration: Infants 6 months

Arm 1: Placebo

Description: Olive oil

Manufacturer: Ocean Nutrition, Ltd

Dose: 650 mg olive oil

Blinding: Randomization was completed by external 

staff via computer software using an unpredictable 

allocation sequence, stratified according to maternal 

and paternal atopic history and parity. Mothers and 

study personnel were unaware of the group 

allocation.

Maternal conditions

Maternal allergies 100

Arm 2: Fish oil group

Manufacturer: Ocean Nutrition Ltd.

Purity Data: fatty acid composition remained 

unchanged over the study period

Dose: 1 capsule contents, to be administered orally, 

prior to feeding in the morning

Maternal conditions

DHA: 280 mg

EPA: 110 mg

Maternal allergies 100

Outcome: eczema (Primary)

Follow-up time: 12 months

Arm 1: 68/167 (40.72%)

Arm 2: 61/156 (39.1%)

Dunstan et al., 200350

Study name: Dunstan

Study dates: 1999-2001

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 98 

Pregnant withdrawals 15 

Pregnant completers 83

Pregnant age: NR (NR) 

NR

Race of Mother: NR 

(100)

Inclusion Criteria: All 

women had a history of 

physician-diagnosed 

allergic rhinitis and/or 

asthma and 1 or more 

positive skin prick tests to 

common allergens 

(house dust mite; grass 

pollens; molds; and cat, 

dog, and cockroach 

extracts)

Exclusion Criteria: 

Start time: Pregnant 20 weeks of gestation

Duration: Pregnant till delivery

Arm 1: Placebo group

Description: 46 women allocated and received 

placebo-olive oil

Manufacturer: Pan Laboratories, Moorebank, NSW, 

Australia

Active ingredients: 66.6% n-9 oleic acid

Dose: 4 (1-g) capsules of olive oil per day

Blinding: Randomization and allocation of capsules 

occurred at a different center separate from the 

Outcome: atopic dermatitis (Secondary)

Follow-up time: 1 year

Arm 1: 13/43 (30.23%)

Arm 2: 18/40 (45.0%)

260
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 1 year

Original, same study, or 

follow-up studies: 

Dunstan, 200844; 

Meldrum, 201551

Women were ineligible 

for the study if they 

smoked; if they had other 

medical problems, 

complicated pregnancies, 

or seafood allergy; or if 

their normal dietary 

intake exceeded 2 meals 

of fish per week.

recruitment of participants. Capsules were 

administered to the participants by someone 

separate from those doing the allocation. The 

capsules in the 2 groups were image-matched.

Total N-3: <1% n-3 PUFAs

Arm 2: Fish oil group

Description: 52 women were randomized to receive 

fish oil

Manufacturer: Ocean Nutrition, Halifax, Nova Scotia, 

Canada

Dose: 4 (1g) fish oil capsules per day 

_x001E__x0007__x0005__x0015__x0013__x0007_ 

_x001E__x0013__x000F_

DHA: 56.0%

EPA: 27.7%

Total N-3: 3.7 g

Furuhjelm et al., 2009173

Study name: NR

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: Sweden

Funding source / conflict: 

Industry, Multiple

foundations and 

Societies

Study follow-up: 1 year

Original, same study, or 

follow-up studies: 

Furuhjelm, 2011172

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 145 

Pregnant withdrawals 28 

Pregnant completers 117

Infants enrolled 145 

Infants withdrawals 28 

Infants completers 117

Mother age: Intervention: 

31.1 years (at delivery) 

Placebo: 31.7 years (at 

delivery) (Intervention: 

4.1 years (at delivery) 

Placebo: 3.9 years (at 

delivery)) NR

Race of Mother: NR 

(100)

Baseline biomarker 

information: Treatment -

mean(sd) mol % EPAInclusion Criteria: a 

family history of past of 

current allergic 

symptoms in at least one 

parent or older child.

Exclusion Criteria: 

Mothers with an allergy 

to soy or fish or 

undergoing treatment 

with anticoagulants or 

commercial w-3 fatty acid 

supplements

Start time: Pregnant 25 weeks of gestation

Duration: Pregnant 15 weeks (i.e., until delivery)

Arm 1: Placebo

Description: 75 women received soy oil as placebo

Manufacturer: Pharma Nord

Active ingredients: w-6 PUFA LA (58%, 2.5 g / day), 

a small amount (6%, 0.28 g / day) of the w-3 PUFA 

LNA and 36 mg a-tocopherol

Viability: alpha-tocopherol was given as an 

antioxidant, a necessary ingredient according to the 

standard procedure of the manufacturer to assure 

the durability of the oil.

Dose: nine soy oil capsules a day

N-6 N-3: 9

Arm 2: w3 group

Description: 70 women are randomized into this 

group

Brand name: Bio Marin capsules

Manufacturer: Pharma Nord, Vejle, Denmark

Active ingredients: 23 mg alpha-tocopherol

Viability: alpha-tocopherol was given as an 

antioxidant, a necessary ingredient according to the 

standard procedure of the manufacturer to assure 

Outcome: IgE associated eczema (Primary)

Follow-up time: 12 months

Arm 1: 15/63 (23.81%)

Arm 2: 4/52 (7.69%)

Follow-up time: 6 months

Arm 1: 13/65 (20.0%)

Arm 2: 4/52 (7.69%)

261
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

1.3 (0.8) DHA- 5.5 (1.1)

AA- 9.2 (1.7) AA/EPA9.1 (4.3) Placebo -

mean(sd) mol % EPA1.2 (0.6) DHA- 5.4 (1.2)

AA- 8.6 (1.5) AA/EPA8.6 (4.0)

Baseline Omega-3 

intake: DHA - 0.2g/day 

EPA- 0.1g/day

the durability of the oil.

Dose: nine 500-mg capsules, once daily

DHA: 1.1g

EPA: 1.6g

N-6 N-3: <0.1

Furuhjelm et al., 2011172

Study name: NR

Study dates: 2003-2007

Study design: Trial 

randomized parallel

Location: Sweden

Funding source / conflict: 

Industry, Multiple

foundations and 

Societies

Study follow-up: 2 years

Original, same study, or 

follow-up studies: 

Furuhjelm, 2009173

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 145 

Pregnant withdrawals 28 

Pregnant completers 117

Infants enrolled 145 

Infants withdrawals 28 

Infants completers 117

Pregnant age: NR (NR) 

NR

Race of Mother: NR 

(100)

Inclusion Criteria: family 

history of current or 

previous allergic 

symptoms, i.e. bronchial 

asthma, eczema, allergic 

food reactions, itching 

and running eyes and 

nose at exposure to 

pollen, pets or other 

known allergens.

Exclusion Criteria: 

Allergy to soya or fish, 

treatment with 

anticoagulants or omega3 fatty acid supplements.

Start time: Pregnant 25 weeks of gestation

Duration: Pregnant 15 weeks (i.e., until delivery)

Arm 1: Placebo

Description: soya bean oil

Manufacturer: Pharma Nord, Vejle, Denmark

Active ingredients: 58% linoleic acid (LA), 2.5 g/day

Viability: the antioxidant a-tocopherol (placebo: 36 

mg/day) to assure the stability of the oil

Dose: nine capsules a day

Blinding: The mothers, as well as the staff handling 

clinical and laboratory follow-up, were blinded to 

group allocation, and the mothers were identified by 

their study number only.

ALA: 6%, 0.28 g/day

Arm 2: w-3 group

Description: w-3 fatty acids

Viability: the antioxidant a-tocopherol (w-3 group: 28 

mg/day) to assure the stability of the oil

Dose: nine capsules a day

DHA: 25% DHA, 1.1 g/day

EPA: 35% EPA, 1.6 g/day

Outcome: any eczema (Primary)

Follow-up time: 2 years

Arm 1: 21/65 (32.31%)

Arm 2: 11/54 (20.37%)

Linnamaa et al., 201079

Study name: NR

Study dates: 2004-2008

Study design: Trial 

randomized parallel

Study Population: 

Healthy infants Healthy 

pregnant women

Infants enrolled 314 

Infants withdrawals 137 

Infants completers 177

Inclusion Criteria: All 

pregnant mothers <16 

weeks of gestation

Exclusion Criteria: Sick 

children and those born 

prematurely who required 

more intensive care 

Start time: Pregnant 8th to 16th weeks of pregnancy 

and then continued Infants when exclusive 

breastfeeding ended

Duration: Pregnant until the end of the exclusive 

breastfeeding period Infants until 2 years of age

Arm 1: Controls

Outcome: atopic dermatitis (Primary)

Follow-up time: 12 months

Arm 1: 52/110 (47.27%)

Arm 2: 33/100 (33.0%)

Follow-up time: 24 months

Arm 1: 10/92 (11.11%)

Arm 2: 9/85 (11.11%)

Follow-up time: 3 months

262
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: Finland

Funding source / conflict: 

Government, Multiple

foundations and 

Societies

Mother age: NR (NR) NR

Race of Mother: NR (NR)

(n=8) Description: Olive oil

Manufacturer: Santagata Luigi s.r.l., Genova, Italia

Dose: 3 g/day for mothers, 1 mL/day for infants

Blinding: NR "double-blind"

ALA: 0

DHA: 0

EPA: 0

EPA-DHA: 0

AA: 0

Total N-3: 0

Other dose 1: LA (18:2n-6): 9 weight% of total

Arm 2: Intervention

Description: Blackcurrant seed oil

Manufacturer: Aromtech Ltd, Tornio, Finland

Dose: 3 g/day for mothers, 1 mL/day for infants

ALA: 14 weight% of total

DHA: 0

EPA: 0

EPA-DHA: 0

AA: 0

Total N-3: 17 weight% of total

Other dose 1: SDA: 3 weight% of total

Arm 1: 14/129 (11.11%)

Arm 2: 12/112 (11.11%)

Manley et al., 2011118

Study name: DINO

Study dates: 2001-2007

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product, Some 

authors serve on 

scientific advisory boards 

for corporations

Study Population: 

Preterm infants Breastfeeding women

Infants enrolled 657 

Infants completers 614

Lactating age: 

Intervention: 29.9 (5.8)

Placebo: 30.2 (5.4)

Infant age: 4 days 

(median)

Race of Mother: NR 

(100%)

Inclusion Criteria: Infants 

born before 33 weeks’ 

gestation, within 5 days 

of the infant commencing 

any enteral feedings.

Exclusion Criteria: major 

congenital or 

chromosomal 

abnormalities, from a 

multiple birth in which not 

all live-born infants were 

eligible, enrolled in other 

trials of fatty acid 

supplementation, or 

mother with 

contraindication to fish oil

Start time: Infants Within 5 days (or less) of starting 

enteral feeding

Duration: Infants NR

Arm 1: Standard DHA diet

Description: Soy bean oil

Manufacturer: Clover Corporation

Dose: 6 capsules per day

Maternal conditions

Infant conditions

Current smoker 25% during pregnancy

Other maternal conditions 

1arm_1_maternal_conditions_other1

Other maternal conditions 10 Birth by C-section: 

69%

Pre-term birth 100%

Low birth weight 18.6%

Arm 2: High DHA

Outcome: eczema (Secondary)

Follow-up time: 12 months

Arm 1: 40/249 (16.06%)

Arm 2: 29/232 (12.5%)

Follow-up time: 12 or 18 months

Arm 1: 67/248 (27.02%)

Arm 2: 61/236 (25.85%)

Follow-up time: 18 months

Arm 1: 51/311 (16.4%)

Arm 2: 48/292 (16.44%)

263
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117;

Collins, 2011105; Atwell, 

2013119; Collins, 2015120

Description: Tuna fish oil

Manufacturer: Clover Corporation

Dose: 6 500-mg DHA-rich tuna oil capsules per day

Maternal conditions

Infant conditions

DHA: DHA to achieve a breast milk concentration 

that was 1% of total fatty acids

Other dose 1: If supplementary formula was 

required, infants were given a high- DHA preterm 

formula (approximately 1.0%DHAand 0.6% AA).

Current smoker 25% during pregnancy

Other maternal conditions 

1arm_2_maternal_conditions_other1

Other maternal conditions 10 Birth by C-section: 

68.3%

Pre-term birth 100%

Low birth weight 18.9%

Marks et al., 2006168

Study name: CAPS

Study dates: 1997-2004

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies

Study follow-up: 5 years

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; Brew, 

2015165; Toelle, 2010169

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 616 

Pregnant withdrawals 

100 Pregnant completers 

516

Infants completers 516

Race of Mother: NR

Inclusion Criteria: 

pregnant women whose 

unborn children were at 

increased risk of 

developing asthma 

because 1 or more 

parents or siblings had 

asthma or wheezing

Exclusion Criteria: with a 

pet cat at home, strict 

vegetarians, women with 

a nonsingleton 

pregnancy, and infants 

born earlier than 36 

weeks of gestation. 

Infants had birth weights 

less than 2.5 kg, 

significant congenital 

malformations, or other 

significant neonatal 

disease.

Start time: Infants from the time the child started 

bottle-feeding, or to solid foods from age 6 months

Duration: NR

Arm 1: Diet control

Description: polyunsaturated oils and spreads, 

containing 40% w6 FA, and Sunola oil capsules

Manufacturer: Crisco-Meadow Lea Foods Inc, 

Sydney, Australia

Blinding: The approach to blinding participants and 

research staff is described in this article’s Online 

Repository at www.jacionline.org.

Arm 2: Active

Description: canola-based oils and spreads, which 

are low in n-6 fatty acids, and tuna oil capsules, 

which contain n-3 fatty acids.

Outcome: current eczema (Secondary)

Follow-up time: 5 years

Arm 1: 59/249 (23.69%)

Arm 2: 54/267 (20.22%)

Mihrshahi et al., 2003166

Study name: CAPS

Study Population: 

Pregnant women with 

allergies

Inclusion Criteria: At least 

one parent or sibling with 

symptoms of asthma as 

Start time: Infants initiation of bottle feeding or 6 

months of age

Outcome: eczema or dermatitis (Primary)

Follow-up time: 18 months

Arm 1: 77/275 (28.1%)

264
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: 1997-2002

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; Brew, 

2015165 Toelle, 2010169

Pregnant enrolled 616 

(all 4 arms) Pregnant 

withdrawals 62 Pregnant 

completers 554

Pregnant age: 28.5 (5.3)

Race of Mother: NR 

(96.9%) Other 

race/ethnicity (Aboriginal 

3.1%)

assessed by screening 

questionnaire, 

Reasonable fluency in 

English, Telephone at 

home, Reside within 30 

km from center of 

recruitment

Exclusion Criteria: Pet 

cat at home, Families on 

strict vegetarian diet, 

Multiple births, Babies 

born earlier than 36 

weeks gestation, with 

congenital malformations 

or other serious disease, 

or requiring major 

surgery or hospitalization 

for greater than 1 week

Duration: Infants NR

Arm 1: Diet Control/HDM control or intervention

Brand name: Sunola oil

Manufacturer: Clover Corporation

Arm 2: Dietary intervention/HDM control or 

intervention

Description: 500mg n-3 rich tuna fish oil supplement

Manufacturer: Clover Corporation

DHA: 76-128 mg

EPA: 18-30 mg

Other dose 1: based on age and fluid intake

Arm 2: 85/279 (30.5%)

Noakes et al., 201288

Study name: SiPS

Study dates: Not reported

Study design: Trial 

randomized parallel

Location: UK

Funding source / conflict: 

Government, None

Original, same study, or 

follow-up studies: Miles, 

201178

Study Population: 

Healthy pregnant women

Pregnant enrolled 123 

Pregnant withdrawals 37 

Pregnant completers 86

Pregnant age: 

Mean(SEM)(n):Control 

group -28.4 (0.6)(61); 

Salmon group- 29.5(0.5) 

(62) (NR) 18-40 years

Race of Mother: NR 

(100)

Inclusion Criteria: age 

18–40 y; >19 wk 

gestation; healthy 

uncomplicated singleton 

pregnancy; infant at risk 

of atopy (one or more 

first-degree relatives of 

the infant affected by 

atopy, asthma or allergy 

by self-report); 

consumption of < 2 

portions oily fish per 

month, excluding tinned 

tuna; and no use of fishoil supplements currently 

or in the previous 3 

months.

Exclusion Criteria: age

<18 or >40 y; <19 wk 

gestation; no first-degree 

Start time: Pregnant 20 weeks of gestation

Duration: Pregnant until birth

Arm 1: Control group

Description: Women in the control group (n = 61) 

were asked to continue their habitual diet

Blinding: Researchers responsible for assessing 

outcome measures (both laboratory and clinical) 

remained blinded to the groups

Arm 2: Salmon group

Description: Women in the salmon group (n = 62) 

were asked to incorporate 2 portions of farmed 

salmon (150 g/portion) into their diet per week

Active ingredients: 30.5 g protein, 16.4 g fat,4.1 mg 

alpha-tocopherol, 1.6 mg gamma-tocopherol, 6 

micro-g vitamin A, 14 micro-g vitamin D3, and 43 

micro-g Selenium

Dose: two 150-g portions per week

DHA: 1.16 g per portion

Outcome: atopic dermatitis (Primary)

Follow-up time: 6 months

Arm 1: 12/48 (25.0%)

Arm 2: 7/38 (18.42%)

265
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

relatives of the infant 

affected by atopy, 

asthma, or allergy; 

consumption of >2 

portions oily fish per 

month, excluding tinned 

tuna; use of fish-oil 

supplements within the 

previous 3 mo; 

participation in another 

research study; known 

diabetes; presence of 

any autoimmune 

disease; learning 

disability; terminal illness; 

and mental health 

problems.

EPA: 0.57g per portion

EPA-DHA: 1.73 per portion

Total N-3: 3.56g per portion

Other dose 1: Docosapentaenoic acid-0.35g

Palmer et al., 201254

Study name: DOMInO

Study dates: 2006-2009

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Zhou, 

201255; Palmer, 201356; 

Makrides, 2014 57

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 706 

Pregnant withdrawals 25 

Pregnant completers 681

Infants enrolled 706 

Infants withdrawals 25 

Infants completers 681

Pregnant age: 

Treatment: 29.6 Placebo: 

29.5 (Treatment: 5.7 

Placebo: 5.6) NR

Race of Mother: NR 

(100)

Inclusion Criteria: 

Included if the unborn 

baby had a mother, 

father, or sibling with a 

history of any medically 

diagnosed allergic 

disease (asthma, allergic 

rhinitis, eczema) and 

they were enrolled from 

the Women’s and 

Children’s Hospital or 

Flinders Medical Centre 

in Adelaide.

Exclusion Criteria: NR

Start time: Pregnant 21 weeks of gestation Infants 

21 weeks of gestation

Duration: Pregnant until delivery Infants till delivery

Arm 1: Placebo

Description: 338 women assigned to control 

supplements-vegetable oil capsules

Dose: three 500 mg vegetable oil capsules daily

Blinding: All capsules were similar in size, shape, 

and color. Neither the women nor the research staff 

were aware of the treatment allocated.

Arm 2: n-3 LCPUFA group

Description: 368 women assigned to fish oil 

concentrate

Brand name: Incromega 500 TG

Manufacturer: Croda Chemicals, East Yorkshire, UK

Dose: e three 500 mg capsules daily

DHA: 800mg

EPA: 100mg

Outcome: eczema with sensitization 

(Primary)

Follow-up time: 1 year

Arm 1: 39/338 (11.54%)

Arm 2: 26/368 (7.07%)

Palmer et al., 201356

Study name: DOMInO

Study Population: 

Children with family 

history of allergy

Inclusion Criteria: 

Women whose infants 

had a parent or sibling 

with a history of any 

Start time: Pregnant <21 weeks gestation

Duration: Pregnant to term

Outcome: eczema (Primary)

Follow-up time: 3 years

Arm 1: 64/338 (18.93%)

Arm 2: 15/368 (4.08%)

266
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: 2006-2011 

(allergy follow-up to 

Domino study)

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government, 

Some authors serve on 

scientific advisory boards 

for corporations

Study follow-up: 3 years

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Palmer, 

201254; Zhou, 201255

Pregnant enrolled 706 

Pregnant completers 638

Infants enrolled 706 

Infants completers 638

Pregnant age: DHA: 28.9

Control: 28.9 (DHA: 5.7) 

Control: 5.6)

Infant age: Birth

Race of Mother: NR 

(100)

medically diagnosed 

allergic disease (asthma, 

allergic rhinitis, eczema)

Exclusion Criteria: 

Already taking a prenatal 

supplement with DHA

Fetus had a known major 

abnormality, Bleeding 

disorder in which tuna oil 

was contraindicated, 

Taking anticoagulant 

therapy A documented 

history of drug or alcohol 

abuse, Participating in 

another fatty acid trial,

Unable to give written 

informed consent, or 

English was not the main 

language spoken at 

home

Arm 1: Control

Description: vegetable oil

Dose: 3 500-mg vegetable oil capsules per day

Blinding: This was a double-blinded study; all 

capsules were similar in size, shape and color

Arm 2: Fish oil

Brand name: Incromega 500 TG,

Manufacturer: Croda Chemicals, East Yorkshire, 

England

Dose: 3 500-mg capsules per day

DHA: 800 mg per day

EPA: 100 mg per day

267
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Peat et al., 2004167

Study name: CAPS

Study dates: 2000-2003

Study design: Trial 

randomized factorial 

design

Location: Australia

Funding source / conflict: 

Industry, Government

Study follow-up: 3 years

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2006168; Brew, 

2015165 Toelle, 2010169

Study Population: 

Pregnant women whose 

unborn children were at 

high risk of developing 

asthma

Pregnant enrolled 616 

Pregnant withdrawals 90 

Pregnant completers 526

Pregnant age: Placebo: 

29.1 Diet: 28.6 (Placebo: 

5.0 Diet: 5.3) NR

Race of Mother: NR 

(100)

Inclusion Criteria: at least 

1 parent or sibling with 

current asthma or 

frequent wheeze as 

assessed by screening 

questionnaire, fluency in 

English, a telephone at 

home, and residence 

within 30 km of the 

recruitment center.

Exclusion Criteria: a pet 

cat at home, a vegetarian 

diet, multiple births, and 

less than 36 weeks 

gestation.

Start time: Infants 6 months of age

Duration: Infants NR

Arm 1: Placebo group

Description: The control group received placebo 

supplement capsules of Sunola oil containing 83% 

monounsaturated oils (Clover Corp) and were 

provided with widely used soybean-based 

polyunsaturated oils and margarines high in omega6 fatty acids for use in all food preparation

Manufacturer: Clover Corp; Goodman Fielder

Blinding: The research team responsible for 

recruitment was blind to the methods of 

randomization until recruitment was complete. The 

research nurses and research assistants who 

undertook the outcome assessments, laboratory 

analyses, and statistical analyses were blind to the 

group allocation of the participants.

Arm 2: Active intervention group

Description: tuna fish oil capsules

Manufacturer: Clover Corp; Goodman Fielder

Dose: 500 mg tuna fish oil capsules daily

Total N-3: 184 mg

Outcome: any eczema (Secondary)

Follow-up time: 3 years

Arm 1: 81/259 (31.3%)

Arm 2: 74/267 (27.7%)

Toelle et al., 2010169

Study name: CAPS

Study dates: 1997-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study follow-up: 8 years

Study Population: 

Healthy infants

Pregnant enrolled 616 

Pregnant completers

Infants enrolled 616 

Infants completers 450

Pregnant age: 28.5 years 

(5.3 years)

Race of Mother: NR (NR)

Inclusion Criteria: 

Pregnant women whose 

unborn children were at 

high risk of developing 

asthma because of a 

family history (at least

one parent or sibling with 

symptoms of asthma as

assessed by screening 

questionnaire), 

reasonable fluency in 

English, telephone at 

home, reside within 30 

km from center of 

recruitment

Exclusion Criteria: Pet 

cat at home, families on 

Start time: Infants birth

Duration: Infants 5 years

Arm 1: Control

Description: Low-n3 capsules and cooking oils

Brand name: Sunola

Active ingredients: Capsules: 7% n-6 FA, 82% 

monounsaturated FA, 9% saturated FA, and 1.7% 

minor FA; cooking oils: 40% n-6 FA, 20% n-9 FA

Dose: Designed to maintain the current n-3 to n-6 

ingested FA ratio in the general population (1:15 to 

1:20)

Blinding: Similar appearance

Total N-3: Capsules: 0.3%; cooking oil: 1.2%

Arm 2: Omega 3 supplementation

Description: High n-3 FA capsules and cooking oils

Outcome: eczema (Secondary)

Follow-up time: 8 yrs

Arm 1: 31/220 (14.2%)

Arm 2: 35/230 (15.3%)

268
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; Brew, 

2015165

strict vegetarian diet, 

multiple births, babies 

born earlier than 36 

weeks gestation, birth 

weight below 2.5 kg, 

babies requiring surgery, 

babies requiring 

hospitalization for more 

than 1 week, babies with 

significant neonatal 

disease, babies with 

congenital malformations

Active ingredients: Capsules: 6% n-6 

polyunsaturated FA, 24% monounsaturated FA, 

28% saturated FA, and 5% minor FA; cooking oil: 

6% n-6 FA, 40% n-9 FA

Blinding: Similar appearance

N-6 N-3: 5:1

Total N-3: Capsules: 37%; cooking oil: 6%

269
Table 23. Observational studies for atopic dermatitis

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Miyake, et al., 2009182

Outcome domain: Atopic

Study name: Osaka maternal and child health 

study

Study dates: 2002-2003

Study design: Observational prospective

Location: Japan

Funding source / conflict: Government, None

Study Population: Healthy infants

Pregnant enrolled 1,002 Pregnant completers 

763

Infants enrolled 1,002 Infants completers 763

Pregnant age: 30.0 (4.0)

Race of Mother: NR (100)

Inclusion Criteria: pregnant women living in 

Neyagawa City, Osaka Prefecture or the 

surrounding cities

Exclusion Criteria: Not reported

Adjustments: Maternal age, 

gestation at baseline, 

residential municipality, family 

income, maternal and 

paternal education, maternal 

and paternal history of 

asthma, atopic eczema and 

allergic rhinitis, maternal 

intake of vitamins D and E 

during pregnancy, changes in 

maternal diet in the previous 1 

month, season when data at 

baseline were collected, 

maternal smoking during 

pregnancy, baby’s older 

siblings, baby’s sex, baby’s 

birth weight, household 

smoking in the same room as 

the infant, breastfeeding 

duration and time of delivery 

before the third survey

Miyake, et al., 2013183

Outcome domain: Atopic

Study name: Kyushu Okinawa Maternal and 

Child Health Study

Study dates: 2007-2010

Study design: Observational prospective

Location: Japan

Funding source / conflict: Industry, Government, 

Multiple foundations and Societies

Follow-up: 23-29 months

Study Population: Healthy infants

Pregnant enrolled 1757 Pregnant completers 

1354

Infants enrolled 1757 Infants completers 1354

Pregnant age: 31.5 (4.1)

Race of Mother: NR (100)

Inclusion Criteria: Women living in one of 7 

prefectures on Kyushu Island who became pregnant 

from 2007-2008

Exclusion Criteria: Failure to complete the study 

surveys

Adjustments: Maternal age, 

gestation at baseline, 

residential municipality, family 

income, maternal and 

paternal education, maternal 

and paternal history of 

asthma, atopic eczema and 

allergic rhinitis, maternal 

intake of vitamins D and E 

during pregnancy, changes in 

maternal diet in the previous 1 

month, season when data at 

baseline were collected, 

maternal smoking during 

pregnancy, baby’s older 

siblings, baby’s sex, baby’s 

birth weight, household 

smoking in the same room as 

the infant, breastfeeding 

duration and time of delivery 

before the third survey

Newson, et al., 2004176 Study Population: Healthy infants Inclusion Criteria: Pregnant women with expected 

date of delivery between April 1, 1991, and 

Adjustments: Child’s sex, 

gestational age at birth, and 

270
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Outcome domain: Atopic

Study name: Avon Longitudinal Study of 

Parents and Children (ALSPAC)

Study dates: Recruitment: April 1, 1991 to 

December 31, 1992 Followup: 42 months

Study design: Observational prospective

Location: UK

Funding source / conflict: Government, Multiple

foundations and Societies

Follow-up: 42 months

Original, same study, or follow-up studies: 

Golding et al., 2001 (ALSPAC)

Pregnant enrolled 4136

Infants enrolled 4202 Infants completers 1762

Infant age: Prenatal

Race of Mother: NR (100%)

December 31, 1992, and place of residence within 

the 3 Bristol-based health districts of the former 

county of Avon, United Kingdom

Exclusion Criteria: NR for enrollment. Exclusion for 

analysis: multiple pregnancies or in small missing 

value categories for various confounders.

birth weight, and for the 

mother’s age, education level, 

housing tenure, parity, 

ethnicity, and smoking in 

pregnancy (for variable 

categories see Table EI in the 

Journal’s Online Repository at 

http://www.mosby.com/jaci), 

as well as maternal atopic 

disease (asthma, eczema, 

rhinoconjunctivitis), child’s 

head circumference at birth ( 

< 33 cm, 33-34.99 cm, 35-

36.99 cm, 37+ cm, unknown), 

child’s crown to heel length at 

birth ( < 48 cm, 48-50.99 cm, 

51-53.99 cm, 54+ cm, 

unknown), mother’s body 

mass index (from 

prepregnancy self-reported 

weight and height; < 18.5 

kg/m2 , 18.5-24.99 kg/m2 , 

25-29.99 kg/m2 , 30+ kg/m2 , 

unknown), breast-feeding 

Notenboom, et al., 2011179

Outcome domain: Atopic

Study name: KOALA Birth Cohort Study

Study dates: Recruitment from October 2000 

onwards and Followup: 6-7 years

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government, 

Multiple foundations and Societies

Follow-up: 3 - 84 months

Study Population: Healthy infants Healthy 

pregnant women

Infants enrolled 1275 Infants completers 1253 

(samples for 815)

Mother age: 32.6 (3.8)

Race of Mother: White European (Dutch 96.3%)

Inclusion Criteria: Conventional participants: 

participation in ongoing study of pelvic girdle pain 

Alternative participants: frequented locations 

associated with organic diet and similar lifestyles

Subsample: participants recruited from January 

2002 onwards who consented to biosampling.

Exclusion Criteria: Current multiple pregnancy n=9 

Prematurity n=15 Perinatal infant death n=2 Down 

syndrome n=4 No response after birth n=51

Adjustments: Adjusted for 

recruitment group, maternal 

age, maternal ethnicity, 

maternal education level, 

maternal smoking during 

pregnancy, parental history of 

atopy, term of gestation, 

season of birth, gender, birth 

weight, mode of delivery, 

exposure to environmental 

tobacco, presence of older 

siblings and sibling atopy, 

breastfeeding, child day care, 

and pets at home

Nwaru, et al., 2012180

Outcome domain: Atopic

Study name: Finnish Type 1 Diabetes Prediction 

Study Population: NR

Pregnant enrolled NR Pregnant completers 

3523

Inclusion Criteria: Newborn infants with human 

leucocyte antigen (HLA)- conferred susceptibility to 

type 1 diabetes recruited from three university 

hospitals in Finland

Adjustments: Sex of child, 

hospital of birth, duration of 

gestation, maternal age at 

delivery, maternal basic 

education, maternal smoking 

271
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

and Prevention Nutrition Study

Study dates: Infants recruited between 20 

October 1997 and 29 February 2004; Followup 

to 5 years of age

Study design: Observational prospective

Location: Finland

Funding source / conflict: Government, Multiple

foundations and Societies

Follow-up: 5 years

Infants enrolled 3253 Infants completers 2441

Infant age: birth

Race of Mother: White European (100%)

Exclusion Criteria: Infants with severe systemic 

disease or anomalies, or both parents nonCaucasian

during pregnancy, mode of 

delivery, number of siblings at 

the time of the child’s birth, 

parental asthma, parental 

allergic rhinitis, pets at home 

by 1 year of age. A second 

adjusted model was 

computed for the FA in which 

potentially confounding 

nutrients, vitamin C, Zn, Se, 

vitamin D and vitamin E were 

included as additional 

covariates

Pike, et al., 2012186

Outcome domain: Atopic

Study name: Southampton Women's Survey

Study dates: 2006-2010

Study design: Observational prospective

Location: UK

Funding source / conflict: Government, Some 

authors serve on scientific advisory boards for 

corporations

Follow-up: Birth to 6 years

Study Population: Healthy infants

Pregnant enrolled

Infants enrolled 1485 Infants completers 865

Pregnant age: 30.4 (3.8)

Race of Mother: NR (100)

Inclusion Criteria: mothers and children in the 

Southampton Women’s Survey

Exclusion Criteria: Infants born = 35 weeks’ 

gestation were excluded to avoid abnormal lung 

development associated with prematurity

Adjustments: Child’s age, 

maternal asthma, and 

paternal rhinitis for airway 

inflammation outcome

Saito, et al., 2010181

Outcome domain: Atopic

Study name: Osaka maternal and child health 

study

Study dates: Recruitment: November 2001 to 

March 2003 Followup: 3-4 months

Study design: Observational prospective

Location: Japan

Funding source / conflict: Government

Study Population: Healthy infants Healthy 

pregnant women

Pregnant completers 771

Infants completers 771

Pregnant age: 29.9 (4.0)

Race of Mother: NR (100%)

Inclusion Criteria: Pregnant women living in 

Neyagawa City (one of the 43 municipalities in 

Osaka Prefecture) and a few municipalities other 

than Neyagawa

Exclusion Criteria: Survey completed outside 3-5 

month postpartum window

Adjustments: Maternal age, 

gestation at baseline, family 

income, maternal and 

paternal education, maternal 

and paternal history of 

asthma, atopic eczema and 

allergic rhinitis, mite allergen 

level from maternal 

bedclothes, vacuuming living 

room, mold in kitchen, 

changes in maternal diet in 

the previous 1 month, season 

when data at baseline were 

collected, baby’s older 

siblings, baby’s sex, baby’s

272
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Follow-up: 3-4 months

birth weight, breastfeeding 

and bathing or showering 

infant.

Standl, et al., 2014177

Outcome domain: Atopic

Study name: LISAplus

Study dates: Recruitment 1997-1999

Study design: Observational prospective

Location: Germany

Funding source / conflict: Government

Follow-up: 10 years

Study Population: Healthy infants

Infants enrolled 436 Infants completers 243

Mother age: 32.7 (3.9) NR

Infant age: Birth (NR) NR

Race of Mother: NR (100)

Inclusion Criteria: NR

Exclusion Criteria: Neonates displaying at least one 

of the following criteria: preterm birth (maturity <37 

gestational weeks), low birth weight (<2,500 g), 

congenital malformation, symptomatic neonatal 

infection, antibiotic medication, hospitalization or 

intensive medical care during neonatal period. In 

addition, newborns from mothers with immunerelated diseases (autoimmune disorders, diabetes, 

hepatitis B), on long-term medication or who abuse 

drugs and/or alcohol, and newborns from parents 

with a nationality other than German or who were 

not born in Germany, were excluded.

Adjustments: Parental 

education, sex, time of followup (2 yr, 6 yr or 10 yr for

eczema; 6 yr and 10 yr for 

asthma, hay fever/allergic 

rhinitis and aeroallergen 

sensitization), age, maternal 

age at birth, parental atopy, 

total sum of fatty acids

Thijs, et al., 2011178

Outcome domain: Atopic

Study name: KOALA Birth Cohort Study

Study dates: 2003

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Government, None

Follow-up: 2 years

Study Population: Healthy pregnant women

Pregnant enrolled 312 Pregnant completers 304

Infants enrolled 312 Infants completers 304

Pregnant age: 33.3 (3.9) NR

Race of Mother: NR (100)

Inclusion Criteria: availability of complete baseline 

data from the 34 weeks pregnancy questionnaire 

and availability of a breast milk sample.

Exclusion Criteria: NR

Adjustments: Recruitment 

group, maternal age, maternal 

education, infant’s gender, 

number of older siblings and 

their atopic history, parental 

atopic history, maternal 

smoking during pregnancy

and/or smoking in presence of 

the infant, place of birth, 

season of breast milk 

collection, duration and 

exclusivity of breastfeeding, 

maternal n-3 fatty acids 

supplement use, maternal 

probiotic supplement use, 

maternal probiotic dairy use, 

maternal antibiotic use during 

lactation, infant’s antibiotic 

use, vaccination schedule, 

dampness of the home, pet 

animals in the home.

273
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Wijga, et al., 2006175

Outcome domain: Atopic

Study name: The Prevention and Incidence of 

Asthma and Mite Allergy (PIAMA) birth cohort 

study

Study dates: 1995-2000

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government

Follow-up: 4 years

Study Population: NR

Pregnant enrolled 276 Pregnant withdrawals 11 

Pregnant completers 265

Infants enrolled 276 Infants withdrawals 11 

Infants completers 265

Pregnant age: 31.0 (3.9) NR

Race of Mother: NR (100)

Inclusion Criteria: Mothers reporting at least 1 of the 

following: (a history of) asthma, current hay fever, 

current allergy for pets, or current allergy for house 

dust or house dust mite were defined as allergic, 

and mothers reporting that they had none of these 

were defined as nonallergic.

Exclusion Criteria: NR

Adjustments: Sex, number of 

older siblings, maternal age, 

maternal smoking during 

pregnancy, and maternal 

body mass index before 

pregnancy

Yu, et al., 2015185

Outcome domain: Atopic

Study dates: Participants recruited between 

June 2009 and September 2010

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Study Population: Healthy infants Healthy 

pregnant women

Infants enrolled 1162 Infants completers 960

Pregnant age: NR (NR) NR

Race of Mother: NR (100%)

Inclusion Criteria: Participants were mother–child 

pairs in the Growing Up in Singapore Towards 

healthy Outcomes (GUSTO) birth cohort.

Exclusion Criteria: NR

Adjustments: In the models, 

we adjusted for maternal 

characteristics including 

maternal age, ethnicity, 

gravidity, education level and 

energy intake. The same was 

done for infant characteristics 

including sex, birth weight, 

gestational age, duration of 

breast-feeding, family history 

of allergic diseases (which 

includes allergic rhinitis, 

eczema and asthma in firstdegree relatives of the 

children (i.e. father, mother 

and/or sibling), exposure to 

environmental tobacco 

smoking, child day care 

attendance and having a cat 

or dog at home up to 18 

months of age.

274
Risk for Allergies 

Key Points

• Among the three prenatal n-3 interventions and two follow-up studies, three found 

associations between maternal n-3 FA supplementation (DHA + EPA, varying doses) and 

lower risk of allergies (denoted by sensitization to egg allergen and positive skin prick 

test). However, in all but one study, these relationships were no longer observed or 

became marginal after adjusting for potential confounders or after long-term follow-up. 

Meta-analysis of three RCTs (n=949) with 12-month food allergy outcomes yielded an

insignificant summary effect. A single trial with ALA supplementation also found no 

relationship.

• In three postnatal n-3 interventions and two follow-up studies, there was no consistent 

association between infant n-3 FA supplementation (DHA or DHA+EPA, varying doses) 

and allergy outcomes. 

• One biomarker study found associations between higher levels of DHA and lower 

incidence of IgE-associated disease as well as lower AA/EPA ratio with higher incidence 

of IgE-associated disease, although these findings were not consistent over time. 

• There was no robust association between n-3 FA exposure (measured through maternal 

dietary intake or breast milk composition) and allergy outcomes among three prospective 

observational studies. The associations found in these studies lost significance after 

adjusting for multiple comparisons or after longer term follow-up. All four studies of n-3 

FA biomarkers (in cord blood or maternal blood sample) and risk of allergy found no 

significant association.

The risk for allergies is an additional outcome of interest that was not included in the original 

review. A total of 11 eligible RCTs (composed of 7 original RCTs and four follow-up 

assessments) and 7 observational studies were included.

Description of Included Studies

Randomized Controlled Trials

Prenatal interventions/exposures

Four RCTs50, 54, 79, 173and two follow-up assessments 56, 172 evaluated prenatal maternal n-3 

FA interventions (see Table 24). Two interventions were exclusively during the prenatal period 

with the mother stopping supplementation at birth.50, 54, 56 The two remaining trials with maternal 

supplementation started during pregnancy and continued into breastfeeding, 79, 172, 173 with one of 

those trials also adding infant supplementation following breastfeeding.

79 All of these trials 

except for one79 recruited pregnant women whose infants were at high risk for atopy (e.g., parent 

diagnosis of allergy, or sibling has diagnosed or suspected allergy). All studies tested DHA and 

DHA+EPA n-3 FAs except for a single RCT that evaluated ALA.79

DHA, DHA Plus EPA Versus placebo

One RCT randomized 145 pregnant women in Sweden to daily n-3 FA (1.6g EPA + 1.1g 

DHA) or placebo (soy oil) supplementation from the 25th gestational week through the exclusive 

breastfeeding period (average 3-4 months). Period prevalence for the first 12 months of life was 

275
lower in adjusted analyses for all skin prick tests (OR 0.36; 95% CI 0.14, 0.95), egg skin prick 

test (OR 0.31, 95% CI 0.11-0.89), and food allergy (OR 0.09, 95% CI 0.01-0.74).173 In a later 

follow-up study at 24 months with 143 infants, marginal differences were observed in crude 

incidence and prevalence rates for food reactions between the treatment groups. In adjusted 

multiple regression models, risk of any positive skin prick test through 24 months was 

marginally but not statistically lower for the n-3 FA group (OR 0.43, 95% CI 0.17, 1.1; 

p=0.06).172

Dunstan et al. (2003) randomized 98 pregnant, atopic Australian women to fish oil (3.7g n-3 

PUFA, 56.0% DHA, 27.7% EPA) or olive oil (4g) daily from 20 weeks gestation until delivery.50

A total of 83 mothers and their children completed the 12-month follow-up. The authors report 

that infants in the fish oil group were less likely to be sensitized to egg allergen (OR 0.34, 95% 

CI 0.11, 1.02; p=0.055). There were no significant differences in other clinical outcomes, 

including food allergy and anaphylaxis, between the fish oil and control groups.50

In a subset of the Docosahexaenoic Acid (DHA) to Optimise Mother Infant Outcome 

(DOMInO) trial, 706 pregnant Australian women whose child was at high risk for genetic allergy 

were randomized to n-3 LCPUFA group (800 mg DHA + 100 mg EPA) or placebo group 

(vegetable oil) from 21 weeks gestation until delivery.54, 56 In a 1-year follow-up, no differences 

were seen between treatment groups for allergic disease with sensitization, allergic disease 

without sensitization, food allergy with sensitization, sensitization with/without allergic disease, 

or allergic disease without sensitization in analyses adjusted and unadjusted for study center, 

parity, maternal history, and sex, although some relationships reached marginal significance.54

The one exception was that the n-3 LCPUFA group were at lower risk for egg sensitization 

compared to the placebo group (RR0.75; 95% CI 0.41, 0.93; p=0.02). In a longer follow-up, no 

differences were observed between treatment groups for allergic disease with sensitization, 

allergic disease without sensitization, food allergy with sensitization, allergic rhinitis with 

sensitization, sensitization during the first 3 years of life or at age 3 in analyses adjusted and 

unadjusted for study center, parity, maternal history, and sex.56

Meta-analysis of the three RCTs with a 12-month follow-up 50, 54, 173 yielded an insignificant

summary effect size for DHA+EPA supplementation and risk of food allergy (OR 0.54 95% CI

0.05, 6.2, I2=42.3%) (Figure 26). 

Figure 26. Food allergy – Intervention given to pregnant women, 12-month follow-up

ALA Versus Placebo

One trial examined ALA supplementation during pregnancy, breastfeeding, and infancy. 79

Specifically, Linnamaa (2010) randomized 313 pregnant Finnish women (<16 weeks gestation) 

276
to blackcurrant seed oil (14% ALA by weight of 3g/d) or olive oil (placebo). The first dose was 

administered between the 8th and 16th week of pregnancy and continued during breastfeeding. 

Once the exclusive breastfeeding period was over, infants received 1 mL/day of supplemental oil 

until age 2 years. Total IgE antibodies were available for 136 infants at 3 and 12 months and 64 

infants at 24 months; results from skin prick tests with egg were available for 238, 202, and 166 

infants at 3, 12, and 25 months, respectively. No significant differences were observed between 

the intervention and placebo groups at any time point.

Postnatal Interventions/Exposures

Three RCTs 118, 142, 168 and two follow-up studies 166, 169 evaluated n-3 FA interventions 

during the postnatal period. One of the RCTs evaluated preterm infants 118 while the remaining 

two RCTs assessed term infants who were at genetic risk for allergy.

142, 168 All RCTs evaluated 

DHA or DHA+EPA n-3 FAs.

DHA or DHA Plus EPA Versus Placebo

One RCT, which enrolled mothers of preterm infants, began the n-3 FA intervention during 

the postnatal breastfeeding period.118 The DINO trial randomized 657 preterm Australian infants 

(<33 weeks gestation) to receive a high-DHA diet (~1% DHA and 0.6% AA) or standard DHA 

diet (~0.35% DHA and 0.6% AA) through breast milk or formula until their expected delivery 

date. Data from parent questionnaires on hay fever were available for 481 infants at 12 months 

and 603 infants at 18 months. In adjusted analyses, infants in the high-DHA diet group had lower 

risk of reported hay fever at 12 or 18 months (RR 0.41; 95% CI 0.18-0.91; p=0.03), but not at 

either time points separately (12 mo RR 0.41, 95% CI 0.15, 1.16; p=0.09; and 18 mo RR 0.75, 

95% CI 0.28, 2.01; p=0.57). Data on special diet for food allergy were available for 480 infants 

at 12 months and 603 infants at 18 months. No differences were seen in food allergy at either

time point (adjusted or unadjusted for gestational age at delivery and gender).

118

In the Infant Fish Oil Supplementation Study (IFOS), 420 infants at high risk for atopy were 

randomized to daily fish oil capsules (0.280 g DHA + 0.110 g EPA) or placebo capsules (olive 

oil) from birth to 6 months. No significant overall difference was observed in the prevalence of 

any allergic disease, overall sensitization, specific sensitization, or food allergy at 12 months 

between the fish oil and placebo groups in both adjusted and unadjusted analyses.

142

One RCT and two follow-up studies on infant n-3 supplementation were conducted as part of

the Childhood Asthma Prevention Study (CAPS).166, 168,

169. In CAPS, 616 pregnant women (<36 

weeks gestation) with a child at high risk for developing asthma were randomized into four

groups, including two with a dietary component (500 g/d tuna fish oil supplement + canola-based 

oils and spreads or placebo supplement + polyunsaturated oils and margarines). The intervention 

began at 6 months or the beginning of formula feeding if that occurred earlier than 6 months. In 

an 18-month follow-up with 543 infants (88% of the total sample size), geometric mean IgE 

concentrations did not differ between the diet intervention and control groups.166 In a 5-year 

follow-up with 516 children (84%), no significant differences were seen between the diet 

intervention and control groups for rhinitis (RR 1.42; 95% CI 0.97, 2.09), any atopy (RR 0.93, 

95% CI 0.76, 1.13), inhalant atopy (RR 0.96, 95% CI 0.78, 1.18), house dust mite atopy (RR

1.04, 95% CI 0.81, 1.33), or IgE (ratio of means, 0.86, 95% CI 0.64, 1.16).168 In an 8-year 

follow-up with 450 children (73%), no significant differences were seen between the diet 

intervention and control groups for atopy (ARR=-0.2, 95% CI -9.9, 9.6), house dust mite allergy 

(ARR=-5.4, 95% CI -14.8, 3.9), or serum IgE > 1000 IU (ARR=1.5, 95% CI -4.9, 7.8). 169

277
Biomarker Studies

One trial examined the association between biomarkers and allergy outcomes.

172 Results 

suggest that higher maternal (p for trend=0.001) plasma phospholipid DHA is significantly 

associated with lower incidence of IgE-associated disease at 12 months of age. Higher infant (p 

for trend=0.003) plasma phospholipid DHA was significantly associated with lower incidence of 

IgE-associated disease at 12 months of age. Infant plasma phospholipid DHA was not 

significantly associated with IgE-associated disease at 3 or 24 months of age. In addition, lower 

maternal plasma phospholipid AA/EPA ratio was associated with higher incidence of IgEassociated disease (p for trend=0.008). Lower quartiles of AA/EPA ratios in infant phospholipids 

at birth and at 3 months of age were associated with lower incidence of IgE-associated disease (p 

= NS for both, but p for trend = 0.01 and 0.03 respectively), but no significant relationship with 

infant phospholipids was seen at 12 or at 24 months. At 12 and 24 months of age, AA/EPA ratios

in infant phospholipids were also not significantly associated with IgE-associated disease.172

Observational Studies

Seven observational studies evaluated the association between some measure of n-3 FA 

exposure and risk of allergies (see Table 25).

175, 177-180, 186, 185

All studies enrolled populations of healthy infants except for one 180 which enrolled infants 

with human leucocyte antigen (HLA)-conferred susceptibility-hence high or moderate genetic 

risk - to type I diabetes. All the studies were prospective cohort studies. The exposures include 

dietary intake of n-3 FA,180 breast milk FA,175, 178 and maternal biomarkers.177, 179, 185, 186 Studies 

were published between 2004 and 2014.

Maternal n-3 FA Intake

A single study evaluated the association between maternal dietary n-3 FA intake and risk of 

allergies.180

A 2012 study examined the association between maternal n-3 FA intake in a cohort of 2441 

newborn infants born between 1997 and 2004 in Finland and risk of allergies after 5 years of 

follow-up. Enrolled infants had a history of human leucocyte antigen (HLA)-conferred 

susceptibility to type I diabetes. Maternal intake of n-3 FA was assessed using a validated FFQ.

High maternal intakes of ALA (HR 0·73; 95 % CI 0·54, 0·98) were associated with a decreased 

risk of allergic rhinitis. Also, higher ratios of n-6: n-3 FA (HR 1·37; 95 % CI 1·07, 1·77) during 

pregnancy were associated with an increased risk of allergic rhinitis in the offspring by 5 years of 

age, adjusted for potential confounding variables. The results however lost their significance 

after adjustment for multiple comparisons.180

n-3 FA Breastmilk Intake

Two studies examined the association between breastmilk n-3 fatty acids and the risk for 

allergies in infants.

175, 178

A 2006 study of 265 mother-infant pairs in Netherland found no relationship between breast 

milk n-3 fatty acid concentration (measured at 3 months postpartum) and sensitization (defined 

as specific IgE higher than 0.35 IU/mL to any of measured allergens) in children with maternal 

history of allergy at 4 years of age. However in children with no maternal history at 4 years of 

age, ALA and ALA/LA ratio were positively associated with sensitization (p<0.05).175

In a 2011 study of 310 mother-infant pairs in the Netherlands, higher concentrations of breast 

milk n-3 fatty acid (EPA+DHA+DPA) were significantly associated with lower risk of allergic 

sensitization at 1year of age (p for trend=0.029), adjusted for recruitment group, maternal age, 

278
maternal education, infant’s gender, number of older siblings and their atopic history, parental 

atopic history, maternal smoking during pregnancy and/or smoking in presence of the infant, 

place of birth, season of breast milk collection, and other potential confounders). However, no 

significant associations were found at 2 years of age.

178

n-3 FA Biomarkers

Four studies examined the association between n-3 FA biomarkers and the risk of 

allergies.

177, 179, 186

In a 2011 study of 1275 children from the KOALA Birth Cohort Study who were followed 

for 6-7 years, no associations were found between maternal plasma phospholipid n-3 fatty acids 

measured at 34–36 weeks of pregnancy and allergic sensitization, allergic rhinoconjunctivitis, or 

high total IgE.179

In a 2012 study of 1485 healthy mother-infant pairs from the Southampton Women’s Survey 

in the UK who were followed for 6 years, no associations were found between maternal plasma 

phospholipid n-3 fatty acids measured at 34 weeks of gestation and risk of atopy (positive skin 

prick test defined as positive wheal >=3mm to a common allergen panel).

186

A 2014 study of 436 infants from the Munich LISA plus birth cohort study in Germany 

found no significant association between n-3 LC-PUFA or n-6/n-3 ratio in cord blood serum and 

hay fever or allergic rhinitis and aeroallergen sensitization at 6 and 10 years’ follow-up.

177

In a 2010 study of 1162 children from the Growing Up in Singapore Towards healthy 

Outcomes (GUSTO) birth cohort study who were followed for 18 months, no significant 

associations were found between maternal plasma phospholipid DHA, EPA, ALA, total n-3 LCPUFA or n-6/n-3 ratio measured at 26-28 weeks of pregnancy and allergic sensitization or 

rhinitis.185

Observational study subgroup analyses

A 2006 study of 265 mother-infant pairs in Netherland stratified its analysis by presence or 

absence of allergy in mothers. The study found no relationship between breast milk n-3 fatty acid 

concentration (measured at 3 months postpartum) and sensitization (defined as specific IgE 

higher than 0.35 IU/mL to any of measured allergens) in children with maternal history of

allergy at 4 years of age. However in children of mothers with no allergy, alpha-linolenic acid 

(18:3n-3) and ALA/LA ratio was positively associated with sensitization at 4 years of age

(p<0.05).175

279
Table 24. RCTs for allergies

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

D'Vaz et al., 2012142

Study name: IFOS

Study dates: 2005-2009

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, None, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Meldrum, 2012140

Study Population: 

Pregnant women with 

allergies

Infants enrolled 420 

Infants completers 323

Pregnant age: Placebo: 

33.2 Fish Oil: 32.5 

(Placebo: 4.2 Fish Oil: 

4.8)

Infant age: Term (39.3 

weeks gestation)

Race of Mother: NR 

(100)

Inclusion Criteria: 

Maternal: Pregnant 

History of doctor 

diagnosed asthma or 

allergic rhinitis Skin prick 

positive to at least one 

allergen

Exclusion Criteria: 

Maternal: Smoking Autoimmune disease Preexisting medical 

conditions other than 

asthma High-risk 

pregnancy Seafood 

allergy Fish eaten more 

than three times per 

week Fish oil 

supplementation already 

taken (in excess of 1000 

mg per day) Exclusion 

from data analysis 

criteria due to protocol 

deviations: Pre-term 

delivery (gestation <36 

weeks) Infant with 

congenital abnormalities 

or significant disease not 

related to intervention

Start time: Infants Birth

Duration: Infants 6 months

Arm 1: Placebo

Description: Olive oil

Manufacturer: Ocean Nutrition, Ltd

Dose: 650 mg olive oil

Blinding: Randomization was completed by external 

staff via computer software using an unpredictable 

allocation sequence, stratified according to maternal 

and paternal atopic history and parity. Mothers and

study personnel were unaware of the group 

allocation.

Maternal conditions

Maternal allergies 100

Arm 2: Fish oil group

Manufacturer: Ocean Nutrition Ltd.

Purity Data: fatty acid composition remained 

unchanged over the study period

Dose: 1 capsule contents, to be administered orally, 

prior to feeding in the morning

Maternal conditions

DHA: 280 mg

EPA: 110 mg

Maternal allergies 100

Outcome: allergic disease (any of IgE

mediated food allergy, eczema or asthma) 

(Primary)

Follow-up time: 12 months

Arm 1: 66/167 (39.52%)

Arm 2: 59/156 (37.82%)

Outcome: food allergy (Primary)

Follow-up time: 12 months

Arm 1: 25/167 (14.97%)

Arm 2: 19/156 (12.18%)

Dunstan et al., 200350

Study name: Dunstan

Study dates: 1999-2001

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 98 

Pregnant withdrawals 15 

Pregnant completers 83

Pregnant age: NR (NR) 

NR

Race of Mother: NR 

Inclusion Criteria: All 

women had a history of 

physician-diagnosed 

allergic rhinitis and/or 

asthma and 1 or more 

positive skin prick tests to 

common allergens 

(house dust mite; grass 

pollens; molds; and cat, 

dog, and cockroach 

extracts)

Start time: Pregnant 20 weeks of gestation

Duration: Pregnant till delivery

Arm 1: Placebo group

Description: 46 women allocated and received 

placebo-olive oil

Manufacturer: Pan Laboratories, Moorebank, NSW, 

Australia

Active ingredients: 66.6% n-9 oleic acid

Dose: 4 (1-g) capsules of olive oil per day

Blinding: Randomization and allocation of capsules 

Outcome: food allergy (Secondary)

Follow-up time: 1 year

Arm 1: 5/43 (11.63%)

Arm 2: 3/40 (7.5%)

280
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Government

Study follow-up: 1 year

Original, same study, or 

follow-up studies: 

Dunstan, 200844; 

Meldrum, 201551

(100) Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked; if they had other 

medical problems, 

complicated pregnancies, 

or seafood allergy; or if 

their normal dietary 

intake exceeded 2 meals 

of fish per week.

occurred at a different center separate from the 

recruitment of participants. Capsules were 

administered to the participants by someone 

separate from those doing the allocation. The 

capsules in the 2 groups were image-matched.

Total N-3: <1% n-3 PUFAs

Arm 2: Fish oil group

Description: 52 women were randomized to receive 

fish oil

Manufacturer: Ocean Nutrition, Halifax, Nova Scotia, 

Canada

Dose: 4 (1g) fish oil capsules per day 

_x001E__x0007__x0005__x0015__x0013__x0007_ 

_x001E__x0013__x000F_

DHA: 56.0%

EPA: 27.7%

Total N-3: 3.7 g

Furuhjelm et al., 2009173

Study name: NR

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: Sweden

Funding source / conflict: 

Industry, Multiple

foundations and 

Societies

Study follow-up: 1 year

Original, same study, or 

follow-up studies: 

Furuhjelm, 2011172

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 145 

Pregnant withdrawals 28 

Pregnant completers 117

Infants enrolled 145 

Infants withdrawals 28 

Infants completers 117

Mother age: Intervention: 

31.1 years (at delivery) 

Placebo: 31.7 years (at 

delivery) (Intervention: 

4.1 years (at delivery) 

Placebo: 3.9 years (at 

delivery)) NR

Race of Mother: NR 

(100)

Baseline biomarker 

information: Treatment -

Inclusion Criteria: a 

family history of past of 

current allergic 

symptoms in at least one 

parent or older child.

Exclusion Criteria: 

Mothers with an allergy 

to soy or fish or 

undergoing treatment 

with anticoagulants or 

commercial w-3 fatty acid 

supplements

Start time: Pregnant 25 weeks of gestation

Duration: Pregnant 15 weeks (i.e., until delivery)

Arm 1: Placebo

Description: 75 women received soy oil as placebo

Manufacturer: Pharma Nord

Active ingredients: w-6 PUFA LA (58%, 2.5 g / day), 

a small amount (6%, 0.28 g / day) of the w-3 PUFA 

LNA and 36 mg a-tocopherol

Viability: alpha-tocopherol was given as an 

antioxidant, a necessary ingredient according to the 

standard procedure of the manufacturer to assure 

the durability of the oil.

Dose: nine soy oil capsules a day

N-6 N-3: 9

Arm 2: w3 group

Description: 70 women are randomized into this 

group

Brand name: Bio Marin capsules

Manufacturer: Pharma Nord, Vejle, Denmark

Active ingredients: 23 mg alpha-tocopherol

Viability: alpha-tocopherol was given as an 

antioxidant, a necessary ingredient according to the 

Outcome: Food Allergy (Primary)

Follow-up time: 12 months

Arm 1: 10/65 (15.38%)

Arm 2: 1/52 (1.92%)

281
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

mean(sd) mol % EPA1.3 (0.8) DHA- 5.5 (1.1)

AA- 9.2 (1.7) AA/EPA9.1 (4.3) Placebo -

mean(sd) mol % EPA1.2 (0.6) DHA- 5.4 (1.2)

AA- 8.6 (1.5) AA/EPA8.6 (4.0)

Baseline Omega-3 

intake: DHA - 0.2g/day 

EPA- 0.1g/day

standard procedure of the manufacturer to assure 

the durability of the oil.

Dose: nine 500-mg capsules, once daily

DHA: 1.1g

EPA: 1.6g

N-6 N-3: <0.1

Furuhjelm et al., 2011172

Study name: NR

Study dates: 2003-2007

Study design: Trial 

randomized parallel

Location: Sweden

Funding source / conflict: 

Industry, Multiple

foundations and 

Societies

Study follow-up: 2 years

Original, same study, or 

follow-up studies: 

Furuhjelm, 2009173

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 145 

Pregnant withdrawals 28 

Pregnant completers 117

Infants enrolled 145 

Infants withdrawals 28 

Infants completers 117

Pregnant age: NR (NR) 

NR

Race of Mother: NR 

(100)

Inclusion Criteria: family 

history of current or 

previous allergic 

symptoms, i.e. bronchial 

asthma, eczema, allergic 

food reactions, itching 

and running eyes and 

nose at exposure to 

pollen, pets or other 

known allergens.

Exclusion Criteria: 

Allergy to soya or fish, 

treatment with 

anticoagulants or omega3 fatty acid supplements.

Start time: Pregnant 25 weeks of gestation

Duration: Pregnant 15 weeks (i.e., until delivery)

Arm 1: Placebo

Description: soya bean oil

Manufacturer: Pharma Nord, Vejle, Denmark

Active ingredients: 58% linoleic acid (LA), 2.5 g/day

Viability: the antioxidant a-tocopherol (placebo: 36 

mg/day) to assure the stability of the oil

Dose: nine capsules a day

Blinding: The mothers, as well as the staff handling 

clinical and laboratory follow-up, were blinded to 

group allocation, and the mothers were identified by 

their study number only.

ALA: 6%, 0.28 g/day

Arm 2: w-3 group

Description: w-3 fatty acids

Viability: the antioxidant a-tocopherol (w-3 group: 28 

mg/day) to assure the stability of the oil

Dose: nine capsules a day

DHA: 25% DHA, 1.1 g/day

EPA: 35% EPA, 1.6 g/day

Outcome: any food reactions (Primary)

Follow-up time: 2 years

Arm 1: 16/65 (24.62%)

Arm 2: 6/54 (11.11%)

Linnamaa et al., 201079

Study name: NR

Study dates: 2004-2008

Study design: Trial 

Study Population: 

Healthy infants Healthy 

pregnant women

Infants enrolled 314 

Infants withdrawals 137 

Infants completers 177

Inclusion Criteria: All 

pregnant mothers <16 

weeks of gestation

Exclusion Criteria: Sick 

children and those born 

prematurely who required 

Start time: Pregnant 8th to 16th weeks of pregnancy 

and then continued Infants when exclusive 

breastfeeding ended

Duration: Pregnant until the end of the exclusive 

breastfeeding period Infants until 2 years of age

Outcome: positive egg skin test 

(Secondary)

Follow-up time: 12 months

Arm 1: 18/104 (17.31%)

Arm 2: 14/98 (14.29%)

Follow-up time: 24 months

Arm 1: 7/87 (8.05%)

282
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

randomized parallel

Location: Finland

Funding source / conflict: 

Government, Multiple

foundations and 

Societies

Mother age: NR (NR) NR

Race of Mother: NR (NR)

more intensive care 

(n=8)

Arm 1: Controls

Description: Olive oil

Manufacturer: Santagata Luigi s.r.l., Genova, Italia

Dose: 3 g/day for mothers, 1 mL/day for infants

Blinding: NR "double-blind"

ALA: 0

DHA: 0

EPA: 0

EPA-DHA: 0

AA: 0

Total N-3: 0

Other dose 1: LA (18:2n-6): 9 weight% of total

Arm 2: Intervention

Description: Blackcurrant seed oil

Manufacturer: Aromtech Ltd, Tornio, Finland

Dose: 3 g/day for mothers, 1 mL/day for infants

ALA: 14 weight% of total

DHA: 0

EPA: 0

EPA-DHA: 0

AA: 0

Total N-3: 17 weight% of total

Other dose 1: SDA: 3 weight% of total

Arm 2: 4/79 (5.06%)

Follow-up time: 3 months

Arm 1: 1/126 (0.79%)

Arm 2: 1/112 (0.89%)

Manley et al., 2011118

Study name: DINO

Study dates: 2001-2007

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product, Some 

authors serve on 

scientific advisory boards 

for corporations

Study Population: 

Preterm infants Breastfeeding women

Infants enrolled 657 

Infants completers 614

Lactating age: 

Intervention: 29.9 (5.8)

Placebo: 30.2 (5.4)

Infant age: 4 days 

(median)

Race of Mother: NR 

(100%)

Inclusion Criteria: Infants 

born before 33 weeks’ 

gestation, within 5 days 

of the infant commencing 

any enteral feedings.

Exclusion Criteria: major 

congenital or 

chromosomal 

abnormalities, from a 

multiple birth in which not 

all live-born infants were 

eligible, enrolled in other 

trials of fatty acid 

supplementation, or 

mother with 

contraindication to fish oil

Start time: Infants Within 5 days (or less) of starting 

enteral feeding

Duration: Infants NR

Arm 1: Standard DHA diet

Description: Soy bean oil

Manufacturer: Clover Corporation

Dose: 6 capsules per day

Maternal conditions

Infant conditions

Current smoker 25% during pregnancy

Other maternal conditions 

1arm_1_maternal_conditions_other1

Other maternal conditions 10 Birth by C-section: 

69%

Pre-term birth 100%

Low birth weight 18.6%

Outcome: hay fever (Secondary)

Follow-up time: 12 months

Arm 1: 13/249 (5.22%)

Arm 2: 5/232 (2.16%)

Follow-up time: 12 or 18 months

Arm 1: 21/244 (8.61%)

Arm 2: 8/231 (3.46%)

Follow-up time: 18 months

Arm 1: 10/311 (3.22%)

Arm 2: 7/292 (2.4%)

283
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117;

Collins, 2011105; Atwell, 

2013119; Collins, 2015120

Arm 2: High DHA

Description: Tuna fish oil

Manufacturer: Clover Corporation

Dose: 6 500-mg DHA-rich tuna oil capsules per day

Maternal conditions

Infant conditions

DHA: DHA to achieve a breast milk concentration 

that was 1% of total fatty acids

Other dose 1: If supplementary formula was 

required, infants were given a high- DHA preterm 

formula (approximately 1.0%DHAand 0.6% AA).

Current smoker 25% during pregnancy

Other maternal conditions 

1arm_2_maternal_conditions_other1

Other maternal conditions 10 Birth by C-section: 

68.3%

Pre-term birth 100%

Low birth weight 18.9%

Marks et al., 2006168

Study name: CAPS

Study dates: 1997-2004

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies

Study follow-up: 5 years

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; Brew, 

2015165; Toelle, 2010169

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 616 

Pregnant withdrawals 

100 Pregnant completers 

516

Infants completers 516

Race of Mother: NR

Inclusion Criteria: 

pregnant women whose 

unborn children were at 

increased risk of 

developing asthma 

because 1 or more 

parents or siblings had 

asthma or wheezing

Exclusion Criteria: with a 

pet cat at home, strict 

vegetarians, women with 

a nonsingleton 

pregnancy, and infants 

born earlier than 36 

weeks of gestation. 

Infants had birth weights 

less than 2.5 kg, 

significant congenital 

malformations, or other 

significant neonatal 

disease.

Start time: Infants from the time the child started 

bottle-feeding, or to solid foods from age 6 months

Duration: NR

Arm 1: Diet control

Description: polyunsaturated oils and spreads, 

containing 40% w6 FA, and Sunola oil capsules

Manufacturer: Crisco-Meadow Lea Foods Inc, 

Sydney, Australia

Blinding: The approach to blinding participants and 

research staff is described in this article’s Online 

Repository at www.jacionline.org.

Arm 2: Active

Description: canola-based oils and spreads, which

are low in n-6 fatty acids, and tuna oil capsules, 

which contain n-3 fatty acids.

Outcome: any atopy (from skin prick test) 

(Secondary)

Follow-up time: 5 years

Arm 1: 108/249 (43.37%)

Arm 2: 109/267 (40.82%)

Outcome: rhinitis (Secondary)

Follow-up time: 5 years

Arm 1: 102/249 (40.96%)

Arm 2: 111/267 (41.57%)

Mihrshahi et al., 2003166 Study Population: 

Pregnant women with 

Inclusion Criteria: At least 

one parent or sibling with 

Start time: Infants initiation of bottle feeding or 6 

months of age

Outcome: any atopy

Follow-up time: 18 months

284
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: CAPS

Study dates: 1997-2002

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; Brew, 

2015165 Toelle, 2010169

allergies

Pregnant enrolled 616 

(all 4 arms) Pregnant 

withdrawals 62 Pregnant 

completers 554

Pregnant age: 28.5 (5.3)

Race of Mother: NR 

(96.9%) Other 

race/ethnicity (Aboriginal 

3.1%)

symptoms of asthma as 

assessed by screening 

questionnaire, 

Reasonable fluency in 

English, Telephone at 

home, Reside within 30 

km from center of 

recruitment

Exclusion Criteria: Pet 

cat at home, Families on 

strict vegetarian diet, 

Multiple births, Babies 

born earlier than 36 

weeks gestation, with 

congenital malformations 

or other serious disease, 

or requiring major 

surgery or hospitalization 

for greater than 1 week

Duration: Infants NR

Arm 1: Diet Control/HDM control or intervention

Brand name: Sunola oil

Manufacturer: Clover Corporation

Arm 2: Dietary intervention/HDM control or 

intervention

Description: 500mg n-3 rich tuna fish oil supplement

Manufacturer: Clover Corporation

DHA: 76-128 mg

EPA: 18-30 mg

Other dose 1: based on age and fluid intake

Arm 1: 58/275 (21.1%)

Arm 2: 51/279 (18.2%)

Palmer et al., 201254

Study name: DOMInO

Study dates: 2006-2009

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Zhou, 

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 706 

Pregnant withdrawals 25 

Pregnant completers 681

Infants enrolled 706 

Infants withdrawals 25 

Infants completers 681

Pregnant age: 

Treatment: 29.6 Placebo: 

29.5 (Treatment: 5.7 

Placebo: 5.6) NR

Race of Mother: NR 

(100)

Inclusion Criteria: 

Included if the unborn 

baby had a mother, 

father, or sibling with a 

history of any medically 

diagnosed allergic 

disease (asthma, allergic 

rhinitis, eczema) and 

they were enrolled from 

the Women’s and 

Children’s Hospital or 

Flinders Medical Centre 

in Adelaide.

Exclusion Criteria: NR

Start time: Pregnant 21 weeks of gestation Infants 

21 weeks of gestation

Duration: Pregnant until delivery Infants till delivery

Arm 1: Placebo

Description: 338 women assigned to control 

supplements-vegetable oil capsules

Dose: three 500 mg vegetable oil capsules daily

Blinding: All capsules were similar in size, shape, 

and color. Neither the women nor the research staff 

were aware of the treatment allocated.

Arm 2: n-3 LCPUFA group

Description: 368 women assigned to fish oil 

concentrate

Brand name: Incromega 500 TG

Manufacturer: Croda Chemicals, East Yorkshire, UK

Dose: e three 500 mg capsules daily

DHA: 800mg

Outcome: food allergy with sensitization 

(Primary)

Follow-up time: 1 year

Arm 1: 11/338 (3.25%)

Arm 2: 11/368 (2.99%)

285
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

201255; Palmer, 201356; 

Makrides, 2014 57

EPA: 100mg

Palmer et al., 201356

Study name: DOMInO

Study dates: 2006-2011 

(allergy follow-up to 

Domino study)

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government, 

Some authors serve on 

scientific advisory boards 

for corporations

Study follow-up: 3 years

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Palmer, 

201254; Zhou, 201255

Study Population: 

Children with family 

history of allergy

Pregnant enrolled 706 

Pregnant completers 638

Infants enrolled 706 

Infants completers 638

Pregnant age: DHA: 28.9

Control: 28.9 (DHA: 5.7) 

Control: 5.6)

Infant age: Birth

Race of Mother: NR 

(100)

Inclusion Criteria: 

Women whose infants 

had a parent or sibling 

with a history of any 

medically diagnosed 

allergic disease (asthma, 

allergic rhinitis, eczema)

Exclusion Criteria: 

Already taking a prenatal 

supplement with DHA

Fetus had a known major 

abnormality, Bleeding 

disorder in which tuna oil 

was contraindicated, 

Taking anticoagulant

therapy A documented 

history of drug or alcohol 

abuse, Participating in 

another fatty acid trial,

Unable to give written 

informed consent, or 

English was not the main 

language spoken at 

home

Start time: Pregnant <21 weeks gestation

Duration: Pregnant to term

Arm 1: Control

Description: vegetable oil

Dose: 3 500-mg vegetable oil capsules per day

Blinding: This was a double-blinded study; all 

capsules were similar in size, shape and color

Arm 2: Fish oil

Brand name: Incromega 500 TG,

Manufacturer: Croda Chemicals, East Yorkshire, 

England

Dose: 3 500-mg capsules per day

DHA: 800 mg per day

EPA: 100 mg per day

Outcome: allergic rhinitis (Primary)

Follow-up time: 3 years

Arm 1: 20/338 (5.92%)

Arm 2: 18/368 (4.89%)

Outcome: food allergy (Primary)

Follow-up time: 3 years

Arm 1: 14/338 (4.14%)

Arm 2: 18/368 (4.89%)

Toelle et al., 2010169

Study name: CAPS

Study dates: 1997-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study Population: 

Healthy infants

Pregnant enrolled 616 

Pregnant completers

Infants enrolled 616 

Infants completers 450

Pregnant age: 28.5 years 

(5.3 years)

Race of Mother: NR (NR)

Inclusion Criteria: 

Pregnant women whose 

unborn children were at 

high risk of developing 

asthma because of a 

family history (at least

one parent or sibling with 

symptoms of asthma as

assessed by screening 

questionnaire), 

reasonable fluency in 

English, telephone at 

home, reside within 30 

km from center of 

recruitment

Start time: Infants birth

Duration: Infants 5 years

Arm 1: Control

Description: Low-n3 capsules and cooking oils

Brand name: Sunola

Active ingredients: Capsules: 7% n-6 FA, 82% 

monounsaturated FA, 9% saturated FA, and 1.7% 

minor FA; cooking oils: 40% n-6 FA, 20% n-9 FA

Dose: Designed to maintain the current n-3 to n-6

ingested FA ratio in the general population (1:15 to 

1:20)

Blinding: Similar appearance

Total N-3: Capsules: 0.3%; cooking oil: 1.2%

Outcome: atopy (Primary)

Follow-up time: 8 yrs

Arm 1: 99/220 (45.0%)

Arm 2: 104/230 (45.1%)

Outcome: rhinitis (Secondary)

Follow-up time: 8 yrs

Arm 1: 65/220 (29.6%)

Arm 2: 70/230 (30.4%)

286
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 8 years

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; Brew, 

2015165

Exclusion Criteria: Pet 

cat at home, families on 

strict vegetarian diet, 

multiple births, babies 

born earlier than 36 

weeks gestation, birth 

weight below 2.5 kg, 

babies requiring surgery, 

babies requiring 

hospitalization for more 

than 1 week, babies with 

significant neonatal 

disease, babies with 

congenital malformations

Arm 2: Omega 3 supplementation

Description: High n-3 FA capsules and cooking oils

Active ingredients: Capsules: 6% n-6 

polyunsaturated FA, 24% monounsaturated FA, 

28% saturated FA, and 5% minor FA; cooking oil: 

6% n-6 FA, 40% n-9 FA

Blinding: Similar appearance

N-6 N-3: 5:1

Total N-3: Capsules: 37%; cooking oil: 6%

287
Table 25. Observational studies for allergies

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Notenboom, et al., 2011179

Outcome domain: Allergies

Study name: KOALA Birth Cohort Study

Study dates: Recruitment from October 2000 

onwards and Followup: 6-7 years

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government, 

Multiple foundations and Societies

Follow-up: 3 - 84 months

Study Population: Healthy infants Healthy 

pregnant women

Infants enrolled 1275 Infants completers 1253 

(samples for 815)

Mother age: 32.6 (3.8)

Race of Mother: White European (Dutch 96.3%)

Inclusion Criteria: Conventional participants: 

participation in ongoing study of pelvic girdle pain 

Alternative participants: frequented locations 

associated with organic diet and similar lifestyles

Subsample: participants recruited from January 

2002 onwards who consented to biosampling.

Exclusion Criteria: Current multiple pregnancy n=9 

Prematurity n=15 Perinatal infant death n=2 Down 

syndrome n=4 No response after birth n=51

Adjustments: Adjusted for 

recruitment group, maternal 

age, maternal ethnicity, 

maternal education level, 

maternal smoking during 

pregnancy, parental history of 

atopy, term of gestation, 

season of birth, gender, birth 

weight, mode of delivery, 

exposure to environmental 

tobacco, presence of older 

siblings and sibling atopy, 

breastfeeding, child day care, 

and pets at home

Nwaru, et al., 2012180

Outcome domain: Allergies

Study name: Finnish Type 1 Diabetes Prediction 

and Prevention Nutrition Study

Study dates: Infants recruited between 20 

October 1997 and 29 February 2004; Followup 

to 5 years of age

Study design: Observational prospective

Location: Finland

Funding source / conflict: Government, Multiple

foundations and Societies

Follow-up: 5 years

Study Population: NR

Pregnant enrolled NR Pregnant completers 

3523

Infants enrolled 3253 Infants completers 2441

Infant age: birth

Race of Mother: White European (100%)

Inclusion Criteria: Newborn infants with human 

leucocyte antigen (HLA)- conferred susceptibility to 

type 1 diabetes recruited from three university 

hospitals in Finland

Exclusion Criteria: Infants with severe systemic 

disease or anomalies, or both parents nonCaucasian

Adjustments: Sex of child, 

hospital of birth, duration of 

gestation, maternal age at 

delivery, maternal basic 

education, maternal smoking 

during pregnancy, mode of 

delivery, number of siblings at 

the time of the child’s birth, 

parental asthma, parental 

allergic rhinitis, pets at home 

by 1 year of age. A second 

adjusted model was 

computed for the FA in which 

potentially confounding 

nutrients, vitamin C, Zn, Se, 

vitamin D and vitamin E were 

included as additional 

covariates

Pike, et al., 2012186

Outcome domain: Allergies

Study name: Southampton Women's Survey

Study dates: 2006-2010

Study Population: Healthy infants

Pregnant enrolled

Infants enrolled 1485 Infants completers 865

Pregnant age: 30.4 (3.8)

Inclusion Criteria: mothers and children in the 

Southampton Women’s Survey

Exclusion Criteria: Infants born = 35 weeks’ 

gestation were excluded to avoid abnormal lung 

development associated with prematurity

Adjustments: Child’s age, 

maternal asthma, and 

paternal rhinitis for airway 

inflammation outcome

288
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Study design: Observational prospective

Location: UK

Funding source / conflict: Government, Some 

authors serve on scientific advisory boards for 

corporations

Follow-up: Birth to 6 years

Race of Mother: NR (100)

Standl, et al., 2014177

Outcome domain: Allergies

Study name: LISAplus

Study dates: Recruitment 1997-1999

Study design: Observational prospective

Location: Germany

Funding source / conflict: Government

Follow-up: 10 years

Study Population: Healthy infants

Infants enrolled 436 Infants completers 243

Mother age: 32.7 (3.9) NR

Infant age: Birth (NR) NR

Race of Mother: NR (100)

Inclusion Criteria: NR

Exclusion Criteria: Neonates displaying at least one 

of the following criteria: preterm birth (maturity <37 

gestational weeks), low birth weight (<2,500 g), 

congenital malformation, symptomatic neonatal 

infection, antibiotic medication, hospitalization or 

intensive medical care during neonatal period. In 

addition, newborns from mothers with immunerelated diseases (autoimmune disorders, diabetes, 

hepatitis B), on long-term medication or who abuse 

drugs and/or alcohol, and newborns from parents 

with a nationality other than German or who were 

not born in Germany, were excluded.

Adjustments: Parental 

education, sex, time of followup (2 yr, 6 yr or 10 yr for 

eczema; 6 yr and 10 yr for 

asthma, hay fever/allergic 

rhinitis and aeroallergen 

sensitization), age, maternal 

age at birth, parental atopy, 

total sum of fatty acids

Thijs, et al., 2011178

Outcome domain: Allergies

Study name: KOALA Birth Cohort Study

Study dates: 2003

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Government, None

Follow-up: 2 years

Study Population: Healthy pregnant women

Pregnant enrolled 312 Pregnant completers 304

Infants enrolled 312 Infants completers 304

Pregnant age: 33.3 (3.9) NR

Race of Mother: NR (100)

Inclusion Criteria: availability of complete baseline 

data from the 34 weeks pregnancy questionnaire 

and availability of a breast milk sample.

Exclusion Criteria: NR

Adjustments: Recruitment 

group, maternal age, maternal 

education, infant’s gender, 

number of older siblings and 

their atopic history, parental 

atopic history, maternal 

smoking during pregnancy

and/or smoking in presence of 

the infant, place of birth, 

season of breast milk 

collection, duration and 

exclusivity of breastfeeding, 

maternal n-3 fatty acids 

supplement use, maternal 

probiotic supplement use, 

maternal probiotic dairy use, 

maternal antibiotic use during 

lactation, infant’s antibiotic 

use, vaccination schedule, 

dampness of the home, pet 

animals in the home.

289
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Wijga, et al., 2006175

Outcome domain: Allergies

Study name: The Prevention and Incidence of 

Asthma and Mite Allergy (PIAMA) birth cohort 

study

Study dates: 1995-2000

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government

Follow-up: 4 years

Study Population: NR

Pregnant enrolled 276 Pregnant withdrawals 11 

Pregnant completers 265

Infants enrolled 276 Infants withdrawals 11 

Infants completers 265

Pregnant age: 31.0 (3.9) NR

Race of Mother: NR (100)

Inclusion Criteria: Mothers reporting at least 1 of the 

following: (a history of) asthma, current hay fever, 

current allergy for pets, or current allergy for house 

dust or house dust mite were defined as allergic, 

and mothers reporting that they had none of these 

were defined as nonallergic.

Exclusion Criteria: NR

Adjustments: Sex, number of 

older siblings, maternal age, 

maternal smoking during 

pregnancy, and maternal 

body mass index before 

pregnancy

Yu, et al., 2015185

Outcome domain: Allergies

Study dates: Participants recruited between 

June 2009 and September 2010

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Study Population: Healthy infants Healthy 

pregnant women

Infants enrolled 1162 Infants completers 960

Pregnant age: NR (NR) NR

Race of Mother: NR (100%)

Inclusion Criteria: Participants were mother–child 

pairs in the Growing Up in Singapore Towards 

healthy Outcomes (GUSTO) birth cohort.

Exclusion Criteria: NR

Adjustments: In the models, 

we adjusted for maternal 

characteristics including 

maternal age, ethnicity, 

gravidity, education level and 

energy intake. The same was 

done for infant characteristics 

including sex, birth weight, 

gestational age, duration of 

breast-feeding, family history 

of allergic diseases (which 

includes allergic rhinitis, 

eczema and asthma in firstdegree relatives of the 

children (i.e. father, mother 

and/or sibling), exposure to 

environmental tobacco 

smoking, child day care 

attendance and having a cat 

or dog at home up to 18 

months of age.

290
Respiratory Illness (Including Asthma)

Key Points 

• In six prenatal n-3 interventions and two follow-up studies, maternal n-3 FA 

supplementation (DHA + EPA, varying doses) had no consistent significant effect on

respiratory illness. Six studies found no significant effect on risk for respiratory 

outcomes; one study found a decreased risk for asthma in the treatment group after 16 

years and another found lower risk of respiratory symptoms at 18 months, though not at 

earlier time points. In addition, meta-analysis of three of the RCTs (n=1315) with 12-

month follow-up of wheeze outcomes yielded an insignificant summary effect. 

• In three postnatal n-3 interventions and four follow-up studies, infant n-3 FA 

supplementation (DHA or DHA+EPA, varying doses) had no robust effect on respiratory 

outcomes. One study found a lower prevalence of wheeze at 18 months in the treatment 

group; however, this finding no longer remained at the 3- or 5-year follow-up. Another 

study found a higher prevalence of wheeze at 8 years of age in the treatment group. 

Pooled analysis of the three RCTs (n=1693) with 18-month follow-up asthma outcomes 

yielded a summary effect that was not significant.

• One biomarker study found higher levels of DHA and DHA + DPA + EPA at 6 months 

were associated with reduced risk of recurrent wheeze in the first 12 months. 

• Four of five prospective observational studies found an inverse association between n-3 

FA (measured through maternal dietary intake or breast milk composition) and risk of 

respiratory outcomes such as wheeze and asthma. The n-3 FA exposures in these studies 

included ALA, DHA, EPA, EPA+DHA, total n-3 PUFA, and n-3/n-6 LCPUFA. Four of 

five prospective observational studies of n-3 FA biomarkers (in cord blood or maternal 

blood sample) found no relationship between n-3 FA biomarkers and risk of respiratory

illness, with only one study reporting higher maternal EPA, DHA, and total n-3 FAs 

being associated with reduced risk of non-atopic persistent/late wheeze. 

Description of Included Studies

Asthma/wheeze is an additional outcome of interest that was not included in the original 

review. A total of 15 eligible studies (comprising of 9 RCTS and 6 follow-up studies) and 10

observational studies were included.

Randomized Controlled Trials

Prenatal maternal interventions/exposures

Eight studies (6 RCTs and 2 follow-up studies) evaluated prenatal maternal n-3 FA 

interventions (see Table 26). 50, 54, 56, 58, 59, 88, 172, 187 All interventions were exclusively during the 

prenatal period with the mother stopping supplementation at birth, except for one that continued 

into breastfeeding.172 Most of the trials recruited pregnant women whose infants were at high 

risk for atopy (e.g., parent diagnosis of allergy, or sibling with diagnosed or suspected allergy), 

except for three that recruited healthy pregnant women.58, 59, 187 All the studies compared DHA 

and DHA+EPA n-3 FAs with placebo.

291
DHA, DHA Plus EPA Versus Placebo

Olsen (2008), followed up with a population-based sample of 533 pregnant women in 

Denmark randomized to 2.7g marine n-3 PUFA, olive oil, or no oil daily from 30 weeks until 

term.187 Medical records were available for 528 children for a 16-year follow-up. The fish oil 

group was less likely to have occurrences of asthma (HR 0.37; 95% CI 0.15, 0.92) and allergic 

asthma (HR 0.13; 95% CI 0.03, 0.60) compared to the olive oil group.

Dunstan (2003) randomized 98 pregnant, atopic Australian women to fish oil (3.7g n-3 

PUFA, 56.0% DHA, 27.7% EPA) or olive oil (4g) daily from 20 weeks gestation until delivery.50

A total of 83 mothers and their children completed the 12-month follow-up. No significant 

differences were seen in respiratory clinical outcomes, including recurrent wheeze, persistent 

cough, or diagnosed asthma, between the fish oil and control groups.50

In the Salmon in Pregnancy Study (SiPS), 123 pregnant women in the UK were randomized 

to the salmon group (300g salmon / week) or control group (no changes in diet) from 20 weeks 

gestation until delivery.88 Clinical outcomes were available for 86 infants at 6 months. No 

differences were seen in the incidence of wheeze, bronchiolitis, or chest infections between the 

salmon and control groups.

88

Another study randomized 1,094 pregnant women in Mexico to n-3 FA supplementation 

(400 mg DHA) or placebo (corn and soy oil) daily from mid-pregnancy (18-22 weeks gestation) 

until delivery.59 A total of 973 women completed the treatment. In crude analyses of respiratory 

symptoms up to age 18 months, DHA supplementation was associated with lower risk of three 

respiratory symptoms : “phlegm with congestion and/or nasal discharge,” fever with phlegm and 

congestion and/or nasal discharge,” and “wheezing with fever” (IRR 0.74; 95% CI 0.63,0.87, 

IRR 0.52; 95% CI 0.38, 0.70, and IRR 0.43, 95% CI 0.21, 0.83, respectively). The authors 

reported significant interactions between the treatment group and the mother’s atopic status on a 

number of respiratory symptoms, indicating a greater protective effect of DHA supplementation 

in children of atopic mothers. An earlier study of the same cohort examined morbidity data for 

849, 834, and 834 infants at 1, 3 and 6 months, respectively.

58 The DHA group and placebo 

groups showed no differences at 1, 3, or 6 months for cough, wheezing, or difficulty breathing. 

The authors reported lower occurrence of cold (defined as any of the following: cough, phlegm, 

nasal congestion, nasal secretion) in the DHA group compared to the placebo group at 1 and 3 

months (37.6% vs 44.6%; P < .05; and 37.8 vs 44.1; P>.05, respectively).

In a subset of the Docosahexaenoic Acid (DHA) to Optimise Mother Infant Outcome 

(DOMInO) trial, 706 pregnant Australian women whose child was at high familial risk for 

allergy were randomized to receive n-3 LCPUFA (800 mg DHA + 100 mg EPA) or placebo 

(vegetable oil) from 21 weeks gestation until delivery.54, 56 A 1-year follow-up was completed 

with 706 infants, but outcomes for respiratory manifestations did not differ between treatment 

groups.54 Asthma with sensitization was rare during the first 3 years of life (6% (SD 1.8) in the 

n-3 LCPUFA group and 5% (SD 1.6) in the placebo group) with no differences between 

treatment groups (Fisher’s exact, p=1.00) .56

One RCT randomized 145 pregnant women in Sweden to daily n-3 FA (1.6g EPA + 1.1g 

DHA) or placebo (soy oil) supplementation from the 25th gestational week through the exclusive 

breastfeeding period (average 3-4 months). In a follow-up study with 143 infants, no differences 

were observed in cumulative asthma (with and without sensitization) through 24 months or 

current asthma (with and without sensitization) at 24 months between the treatment groups.172

Meta-analysis of three RCTs with a 12-month follow-up 50, 58, 88 showed no significant effect 

of DHA supplementation on risk of wheeze (OR 0.95 95% CI 0.77,1.13, I2=0%)) (Figure 27). 

292
Figure 27. Wheeze – Intervention given to pregnant women, 12-month follow-up

Postnatal maternal interventions/exposures

Three RCTs 118, 119, 142, 166 and four follow-up studies 167, 168,

169 119 evaluated n-3 FA 

interventions during the postnatal period. One of the RCTs evaluated preterm infants, and the 

remaining RCTs assessed term infants who were at genetic risk for allergy. All RCTs evaluated 

DHA or DHA+EPA.

DHA, DHA Plus AA, or DHA Plus EPA Versus Placebo

The DINO trial began the n-3 FA intervention during the postnatal breastfeeding period.118, 

119 This study randomized 657 preterm Australian infants (<33 weeks gestation) to receive a 

high-DHA diet (~1% DHA and 0.6% AA) or standard DHA diet ( ~0.35% DHA and 0.6% AA) 

through breast milk or formula until their expected delivery date. Data on asthma were available

from a parent questionnaire for 481 infants at 12 months and 603 infants at 18 months. No 

differences were seen in asthma at either time point (adjusted or unadjusted for gestational age at 

delivery and gender).

118 Data on re-hospitalization were available for 648, 626, 615, and 611 at 

term, 4, 12, and 18 months’ corrected age, respectively. No significant differences were observed

between the high-DHA and standard DHA groups in prevalence of any hospitalization or the 

mean number of admissions for lower respiratory tract conditions such as wheezing and asthma, 

after 18 months.119

In the Infant Fish Oil Supplementation Study (IFOS), 420 infants at high risk for atopy were 

randomized to daily fish oil capsules (280 mg DHA + 110 mg EPA) or placebo capsules (olive 

oil) from birth to 6 months. No significant overall difference was observed in the prevalence of 

asthma at 12 months between the fish oil and placebo groups in unadjusted and adjusted 

analyses. Similarly, no differences were seen in wheeze or persistent coughing at 6 or 12 

months.142

Four publications on infant n-3 supplementation came from the Childhood Asthma 

Prevention Study (CAPS).166-168 In CAPS, 616 pregnant women (<36 weeks gestation) whose 

children were at high risk for developing asthma were randomized into 4 groups, including 2 

with a dietary component (500 mg tuna fish oil supplement + canola-based oils and spreads or 

placebo supplement + polyunsaturated oils and margarines) from 6 months. In an 18-month 

293
follow-up with 543 infants (88% of the total sample size), the prevalence of wheeze was 9.8 

percentage points lower and the prevalence of wheeze lasting longer than 1 week was 7.8 

percentage points lower in the diet intervention group than in the control group (p=0.02 and 

p=0.04, respectively).166 In a 3-year follow-up with 526 infants, no between-group differences 

were observed in the prevalence of asthma or wheeze, although mild cough was reduced by 7.1% 

and moderate cough by 4.1% in the diet group (p=0.03), with a larger reduction of 10.0% (95% 

CI 3.7, 16.4) in atopic cough when stratified by atopy.167 In a 5-year follow-up with 516 children 

(84%), no significant differences were observed between the diet intervention and control groups 

for probable current asthma (RR=1.13; 95% CI 0.82, 1.57) or cough without cold (RR=1.42, 

95% CI 0.97, 2.09).168 In an 8-year follow-up with 450 children (73%), no significant differences 

were seen between the diet intervention and control groups for asthma (ARR=-4.8, 95% CI -

12.5, 2.9). The prevalence of wheeze was higher in the diet intervention group compared with 

the diet control group (ARR=-8.6, 95% CI -16.8, -0.4).169

Meta-analysis of three RCTs with an 18-month follow-up 118, 142, 166 showed no significant 

effect for DHA supplementation on risk of asthma (OR [95% CI]= 1.06CI[0.73,1.54], I2=0%) 

(Figure 28). 

Figure 28. Asthma – Intervention given to infants, 18-month follow-up

Biomarker Studies

A single RCT examined associations between biomarkers and respiratory outcomes. Results 

suggest that elevated plasma levels of DHA (P = .027) and total n-3 PUFA (EPA + DPA + DHA) 

at 6 months were associated with a reduced risk of recurrent wheeze in the first 12 months of life

(P = .028).

142

Observational Studies

Ten observational studies evaluated the association between some measure of n-3 FA 

exposure and risk of respiratory illnesses (see Table 27).

175-177, 179, 182-184, 186, 188, 185

All studies enrolled populations of healthy infants except for one188 that enrolled infants who 

had high or moderate genetic risk of type I diabetes. All the studies were prospective cohort 

studies. The exposures included dietary intake of n-3 FA, 182, 183, 188 breast milk FA,175, 184 and 

maternal biomarkers.176, 177, 179, 185, 186 Included studies were published between 2004 and 2014.

294
n-3 FA Intake

We identified three studies that evaluated the association between dietary n-3 FA intake and 

risk of respiratory illness.

182, 183, 188

Lumia (2011), in their analysis of 2679 infant-mother pairs from the Finnish Type 1 Diabetes 

Prediction and Prevention (DIPP) Nutrition Study, examined the association between maternal 

dietary intake during the 8th month of pregnancy (assessed by a validated 181-item FFQ) and risk 

of asthma in offspring at 5 years of age. Enrolled infants had a high to moderate risk of type I 

diabetes. Low maternal intakes of ALA (lowest quartile vs. mid-half HR 1.70 [95% CI 1.14–

2.53]) and total n-3-polyunsaturated fatty acids (PUFA) (HR 1.66 [95% CI 1.11–2.48]) during 

pregnancy were associated with an increased risk of asthma in the offspring, while a low intake 

of AA(HR 0.52 [95% CI 0.32–0.84)]) were associated with a decreased risk of asthma after 

adjusting for potential confounders. Adjusting for Vitamin D intake did not change the results.188

In a 2009 study of 763 healthy mother-infant pairs from the Osaka Maternal and Child 

Health Study in Japan, higher maternal intakes of ALA and DHA during pregnancy were

independently associated with a reduced risk of wheeze in the offspring (adjusted ORs between 

extreme quartiles 0.52 [95% CI 0.28 to 0.97] and 0.37 [95% CI 0.15 to 0.91], respectively).182

Maternal dietary intake was assessed with a validated diet history questionnaire during 

pregnancy, and wheeze was assessed by maternal report based on the International Study of 

Asthma and Allergies in Childhood for offspring at 16-24 months postpartum.

In a 2013 study of 1,354 healthy mother-infant pairs from the Kyushu Okinawa Maternal and 

Child Health Study (KOMCHS) in Japan, higher maternal intake of EPA (p for trend = 0.02) and 

EPA plus DHA (p for trend = 0.02) during pregnancy were associated with a reduced risk of 

wheeze in the offspring 183 Maternal dietary intake was assessed with a dietary history 

questionnaire during pregnancy while infantile wheeze was assessed by parental report based on 

the International Study of Asthma and Allergies in Childhood for offspring at 23-29 months 

postpartum.

n-3 FA Breastmilk Intake

Two studies examined the association between breastmilk n-3 fatty acids and the risk of 

respiratory illness.

175, 184

A 2006 study of 265 mother-infant pairs in the Netherlands found an inverse association of

breast milk DHA concentration (measured at 3 months postpartum) and n-3/ n-6 LCPFA ratio 

with risk of asthma in 4-year-old children of mothers with allergy(p<0.05).175

A 2012 study of 580 infants in Spain found no significant association between colostrum n-3 

LC-PUFA and risk of wheeze and lower respiratory tract infection during the first 14 months of 

life.

184 Colostrum was collected only for a random subsample (n=352) with n-3 LC-PUFA values 

imputed for the rest of the sample, however no differences were found in analyses with the 

colostrum subsample only. 

n-3 FA Biomarkers

Five studies examined the association between n-3 FA biomarkers and children’s risk of 

respiratory illness.176, 177, 179, 185, 186

A 2004 study of 1238 mother-infant pairs conducted in the UK found a positive association 

between the ratio of linoleic acid to ALA in cord blood and later-onset wheeze at 30-42 months 

of age (OR 1.30 95% CI 1.04-1.61; P = .019), after adjusting for potential confounders. 

However, the association was no longer significant after adjusting for multiple comparisons. No 

295
significant associations were observed for late pregnancy maternal plasma phospholipid fatty 

acid exposures (n=2945).

176

In a 2011 study of 1275 children from the KOALA Birth Cohort Study who were followed 

for 6–7 years, no associations were found between maternal plasma phospholipid n-3 fatty acids 

measured at 34–36 weeks of pregnancy and risk of developing asthma or parentally reported 

wheeze.179

In a 2012 study of 1485 healthy mother-infant pairs from the Southampton Women’s Survey 

in the UK who were followed for 6 years, the plasma phospholipid n-3 to n-6 FA ratio was not 

associated with childhood wheeze, airway inflammation, or childhood Forced Expiratory 

Volume (FEV1, a measure of lung function). However, higher maternal EPA, DHA, and total n-3 

FA were associated with reduced risk of non-atopic persistent/late wheeze (RR 0.57, 0.67 and 

0.69, respectively; P = 0.01, 0.015, and 0.021, respectively). Also, maternal plasma phosphatidyl 

choline AA was positively associated with airway inflammation (P = 0.024).186

A 2014 study of 436 infants from the Munich LISAplus birth cohort study in Germany found 

no significant association between n-3 LC-PUFA or n-6/n-3 ratio in cord blood and risk of 

asthma at 6 and 10 year follow-up.

177

In a 2010 study of 1162 children from the Growing Up in Singapore Towards healthy 

Outcomes (GUSTO) birth cohort study who were followed for 18 months, no significant 

associations were found between maternal plasma phospholipid DHA, EPA, ALA, total n-3 LCPUFA or n-6/n-3 ratio measured at 26-28 weeks of pregnancy and wheezing.185

Observational study subgroup analyses

None of the studies reported subgroup analyses.

296
Table 26. RCTs for respiratory illness

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Atwell et al., 2013119

Study name: DINO

Study dates: 2001-2005

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product, Some 

authors serve on 

scientific advisory boards 

for corporations

Study follow-up: 18 

months corrected age

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Collins, 2015120

Study Population: 

Preterm infants

Infants enrolled 657 

Infants completers 648

Infant age: birth

Race of Mother: White 

European (90.5%) Other 

race/ethnicity (9.5%)

Inclusion Criteria: Infants 

were eligible if born 

before 33 weeks’ 

gestation

Exclusion Criteria: Infants 

in other trials of fatty acid 

supplementation, or with 

major congenital or 

chromosomal 

abnormalities, or 

maternal contraindication 

for tuna oil ingestion 

(allergy or coagulopathy) 

were excluded.

Start time: Infants birth

Duration: Infants to 40 weeks’ postmenstrual age 

(term)

Arm 1: Standard DHA

Description: Placebo/control group (soy oil)

Dose: 6 soy oil capsules/ daily

Blinding: capsules given to breastfeeding mothers or 

added to formula

DHA: 0.35% in preterm formula

Arm 2: High DHA

Description: DHA maternal supplements or 

supplemented preterm formula

Dose: 6 tuna oil capsules daily

DHA: 900 mg in capsules or 1% infant formula

Outcome: one or more hospitalizations for 

lower respiratory conditions (Secondary)

Follow-up time: 18 months

Arm 1: 82/335 (24.48%)

Arm 2: 72/322 (22.36%)

D'Vaz et al., 2012142

Study name: IFOS

Study dates: 2005-2009

Study design: Trial 

randomized parallel

Location: Australia

Study Population: 

Pregnant women with 

allergies

Infants enrolled 420 

Infants completers 323

Pregnant age: Placebo: 

33.2 Fish Oil: 32.5 

(Placebo: 4.2 Fish Oil: 

4.8)

Inclusion Criteria: 

Maternal: Pregnant 

History of doctor 

diagnosed asthma or 

allergic rhinitis Skin prick 

positive to at least one 

allergen

Exclusion Criteria: 

Maternal: Smoking Autoimmune disease PreStart time: Infants Birth

Duration: Infants 6 months

Arm 1: Placebo

Description: Olive oil

Manufacturer: Ocean Nutrition, Ltd

Dose: 650 mg olive oil

Blinding: Randomization was completed by external 

staff via computer software using an unpredictable 

allocation sequence, stratified according to maternal 

Outcome: asthma (Primary)

Follow-up time: 12 months

Arm 1: 0/167 (0.0%)

Arm 2: 0/156 (0.0%)

Outcome: persistent cough (Primary)

Follow-up time: 12 months

Arm 1: 38/167 (22.75%)

Arm 2: 42/156 (26.92%)

Follow-up time: 6 months

Arm 1: 27/167 (16.17%)

Arm 2: 19/156 (12.18%)

297
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, None, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Meldrum, 2012140

Infant age: Term (39.3 

weeks gestation)

Race of Mother: NR 

(100)

existing medical 

conditions other than 

asthma High-risk 

pregnancy Seafood 

allergy Fish eaten more 

than three times per 

week Fish oil 

supplementation already 

taken (in excess of 1000 

mg per day) Exclusion 

from data analysis 

criteria due to protocol 

deviations: Pre-term 

delivery (gestation <36 

weeks) Infant with 

congenital abnormalities 

or significant disease not 

related to intervention

and paternal atopic history and parity. Mothers and 

study personnel were unaware of the group 

allocation.

Maternal conditions

Maternal allergies 100

Arm 2: Fish oil group

Manufacturer: Ocean Nutrition Ltd.

Purity Data: fatty acid composition remained 

unchanged over the study period

Dose: 1 capsule contents, to be administered orally, 

prior to feeding in the morning

Maternal conditions

DHA: 280 mg

EPA: 110 mg

Maternal allergies 100

Outcome: recurrent wheeze (Primary)

Follow-up time: 12 months

Arm 1: 16/167 (9.58%)

Arm 2: 21/156 (13.46%)

Follow-up time: 6 months

Arm 1: 27/167 (16.17%)

Arm 2: 23/156 (14.74%)

Dunstan et al., 200350

Study name: Dunstan

Study dates: 1999-2001

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government

Study follow-up: 1 year

Original, same study, or 

follow-up studies: 

Dunstan, 200844; 

Meldrum, 201551

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 98 

Pregnant withdrawals 15 

Pregnant completers 83

Pregnant age: NR (NR) 

NR

Race of Mother: NR 

(100)

Inclusion Criteria: All 

women had a history of 

physician-diagnosed 

allergic rhinitis and/or 

asthma and 1 or more 

positive skin prick tests to 

common allergens 

(house dust mite; grass 

pollens; molds; and cat, 

dog, and cockroach 

extracts)

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked; if they had other 

medical problems, 

complicated pregnancies, 

or seafood allergy; or if 

their normal dietary 

intake exceeded 2 meals 

of fish per week.

Start time: Pregnant 20 weeks of gestation

Duration: Pregnant till delivery

Arm 1: Placebo group

Description: 46 women allocated and received 

placebo-olive oil

Manufacturer: Pan Laboratories, Moorebank, NSW, 

Australia

Active ingredients: 66.6% n-9 oleic acid

Dose: 4 (1-g) capsules of olive oil per day

Blinding: Randomization and allocation of capsules 

occurred at a different center separate from the 

recruitment of participants. Capsules were 

administered to the participants by someone 

separate from those doing the allocation. The 

capsules in the 2 groups were image-matched.

Total N-3: <1% n-3 PUFAs

Arm 2: Fish oil group

Description: 52 women were randomized to receive 

fish oil

Manufacturer: Ocean Nutrition, Halifax, Nova Scotia, 

Canada

Dose: 4 (1g) fish oil capsules per day 

Outcome: asthma (Secondary)

Follow-up time: 1 year

Arm 1: 6/43 (13.95%)

Arm 2: 2/40 (5.0%)

Outcome: chronic cough (Secondary)

Follow-up time: 1 year

Arm 1: 11/43 (25.58%)

Arm 2: 5/40 (12.5%)

Outcome: recurrent wheeze (Secondary)

Follow-up time: 1 year

Arm 1: 12/43 (27.91%)

Arm 2: 10/40 (25.0%)

298
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

_x001E__x0007__x0005__x0015__x0013__x0007_ 

_x001E__x0013__x000F_

DHA: 56.0%

EPA: 27.7%

Total N-3: 3.7 g

Escamilla-Nunez et al., 

201459

Study name: POSGRAD

Study dates: 2005-2009

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Stein, 201233; ImhoffKunsch, 201158;

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 1,040 

Pregnant completers 973

Pregnant age: 26.3 (4.8) 

18-35

Race of Mother: Hispanic 

(100% Mexican)

Baseline Omega-3 

intake: DHA median 

(25th, 75th percentile), 

mg/d: 55(37, 99)

Inclusion Criteria: 

Maternal age 18 - 35 

years, recruited between 

18 and 22 weeks of 

gestation. Willingness to 

breastfeed exclusively or 

predominantly during at 

least the first 3 months of 

life of the newborn and

with the intention to live 

in their area of residence 

for at least 2 years after 

delivery

Exclusion Criteria: Highrisk pregnancies 

(pregnancy 

complications, including 

premature placental 

abruption, preeclampsia, 

pregnancy-induced 

hypertension, severe 

bleeding episode in 

pregnancy or lipid 

absorption disorders; 

Regular consumption of 

fish oil or DHA 

supplements; Chronic 

use of certain 

medications (e.g., drugs 

for epilepsy)

Start time: Pregnant 18-22 weeks gestation

Duration: Pregnant to term

Arm 1: Placebo

Description: olive oil capsule

Dose: 2 capsules per day

Arm 2: DHA

Description: Algal DHA

Manufacturer: Martek Biosciences

Dose: 2 capsules of 200mg each

DHA: 200 mg algal DHA/capsule

Outcome: breathing difficulty (number of 

episodes)

Follow-up time: 18 months

Arm 1: 48/440

Arm 2: 47/429

Outcome: cough (number of episodes)

Follow-up time: 18 months

Arm 1: 1151/440

Arm 2: 1178/429

Outcome: phlegm with congestion and/or 

nasal discharge, fever with phlegm and 

congestion and/or nasal discharge, or 

wheezing with fever (Primary)

Follow-up time: 18 months

Arm 1: 49/440 (11.11%)

Arm 2: 48/429 (11.11%)

Outcome: wheezing (number of episodes)

Follow-up time: 18 months

Arm 1: 262/440

Arm 2: 252/429

Furuhjelm et al., 2011172

Study name: NR

Study dates: 2003-2007

Study design: Trial 

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 145 

Pregnant withdrawals 28 

Pregnant completers 117

Inclusion Criteria: family 

history of current or 

previous allergic 

symptoms, i.e. bronchial 

asthma, eczema, allergic 

food reactions, itching 

and running eyes and 

Start time: Pregnant 25 weeks of gestation

Duration: Pregnant 15 weeks (i.e., until delivery)

Arm 1: Placebo

Description: soya bean oil

Manufacturer: Pharma Nord, Vejle, Denmark

Outcome: any asthma (Primary)

Follow-up time: 2 years

Arm 1: 8/65 (12.31%)

Arm 2: 7/54 (12.96%)

Outcome: any rhinoconjunctivitis (Primary)

Follow-up time: 2 years

Arm 1: 2/65 (3.08%)

299
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

randomized parallel

Location: Sweden

Funding source / conflict: 

Industry, Multiple

foundations and 

Societies

Study follow-up: 2 years

Original, same study, or 

follow-up studies: 

Furuhjelm, 2009173

Infants enrolled 145 

Infants withdrawals 28 

Infants completers 117

Pregnant age: NR (NR) 

NR

Race of Mother: NR 

(100)

nose at exposure to 

pollen, pets or other 

known allergens.

Exclusion Criteria: 

Allergy to soya or fish, 

treatment with 

anticoagulants or omega3 fatty acid supplements.

Active ingredients: 58% linoleic acid (LA), 2.5 g/day

Viability: the antioxidant a-tocopherol (placebo: 36 

mg/day) to assure the stability of the oil

Dose: nine capsules a day

Blinding: The mothers, as well as the staff handling 

clinical and laboratory follow-up, were blinded to 

group allocation, and the mothers were identified by 

their study number only.

ALA: 6%, 0.28 g/day

Arm 2: w-3 group

Description: w-3 fatty acids

Viability: the antioxidant a-tocopherol (w-3 group: 28 

mg/day) to assure the stability of the oil

Dose: nine capsules a day

DHA: 25% DHA, 1.1 g/day

EPA: 35% EPA, 1.6 g/day

Arm 2: 2/54 (3.7%)

Imhoff-Kunsch et al., 

201158

Study name: POSGRAD

Study dates: February 

2005 - February 2007

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / conflict: 

Government, March of 

Dimes

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Stein, 201233; EscamillaNunez, 201459;

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561

Study Population: 

Healthy pregnant women

Pregnant enrolled 1094

Pregnant completers 851

Infants enrolled 851 

Infants completers 834

Pregnant age: DHA: 26.3 

Placebo:20.5 (DHA: 4.9 

Placebo: 1.9)

Race of Mother: NR 

(100%)

Inclusion Criteria: 

Women were considered 

for inclusion in the study 

if they were in gestation 

week 18 to 22, were 

aged 18 to 35 years, 

planned to deliver at the 

IMSS General Hospital in 

Cuernavaca, planned to 

predominantly breastfeed 

for at least 3 months, and 

planned to live in the 

area for 2 years after 

delivery

Exclusion Criteria: 

Exclusion criteria 

included (1) high-risk 

pregnancy, (2) lipid 

metabolism/absorption 

disorders, (3) regular 

intake of fish oil or DHA 

supplements, or (4) 

chronic use of certain 

medications.

Start time: Pregnant 18 to 22 weeks gestation

Duration: Pregnant until parturition

Arm 1: Placebo

Description: Placebo/control corn and soy oil 

capsule

Dose: 2 capsules daily

Blinding: The placebo capsules, which were similar 

in appearance and taste to the DHA capsules, 

contained a corn and soy oil blend with no added 

antioxidants. All participants and members of the 

study team were blinded to the treatment scheme 

throughout the intervention period of the study. Data 

were unblinded for the analytical study team after 

the last infant in the study was born and had 

reached the age of 6 months.

Arm 2: DHA

Description: DHA capsule

Manufacturer: Martek Biosciences Corporation, 

Columbia, MD

Dose: 2 capsules daily

DHA: 200mg/ capsule

Outcome: cold (any of cough, phlegm, 

nasal congestion, nasal secretion) 

(Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 190/427 (44.6%)

Arm 2: 159/422 (37.6%)

Follow-up time: 3 months

Arm 1: 185/419 (44.1%)

Arm 2: 157/415 (37.8%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 193/414 (46.6%)

Arm 2: 194/420 (46.2%)

Outcome: cough (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 47/427 (11.0%)

Arm 2: 40/422 (9.5%)

Follow-up time: 3 months

Arm 1: 100/419 (23.9%)

Arm 2: 80/415 (19.3%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 136/414 (32.9%)

Arm 2: 139/420 (33.1%)

300
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Outcome: difficulty breathing (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 10/427 (2.3%)

Arm 2: 10/422 (2.4%)

Follow-up time: 3 months

Arm 1: 10/419 (2.4%)

Arm 2: 12/415 (2.9%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 7/414 (1.7%)

Arm 2: 6/420 (1.4%)

Outcome: nasal congestion (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 140/427 (32.8%)

Arm 2: 119/422 (28.2%)

Follow-up time: 3 months

Arm 1: 119/419 (28.4%)

Arm 2: 104/415 (25.1%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 116/414 (28.0%)

Arm 2: 124/420 (29.6%)

Outcome: nasal secretion (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 46/427 (10.8%)

Arm 2: 30/422 (7.1%)

Follow-up time: 3 months

Arm 1: 72/419 (17.2%)

Arm 2: 62/415 (14.9%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 122/414 (29.5%)

Arm 2: 118/420 (28.2%)

Outcome: phlegm (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 82/427 (19.2%)

Arm 2: 71/422 (16.8%)

Follow-up time: 3 months

Arm 1: 78/419 (18.6%)

Arm 2: 81/415 (19.5%)

301
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 100/414 (24.2%)

Arm 2: 100/420 (23.9%)

Outcome: wheezing (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 30/427 (7.0%)

Arm 2: 35/422 (8.3%)

Follow-up time: 3 months

Arm 1: 34/419 (8.1%)

Arm 2: 29/415 (7.0%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 45/414 (10.9%)

Arm 2: 50/420 (11.9%)

Manley et al., 2011118

Study name: DINO

Study dates: 2001-2007

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product, Some 

authors serve on 

scientific advisory boards 

for corporations

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Study Population: 

Preterm infants Breastfeeding women

Infants enrolled 657 

Infants completers 614

Lactating age: 

Intervention: 29.9 (5.8)

Placebo: 30.2 (5.4)

Infant age: 4 days 

(median)

Race of Mother: NR 

(100%)

Inclusion Criteria: Infants 

born before 33 weeks’ 

gestation, within 5 days 

of the infant commencing 

any enteral feedings.

Exclusion Criteria: major 

congenital or 

chromosomal 

abnormalities, from a 

multiple birth in which not 

all live-born infants were 

eligible, enrolled in other 

trials of fatty acid

supplementation, or 

mother with 

contraindication to fish oil

Start time: Infants Within 5 days (or less) of starting 

enteral feeding

Duration: Infants NR

Arm 1: Standard DHA diet

Description: Soy bean oil

Manufacturer: Clover Corporation

Dose: 6 capsules per day

Maternal conditions

Infant conditions

Current smoker 25% during pregnancy

Other maternal conditions 

1arm_1_maternal_conditions_other1

Other maternal conditions 10 Birth by C-section: 

69%

Pre-term birth 100%

Low birth weight 18.6%

Arm 2: High DHA

Description: Tuna fish oil

Manufacturer: Clover Corporation

Dose: 6 500-mg DHA-rich tuna oil capsules per day

Maternal conditions

Infant conditions

DHA: DHA to achieve a breast milk concentration 

that was 1% of total fatty acids

Outcome: asthma (Secondary)

Follow-up time: 12 months

Arm 1: 25/249 (10.04%)

Arm 2: 18/232 (7.76%)

Follow-up time: 12 or 18 months

Arm 1: 53/252 (21.03%)

Arm 2: 47/237 (19.83%)

Follow-up time: 18 months

Arm 1: 46/311 (14.79%)

Arm 2: 41/292 (14.04%)

302
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Smithers, 2010117;

Collins, 2011105; Atwell, 

2013119; Collins, 2015120

Other dose 1: If supplementary formula was 

required, infants were given a high- DHA preterm 

formula (approximately 1.0%DHAand 0.6% AA).

Current smoker 25% during pregnancy

Other maternal conditions 

1arm_2_maternal_conditions_other1

Other maternal conditions 10 Birth by C-section: 

68.3%

Pre-term birth 100%

Low birth weight 18.9%

Marks et al., 2006168

Study name: CAPS

Study dates: 1997-2004

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, Multiple

foundations and 

Societies

Study follow-up: 5 years

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; Brew, 

2015165; Toelle, 2010169

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 616 

Pregnant withdrawals 

100 Pregnant completers 

516

Infants completers 516

Race of Mother: NR

Inclusion Criteria: 

pregnant women whose 

unborn children were at 

increased risk of 

developing asthma 

because 1 or more 

parents or siblings had 

asthma or wheezing

Exclusion Criteria: with a 

pet cat at home, strict 

vegetarians, women with 

a nonsingleton 

pregnancy, and infants 

born earlier than 36 

weeks of gestation. 

Infants had birth weights 

less than 2.5 kg, 

significant congenital 

malformations, or other 

significant neonatal 

disease.

Start time: Infants from the time the child started 

bottle-feeding, or to solid foods from age 6 months

Duration: NR

Arm 1: Diet control

Description: polyunsaturated oils and spreads, 

containing 40% w6 FA, and Sunola oil capsules

Manufacturer: Crisco-Meadow Lea Foods Inc, 

Sydney, Australia

Blinding: The approach to blinding participants and 

research staff is described in this article’s Online 

Repository at www.jacionline.org.

Arm 2: Active

Description: canola-based oils and spreads, which 

are low in n-6 fatty acids, and tuna oil capsules, 

which contain n-3 fatty acids.

Outcome: cough without cold (Secondary)

Follow-up time: 5 years

Arm 1: 36/249 (14.46%)

Arm 2: 55/267 (20.6%)

Outcome: frequent wheeze (Secondary)

Follow-up time: 5 years

Arm 1: 4/249 (1.61%)

Arm 2: 5/267 (1.87%)

Outcome: probable current asthma 

(Primary)

Follow-up time: 5 years

Arm 1: 51/249 (20.48%)

Arm 2: 62/267 (23.22%)

Mihrshahi et al., 2003166

Study name: CAPS

Study dates: 1997-2002

Study design: Trial 

randomized parallel

Location: Australia

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 616 

(all 4 arms) Pregnant 

withdrawals 62 Pregnant 

completers 554

Pregnant age: 28.5 (5.3)

Inclusion Criteria: At least 

one parent or sibling with 

symptoms of asthma as 

assessed by screening 

questionnaire, 

Reasonable fluency in 

English, Telephone at 

home, Reside within 30 

km from center of 

recruitment

Start time: Infants initiation of bottle feeding or 6 

months of age

Duration: Infants NR

Arm 1: Diet Control/HDM control or intervention

Brand name: Sunola oil

Manufacturer: Clover Corporation

Arm 2: Dietary intervention/HDM control or 

Outcome: asthma (Primary)

Follow-up time: 18 months

Arm 1: 34/275 (12.5%)

Arm 2: 41/279 (14.7%)

Outcome: wheeze ever (Primary)

Follow-up time: 18 months

Arm 1: 145/275 (52.6%)

Arm 2: 119/279 (42.8%)

303
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / conflict: 

Government, Multiple

foundations and 

Societies, Manufacturer 

supplied product

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; Brew, 

2015165 Toelle, 2010169

Race of Mother: NR 

(96.9%) Other 

race/ethnicity (Aboriginal 

3.1%)

Exclusion Criteria: Pet 

cat at home, Families on 

strict vegetarian diet, 

Multiple births, Babies 

born earlier than 36 

weeks gestation, with 

congenital malformations 

or other serious disease, 

or requiring major 

surgery or hospitalization 

for greater than 1 week

intervention

Description: 500mg n-3 rich tuna fish oil supplement

Manufacturer: Clover Corporation

DHA: 76-128 mg

EPA: 18-30 mg

Other dose 1: based on age and fluid intake

Noakes et al., 201288

Study name: SiPS

Study dates: Not reported

Study design: Trial 

randomized parallel

Location: UK

Funding source / conflict: 

Government, None

Original, same study, or 

follow-up studies: Miles, 

201178

Study Population: 

Healthy pregnant women

Pregnant enrolled 123 

Pregnant withdrawals 37 

Pregnant completers 86

Pregnant age: 

Mean(SEM)(n):Control 

group -28.4 (0.6)(61); 

Salmon group- 29.5(0.5) 

(62) (NR) 18-40 years

Race of Mother: NR 

(100)

Inclusion Criteria: age 

18–40 y; >19 wk 

gestation; healthy 

uncomplicated singleton 

pregnancy; infant at risk 

of atopy (one or more 

first-degree relatives of 

the infant affected by 

atopy, asthma or allergy 

by self-report); 

consumption of < 2 

portions oily fish per 

month, excluding tinned 

tuna; and no use of fishoil supplements currently 

or in the previous 3 

months.

Exclusion Criteria: age

<18 or >40 y; <19 wk 

gestation; no first-degree 

relatives of the infant 

affected by atopy, 

asthma, or allergy; 

consumption of >2 

portions oily fish per 

month, excluding tinned 

tuna; use of fish-oil 

Start time: Pregnant 20 weeks of gestation

Duration: Pregnant until birth

Arm 1: Control group

Description: Women in the control group (n = 61) 

were asked to continue their habitual diet

Blinding: Researchers responsible for assessing 

outcome measures (both laboratory and clinical) 

remained blinded to the groups

Arm 2: Salmon group

Description: Women in the salmon group (n = 62) 

were asked to incorporate 2 portions of farmed 

salmon (150 g/portion) into their diet per week

Active ingredients: 30.5 g protein, 16.4 g fat,4.1 mg 

alpha-tocopherol, 1.6 mg gamma-tocopherol, 6 

micro-g vitamin A, 14 micro-g vitamin D3, and 43 

micro-g Selenium

Dose: two 150-g portions per week

DHA: 1.16 g per portion

EPA: 0.57g per portion

EPA-DHA: 1.73 per portion

Total N-3: 3.56g per portion

Other dose 1: Docosapentaenoic acid-0.35g

Outcome: chest infection (Secondary)

Follow-up time: 6 months

Arm 1: 1/46 (2.17%)

Arm 2: 3/37 (8.11%)

Outcome: pneumonia/bronchiolitis 

(Secondary)

Follow-up time: 6 months

Arm 1: 1/46 (2.17%)

Arm 2: 1/37 (2.7%)

Outcome: wheeze (Secondary)

Follow-up time: 6 months

Arm 1: 11/46 (23.91%)

Arm 2: 7/37 (18.92%)

304
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

supplements within the 

previous 3 mo; 

participation in another 

research study; known 

diabetes; presence of 

any autoimmune 

disease; learning 

disability; terminal illness; 

and mental health 

problems.

Olsen et al., 2008187

Study name: NR

Study dates: 1989-2006

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / conflict: 

Multiple foundations and 

Societies

Study follow-up: 16 years

Study Population: 

Healthy pregnant women

Pregnant enrolled 533

Infants enrolled 531 

Infants completers 522

Pregnant age: Fish oil: 

29.4 Olive oil: 29.7 No 

oil: 29.1 (Fish oil: (4.4) 

Olive oil: (4.3) No oil: 

(4.1)) NR

Race of Mother: NR 

(100)

Inclusion Criteria: 

Women seen in the main 

midwife clinic in Aarhus 

Denmark at week 30 

gestation

Exclusion Criteria: 

History of placental 

abruption in a previous 

pregnancy or a serious 

bleeding episode in the 

current pregnancy; 

multiple pregnancies; 

allergy to fish; regular 

use of fish oil or 

prostaglandin inhibitors

Start time: Pregnant 30 weeks gestation

Duration: Pregnant to term

Arm 1: Control

Description: Olive oil

Active ingredients: 72% oleic acid

Dose: 4 one gram capsules

Blinding: Gelatin capsules were colored, and the 

capsules and their boxes looked identical.

ALA: 12%

Arm 2: Fish oil

Brand name: Pikasol Fish Oil

Manufacturer: Lube Limited

Active ingredients: 2mg tocopherol/ml

Dose: 4 1-gm capsules

EPA: 32%

EPA-DHA: 23%

Total N-3: 2.7g marine n-3PUFA/day

Arm 3: No oil

Description: no intervention at all

Outcome: asthma (all types) (Secondary)

Follow-up time: 16 years

Arm 1: 11/136 (8.09%)

Arm 2: 8/263 (3.04%)

Arm 3: 3/129 (2.33%)

Outcome: asthma (allergic) (Secondary)

Follow-up time: 16 years

Arm 1: 8/136 (5.88%)

Arm 2: 2/263 (0.76%)

Arm 3: 0/129 (0.0%)

Palmer et al., 201254

Study name: DOMInO

Study dates: 2006-2009

Study design: Trial 

randomized parallel

Location: Australia

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 706 

Pregnant withdrawals 25 

Pregnant completers 681

Infants enrolled 706 

Infants withdrawals 25 

Inclusion Criteria: 

Included if the unborn 

baby had a mother, 

father, or sibling with a 

history of any medically 

diagnosed allergic 

disease (asthma, allergic 

rhinitis, eczema) and 

they were enrolled from 

the Women’s and 

Start time: Pregnant 21 weeks of gestation Infants 

21 weeks of gestation

Duration: Pregnant until delivery Infants till delivery

Arm 1: Placebo

Description: 338 women assigned to control 

supplements-vegetable oil capsules

Dose: three 500 mg vegetable oil capsules daily

Blinding: All capsules were similar in size, shape, 

Outcome: respiratory tract infection 

(Secondary)

Follow-up time: 1 year

Arm 1: 66/338 (19.53%)

Arm 2: 65/368 (17.66%)

305
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / conflict: 

Industry, Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Zhou, 

201255; Palmer, 201356; 

Makrides, 2014 57

Infants completers 681

Pregnant age: 

Treatment: 29.6 Placebo: 

29.5 (Treatment: 5.7 

Placebo: 5.6) NR

Race of Mother: NR 

(100)

Children’s Hospital or 

Flinders Medical Centre 

in Adelaide.

Exclusion Criteria: NR

and color. Neither the women nor the research staff 

were aware of the treatment allocated.

Arm 2: n-3 LCPUFA group

Description: 368 women assigned to fish oil 

concentrate

Brand name: Incromega 500 TG

Manufacturer: Croda Chemicals, East Yorkshire, UK

Dose: e three 500 mg capsules daily

DHA: 800mg

EPA: 100mg

Palmer et al., 201356

Study name: DOMInO

Study dates: 2006-2011 

(allergy follow-up to 

Domino study)

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Industry, Government, 

Some authors serve on 

scientific advisory boards 

for corporations

Study follow-up: 3 years

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Palmer, 

201254; Zhou, 201255

Study Population: 

Children with family 

history of allergy

Pregnant enrolled 706 

Pregnant completers 638

Infants enrolled 706 

Infants completers 638

Pregnant age: DHA: 28.9

Control: 28.9 (DHA: 5.7) 

Control: 5.6)

Infant age: Birth

Race of Mother: NR 

(100)

Inclusion Criteria: 

Women whose infants 

had a parent or sibling 

with a history of any 

medically diagnosed 

allergic disease (asthma, 

allergic rhinitis, eczema)

Exclusion Criteria: 

Already taking a prenatal 

supplement with DHA

Fetus had a known major 

abnormality, Bleeding 

disorder in which tuna oil 

was contraindicated, 

Taking anticoagulant 

therapy A documented 

history of drug or alcohol 

abuse, Participating in 

another fatty acid trial,

Unable to give written 

informed consent, or 

English was not the main 

language spoken at 

home

Start time: Pregnant <21 weeks gestation

Duration: Pregnant to term

Arm 1: Control

Description: vegetable oil

Dose: 3 500-mg vegetable oil capsules per day

Blinding: This was a double-blinded study; all 

capsules were similar in size, shape and color

Arm 2: Fish oil

Brand name: Incromega 500 TG,

Manufacturer: Croda Chemicals, East Yorkshire, 

England

Dose: 3 500-mg capsules per day

DHA: 800 mg per day

EPA: 100 mg per day

Outcome: asthma (Primary)

Follow-up time: 3 years

Arm 1: 5/338 (1.48%)

Arm 2: 6/368 (1.63%)

306
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Peat et al., 2004167

Study name: CAPS

Study dates: 2000-2003

Study design: Trial 

randomized factorial 

design

Location: Australia

Funding source / conflict: 

Industry, Government

Study follow-up: 3 years

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2006168; Brew, 

2015165 Toelle, 2010169

Study Population: 

Pregnant women whose 

unborn children were at 

high risk of developing 

asthma

Pregnant enrolled 616 

Pregnant withdrawals 90 

Pregnant completers 526

Pregnant age: Placebo: 

29.1 Diet: 28.6 (Placebo: 

5.0 Diet: 5.3) NR

Race of Mother: NR 

(100)

Inclusion Criteria: at least 

1 parent or sibling with 

current asthma or 

frequent wheeze as 

assessed by screening 

questionnaire, fluency in 

English, a telephone at 

home, and residence 

within 30 km of the 

recruitment center.

Exclusion Criteria: a pet 

cat at home, a vegetarian 

diet, multiple births, and 

less than 36 weeks 

gestation.

Start time: Infants 6 months of age

Duration: Infants NR

Arm 1: Placebo group

Description: The control group received placebo 

supplement capsules of Sunola oil containing 83% 

monounsaturated oils (Clover Corp) and were 

provided with widely used soybean-based 

polyunsaturated oils and margarines high in omega6 fatty acids for use in all food preparation

Manufacturer: Clover Corp; Goodman Fielder

Blinding: The research team responsible for 

recruitment was blind to the methods of 

randomization until recruitment was complete. The 

research nurses and research assistants who 

undertook the outcome assessments, laboratory 

analyses, and statistical analyses were blind to the 

group allocation of the participants.

Arm 2: Active intervention group

Description: tuna fish oil capsules

Manufacturer: Clover Corp; Goodman Fielder

Dose: 500 mg tuna fish oil capsules daily

Total N-3: 184 mg

Outcome: any asthma (Primary)

Follow-up time: 3 years

Arm 1: 108/259 (41.7%)

Arm 2: 107/267 (40.07%)

Outcome: any cough (Primary)

Follow-up time: 3 years

Arm 1: 157/259 (60.62%)

Arm 2: 132/267 (49.44%)

Outcome: any wheeze (Secondary)

Follow-up time: 3 years

Arm 1: 108/259 (41.7%)

Arm 2: 107/267 (40.07%)

Toelle et al., 2010169

Study name: CAPS

Study dates: 1997-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / conflict: 

Government, 

Manufacturer supplied 

product

Study follow-up: 8 years

Study Population: 

Healthy infants

Pregnant enrolled 616 

Pregnant completers

Infants enrolled 616 

Infants completers 450

Pregnant age: 28.5 years 

(5.3 years)

Race of Mother: NR (NR)

Inclusion Criteria: 

Pregnant women whose 

unborn children were at 

high risk of developing 

asthma because of a 

family history (at least

one parent or sibling with 

symptoms of asthma as

assessed by screening 

questionnaire), 

reasonable fluency in 

English, telephone at 

home, reside within 30 

km from center of 

recruitment

Exclusion Criteria: Pet 

cat at home, families on 

Start time: Infants birth

Duration: Infants 5 years

Arm 1: Control

Description: Low-n3 capsules and cooking oils

Brand name: Sunola

Active ingredients: Capsules: 7% n-6 FA, 82% 

monounsaturated FA, 9% saturated FA, and 1.7% 

minor FA; cooking oils: 40% n-6 FA, 20% n-9 FA

Dose: Designed to maintain the current n-3 to n-6 

ingested FA ratio in the general population (1:15 to 

1:20)

Blinding: Similar appearance

Total N-3: Capsules: 0.3%; cooking oil: 1.2%

Arm 2: Omega 3 supplementation

Description: High n-3 FA capsules and cooking oils

Outcome: asthma (Primary)

Follow-up time: 8 yrs

Arm 1: 44/220 (20.0%)

Arm 2: 57/230 (24.8%)

Outcome: wheeze (Primary)

Follow-up time: 8 yrs

Arm 1: 51/220 (23.2%)

Arm 2: 73/230 (31.7%)

307
Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; Brew, 

2015165

strict vegetarian diet, 

multiple births, babies 

born earlier than 36 

weeks gestation, birth 

weight below 2.5 kg, 

babies requiring surgery, 

babies requiring 

hospitalization for more 

than 1 week, babies with 

significant neonatal 

disease, babies with 

congenital malformations

Active ingredients: Capsules: 6% n-6 

polyunsaturated FA, 24% monounsaturated FA, 

28% saturated FA, and 5% minor FA; cooking oil: 

6% n-6 FA, 40% n-9 FA

Blinding: Similar appearance

N-6 N-3: 5:1

Total N-3: Capsules: 37%; cooking oil: 6%

308
Table 27. Observational studies for respiratory illness

Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Lumia, et al., 2011188

Outcome domain: Respiratory illness

Study name: Finnish Type 1 Diabetes Prediction 

and Prevention Nutrition Study

Study dates: 1997-2004

Study design: NR

Location: Finland

Funding source / conflict: Industry, Government, 

Multiple foundations and Societies, None

Follow-up: 5 years

Study Population: NR

Infants enrolled 2908 Infants completers 2679

Pregnant age: 14.8% <25 years at birth 35.4% 

25-29 years 30.4% 30-34 years 19.5% =35 

years

Race of Mother: White European (100%)

Inclusion Criteria: infants at three university 

hospitals in Finland (Turku, Tampere and 

Oulu) whose cord blood was screened for 

HLA-conferred genetic susceptibility to type 1 

diabetes (HLA-DQB1) and were found to have 

high or moderate genetic risk of type 1 

diabetes

Exclusion Criteria: Severe congenital 

malformations or diseases, parents of nonCaucasian origin or parents who did not have 

a working knowledge of Finnish, Swedish or 

English

Adjustments: Maternal age, mode of 

delivery, duration of gestation, 

number of earlier deliveries, birth 

weight, sex of the child, area of 

birth, maternal smoking during 

pregnancy, parental asthma or 

allergic rhinitis, maternal vocational 

education, pets at home, farming, 

contact with cow stable during the 

first year of life and the duration of 

total breastfeeding

Miyake, et al., 2009182

Outcome domain: Respiratory illness

Study name: Osaka maternal and child health 

study

Study dates: 2002-2003

Study design: Observational prospective

Location: Japan

Funding source / conflict: Government, None

Study Population: Healthy infants

Pregnant enrolled 1,002 Pregnant completers 

763

Infants enrolled 1,002 Infants completers 763

Pregnant age: 30.0 (4.0)

Race of Mother: NR (100)

Inclusion Criteria: pregnant women living in 

Neyagawa City, Osaka Prefecture or the 

surrounding cities

Exclusion Criteria: Not reported

Adjustments: Maternal age, 

gestation at baseline, residential 

municipality, family income, 

maternal and paternal education, 

maternal and paternal history of 

asthma, atopic eczema and allergic 

rhinitis, maternal intake of vitamins 

D and E during pregnancy, changes 

in maternal diet in the previous 1 

month, season when data at 

baseline were collected, maternal 

smoking during pregnancy, baby’s 

older siblings, baby’s sex, baby’s 

birth weight, household smoking in 

the same room as the infant, 

breastfeeding duration and time of 

delivery before the third survey

Miyake, et al., 2013183

Outcome domain: Respiratory illness

Study name: Kyushu Okinawa Maternal and 

Child Health Study

Study dates: 2007-2010

Study Population: Healthy infants

Pregnant enrolled 1757 Pregnant completers 

1354

Infants enrolled 1757 Infants completers 1354

Pregnant age: 31.5 (4.1)

Inclusion Criteria: Women living in one of 7 

prefectures on Kyushu Island who became 

pregnant from 2007-2008

Exclusion Criteria: Failure to complete the 

study surveys

Adjustments: Maternal age, 

gestation at baseline, residential 

municipality, family income, 

maternal and paternal education, 

maternal and paternal history of 

asthma, atopic eczema and allergic 

rhinitis, maternal intake of vitamins 

D and E during pregnancy, changes 

in maternal diet in the previous 1 

309
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Study design: Observational prospective

Location: Japan

Funding source / conflict: Industry, Government, 

Multiple foundations and Societies

Follow-up: 23-29 months

Race of Mother: NR (100) month, season when data at 

baseline were collected, maternal 

smoking during pregnancy, baby’s 

older siblings, baby’s sex, baby’s 

birth weight, household smoking in 

the same room as the infant, 

breastfeeding duration and time of 

delivery before the third survey

Morales, et al., 2012184

Outcome domain: Respiratory illness

Study name: INfancia y Medio Ambiente (INMA) 

Project

Study dates: 2004-2007

Study design: Observational prospective

Location: Spain

Funding source / conflict: Government

Follow-up: 14 months

Study Population: Healthy infants Healthy 

pregnant women

Pregnant enrolled 622 Pregnant completers 580

Infants enrolled 622 Infants completers 580

Mother age: 31.6 (4.2)

Race of Mother: NR (100)

Inclusion Criteria: to be resident in the study 

area, to be at least 16 years old, to have a 

singleton pregnancy, to not have followed any 

program of assisted reproduction, to wish to 

deliver in the reference hospital, and to have 

no communication problems

Exclusion Criteria: NR

Adjustments: Child gender, 

maternal social class, siblings at 

birth, maternal smoking in 

pregnancy, and DDE levels in cord 

blood for wheezing outcome

Newson, et al., 2004176

Outcome domain: Respiratory illness

Study name: Avon Longitudinal Study of 

Parents and Children (ALSPAC)

Study dates: Recruitment: April 1, 1991 to 

December 31, 1992 Followup: 42 months

Study design: Observational prospective

Location: UK

Funding source / conflict: Government, Multiple

foundations and Societies

Follow-up: 42 months

Original, same study, or follow-up studies: 

Golding et al., 2001 (ALSPAC)

Study Population: Healthy infants

Pregnant enrolled 4136

Infants enrolled 4202 Infants completers 1762

Infant age: Prenatal

Race of Mother: NR (100%)

Inclusion Criteria: Pregnant women with 

expected date of delivery between April 1, 

1991, and December 31, 1992, and place of 

residence within the 3 Bristol-based health 

districts of the former county of Avon, United 

Kingdom

Exclusion Criteria: NR for enrollment. 

Exclusion for analysis: multiple pregnancies or 

in small missing value categories for various 

confounders.

Adjustments: Child’s sex, 

gestational age at birth, and birth 

weight, and for the mother’s age, 

education level, housing tenure, 

parity, ethnicity, and smoking in 

pregnancy (for variable categories 

see Table EI in the Journal’s Online 

Repository at 

http://www.mosby.com/jaci), as well 

as maternal atopic disease (asthma, 

eczema, rhinoconjunctivitis), child’s 

head circumference at birth ( < 33 

cm, 33-34.99 cm, 35-36.99 cm, 37+ 

cm, unknown), child’s crown to heel 

length at birth ( < 48 cm, 48-50.99 

cm, 51-53.99 cm, 54+ cm, 

unknown), mother’s body mass 

index (from prepregnancy selfreported weight and height; < 18.5 

kg/m2 , 18.5-24.99 kg/m2 , 25-

29.99 kg/m2 , 30+ kg/m2 , 

unknown), breast-feeding

310
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Notenboom, et al., 2011179

Outcome domain: Respiratory illness

Study name: KOALA Birth Cohort Study

Study dates: Recruitment from October 2000 

onwards and Followup: 6-7 years

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government, 

Multiple foundations and Societies

Follow-up: 3 - 84 months

Study Population: Healthy infants Healthy 

pregnant women

Infants enrolled 1275 Infants completers 1253 

(samples for 815)

Mother age: 32.6 (3.8)

Race of Mother: White European (Dutch 96.3%)

Inclusion Criteria: Conventional participants: 

participation in ongoing study of pelvic girdle 

pain Alternative participants: frequented 

locations associated with organic diet and 

similar lifestyles Subsample: participants 

recruited from January 2002 onwards who 

consented to biosampling.

Exclusion Criteria: Current multiple pregnancy 

n=9 Prematurity n=15 Perinatal infant death 

n=2 Down syndrome n=4 No response after 

birth n=51

Adjustments: Adjusted for 

recruitment group, maternal age, 

maternal ethnicity, maternal 

education level, maternal smoking 

during pregnancy, parental history 

of atopy, term of gestation, season 

of birth, gender, birth weight, mode 

of delivery, exposure to 

environmental tobacco, presence of 

older siblings and sibling atopy, 

breastfeeding, child day care, and 

pets at home

Pike, et al., 2012186

Outcome domain: Respiratory illness

Study name: Southampton Women's Survey

Study dates: 2006-2010

Study design: Observational prospective

Location: UK

Funding source / conflict: Government, Some 

authors serve on scientific advisory boards for 

corporations

Follow-up: Birth to 6 years

Study Population: Healthy infants

Pregnant enrolled

Infants enrolled 1485 Infants completers 865

Pregnant age: 30.4 (3.8)

Race of Mother: NR (100)

Inclusion Criteria: mothers and children in the 

Southampton Women’s Survey

Exclusion Criteria: Infants born = 35 weeks’ 

gestation were excluded to avoid abnormal 

lung development associated with prematurity

Adjustments: Child’s age, maternal 

asthma, and paternal rhinitis for 

airway inflammation outcome

Standl, et al., 2014177

Outcome domain: Respiratory illness

Study name: LISAplus

Study dates: Recruitment 1997-1999

Study design: Observational prospective

Location: Germany

Study Population: Healthy infants

Infants enrolled 436 Infants completers 243

Mother age: 32.7 (3.9) NR

Infant age: Birth (NR) NR

Race of Mother: NR (100)

Inclusion Criteria: NR

Exclusion Criteria: Neonates displaying at 

least one of the following criteria: preterm birth 

(maturity <37 gestational weeks), low birth 

weight (<2,500 g), congenital malformation, 

symptomatic neonatal infection, antibiotic 

medication, hospitalization or intensive 

medical care during neonatal period. In 

addition, newborns from mothers with 

immune-related diseases (autoimmune 

disorders, diabetes, hepatitis B), on long-term 

Adjustments: Parental education, 

sex, time of follow-up (2 yr, 6 yr or 

10 yr for eczema; 6 yr and 10 yr for 

asthma, hay fever/allergic rhinitis 

and aeroallergen sensitization), 

age, maternal age at birth, parental 

atopy, total sum of fatty acids

311
Author, Year, Outcome domain, Study, 

Location, Funding Source, Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Funding source / conflict: Government

Follow-up: 10 years

medication or who abuse drugs and/or 

alcohol, and newborns from parents with a 

nationality other than German or who were not 

born in Germany, were excluded.

Wijga, et al., 2006175

Outcome domain: Respiratory illness

Study name: The Prevention and Incidence of 

Asthma and Mite Allergy (PIAMA) birth cohort 

study

Study dates: 1995-2000

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government

Follow-up: 4 years

Study Population: NR

Pregnant enrolled 276 Pregnant withdrawals 11 

Pregnant completers 265

Infants enrolled 276 Infants withdrawals 11 

Infants completers 265

Pregnant age: 31.0 (3.9) NR

Race of Mother: NR (100)

Inclusion Criteria: Mothers reporting at least 1 

of the following: (a history of) asthma, current 

hay fever, current allergy for pets, or current 

allergy for house dust or house dust mite were 

defined as allergic, and mothers reporting that 

they had none of these were defined as 

nonallergic.

Exclusion Criteria: NR

Adjustments: Sex, number of older 

siblings, maternal age, maternal 

smoking during pregnancy, and 

maternal body mass index before 

pregnancy

Yu, et al., 2015185

Outcome domain: Respiratory illness

Study dates: Participants recruited between 

June 2009 and September 2010

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Study Population: Healthy infants Healthy 

pregnant women

Infants enrolled 1162 Infants completers 960

Pregnant age: NR (NR) NR

Race of Mother: NR (100%)

Inclusion Criteria: Participants were mother–

child pairs in the Growing Up in Singapore 

Towards healthy Outcomes (GUSTO) birth 

cohort.

Exclusion Criteria: NR

Adjustments: In the models, we 

adjusted for maternal characteristics 

including maternal age, ethnicity, 

gravidity, education level and 

energy intake. The same was done 

for infant characteristics including 

sex, birth weight, gestational age, 

duration of breast-feeding, family 

history of allergic diseases (which 

includes allergic rhinitis, eczema 

and asthma in first-degree relatives 

of the children (i.e. father, mother 

and/or sibling), exposure to 

environmental tobacco smoking, 

child day care attendance and 

having a cat or dog at home up to 

18 months of age.

312
Key Question 3: Maternal or Childhood Adverse Events

– What are the short and long-term risks related to maternal intake of n-3s during 

pregnancy or breastfeeding on

• Pregnant women

• Breastfeeding women

• Term or preterm human infants at or after birth

– What are the short and long-term risks associated with intakes of n-3s by human 

infants (as maternal breast milk or infant formula supplemented with n-3 FA)?

– Are adverse events associated with specific sources or doses? 

Key Points

Antenatal supplementation

• Among ten RCTs that reported on maternal adverse events associated with prenatal 

supplementation, three provided no usable data, three reported no difference between 

intervention groups, four reported increased GI complaints in the n-3 FA supplemented 

groups; and one reported a statistically insignificant increase in the incidence of preterm 

birth in the n-3 FA supplemented group. Among five RCTs that reported on infant AEs 

associated with antenatal maternal supplementation, one study provided no usable data; 

one study found no difference between groups, except for longer duration of two types of 

symptoms in infants of supplemented mothers; another study found a decrease in risk for 

SAEs among infants of supplemented mothers; a fourth found a small but significant 

increase in risk for respiratory distress among infants of supplemented mothers but no 

other differences; and a fifth noted one case each of a later infancy neoplasia and 

intractable seizure disorder in the n-3 FA-supplemented group, neither of which were 

attributed to prenatal use of the n-3 FA supplements. 

Supplementation of preterm infants

• Among four RCTs reporting on AEs in supplemented preterm infants, no differences 

were observed in SAEs or AEs (except for an increase in gas in one study, compared with 

placebo). Two reported no differences in adverse outcomes known to be associated with 

preterm birth, and one reported no differences in such outcomes with the exception of 

two findings.

Supplementation of healthy term infants

• Among five RCTs reporting on AEs in supplemented healthy term infants, two studies 

reported a significant increase in non-serious AEs in the placebo group, and only one 

study, a dose-response assessment of DHA, reported an increase in the incidence of an 

AE, watery eyes, in infants receiving the middle dose of DHA.

Description of Included Studies

A total of 20 RCTs described or reported assessing adverse events in 20 publications (see 

Table 28).

29, 31, 32, 35, 58, 98, 107, 108, 111-114, 116, 121, 137, 139, 172, 173 Seven of the studies administered 

supplements to pregnant or breastfeeding women, 29, 31, 32, 35, 50, 58, 98, 130, 172, 173 Ten administered 

supplements to infants.

107, 108, 111-114, 116, 121, 137, 139 One study administered supplements to both 

313
mothers and infants).173 This study reported only one adverse event that was not attributed to 

supplementation with either the intervention or placebo formula. We identified no observational 

studies that reported on adverse effects of exposure to n-3 FA.

Maternal Supplementation

Maternal Outcomes

Of the studies that conducted maternal interventions and reported on maternal outcomes, two

reported no adverse events by study arm130, 172 and one did not identify the AEs or attribute them 

to a study arm98. Incidence of maternal AEs in four of the remaining five studies did not differ 

between intervention and placebo groups. 

A 2003 study randomized 89 breastfeeding women at risk for postpartum depression to 

0.2g/d DHA or placebo in the immediate postpartum period; the duration of the intervention was 

4 months. The study reported that no women withdrew because of adverse effects of the 

supplement.98

Another 2003 study randomized 98 pregnant women in Australia to fish oil (3.7 g of n-3 

PUFAs with 56.0% as DHA and 27.7% as EPA) or placebo capsules daily from 20 weeks 

gestation through term.50 Seven women in the fish oil group and one woman in the placebo 

group dropped out, complaining of nausea. Three women in the fish oil group and one woman in 

the placebo group experienced a preterm birth, although the authors did not attribute this 

outcome to the intervention.

A 2010 study in Sweden randomized 145 pregnant women in the 25th week of gestation to 

fish oil capsules that provided 1.6g EPA and 1.1g DHA per day or soy bean oil capsules as 

placebo; supplementation continued through 3.5 months postpartum. This study did not report 

AEs by study arm.172, 173

A 2011 multisite European study randomized 315 pregnant women to receive fish oil alone, 

fish oil plus 5-MTHF, 5-MTHF alone or placebo daily. This study did not report AEs by study 

arm.130

A 2013 U.S. Phase III RCT randomized 350 pregnant women to supplements containing 

40% DHA (percent of total fats by weight) and 5% AA (the placebo contained ALA and DHA). 

This study found no significant differences between intervention groups in any of 13 categories 

of maternal AEs and SAEs.31

A 2010 multisite Australian trial, the DOMInO trial, randomized 2,399 women at less than 

21 weeks gestation to daily supplements of 0.8g/d DHA or placebo through term.35 The authors 

reported more gastrointestinal distress but less diarrhea among the women who received DHAcontaining supplements. This study also reported no serious adverse events (SAEs) in the 

mothers.35

A 2010 study in Mexico randomized 1,094 pregnant women at 18 to 22 weeks gestation to a 

supplement of 0.4 g/d algal DHA or a placebo. This study reported no difference in the incidence 

of vomiting or nausea between the two groups and reported no SAEs among mothers.

32

A 2010 U.S. study randomized 852 women at high risk of recurrent preterm birth to a daily 

supplement (1.2g/d EPA: 0.8g/d DHA) or matching placebo from 16 to 22 through 36 weeks of 

gestation, and reported an increase in gastrointestinal complaints among n-3 supplemented 

mothers (burping, p=0.001, vomiting p=0.005, bad taste p=0.002).29

314
Infant Outcomes

Among studies with maternal supplementation that reported on infant outcomes, five 

reported on AEs in infants. One of the four found no differences in a large number of infant 

birth-associated AEs.31

A 2003 study randomized 98 pregnant women in Australia to fish oil (3.7 g of n-3 PUFAs 

with 56.0% as DHA and 27.7% as EPA) or placebo capsules daily from 20 weeks gestation 

through term.50 The authors noted one case each of a later infancy neoplasia and intractable 

seizure disorder in the fish oil group, neither of which they attributed to prenatal use of n-3 FA 

supplements.

A 2010 study in Mexico randomized 1,094 pregnant women at 18 to 22 weeks gestation to a 

supplement of 0.4 g/d algal DHA or a placebo. The effects of maternal supplementation on infant 

health and adverse health outcomes were assessed at birth 32 and at 1, 3, and 6 months.58 At birth, 

total AEs and SAEs (including congenital anomalies) did not differ between groups of infants.32

Maternal reports of symptoms of illnesses and duration of illnesses, including fever, vomiting, 

diarrhea, rash and other illnesses did not differ between groups at 1, 3, or 6 months of age. 

However, the relative risk of longer duration of rash was greater for infants of DHAsupplemented mothers than for infants of control mothers at 1 month (RR1.22[1.05, 1.41]); the 

relative risk for longer duration of “other illnesses” was less for infants of DHA-supplemented 

mothers at 3 months (RR 0.77[0.62, 0.95]), and at 6 months, the relative risk for longer duration 

of vomiting was greater (RR1.74[1.19, 2.54]) and for rash (RR 0.77[0.64, 0.94]) and other 

illnesses (0.75[0.59, 0.94]) was less for infants of DHA-supplemented mothers.58

A 2010 multisite Australian trial, the DOMInO trial, randomized 2,399 women at less than 

21 weeks gestation to daily supplements of 0.8g/d DHA or placebo through term.35 The authors 

reported fewer SAEs among infants of n-3 FA supplemented mothers than among infants of 

mothers who received the placebo supplements during the first 18 months of life, including a 

decreased risk for any admission to a neonatal intensive care unit (RR 0.57[0.34, 0.97]) and 

decreased risk for death (RR0.33[0.11, 1.03]). No difference in the risk for major congenital 

anomalies was observed between the groups.35

A 2010 U.S. study randomized 852 women at high risk of recurrent preterm birth to a daily 

supplement (1.2g/d EPA: 0.8g/d DHA) or matching placebo from 16 to 22 through 36 weeks of 

gestation. This study observed an increase in the risk for respiratory distress at birth among 

infants of the n-3 FA supplemented mothers compared with infants of mothers given the placebo 

supplement, but no other differences between the groups.29

Infant Supplementation

Among studies of infant supplementation alone, four enrolled preterm infants, and five

enrolled healthy term infants. All randomized infants to a supplement containing combinations 

of DHA and AA.

Preterm Infants

A small study conducted in Taiwan that randomized 27 larger preterm infants to receive 

formula supplemented with 0.05% DHA and 0.1% AA or the identical formula without 

LCPUFA reported no SAEs in either group over the first year of life.137

A multisite Australian study that randomized 657 preterm infants to higher-concentration 

DHA formula (1.0%DHAand 0.6% AA) or lower-concentration DHA formula (0.6% DHA 0.6% 

AA) compared adverse birth outcomes associated with prematurity between groups, and 

observed no difference in rates of mortality, necrotizing enterocolitis (NEC), retinopathy of 

315
prematurity (ROP), interventricular hemorrhage, seizures, blindness, hearing loss, of need for 

oxygen.116

A 2005 U.S. study that randomized preterm infants to one of three infant formulas 

supplemented with algal DHA (0.017g/100 ml) and AA (0.034 g/100ml), the same 

concentrations of fish DHA and algal AA, or placebo oils also reported no difference among the 

groups with respect to parental reports of fussiness, diarrhea, or constipation (data not shown), 

but more gas than usual among the algal DHA and fish DHA-supplemented groups of infants at 

40 weeks and 44 weeks post-menstrual age (p<0.05) but no differences at 53 or 57 weeks.108

This study also found no differences in multiple adverse outcomes that are associated with 

preterm birth. 

A 2008 study in Norway that randomized preterm infants to a supplement added to breast 

milk (0.032g DHA and 0.031 g AA or placebo per100 ml milk) found no difference in 

“registered” AEs between the groups.107 However, the study reported a non-statistically 

significant increase in two adverse outcomes associated with preterm birth in the infants who 

received supplemented milk: longer duration of need for both nasal continuous positive airway 

pressure treatment (28 vs 13 days) and oxygen (13 vs 8 days).

Healthy Term Infants

Included studies of healthy term infants recruited, randomized, and initiated interventions in 

the first week of life. 

A 2005 U.S. study randomized 103 healthy term infants (born at one of two hospitals) to two 

commercial infant formula products: Enfamil with iron supplemented with DHA (0.36% of total 

fatty acids) and AA (0.72% of total fatty acids) or not supplemented.111 Withdrawal from the 

study due to gastrointestinal intolerance of the study formula or to illness not attributable to the 

formula was assessed over 12 months; at no time did withdrawal from the supplemented formula 

group due to gastrointestinal effects significantly exceed that of the group receiving control 

formula. Likewise, withdrawal due to other infant conditions was the same across study groups.

A 2007 multisite U.S. study randomized 244 healthy term infants to receive a soy formula 

fortified with 0.017g DHA/100 kcal from algal oil and 0.034g AA/100 kcal or a control formula 

for 4 months.114 No significant differences were observed between groups for AEs except for the 

following: gastrointestinal reflux was higher in the controls than in the supplemented group (p = 

0.009); the incidence of metabolic or nutritional difficulties (weight loss, poor weight gain, and 

Type 1 glutaric acidemia) was higher in controls than in the supplemented group (p = 0.013). 

The numbers of SAEs were the same for each group, and none were attributed to the study 

products. 

A 2008 Canadian study randomized 30 healthy term infants to one of two formulas: S-26 

Gold supplemented with 0.2% DHA and 0.34% AA (by weight) or the same formula without 

LCPUFA.112 The authors reported no difference between the groups in the incidence of nonserious AEs (e.g., gas, spit-ups, cramps, vomiting, mucus or blood in stools) as reported by 

mothers or in laboratory values at 2 or 6 weeks. 

The 2010 DIAMOND study, a multisite U.S. study, randomized healthy term infants to 

receive formula supplemented with one of three levels of DHA (0.32%, 0.64%, and 0.96%) and 

0.64% AA. No differences were observed in the proportions of infants with at least one AE; in 

any of the 86 symptoms assessed, with the exception of watery eyes (increased only in the 0.64% 

DHA group); and in the numbers with at least one SAE.121 The association between one case of 

sepsis in an infant in the 0.64% DHA group and diet could not be definitively established.

316
A 2014 study in Serbia randomized 213 healthy term infants to one of two types of formula: 

a standard formula fortified with DHA and AA (0.011g/100kcal each) or the same formula 

without LCPUFA (a reference group was breastfed).113 At 4 months of age, the incidence of total 

AEs was nearly 50% higher in the infants receiving the control formula (45 percent) than in the 

infants receiving the fortified formula (24%, p=0.003). The proportion of infants who 

experienced non-serious AEs was three times higher in the control group as in the fortified 

formula group (41.3 percent vs. 13.6 percent), although the proportions of AE by type were 

similar across the two groups (e.g., 50 percent were respiratory tract infections, 24 percent were 

skin infection/eczema, and 10 percent were gastrointestinal problems). The proportion of infants 

who experienced an SAE was higher in the intervention group than in the control group (10.2 

percent vs. 3.3 percent), but the authors attributed only one SAE per group (a combination of 

gastrointestinal complaints) to formula consumption.

317
Table 28. Adverse events

Author, Year,

Study Intervention group and Adverse Event

Dunstan, et al., 200350 Intervention: Pregnant women

Maternal nausea

Fish oil 7/52

Control 1/46

Preterm birth

Fish oil 3/52

Control 1/46

Neoplastic condition of infancy

Fish oil 1/42

Control 0/43

Intractable infantile seizure disorder

Fish oil 1/42

Control 0/43

Carlson et al., 201331 Maternal Serious Adverse Events

Miscarriage

DHA 4/154

Control 3/147

Other prenatal maternal 

hospitalization

DHA 14/154

Control 15/147

Postpartum hospitalization

DHA 1/154

Control 3/147

Infant Serious Adverse Events

Hospitalization and death

DHA 26/154

Control 31/147

Congenital anomalies

DHA 5/154

Control 2/147

Non-serious Adverse Events

Body

DHA 81/154

Control 83/147

Cardiovascular and blood

DHA 80/154

Control 82/147

Eye, Ear, Nose, Throat

DHA 16/154

Control 8/147

Gastrointestinal

DHA 59/154

Control 69/147

Head, Neck, Mental well-being

DHA 38/154

Control 19/147

Infant

DHA 110/154

Control 120/147

Metabolic and Nutrition

DHA 38/154

Control 39/147

Unable to Categorize

DHA 3/154

Control 3/147

Pregnancy, Delivery

DHA 89/154

Control 80/147

Respiratory

DHA 29/154

Control 26/147

Skin

DHA 11/154

Control 10/147

Urogenital

DHA 70/154

Control 85/147

318
Author, Year,

Study Intervention group and Adverse Event

Imhoff-Kunsch et al., 201158 Intervention:

congenital anomalies at birth

DHA 16/547 (2.93%)

control 15/547 (2.74%)

infant deaths

DHA 4/547 (0.73%)

control 8/547 (1.46%)

nausea

DHA 184/547 (33.7%)

control 166/547 (30.3%)

serious adverse event

DHA 25/547 (4.57%)

control 21/547 (3.84%)

stillbirths

DHA 2/547 (0.37%)

control 3/547 (0.55%)

vomiting

DHA 147/547 (26.9%)

control 130/547 (23.8%)

Agostoni et al., 2009139 Intervention: Healthy term infants

any adverse event

Intervention 0/580 (0%)

control 0/580 (0%)

319
Author, Year,

Study Intervention group and Adverse Event

Fleddermann et al., 2014113

Name of study: BeMIM (Belgrade-Munch Infant Milk 

Tri

Intervention: Healthy term infants

formula associated serious AE

Breast-fed 0/45 (0%)

Control 1/92 (1.09%)

Intervention 1/88 (1.14%)

gastrointestinal

Breast-fed 2/45 (4.44%)

Control 6/92 (6.52%)

Intervention 1/88 (1.14%)

not formula associated serious AE

Breast-fed 4/45 (8.89%)

Control 2/92 (2.17%)

Intervention 8/88 (9.09%)

others

Breast-fed 5/45 (11.11%)

Control 3/92 (3.26%)

Intervention 3/88 (3.41%)

respiratory

Breast-fed 18/45 (40%)

Control 21/92 (22.83%)

Intervention 6/88 (6.82%)

skin

Breast-fed 14/45 (31.11%)

Control 7/92 (7.61%)

Intervention 1/88 (1.14%)

total AE

Breast-fed 45/45 (100%)

Control 41/92 (44.57%)

Intervention 21/88 (23.86%)

total non-serious AE

Breast-fed 41/45 (22.2%)

Control 38/92 (41.3%)

Intervention 12/88 (13.6%)

total serious AE

Breast-fed 4/45 (2.2%)

Control 3/92 (3.3%)

Intervention 9/88 (10.2%)

urinary tract

Breast-fed 2/45 (4.44%)

Control 1/92 (1.09%)

Intervention 1/88 (1.14%)

320
Author, Year,

Study Intervention group and Adverse Event

Birch et al., 2010121

Name of study: Diamond

Intervention: Infant

at least one adverse event

0.32 % DHA 76/83 (91.57%)

0.64 % DHA 80/84 (95.24%)

0.96% DHA 80/87 (91.95%)

control 75/85 (88.24%)

at least one serious adverse event

0.32 % DHA 6/83 (7.23%)

0.64 % DHA 6/84 (7.14%)

0.96% DHA 6/87 (6.9%)

control 7/85 (8.24%)

infant watery eyes

0.32 % DHA 1/83 (1.2%)

0.64 % DHA 4/84 (4.76%)

0.96% DHA 0/87 (0%)

control 0/85 (0%)

report of sepsis

0.32 % DHA 0/83 (0%)

0.64 % DHA 1/84 (1.19%)

0.96% DHA 0/87 (0%)

control 0/85 (0%)

Field et al., 2008112 Intervention: Infant

"no difference among groups in the incidence of minor adverse 

events (gas, spit-ups, cramps, vomiting and mucus or blood in 

stools)

./. (.%)

Carlson et al., 201331

Furuhjelm et al., 2011172 Intervention: Maternal

discontinuation due to abdominal pain

3/145 (2.07%)

discontinuation due to inability to swallow capsule

9/145 (6.21%)

discontinuation due to nausea

6/145 (4.14%)

321
Author, Year,

Study Intervention group and Adverse Event

Makrides et al., 201035

Name of study: DOMInO

Intervention: Maternal

infant at least one adverse event (admission to level III (intensive 

care) hospital treatment, major congenital abnormality, or death)

DHA 36/1197 (3.01%)

control 54/1202 (4.49%)

infant death

DHA 4/1197 (0.33%)

control 12/1202 (1%)

infant major congenital abnormality

DHA 15/1197 (1.25%)

control 11/1202 (0.92%)

infant with any admission to neonatal intensive care

DHA 21/1197 (1.75%)

control 37/1202 (3.08%)

mother any level III antenatal hospitalization

DHA 2/1197 (0.17%)

control 2/1202 (0.17%)

mother death

DHA 0/1197 (0%)

control 0/1202 (0%)

Llorente et al., 200398

Name of study: Unnamed Trial A

Intervention: Maternal

no withdrawals due to adverse events

DHA 0/44 (0%)

placebo 0/45 (0%)

Ramakrishnan et al., 201032

Name of study: POSGRAD

Intervention: Maternal

infant born with congenital anomalies (spina bifida, heart 

malformations, considered unrelated to intervention)

DHA 16/547 (2.93%)

control 15/547 (2.74%)

infant death

DHA 4/547 (0.73%)

control 8/547 (1.46%)

stillbirths

DHA 2/547 (0.37%)

control 3/547 (0.55%)

total serious adverse events

DHA 25/547 (4.57%)

control 21/547 (3.84%)

women reported nausea

DHA 184/547 (33.7%)

control 166/547 (30.3%)

women reported vomiting

DHA 147/547 (26.9%)

control 130/547 (23.8%)

322
Author, Year,

Study Intervention group and Adverse Event

Harper et al., 201029 Intervention: Maternal

admission to intensive/intermediate care nursery

omega3 110/427 (25.9%)

placebo 99/410 (24.6%)

bronchopulmonary dysplasia

omega3 9/425 (2.1%)

placebo 6/403 (1.5%)

interventricular hemorrhage, any grade

omega3 10/427 (2.4%)

placebo 9/410 (2.2%)

interventricular hemorrhage, grade 3-4

omega3 5/427 (1.2%)

placebo 3/410 (0.7%)

necrotizing enterocolitis

omega3 3/427 (0.7%)

placebo 4/410 (1%)

patent ductus arteriosus

omega3 11/427 (2.6%)

placebo 7/410 (1.7%)

pregnancy loss or neonatal death

omega3 16/434 (3.7%)

placebo 17/418 (4.1%)

proven sepsis

omega3 5/427 (1.2%)

placebo 3/410 (0.7%)

received surfactant

omega3 38/425 (8.9%)

placebo 29/403 (7.2%)

respiratory distress syndrome

omega3 59/425 (13.9%)

placebo 35/403 (8.7%)

retinopathy of prematurity

omega3 5/427 (1.2%)

placebo 4/410 (1%)

transient tachypnea

omega3 31/425 (7.3%)

placebo 24/403 (6%)

Furuhjelm et al., 2009173 Intervention: Maternal and infant

infant born with an atrioventricular defect and a coarctation of the 

aorta and needed surgery

Intervention 1/52 (1.92%)

control 0/65 (.%)

Fang et al., 2005137 Intervention: Preterm infants

serious AE

Neoangelac 0/11 (0%)

Neoangelac Plus 0/16 (0%)

323
Author, Year,

Study Intervention group and Adverse Event

Clandinin et al., 2005108 Intervention: Preterm infants

adverse events for nervous system

control 19/119 (16%)

fish-DHA 8/130 (6%)

bronchopulmonary dysplasia

algal-DHA 16/112 (15%)

control 17/119 (15%)

fish-DHA 21/130 (17%)

confirmed sepsis

algal-DHA 19/112 (17%)

control 16/119 (13%)

fish-DHA 19/130 (15%)

death during initial hospitalization

control 2/119 (1.68%)

fish-DHA 3/130 (2.31%)

interventricular hemorrhage

algal-DHA 14/112 (13%)

control 32/119 (29%)

fish-DHA 33/130 (27%)

necrotizing enterocolitis

algal-DHA 6/112 (5%)

control 3/119 (3%)

fish-DHA 7/130 (5%)

retinopathy of prematurity

algal-DHA 35/112 (47%)

control 31/119 (42%)

fish-DHA 53/130 (58%)

324
Author, Year,

Study Intervention group and Adverse Event

Henriksen et al., 2008107

Name of study: Unnamed Trial D

Intervention: Preterm infants

NEC, treated, proven

control 0/73 (0%)

intervention 1/68 (1.5%)

NEC, treated, suspected

control 0/73 (0%)

intervention 1/68 (1.5%)

died before discharge

control 2/73 (3%)

intervention 0/68 (0%)

intracranial hemorrhage, grade 1

control 7/73 (10%)

intervention 6/68 (9%)

intracranial hemorrhage, grade 2

control 5/73 (7%)

intervention 3/68 (5%)

intracranial hemorrhage, grade 3-4

control 1/73 (1.5%)

intervention 2/68 (3%)

need for respiratory support

control 29/73 (40%)

intervention 31/68 (46%)

periventricular leukomalacia, 1 or 2 cysts on 1 side

control 0/73 (0%)

intervention 3/68 (4.5%)

periventricular leukomalacia, >2 cysts or bilateral

control 1/73 (1.5%)

intervention 1/68 (1.5%)

retinopathy, any retinopathy

control 13/73 (18%)

intervention 8/68 (12%)

retinopathy, treated retinopathy

control 3/73 (4%)

intervention 3/68 (4%)

325
Author, Year,

Study Intervention group and Adverse Event

Makrides et al., 2009116

Name of study: DINO

Intervention: Preterm infants

Death

high DHA 9/322 (8.89%)

standard DHA 9/335 (2.8%)

blindness

high DHA 0/322 (5.07%)

standard DHA 1/335 (0%)

hearing loss

high DHA 0/322 (0.3%)

standard DHA 1/335 (0%)

interventricular hemorrhage

high DHA 45/322 (2.09%)

standard DHA 44/335 (13.98%)

necrotizing enterocolitis

high DHA 14/322 (2.69%)

standard DHA 7/335 (4.35%)

need for oxygen treatment

high DHA 60/322 (0.3%)

standard DHA 84/335 (18.63%)

retinopathy of prematurity

high DHA 74/322 (13.13%)

standard DHA 73/335 (22.98%)

seizures

high DHA 7/322 (21.79%)

standard DHA 17/335 (2.17%)

326
Author, Year,

Study Intervention group and Adverse Event

Hoffman et al., 2008114 Intervention: Term infants

diarrhea

DHA+ARA 5/96 (5.21%)

control 8/86 (9.3%)

fussiness

DHA+ARA 6/96 (6.25%)

control 6/86 (6.98%)

gastroesophageal reflux

DHA+ARA 3/96 (3.13%)

control 13/86 (15.12%)

poor weight gain

DHA+ARA 0/96 (0%)

control 2/86 (2.33%)

serious AE unrelated to intervention

DHA+ARA 6/96 (6.25%)

control 6/86 (6.98%)

type 1 glutaric acidemia

DHA+ARA 0/96 (0%)

control 1/86 (1.16%)

vomiting

DHA+ARA 4/96 (4.17%)

control 8/86 (9.3%)

weight loss

DHA+ARA 0/96 (0%)

control 3/86 (3.49%)

Birch et al., 2005111 Intervention: Term infants

withdrawal due to gastrointestinal intolerance

LCP 17 wk 0/46 (0%)

LCP 39 wk 1/44 (2.27%)

LCP 52 wk 0/42 (0%)

LCP 6 wk 4/47 (8.51%)

control 17 wk 2/46 (4.35%)

control 39 wk 0/46 (0%)

control 52 wk 0/44 (0%)

control 6 wk 3/48 (6.25%)

withdrawal due to infant illness unrelated to formula

LCP 17 wk 1/46 (2.17%)

LCP 39 wk 1/44 (2.27%)

LCP 52 wk 0/42 (0%)

LCP 6 wk 0/47 (0%)

control 17 wk 0/46 (0%)

control 39 wk 0/46 (0%)

control 52 wk 1/44 (2.27%)

control 6 wk 0/48 (0%)

327
Discussion

Overall Summary of Key Findings 

For this systematic review, we identified 74 RCTs (in 75 publications) and 43 eligible 

prospective longitudinal studies and nested case-control studies that were eligible for inclusion 

based on the prespecified inclusion criteria. Most of the RCTs evaluated the effects of marine oil 

supplements on prenatal weight gain (risk for low birth weight) and length of gestation (risk for 

preterm birth) or the effects of DHA with or without AA as supplements or added to infant 

formulas on infant neural and cognitive development. Most observational studies assessed the 

association between the status of particular n-3 FA and developmental outcomes. 

Within each category of analysis (by outcome, target of intervention, n-3 FA, and study 

design), studies diverged greatly with respect to the sources, doses, and durations of interventions; 

definitions or tests used to measure outcomes; and follow-up times. For outcomes such as visual, 

neurological, and cognitive development, by necessity, the tests used over time (in studies with 

multiple follow-ups) changed to match maturity level. As a result, it was challenging to identify 

groups of studies that were sufficiently similar to pool, even with studies from the original report. 

In addition, many RCTs employed and reported the results of numerous outcome measures, which 

were often internally inconsistent or showed no apparent pattern over time. The majority of studies 

did not find statistically significant findings. A small number of observational studies that were 

excluded from the original report met the inclusion criteria for the current report, and the 

observational studies identified for the current report seldom assessed outcomes that were similar 

to those assessed in RCTs. Additional challenges are described in the Limitations section below.

The original report found inconsistent effects of prenatal maternal supplementation with DHA

on length of gestation and the risk for preterm birth and a consistent finding of no effects of 

prenatal maternal supplementation with EPA+DHA among a large number of RCTs. The current 

report found similar findings for these outcomes in RCTs.

For the current report, pooled analysis of 11 RCTs among healthy pregnant women found a 

significant increase in length of gestations among mothers who received algal DHA or DHAenriched fish oil (WMD +0.34 [95% CI 0.02, 0.67] weeks) compared to placebo. Pooled analysis 

of 7 RCTs showed no significant effect of DHA or DHA-enriched fish oil on the incidence of 

preterm birth.

Pooled analysis of 5 RCTs showed that maternal fish oil supplementation (EPA+DHA) among 

healthy pregnant women had no significant effects on gestational age. Pooled analysis of 9 RCTs 

(in four publications) found no effects of EPA+DHA supplementation on the incidence of preterm 

birth. Prospective studies are sparse and found no consistent associations of maternal exposures 

with outcomes related to length of gestation or preterm birth.

The original report did not find a significant effect of maternal n-3 FA supplementation on the 

risk for low birth weight or SGA or a clear association of any maternal biomarkers with risk for 

low birth weight or birth weight itself. For the current report, we found a moderate level of 

evidence that maternal supplementation with DHA may increase birth weight, and a low level of 

evidence that maternal supplementation with EPA+DHA may not have significant effects on birth 

weight. Pooled analysis of 12 RCTs showed significantly higher birth weights among infants

(mixed term and preterm) whose health pregnant women received algal DHA or DHA-enriched 

fish oil compared with placebo (WMD [95% CI]=90.12 [2.63, 177.62] grams). Pooled analysis of 

five RCTs found no effect of maternal EPA+DHA supplementation on infant birth weight. One 

RCT that assessed the effects of ALA on infant birth weight showed no effects. These findings are 

328
consistent with prospective studies, which found that higher maternal blood DHA concentrations 

were associated with higher birth weight. 

There is also a low level of evidence that maternal supplementation with EPA+DHA may not 

have significant effects on risk for delivering a low birth weight infant among at-risk pregnant 

women, but the evidence is insufficient for the effects of maternal supplementation with DHA on 

risk for delivering a low birth weight infant among healthy pregnant women. Pooled analysis of 

four RCTs showed no significant effects of DHA+EPA supplementation (doses ranged from 2.0 to 

3 g/d) on the incidence of small for gestational age between DHA+EPA supplementation and 

control groups (OR [95% CI]=1.00, CI[0.70, 1.43]). Two RCTs identified for the current study 

that assessed the effects of DHA alone or DHA-enriched fish oil both showed no significant 

effects on the risk for delivering a low birth weight infant among women who were not at risk.

Observational studies were sparse and showed mostly no associations between n-3 intake or 

biomarkers and these outcomes.

The outcome of risk for antenatal and postnatal depression was a new one for this review. 

Three of the four RCTs that assessed the effects of prenatal supplementation with DHA alone, 

DHA+AA, or EPA-enriched fish oil or postnatal supplementation with DHA alone found no 

effects on risk for developing perinatal depression among healthy pregnant women. Prospective 

studies found inconsistent associations of maternal n3FA levels and risk of developing perinatal 

depression. 

The original report found no consistent effect of maternal supplementation with n-3FA on the 

risk for gestational hypertension or preeclampsia. Pooling one study identified for the current 

report and two studies from the original report that randomized high-risk women to DHA 

supplements or placebo resulted in no difference in the risk for gestational hypertension or 

preeclampsia (OR 0.94[0.66, 1.34], I2

=0% (n=2,818); pooling studies of women not at high risk 

wo were randomized to fish oil or placebo also showed no effect (OR 1.04 [0.76 , 1.42], I2= 0%). 

The original report found no, or inconsistent, effects of maternal supplementation or infant 

formula fortification on postnatal growth patterns. For the current report, pooled analysis of five 

RCTs of prenatal supplementation with DHA and EPA or fish oil showed no significant effects on 

weight, length, or head circumference at 18 months. Pooled analysis of three studies of 

fortification of infant formula with DHA and AA also showed no effects on postnatal weight and 

length at 4 months among preterm infants.

The original report found no consistent effect of maternal or infant supplementation with n-3 

FA on neurological developmental outcomes and inconsistent associations with biomarkers. 

Likewise, RCTs identified for the current report found no consistent effects of n-3 FA alone or in 

combination with n-6 FA on any of these outcomes compared with placebo. Two studies reported 

a positive effect of formula supplemented with DHA and AA on Bayley’s PDI scores (an index of 

motor development) in preterm infants at 12 and 18 months, and two RCTs reported positive 

effects on brainstem maturation but mixed effects on gross motor control in term infants 

supplemented with DHA and similarly mixed effects of DHA plus AA. 

The original report found inconsistent effects of maternal and infant supplementation with n-3 

FA on visual acuity development and inconsistencies between behavioral measures and 

electrophysiological measures (VEP). The current report identified one RCT that found that DHA 

supplementation of breast-feeding mothers resulted in improvement in one VEP outcome at 4 and 

8 months of age but not at 5 years of age. We pooled five studies (four from the original report and 

one newly identified) that assessed the effects of supplementing infant formula with any n-3 FA 

on visual acuity development in preterm infants at 4 and 6 months and saw no significant effect of 

329
the intervention over that of placebo, although the effect approached borderline significance. 

Pooling studies (eight from the original report and two identified for the current report) of the 

effects of supplementing infant formula with any n-3 FA or with DHA plus AA on visual acuity 

among term infants showed small but significant effects at 2 months using behavioral methods, 

and at 4 and 12 months using VEP. Thus, results across time and outcome measure were 

inconsistent. 

The original report found inconsistent effects of n-3 FA supplementation on cognitive 

development. We identified ten RCTs of pregnant women that reported cognitive outcomes in 

their offspring (including the only RCT identified in the prior systematic review); only two 

reported significant results. Six RCTs, including two from the previous AHRQ review, reported 

on supplementation for lactating women; none reported significant results. The prior AHRQ 

review included six RCTs in pre-term infants that reported cognitive outcomes, while the current 

one identified an additional six reports on five RCTs. Seven RCTs of pre-term infants reported the 

Bayley MDI score at 18 to 24 months of age; the pooled difference between the intervention and 

placebo groups was significant. The other RCTs reported mixed results. Two studies found no

lasting differences during longterm (8 to 10 years) followup. Regarding healthy infants, the prior 

AHRQ review reported that six of eight RCTs did not find a significant difference between 

intervention and placebo groups in Bayley MDI scores. The current review identified five 

additional reports on four RCTs that measured cognitive outcomes. The pooled difference in MDI 

scores at 18 months was not significant when 3 RCTs were pooled. The RCTs that could not be 

pooled reported insignificant results regarding cognitive outcomes. Among six observational 

studies identified for the current report, only one association was noted: In one study that 

controlled for 18 potential confounders, low levels of AA were associated with lower performance 

IQ and high levels of adrenic acid were associated with lower verbal IQ at age 8; low levels of 

DHA were associated with lower verbal and full scale IQ, however, the authors caution that the 

effect sizes were small. In sum, there is moderate evidence that maternal n-3 supplementation has 

no effect on cognitive outcomes of offspring, while there is low strength evidence that 

supplementing formula for per-term infants may have a positive effect on cognitive outcomes at 

18 months. However, there is insufficient evidence regarding long-term difference in cognitive 

outcomes. Developmental outcomes newly included for the current report were the risk for Autism 

Spectrum Disorders (ASD), Learning Disorders, and Attention Deficit Hyperactivity Disorder 

(ADHD). Two RCTs were identified that assessed the association between n-3 FA and the risk for 

ASD; one studied supplements for pregnant women and the other supplemented formula for preterm infants. Both found no association with diagnosis of ASD. One large observational study on 

this topic was identified; women with the highest quartile of total PUFA intake while pregnant 

were at lower risk of having a child with ASD than women in the lowest quartile (RR 0.67; 95% 

CI 0.49, 0.92), after controlling for many important potential confounders. The authors advised 

that the results should be interpreted with caution, given the small number of cases (317 cases with 

ASD, 17,728 comparison mothers). Regarding ADHD, two RCTs of pre-term infants and one 

RCT of pregnant women measured attention or reported diagnoses of ADHD at long-term followup; each reported no association between supplementation and these outcomes.

Additional outcomes newly included in the current report were risks for atopic 

dermatitis/eczema, risks for allergies, and risks for respiratory illnesses, including asthma. A 

number of studies were conducted in mothers or infants at high familial risk for allergies or 

asthma. Three of four prenatal and three postnatal n-3 FA supplementation studies showed no 

significant effects on the risk for atopic dermatitis/eczema. Six of seven prospective observational 

330
studies also found no associations between n-3 FA exposures and risk for atopic 

dermatitis/eczema; however studies that assessed the association of n-3 FA biomarkers with this 

risk found inconsistent associations with higher plasma levels of DHA, erythrocyte EPA, AA 

levels, and EPA/AA ratios. Metaanalysis of three RCTs that assessed the effect of maternal 

supplementation with DHA plus EPA showed a reduction in the risk for food allergies that was 

not statistically significant. Prospective observational studies showed no consistent associations of 

maternal or infant n-3 FA exposures with risk for allergies. Among seven RCTs that assessed the 

effect of prenatal n-3 FA supplementation on the risk for respiratory illnesses, only two reported 

significant effects, decreases in the risk for asthma, but these effects were not consistent over time. 

A metaanalysis of three postnatal interventions that assessed the effects of fortified formula on risk 

for wheeze found no significant summary effect. Prospective observational studies and biomarker 

studies reported inconsistent associations between various postnatal n-3 FA and n-6 FA exposures 

and risk for respiratory illnesses.

The original report identified 21 RCTs that reported on adverse events with n-3 FA 

supplementation in pregnant women, breastfeeding mothers, and preterm and term infants. Overall 

they found that n-3 FA supplements and fortified formulas were well tolerated. Pregnant and 

breastfeeding women reported no serious adverse events, and adverse events in these groups were 

limited to mild GI symptoms. Among both preterm and term infants, adverse events were largely 

limited to GI symptoms also, with most serious adverse events attributable to morbidities 

associated with prematurity. The current report identified 18 RCTs that reported on adverse 

events. The profile of both non-serious and serious adverse events in this report was identical to 

that of the original report. None of the observational studies identified for the current report 

described adverse events.

Too few studies assessed the effects of increasing doses of n-3 FA using similar populations 

and outcome measures to enable dose-response or threshold estimation.

Few studies stratified outcomes according to risk groups, so it was usually not possible to 

assess whether the effectiveness of omega-3 interventions depended on level of risk. In addition, 

no studies stratified outcomes by baseline n-3 FA status, so it is not possible to assess whether 

adequacy of n-3 FA status might account for differences in outcomes across (or lack of outcomes 

within) studies.

Limitations

Overall, both RCTs and observational studies included in this review had numerous quality 

concerns that could increase the risk for bias. Across RCTs, the most common risk-of-bias 

limitation was a lack of intention-to-treat analyses (54 percent of the included RCTs analyzed data 

per protocol). Of 95 included articles reporting on RCTs, 36 percent failed to describe allocation 

concealment sufficiently to determine whether it was adequate (and many studies failed to 

describe recruitment methods). Blinding of study participants contributed only slightly to potential 

risk of bias because participants were usually infants or children and outcomes were usually 

clinically apparent or assessed in a clinical laboratory. Thirty-seven percent of RCTs were at risk 

of attrition bias due to overall dropout rates greater than 20 percent, although most studies reported 

similar dropout rates between groups. Although 87 percent of the included RCTs reported similar 

baseline demographic characteristics between groups, 57 percent did not report baseline n-3 FA 

intake or status. This omission is a critical concern because baseline n-3 FA status likely affects 

response to changes in n-3 FA intake. 

331
Across observational studies, the most common risk of bias limitation was the lack of 

representativeness of the cohorts to the population of interest: 35 percent were judged to be select 

populations or only somewhat representative. In most cases, these populations were described as 

having high intakes of fish; in several cases, the populations were at higher than average risk for 

the outcome of interest or another condition. Another reporting inadequacy related to the ranges 

and distribution of n-3 FA exposures: Of included observational studies, most of the n-3 FA 

dietary intake assessments included only dietary sources (not n-3 FA supplements). 

Few studies reported adverse events, but among the 20 studies that did report adverse events, 

60 percent did not predefine or prespecify adverse events to be queried, and none used a 

recognized categorization system to prespecify or sort categories or levels of intensity of adverse 

events reported. Only 35 percent reported an active mode of collection of adverse event 

information, and of the studies that reported serious adverse events (or lack thereof), most did not 

define “serious adverse event.” Of additional concern, studies of preterm infants often comingled 

morbidities associated with prematurity (such as bronchopulmonary dysplasia and retinopathy of 

prematurity) and adverse events that might be associated with the intervention. Only one study 

that met inclusion criteria considered whether mercury exposure could account for the findings on 

the effects of fish oil intake, but the findings were equivocal.

The population profiles differed somewhat between RCTs and observational studies. 

Understandably, a number of the RCTs were conducted in women at risk for premature birth, 

gestational hypertension, a low birth weight infant, or women with a personal or family history of 

allergy or asthma. However, most observational studies examining the associations between 

dietary n-3 FA intake or biomarkers of n-3 FA intake and birth, respiratory, allergy, or 

developmental outcomes were conducted in generally healthy populations. Most RCTs were also 

small in size, although most reported doing power calculations. Observational studies that enrolled 

fewer than 250 were excluded by design. 

Study interventions or measured exposures tended to be highly heterogeneous. Studies that 

labeled themselves as studies of DHA alone often included some amount of EPA as well as n-6 

FA (usually AA). Fish oil studies did not always report the oil’s concentration of n-3 and n-6 FA 

in addition to the one of interest. Few studies assessed the effects of EPA alone and only one study 

assessed the effects of ALA alone. Of most concern was the heterogeneity in the description of the 

n-3 and n-6 FA contents of infant formulas and the systematic lack of assessment of formula 

intake (realizing the difficulty of this measurement in human infants). Few trials compared n-3 FA 

dose, formulation (e.g., ratio of EPA to DHA), or source. No trial compared different n-3 to n-6 

FA ratios of supplements or intake. None of the observational studies attempted to determine a 

threshold effect of any associations between n-3 FA and the outcome of interest. Some 

observational studies failed to report median or range data of n-3 FA levels within quantiles, 

confidence intervals (or equivalent) of association hazard ratios, or conducted only linear analyses 

across a full range of n-3 FA values. In addition, studies varied in the range of n-3 FA status (e.g., 

intake level) within each study. The applicability of many of the observational studies to the U.S. 

population may also be limited by the higher baseline intakes of fish and other n-3 FA-containing 

foods and supplements among the populations in these studies.

Among studies that assessed associations between biomarkers of n-3 FA status and an 

outcome of interest, so many different n-3 FA biomarkers were investigated, that it was 

impossible to make comparisons across studies.

Another limitation of many of the studies was the inability or failure to control for potentially 

confounding factors. Observational studies often corrected for a large number of potential 

332
confounders, but many important factors could not be or were not measured; this issue is 

magnified for long-term follow up studies of cognitive development, where environmental factors 

were seldom considered. RCTs that reported cognitive outcomes at long-term follow up also 

rarely controlled for potential confounders, although they did report baseline data on 

characteristics such as SES and parent education, which were usually statistically similar among 

placebo and intervention groups.

For the outcomes related to infant and child development (except for growth patterns), tests 

used to measure most outcomes were numerous and heterogeneous across studies regardless of the 

study designs, and follow-up times varied widely. As a result, studies for a number of outcomes of 

interest could not be pooled, either with studies identified for the original report or with newly 

identified studies. In addition, the multiplicity of measures all but ensured that some outcome 

measure would produce a significant effect. Understandably, studies of cognitive, neurological, 

and visual acuity development with multiple follow-up points were required to use age/stageappropriate outcome measures, but they seldom attempted to account for these changes in outcome 

measures.

The RCTs and observational studies differed in a number of ways, making it difficult to 

compare outcomes across the two study designs. Of note, the doses of n-3 FA supplements in 

RCTs were often much higher than the highest intake reported for observational studies. 

Furthermore, not all observational studies explicitly included n-3 FA supplements in their 

assessment of intake, and almost none of the RCTs attempted to account for background fish or n3 FA intake as an effect modifier. For a very small number of RCTs where no significant 

differences in outcomes were observed between intervention and placebo treatments, posthoc 

analysis found an association between a biomarker of n-3 FA and the outcome of interest. This 

observation would seem to suggest that the apparent lack of effect of the intervention on the 

outcome of interest might be attributable to the participants having had adequate baseline n-3 FA 

status. However, the number of studies that conducted these follow-up analyses was too small to 

draw definitive conclusions. Likewise, very few RCTs assessed reported baseline dietary intakes 

of n-3 FA or biomarker status.

Finally, due to the significant heterogeneity across studies, the interpretation of overall metaanalysis results is limited. Only a small number of RCTs conducted dose response assessments 

(usually with poor results). For those reasons, we did not attempt to do dose-response metaanalysis of observational studies and performed only a small number of meta-regressions on doseresponse across RCTs. 

Future Research Recommendations 

Future RCTs should be designed to determine whether particular populations or individuals 

are more likely to benefit from n-3 FA supplements or fortified formulas, e.g., individuals with 

relatively low baseline intakes of n-3 FA. 

Therefore, studies need to measure—and match intervention groups according to—baseline n3 FA biomarker status (although the current report has not clearly revealed the most relevant 

biomarkers). Researchers need to reach consensus on standardized formulations and on reporting 

of concentrations for interventions. The results of this review should help guide these decisions.

Studies also need to ascertain whether n-3 FA are more effective in individuals at increased 

risk for particular conditions (such as low birth weight, preterm birth, gestational hypertension, or 

for infants, risk for delayed visual acuity development or atopy). 

333
Some recent evidence suggests that individuals’ abilities to benefit from dietary 

supplementation with n-3 FA (or breastfeeding) is influenced by polymorphisms within the gene 

encoding FADs2, an enzyme involved in the desaturation of fatty acids to convert precursors to 

LCPUFAs such as DHA. If these findings are confirmed, future studies may need to perform 

genetic profiles on potential participants and to exclude those who are genetically incapable of 

responding to supplementation.

Finally, identifying the most promising and clinically relevant outcome measures will be 

important to expanding the strength of the evidence base for the effectiveness of supplemental n-3 

FA for maternal and childhood outcomes. The findings of large cohort studies are still needed to 

assess the potential role of n-3 FA status in the risk for conditions such as autism spectrum 

disorder, learning disabilities, and ADHD; however, it may be necessary first to identify clear 

intermediate risk factors for these conditions, because the length of follow-up needed for diagnosis 

of the conditions themselves greatly increases the potential interference of other confounding 

factors.

Conclusions

Maternal Exposures and Birth Outcomes

Strength of evidence (SoE) is low for a small positive effect of algal docosahexaenoic acid 

(DHA) or DHA-enriched fish oil on length of gestation compared with placebo; strength of 

evidence is low regarding an apparent lack of effect of DHA or DHA-rich fish oil on risk for 

preterm birth. Strength of evidence is insufficient to draw conclusions about effects or associations 

for other n-3 FA alone or in combination. Observational studies did not show consistent 

associations of n-3 FA exposures (intake measurements or biomarkers) with these outcomes. 

SoE is also moderate for a positive effect of algal DHA or DHA-enriched fish oil on birth 

weight but strength of evidence is insufficient to draw conclusions for the effects of most n-3 FA 

interventions on low birth weight or small-for-gestational age (SGA) infants; maternal n-3 FA 

biomarkers were significantly associated with birth weight, and low SoE supports an association 

of low early pregnancy plasma EPA and risk for SGA. 

A low SoE supports a lack of effect of DHA or DHA-rich fish oil on (or association of n-3 FA 

with) risk for gestational hypertension SoE is insufficient to draw conclusions about the effects of 

other n-3 FA interventions, either pre- or postnatal.

A moderate SoE supports a lack of effect of DHA supplementation on the risk for gestational 

hypertension or preeclampsia among high-risk pregnant women. SoE is insufficient to draw 

conclusions regarding the effects of other interventions.

Infant and Child Outcomes

A moderate SoE supports a lack of effect of prenatal maternal supplementation with fish oil or 

DHA plus EPA on postnatal growth patterns (attainment of weight, length, and head 

circumference); a low SoE supports a lack of effect of pre- and postpartum maternal 

supplementation on these outcomes. SoE is insufficient to draw conclusions about the effects of 

other pre- or postnatal maternal interventions. A low SoE supports a lack of effect of DHA plus 

AA-fortified infant formulas on growth patterns of preterm or term infants. SoE is insufficient 

regarding effects of other n-3 FA or supplementation at other times on growth patterns.

334
A moderate SoE supports a lack of consistent effect of prenatal DHA on development of visual 

acuity in infants. SoE is insufficient to draw conclusions regarding the effects of other n-3 FA 

supplementation of pregnant or breastfeeding women on visual acuity. A low SoE supports a lack 

of effect of supplementation of infant formula with any n-3 FA on visua acuity measured in 

preterm infants at 4 or 6 months corrected age. A moderate SoE supports an effect of 

supplementation of infant formula with any n-3 FA on VEP-measured visual acuity development 

in term infants at 4 and 12 months of age but not on visual acuity measured using behavioral 

methods. A low SoE supports a small positive effect of supplementation of term infant formula 

with DHA plus AA on VEP but not on visual acuity measured using behavioral methods in term 

infants at 4 and 12 months. 

A low SoE supports inconsistent effects of prenatal DHA on any measure of neurological 

development; insufficient SoE supports conclusions regarding the effects of any other n-3 FA 

supplementation of pregnant or breastfeeding mothers, or supplementation of preterm or term 

infants on measures of neurological development or associations of prenatal n-3 FA biomarker 

status and n-3 FA intakes with infant neurological development. 

Regarding cognitive developmental outcomes, a moderate SoE supports a lack of effect of 

supplementation of pregnant women with either DHA plus AA or DHA plus EPA on cognitive 

outcomes in offspring. A low SoE supports lack of consistent effect of n-3 supplementation for 

full term infants on cognitive outcomes; there is moderate SoE that supplementing pre-term 

infants’ formula with DHA plus AA may have a positive effect on infant cognition. There is 

insufficient evidence that any n-3 infant supplements are associated with long-term cognitive 

outcomes. 

A low SoE supports the conclusion that n-3 FA status is unrelated to risk for autism spectrum 

disorders or ADHD. 

A low SoE supports inconsistent effects of prenatal or postnatal n-3 FA supplementation on 

the risk for atopic dermatitis/eczema and allergies and associations of biomarkers and intakes with 

these outcomes. A moderate SoE supports a lack of effect of prenatal and postnatal infant n-3 FA 

supplementation on the risk for asthma and other respiratory illnesses. A low level of evidence 

supports inconsistent associations between n-3 FA exposures and risk for respiratory illnesses.

Table 29 summarizes the findings for which we identified a low, moderate, or high strength of 

evidence (SoE) for an effect or no effect of n-3 FA. 

Adverse Events

A moderate SoE supports a lack of serious adverse events (AEs) among pregnant women and 

infants who consume supplemental n-3 FA or foods fortified with n-3 FA; a moderate SoE 

supports a lack of non-serious AEs, with the exception of an increased risk for mild 

gastrointestinal symptoms, among pregnant women and infants who consume supplemental n-3 

FA. 

Overall Conclusions

Most studies identified for this report examined the effects of marine oil (or other 

combinations of DHA and EPA) supplements on pregnant or breastfeeding women or the effects 

of infant formula fortified with DHA plus arachidonic acid. With the exception of small effects on 

birth weight and length of gestation (confirming the findings of the original report), n-3 FA 

supplementation or fortification has no consistent evidence of effects on peripartum maternal or 

335
infant health outcomes. No effects of n-3 FA were seen on gestational hypertension, peripartum 

depression, or postnatal growth. Apparent effects of n-3 FA supplementation were inconsistent 

across assessment methods and followup times for outcomes related to infant visual acuity and 

cognitive development and prevention of allergy and asthma. Evidence was insufficient to draw 

conclusions regarding effects of n-3 FA on or associations of n-3 FA exposures with autism 

spectrum disorders, ADHD, and learning disabilities. Future RCTs need to assess standardized 

preparations of n-3 and n-6 FA, using a select group of clinically important outcomes, on 

populations with baseline n-3 FA intakes typical of those of most western populations. 

336
Table 29. Conclusions with strength of evidence for an effect or lack of effect

Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

Maternal outcomes

Length of gestation Healthy pregnant women:

n-3 FA*d supplementation 

12 RCTs

4 observational studies

Moderate RCTs: Increase in 

gestational length compared 

with placebo

Meta-analysis of 12 RCTs in 

update: 

WMD 0.33 (95% CI 0.04, 

0.62) weeks.

Observational studies: No 

associations.

Original report: mixed 

findings

.

Length of gestation Healthy pregnant women:

Algal DHA or DHA-enriched fish oil 

supplementation 

11 RCTs

4 observational studies

Moderate RCTs: Increase in 

gestational length compared 

with placebo

Meta-analysis of 11 RCTs in 

update: WMD 0.34 (95% CI 

0.02, 0.67) weeks

Observational studies: No 

associations.

Original report: mixed 

findings

Length of gestation Healthy pregnant women:

EPA+DHA fish oil supplementation

7 RCTs

4 observational studies

Low RCTs: No significant effects 

on gestational length

compared with placebo

Observational studies: 3 of 4 

found no association. 

Original report: no effects 

founde

Risk for preterm birth Healthy pregnant women:

Algal DHA or DHA-enriched fish oil 

supplementation

7 RCTs Low RCTs: No significant effects 

on the incidence of preterm 

birth compared with placebo

Meta-analysis of 7 RCTs: 

OR 0.87 (95% CI 0.66, 1.15)

Risk for preterm birth At-risk pregnant women:

EPA+DHA fish oil supplementation 

9 RCTs

2 observational studies

Low RCTs:No significant effects 

on the incidence of preterm 

birth compared with placebo

Meta-analysis of 9 RCTs: 

0.86 (95% CI 0.65, 1.15)

Observational studies 

337
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

showed mixed results.

Birth weight Healthy pregnant women:

n-3 FA* supplementation

16 RCTs

10 observational studies

Moderate RCTs: Significant Increase 

in birth weight compared 

with placebo

Meta-analysis of 16 RCTs in 

update: WMD 74.8 (95% CI 

12.4, 137.17) grams.

Observational studies of 

dietary intake, supplement 

use, and biomarkers 

generally showed positive 

associations with birth 

weight.

Original report: Mixed 

findings

Birth weight Healthy pregnant women:

Algal DHA or DHA-enriched fish oil 

supplementation

12 RCTs

3 observational studies

Moderate RCTs: Significant Increase 

in birth weight compared 

with placebo

Meta-analysis of 12 RCTs: 

WMD 90.12 (95% CI 2.62, 

177.62) grams

Observational studies 

showed associations 

between DHA intake and 

biomarkers and birth weight.

Original report: mixed 

findings

Birth weight Healthy pregnant women:

EPA+DHA fish oil supplementation

5 RCTs

4 observational studies

Low RCTs: No significant effects 

on birth weight compared 

with placebo

Meta-analysis of 5 RCTs: 

WMD 37.89 (95% CI -19.53, 

95.31) grams

Observational studies 

showed mixed associations 

with birth weight.

Original report: no effects

Low birth weight Healthy pregnant women:

Algal DHA or DHA-enriched fish oil 

supplementation

4 RCTs Low RCTs: No significant effects 

on risk of low birth weight 

compared with placebo

Meta-analysis of 4 RCTs: 

OR 0.72 (95% CI 0.43, 1.11)

SGA / IUGR At-risk pregnant women: 

EPA+DHA or fish oil supplementation 

4 RCTs

2 observational studies

Low RCTs: No significant effects 

on SGA/IUGR compared 

338
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

with placebo

Observational studies: no 

consistent association with 

SGA

Meta-analysis of 4 RCTs: 

OR 1.00 (95% CI 0.70, 1.43)

Gestational hypertension Normal-risk pregnant women: 

DHA supplementation 

3 RCTs Low RCTs: No significant effect 

on risk for gestational 

hypertension in normal risk 

women

Meta-analysis of 3 RCTs 

OR 0.94 (95% CI 0.66, 1.34)

Gestational hypertension High-risk pregnant women:

Marine oil supplementation 

3 RCTs Moderate RCTs: No significant effect 

on risk for gestational 

hypertension among highrisk women

Meta-analysis of 3 RCTs 

OR 1.04 (95% CI 0.76 , 

1.42)

Peripartum depression Pregnant women:

Prenatal DHA, DHA-rich fish oil,

DHA+AA, EPA+DHA/fish oil, or any n3 FA

4 RCTs

8 observational studies

Low RCTs: Nosignificant effect 

on risk for peripartum 

depression across studies.

Observational studies 

showed no associations with 

risk for depression.e

Infant and child outcomes

Postnatal growth patterns Pregnant women:

Fish oil or DHA+EPA supplementation 

7 RCTs

2 observational studies

Moderate RCTs: No significant effect 

on postnatal growth patterns 

among healthy term infants. 

Observational studies: 

Consistent with RCTse

Postnatal growth patterns Breastfeeding women:

Supplementation with any n-3FA

6 RCTs

1 observational study

Low RCTs: No- significant effect 

on postnatal growth patterns

Observational study: 

consistent with RCTse

Postnatal growth patterns Preterm or term infants:

Feeding infant formula fortified with 

DHA+AA 

47 RCTs Low RCTs: No significant effect 

on postnatal growth 

patternse

Visual acuity Pregnant women:

Supplementation with DHA-enriched 

fish oil

4 RCTs Low RCTs: No significant effect 

on development of visual 

acuity in infants.e

Visual acuity Preterm infants:

Feeding infant formula supplemented 

with any n-3 FA

5 RCTs Low VEP

RCTs: No significant effect 

in preterm infants 4 months

339
Outcome Intervention/Exposure Study Design

a Strength of Evidenceb Conclusionc

corrected age 

WMD -0.06 (−0.12; 0.01)

Visual acuity Preterm infants:

Feeding infant formula supplemented 

with any n-3 FA

5 RCTs Low VEP

RCTs: No significant effect 

on development of visual 

acuity in preterm infants 6

months corrected age WMD -0.04 (-0.09, 0.01)

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

6 RCTs Low Behavioral measures 

RCTs: Significant effect at 2 

months

WMD 0.07 (0.00, 0.14) six 

RCTs

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

6 RCTs Low VEP

RCTs: No significant effect 

at 2 months

WMD 0.07[-0.03, 0.17], six 

RCTs

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

6 RCTs Low Behavioral measures 

RCTs: No significant effect 

at 4 months

WMD -0.05 (-0.08, 0.01) six 

RCTs

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

6 RCTs Moderate VEP

RCTs: Significant effect at 4 

months

WMD -0.10(-0.14, -0.07), six 

RCTs

Visual acuityTerm infants:

Feeding infant formula supplemented 

with any n-3 FA

8 RCTs Low Behavioral measures

RCTs:No significant effect of n-3 FA at 12 months WMD -

0.10 (-0.14, 

-0.07)

Visual acuity Term infants:

Feeding infant formula supplemented 

with any n-3 FA

8 RCTs Moderate VEP 

RCTs: Significant effect of n-

3 FA at 12 months

WMD -0.14 

(-0.17, -0.12)

Visual acuity Term infants:

Feeding DHA plus AA-fortified infant 

formula

7 RCTs Low VEP

RCTs: Significant effect of 

DHA+AAat 4 months.

WMD -0.10(-0.14, -0.07)

Visual acuity Term infants:

Feeding DHA plus AA-fortified infant 

6 RCTs Moderate VEP

RCTs: Significant effect of 

340
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

formula DHA+AA at 12 months

WMD -0.14 (-0.17, -0.12)

Neurological development Pregnant women:

Supplementation with any n-3 FA

17 RCTs

5 observational studies

Low RCTs: No significant effects 

on measures of neurological 

development across studies 

(insufficient numbers of 

studies of any outcomes to 

pool) consistent with 

observational studies.e

Cognitive development Pregnant women:

Supplementation with 

DHA+EPA or DHA + AA

10 RCTs Moderate RCTs: No significant effects

on cognitive development

across studiese

Cognitive development Preterm infants:

Supplementation with any n-3 FA

11 RCTs Moderate RCTs: Significant increase in 

cognitive (MDI) scores

WMD 2.24; (95% CI 0.05, 

4.43)

Cognitive development Term infants:

Supplementation with DHA+ AA

12 RCTs Low RCTs: No significant effect 

on cognitive development at 

18-24 months 

WMD 0.75, 95% CI -9.29, 

10.79

Autism Spectrum Disorders

(ASD)

Pregnant women or preterm infants:

Supplementation with DHA

2 RCTs

1 observational study

Low RCTs: No significant effect 

on risk for ASD; association 

shown for intake of n-3 FA in 

observational studye

ADHD Pregnant women or preterm infants:

Supplementation with DHA

3 RCTs Low RCTs: No significant effect 

on risk for ADHDe

Atopic dermatitis/ eczema Pregnant women:

Supplementation with any n-3 FA or 

exposures as assessed by biomarkers

4 RCTs Low RCTs: No significant (and 

inconsistent) effects on risk 

for atopic dermatitis/eczema

Atopic dermatitis/ eczema Breastfeeding women or infants: 

Supplementation of mothers or infants 

through formula fortification with any n3 FA or exposure as assessed with 

biomarkers 

3 RCTs 

7 observational studies

Low RCTs: No significant (and 

inconsistent) effects on risk 

for atopic dermatitis/eczema

across RCTs, consistent 

with observational studiese

Allergies Pregnant women:

Supplementation with any n-3 FA or 

exposures as assessed by biomarkers

3 RCTs

4 observational studies

(including 3 biomarker 

studies)

Low RCTs: No significant effect 

on the risk for food allergy at 

12 months 

OR 0.54 (95% CI 0.05, 6.2); 

Observational studies: no 

consistent association of 

biomarkers and risk for 

341
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

allergy 

Allergies Breastfeeding women or infants:

Supplementation of mothers or infants 

through formula fortification with any n3 FA or exposure as assessed by 

biomarkers

3 RCTs

2 observational studies

Low RCTs: No significant effect 

on the risk for food or dust 

mite allergy and no 

association of breastmilk or 

infant biomarkers and risk 

for allergies across 

observational studiese

Asthma and other respiratory 

illnesses

Pregnant women:

Supplementation with any n-3 FA

6 RCTs Moderate RCTs: No significant effect 

on the risk for asthma and 

other respiratory illnesses

Meta-analysis of 3 RCTs OR 

0.95 95% CI 0.77, 1.16

Asthma and other respiratory 

illnesses

Breastfeeding women or infants:

Supplementation of mothers or infants

through formula fortification with any n3 FA

3 RCTs Moderate RCTs: No significant effect 

on the risk for asthma and 

other respiratory illnessese

Asthma and other respiratory 

illnesses

Pregnant women or infants:

Any n-3 FA exposures 

10 observational studies Low Observational Studies: 

Inconsistent associations 

with risk for respiratory 

illnesses across studies.

e

Asthma and other respiratory 

illnesses: Wheeze

Breastfeeding women or infants:

Supplementation of mothers or infants 

through formula fortification with DHA

3 RCTs

5 observational studies

4 biomarkers studies

Low RCTs: No significant effect 

on risk for wheeze at 12 

months; meta-analysis of 3 

RCTs:

OR 1.06 (95% CI 0.73,1.54)

Observational studies: 

showed Inconsistent 

associations with risk for 

wheeze across studies

Adverse events

Maternal adverse events

Non-serious

Pregnant or breastfeeding women:

Supplementation with n-3 FA in the 

form of fish oil

9 RCTs Moderate RCTs: Increased risk for 

mild gastrointestinal 

symptoms but no other 

consistent non-serious 

adverse events.

e

Maternal adverse events 

serious

Pregnant or breastfeeding women:

Supplementation with n-3 FA in the 

form of fish oil

4 RCTs Moderate RCTs: No significant 

difference in risk for serious 

adverse events.

e

Infant adverse events nonseriousHealthy term infants or preterm 

infants:

Supplementation with n-3 FA in the 

form of fish oil alone or added to infant 

13 RCTs Moderate RCTs:Increased risk for mild 

gastrointestinal symptoms 

across studies but no other 

consistent non-serious 

342
Outcome Intervention/Exposure Study Designa Strength of Evidenceb Conclusionc

formula adverse events.

e

Infant adverse events serious Healthy term infants: Supplementation 

with n-3 FA in the form of fish oil

6 RCTs Moderate RCTs:No significant 

difference in risk for serious 

adverse events.

e

Infant adverse events serious Preterm infants:

Supplementation with n-3 FA in the 

form of fish oil

RCTs Low RCTs:No significant 

difference in risk for serious 

events associated with 

preterm birth.

e

AA = arachidonic acid; ALA = alpha linolenic acid; CI = confidence interval; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; IUGR = intrauterine 

growth retardation; n-3 FA = omega-3 fatty acid; OR odds ratio; RCT = randomized controlled trial; SGA = small for gestational age; VEP = visual evoked 

potentials; WMD = weighted mean difference

a

Figures represent numbers of studies considered as evidence in drawing the conclusion; b

Strength of evidence (SoE) was assessed using a modification of the GRADE method; the assessments for each domain considered in assigning the overall SoE 

grade are provided in Appendix G for each outcome; RCT outcomes were compared with observational study outcomes, when available, to contribute to the 

“consistency” domain; c

Meta-analysis results are shown for all outcomes for which studies were pooled; remaining conclusions are based on trends across studies; d

Any n-3 FA refers to a pooled analysis of studies that employed any or unspecified n-3 FA; e

RCTs determined to be too heterogeneous to permit pooling.

343
References

1. Institute of Medicine of the National Academies. 

Dietary reference intakes for energy, carbohydrate, 

fiber, fat, fatty acids, cholesterol, protein, and amino 

acids / Panel on Macronutrients, Panel on the 

Definition of Dietary Fiber, Subcommittee on Upper 

Reference Levels of Nutrients, Subcommittee on 

Interpretation and Uses of Dietary Reference Intakes, 

and the Standing Committee on the Scientific 

Evaluation of Dietary Reference Intakes, Food and 

Nutrition Board. Available at: 

http://www.nal.usda.gov/fnic/DRI/DRI_Energy/energ

y_full_report.pdf The National Academies Press. 

Washington, DC: 2005.

2. Lewin GA, Schachter HM, Yuen D, et al. Effects 

of omega-3 fatty acids on child and maternal health. 

Evidence report/technology assessment. 2005 

Aug;(2005)(118):1-11.

3. Gould JF, Makrides M, Colombo J, et al. 

Randomized controlled trial of maternal omega-3 

long-chain PUFA supplementation during pregnancy 

and early childhood development of attention, 

working memory, and inhibitory control. Am J Clin 

Nutr. 2014 Apr;99(4):851-9. PMID: 24522442.

4. Schoeller DA, Thomas D, Archer E, et al. Selfreport-based estimates of energy intake offer an 

inadequate basis for scientific conclusions. Am J Clin 

Nutr. 2013 Jun;97(6):1413-5. PMID: 23689494.

5. Archer E, Hand GA, Blair SN. Validity of US 

Nutritional Surveillance: National Health and 

Nutrition Examination Survey Caloric Energy Intake 

Data, 1971-2010. PLoS One. 2013 Oct 9;8(10)PMID: 

WOS:000325810900079.

6. Fekete K, Marosvolgyi T, Jakobik V, et al. 

Methods of assessment of n-3 long-chain 

polyunsaturated fatty acid status in humans: a 

systematic review. Am J Clin Nutr. 2009 

Jun;89(6):2070S-84S. PMID: 19420097.

7. Serra-Majem L, Nissensohn M, Overby NC, et al. 

Dietary methods and biomarkers of omega 3 fatty 

acids: a systematic review. Br J Nutr. 2012 Jun;107 

Suppl 2:S64-76. PMID: 22591904.

8. Hill AB. The Environment and Disease: 

Association or Causation? Proc R Soc Med. 1965 

May;58:295-300. PMID: 14283879.

9. Methods Guide for Effectiveness and Comparative 

Effectiveness Reviews. AHRQ Publication No. 

10(14)-EHC063-EF. Rockville, MD: Agency for 

Healthcare Research and Quality. January 2014. 

Chapters available at: 

www.effectivehealthcare.ahrq.gov.

10. American College of Obstetricians, 

Gynecologists. Committee on Obstetric, Practice. 

Committee opinion no. 453: Screening for depression 

during and after pregnancy. Obstet Gynecol. 2010 

Feb;115(2 Pt 1):394-5. PMID: 20093921. 

11. Higgins JP, Altman DG, Gotzsche PC, et al. The 

Cochrane Collaboration's tool for assessing risk of 

bias in randomised trials. BMJ. 2011;343:d5928. 

PMID: 22008217.

12. Wells G, Shea B, O'Connell J, et al. The 

Newcastle-Ottawa Scale (NOS) for assessing the 

quality of nonrandomised studies in meta-analysis. 

2010. 

http://www.ohri.ca/programs/clinical_epidemiology/o

xford.asp. Accessed on May 5 2014.

13. Lichtenstein AH, Yetley EA, Lau J. Application 

of systematic review methodology to the field of 

nutrition. J Nutr. 2008 Dec;138(12):2297-306. PMID: 

19022948.

14. Chung M, Balk EM, Ip S, et al. Reporting of 

systematic reviews of micronutrients and health: a 

critical appraisal. Am J Clin Nutr. 2009 

Apr;89(4):1099-113. PMID: 19244363.

344
15. Newberry SJ, Chung M, Shekelle PG, et al. 

Vitamin D and Calcium: A Systematic Review of 

Health Outcomes (Update). Evidence 

Report/Technology Assessment No. 217. (Prepared by 

the Southern California Evidence-based Practice 

Center under Contract No. 290-2012-00006-I.) AHRQ 

Publication No. 14-E004-EF. Rockville, MD: Agency 

for Healthcare Research and Quality. September 2014.

16. Chou R, Aronson N, Atkins D, et al. Assessing 

Harms When Comparing Medical Interventions. 

Methods Guide for Effectiveness and Comparative 

Effectiveness Reviews. Rockville (MD); 2008.

17. Hartung J. An alternative method for metaanalysis. Biometrical Journal. 1999;41(8):901-16. 

PMID: 15206538.

18. Hartung J, Knapp G. A refined method for the 

meta-analysis of controlled clinical trials with binary 

outcome. Stat Med. 2001 Dec 30;20(24):3875-89. 

PMID: 11782040.

19. Sidik K, Jonkman JN. Robust variance estimation 

for random effects meta-analysis. Computational 

Statistics & Data Analysis. 2006;50(12):3681-701.

20. Sánchez-Meca J, Marín-Martínez F. Confidence 

intervals for the overall effect size in random-effects 

meta-analysis. Psychol Methods. 2008 Mar;13(1):31-

48. PMID: 18331152.

21. Higgins JP, Thompson SG, Deeks JJ, et al. 

Measuring inconsistency in meta-analyses. BMJ. 2003 

Sep 6;327(7414):557-60. PMID: 12958120.

22. R Core Team (2015). R: A language and 

environment for statistical computing. Vienna, 

Austria: Computing RFfS. http://www.R-project.org/.

23. Shekelle PG, Motala A, Johnsen B, et al. 

Assessment of a method to detect signals for updating 

systematic reviews. Syst Rev. 2014;3:13. PMID: 

24529068.

24. Hamling J, Lee P, Weitkunat R, et al. Facilitating 

meta-analyses by deriving relative effect and precision 

estimates for alternative comparisons from a set of 

estimates presented by exposure level or disease 

category. Stat Med. 2008 Mar 30;27(7):954-70. 

PMID: 17676579.

25. Ahmadzai N, Newberry SJ, Maglione MA, et al. 

A surveillance system to assess the need for updating 

systematic reviews. Syst Rev. 2013;2:104. PMID: 

24225065.

26. Greenland S, Longnecker MP. Methods for trend 

estimation from summarized dose-response data, with 

applications to meta-analysis. Am J Epidemiol. 1992 

Jun 1;135(11):1301-9. PMID: 1626547.

27. Orsini N, Li R, Wolk A, et al. Meta-analysis for 

linear and nonlinear dose-response relations: 

examples, an evaluation of approximations, and 

software. Am J Epidemiol. 2012 Jan 1;175(1):66-73. 

PMID: 22135359.

28. Olsen SF, Secher NJ, Tabor A, et al. Randomised 

clinical trials of fish oil supplementation in high risk 

pregnancies. Fish Oil Trials In Pregnancy (FOTIP) 

Team. BJOG. 2000 Mar;107(3):382-95. PMID: 

10740336.

29. Harper M, Thom E, Klebanoff MA, et al. Omega3 fatty acid supplementation to prevent recurrent 

preterm birth: a randomized controlled trial. Obstet 

Gynecol. 2010 Feb;115(2 Pt 1):234-42. PMID: 

20093894.

30. Pietrantoni E, Del Chierico F, Rigon G, et al. 

Docosahexaenoic acid supplementation during 

pregnancy: a potential tool to prevent membrane 

rupture and preterm labor. Int J Mol Sci. 

2014;15(5):8024-36. PMID: 24810692.

31. Carlson SE, Colombo J, Gajewski BJ, et al. DHA 

supplementation and pregnancy outcomes. Am J Clin 

Nutr. 2013 Apr;97(4):808-15. PMID: 23426033.

345
32. Ramakrishnan U, Stein AD, Parra-Cabrera S, et 

al. Effects of docosahexaenoic acid supplementation 

during pregnancy on gestational age and size at birth: 

randomized, double-blind, placebo-controlled trial in 

Mexico. Food Nutr Bull. 2010 Jun;31(2 Suppl):S108-

16. PMID: 20715595.

33. Stein AD, Wang M, Rivera JA, et al. Auditoryand visual-evoked potentials in Mexican infants are 

not affected by maternal supplementation with 400 

mg/d docosahexaenoic acid in the second half of 

pregnancy. J Nutr. 2012 Aug;142(8):1577-81. PMID: 

22739364.

34. Stein AD, Wang M, Martorell R, et al. Growth to 

age 18 months following prenatal supplementation 

with docosahexaenoic acid differs by maternal 

gravidity in Mexico.[Erratum appears in J Nutr. 2011 

Sep;141(9):1762]. J Nutr. 2011 Feb;141(2):316-20. 

PMID: 21178082.

35. Makrides M, Gibson RA, McPhee AJ, et al. 

Effect of DHA supplementation during pregnancy on 

maternal depression and neurodevelopment of young 

children: a randomized controlled trial. JAMA. 2010 

Oct 20;304(15):1675-83. PMID: 20959577.

36. van Goor SA, Dijck-Brouwer DA, Doornbos B, et 

al. Supplementation of DHA but not DHA with 

arachidonic acid during pregnancy and lactation 

influences general movement quality in 12-week-old 

term infants. Br J Nutr. 2010 Jan;103(2):235-42. 

PMID: 19703327.

37. Hauner H, Much D, Vollhardt C, et al. Effect of 

reducing the n-6:n-3 long-chain PUFA ratio during 

pregnancy and lactation on infant adipose tissue 

growth within the first year of life: an open-label 

randomized controlled trial. Am J Clin Nutr. 2012 

Feb;95(2):383-94. PMID: 22205307.

38. Courville AB, Harel O, Lammi-Keefe CJ. 

Consumption of a DHA-containing functional food 

during pregnancy is associated with lower infant 

ponderal index and cord plasma insulin concentration. 

Br J Nutr. 2011 Jul;106(2):208-12. PMID: 21521543.

39. Judge MP, Harel O, Lammi-Keefe CJ. Maternal 

consumption of a docosahexaenoic acid-containing 

functional food during pregnancy: benefit for infant 

performance on problem-solving but not on 

recognition memory tasks at age 9 mo. Am J Clin 

Nutr. 2007 Jun;85(6):1572-7. PMID: 17556695.

40. Judge MP, Cong X, Harel O, et al. Maternal 

consumption of a DHA-containing functional food 

benefits infant sleep patterning: an early 

neurodevelopmental measure. Early Hum Dev. 2012 

Jul;88(7):531-7. PMID: 22269042.

41. Lucia Bergmann R, Bergmann KE, HaschkeBecher E, et al. Does maternal docosahexaenoic acid 

supplementation during pregnancy and lactation lower 

BMI in late infancy? J Perinat Med. 2007;35(4):295-

300. PMID: 17547539.

42. Mozurkewich EL, Clinton CM, Chilimigras JL, et 

al. The Mothers, Omega-3, and Mental Health Study: 

a double-blind, randomized controlled trial. Am J 

Obstet Gynecol. 2013 Apr;208(4):313.e1-9. PMID: 

23531328.

43. Min Y, Djahanbakhch O, Hutchinson J, et al. 

Effect of docosahexaenoic acid-enriched fish oil 

supplementation in pregnant women with Type 2 

diabetes on membrane fatty acids and fetal body 

composition--double-blinded randomized placebocontrolled trial. Diabet Med. 2014 Nov;31(11):1331-

40. PMID: 24925713.

44. Dunstan JA, Simmer K, Dixon G, et al. Cognitive 

assessment of children at age 2(1/2) years after 

maternal fish oil supplementation in pregnancy: a 

randomised controlled trial. Archives of Disease in 

Childhood Fetal & Neonatal Edition. 2008 

Jan;93(1):F45-50. PMID: 17185423.

45. Knudsen VK, Hansen HS, Osterdal ML, et al. 

Fish oil in various doses or flax oil in pregnancy and 

timing of spontaneous delivery: a randomised 

controlled trial. BJOG. 2006 May;113(5):536-43. 

PMID: 16579802.

346
46. Oken E, Kleinman KP, Olsen SF, et al. 

Associations of seafood and elongated n-3 fatty acid 

intake with fetal growth and length of gestation: 

results from a US pregnancy cohort. Am J Epidemiol. 

2004 Oct 15;160(8):774-83. PMID: 15466500.

47. Badart-Smook A, van Houwelingen AC, Al MD, 

et al. Fetal growth is associated positively with 

maternal intake of riboflavin and negatively with 

maternal intake of linoleic acid. J Am Diet Assoc. 

1997 8/1997;97(8):867-70.

48. Molto-Puigmarti C, van Dongen MC, Dagnelie 

PC, et al. Maternal but not fetal FADS gene variants 

modify the association between maternal long-chain 

PUFA intake in pregnancy and birth weight. J Nutr. 

2014 Sep;144(9):1430-7. PMID: 24991040.

49. Klebanoff MA, Harper M, Lai Y, et al. Fish 

consumption, erythrocyte fatty acids, and preterm 

birth. Obstet Gynecol. 2011 May;117(5):1071-7. 

PMID: 21508745.

50. Dunstan JA, Mori TA, Barden A, et al. Fish oil 

supplementation in pregnancy modifies neonatal 

allergen-specific immune responses and clinical 

outcomes in infants at high risk of atopy: a 

randomized, controlled trial. J Allergy Clin Immunol. 

2003 Dec;112(6):1178-84. PMID: 14657879.

51. Meldrum S, Dunstan JA, Foster JK, et al. 

Maternal fish oil supplementation in pregnancy: a 12 

year follow-up of a randomised controlled trial. 

Nutrients. 2015 Mar;7(3):2061-7. PMID: 25803546.

52. Bergmann RL, Bergmann KE, Richter R, et al. 

Does docosahexaenoic acid (DHA) status in 

pregnancy have any impact on postnatal growth? Sixyear follow-up of a prospective randomized doubleblind monocenter study on low-dose DHA 

supplements. J Perinat Med. 2012 

November;40(6):677-84. PMID: 2012678258.

53. Smithers LG, Gibson RA, Makrides M. Maternal 

supplementation with docosahexaenoic acid during 

pregnancy does not affect early visual development in 

the infant: a randomized controlled trial. Am J Clin 

Nutr. 2011 Jun;93(6):1293-9. PMID: 21490140.

54. Palmer DJ, Sullivan T, Gold MS, et al. Effect of 

n-3 long chain polyunsaturated fatty acid 

supplementation in pregnancy on infants' allergies in 

first year of life: randomised controlled trial. BMJ. 

2012;344:e184. PMID: 22294737.

55. Zhou SJ, Yelland L, McPhee AJ, et al. Fish-oil 

supplementation in pregnancy does not reduce the risk 

of gestational diabetes or preeclampsia. Am J Clin 

Nutr. 2012 Jun;95(6):1378-84. PMID: 22552037.

56. Palmer DJ, Sullivan T, Gold MS, et al. 

Randomized controlled trial of fish oil 

supplementation in pregnancy on childhood allergies. 

Allergy. 2013 Nov;68(11):1370-6. PMID: 24111502.

57. Makrides M, Gould JF, Gawlik NR, et al. Fouryear follow-up of children born to women in a 

randomized trial of prenatal DHA supplementation. 

JAMA. 2014 May 7;311(17):1802-4. PMID: 

24794375.

58. Imhoff-Kunsch B, Stein AD, Martorell R, et al. 

Prenatal docosahexaenoic acid supplementation and 

infant morbidity: randomized controlled trial. 

Pediatrics. 2011 Sep;128(3):e505-12. PMID: 

21807696.

59. Escamilla-Nunez MC, Barraza-Villarreal A, 

Hernandez-Cadena L, et al. Omega-3 fatty acid 

supplementation during pregnancy and respiratory 

symptoms in children. Chest. 2014 Aug;146(2):373-

82. PMID: 24626819.

60. Gonzalez-Casanova I, Stein AD, Hao W, et al. 

Prenatal Supplementation with Docosahexaenoic Acid 

Has No Effect on Growth through 60 Months of Age. 

J Nutr. 2015 Jun;145(6):1330-4. PMID: 25926416.

61. Ramakrishnan U, Stinger A, DiGirolamo AM, et 

al. Prenatal Docosahexaenoic Acid Supplementation 

and Offspring Development at 18 Months: 

Randomized Controlled Trial. PLoS One. 

2015;10(8):e0120065. PMID: 26262896.

347
62. Bouwstra H, Dijck-Brouwer DA, Wildeman JA, 

et al. Long-chain polyunsaturated fatty acids have a 

positive effect on the quality of general movements of 

healthy term infants. Am J Clin Nutr. 2003 

Aug;78(2):313-8. PMID: 12885715.

63. Bouwstra H, Dijck-Brouwer DA, Boehm G, et al. 

Long-chain polyunsaturated fatty acids and 

neurological developmental outcome at 18 months in 

healthy term infants. Acta Paediatr. 2005 

Jan;94(1):26-32. PMID: 15858956.

64. de Jong C, Kikkert HK, Fidler V, et al. The 

Groningen LCPUFA study: no effect of postnatal 

long-chain polyunsaturated fatty acids in healthy term 

infants on neurological condition at 9 years. Br J Nutr. 

2010 Aug;104(4):566-72. PMID: 20370943.

65. de Jong C, Kikkert HK, Fidler V, et al. Effects of 

long-chain polyunsaturated fatty acid supplementation 

of infant formula on cognition and behaviour at 9 

years of age. Dev Med Child Neurol. 2012 

Dec;54(12):1102-8. PMID: 23066842.

66. van Goor SA, Dijck-Brouwer DA, Erwich JJ, et 

al. The influence of supplemental docosahexaenoic 

and arachidonic acids during pregnancy and lactation 

on neurodevelopment at eighteen months. 

Prostaglandins Leukot Essent Fatty Acids; 2011. p. 

139-46.

67. Al MD, van Houwelingen AC, Badart-Smook A, 

et al. The essential fatty acid status of mother and 

child in pregnancy-induced hypertension: a 

prospective longitudinal study. Am J Obstet Gynecol. 

1995 5/1995;172(5):1605-14.

68. Clausen T, Slott M, Solvoll K, et al. High intake 

of energy, sucrose, and polyunsaturated fatty acids is 

associated with increased risk of preeclampsia. Am J 

Obstet Gynecol. 2001 Aug;185(2):451-8. PMID: 

11518908.

69. Oken E, Ning Y, Rifas-Shiman SL, et al. Diet 

during pregnancy and risk of preeclampsia or 

gestational hypertension. Ann Epidemiol. 2007 

Sep;17(9):663-8. PMID: 17521921.

70. Olafsdottir AS, Skuladottir GV, Thorsdottir I, et 

al. Relationship between high consumption of marine 

fatty acids in early pregnancy and hypertensive 

disorders in pregnancy. BJOG. 2006 Mar;113(3):301-

9. PMID: 16487202.

71. Lim WY, Chong M, Calder PC, et al. Relations of 

plasma polyunsaturated Fatty acids with blood 

pressures during the 26th and 28th week of gestation 

in women of Chinese, Malay, and Indian ethnicity. 

Medicine. 2015 Mar;94(9):e571. PMID: 25738474.

72. Muthayya S, Dwarkanath P, Thomas T, et al. The 

effect of fish and omega-3 LCPUFA intake on low 

birth weight in Indian pregnant women. Eur J Clin 

Nutr. 2009 Mar;63(3):340-6. PMID: 17957193.

73. Smits LJ, Elzenga HM, Gemke RJ, et al. The 

association between interpregnancy interval and birth 

weight: what is the role of maternal polyunsaturated 

fatty acid status? BMC Pregnancy Childbirth. 

2013;13:23. PMID: 23351191.

74. Gustafson KM, Carlson SE, Colombo J, et al. 

Effects of docosahexaenoic acid supplementation 

during pregnancy on fetal heart rate and variability: a 

randomized clinical trial. Prostaglandins Leukotrienes 

& Essential Fatty Acids. 2013 May;88(5):331-8. 

PMID: 23433688.

75. Mulder KA, King DJ, Innis SM. Omega-3 fatty 

acid deficiency in infants before birth identified using 

a randomized trial of maternal DHA supplementation 

in pregnancy. PLoS ONE [Electronic Resource]. 

2014;9(1):e83764. PMID: 24427279.

76. Helland IB, Smith L, Blomen B, et al. Effect of 

supplementing pregnant and lactating mothers with n3 very-long-chain fatty acids on children's IQ and 

body mass index at 7 years of age. Pediatrics. 2008 

Aug;122(2):e472-9. PMID: 18676533.

77. Tofail F, Kabir I, Hamadani JD, et al. 

Supplementation of fish-oil and soy-oil during 

pregnancy and psychomotor development of infants. 

Journal of Health, Population & Nutrition. 2006 

Mar;24(1):48-56. PMID: 16796150.

348
78. Miles EA, Noakes PS, Kremmyda LS, et al. The 

Salmon in Pregnancy Study: study design, subject 

characteristics, maternal fish and marine n-3 fatty acid 

intake, and marine n-3 fatty acid status in maternal 

and umbilical cord blood. Am J Clin Nutr. 2011 

Dec;94(6 Suppl):1986S-92S. PMID: 21849598.

79. Linnamaa P, Savolainen J, Koulu L, et al. 

Blackcurrant seed oil for prevention of atopic 

dermatitis in newborns: a randomized, double-blind, 

placebo-controlled trial. Clin Exp Allergy. 2010 

Aug;40(8):1247-55. PMID: 20545710.

80. Drouillet P, Forhan A, De Lauzon-Guillain B, et 

al. Maternal fatty acid intake and fetal growth: 

evidence for an association in overweight women. The 

'EDEN mother-child' cohort (study of pre- and early 

postnatal determinants of the child's development and 

health). Br J Nutr. 2009 Feb;101(4):583-91. PMID: 

18631416.

81. Brantsaeter AL, Birgisdottir BE, Meltzer HM, et 

al. Maternal seafood consumption and infant birth 

weight, length and head circumference in the 

Norwegian Mother and Child Cohort Study. Br J Nutr. 

2012 Feb;107(3):436-44. PMID: 21767447.

82. Olafsdottir AS, Magnusardottir AR, 

Thorgeirsdottir H, et al. Relationship between dietary 

intake of cod liver oil in early pregnancy and 

birthweight. BJOG. 2005 Apr;112(4):424-9. PMID: 

15777439.

83. Much D, Brunner S, Vollhardt C, et al. Effect of 

dietary intervention to reduce the n-6/n-3 fatty acid 

ratio on maternal and fetal fatty acid profile and its 

relation to offspring growth and body composition at 1 

year of age. Eur J Clin Nutr. 2013 Mar;67(3):282-8. 

PMID: 23340492.

84. Dirix CE, Kester AD, Hornstra G. Associations 

between neonatal birth dimensions and maternal 

essential and trans fatty acid contents during 

pregnancy and at delivery. Br J Nutr. 2009 

Feb;101(3):399-407. PMID: 18613984.

85. Mohanty AF, Thompson ML, Burbacher TM, et 

al. Periconceptional Seafood Intake and Fetal Growth. 

Paediatr Perinat Epidemiol. 2015 Sep;29(5):376-87. 

PMID: 26147526.

86. Helland IB, Saugstad OD, Smith L, et al. Similar 

effects on infants of n-3 and n-6 fatty acids 

supplementation to pregnant and lactating women. 

Pediatrics. 2001 Nov;108(5):E82. PMID: 11694666.

87. Helland IB, Smith L, Saarem K, et al. Maternal 

supplementation with very-long-chain n-3 fatty acids 

during pregnancy and lactation augments children's IQ 

at 4 years of age. Pediatrics. 2003 Jan;111(1):e39-44. 

PMID: 12509593.

88. Noakes PS, Vlachava M, Kremmyda LS, et al. 

Increased intake of oily fish in pregnancy: effects on 

neonatal immune responses and on clinical outcomes 

in infants at 6 mo. Am J Clin Nutr. 2012 

Feb;95(2):395-404. PMID: 22218160.

89. Bernard JY, De Agostini M, Forhan A, et al. The 

dietary n6:n3 fatty acid ratio during pregnancy is 

inversely associated with child neurodevelopment in 

the EDEN mother-child cohort. J Nutr. 2013 

Sep;143(9):1481-8. PMID: 23902952.

90. Doornbos B, van Goor SA, Dijck-Brouwer DA, et 

al. Supplementation of a low dose of DHA or 

DHA+AA does not prevent peripartum depressive 

symptoms in a small population based sample. Prog 

Neuropsychopharmacol Biol Psychiatry. 2009 Feb 

1;33(1):49-52. PMID: 18955102.

91. Judge MP, Beck CT, Durham H, et al. Pilot trial 

evaluating maternal docosahexaenoic acid 

consumption during pregnancy: Decreased postpartum 

depressive symptomatology. International Journal of 

Nursing Sciences; 2014. p. 339-45.

92. Strom M, Mortensen EL, Halldorsson TI, et al. 

Fish and long-chain n-3 polyunsaturated fatty acid 

intakes during pregnancy and risk of postpartum 

depression: a prospective study based on a large 

national birth cohort. Am J Clin Nutr. 2009 

Jul;90(1):149-55. PMID: 19474139.

349
93. Miyake Y, Sasaki S, Yokoyama T, et al. Risk of 

postpartum depression in relation to dietary fish and 

fat intake in Japan: The Osaka Maternal and Child 

Health Study. Psychol Med. 2006 Dec, 

2006;36(12):1727-35. PMID: 2007-00772-008.

94. Leung BM, Kaplan BJ, Field CJ, et al. Prenatal 

micronutrient supplementation and postpartum 

depressive symptoms in a pregnancy cohort. BMC 

Pregnancy Childbirth. 2013;13:2. PMID: 23324464.

95. Chong MF, Ong YL, Calder PC, et al. LongChain polyunsaturated fatty acid status during 

pregnancy and maternal mental health in pregnancy 

and the postpartum period: results from the GUSTO 

study. J Clin Psychiatry. 2015 Jul;76(7):e848-56. 

PMID: 26231011.

96. Sallis H, Steer C, Paternoster L, et al. Perinatal 

depression and omega-3 fatty acids: a Mendelian 

randomisation study. J Affect Disord. 2014 

Sep;166:124-31. PMID: 25012420.

97. Parker G, Hegarty B, Granville‐Smith I, et al. Is 

essential fatty acid status in late pregnancy predictive 

of post‐natal depression? Acta Psychiatr Scand. 2015 

Feb, 2015;131(2):148-56. PMID: 2014-32696-001.

98. Llorente AM, Jensen CL, Voigt RG, et al. Effect 

of maternal docosahexaenoic acid supplementation on 

postpartum depression and information processing. 

Am J Obstet Gynecol. 2003 May;188(5):1348-53. 

PMID: 12748510.

99. Isaacs EB, Ross S, Kennedy K, et al. 10-year 

cognition in preterms after random assignment to fatty 

acid supplementation in infancy. Pediatrics. 2011 

Oct;128(4):e890-8. PMID: 21930549.

100. Malcolm CA, McCulloch DL, Montgomery C, et 

al. Maternal docosahexaenoic acid supplementation 

during pregnancy and visual evoked potential 

development in term infants: a double blind, 

prospective, randomised trial. Archives of Disease in 

Childhood Fetal & Neonatal Edition. 2003 

Sep;88(5):F383-90. PMID: 12937042.

101. Much D, Brunner S, Vollhardt C, et al. Breast 

milk fatty acid profile in relation to infant growth and 

body composition: results from the INFAT study. 

Pediatr Res. 2013 Aug;74(2):230-7. PMID: 23715519.

102. Lauritzen L, Hoppe C, Straarup EM, et al. 

Maternal fish oil supplementation in lactation and 

growth during the first 2.5 years of life. Pediatr Res. 

2005 Aug;58(2):235-42. PMID: 16006428.

103. Scholtens S, Wijga AH, Smit HA, et al. Longchain polyunsaturated fatty acids in breast milk and 

early weight gain in breast-fed infants. Br J Nutr. 2009 

Jan;101(1):116-21. PMID: 18492299.

104. Smithers LG, Gibson RA, McPhee A, et al. 

Higher dose of docosahexaenoic acid in the neonatal 

period improves visual acuity of preterm infants: 

results of a randomized controlled trial. Am J Clin 

Nutr. 2008 Oct;88(4):1049-56. PMID: 18842793.

105. Collins CT, Makrides M, Gibson RA, et al. Preand post-term growth in pre-term infants 

supplemented with higher-dose DHA: a randomised 

controlled trial. Br J Nutr. 2011 Jun;105(11):1635-43. 

PMID: 21443815.

106. Groh-Wargo S, Jacobs J, Auestad N, et al. Body 

composition in preterm infants who are fed long-chain 

polyunsaturated fatty acids: a prospective, 

randomized, controlled trial. Pediatr Res. 2005 

May;57(5 Pt 1):712-8. PMID: 15718356.

107. Henriksen C, Haugholt K, Lindgren M, et al. 

Improved cognitive development among preterm 

infants attributable to early supplementation of human 

milk with docosahexaenoic acid and arachidonic acid. 

Pediatrics. 2008 Jun;121(6):1137-45. PMID: 

18519483.

108. Clandinin MT, Van Aerde JE, Merkel KL, et al. 

Growth and development of preterm infants fed infant 

formulas containing docosahexaenoic acid and 

arachidonic acid. J Pediatr. 2005 Apr;146(4):461-8. 

PMID: 15812447.

350
109. Lagemaat M, Rotteveel J, Muskiet FA, et al. 

Post term dietary-induced changes in DHA and AA 

status relate to gains in weight, length, and head 

circumference in preterm infants. Prostaglandins 

Leukot Essent Fatty Acids; 2011. p. 311-6.

110. Sala-Vila A, Castellote AI, Campoy C, et al. The 

source of long-chain PUFA in formula supplements 

does not affect the fatty acid composition of plasma 

lipids in full-term infants. J Nutr. 2004 

Apr;134(4):868-73. PMID: 15051839.

111. Birch EE, Castaneda YS, Wheaton DH, et al. 

Visual maturation of term infants fed long-chain 

polyunsaturated fatty acid-supplemented or control 

formula for 12 mo. Am J Clin Nutr. 2005 

Apr;81(4):871-9. PMID: 15817866.

112. Field CJ, Van Aerde JE, Robinson LE, et al. 

Effect of providing a formula supplemented with 

long-chain polyunsaturated fatty acids on immunity in 

full-term neonates. Br J Nutr. 2008 Jan;99(1):91-9. 

PMID: 17640422.

113. Fleddermann M, Demmelmair H, Grote V, et al. 

Infant formula composition affects energetic 

efficiency for growth: the BeMIM study, a 

randomized controlled trial. Clin Nutr. 2014 

Aug;33(4):588-95. PMID: 24411489.

114. Hoffman D, Ziegler E, Mitmesser SH, et al. Soybased infant formula supplemented with DHA and 

ARA supports growth and increases circulating levels 

of these fatty acids in infants. Lipids. 2008 

Jan;43(1):29-35. PMID: 17912568.

115. Currie LM, Tolley EA, Thodosoff JM, et al. 

Long chain polyunsaturated fatty acid 

supplementation in infancy increases length- and 

weight-for-age but not BMI to 6 years when 

controlling for effects of maternal smoking. 

Prostaglandins Leukot Essent Fatty Acids; 2015. p. 1-

6.

116. Makrides M, Gibson RA, McPhee AJ, et al. 

Neurodevelopmental outcomes of preterm infants fed 

high-dose docosahexaenoic acid: a randomized 

controlled trial. JAMA. 2009 Jan 14;301(2):175-82. 

PMID: 19141765.

117. Smithers LG, Collins CT, Simmonds LA, et al. 

Feeding preterm infants milk with a higher dose of 

docosahexaenoic acid than that used in current 

practice does not influence language or behavior in 

early childhood: a follow-up study of a randomized 

controlled trial. Am J Clin Nutr. 2010 Mar;91(3):628-

34. PMID: 20053878.

118. Manley BJ, Makrides M, Collins CT, et al. 

High-dose docosahexaenoic acid supplementation of 

preterm infants: respiratory and allergy outcomes. 

Pediatrics. 2011 Jul;128(1):e71-7. PMID: 21708809.

119. Atwell K, Collins CT, Sullivan TR, et al. 

Respiratory hospitalisation of infants supplemented 

with docosahexaenoic acid as preterm neonates. J 

Paediatr Child Health. 2013 Jan;49(1):E17-22. PMID: 

23279074.

120. Collins CT, Gibson RA, Anderson PJ, et al. 

Neurodevelopmental outcomes at 7 years' corrected 

age in preterm infants who were fed high-dose 

docosahexaenoic acid to term equivalent: a follow-up 

of a randomised controlled trial. BMJ Open. 

2015;5(3):e007314. PMID: 25787990.

121. Birch EE, Carlson SE, Hoffman DR, et al. The 

DIAMOND (DHA Intake And Measurement Of 

Neural Development) Study: a double-masked, 

randomized controlled clinical trial of the maturation 

of infant visual acuity as a function of the dietary level 

of docosahexaenoic acid. Am J Clin Nutr. 2010 

Apr;91(4):848-59. PMID: 20130095.

122. Drover JR, Hoffman DR, Castaneda YS, et al. 

Cognitive function in 18-month-old term infants of the 

DIAMOND study: a randomized, controlled clinical 

trial with multiple dietary levels of docosahexaenoic 

acid. Early Hum Dev. 2011 Mar;87(3):223-30. PMID: 

21295417.

123. Drover JR, Felius J, Hoffman DR, et al. A 

randomized trial of DHA intake during infancy: 

school readiness and receptive vocabulary at 2-3.5 

years of age. Early Hum Dev. 2012 Nov;88(11):885-

91. PMID: 22835597.

351
124. Colombo J, Carlson SE, Cheatham CL, et al. 

Long-term effects of LCPUFA supplementation on 

childhood cognitive outcomes. Am J Clin Nutr. 2013 

Aug;98(2):403-12. PMID: 23803884.

125. Westerberg AC, Schei R, Henriksen C, et al. 

Attention among very low birth weight infants 

following early supplementation with 

docosahexaenoic and arachidonic acid. Acta Paediatr. 

2011 Jan, 2011;100(1):47-52. PMID: 2011-00884-

015.

126. Almaas AN, Tamnes CK, Nakstad B, et al. 

Long-chain polyunsaturated fatty acids and cognition 

in VLBW infants at 8 years: an RCT. Pediatrics. 2015 

Jun;135(6):972-80. PMID: 25986018.

127. Lauritzen L, Jorgensen MH, Mikkelsen TB, et 

al. Maternal fish oil supplementation in lactation: 

Effect on visual acuity and n-3 fatty acid content of 

infant erythrocytes. Lipids. 2004 March;39(3):195-

206. PMID: 2004247529 MEDLINE PMID 15233397 

(http://www.ncbi.nlm.nih.gov/pubmed/15233397).

128. Lauritzen L, Jorgensen MH, Olsen SF, et al. 

Maternal fish oil supplementation in lactation: effect 

on developmental outcome in breast-fed infants. 

Reprod Nutr Dev. 2005 Sep-Oct;45(5):535-47. PMID: 

16188206.

129. Cheatham CL, Nerhammer AS, Asserhoj M, et 

al. Fish oil supplementation during lactation: Effects 

on cognition and behavior at 7 years of age. Lipids. 

2011 July;46(7):637-45. PMID: 2011364320 

MEDLINE PMID 21512889 

(http://www.ncbi.nlm.nih.gov/pubmed/21512889).

130. Escolano-Margarit MV, Ramos R, Beyer J, et al. 

Prenatal DHA status and neurological outcome in 

children at age 5.5 years are positively associated. J 

Nutr. 2011 Jun;141(6):1216-23. PMID: 21525247.

131. Sun Y, Vestergaard M, Christensen J, et al. 

Intake of marine n-3 fatty acids during pregnancy and 

risk for epilepsy in the offspring: a population-based 

cohort study. Epilepsy Res. 2010 Oct;91(2-3):267-72. 

PMID: 20739149.

132. Valent F, Mariuz M, Bin M, et al. Associations 

of prenatal mercury exposure from maternal fish 

consumption and polyunsaturated fatty acids with 

child neurodevelopment: a prospective cohort study in 

Italy. J Epidemiol. 2013 Sep 5;23(5):360-70. PMID: 

23933621.

133. Bouwstra H, Dijck-Brouwer DJ, Decsi T, et al. 

Relationship between umbilical cord essential fatty 

acid content and the quality of general movements of 

healthy term infants at 3 months. Pediatr Res. 2006 

May;59(5):717-22. PMID: 16627888.

134. Bakker EC, Hornstra G, Blanco CE, et al. 

Relationship between long-chain polyunsaturated fatty 

acids at birth and motor function at 7 years of age. Eur 

J Clin Nutr. 2009 Apr;63(4):499-504. PMID: 

18091766.

135. Jensen CL, Voigt RG, Llorente AM, et al. 

Effects of early maternal docosahexaenoic acid intake 

on neuropsychological status and visual acuity at five 

years of age of breast-fed term infants. J Pediatr. 2010 

Dec;157(6):900-5. PMID: 20655543.

136. Jensen CL, Voigt RG, Prager TC, et al. Effects 

of maternal docosahexaenoic acid intake on visual 

function and neurodevelopment in breastfed term 

infants. Am J Clin Nutr. 2005 Jul;82(1):125-32. 

PMID: 16002810.

137. Fang PC, Kuo HK, Huang CB, et al. The effect 

of supplementation of docosahexaenoic acid and 

arachidonic acid on visual acuity and 

neurodevelopment in larger preterm infants. Chang 

Gung Med J. 2005 Oct;28(10):708-15. PMID: 

16382755.

138. Unay B, Sarici SU, Ulas UH, et al. Nutritional 

effects on auditory brainstem maturation in healthy 

term infants. Archives of Disease in Childhood Fetal 

& Neonatal Edition. 2004 Mar;89(2):F177-9. PMID: 

14977907.

352
139. Agostoni C, Zuccotti GV, Radaelli G, et al. 

Docosahexaenoic acid supplementation and time at 

achievement of gross motor milestones in healthy 

infants: a randomized, prospective, double-blind, 

placebo-controlled trial. Am J Clin Nutr. 2009 

Jan;89(1):64-70. PMID: 19056592.

140. Meldrum SJ, D'Vaz N, Simmer K, et al. Effects 

of high-dose fish oil supplementation during early 

infancy on neurodevelopment and language: a 

randomised controlled trial. Br J Nutr. 2012 Oct 

28;108(8):1443-54. PMID: 22348468.

141. Campoy C, Escolano-Margarit MV, Ramos R, et 

al. Effects of prenatal fish-oil and 5-

methyltetrahydrofolate supplementation on cognitive 

development of children at 6.5 y of age. Am J Clin 

Nutr. 2011 Dec;94(6 Suppl):1880S-8S. PMID: 

21849596.

142. D'Vaz N, Meldrum SJ, Dunstan JA, et al. 

Postnatal fish oil supplementation in high-risk infants 

to prevent allergy: randomized controlled trial. 

Pediatrics. 2012 Oct;130(4):674-82. PMID: 

22945403.

143. Julvez J, Guxens M, Carsin AE, et al. A cohort 

study on full breastfeeding and child 

neuropsychological development: The role of 

maternal social, psychological, and nutritional factors. 

Dev Med Child Neurol. 2014 Feb, 2014;56(2):148-56. 

PMID: 2014-01562-009.

144. Guxens M, Mendez MA, Molto-Puigmarti C, et 

al. Breastfeeding, long-chain polyunsaturated fatty 

acids in colostrum, and infant mental development. 

Pediatrics. 2011 Oct;128(4):e880-9. PMID: 21930546.

145. Innis SM, Friesen RW. Essential n-3 fatty acids 

in pregnant women and early visual acuity maturation 

in term infants. Am J Clin Nutr. 2008 Mar;87(3):548-

57. PMID: 18326591.

146. Birch EE, Garfield S, Castaneda Y, et al. Visual 

acuity and cognitive outcomes at 4 years of age in a 

double-blind, randomized trial of long-chain 

polyunsaturated fatty acid-supplemented infant 

formula. Early Hum Dev. 2007 May;83(5):279-84. 

PMID: 17240089.

147. Carlson SE, Werkman SH, Rhodes PG, et al. 

Visual-acuity development in healthy preterm infants: 

effect of marine-oil supplementation. Am J Clin Nutr. 

1993 7/1993;58(1):35-42.

148. Carlson SE, Werkman SH, Tolley EA. Effect of 

long-chain n-3 fatty acid supplementation on visual 

acuity and growth of preterm infants with and without 

bronchopulmonary dysplasia. Am J Clin Nutr. 1996 

5/1996;63(5):687-97.

149. van Wezel-Meijler G, van der Knaap MS, 

Huisman J, et al. Dietary supplementation of longchain polyunsaturated fatty acids in preterm infants: 

effects on cerebral maturation. Acta Paediatr. 

2002;91(9):942-50. PMID: 12412870.

150. Birch EE, Hoffman DR, Uauy R, et al. Visual 

acuity and the essentiality of docosahexaenoic acid 

and arachidonic acid in the diet of term infants. 

Pediatr Res. 1998 Aug;44(2):201-9. PMID: 9702915.

151. Auestad N, Montalto MB, Hall RT, et al. Visual 

acuity, erythrocyte fatty acid composition, and growth 

in term infants fed formulas with long chain 

polyunsaturated fatty acids for one year. Ross 

Pediatric Lipid Study. Pediatr Res. 1997 

1/1997;41(1):1-10.

152. Birch EE, Hoffman DR, Castaneda YS, et al. A 

randomized controlled trial of long-chain 

polyunsaturated fatty acid supplementation of formula 

in term infants after weaning at 6 wk of age. Am J 

Clin Nutr. 2002 Mar;75(3):570-80. PMID: 11864865.

153. Hoffman DR, Birch EE, Castaneda YS, et al. 

Visual function in breast-fed term infants weaned to 

formula with or without long-chain polyunsaturates at 

4 to 6 months: a randomized clinical trial. J Pediatr. 

2003 6/2003;142(6):669-77.

154. Werkman SH, Carlson SE. A randomized trial of 

visual attention of preterm infants fed 

docosahexaenoic acid until nine months. Lipids. 1996 

1/1996;31(1):91-7.

353
155. Gibson RA, Neumann MA, Makrides M. Effect 

of increasing breast milk docosahexaenoic acid on 

plasma and erythrocyte phospholipid fatty acids and 

neural indices of exclusively breast fed infants. Eur J 

Clin Nutr. 1997 9/1997;51(9):578-84.

156. Agostoni C, Marangoni F, Giovannini M, et al. 

Prolonged breast-feeding (six months or more) and 

milk fat content at six months are associated with 

higher developmental scores at one year of age within 

a breast-fed population. Adv Exp Med Biol. 

2001;501:137-41. PMID: 11787675.

157. O'Connor DL, Hall R, Adamkin D, et al. Growth 

and development in preterm infants fed long-chain 

polyunsaturated fatty acids: a prospective, randomized 

controlled trial. Pediatrics. 2001 Aug;108(2):359-71. 

PMID: 11483801.

158. Fewtrell MS, Morley R, Abbott RA, et al. 

Double-blind, randomized trial of long-chain 

polyunsaturated fatty acid supplementation in formula 

fed to preterm infants. Pediatrics. 2002 Jul;110(1 Pt 

1):73-82. PMID: 12093949.

159. Fewtrell MS, Abbott RA, Kennedy K, et al. 

Randomized, double-blind trial of long-chain 

polyunsaturated fatty acid supplementation with fish 

oil and borage oil in preterm infants. J Pediatr. 2004 

Apr;144(4):471-9. PMID: 15069395.

160. Carlson SE, Werkman SH. A randomized trial of 

visual attention of preterm infants fed 

docosahexaenoic acid until two months. Lipids. 1996 

1/1996;31(1):85-90.

161. Lucas A, Stafford M, Morley R, et al. Efficacy 

and safety of long-chain polyunsaturated fatty acid 

supplementation of infant-formula milk: a randomised 

trial.[comment]. Lancet. 1999 

12/4/1999;354(9194):1948-54.

162. Keim SA, Daniels JL, Siega-Riz AM, et al. 

Breastfeeding and long-chain polyunsaturated fatty 

acid intake in the first 4 post-natal months and infant 

cognitive development: an observational study. 

Matern Child Nutr. 2012 Oct;8(4):471-82. PMID: 

21615865.

163. Bakker EC, Ghys AJ, Kester AD, et al. Longchain polyunsaturated fatty acids at birth and 

cognitive function at 7 y of age. Eur J Clin Nutr. 2003 

Jan;57(1):89-95. PMID: 12548302.

164. Steer CD, Lattka E, Koletzko B, et al. Maternal 

fatty acids in pregnancy, FADS polymorphisms, and 

child intelligence quotient at 8 y of age. Am J Clin 

Nutr. 2013 Dec;98(6):1575-82. PMID: 24067669.

165. Brew BK, Toelle BG, Webb KL, et al. Omega-3 

supplementation during the first 5 years of life and 

later academic performance: a randomised controlled 

trial. Eur J Clin Nutr. 2015 Apr;69(4):419-24. PMID: 

25117999.

166. Mihrshahi S, Peat JK, Marks GB, et al. 

Eighteen-month outcomes of house dust mite 

avoidance and dietary fatty acid modification in the 

Childhood Asthma Prevention Study (CAPS) J 

Allergy Clin Immunol. 2003 Apr;111(4):735. J 

Allergy Clin Immunol; 2003. p. 162-8.

167. Peat JK, Mihrshahi S, Kemp AS, et al. Threeyear outcomes of dietary fatty acid modification and 

house dust mite reduction in the Childhood Asthma 

Prevention Study. J Allergy Clin Immunol. 2004 

Oct;114(4):807-13. PMID: 15480319.

168. Marks GB, Mihrshahi S, Kemp AS, et al. 

Prevention of asthma during the first 5 years of life: a 

randomized controlled trial. J Allergy Clin Immunol. 

2006 Jul;118(1):53-61. PMID: 16815138.

169. Toelle BG, Ng KK, Crisafulli D, et al. Eightyear outcomes of the Childhood Asthma Prevention 

Study. J Allergy Clin Immunol. 2010 Aug;126(2):388-

9, 9.e1-3. PMID: 20646752.

170. Willatts P, Forsyth S, Agostoni C, et al. Effects 

of long-chain PUFA supplementation in infant 

formula on cognitive function in later childhood. Am J 

Clin Nutr. 2013 Aug;98(2):536S-42S. PMID: 

23783296.

354
171. Lyall K, Munger KL, O'Reilly EJ, et al. 

Maternal dietary fat intake in association with autism 

spectrum disorders. Am J Epidemiol. 2013 Jul 

15;178(2):209-20. PMID: 23813699.

172. Furuhjelm C, Warstedt K, Fageras M, et al. 

Allergic disease in infants up to 2 years of age in 

relation to plasma omega-3 fatty acids and maternal 

fish oil supplementation in pregnancy and lactation. 

Pediatr Allergy Immunol. 2011 Aug;22(5):505-14. 

PMID: 21332799.

173. Furuhjelm C, Warstedt K, Larsson J, et al. Fish 

oil supplementation in pregnancy and lactation may 

decrease the risk of infant allergy. Acta Paediatr. 2009 

Sep;98(9):1461-7. PMID: 19489765.

174. Denburg JA, Hatfield HM, Cyr MM, et al. Fish 

oil supplementation in pregnancy modifies neonatal 

progenitors at birth in infants at risk of atopy. Pediatr 

Res. 2005 Feb;57(2):276-81. PMID: 15585690.

175. Wijga AH, van Houwelingen AC, Kerkhof M, et 

al. Breast milk fatty acids and allergic disease in 

preschool children: the Prevention and Incidence of 

Asthma and Mite Allergy birth cohort study. J Allergy 

Clin Immunol. 2006 Feb;117(2):440-7. PMID: 

16461146.

176. Newson RB, Shaheen SO, Henderson AJ, et al. 

Umbilical cord and maternal blood red cell fatty acids 

and early childhood wheezing and eczema. J Allergy 

Clin Immunol. 2004 Sep;114(3):531-7. PMID: 

15356553.

177. Standl M, Demmelmair H, Koletzko B, et al. 

Cord blood LC-PUFA composition and allergic 

diseases during the first 10 yr. Results from the 

LISAplus study. Pediatr Allergy Immunol. 2014 

Jun;25(4):344-50. PMID: 24576150.

178. Thijs C, Muller A, Rist L, et al. Fatty acids in 

breast milk and development of atopic eczema and 

allergic sensitisation in infancy. Allergy. 2011 

Jan;66(1):58-67. PMID: 20659079.

179. Notenboom ML, Mommers M, Jansen EH, et al. 

Maternal fatty acid status in pregnancy and childhood 

atopic manifestations: KOALA Birth Cohort Study. 

Clin Exp Allergy. 2011 Mar;41(3):407-16. PMID: 

21255139.

180. Nwaru BI, Erkkola M, Lumia M, et al. Maternal 

intake of fatty acids during pregnancy and allergies in 

the offspring. Br J Nutr. 2012 Aug;108(4):720-32. 

PMID: 22067943.

181. Saito K, Yokoyama T, Miyake Y, et al. Maternal 

meat and fat consumption during pregnancy and 

suspected atopic eczema in Japanese infants aged 3-4 

months: the Osaka Maternal and Child Health Study. 

Pediatr Allergy Immunol. 2010 Feb;21(1 Pt 1):38-46. 

PMID: 19552790.

182. Miyake Y, Sasaki S, Tanaka K, et al. Maternal 

fat consumption during pregnancy and risk of wheeze 

and eczema in Japanese infants aged 16-24 months: 

the Osaka Maternal and Child Health Study. Thorax. 

2009 Sep;64(9):815-21. PMID: 19497922.

183. Miyake Y, Tanaka K, Okubo H, et al. Maternal 

fat intake during pregnancy and wheeze and eczema in 

Japanese infants: the Kyushu Okinawa Maternal and 

Child Health Study. Ann Epidemiol. 2013 

Nov;23(11):674-80. PMID: 24094480.

184. Morales E, Garcia-Esteban R, Guxens M, et al. 

Effects of prolonged breastfeeding and colostrum fatty 

acids on allergic manifestations and infections in 

infancy. Clin Exp Allergy. 2012 Jun;42(6):918-28. 

PMID: 22909163.

185. Yu YM, Chan YH, Calder PC, et al. Maternal 

PUFA status and offspring allergic diseases up to the 

age of 18 months. Br J Nutr. 2015 Mar 28;113(6):975-

83. PMID: 25746049.

186. Pike KC, Calder PC, Inskip HM, et al. Maternal 

plasma phosphatidylcholine fatty acids and atopy and 

wheeze in the offspring at age of 6 years. Clin Dev 

Immunol. 2012;2012:474613. PMID: 23049600.

355
187. Olsen SF, Osterdal ML, Salvig JD, et al. Fish oil 

intake compared with olive oil intake in late 

pregnancy and asthma in the offspring: 16 y of 

registry-based follow-up from a randomized 

controlled trial. Am J Clin Nutr. 2008 Jul;88(1):167-

75. PMID: 18614738.

188. Lumia M, Luukkainen P, Tapanainen H, et al. 

Dietary fatty acid composition during pregnancy and 

the risk of asthma in the offspring. Pediatr Allergy 

Immunol. 2011 Dec;22(8):827-35. PMID: 21929596.

356
Abbreviations/Acronyms

Abbreviation Meaning

ALA Α-linolenic acid

AA Arachidonic Acid

AE Adverse event

AHRQ Agency for Healthcare Research and Quality

ASD Autism Spectrum Disorder

BDI Beck Depression Inventory

BMI Body mass index

CI Confidence Interval

DHA Docosahexaenoic acid

DPA Docosapentaenoic acid

EAR Estimated Average Requirement

EEG Electroencephalogram

EFA Essential fatty acid

EPA Eicosapentaenoic acid

EPC Evidence-based Practice Center

EPDS

FOS

Edinburgh Pregnancy Depression Scale

Fructooligosaccharide

GHTN

Hg

Gestational hypertension

Mercury

HR Hazard ratio

IUGR Intrauterine growth retardation

KQ Key Question

LBW Low birth weight

LCPUFA Long-chain polyunsaturated fatty acid

MA Meta-analysis

MDI

Mg

Mental Development Index

Milligram

n-3 FA Omega-3 fatty acid(s)

n-6 FA Omega-6 fatty acid(s)

NOS Newcastle-Ottawa Scale or Neurological Optimality Score

NR Not reported

ODS Office of Dietary Supplements

OR Odds ratio

PDI Psychomotor Development Index

PE Preeclampsia or eclampsia

PPD Post- or peripartum depression

PUFA

RBC

Polyunsaturated fatty acid

Red blood cell

RCT Randomized controlled trial

RoB Risk of bias

RR

SD

Risk ratio

Standard deviation

SDA Stearidonic acid

357
SGA Small for gestational age

SBP

SR

Systolic blood pressure

Systematic review

TEP

UK

Technical Expert Panel

United Kingdom

358
A-1

Appendix A. Search Strategy

DATABASE SEARCHED & TIME PERIOD COVERED:

 PsycINFO – 1/1/2000-8/24/2015

LANGUAGE:

 English

SEARCH STRATEGY:

[ TI ( omega 3 or omega-3 or omega3 OR polyunsaturated or pufa or dha or epa or "long chain" or longchain or longchain OR Docosapentanoic or docosapentaenoic or docosahexanoic or docosahexaenoic or 

dpa or dha OR eicosapentanoic or eicosapentaenoic or icosapent* ) OR SU ( omega 3 or omega-3 or 

omega3 OR polyunsaturated or pufa or dha or epa or "long chain" or long-chain or longchain OR 

Docosapentanoic or docosapentaenoic or docosahexanoic or docosahexaenoic or dpa or dha OR 

eicosapentanoic or eicosapentaenoic or icosapent* ) OR AB ( omega 3 or omega-3 or omega3 OR 

polyunsaturated or pufa or dha or epa or "long chain" or long-chain or longchain OR Docosapentanoic or 

docosapentaenoic or docosahexanoic or docosahexaenoic or dpa or dha OR eicosapentanoic or 

eicosapentaenoic or icosapent* )

OR

TI ( ((fatty acid or fatty acids*) and essential ) OR "fish oil" or "fish oils" or linolenic or alpha-linolenic OR 

alphalinolenic or alpha-linolenic OR linolenate or cervonic or timnodonic or stearidonic ) OR SU ( ((fatty 

acid or fatty acids*) and essential ) OR "fish oil" or "fish oils" or linolenic or alpha-linolenic OR 

alphalinolenic or alpha-linolenic OR linolenate or cervonic or timnodonic or stearidonic ) OR AB ( ((fatty 

acid or fatty acids*) and essential ) OR "fish oil" or "fish oils" or linolenic or alpha-linolenic OR 

alphalinolic or alpha-linolenic OR linolenate or cervonic or timnodonic or stearidonic )

OR

((n 3 or n3 or n-3) and (oil or oils or pufa or fatty acid or fatty acids)) OR ((menhaden or flax or flaxseed 

or flax seed or linseed or rape seed or rapeseed or canola or soy or soybean or walnut or mustard seed 

or perilla or shiso) and (oil or oils)) OR walnut* or butternut*or soybean* or "pumpkin seed" or 

pumpkinseed* OR "cod liver oil" or "codliver oil" or "marine oil" or "marine oils" or "marine fat" ) OR SU 

( ((n 3 or n3 or n-3) and (oil or oils or pufa or fatty acid or fatty acids)) OR ((menhaden or flax or flaxseed 

or flax seed or linseed or rape seed or rapeseed or canola or soy or soybean or walnut or mustard seed 

or perilla or shiso) and (oil or oils)) OR walnut* or butternut*or soybean* or "pumpkin seed" or 

pumpkinseed* OR "cod liver oil" or "codliver oil" or "marine oil" or "marine oils" or "marine fat" ) OR AB 

( ((n 3 or n3 or n-3) and (oil or oils or pufa or fatty acid or fatty acids)) OR ((menhaden or flax or flaxseed 

or flax seed or linseed or rape seed or rapeseed or canola or soy or soybean or walnut or mustard seed 

or perilla or shiso) and (oil or oils)) OR walnut* or butternut*or soybean* or "pumpkin seed" or 

pumpkinseed* OR "cod liver oil" or "codliver oil" or "marine oil" or "marine oils" or "marine fat" )

OR

TI ( salmon or mackerel or herring or tuna or halibut or seaweed or anchov* or sardine* OR Ropufa or 

MaxEPA or Omacor or Efamed or ResQ or Epagis or Almarin or Coromega or Lovaza or Vascepa or 

icosapent ethyl OR ((fish n3 consum*) or (fish n3 intake) or (fish n3 diet*)) OR mediterranean n3 diet* ) 

OR SU ( salmon or mackerel or herring or tuna or halibut or seaweed or anchov* or sardine* OR Ropufa 

or MaxEPA or Omacor or Efamed or ResQ or Epagis or Almarin or Coromega or Lovaza or Vascepa or 

icosapent ethyl OR ((fish n3 consum*) or (fish n3 intake) or (fish n3 diet*)) OR mediterranean n3 diet* ) 

OR AB ( salmon or mackerel or herring or tuna or halibut or seaweed or anchov* or sardine* OR Ropufa 
A-2

or MaxEPA or Omacor or Efamed or ResQ or Epagis or Almarin or Coromega or Lovaza or Vascepa or 

icosapent ethyl OR ((fish n3 consum*) or (fish n3 intake) or (fish n3 diet*)) OR mediterranean n3 diet* ) ]

AND

[ TI ( growth OR ((child* n3 development) or gestational age or premature infant or low birth weight OR 

( gestat* and (age* or durat* or week*)) OR prematur* or preterm or pre-term OR ( low n3 (birthweight 

or weight)) ) OR SU ( growth OR ((child* n3 development) or gestational age or premature infant or low 

birth weight OR ( gestat* and (age* or durat* or week*)) OR prematur* or preterm or pre-term OR ( low 

n3 (birthweight or weight)) ) OR SU ( growth OR ((child* n3 development) or gestational age or 

premature infant or low birth weight OR ( gestat* and (age* or durat* or week*)) OR prematur* or 

preterm or pre-term OR ( low n3 (birthweight or weight)) ) OR AB ( growth OR ((child* n3 development) 

or gestational age or premature infant or low birth weight OR ( gestat* and (age* or durat* or week*)) 

OR prematur* or preterm or pre-term OR ( low n3 (birthweight or weight)) )

OR

TI ( newborn or neonat* OR Retinopathy n3 Prematurity OR retrolental fibroplasia* OR ADHD or 

attention deficit disorder* OR atopic n3 dermatitis ) OR SU ( newborn or neonat* OR Retinopathy n3 

Prematurity OR retrolental fibroplasia* OR ADHD or attention deficit disorder* OR atopic n3 dermatitis ) 

OR AB ( newborn or neonat* OR Retinopathy n3 Prematurity OR retrolental fibroplasia* OR ADHD or 

attention deficit disorder* OR atopic n3 dermatitis ) 

OR

TI ( autism OR autistic OR asperger* OR ados OR hypersensitiv* OR allerg* OR ( Fetal AND growth AND 

retard* ) OR ( Embryo* AND Fetal Development ) OR ( Fetus OR ((fetal OR fetus OR intrauterine) AND 

(growth OR develop*)) ) ) OR SU ( autism OR autistic OR asperger* OR ados OR hypersensitiv* OR allerg* 

OR ( Fetal AND growth AND retard* ) OR ( Embryo* AND Fetal Development ) OR ( Fetus OR ((fetal OR 

fetus OR intrauterine) AND (growth OR develop*)) ) ) OR AB (( autism OR autistic OR asperger* OR ados 

OR hypersensitiv* OR allerg* OR ( Fetal AND growth AND retard* ) OR ( Embryo* AND Fetal 

Development ) OR ( Fetus OR ((fetal OR fetus OR intrauterine) AND (growth OR develop*)) ) )

OR

TI ( Preeclamp* OR pre-eclamp* OR (Pregnan* AND Toxemi*) OR ( (Gestation* OR pregnan*) AND 

(hypertens* OR toxemi*) ) OR ( gestat* AND (child* OR newborn* OR infan* OR neonat* OR baby OR 

babies OR pediatr* OR paediatr*) ) OR ( depression AND (postpartum OR postnatal OR post-partum OR 

post-natal OR post partum OR post natal OR ante-natal OR antenatal OR ante natal) ) OR ( grow* near/3 

(child* OR infant* OR infancy) ) ) OR SU (Preeclamp* OR pre-eclamp* OR (Pregnan* AND Toxemi*) OR ( 

(Gestation* OR pregnan*) AND (hypertens* OR toxemi*) ) OR ( gestat* AND (child* OR newborn* OR 

infan* OR neonat* OR baby OR babies OR pediatr* OR paediatr*) ) OR ( depression AND (postpartum OR 

postnatal OR post-partum OR post-natal OR post partum OR post natal OR ante-natal OR antenatal OR 

ante natal) ) OR ( grow* near/3 (child* OR infant* OR infancy) ) ) OR AB ( Preeclamp* OR pre-eclamp* 

OR (Pregnan* AND Toxemi*) OR ( (Gestation* OR pregnan*) AND (hypertens* OR toxemi*) ) OR ( 

gestat* AND (child* OR newborn* OR infan* OR neonat* OR baby OR babies OR pediatr* OR paediatr*) 

) OR ( depression AND (postpartum OR postnatal OR post-partum OR post-natal OR post partum OR post 

natal OR ante-natal OR antenatal OR ante natal) ) OR ( grow* near/3 (child* OR infant* OR infancy) ) ) 

OR

TI ( ( congenital AND (vision near/3 disorder*) ) OR ( (learning near/3 disorder*) OR dyslexi* OR 

discalculi* ) OR ( (respiratory near/3 illness) OR asthma* OR wheez* OR respiratory syncitial virus ) ) OR 

SU ( ( congenital AND (vision near/3 disorder*) ) OR ( (learning near/3 disorder*) OR dyslexi* OR 

discalculi* ) OR ( (respiratory near/3 illness) OR asthma* OR wheez* OR respiratory syncitial virus ) ) OR 

AB ( ( congenital AND (vision near/3 disorder*) ) OR ( (learning near/3 disorder*) OR dyslexi* OR 

discalculi* ) OR ( (respiratory near/3 illness) OR asthma* OR wheez* OR respiratory syncitial virus ) ) ]
A-3

AND

Population Group: Human 

Search modes - Find all search terms 

=====================================================================================

DATABASE SEARCHED & TIME PERIOD COVERED:

Medline on OVID – 1/1/2000-8/25/2015

LANGUAGE:

 English

SEARCH STRATEGY:

1 exp Growth/ or exp Gestational Age/ or Infant, Premature/ or Infant, Low Birth Weight/ 

2 limit 1 to (english language and yr="2014 - 2015") 

3 (gestat* and (age* or durat* or week*)).mp. 

4 limit 3 to (english language and yr="2014 - 2015") 

5 (prematur* or preterm or pre-term).mp. 

6 limit 5 to (english language and yr="2014 - 2015") 

7 ((Infant* or baby) adj3 (low adj3 (birthweight or weight))).mp. 

8 limit 7 to (english language and yr="2014 - 2015") 

9 ((Infant$ or baby or birth) adj3 (prematur$ or gestational age)).mp. 

10 limit 9 to (english language and yr="2014 - 2015") 

11 (newborn or neonatal).mp. 

12 limit 11 to (english language and yr="2014 - 2015") 

13 Retinopathy of Prematurity/ 

14 limit 13 to (english language and yr="2014 - 2015") 

15 retrolental fibroplasia$.mp. 

16 limit 15 to (english language and yr="2014 - 2015") 

17 Retinopathy of Prematurity.tw. 

18 limit 17 to (english language and yr="2014 - 2015") 
A-4

527 

19 Attention Deficit Disorder with Hyperactivity/ or ADHD.mp. or attention deficit disorder*.mp. 

20 limit 19 to (english language and yr="2014 - 2015") 

21 Dermatitis, Atopic/ or (atopic adj3 dermatitis).mp. 

22 limit 21 to (english language and yr="2014 - 2015") 

23 (autism or autistic).mp. or Autistic Disorder/ or asperger*.mp. or Asperger Syndrome/ 

24 limit 23 to (english language and yr="2014 - 2015") 

25 ados.mp. 

26 limit 25 to (english language and yr="2014 - 2015") 

27 Hypersensitivity/ or allerg*.mp. 

28 limit 27 to (english language and yr="2014 - 2015") 

29 Fetal Growth Retardation/ 

30 limit 29 to (english language and yr="2014 - 2015") 

31 exp Embryo/ and Fetal Development/ 

32 limit 31 to (english language and yr="2014 - 2015") 

33 exp Fetus/ 

34 limit 33 to (english language and yr="2014 - 2015") 

35 ((fetal or fetus or intrauterine) adj3 (growth or develop$)).mp. 

36 limit 35 to (english language and yr="2014 - 2015") 

37 Pre-Eclampsia/ 

38 limit 37 to (english language and yr="2014 - 2015") 

39 (Preeclamp$ or pre-eclamp*).mp. 

40 limit 39 to (english language and yr="2014 - 2015") 

41 (Pregnan$ adj10 Toxemia$).mp. 
A-5

42 limit 41 to (english language and yr="2014 - 2015") 

43 ((gestation$ or pregnan$) and (hypertens$ or toxemia$)).mp. 

44 limit 43 to (english language and yr="2014 - 2015") 

45 (gestat$ and (child$ or newborn$ or infan$ or neonat$ or baby or babies or pediatr$ or 

paediatr$)).mp. 

46 limit 45 to (english language and yr="2014 - 2015") 

47 Depression, Postpartum/ or (depression adj3 (postpartum or postnatal or post-partum or post-natal 

or post partum or post natal or ante-natal or antenatal or ante natal)).mp. 

48 limit 47 to (english language and yr="2014 - 2015") 

49 (grow* adj3 (child* or infant* or infancy)).mp. 

50 limit 49 to (english language and yr="2014 - 2015") 

51 congenital.mp. and (Vision Disorders/ or (vision adj3 disorder*).mp.) {Including Related Terms} 

52 limit 51 to (english language and yr="2014 - 2015") 

53 Learning Disorders/ or (learning adj3 disorder*).mp. or dyslexi*.mp. or discalculi*.mp.

54 limit 53 to (english language and yr="2014 - 2015") 

55 ((respiratory adj3 illness) or asthma* or wheez* or respiratory syncitial virus).mp. 

56 limit 55 to (english language and yr="2014 - 2015") 

57 2 or 4 or 6 or 8 or 10 or 12 or 14 or 16 or 18 or 20 or 22 or 24 or 26 or 28 or 30 or 32 or 34 or 36 or 

38 or 40 or 42 or 44 or 46 or 48 or 50 or 52 or 54 or 56 

58 exp fatty acids, omega-3/ 

59 limit 58 to (english language and yr="2014 - 2015") 

60 fatty acids, essential/ or linolenic acids/ or exp fish oils/ 

61 limit 60 to (english language and yr="2014 - 2015") 

62 (omega 3 or omega-3 or omega3).mp. 

63 limit 62 to (english language and yr="2014 - 2015") 

64 (polyunsaturated fat$ or pufa or dha or epa or long chain or longchain).mp. 
A-6

65 limit 64 to (english language and yr="2014 - 2015") 

66 Docosapenta?noic.mp. 

67 limit 66 to (english language and yr="2014 - 2015") 

68 DPA.mp. 

69 limit 68 to (english language and yr="2014 - 2015") 

70 ((omega-3 or omega 3 or omega3) and fatty acid$).mp. 

71 limit 70 to (english language and yr="2014 - 2015") 

72 ((n 3 or n3 or n-3) and (oil$ or pufa or fatty acid$ or omega 3)).mp. 

73 limit 72 to (english language and yr="2014 - 2015") 

74 Docosahexaenoic Acids/ 

75 limit 74 to (english language and yr="2014 - 2015") 

76 docosahexa?noic.mp. 

77 limit 76 to (english language and yr="2014 - 2015") 

78 Eicosapentaenoic Acid/

79 limit 78 to (english language and yr="2014 - 2015") 

80 eicosapenta?noic.mp. 

81 limit 80 to (english language and yr="2014 - 2015") 

82 icosapent?enoic.mp. 

83 limit 82 to (english language and yr="2014 - 2015") 

84 (alpha linolenic or alphalinolenic or alpha-linolenic).mp. 

85 limit 84 to (english language and yr="2014 - 2015") 

86 (linolenate or cervonic or timnodonic or stearidonic).mp. 

87 limit 86 to (english language and yr="2014 - 2015") 

88 menhaden oil$.mp. 
A-7

89 limit 88 to (english language and yr="2014 - 2015") 

90 ((flax or flaxseed or flax seed or linseed or rape seed or rapeseed or canola or soy or soybean or 

walnut or mustard seed or perilla or shiso) adj2 oil$).mp. 

91 limit 90 to (english language and yr="2014 - 2015") 

92 (walnut$ or butternut$ or soybean$ or pumpkin seed$).mp. 

93 limit 92 to (english language and yr="2014 - 2015") 

94 (fish adj2 oil$).mp. 

95 limit 94 to (english language and yr="2014 - 2015") 

96 (cod liver oil$ or codliver oil$ or marine oil$ or marine fat$).mp. 

97 limit 96 to (english language and yr="2014 - 2015") 

98 (salmon or mackerel or herring or tuna or halibut or seaweed or anchov$ or sardine$).mp. 

99 limit 98 to (english language and yr="2014 - 2015") 

100 (Ropufa or MaxEPA or Omacor or Efamed or ResQ or Epagis or Almarin or Coromega or Lovaza or 

Vascepa or icosapent ethyl).mp. 

101 limit 100 to (english language and yr="2014 - 2015") 

102 (fish consumption or fish intake or (fish adj2 diet$)).mp. 

103 limit 102 to (english language and yr="2014 - 2015") 

104 (mediterranean adj diet$).mp. 

105 limit 104 to (english language and yr="2014 - 2015") 

106 ((red blood cell or phospholipid or plasma fatty acid or plasma or phospholipid or triacylglycerol or 

cholesteryl or ester or adipos$ or fatty acid or erythrocyte or ghost or platelet or granulocyte or 

neutrophil or mononuclear or LDL or HDL) and (DHA or docosahexa?noic or EPA or eicosapenta?noic or 

SDA or stearidonic or omega)).mp. 

107 limit 106 to (english language and yr="2014 - 2015") 

108 59 or 61 or 63 or 65 or 67 or 69 or 71 or 73 or 75 or 77 or 79 or 81 or 83 or 85 or 87 or 89 or 91 or 

93 or 95 or 97 or 99 or 101 or 103 or 105 or 107 

109 57 and 108 
A-8

110 (randomized controlled trial or clinical trial or controlled clinical trial or evaluation studies or 

multicenter study).pt. 

111 limit 110 to (english language and yr="2014 - 2015") 

112 (exp clinical trial/ or evaluation studies or follow-up studies or prospective studies or exp 

randomized controlled trials/ or exp Randomized Controlled Trials as Topic/) {Including Related Terms} 

113 limit 112 to (english language and yr="2014 - 2015") 

114 exp random allocation/ or exp double-blind method/ or exp single-blind method/ 

115 limit 114 to (english language and yr="2014 - 2015") 

116 exp placebos/ or exp longitudinal studies/ or exp cohort studies/ 

117 limit 116 to (english language and yr="2014 - 2015") 

118 ("prospective studies" or "prospective study").af. 

119 limit 118 to (english language and yr="2014 - 2015") 

120 Cross-Sectional Studies.sh. 

121 limit 120 to (english language and yr="2014 - 2015") 

122 (clin$ adj trial$).af. 

123 limit 122 to (english language and yr="2014 - 2015") 

124 ((evaluation adj3 study) or (evaluation adj3 studies)).af. 

125 limit 124 to (english language and yr="2014 - 2015") 

126 (followup or follow-up or (follow$ adj2 up)).af. NOTE: SEARCH ENGINE DID NOT ACCEPT THIS AS A 

PHRASE

127 limit 126 to (english language and yr="2014 - 2015") 

128 (follow-up or "follow up").af. NOTE: SEARCH ENGINE DID NOT ACCEPT THIS AS A PHRASE

129 limit 128 to (english language and yr="2014 - 2015") 

130 

("following up" or "followed up").af. NOTE: SEARCH ENGINE DID NOT ACCEPT THIS AS A PHRASE
A-9

131 limit 130 to (english language and yr="2014 - 2015") 

132 ((prospective adj3 study) or (prospective adj3 studies)).af. 

133 limit 132 to (english language and yr="2014 - 2015") 

134 (prospective adj3 observational).af. 

135 limit 134 to (english language and yr="2014 - 2015") 

136 (multicenter or multi-center).af. 

137 limit 136 to (english language and yr="2014 - 2015") 

138 (random$ or rct$).af. 

139 limit 138 to (english language and yr="2014 - 2015") 

140 ((singl$ or doubl$ or trebl$ or tripl$) adj (blind$ or mask$)).af. 

141 limit 140 to (english language and yr="2014 - 2015") 

142 (placebo$ or comparative study or longitudinal or cohort* or observational or cross section$ or 

cross-section$ or food frequency questionnaire$).af. 

143 limit 142 to (english language and yr="2014 - 2015") 

144 "before-and-after".af. NOTE: SEARCH ENGINE DID NOT ACCEPT THIS AS A PHRASE

145 limit 144 to (english language and yr="2014 - 2015") 

146 ((before adj2 after) or single-arm or "single arm").af. 

147 limit 146 to (english language and yr="2014 - 2015") 

148 (single-arm or "single arm").af. 

149 limit 148 to (english language and yr="2014 - 2015") 

150 "before-and-after".af. NOTE: SEARCH ENGINE DID NOT ACCEPT THIS AS A PHRASE

151 limit 150 to (english language and yr="2014 - 2015") 

152 111 or 113 or 115 or 117 or 119 or 121 or 123 or 125 or 127 or 129 or 131 or 133 or 135 or 137 or 

139 or 141 or 143 or 145 or 147 or 149 or 151 

153 109 and 152 
A-10

=====================================================================================

DATABASE SEARCHED & TIME PERIOD COVERED:

Embase – 1/1/2000-8/25/2015

LANGUAGE:

 English

SEARCH STRATEGY:

#1 'body growth'/exp OR 'body growth' OR 'child development'/exp OR 'child development' OR 

'gestational age'/exp OR 'gestational age' OR 'prematurity'/exp OR 'prematurity' OR 'low birth 

weight'/exp OR 'low birth weight'

#2 gestat* AND (age* OR durat* OR week*)

#3 premature* OR preterm OR 'pre term'

#4 infant* OR 'baby'/exp OR baby AND low AND ('birthweight'/exp OR birthweight OR 'weight'/exp OR 

weight)

#5 'newborn'/exp OR newborn OR neonat*

#6 'retrolental fibroplasia'/exp OR 'retrolental fibroplasia' OR 'attention deficit disorder'/exp OR 

'attention deficit disorder' OR 'atopic dermatitis'/exp OR 'atopic dermatitis' OR 'autism'/exp OR 'autism' 

OR 'hypersensitivity'/exp OR 'hypersensitivity'

#7 retrolental AND fibroplas* OR retinopathy NEAR/2 prematurity OR ('attention'/exp OR attention 

AND deficit AND ('disorder'/exp OR disorder)) OR 'adhd'/exp OR adhd OR atopic NEAR/3 dermatitis OR 

'autism'/exp OR autism OR autistic OR asperger* OR ados OR allerg*

#8 retrolental AND fibroplas* OR retinopathy NEAR/2 prematurity OR ('attention' OR 'attention'/exp OR 

attention AND deficit AND ('disorder' OR 'disorder'/exp OR disorder)) OR 'adhd' OR 'adhd'/exp OR adhd 

OR atopic NEAR/3 dermatitis OR 'autism' OR 'autism'/exp OR autism OR autistic OR asperger* OR ados 

OR allerg*

#9 'intrauterine growth retardation'/exp OR 'intrauterine growth retardation' OR 'prenatal 

development'/exp OR 'prenatal development' OR 'fetus'/exp OR 'fetus' OR 'preeclampsia'/exp OR 

'preeclampsia' OR 'puerperal depression'/exp OR 'puerperal depression'

#10 (fetal OR fetus OR intrauterine) NEAR/3 (growth OR develop*)

#11 preeclamp* OR 'pre eclampsia'/exp OR 'pre eclampsia'

#12 pregnan* NEAR/10 toxemi*

#13 gestation* OR pregnan* AND (hypertens* OR toxemi*)
A-11

#14 gestation* AND (child* OR newborn* OR infan* OR neonat* OR 'baby'/exp OR baby OR babies OR 

pediatr* OR paediatr*)

#15 depression NEAR/3 (postpartum OR postnatal OR 'post partum' OR 'post natal' OR antenatal OR 

'ante natal')

#16 grow* NEAR/3 (child* OR infant* OR infancy)

#17 'visual disorder'/exp OR 'visual disorder' AND congenital

#18 congenital AND ('vision'/exp OR vision OR visual) AND disorder*

#19 'learning disorder'/exp OR 'learning disorder' OR learning NEAR/3 disorder* OR dyslexi* OR 

discalculi*

#20 respiratory NEAR/3 illness OR respiratory NEAR/3 disease* OR respiratory NEAR/3 condition* OR 

asthma* OR wheez* OR (respiratory AND syncytial AND ('virus'/exp OR virus))

#21 infant* OR 'baby'/exp OR baby AND (premature* OR gestational) AND ('age'/exp OR age)

#22 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR 

#15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21

#23 #3 AND (2014:py OR 2015:py)

#24 #3 AND (2014:py OR 2015:py) AND [english]/lim

#25 'icosapentaenoic acid'/exp OR 'icosapentaenoic acid'

#26 'docosahexaenoic acid'/exp OR 'docosahexaenoic acid'

#27 'omega 3 fatty acid'/exp OR 'omega 3 fatty acid'

#28 'essential fatty acid'/exp OR 'essential fatty acid'

#29 'fish oil'/exp OR 'fish oil'

#30 'omega 3'/exp OR 'omega 3' OR ('omega'/exp OR omega AND 3) OR omega3 OR (polyunsaturated 

AND fat*) OR pufa OR dha OR epa OR dpa OR (long AND chain) OR 'long chain'

#31 'docosapentaenoic acid'/exp OR 'docosapentaenoic acid' OR docosapent* OR docosahex* OR 

eicosapent* OR icosapent*

#32 n3 OR 'n 3' OR (n AND 3) AND (oil* OR pufa OR fatty) AND acid*

#33 alpha AND linolenic OR alphalinolenic OR 'alpha linolenic'

#34 linolenate* OR cervonic OR timnodonic OR stearidonic
A-12

#35 menhaden NEAR/3 oil*

#36 flax* OR 'linseed' OR 'linseed'/exp OR linseed OR ('rape' OR 'rape'/exp OR rape AND ('seed' OR 

'seed'/exp OR seed)) OR 'rapeseed' OR 'rapeseed'/exp OR rapeseed

#37 'canola' OR 'canola'/exp OR canola OR soy OR soybean* OR 'walnut' OR 'walnut'/exp OR walnut

#38 'mustard' OR 'mustard'/exp OR mustard AND ('seed' OR 'seed'/exp OR seed)

#39 'perilla' OR 'perilla'/exp OR perilla OR shiso

#40 walnut* OR butternut* OR soybean* OR ('pumpkin' OR 'pumpkin'/exp OR pumpkin AND ('seed' OR 

'seed'/exp OR seed)) OR pumpkinseed*

#41 fish NEAR/2 oil*

#42 cod AND ('liver' OR 'liver'/exp OR liver) AND oil* OR (codliver AND oil*) OR (marine AND oil*) OR 

(marine AND ('fat'/exp OR fat))

#43 'salmon' OR 'salmon'/exp OR salmon OR mackerel OR 'herring' OR 'herring'/exp OR herring OR 

'tuna' OR 'tuna'/exp OR tuna OR 'halibut' OR 'halibut'/exp OR halibut OR 'seaweed' OR 'seaweed'/exp 

OR seaweed OR anchov* OR sardine*

#44 ropufa OR 'maxepa' OR 'maxepa'/exp OR maxepa OR 'omacor' OR 'omacor'/exp OR omacor OR 

'efamed' OR 'efamed'/exp OR efamed OR resq OR epagis OR almarin OR coromega OR 'lovaza' OR 

'lovaza'/exp OR lovaza OR 'vascepa' OR 'vascepa'/exp OR vascepa OR ('icosapent' OR 'icosapent'/exp OR 

icosapent AND ethyl)

#45 fish NEAR/2 consum* OR fish NEAR/2 intake OR fish NEAR/2 diet

#46 'mediterranean diet'/exp OR 'mediterranean diet'

#47 red AND ('blood' OR 'blood'/exp OR blood) AND ('cell' OR 'cell'/exp OR cell) OR ('plasma' OR 

'plasma'/exp OR plasma AND fatty AND ('acid' OR 'acid'/exp OR acid)) OR 'plasma' OR 'plasma'/exp OR 

plasma OR 'phospholipid' OR 'phospholipid'/exp OR phospholipid OR 'triacylglycerol' OR 

'triacylglycerol'/exp OR triacylglycerol OR cholesteryl OR 'ester' OR 'ester'/exp OR ester OR adipos* OR 

(fatty AND ('acid' OR 'acid'/exp OR acid)) OR 'erythrocyte' OR 'erythrocyte'/exp OR erythrocyte OR ghost 

OR 'platelet' OR 'platelet'/exp OR platelet OR 'granulocyte' OR 'granulocyte'/exp OR granulocyte OR 

'neutrophil' OR 'neutrophil'/exp OR neutrophil OR mononuclear OR 'ldl' OR 'ldl'/exp OR ldl OR 'hdl' OR 

'hdl'/exp OR hdl AND (dha OR docosahexa?noic OR epa OR eicosapenta?noic OR sda OR stearidonic OR 

'omega' OR 'omega'/exp OR omega)

#48 #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 

OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47

#49 #22 AND #48
A-13

#50 #34 AND (2014:py OR 2015:py)

#51 #34 AND (2014:py OR 2015:py) AND [english]/lim

#52 #34 AND (2014:py OR 2015:py) AND [humans]/lim

NUMBER OF RESULTS: 56

================================================================================

DATABASE SEARCHED & TIME PERIOD COVERED:

 Cochrane Databases – 1/1/2000-8/26/2015

LANGUAGE:

 English

SEARCH STRATEGY:

#1 MeSH descriptor: [Fatty Acids, Omega-3] explode all trees

 

 #2 MeSH descriptor: [Fatty Acids, Essential] explode all trees

 

 #3 MeSH descriptor: [Linolenic Acids] explode all trees

 

 #4 MeSH descriptor: [Fish Oils] explode all trees

 

 #5 MeSH descriptor: [Docosahexaenoic Acids] explode all trees

 #6 MeSH descriptor: [Eicosapentaenoic Acid] explode all trees

 

 #7 omega 3 or omega-3 or omega3:ti,ab,kw (Word variations have been searched)

 

 #8 polyunsaturated or pufa or dha or epa or "long chain" or long-chain or longchain:ti,ab,kw (Word 

variations have been searched)

 #9 Docosapentanoic or docosapentaenoic or docosahexanoic or docosahexaenoic or dpa or 

dha:ti,ab,kw (Word variations have been searched)

 

 #10 icosapentanoic or eicosapentaenoic or icosapent*:ti,ab,kw (Word variations have been searched)

 

 #11 (fatty acid or fatty acids*) and essential:ti,ab,kw (Word variations have been searched)

 #12 "fish oil" or "fish oils" or linolenic or alpha-linolenic:ti,ab,kw (Word variations have been searched)

 #13 alphalinolenic or alpha-linolenic:ti,ab,kw (Word variations have been searched)

 #14 linolenate or cervonic or timnodonic or stearidonic:ti,ab,kw (Word variations have been searched)

 
A-14

 #15 (n 3 or n3 or n-3) and (oil or oils or pufa or fatty acid or fatty acids):ti,ab,kw (Word variations have 

been searched)

 #16 menhaden or flax or flaxseed or flax seed or linseed or rape seed or rapeseed or canola or 

soy:ti,ab,kw (Word variations have been searched)

 

 #17 soybean or walnut or mustard seed or perilla or shiso:ti,ab,kw (Word variations have been 

searched)

 

 #18 walnut* or butternut* or soybean* or "pumpkin seed" or pumpkinseed*:ti,ab,kw (Word variations 

have been searched)

 #19 "cod liver oil" or "codliver oil" or "marine oil" or "marine oils" or "marine fat":ti,ab,kw (Word 

variations have been searched)

 #20 salmon or mackerel or herring or tuna or halibut or seaweed or anchov* or sardine*:ti,ab,kw 

(Word variations have been searched)

 #21 Ropufa or MaxEPA or Omacor or Efamed or ResQ or Epagis or Almarin or Coromega or 

Lovaza:ti,ab,kw (Word variations have been searched)

 #22 Vascepa or icosapent ethyl:ti,ab,kw (Word variations have been searched)

 #23 (fish near/3 consum*) or (fish near/3 intake) or (fish near/3 diet*):ti,ab,kw (Word variations have 

been searched)

 

 #24 mediterranean near/3 diet*:ti,ab,kw (Word variations have been searched)

 #25 red blood cell or phospholipid or plasma fatty acid or plasma or phospholipid or 

triacylglycerol:ti,ab,kw (Word variations have been searched)

 #26 cholesteryl or ester or adipos* or fatty acid or erythrocyte or ghost or platelet or 

granulocyte:ti,ab,kw (Word variations have been searched)

 

 #27 neutrophil or mononuclear or LDL or HDL:ti,ab,kw (Word variations have been searched)

 

 #28 EPA or SDA or stearidonic or omega:ti,ab,kw (Word variations have been searched)

 #29 #25 or #26 or #27

 #30 #29 and #28

 #34 MeSH descriptor: [Growth] explode all trees

 

 #35 MeSH descriptor: [Child Development] explode all trees

 

 #36 MeSH descriptor: [Gestational Age] explode all trees
A-15

 #37 MeSH descriptor: [Infant, Premature] explode all trees

 #38 MeSH descriptor: [Infant, Premature] explode all trees

 

 #39 MeSH descriptor: [Infant, Low Birth Weight] explode all trees

 #40 MeSH descriptor: [Retinopathy of Prematurity] explode all trees

 #41 MeSH descriptor: [Attention Deficit Disorder with Hyperactivity] explode all trees

 

 #42 MeSH descriptor: [Dermatitis, Atopic] explode all trees

 #43 MeSH descriptor: [Autistic Disorder] explode all trees

 #44 MeSH descriptor: [Hypersensitivity] explode all trees

 #45 MeSH descriptor: [Fetal Growth Retardation] explode all trees

 #46 MeSH descriptor: [Embryonic and Fetal Development] explode all trees

 #47 MeSH descriptor: [Fetus] explode all trees

 #48 MeSH descriptor: [Pre-Eclampsia] explode all trees

 

 #49 MeSH descriptor: [Depression, Postpartum] explode all trees

 #50 MeSH descriptor: [Vision Disorders] explode all trees

 #51 growth or (child* next/3 development) or gestational age or premature infant or low birth 

weight:ti,ab,kw (Word variations have been searched)

 #52 gestat* and (age* or durat* or week*):ti,ab,kw (Word variations have been searched)

 

 #53 prematur* or preterm or pre-term:ti,ab,kw (Word variations have been searched)

 #54 low near/3 (birthweight or weight):ti,ab,kw (Word variations have been searched)

 #55 newborn or neonat*:ti,ab,kw (Word variations have been searched)

 #56 Retinopathy near/3 Prematurity:ti,ab,kw (Word variations have been searched)

 #57 retrolental fibroplasia*:ti,ab,kw (Word variations have been searched)

 #58 ADHD or attention deficit disorder*:ti,ab,kw (Word variations have been searched)

 #59 atopic near/3 dermatitis:ti,ab,kw (Word variations have been searched)

 #60 autism or autistic or asperger*:ti,ab,kw (Word variations have been searched)
A-16

 #61 ados or hypersensitiv* or allerg*:ti,ab,kw (Word variations have been searched)

 

 #62 Fetal and growth and retard*:ti,ab,kw (Word variations have been searched)

 

 #63 Embryo* and Fetal Development:ti,ab,kw (Word variations have been searched)

 #64 Fetus or ((fetal or fetus or intrauterine) and (growth or develop*)):ti,ab,kw (Word variations have 

been searched)

 

 #65 (Preeclamp* or pre-eclamp*) or (Pregnan* and Toxemi*):ti,ab,kw (Word variations have been 

searched)

 #66 (Gestation* or pregnan*) and (hypertens* or toxemi*):ti,ab,kw (Word variations have been 

searched)

 

 #67 gestat* and (child*or newborn* or infan* or neonat*or baby or babies or pediatr* or 

paediatr*):ti,ab,kw (Word variations have been searched)

 

 #68 depression and (postpartum or postnatal or post-partum or post-natal or post partum or post natal 

or ante-natal or antenatal or ante natal):ti,ab,kw (Word variations have been searched)

 #69 grow* near/3 (child* or infant* or infancy):ti,ab,kw (Word variations have been searched)

 #70 congenital and (vision near/3 disorder*):ti,ab,kw (Word variations have been searched)

 

 #71 (learning near/3 disorder*) or dyslexi* or discalculi*:ti,ab,kw (Word variations have been searched)

 

 #72 (respiratory near/3 illness) or asthma* or wheez* or respiratory syncitial virus:ti,ab,kw (Word 

variations have been searched)

 

 #73 #34 or #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or 

#48 or #49 or #50

 #74 #51 or #52 or #53 or #54 or #55 or #56 or #57 or #58 or #59 or #60 or #61 or #62 or #63 or #64 or 

#65 or #66 or #67 or #68 or #69 or #70 or #71 or #72

 #75 #73 or #74

 #76 #33 and #75

LIMITED TO 2014-2015

===========================================================================

PUBMED “SIMILAR ARTICLE” SEARCH ON BABIN 2000:

Alpha linolenic acid in cholesterol esters: a marker of alphalinolenic acid intake in newborns.

Babin F, Rodriguez A, Sarda P, Vandeputte B, Mendy F, Descomps B.
A-17

Eur J Clin Nutr. 2000 Nov;54(11):840-3.

PMID: 11114678

===========================================================================

WEB OF SCIENCE FORWARD SEARCH ON BABIN 2000:

===========================================================================

SCOPUS FORWARD SEARCH ON BABIN 2000:

===========================================================================

DATABASE SEARCHED & TIME PERIOD COVERED:

CAB ABSTRACTS – 1/1/2000-8/28/2015

LANGUAGE:

 English

SEARCH STRATEGY:

ti(omega-3 OR omega3 OR "omega 3" OR "essential fatty acid" OR "essential fatty acids" OR linolenic OR 

"fish oil" OR "fish oils" OR polyunsaturated OR pufa OR dha OR epa OR long chain OR longchain OR 

Docosapentanoic OR Docosapentaenoic OR Docosahexaenoic OR Eicosapentaenoic OR icosapentaenoic 

OR ((n 3 OR n3 OR n-3) AND (oil OR pufa OR fatty acid OR omega 3)) OR alpha linolenic OR alphalinolenic 

OR alpha-linolenic OR linolenate OR cervonic OR timnodonic OR stearidonic OR butternut OR soybean 

OR pumpkin seed OR menhaden OR flax OR flaxseed OR flax seed OR linseed OR rape seed OR rapeseed 

OR canola OR soy OR soybean OR walnut OR mustard seed OR perilla OR shiso OR walnut OR "cod liver 

oil" OR "codliver oil" OR "marine oil" OR "marine oils" OR "marine fat" OR salmon OR mackerel OR 

herring OR tuna OR halibut OR seaweed OR anchov* OR sardine* OR Ropufa OR MaxEPA OR Omacor OR 

Efamed OR ResQ OR Epagis OR Almarin OR Coromega OR Lovaza OR Vascepa OR icosapent ethyl OR (fish 

AND (consum* OR intake OR diet*) ) OR “mediterranean diet” OR ((“Red blood cell” OR “red blood cells” 

OR phospholipid* OR plasma OR triacylglycerol OR cholesteryl OR ester OR adipos* OR fatty acid OR 

fatty acids OR erythrocyte OR ghost OR platelet* OR granulocyte OR neutrophil OR mononuclear OR LDL 

OR HDL) AND (EPA OR SDA OR stearidonic OR omega*))) 

AND

ti(("Child Development" OR (gestat* AND (age* OR durat* OR week*)) OR prematur* OR preterm OR 

pre-term OR ((Infant* OR baby) AND (birthweight OR birth-weight OR weight)) OR newborn OR neonatal 

OR (grow* AND (child* OR infant* OR infancy)) OR "Retinopathy of Prematurity" OR "retrolental 

fibroplasia" OR ADHD OR attention deficit disorder* OR "atopic dermatitis" OR (congenital AND ("vision 

disorder")) OR "learning disorder" OR "learning disorders" OR dyslexi* OR discalculi* OR "respiratory 

illness" OR asthma* OR wheez* OR respiratory syncitial virus OR autism OR autistic OR Asperger* OR 

ados OR hypersensitiv* OR allerg* OR (Fetal AND growth AND retard*) OR ((embryo* OR Fetus OR fetal 

OR fetus OR intrauterine) AND (growth OR develop*)) OR Preeclamp* OR pre-eclamp* OR ((Gestation* 

OR pregnan*) AND (hypertens* OR toxemi*)) OR (gestat* AND (child*or newborn* OR infan* OR 

neonat*or baby OR babies OR pediatr* OR paediatr*)) OR (depression AND (postpartum OR postnatal 

OR post-partum OR post-natal OR post partum OR post natal OR ante-natal OR antenatal OR ante natal)) 

OR (grow* AND (child* OR infant* OR infancy)))) 
B-1

Appendix B. List of Excluded Studies

This appendix lists all studies (publications) that were identified in our literature searches that 

were subsequently excluded during abstract or full-text screening. Among these excluded 

publications were some that were included in the original report. Most of the studies included in 

the original report were subsequently included in our analyses, but for the sole purpose of 

tracking the article flow from our literature searches and the reasons for exclusion, we counted 

the publications from the original report that appeared in our searches as having been excluded.

Studies included in the original report that were also identified in our 

searches – N=31

1. Agostoni C, Marangoni F, Giovannini M, et al. Prolonged breast-feeding (six months or 

more) and milk fat content at six months are associated with higher developmental scores at one 

year of age within a breast-fed population. Adv Exp Med Biol. 2001;501:137-41. PMID: 

11787675.

2. Auestad N, Halter R, Hall RT, et al. Growth and development in term infants fed long-chain 

polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate 

study. Pediatrics. 2001 Aug;108(2):372-81. PMID: 11483802.

3. Auestad N, Scott DT, Janowsky JS, et al. Visual, cognitive, and language assessments at 39 

months: a follow-up study of children fed formulas containing long-chain polyunsaturated fatty 

acids to 1 year of age. Pediatrics. 2003 Sep;112(3 Pt 1):e177-83. PMID: 12949309.

4. Birch EE, Birch DG, Hoffman DR, et al. Dietary essential fatty acid supply and visual acuity 

development. Invest Ophthalmol Vis Sci. 1992 10/1992;33(11):3242-53.

5. Birch EE, Garfield S, Hoffman DR, et al. A randomized controlled trial of early dietary 

supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev 

Med Child Neurol. 2000 Mar;42(3):174-81. PMID: 10755457.

6. Birch EE, Hoffman DR, Castaneda YS, et al. A randomized controlled trial of long-chain 

polyunsaturated fatty acid supplementation of formula in term infants after weaning at 6 wk of 

age. Am J Clin Nutr. 2002 Mar;75(3):570-80. PMID: 11864865.

7. Carlson SE, Werkman SH, Rhodes PG, et al. Visual-acuity development in healthy preterm 

infants: effect of marine-oil supplementation. Am J Clin Nutr. 1993 7/1993;58(1):35-42.

8. de Groot RH, Hornstra G, van Houwelingen AC, et al. Effect of alpha-linolenic acid 

supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status 

and pregnancy outcome. Am J Clin Nutr. 2004 Feb;79(2):251-60. PMID: 14749231.

9. Fewtrell MS, Abbott RA, Kennedy K, et al. Randomized, double-blind trial of long-chain 

polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. J 

Pediatr. 2004 Apr;144(4):471-9. PMID: 15069395.
B-2

10. Fewtrell MS, Morley R, Abbott RA, et al. Double-blind, randomized trial of long-chain 

polyunsaturated fatty acid supplementation in formula fed to preterm infants. Pediatrics. 2002 

Jul;110(1 Pt 1):73-82. PMID: 12093949.

11. Ghys A, Bakker E, Hornstra G, et al. Red blood cell and plasma phospholipid arachidonic 

and docosahexaenoic acid levels at birth and cognitive development at 4 years of age. Early Hum 

Dev. 2002 Oct;69(1-2):83-90. PMID: 12324186.

12. Helland IB, Saugstad OD, Smith L, et al. Similar effects on infants of n-3 and n-6 fatty acids 

supplementation to pregnant and lactating women. Pediatrics. 2001 Nov;108(5):E82. PMID: 

11694666.

13. Helland IB, Smith L, Saarem K, et al. Maternal supplementation with very-long-chain n-3

fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics. 

2003 Jan;111(1):e39-44. PMID: 12509593.

14. Hoffman DR, Birch EE, Birch DG, et al. Impact of early dietary intake and blood lipid 

composition of long-chain polyunsaturated fatty acids on later visual development. J Pediatr 

Gastroenterol Nutr. 2000 Nov;31(5):540-53. PMID: 11144440.

15. Innis SM, Adamkin DH, Hall RT, et al. Docosahexaenoic acid and arachidonic acid enhance 

growth with no adverse effects in preterm infants fed formula. J Pediatr. 2002 May;140(5):547-

54. PMID: 12032520.

16. Innis SM, Gilley J, Werker J. Are human milk long-chain polyunsaturated fatty acids related 

to visual and neural development in breast-fed term infants? J Pediatr. 2001 Oct;139(4):532-8. 

PMID: 11598600.

17. Koletzko B, Sauerwald U, Keicher U, et al. Fatty acid profiles, antioxidant status, and 

growth of preterm infants fed diets without or with long-chain polyunsaturated fatty acids. A 

randomized clinical trial. Eur J Nutr. 2003 Oct;42(5):243-53. PMID: 14569405.

18. Makrides M, Neumann MA, Jeffrey B, et al. A randomized trial of different ratios of linoleic 

to alpha-linolenic acid in the diet of term infants: effects on visual function and growth. Am J 

Clin Nutr. 2000 Jan;71(1):120-9. PMID: 10617956.

19. Makrides M, Neumann MA, Simmer K, et al. A critical appraisal of the role of dietary longchain polyunsaturated fatty acids on neural indices of term infants: a randomized, controlled 

trial. Pediatrics. 2000 Jan;105(1 Pt 1):32-8. PMID: 10617701.

20. Malcolm CA, Hamilton R, McCulloch DL, et al. Scotopic electroretinogram in term infants 

born of mothers supplemented with docosahexaenoic acid during pregnancy. Invest Ophthalmol 

Vis Sci. 2003 Aug;44(8):3685-91. PMID: 12882824.
B-3

21. Morris G, Moorcraft J, Mountjoy A, et al. A novel infant formula milk with added longchain polyunsaturated fatty acids from single-cell sources: a study of growth, satisfaction and 

health. Eur J Clin Nutr. 2000 Dec;54(12):883-6. PMID: 11114686.

22. O'Connor DL, Hall R, Adamkin D, et al. Growth and development in preterm infants fed 

long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Pediatrics. 

2001 Aug;108(2):359-71. PMID: 11483801.

23. Olsen SF, Secher NJ, Tabor A, et al. Randomised clinical trials of fish oil supplementation 

in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. BJOG. 2000 

Mar;107(3):382-95. PMID: 10740336.

24. Rocquelin G, Tapsoba S, Kiffer J, et al. Human milk fatty acids and growth of infants in 

Brazzaville (The Congo) and Ouagadougou (Burkina Faso). Public Health Nutr. 2003 

May;6(3):241-8. PMID: 12740073.

25. SanGiovanni JP, Parra-Cabrera S, Colditz GA, et al. Meta-analysis of dietary essential fatty 

acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in 

healthy preterm infants. Pediatrics. 2000 Jun;105(6):1292-8. PMID: 10835071.

26. Smuts CM, Huang M, Mundy D, et al. A randomized trial of docosahexaenoic acid 

supplementation during the third trimester of pregnancy. Obstet Gynecol. 2003 Mar;101(3):469-

79. PMID: 12636950.

27. van Wezel-Meijler G, van der Knaap MS, Huisman J, et al. Dietary supplementation of 

long-chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation. Acta 

Paediatr. 2002;91(9):942-50. PMID: 12412870.

28. Vanderhoof J, Gross S, Hegyi T. A multicenter long-term safety and efficacy trial of preterm 

formula supplemented with long-chain polyunsaturated fatty acids. J Pediatr Gastroenterol Nutr. 

2000 Aug;31(2):121-7. PMID: 10941962.

29. Voigt RG, Jensen CL, Fraley JK, et al. Relationship between omega3 long-chain 

polyunsaturated fatty acid status during early infancy and neurodevelopmental status at 1 year of 

age. J Hum Nutr Diet. 2002 Apr;15(2):111-20. PMID: 11972740.

30. Williams C, Birch EE, Emmett PM, et al. Stereoacuity at age 3.5 y in children born full-term 

is associated with prenatal and postnatal dietary factors: a report from a population-based cohort 

study. Am J Clin Nutr. 2001 Feb;73(2):316-22. PMID: 11157330.

31. Xiang M, Alfven G, Blennow M, et al. Long-chain polyunsaturated fatty acids in human 

milk and brain growth during early infancy. Acta Paediatr. 2000 Feb;89(2):142-7. PMID: 

10709881.

Not a human study- N=4
B-4

1. Das UN. Can memory be improved? A discussion on the role of ras, GABA, acetylcholine, 

NO, insulin, TNF-α, and long-chain polyunsaturated fatty acids in memory formation and 

consolidation. Brain Dev. 2003 Jun, 2003;25(4):251-61. PMID: 2006-00473-006.

2. Field CJ, Van Aerde JE, Robinson LE, et al. Feeding a formula supplemented with long chain 

polyunsaturated fatty acids modifies the "ex vivo" cytokine responses to food proteins in infants 

at low risk for allergy. Pediatr Res. 2008 Oct;64(4):411-7. PMID: 18552712.

3. Fu Z, Lofqvist CA, Shao Z, et al. Dietary omega-3 polyunsaturated fatty acids decrease 

retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase 

adiponectin. Am J Clin Nutr. 2015 Apr;101(4):879-88. PMID: 25833984.

4. Russell KL. N-3 fatty acids and juvenile traumatic brain injury: Effects of dietary n-3 fatty 

acid content, n-3 fatty acid status, and orally dosed fish oil on sensorimotor and biochemical 

outcomes. Dissertation Abstracts International: Section B: The Sciences and Engineering. 2014 

2014;74(11-B(E))PMID: 2014-99100-341.

Not omega-3 - N=53

1. Akobeng Anthony K, Thomas Adrian G. Enteral nutrition for maintenance of remission in 

Crohn's disease. Cochrane Database of Systematic Reviews: John Wiley & Sons, Ltd; 2007.

2. Andres A, Casey PH, Cleves MA, et al. Body fat and bone mineral content of infants fed 

breast milk, cow's milk formula, or soy formula during the first year of life. J Pediatr. 2013 

Jul;163(1):49-54. PMID: 23375908.

3. Arslanoglu S, Moro GE, Ziegler EE. Adjustable fortification of human milk fed to preterm 

infants: does it make a difference? J Perinatol. 2006 Oct;26(10):614-21. PMID: 16885989.

4. Benefice E, Monrroy SJ, Rodriguez RW. A nutritional dilemma: fish consumption, mercury 

exposure and growth of children in Amazonian Bolivia. Int J Environ Health Res. 2008 

Dec;18(6):415-27. PMID: 19031146.

5. Bitsanis D, Ghebremeskel K, Moodley T, et al. Gestational diabetes mellitus enhances 

arachidonic and docosahexaenoic acids in placental phospholipids. Lipids. 2006 Apr;41(4):341-

6. PMID: 16808147.

6. Brookes KJ, Chen W, Xu X, et al. Association of fatty acid desaturase genes with attentiondeficit/hyperactivity disorder. Biol Psychiatry. 2006 Nov 15;60(10):1053-61. PMID: 16893529.

7. Brown CM, Austin DW, Busija L. Observable essential fatty acid deficiency markers and 

autism spectrum disorder. Breastfeed Rev. 2014 Jul;22(2):21-6. PMID: 25109097.

8. Burns J, Boogaard H, Turley R, et al. Interventions to reduce ambient particulate matter air 

pollution and their effect on health. Cochrane Database of Systematic Reviews: John Wiley & 

Sons, Ltd; 2014.
B-5

9. Caritis SN, Venkataramanan R, Thom E, et al. Relationship between 17-alpha 

hydroxyprogesterone caproate concentration and spontaneous preterm birth. Am J Obstet 

Gynecol. 2014 Feb;210(2):128.e1-6. PMID: 24113254.

10. Chisaguano AM, Montes R, Castellote AI, et al. Elaidic, vaccenic, and rumenic acid status 

during pregnancy: association with maternal plasmatic LC-PUFAs and atopic manifestations in 

infants. Pediatr Res. 2014 Nov;76(5):470-6. PMID: 25119335.

11. Colome G, Sierra C, Blasco J, et al. Intestinal permeability in different feedings in infancy. 

Acta Paediatr. 2007 Jan;96(1):69-72. PMID: 17187607.

12. D'Auria E, Sala M, Lodi F, et al. Nutritional value of a rice-hydrolysate formula in infants 

with cows' milk protein allergy: a randomized pilot study. J Int Med Res. 2003 MayJun;31(3):215-22. PMID: 12870375.

13. Dennis CL, Dowswell T. Interventions (other than pharmacological, psychosocial or 

psychological) for treating antenatal depression. Cochrane Database of Systematic Reviews. 

2013;7:CD006795. PMID: 23904069.

14. Després C, Beuter A, Richer F, et al. Neuromotor functions in Inuit preschool children 

exposed to Pb, PCBs, and Hg. Neurotoxicol Teratol. 2005 Mar-Apr, 2005;27(2):245-57. PMID: 

2005-02816-006.

15. Dotterud CK, Storro O, Simpson MR, et al. The impact of pre- and postnatal exposures on 

allergy related diseases in childhood: a controlled multicentre intervention study in primary 

health care. BMC Public Health. 2013;13:123. PMID: 23394141.

16. Fomon SJ, Thomas LN, Filer LJ, Jr., et al. Food consumption and growth of normal infants 

fed milk-based formulas. Acta Paediatr Scand. 1971 1971;223(Suppl):1-36.

17. Ford JH. Preconception risk factors and SGA babies: Papilloma virus, omega 3 and fat 

soluble vitamin deficiencies. Early Hum Dev. 2011 Dec;87(12):785-9. PMID: 21705161.

18. Fugh-Berman A, Kronenberg F. Complementary and alternative medicine (CAM) in 

reproductive-age women: a review of randomized controlled trials (Structured abstract). Reprod 

Toxicol; 2003. p. 137-52.

19. Garcia-Marcos L, Castro-Rodriguez JA, Weinmayr G, et al. Influence of Mediterranean diet 

on asthma in children: a systematic review and meta-analysis. Pediatr Allergy Immunol. 2013 

Jun;24(4):330-8. PMID: 23578354.

20. Heppe DH, Kiefte-de Jong JC, Durmus B, et al. Parental, fetal, and infant risk factors for 

preschool overweight: the Generation R Study. Pediatr Res. 2013 Jan;73(1):120-7. PMID: 

23138398.
B-6

21. Klenoff-Brumberg HL, Genen LH. High versus low medium chain triglyceride content of 

formula for promoting short term growth of preterm infants. Cochrane Database of Systematic 

Reviews. 2003(1):CD002777. PMID: 12535437.

22. Koo WW, Hammami M, Margeson DP, et al. Reduced bone mineralization in infants fed 

palm olein-containing formula: a randomized, double-blinded, prospective trial. Pediatrics. 2003 

May;111(5 Pt 1):1017-23. PMID: 12728082.

23. Laitinen K, Hoppu U, Hamalainen M, et al. Breast milk fatty acids may link innate and 

adaptive immune regulation: analysis of soluble CD14, prostaglandin E2, and fatty acids. Pediatr 

Res. 2006 May;59(5):723-7. PMID: 16627889.

24. Lasekan J, Baggs G, Acosta S, et al. Soy protein-based infant formulas with supplemental 

fructooligosaccharides: Gastrointestinal tolerance and hydration status in newborn infants. 

Nutrients; 2015. p. 3022-37.

25. Lassi Zohra S, Salam Rehana A, Haider Batool A, et al. Folic acid supplementation during 

pregnancy for maternal health and pregnancy outcomes. Cochrane Database of Systematic 

Reviews: John Wiley & Sons, Ltd; 2013.

26. Linday LA. Cod liver oil, young children, and upper respiratory tract infections. J Am Coll 

Nutr. 2010 Dec;29(6):559-62. PMID: 21677119.

27. Luoto R, Kinnunen TI, Aittasalo M, et al. Primary prevention of gestational diabetes 

mellitus and large-for-gestational-age newborns by lifestyle counseling: a cluster-randomized 

controlled trial. PLoS Medicine / Public Library of Science. 2011 May;8(5):e1001036. PMID: 

21610860.

28. Lynch ML, Huang LS, Cox C, et al. Varying coefficient function models to explore 

interactions between maternal nutritional status and prenatal methylmercury toxicity in the 

Seychelles Child Development Nutrition Study.[Erratum appears in Environ Res. 2011 

Nov;111(8):1334]. Environ Res. 2011 Jan;111(1):75-80. PMID: 20961536.

29. Martinez-Gonzalez MA, Bes-Rastrollo M. Nut consumption, weight gain and obesity: 

Epidemiological evidence. Nutrition Metabolism & Cardiovascular Diseases. 2011 Jun;21 Suppl 

1:S40-5. PMID: 21216574.

30. Mendez MA, Anthony MS, Arab L. Soy-based formulae and infant growth and 

development: a review. J Nutr. 2002 Aug;132(8):2127-30. PMID: 12163650.

31. Mikkelsen TB, Osterdal ML, Knudsen VK, et al. Association between a Mediterranean-type 

diet and risk of preterm birth among Danish women: a prospective cohort study. Acta Obstet 

Gynecol Scand. 2008;87(3):325-30. PMID: 18307073.

32. Muche-Borowski C, Kopp M, Reese I, et al. Allergy prevention. Deutsches Arzteblatt 

International. 2009 Sep;106(39):625-31. PMID: 19890407.
B-7

33. Muche-Borowski C, Kopp M, Reese I, et al. Allergy prevention. Journal der Deutschen 

Dermatologischen Gesellschaft. 2010 Sep;8(9):718-24. PMID: 19878402.

34. Muckle G, Ayotte P, Dewailly EE, et al. Prenatal exposure of the northern Quebec Inuit 

infants to environmental contaminants. Environ Health Perspect. 2001 Dec;109(12):1291-9. 

PMID: 11748038.

35. Murrin C, Shrivastava A, Kelleher CC, et al. Maternal macronutrient intake during 

pregnancy and 5 years postpartum and associations with child weight status aged five. Eur J Clin 

Nutr. 2013 Jun;67(6):670-9. PMID: 23612514.

36. Nachmias N, Landman Y, Danon YL, et al. Soy allergy following early soy feeding in 

neonates. Israel Medical Association Journal: Imaj. 2010 Nov;12(11):684-6. PMID: 21243869.

37. Netting MJ, Middleton PF, Makrides M. Does maternal diet during pregnancy and lactation 

affect outcomes in offspring? A systematic review of food-based approaches. Nutrition. 2014 

Nov-Dec;30(11-12):1225-41. PMID: 25280403.

38. Niinivirta K, Isolauri E, Laakso P, et al. Dietary counseling to improve fat quality during 

pregnancy alters maternal fat intake and infant essential fatty acid status. J Nutr. 2011 

Jul;141(7):1281-5. PMID: 21593355.

39. Piacentini G, Peroni D, Bessi E, et al. Molecular characterization of intestinal microbiota in 

infants fed with soymilk. J Pediatr Gastroenterol Nutr. 2010 Jul;51(1):71-6. PMID: 20543718.

40. Qureshi NA, Al-Bedah AM. Mood disorders and complementary and alternative medicine: 

A literature review. Neuropsychiatr Dis Treat. 2013 May 13, 2013;9:ArtID 639 - 58. PMID: 

2013-21282-001.

41. Rask-Nissila L, Jokinen E, Terho P, et al. Effects of diet on the neurologic development of 

children at 5 years of age: the STRIP project. J Pediatr. 2002 Mar;140(3):328-33. PMID: 

11953731.

42. Rumbold A, Duley L, Crowther Caroline A, et al. Antioxidants for preventing preeclampsia. Cochrane Database of Systematic Reviews: John Wiley & Sons, Ltd; 2008.

43. Say L, Gülmezoglu AM, Hofmeyr GJ. Maternal nutrient supplementation for suspected 

impaired fetal growth. Cochrane Database of Systematic Reviews: John Wiley & Sons, Ltd; 

2003.

44. Scholl TO, Leskiw M, Chen X, et al. Oxidative stress, diet, and the etiology of preeclampsia. 

Am J Clin Nutr. 2005 Jun;81(6):1390-6. PMID: 15941892.
B-8

45. Shoji H, Hisata K, Suzuki M, et al. Effects of parenteral soybean oil lipid emulsion on the 

long-chain polyunsaturated fatty acid profile in very-low-birth-weight infants. Acta Paediatr. 

2011 Jul;100(7):972-6. PMID: 21366690.

46. Simpson A, Custovic A. Allergen avoidance in the primary prevention of asthma. Curr Opin 

Allergy Clin Immunol. 2004 Feb;4(1):45-51. PMID: 15090919.

47. Suren P, Roth C, Bresnahan M, et al. Association between maternal use of folic acid 

supplements and risk of autism spectrum disorders in children. JAMA. 2013 Feb 13;309(6):570-

7. PMID: 23403681.

48. Suzuki K, Nakai K, Sugawara T, et al. Neurobehavioral effects of prenatal exposure to 

methylmercury and PCBs, and seafood intake: neonatal behavioral assessment scale results of 

Tohoku study of child development. Environ Res. 2010 Oct;110(7):699-704. PMID: 20673887.

49. Tofail F, Hamadani JD, Ahmed AZ, et al. The mental development and behavior of lowbirth-weight Bangladeshi infants from an urban low-income community. Eur J Clin Nutr. 2012 

Feb;66(2):237-43. PMID: 21952697.

50. Tomedi LE, Chang CC, Newby PK, et al. Pre-pregnancy obesity and maternal nutritional 

biomarker status during pregnancy: a factor analysis. Public Health Nutr. 2013 Aug;16(8):1414-

8. PMID: 23522785.

51. Trock BJ, Hilakivi-Clarke L, Clarke R. Meta-analysis of soy intake and breast cancer risk. J 

Natl Cancer Inst. 2006 Apr 5;98(7):459-71. PMID: 16595782.

52. Wang H, Jiang H, Yang L, et al. Impacts of dietary fat changes on pregnant women with 

gestational diabetes mellitus: a randomized controlled study. Asia Pac J Clin Nutr. 

2015;24(1):58-64. PMID: 25740743.

53. Zachos M, Tondeur M, Griffiths Anne M. Enteral nutritional therapy for induction of 

remission in Crohn's disease. Cochrane Database of Systematic Reviews: John Wiley & Sons, 

Ltd; 2007.

Not in English- N=1

1. Patin RV, Vitolo MR, Valverde MA, et al. The influence of sardine consumption on the 

omega-3 fatty acid content of mature human milk. Jornal de Pediatria. 2006 Jan-Feb;82(1):63-9. 

PMID: 16532150.

Treatment study, not prevention/risk study - N=29

1. Anderson G, Maes M. Postpartum depression: Psychoneuroimmunological underpinnings and 

treatment. Neuropsychiatr Dis Treat. 2013 Feb 20, 2013;9:ArtID 277-87. PMID: 2013-07025-

001.
B-9

2. Belanger SA, Vanasse M, Spahis S, et al. Omega-3 fatty acid treatment of children with 

attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study. 

Paediatr Child Health. 2009 Feb;14(2):89-98. PMID: 19436468.

3. Bent S, Bertoglio K, Hendren RL. Omega-3 fatty acids for autistic spectrum disorder: a 

systematic review. J Autism Dev Disord. 2009 Aug;39(8):1145-54. PMID: 19333748.

4. Bent S, Bertoglio K, Hendren RL. Omega-3 fatty acids for autism spectrum disorder: A 

systematic review. J Autism Dev Disord. 2009 Aug, 2009;39(8):1145-54. PMID: 2010-05191-

005.

5. Bent S, Hendren RL, Zandi T, et al. Internet-based, randomized, controlled trial of omega-3 

fatty acids for hyperactivity in autism. J Am Acad Child Adolesc Psychiatry. 2014 

Jun;53(6):658-66. PMID: 24839884.

6. Clayton EH, Hanstock TL, Garg ML, et al. Long chain omega-3 polyunsaturated fatty acids 

in the treatment of psychiatric illnesses in children and adolescents. Acta Neuropsychiatrica. 

2007 Apr, 2007;19(2):92-103. PMID: 2007-05812-003.

7. Covar R, Gleason M, Macomber B, et al. Impact of a novel nutritional formula on asthma 

control and biomarkers of allergic airway inflammation in children. Clin Exp Allergy. 2010 

Aug;40(8):1163-74. PMID: 20545703.

8. Curtis LT, Patel K. Nutritional and environmental approaches to preventing and treating 

autism and attention deficit hyperactivity disorder (ADHD): A review. The Journal of 

Alternative and Complementary Medicine. 2008 Jan, 2008;14(1):79-85. PMID: 2008-01611-002.

9. Freeman MP, Hibbeln JR, Wisner KL, et al. Omega-3 fatty acids: Evidence basis for 

treatment and future research in psychiatry. J Clin Psychiatry. 2006 Dec, 2006;67(12):1954-67. 

PMID: 2007-07422-017.

10. Gil-Campos M, Sanjurjo Crespo P. Omega 3 fatty acids and inborn errors of metabolism. Br 

J Nutr. 2012 Jun;107 Suppl 2:S129-36. PMID: 22591887.

11. Gool CJ, Zeegers MP, Thijs C. Oral essential fatty acid supplementation in atopic dermatitis: 

a meta-analysis of placebo-controlled trials (Structured abstract). Br J Dermatol; 2004. p. 728-

40.

12. Gustafsson PA, Birberg-Thornberg U, Duchen K, et al. EPA supplementation improves 

teacher-rated behaviour and oppositional symptoms in children with ADHD. Acta Paediatr. 2010 

Oct;99(10):1540-9. PMID: 20491709.

13. James S, Montgomery P, Williams K. Omega-3 fatty acids supplementation for autism 

spectrum disorders (ASD). Cochrane Database of Systematic Reviews. 2011(11):CD007992. 

PMID: 22071839.
B-10

14. Johnson M, Mansson JE, Ostlund S, et al. Fatty acids in ADHD: plasma profiles in a 

placebo-controlled study of Omega 3/6 fatty acids in children and adolescents. Attention Deficit 

and Hyperactivity Disorders. 2012 Dec;4(4):199-204. PMID: 22753087.

15. Mankad D, Dupuis A, Smile S, et al. A randomized, placebo controlled trial of omega-3 

fatty acids in the treatment of young children with autism. Mol Autism. 2015;6:18. PMID: 

25798215.

16. Manor I, Magen A, Keidar D, et al. Safety of phosphatidylserine containing omega3 fatty 

acids in ADHD children: a double-blind placebo-controlled trial followed by an open-label 

extension. European Psychiatry: the Journal of the Association of European Psychiatrists. 2013 

Aug;28(6):386-91. PMID: 23312676.

17. Meldrum SJ, D'Vaz N, Dunstan J, et al. The Infant Fish Oil Supplementation Study (IFOS): 

design and research protocol of a double-blind, randomised controlled n--3 LCPUFA 

intervention trial in term infants. Contemp Clin Trials. 2011 Sep;32(5):771-8. PMID: 21718804.

18. Oliver C, Watson H. Omega-3 fatty acids for cystic fibrosis. Cochrane Database of 

Systematic Reviews: John Wiley & Sons, Ltd; 2013.

19. Ooi YP, Weng SJ, Jang LY, et al. Omega-3 fatty acids in the management of autism 

spectrum disorders: findings from an open-label pilot study in Singapore. Eur J Clin Nutr. 2015 

Aug;69(8):969-71. PMID: 25804268.

20. Politi P, Rocchetti M, Emanuele E, et al. Randomized placebo-controlled trials of omega-3 

polyunsaturated fatty acids in psychiatric disorders: a review of the current literature. Current 

Drug Discovery Technologies. 2013 Sep;10(3):245-53. PMID: 21838664.

21. Raz R, Carasso RL, Yehuda S. The influence of short-chain essential fatty acids on children 

with attention-deficit/hyperactivity disorder: a double-blind placebo-controlled study. J Child 

Adolesc Psychopharmacol. 2009 Apr;19(2):167-77. PMID: 19364294.

22. Raz R, Gabis L. Essential fatty acids and attention-deficit-hyperactivity disorder: a 

systematic review. Dev Med Child Neurol. 2009 Aug;51(8):580-92. PMID: 19549202.

23. Sinn N, Bryan J, Wilson C. Cognitive effects of polyunsaturated fatty acids in children with 

attention deficit hyperactivity disorder symptoms: a randomised controlled trial. Prostaglandins 

Leukotrienes & Essential Fatty Acids. 2008 Apr-May;78(4-5):311-26. PMID: 18514501.

24. Smith LJ, Kalhan R, Wise RA, et al. Effect of a soy isoflavone supplement on lung function 

and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial. 

JAMA. 2015 May 26;313(20):2033-43. PMID: 26010632.

25. Spahis S, Vanasse M, Belanger SA, et al. Lipid profile, fatty acid composition and pro- and 

anti-oxidant status in pediatric patients with attention-deficit/hyperactivity disorder. 
B-11

Prostaglandins Leukotrienes & Essential Fatty Acids. 2008 Jul-Aug;79(1-2):47-53. PMID: 

18757191.

26. Transler C, Eilander A, Mitchell S, et al. The impact of polyunsaturated fatty acids in 

reducing child attention deficit and hyperactivity disorders. Journal of Attention Disorders. 2010 

Nov;14(3):232-46. PMID: 20424008.

27. Tsuchimine S, Saito M, Kaneko S, et al. Decreased serum levels of polyunsaturated fatty 

acids and folate, but not brain-derived neurotrophic factor, in childhood and adolescent females 

with depression. Psychiatry Res. 2015 Jan 30, 2015;225(1-2):187-90. PMID: 2014-52502-001.

28. van Gool CJ, Zeegers MP, Thijs C. Oral essential fatty acid supplementation in atopic 

dermatitis-a meta-analysis of placebo-controlled trials. Br J Dermatol. 2004 Apr;150(4):728-40. 

PMID: 15099370.

29. Wu Q, Zhou T, Ma L, et al. Protective effects of dietary supplementation with natural 

omega-3 polyunsaturated fatty acids on the visual acuity of school-age children with lower IQ or 

attention-deficit hyperactivity disorder. Nutrition. 2015 Jul-Aug;31(7-8):935-40. PMID: 

26015389.

Study design - N=53

1. Al-Tamer YY, Mahmood AA. Fatty-acid composition of the colostrum and serum of fullterm 

and preterm delivering Iraqi mothers. Eur J Clin Nutr. 2004 Aug;58(8):1119-24. PMID: 

15054424.

2. Arnold LE. Fish oil is not snake oil. J Am Acad Child Adolesc Psychiatry. 2011 Oct, 

2011;50(10):969-71. PMID: 2011-22667-007.

3. Bawadi HA, Al-Kuran O, Al-Bastoni LA, et al. Gestational nutrition improves outcomes of 

vaginal deliveries in Jordan: an epidemiologic screening. Nutr Res. 2010 Feb;30(2):110-7. 

PMID: 20226996.

4. Beck M, Zelczak G, Lentze MJ. Abnormal fatty acid composition in umbilical cord blood of 

infants at high risk of atopic disease. Acta Paediatr. 2000 Mar;89(3):279-84. PMID: 10772274.

5. Berman D, Limb R, Somers E, et al. Prenatal omega-3 supplementation and risk of eczema 

among offspring at age 36 months: Long-term follow-up of the mothers, omega-3, & mental 

health trial. Am J Obstet Gynecol; 2015. p. S162.

6. Best K, Makrides M, Gold M. Effect of maternal dietary long chain polyunsaturated fatty acid 

intake during pregnancy on clinical outcomes of allergic disease in the offspring: A systematic 

review. Intern Med J; 2014. p. 2.
B-12

7. Best K, Sullivan T, Gold M, et al. Six-year follow up of children at high hereditary risk of 

allergy, born to mothers supplemented with docosahexaenoic acid (DHA) in the domino trial. J 

Paediatr Child Health; 2015. p. 58.

8. Bjerve KS, Thoresen L, Bonaa K, et al. Clinical studies with alpha-linolenic acid and longchain n-3 fatty acids. Nutrition. 1992 3/1992;8(2):130-2.

9. Bodnar LM, Wisner KL, Luther JF, et al. An exploratory factor analysis of nutritional 

biomarkers associated with major depression in pregnancy. Public Health Nutr. 2012 

Jun;15(6):1078-86. PMID: 22152590.

10. Brigandi SA, Shao H, Qian SY, et al. Autistic children exhibit decreased levels of essential 

Fatty acids in red blood cells. Int J Mol Sci. 2015;16(5):10061-76. PMID: 25946342.

11. Carlsen K, Pedersen L, Bonnelykke K, et al. Association between whole-blood 

polyunsaturated fatty acids in pregnant women and early fetal weight. Eur J Clin Nutr. 2013 

Sep;67(9):978-83. PMID: 23756387.

12. Cosatto VF, Else PL, Meyer BJ. Do pregnant women and those at risk of developing postnatal depression consume lower amounts of long chain omega-3 polyunsaturated fatty acids? 

Nutrients. 2010 Feb;2(2):198-213. PMID: 22254016.

13. Crawford MA, Costeloe K, Doyle W, et al. Potential diagnostic value of the umbilical artery 

as a definition of neural fatty acid status of the fetus during its growth: the umbilical artery as a 

diagnostic tool. Biochem Soc Trans. 1990 10/1990;18(5):761-6.

14. Crawford MA, Doyle W, Drury P, et al. n-6 and n-3 fatty acids during early human 

development. J Intern Med. 1989 1989;225(731 Suppl):159-69.

15. Dirix CE, Kester AD, Hornstra G. Associations between term birth dimensions and prenatal 

exposure to essential and trans fatty acids. Early Hum Dev. 2009 Aug;85(8):525-30. PMID: 

19477608.

16. Drover JR. 'Three randomized controlled trials of early long-chain polyunsaturated fatty acid 

supplementation on means-end problem solving in nine month-olds': Addendum. Child Dev. 

2012 Nov-Dec, 2012;83(6):2139. PMID: 2012-31193-022.

17. Felton CV, Chang TC, Crook D, et al. Umbilical vessel wall fatty acids after normal and 

retarded fetal growth. Archives of Disease in Childhood Fetal & Neonatal Edition. 1994 

1/1994;70(1):F36-F9.

18. Gianni ML, Roggero P, Baudry C, et al. The influence of a formula supplemented with dairy 

lipids and plant oils on the erythrocyte membrane omega-3 fatty acid profile in healthy full-term 

infants: a double-blind randomized controlled trial. BMC Pediatr. 2012;12:164. PMID: 

23072617.
B-13

19. Grigoriadis S, Barrett J, Pittini R, et al. Omega-3 supplements in pregnancy: are we too late 

to identify the possible benefits? Journal of Obstetrics & Gynaecology Canada: JOGC. 2010 

Mar;32(3):209-16. PMID: 20500964.

20. Haby MM, Peat JK, Marks GB, et al. Asthma in preschool children: prevalence and risk 

factors. Thorax. 2001 Aug;56(8):589-95. PMID: 11462059.

21. Harper M. Randomized controlled trial of omega-3 fatty acid supplementation for recurrent 

preterm birth prevention. Am J Obstet Gynecol; 2007. p. S2, Abstract no: 3.

22. Harper M. Low maternal omega-3 levels prior to 22 weeks' gestation are associated with 

preterm delivery and low fish intake. Am J Obstet Gynecol; 2009. p. S172-s3.

23. Hauner H, Vollhardt C, Schneider KT, et al. The impact of nutritional fatty acids during 

pregnancy and lactation on early human adipose tissue development. Rationale and design of the 

INFAT study. Ann Nutr Metab. 2009;54(2):97-103. PMID: 19295192.

24. Iranpour R, Kelishadi R, Babaie S, et al. Comparison of long chain polyunsaturated fatty 

acid content in human milk in preterm and term deliveries and its correlation with mothers' diet. 

J Res Med Sci. 2013 Jan;18(1):1-5. PMID: 23901333.

25. Kar S, Thangaratinam S, Wong M, et al. Can essential fatty acids prevent early preterm 

delivery? A meta-analysis of evidence (Provisional abstract). Database of Abstracts of Reviews 

of Effects; 2014. p. A15.

26. Kazemian E, Dorosty-Motlagh AR, Sotoudeh G, et al. Nutritional status of women with 

gestational hypertension compared with normal pregnant women. Hypertens Pregnancy. 2013 

May;32(2):146-56. PMID: 23725080.

27. Keim SA. Long-chain polyunsaturated fatty acids in breast milk and infant formula, 

maternal perinatal mental health, and infant development. Dissertation Abstracts International: 

Section B: The Sciences and Engineering. 2009 2009;70(4-B):2170. PMID: 2009-99200-299.

28. Kirby A, Woodward A, Jackson S, et al. Childrens' learning and behaviour and the 

association with cheek cell polyunsaturated fatty acid levels. Res Dev Disabil. 2010 MayJun;31(3):731-42. PMID: 20172688.

29. Koletzko B, Braun M. Arachidonic acid and early human growth: is there a relation? Ann 

Nutr Metab. 1991 1991;35(3):128-31.

30. Kovacs A, Funke S, Marosvolgyi T, et al. Fatty acids in early human milk after preterm and 

full-term delivery. J Pediatr Gastroenterol Nutr. 2005 Oct;41(4):454-9. PMID: 16205514.

31. Kramer MS, Kahn SR, Platt RW, et al. Antioxidant vitamins, long-chain fatty acids, and 

spontaneous preterm birth. Epidemiology. 2009 Sep;20(5):707-13. PMID: 19568173.
B-14

32. Kuipers RS, Luxwolda MF, Dijck-Brouwer DA, et al. Differences in preterm and term milk 

fatty acid compositions may be caused by the different hormonal milieu of early parturition. 

Prostaglandins Leukotrienes & Essential Fatty Acids. 2011 Dec;85(6):369-79. PMID: 21903369.

33. Kuriki K, Nagaya T, Tokudome Y, et al. Plasma concentrations of (n-3) highly unsaturated 

fatty acids are good biomarkers of relative dietary fatty acid intakes: a cross-sectional study. J 

Nutr. 2003 Nov;133(11):3643-50. PMID: 14608088.

34. Labadaridis I, Moraitou M, Theodoraki M, et al. Linoleic and arachidonic acid in perinatal 

asphyxia and prematurity. J Matern Fetal Neonatal Med. 2007 Aug;20(8):623-6. PMID: 

17674280.

35. Lauritzen L, Halkjaer LB, Mikkelsen TB, et al. Fatty acid composition of human milk in 

atopic Danish mothers. Am J Clin Nutr. 2006 Jul;84(1):190-6. PMID: 16825695.

36. Lof M, Hilakivi-Clarke L, Sandin SS, et al. Dietary fat intake and gestational weight gain in 

relation to estradiol and progesterone plasma levels during pregnancy: a longitudinal study in 

Swedish women. BMC Womens Health. 2009;9:10. PMID: 19402915.

37. Marangell LB, Martinez JM, Zboyan HA, et al. Omega-3 Fatty Acids for the Prevention of 

Postpartum Depression: Negative Data From a Preliminary, Open-Label Pilot Study. Depress 

Anxiety. 2004 2004;19(1):20-3. PMID: 2004-11482-003.

38. McCulloch D, Malcolm CA, Montgomery C, et al. Maternal fish oil supplementation and 

visual maturation in term infants. American Academy of Optometry; 2002.

39. Mehendale S, Kilari A, Dangat K, et al. Fatty acids, antioxidants, and oxidative stress in preeclampsia. Int J Gynaecol Obstet. 2008 Mar;100(3):234-8. PMID: 17977540.

40. Mihrshahi S, Peat JK, Webb K, et al. Effect of omega-3 fatty acid concentrations in plasma 

on symptoms of asthma at 18 months of age. Pediatr Allergy Immunol. 2004 Dec;15(6):517-22. 

PMID: 15610365.

41. Mozurkewich E, Chilimigras J, Klemens C, et al. The mothers, Omega-3 and mental health 

study. BMC Pregnancy Childbirth. 2011;11:46. PMID: 21696635.

42. Murray KE, Nyp SS. Postpartum depression. J Dev Behav Pediatr. 2011 Feb-Mar, 

2011;32(2):175. PMID: 2011-03393-021.

43. Savino F, Serraino P, Prino A, et al. Arachidonic (AA) and docosahexaenoic (DHA) acid 

content in healthy infants fed with an HA milk formula supplemented with LCPUFA and in 

breast fed infants. Adv Exp Med Biol. 2000;478:411-2. PMID: 11065107.

44. Schindler T, Gladman L, Sinn John KH, et al. Polyunsaturated fatty acid supplementation in 

infancy for the prevention of allergy and food hypersensitivity. Cochrane Database of 

Systematic Reviews: John Wiley & Sons, Ltd; 2012.
B-15

45. Shiraishi M, Matsuzaki M, Yatsuki Y, et al. Associations of dietary intake and plasma 

concentrations of eicosapentaenoic and docosahexaenoic acid with prenatal depressive 

symptoms in Japan. Nurs Health Sci. 2015 Jun, 2015;17(2):257-62. PMID: 2015-19000-017.

46. Suzuki T. Maternal depression and child development after prenatal DHA supplementation. 

JAMA. 2011 Jan 26;305(4):359-60; author reply 60-1. PMID: 21266681.

47. Thorp JM, Jr., Rice MM, Harper M, et al. Advanced lipoprotein measures and recurrent 

preterm birth. Am J Obstet Gynecol. 2013 Oct;209(4):342.e1-7. PMID: 23770464.

48. Thorsdottir I, Birgisdottir BE, Halldorsdottir S, et al. Association of fish and fish liver oil 

intake in pregnancy with infant size at birth among women of normal weight before pregnancy in 

a fishing community. Am J Epidemiol. 2004 Sep 1;160(5):460-5. PMID: 15321843.

49. Tinoco SM, Sichieri R, Setta CL, et al. n-3 polyunsaturated fatty acids in milk is associate to 

weight gain and growth in premature infants. Lipids Health Dis. 2009;8:23. PMID: 19558659.

50. Udell T, Makrides M, Gibson RA. The effect of infant diets supplemented with alphalinolenic acid on growth and development: a systematic review and meta-analysis of randomised 

controlled trials. Asia Pac J Clin Nutr. 2003;12 Suppl:S45. PMID: 15023661.

51. Verly-Miguel MVB, Farias DR, Pinto TdJP, et al. Serum docosahexaenoic acid (DHA) is 

inversely associated with anxiety disorders in early pregnancy. J Anxiety Disord. 2015 Mar, 

2015;30:34-40. PMID: 2015-11323-008.

52. Vik T. Early environment, early feeding, and later development: Should milk formula be 

supplemented with polyunsaturated fatty acids? Dev Med Child Neurol. 2012 Dec, 

2012;54(12):1074-5. PMID: 2012-31127-005.

53. Xiang M, Harbige LS, Zetterstrom R. Long-chain polyunsaturated fatty acids in Chinese and 

Swedish mothers: diet, breast milk and infant growth. Acta Paediatr. 2005 Nov;94(11):1543-9. 

PMID: 16303692.

Population not of interest - N=37

1. Andersen AD, Michaelsen KF, Hellgren LI, et al. A randomized controlled intervention with 

fish oil versus sunflower oil from 9 to 18 months of age: exploring changes in growth and 

skinfold thicknesses. Pediatr Res; 2011. p. 368-74.

2. Barman M, Jonsson K, Sandin A, et al. Serum fatty acid profile does not reflect seafood 

intake in adolescents with atopic eczema. Acta Paediatr. 2014 Sep;103(9):968-76. PMID: 

24837739.
B-16

3. Bolte G, Kompauer I, Fobker M, et al. Fatty acids in serum cholesteryl esters in relation to 

asthma and lung function in children. Clin Exp Allergy. 2006 Mar;36(3):293-302. PMID: 

16499639.

4. Burns JS, Dockery DW, Neas LM, et al. Low dietary nutrient intakes and respiratory health in 

adolescents. Chest. 2007 Jul;132(1):238-45. PMID: 17475634.

5. Chatchatee P, Lee WS, Carrilho E, et al. Effects of growing-up milk supplemented with 

prebiotics and LCPUFAs on infections in young children. J Pediatr Gastroenterol Nutr. 2014 

Apr;58(4):428-37. PMID: 24614142.

6. Colter AL, Cutler C, Meckling KA. Fatty acid status and behavioural symptoms of attention 

deficit hyperactivity disorder in adolescents: a case-control study. Nutr J. 2008;7:8. PMID: 

18275609.

7. Cooper RE, Tye C, Kuntsi J, et al. Omega-3 polyunsaturated fatty acid supplementation and 

cognition: A systematic review and meta-analysis. Journal of Psychopharmacology. 2015 

Jul;29(7):753-63. PMID: 26040902.

8. de Jong C, Boehm G, Kikkert HK, et al. The Groningen LCPUFA study: No effect of shortterm postnatal long-chain polyunsaturated fatty acids in healthy term infants on cardiovascular 

and anthropometric development at 9 years. Pediatr Res. 2011 Oct;70(4):411-6. PMID: 

21705958.

9. El-Ansary AK, Bacha AG, Al-Ayahdi LY. Impaired plasma phospholipids and relative 

amounts of essential polyunsaturated fatty acids in autistic patients from Saudi Arabia. Lipids 

Health Dis. 2011;10:63. PMID: 21513514.

10. Engel S, Tronhjem KM, Hellgren LI, et al. Docosahexaenoic acid status at 9 months is 

inversely associated with communicative skills in 3-year-old girls. Matern Child Nutr. 2013 

Oct;9(4):499-510. PMID: 22642227.

11. Eriksson S, Mellstrom D, Strandvik B. Fatty acid pattern in serum is associated with bone 

mineralisation in healthy 8-year-old children. Br J Nutr. 2009 Aug;102(3):407-12. PMID: 

19175947.

12. Freeman MP. Complementary and alternative medicine for perinatal depression. J Affect 

Disord. 2009 Jan;112(1-3):1-10. PMID: 18692251.

13. Freeman MP, Cohen LS, McInerney K. Omega-3 Fatty acids and gestational length in a 

high-risk psychiatric population due to psychiatric morbidity and medication exposure during 

pregnancy. J Clin Psychopharmacol. 2014 Oct;34(5):627-32. PMID: 25006815.

14. Geppert J, Demmelmair H, Hornstra G, et al. Co-supplementation of healthy women with 

fish oil and evening primrose oil increases plasma docosahexaenoic acid, gamma-linolenic acid 
B-17

and dihomo-gamma-linolenic acid levels without reducing arachidonic acid concentrations. Br J 

Nutr. 2008 Feb;99(2):360-9. PMID: 17678567.

15. Gow RV, Sumich A, Vallee-Tourangeau F, et al. Omega-3 fatty acids are related to 

abnormal emotion processing in adolescent boys with attention deficit hyperactivity disorder. 

Prostaglandins Leukotrienes & Essential Fatty Acids. 2013 Jun;88(6):419-29. PMID: 23660373.

16. Gow RV, Vallee-Tourangeau F, Crawford MA, et al. Omega-3 fatty acids are inversely 

related to callous and unemotional traits in adolescent boys with attention deficit hyperactivity 

disorder. Prostaglandins Leukotrienes & Essential Fatty Acids. 2013 Jun;88(6):411-8. PMID: 

23664595.

17. Greatrex JC, Drasdo N, Dresser K. Scotopic sensitivity in dyslexia and requirements for 

DHA supplementation. Lancet. 2000 Apr 22;355(9213):1429-30. PMID: 10791530.

18. Hoffman DR, Theuer RC, Castaneda YS, et al. Maturation of visual acuity is accelerated in 

breast-fed term infants fed baby food containing DHA-enriched egg yolk. J Nutr. 2004 

Sep;134(9):2307-13. PMID: 15333721.

19. Kuratko CN, Barrett EC, Nelson EB, et al. The relationship of docosahexaenoic acid (DHA) 

with learning and behavior in healthy children: a review. Nutrients. 2013 Jul;5(7):2777-810. 

PMID: 23877090.

20. Li F, Jin X, Liu B, et al. Follow-up formula consumption in 3- to 4-year-olds and respiratory 

infections: An RCT. Pediatrics; 2014. p. e1533-e40.

21. Lim Andy KH, Manley Karen J, Roberts Matthew A, et al. Fish oil for kidney transplant 

recipients. Cochrane Database of Systematic Reviews: John Wiley & Sons, Ltd; 2007.

22. Oddy WH, de Klerk NH, Kendall GE, et al. Ratio of omega-6 to omega-3 fatty acids and 

childhood asthma. J Asthma. 2004;41(3):319-26. PMID: 15260465.

23. Ohlund I, Hornell A, Lind T, et al. Dietary fat in infancy should be more focused on quality 

than on quantity. Eur J Clin Nutr. 2008 Sep;62(9):1058-64. PMID: 17579652.

24. Orlando MS, Dziorny AC, Harrington D, et al. Associations between prenatal and recent 

postnatal methylmercury exposure and auditory function at age 19 years in the Seychelles Child 

Development Study. Neurotoxicology and Teratology S2- Neurobehavioral Toxicology & 

Teratology. 2014 Nov, 2014;46:68-76. PMID: 2014-54684-011.

25. Ortiz-Espejo M, Perez-Navero JL, Munoz-Villanueva MC, et al. Nutritional assessment in 

neonatal and prepubertal children with a history of extrauterine growth restriction. Early Hum 

Dev. 2013 Sep;89(9):763-8. PMID: 23827379.

26. Portwood MM. The role of dietary fatty acids in children's behaviour and learning. Nutr 

Health. 2006;18(3):233-47. PMID: 17180869.
B-18

27. Pulakka A, Ashorn U, Cheung YB, et al. Effect of 12-month intervention with lipid-based 

nutrient supplements on physical activity of 18-month-old Malawian children: A randomised, 

controlled trial. Eur J Clin Nutr; 2015. p. 173-8.

28. Rudiger M, von Baehr A, Haupt R, et al. Preterm infants with high polyunsaturated fatty 

acid and plasmalogen content in tracheal aspirates develop bronchopulmonary dysplasia less 

often. Crit Care Med. 2000 May;28(5):1572-7. PMID: 10834714.

29. Rytter D, Bech BH, Halldorsson T, et al. No association between the intake of marine n-3 

PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk 

in the 20-year-old offspring. Br J Nutr. 2013 Dec 14;110(11):2037-46. PMID: 23680230.

30. Rzehak P, Thijs C, Standl M, et al. Variants of the FADS1 FADS2 gene cluster, blood levels 

of polyunsaturated fatty acids and eczema in children within the first 2 years of life. PLoS ONE 

[Electronic Resource]. 2010;5(10):e13261. PMID: 20948998.

31. Scalabrin D, Stolz S, Zhuang W, et al. Impact of formula containing docosahexaenoic acid, 

prebiotics, and beta-glucan on allergic manifestations in young children. J Allergy Clin 

Immunol; 2014. p. Ab211.

32. Scassellati C, Bonvicini C, Faraone SV, et al. Biomarkers and attention-deficit/hyperactivity 

disorder: A systematic review and meta-analyses. J Am Acad Child Adolesc Psychiatry. 2012 

Oct, 2012;51(10):1003-19. PMID: 2012-26793-010.

33. Schnappinger M, Sausenthaler S, Linseisen J, et al. Fish consumption, allergic sensitisation 

and allergic diseases in adults. Ann Nutr Metab. 2009;54(1):67-74. PMID: 19270447.

34. Schwartz J, Dube K, Sichert-Hellert W, et al. Modification of dietary polyunsaturated fatty 

acids via complementary food enhances n-3 long-chain polyunsaturated fatty acid synthesis in 

healthy infants: a double blinded randomised controlled trial. Arch Dis Child. 2009 

Nov;94(11):876-82. PMID: 19193660.

35. Skilton MR, Mikkila V, Wurtz P, et al. Fetal growth, omega-3 (n-3) fatty acids, and 

progression of subclinical atherosclerosis: preventing fetal origins of disease? The 

Cardiovascular Risk in Young Finns Study. Am J Clin Nutr. 2013 Jan;97(1):58-65. PMID: 

23151534.

36. Thienprasert A, Samuhaseneetoo S, Popplestone K, et al. Fish oil n-3 polyunsaturated fatty 

acids selectively affect plasma cytokines and decrease illness in Thai schoolchildren: a 

randomized, double-blind, placebo-controlled intervention trial. J Pediatr. 2009 Mar;154(3):391-

5. PMID: 18930251.

37. Tichelaar HY, Steyn NP, Nel JH, et al. Effect of catfish supplementation on the fatty acid 

status and growth of undernourished rural preschool children under 6 years of age: an 

intervention trial in Lebowa, South Africa. Asia Pac J Clin Nutr. 1999 1999;8(2):96-105.
B-19

Not oral intake - N=10

1. Bialecka-Pikul M, Lauterbach R, Pawlik D. May the supplementation of lipid emulsion 

containing DHA in VLBW infants influence their psychological development evaluated at three 

years of age? Preliminary study. Medycyna Wieku Rozwojowego. 2014 Oct-Dec;18(4):432-8. 

PMID: 25874780.

2. Demirel G, Oguz SS, Celik IH, et al. The metabolic effects of two different lipid emulsions 

used in parenterally fed premature infants--a randomized comparative study. Early Hum Dev. 

2012 Jul;88(7):499-501. PMID: 22245235.

3. Lehner F, Demmelmair H, Roschinger W, et al. Metabolic effects of intravenous LCT or 

MCT/LCT lipid emulsions in preterm infants. J Lipid Res. 2006 Feb;47(2):404-11. PMID: 

16299352.

4. Pawlik D, Lauterbach R, Walczak M, et al. Docosahexaenoic acid (DHA) concentration in 

very low birth weight newborns receiving a fish-oil based fat emulsion from the first day of life. 

Preliminary clinical observation. Medycyna Wieku Rozwojowego. 2011 Jul-Sep;15(3):312-7. 

PMID: 22006486.

5. Rodriguez A, Raederstorff D, Sarda P, et al. Preterm infant formula supplementation with 

alpha linolenic acid and docosahexaenoic acid. Eur J Clin Nutr. 2003 Jun;57(6):727-34. PMID: 

12792656.

6. Saint-Amour D, Roy MS, Bastien C, et al. Alterations of visual evoked potentials in 

preschool Inuit children exposed to methylmercury and polychlorinated biphenyls from a marine 

diet. Neurotoxicology. 2006 Jul;27(4):567-78. PMID: 16620993.

7. Stark KD, Beblo S, Murthy M, et al. Alcohol consumption in pregnant, black women is 

associated with decreased plasma and erythrocyte docosahexaenoic acid. Alcoholism: Clinical & 

Experimental Research. 2005 Jan;29(1):130-40. PMID: 15654301.

8. Strommen K, Blakstad EW, Moltu SJ, et al. Enhanced nutrient supply to very low birth 

weight infants is associated with improved white matter maturation and head growth. 

Neonatology; 2014. p. 68-75.

9. Wadhwani N, Patil V, Pisal H, et al. Altered maternal proportions of long chain 

polyunsaturated fatty acids and their transport leads to disturbed fetal stores in preeclampsia. 

Prostaglandins Leukotrienes & Essential Fatty Acids. 2014 Jul-Aug;91(1-2):21-30. PMID: 

24928794.

10. Webb AN, Hardy P, Peterkin M, et al. Tolerability and safety of olive oil-based lipid 

emulsion in critically ill neonates: a blinded randomized trial. Nutrition. 2008 Nov-Dec;24(11-

12):1057-64. PMID: 18619813.
B-20

No outcomes of interest- N=75

1. Antonakou A, Skenderi KP, Chiou A, et al. Breast milk fat concentration and fatty acid 

pattern during the first six months in exclusively breastfeeding Greek women. Eur J Nutr. 2013 

Apr;52(3):963-73. PMID: 22752261.

2. Babin F, Rodriguez A, Sarda P, et al. Alpha linolenic acid in cholesterol esters: a marker of 

alphalinolenic acid intake in newborns. Eur J Clin Nutr. 2000 Nov;54(11):840-3. PMID: 

11114678.

3. Barden AE, Dunstan JA, Beilin LJ, et al. n -- 3 fatty acid supplementation during pregnancy 

in women with allergic disease: effects on blood pressure, and maternal and fetal lipids. Clin Sci. 

2006 Oct;111(4):289-94. PMID: 16822237.

4. Barden AE, Mori TA, Dunstan JA, et al. Fish oil supplementation in pregnancy lowers F2-

isoprostanes in neonates at high risk of atopy. Free Radic Res. 2004 Mar;38(3):233-9. PMID: 

15129731.

5. Bisgaard H, Vissing NH, Carson CG, et al. Deep phenotyping of the unselected 

COPSAC2010 birth cohort study. Clin Exp Allergy. 2013 Dec;43(12):1384-94. PMID: 

24118234.

6. Blumfield ML, Nowson C, Hure AJ, et al. Lower Protein-to-Carbohydrate Ratio in Maternal 

Diet is Associated with Higher Childhood Systolic Blood Pressure up to Age Four Years. 

Nutrients. 2015 May;7(5):3078-93. PMID: 25919307.

7. Bokor S, Koletzko B, Decsi T. Systematic review of fatty acid composition of human milk 

from mothers of preterm compared to full-term infants. Ann Nutr Metab. 2007;51(6):550-6. 

PMID: 18227623.

8. Bosaeus M, Hussain A, Karlsson T, et al. A randomized longitudinal dietary intervention 

study during pregnancy: effects on fish intake, phospholipids, and body composition. Nutr J. 

2015;14:1. PMID: 25554072.

9. Bowers K, Tobias DK, Yeung E, et al. A prospective study of prepregnancy dietary fat intake 

and risk of gestational diabetes. Am J Clin Nutr. 2012 Feb;95(2):446-53. PMID: 22218158.

10. Brenna JT, Salem N, Jr., Sinclair AJ, et al. alpha-Linolenic acid supplementation and 

conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot 

Essent Fatty Acids. 2009 Feb-Mar;80(2-3):85-91. PMID: 19269799.

11. Brunner S, Schmid D, Huttinger K, et al. Effect of reducing the n-6/n-3 fatty acid ratio on 

the maternal and fetal leptin axis in relation to infant body composition. Obesity. 2014 

Jan;22(1):217-24. PMID: 23596009.
B-21

12. Chen X, Scholl TO, Leskiw M, et al. Differences in maternal circulating fatty acid 

composition and dietary fat intake in women with gestational diabetes mellitus or mild 

gestational hyperglycemia. Diabetes Care. 2010 Sep;33(9):2049-54. PMID: 20805277.

13. Choi AL, Mogensen UB, Bjerve KS, et al. Negative confounding by essential fatty acids in 

methylmercury neurotoxicity associations. Neurotoxicol Teratol. 2014 Mar, 2014;42:85-92. 

PMID: 2014-11099-012.

14. Courage ML, McCloy UR, Herzberg GR, et al. Visual acuity development and fatty acid 

composition of erythrocytes in full-term infants fed breast milk, commercial formula, or 

evaporated milk. J Dev Behav Pediatr. 1998 2/1998;19(1):9-17.

15. Dangat K, Kilari A, Mehendale S, et al. Preeclampsia alters milk neurotrophins and long 

chain polyunsaturated fatty acids. Int J Dev Neurosci. 2014 Apr, 2014;33:115-21. PMID: 2014-

06665-016.

16. Das UN. Polyunsaturated fatty acids and their metabolites in the pathobiology of 

schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Apr 5, 2013;42:122-34. 

PMID: 2012-18508-001.

17. de Groot RH, Adam J, Jolles J, et al. Alpha-linolenic acid supplementation during human 

pregnancy does not effect cognitive functioning. Prostaglandins Leukotrienes & Essential Fatty 

Acids. 2004 Jan;70(1):41-7. PMID: 14643178.

18. Donahue SM, Rifas-Shiman SL, Olsen SF, et al. Associations of maternal prenatal dietary 

intake of n-3 and n-6 fatty acids with maternal and umbilical cord blood levels. Prostaglandins 

Leukotrienes & Essential Fatty Acids. 2009 May-Jun;80(5-6):289-96. PMID: 19380219.

19. Dunstan JA, Mitoulas LR, Dixon G, et al. The effects of fish oil supplementation in 

pregnancy on breast milk fatty acid composition over the course of lactation: a randomized 

controlled trial. Pediatr Res. 2007 Dec;62(6):689-94. PMID: 17957152.

20. Dunstan JA, Mori TA, Barden A, et al. Maternal fish oil supplementation in pregnancy 

reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clin Exp Allergy. 

2003 Apr;33(4):442-8. PMID: 12680858.

21. D'Vaz N, Meldrum SJ, Dunstan JA, et al. Fish oil supplementation in early infancy 

modulates developing infant immune responses. Clin Exp Allergy. 2012 Aug;42(8):1206-16. 

PMID: 22805468.

22. Escolano-Margarit MV, Campoy C, Ramirez-Tortosa MC, et al. Effects of fish oil 

supplementation on the fatty acid profile in erythrocyte membrane and plasma phospholipids of 

pregnant women and their offspring: a randomised controlled trial. Br J Nutr. 2013 

May;109(9):1647-56. PMID: 22947225.
B-22

23. Field CJ, Van Aerde JE, Goruk S, et al. Effect of feeding a formula supplemented with longchain polyunsaturated fatty acids for 14 weeks improves the ex vivo response to a mitogen and 

reduces the response to a soy protein in infants at low risk for allergy. J Pediatr Gastroenterol 

Nutr. 2010 Jun;50(6):661-9. PMID: 20386325.

24. Forsyth JS, Willatts P, Agostoni C, et al. Long chain polyunsaturated fatty acid 

supplementation in infant formula and blood pressure in later childhood: follow up of a 

randomised controlled trial. BMJ. 2003 May 3;326(7396):953. PMID: 12727766.

25. Franke C, Demmelmair H, Decsi T, et al. Influence of fish oil or folate supplementation on 

the time course of plasma redox markers during pregnancy. Br J Nutr. 2010 Jun;103(11):1648-

56. PMID: 20211038.

26. Furuhjelm C, Jenmalm MC, Falth-Magnusson K, et al. Th1 and Th2 chemokines, vaccineinduced immunity, and allergic disease in infants after maternal -3 fatty acid supplementation 

during pregnancy and lactation. Pediatr Res. 2011 Mar;69(3):259-64. PMID: 21099447.

27. Garcia C, Millet V, Coste TC, et al. French mothers' milk deficient in DHA contains 

phospholipid species of potential interest for infant development. J Pediatr Gastroenterol Nutr. 

2011 Aug;53(2):206-12. PMID: 21788764.

28. Garcia-Rodriguez CE, Olza J, Aguilera CM, et al. Plasma inflammatory and vascular 

homeostasis biomarkers increase during human pregnancy but are not affected by oily fish 

intake. J Nutr. 2012 Jul;142(7):1191-6. PMID: 22623389.

29. Ghebremeskel K, Min Y, Crawford MA, et al. Blood fatty acid composition of pregnant and 

nonpregnant Korean women: red cells may act as a reservoir of arachidonic acid and 

docosahexaenoic acid for utilization by the developing fetus. Lipids. 2000 May;35(5):567-74. 

PMID: 10907792.

30. Gold DR, Willwerth BM, Tantisira KG, et al. Associations of cord blood fatty acids with 

lymphocyte proliferation, IL-13, and IFN-gamma. J Allergy Clin Immunol. 2006 

Apr;117(4):931-8. PMID: 16630954.

31. Gould JF, Makrides M, Colombo J, et al. Randomized controlled trial of maternal omega-3 

long-chain PUFA supplementation during pregnancy and early childhood development of 

attention, working memory, and inhibitory control. Am J Clin Nutr. 2014 Apr;99(4):851-9. 

PMID: 24522442.

32. Grandjean P, Bjerve KS, Weihe P, et al. Birthweight in a fishing community: significance of 

essential fatty acids and marine food contaminants. Int J Epidemiol. 2001 Dec;30(6):1272-8. 

PMID: 11821327.

33. Granot E, Jakobovich E, Rabinowitz R, et al. DHA supplementation during pregnancy and 

lactation affects infants' cellular but not humoral immune response. Mediators Inflamm. 

2011;2011:493925. PMID: 21941411.
B-23

34. Guerra A, Demmelmair H, Toschke AM, et al. Three-year tracking of fatty acid composition 

of plasma phospholipids in healthy children. Ann Nutr Metab. 2007;51(5):433-8. PMID: 

18025816.

35. Harper M, Li L, Zhao Y, et al. Change in mononuclear leukocyte responsiveness in 

midpregnancy and subsequent preterm birth. Obstet Gynecol. 2013 Apr;121(4):805-11. PMID: 

23635681.

36. Hawkes JS, Bryan DL, Neumann MA, et al. Transforming growth factor beta in human milk 

does not change in response to modest intakes of docosahexaenoic acid. Lipids; 2001. p. 1179-

81.

37. Helmersson-Karlqvist J, Miles EA, Vlachava M, et al. Enhanced prostaglandin F2alpha 

formation in human pregnancy and the effect of increased oily fish intake: results from the 

Salmon in Pregnancy Study. Prostaglandins Leukotrienes & Essential Fatty Acids. 2012 JanFeb;86(1-2):35-8. PMID: 22047909.

38. Hodge WG, Barnes D, Schachter HM, et al. The evidence for efficacy of omega-3 fatty 

acids in preventing or slowing the progression of retinitis pigmentosa: a systematic review. Can J 

Ophthalmol. 2006 Aug;41(4):481-90. PMID: 16883366.

39. Hoppu U, Isolauri E, Koskinen P, et al. Diet and blood lipids in 1-4 year-old children. 

Nutrition Metabolism & Cardiovascular Diseases. 2013 Oct;23(10):980-6. PMID: 23182924.

40. Jirapinyo P, Densupsoontorn N, Wiraboonchai D, et al. Fatty acid composition in breast 

milk from 4 regions of Thailand. J Med Assoc Thai. 2008 Dec;91(12):1833-7. PMID: 19133517.

41. Kennedy K, Ross S, Isaacs EB, et al. The 10-year follow-up of a randomised trial of longchain polyunsaturated fatty acid supplementation in preterm infants: effects on growth and blood 

pressure. Arch Dis Child. 2010 Aug;95(8):588-95. PMID: 20515959.

42. Kohlboeck G, Glaser C, Tiesler C, et al. Effect of fatty acid status in cord blood serum on 

children's behavioral difficulties at 10 y of age: results from the LISAplus Study. Am J Clin 

Nutr. 2011 Dec;94(6):1592-9. PMID: 22071708.

43. Krauss-Etschmann S, Hartl D, Rzehak P, et al. Decreased cord blood IL-4, IL-13, and CCR4 

and increased TGF-beta levels after fish oil supplementation of pregnant women. J Allergy Clin 

Immunol. 2008 Feb;121(2):464-70.e6. PMID: 17980419.

44. Larnkjaer A, Hoppe C, Molgaard C, et al. The effects of whole milk and infant formula on 

growth and IGF-I in late infancy. Eur J Clin Nutr. 2009 Aug;63(8):956-63. PMID: 19174829.

45. Larque E, Pagan A, Prieto MT, et al. Placental fatty acid transfer: a key factor in fetal 

growth. Ann Nutr Metab. 2014;64(3-4):247-53. PMID: 25300267.
B-24

46. Lee HS, Barraza-Villarreal A, Hernandez-Vargas H, et al. Modulation of DNA methylation 

states and infant immune system by dietary supplementation with -3 PUFA during pregnancy in 

an intervention study. Am J Clin Nutr. 2013 Aug;98(2):480-7. PMID: 23761484.

47. Lopez-Lopez A, Lopez-Sabater MC, Campoy-Folgoso C, et al. Fatty acid and sn-2 fatty acid 

composition in human milk from Granada (Spain) and in infant formulas. Eur J Clin Nutr. 2002 

Dec;56(12):1242-54. PMID: 12494309.

48. Makela J, Linderborg K, Niinikoski H, et al. Breast milk fatty acid composition differs 

between overweight and normal weight women: the STEPS Study. Eur J Nutr. 2013 

Mar;52(2):727-35. PMID: 22639073.

49. Martin Alvarez E, Pena-Caballero M, Hurtado-Suazo JA, et al. Variability in adipokines 

profile of newborns and their mothers after DHA supplementation in pregnancy. Arch Dis 

Child; 2014. p. A131.

50. Oken E, Guthrie LB, Bloomingdale A, et al. A pilot randomized controlled trial to promote 

healthful fish consumption during pregnancy: the Food for Thought Study. Nutr J. 2013;12:33. 

PMID: 23496848.

51. Olsen SF, Hansen HS, Sorensen TI, et al. Intake of marine fat, rich in (n-3)-polyunsaturated 

fatty acids, may increase birthweight by prolonging gestation. Lancet. 1986 

8/16/1986;2(8503):367-9.

52. Pinto TJ, Farias DR, Rebelo F, et al. Lower inter-partum interval and unhealthy life-style 

factors are inversely associated with n-3 essential fatty acids changes during pregnancy: a 

prospective cohort with Brazilian women. PLoS ONE [Electronic Resource]. 

2015;10(3):e0121151. PMID: 25822204.

53. Pivik RT, Dykman RA, Jing H, et al. Early infant diet and the omega 3 fatty acid DHA: 

effects on resting cardiovascular activity and behavioral development during the first half-year of 

life. Dev Neuropsychol. 2009;34(2):139-58. PMID: 19267292.

54. Prescott SL, Barden AE, Mori TA, et al. Maternal fish oil supplementation in pregnancy 

modifies neonatal leukotriene production by cord-blood-derived neutrophils. Clin Sci. 2007 

Nov;113(10):409-16. PMID: 17596121.

55. Prescott SL, Irvine J, Dunstan JA, et al. Protein kinase Czeta: a novel protective neonatal Tcell marker that can be upregulated by allergy prevention strategies. J Allergy Clin Immunol. 

2007 Jul;120(1):200-6. PMID: 17544492.

56. Ramirez M, Gallardo EM, Souto AS, et al. Plasma fatty-acid composition and antioxidant 

capacity in low birth-weight infants fed formula enriched with n-6 and n-3 long-chain 

polyunsaturated fatty acids from purified phospholipids. Clin Nutr. 2001 Feb;20(1):69-76. 

PMID: 11161546.
B-25

57. Ramon R, Ballester F, Aguinagalde X, et al. Fish consumption during pregnancy, prenatal 

mercury exposure, and anthropometric measures at birth in a prospective mother-infant cohort 

study in Spain. Am J Clin Nutr. 2009 Oct;90(4):1047-55. PMID: 19710189.

58. Ribeiro P, Carvalho FD, Abreu Ade A, et al. Effect of fish oil supplementation in pregnancy 

on the fatty acid composition of erythrocyte phospholipids and breast milk lipids.[Erratum 

appears in Int J Food Sci Nutr. 2012 Nov;63(7):893]. Int J Food Sci Nutr. 2012 Feb;63(1):36-40. 

PMID: 21707451.

59. Riva E, Grandi F, Massetto N, et al. Polychlorinated biphenyls in colostral milk and visual 

function at 12 months of life. Acta Paediatr. 2004 Aug;93(8):1103-7. PMID: 15456203.

60. Romero VC, Somers EC, Stolberg V, et al. Developmental programming for allergy: a 

secondary analysis of the Mothers, Omega-3, and Mental Health Study. Am J Obstet Gynecol. 

2013 Apr;208(4):316.e1-6. PMID: 23531329.

61. Sauerwald UC, Fink MM, Demmelmair H, et al. Effect of different levels of 

docosahexaenoic acid supply on fatty acid status and linoleic and alpha-linolenic acid conversion 

in preterm infants. J Pediatr Gastroenterol Nutr. 2012 Mar;54(3):353-63. PMID: 22008957.

62. Sedlmeier EM, Brunner S, Much D, et al. Human placental transcriptome shows sexually 

dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain 

polyunsaturated fatty acid intervention during pregnancy. BMC Genomics. 2014;15:941. PMID: 

25348288.

63. Siahanidou T, Margeli A, Lazaropoulou C, et al. Circulating adiponectin in preterm infants 

fed long-chain polyunsaturated fatty acids (LCPUFA)-supplemented formula--a randomized 

controlled study. Pediatr Res. 2008 Apr;63(4):428-32. PMID: 18356752.

64. Skilton MR, Ayer JG, Harmer JA, et al. Impaired fetal growth and arterial wall thickening: a 

randomized trial of -3 supplementation. Pediatrics. 2012 Mar;129(3):e698-703. PMID: 

22351892.

65. Smithers LG, Markrides M, Gibson RA. Human milk fatty acids from lactating mothers of 

preterm infants: a study revealing wide intra- and inter-individual variation. Prostaglandins 

Leukotrienes & Essential Fatty Acids. 2010 Jul;83(1):9-13. PMID: 20417081.

66. Smuts CM, Borod E, Peeples JM, et al. High-DHA eggs: feasibility as a means to enhance 

circulating DHA in mother and infant. Lipids. 2003 Apr;38(4):407-14. PMID: 12848286.

67. Steenweg-de Graaff JC, Tiemeier H, Basten MG, et al. Maternal LC-PUFA status during 

pregnancy and child problem behavior: the Generation R Study. Pediatr Res. 2015 

Mar;77(3):489-97. PMID: 25521921.

68. Steer CD, Davey Smith G, Emmett PM, et al. FADS2 polymorphisms modify the effect of 

breastfeeding on child IQ. PLoS One. 2010;5(7):e11570. PMID: 20644632.
B-26

69. Stokes-Riner A, Thurston SW, Myers GJ, et al. Corrigendum to “A longitudinal analysis of 

prenatal exposure to methylmercury and fatty acids in the Seychelles”. Neurotoxicol Teratol. 

2011 Jul-Aug, 2011;33(4):485-6. PMID: 2011-16153-004.

70. Storck Lindholm E, Strandvik B, Altman D, et al. Different fatty acid pattern in breast milk 

of obese compared to normal-weight mothers. Prostaglandins Leukotrienes & Essential Fatty 

Acids. 2013 Mar;88(3):211-7. PMID: 23273824.

71. Storro O, Oien T, Dotterud CK, et al. A primary health-care intervention on pre- and 

postnatal risk factor behavior to prevent childhood allergy. The Prevention of Allergy among 

Children in Trondheim (PACT) study. BMC Public Health. 2010;10:443. PMID: 20667103.

72. Vivatvakin B, Mahayosnond A, Theamboonlers A, et al. Effect of a whey-predominant 

starter formula containing LCPUFAs and oligosaccharides (FOS/GOS) on gastrointestinal 

comfort in infants. Asia Pac J Clin Nutr. 2010;19(4):473-80. PMID: 21147707.

73. Warstedt K, Furuhjelm C, Duchen K, et al. The effects of omega-3 fatty acid 

supplementation in pregnancy on maternal eicosanoid, cytokine, and chemokine secretion. 

Pediatr Res. 2009 Aug;66(2):212-7. PMID: 19390480.

74. West AA, Yan J, Jiang X, et al. Choline intake influences phosphatidylcholine DHA 

enrichment in nonpregnant women but not in pregnant women in the third trimester. Am J Clin 

Nutr. 2013 Apr;97(4):718-27. PMID: 23446897.

75. Zhang L. The effects of essential fatty acids preparation in the treatment of intrauterine 

growth retardation. Am J Perinatol. 1997 10/1997;14(9):535-7.

Does not address a KQ - N=2

1. Belfort MB, Rifas-Shiman SL, Sullivan T, et al. Infant growth before and after term: effects 

on neurodevelopment in preterm infants. Pediatrics. 2011 Oct;128(4):e899-906. PMID: 

21949135.

2. van Gool CJ, Thijs C, Dagnelie PC, et al. Determinants of neonatal IgE level: parity, maternal 

age, birth season and perinatal essential fatty acid status in infants of atopic mothers. Allergy. 

2004 Sep;59(9):961-8. PMID: 15291904.

Only exposure/intervention was total fish intake - N=14

1. Drouillet P, Kaminski M, De Lauzon-Guillain B, et al. Association between maternal seafood 

consumption before pregnancy and fetal growth: evidence for an association in overweight 

women. The EDEN mother-child cohort. Paediatr Perinat Epidemiol. 2009 Jan;23(1):76-86. 

PMID: 19228317.
B-27

2. Fereidooni B, Jenabi E. The use of omega 3 on pregnancy outcomes: a single-center study. 

JPMA - Journal of the Pakistan Medical Association. 2014 Dec;64(12):1363-5. PMID: 

25842578.

3. Gale CR, Robinson SM, Godfrey KM, et al. Oily fish intake during pregnancy--association 

with lower hyperactivity but not with higher full-scale IQ in offspring. J Child Psychol 

Psychiatry. 2008 Oct;49(10):1061-8. PMID: 18422546.

4. Leventakou V, Roumeliotaki T, Martinez D, et al. Fish intake during pregnancy, fetal growth, 

and gestational length in 19 European birth cohort studies. Am J Clin Nutr. 2014 Mar;99(3):506-

16. PMID: 24335057.

5. Luxwolda MF, Kuipers RS, Sango WS, et al. A maternal erythrocyte DHA content of 

approximately 6 g% is the DHA status at which intrauterine DHA biomagnifications turns into 

bioattenuation and postnatal infant DHA equilibrium is reached. Eur J Nutr. 2012 Sep;51(6):665-

75. PMID: 21952690.

6. Lv N, Xiao L, Ma J. Dietary pattern and asthma: a systematic review and meta-analysis. J 

Asthma Allergy. 2014;7:105-21. PMID: 25143747.

7. Magnusson J, Kull I, Rosenlund H, et al. Fish consumption in infancy and development of 

allergic disease up to age 12 y. Am J Clin Nutr. 2013 Jun;97(6):1324-30. PMID: 23576046.

8. Maslova E, Strom M, Oken E, et al. Fish intake during pregnancy and the risk of child asthma 

and allergic rhinitis - longitudinal evidence from the Danish National Birth Cohort. Br J Nutr. 

2013 Oct;110(7):1313-25. PMID: 23473120.

9. Nafstad P, Nystad W, Magnus P, et al. Asthma and allergic rhinitis at 4 years of age in 

relation to fish consumption in infancy. J Asthma. 2003 Jun;40(4):343-8. PMID: 12870829.

10. Oien T, Storro O, Johnsen R. Do early intake of fish and fish oil protect against eczema and 

doctor-diagnosed asthma at 2 years of age? A cohort study. J Epidemiol Community Health. 

2010 Feb;64(2):124-9. PMID: 19666630.

11. Oken E, Osterdal ML, Gillman MW, et al. Associations of maternal fish intake during 

pregnancy and breastfeeding duration with attainment of developmental milestones in early 

childhood: a study from the Danish National Birth Cohort. Am J Clin Nutr. 2008 Sep;88(3):789-

96. PMID: 18779297.

12. Olsen SF, Secher NJ. Low consumption of seafood in early pregnancy as a risk factor for 

preterm delivery: prospective cohort study. BMJ. 2002 Feb 23;324(7335):447. PMID: 11859044.

13. Rossary A, Farges MC, Lamas B, et al. Increased consumption of salmon during pregnancy 

partly prevents the decline of some plasma essential amino acid concentrations in pregnant 

women. Clin Nutr. 2014 Apr;33(2):267-73. PMID: 23684555.
B-28

14. Sagiv SK, Thurston SW, Bellinger DC, et al. Prenatal exposure to mercury and fish 

consumption during pregnancy and attention-deficit/hyperactivity disorder-related behavior in 

children.[Summary for patients in Arch Pediatr Adolesc Med. 2012 Dec;166(12):1188; PMID: 

23208646]. Arch Pediatr Adolesc Med. 2012 Dec;166(12):1123-31. PMID: 23044994.

Biomarkers only - N=39

1. Bascunan KA, Valenzuela R, Chamorro R, et al. Polyunsaturated fatty acid composition of 

maternal diet and erythrocyte phospholipid status in Chilean pregnant women. Nutrients. 2014 

Nov;6(11):4918-34. PMID: 25386693.

2. Bergmann RL, Haschke-Becher E, Klassen-Wigger P, et al. Supplementation with 200 

mg/day docosahexaenoic acid from mid-pregnancy through lactation improves the 

docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants. 

Ann Nutr Metab. 2008;52(2):157-66. PMID: 18446020.

3. Berseth CL, Harris CL, Wampler JL, et al. Liquid human milk fortifier significantly improves 

docosahexaenoic and arachidonic acid status in preterm infants. Prostaglandins Leukotrienes & 

Essential Fatty Acids. 2014 Sep;91(3):97-103. PMID: 24863250.

4. Boris J, Jensen B, Salvig JD, et al. A randomized controlled trial of the effect of fish oil 

supplementation in late pregnancy and early lactation on the n-3 fatty acid content in human 

breast milk. Lipids. 2004 Dec;39(12):1191-6. PMID: 15736915.

5. Carnielli VP, Simonato M, Verlato G, et al. Synthesis of long-chain polyunsaturated fatty 

acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids. Am J Clin 

Nutr. 2007 Nov;86(5):1323-30. PMID: 17991642.

6. Clandinin MT, Aerde Jv, Parrott A, et al. Assessment of feeding different amounts of 

arachidonic and docosahexaenoic acids in preterm infant formulas on the fatty acid content of 

lipoprotein lipids. Acta Paediatr. /8/1999;88(8):890-6.

7. Clandinin MT, Aerde Jv, Parrott A, et al. Assessment of the efficacious dose of arachidonic 

and docosahexaenoic acids in preterm infant formulas: fatty acid composition of erythrocyte 

membrane lipids. Pediatr Res. 1997 /4/1997;42(6):819-25.

8. Courville AB, Keplinger MR, Judge MP, et al. Plasma or red blood cell phospholipids can be 

used to assess docosahexaenoic acid status in women during pregnancy. Nutr Res. 2009 

Mar;29(3):151-5. PMID: 19358928.

9. De Vriese SR, Dhont M, Christophe AB. FA composition of cholesteryl esters and 

phospholipids in maternal plasma during pregnancy and at delivery and in cord plasma at birth. 

Lipids. 2003 Jan;38(1):1-7. PMID: 12669812.
B-29

10. Decsi T, Campoy C, Koletzko B. Effect of N-3 polyunsaturated fatty acid supplementation 

in pregnancy: the Nuheal trial. Adv Exp Med Biol. 2005;569:109-13. PMID: 16137113.

11. Decsi T, Kelemen B, Minda H, et al. Effect of type of early infant feeding on fatty acid 

composition of plasma lipid classes in full-term infants during the second 6 months of life. J 

Pediatr Gastroenterol Nutr. 2000 May;30(5):547-51. PMID: 2000178174 MEDLINE PMID 

10817286 (http://www.ncbi.nlm.nih.gov/pubmed/10817286).

12. Dunstan JA, Mori TA, Barden A, et al. Effects of n-3 polyunsaturated fatty acid 

supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition. Eur J 

Clin Nutr. 2004 Mar;58(3):429-37. PMID: 14985680.

13. Dunstan JA, Roper J, Mitoulas L, et al. The effect of supplementation with fish oil during 

pregnancy on breast milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid 

composition. Clin Exp Allergy. 2004 Aug;34(8):1237-42. PMID: 15298564.

14. Friesen RW, Innis SM. Linoleic acid is associated with lower long-chain n-6 and n-3 fatty 

acids in red blood cell lipids of Canadian pregnant women. Am J Clin Nutr. 2010 Jan;91(1):23-

31. PMID: 19923368.

15. Garcia-Rodriguez CE, Mesa MD, Olza J, et al. Does consumption of two portions of salmon 

per week enhance the antioxidant defense system in pregnant women? Antioxidants & Redox 

Signaling. 2012 Jun 15;16(12):1401-6. PMID: 22229304.

16. Hansen IB, Friis-Hansen B, Clausen J. The fatty acid composition of umbilical cord serum, 

infant serum and maternal serum and its relation to the diet. Z Ernahrungswiss. 1969 

7/1969;9(4):352-63.

17. Helland IB, Saugstad OD, Saarem K, et al. Supplementation of n-3 fatty acids during 

pregnancy and lactation reduces maternal plasma lipid levels and provides DHA to the infants. J 

Matern Fetal Neonatal Med. 2006 Jul;19(7):397-406. PMID: 16923694.

18. Hoffman DR, Wheaton DK, James KJ, et al. Docosahexaenoic acid in red blood cells of 

term infants receiving two levels of long-chain polyunsaturated fatty acids. J Pediatr 

Gastroenterol Nutr. 2006 Mar;42(3):287-92. PMID: 16540798.

19. Imhoff-Kunsch B, Stein AD, Villalpando S, et al. Docosahexaenoic acid supplementation 

from mid-pregnancy to parturition influenced breast milk fatty acid concentrations at 1 month 

postpartum in Mexican women. J Nutr. 2011 Feb;141(2):321-6. PMID: 21178076.

20. Innis SM, Elias SL. Intakes of essential n-6 and n-3 polyunsaturated fatty acids among 

pregnant Canadian women. Am J Clin Nutr. 2003 Feb;77(2):473-8. PMID: 12540410.

21. Kaempf-Rotzoll DE, Hellstern G, Linderkamp O. Influence of long-chain polyunsaturated 

fatty acid formula feeds on vitamin E status in preterm infants. Int J Vitam Nutr Res. 2003 

Oct;73(5):377-87. PMID: 14639802.
B-30

22. Krauss-Etschmann S, Shadid R, Campoy C, et al. Effects of fish-oil and folate 

supplementation of pregnant women on maternal and fetal plasma concentrations of 

docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Am J 

Clin Nutr. 2007 May;85(5):1392-400. PMID: 17490978.

23. Lapillonne A, Brossard N, Claris O, et al. Erythrocyte fatty acid composition in term infants 

fed human milk or a formula enriched with a low eicosapentanoic acid fish oil for 4 months. Eur 

J Pediatr. 2000 Jan-Feb;159(1-2):49-53. PMID: 10653329.

24. Lapillonne A, Picaud JC, Chirouze V, et al. The use of low-EPA fish oil for long-chain 

polyunsaturated fatty acid supplementation of preterm infants. Pediatr Res. 2000 Dec;48(6):835-

41. PMID: 11102555.

25. Marc I, Plourde M, Lucas M, et al. Early docosahexaenoic acid supplementation of mothers 

during lactation leads to high plasma concentrations in very preterm infants. J Nutr. 2011 

Feb;141(2):231-6. PMID: 21169226.

26. Montgomery C, Speake BK, Cameron A, et al. Maternal docosahexaenoic acid 

supplementation and fetal accretion. Br J Nutr. 2003 Jul;90(1):135-45. PMID: 12844385.

27. Moya M, Cortes E, Juste M, et al. Fatty acid absorption in preterms on formulas with and

without long-chain polyunsaturated fatty acids and in terms on formulas without these added. 

Eur J Clin Nutr. 2001 Sep;55(9):755-62. PMID: 11528489.

28. Muhlhausler BS, Gibson RA, Yelland LN, et al. Heterogeneity in cord blood DHA 

concentration: Towards an explanation. Prostaglandins Leukotrienes & Essential Fatty Acids. 

2014 Oct;91(4):135-40. PMID: 25123061.

29. Niinivirta K, Laakso P, Linderborg K, et al. Maternal dietary counseling during pregnancy 

and infant fatty acid profiles. Int J Food Sci Nutr. 2014 May;65(3):268-72. PMID: 24224882.

30. Otto SJ, van Houwelingen AC, Badart-Smook A, et al. Changes in the maternal essential 

fatty acid profile during early pregnancy and the relation of the profile to diet. Am J Clin Nutr. 

2001 Feb;73(2):302-7. PMID: 11157328.

31. Otto SJ, van Houwelingen AC, Badart-Smook A, et al. Comparison of the peripartum and 

postpartum phospholipid polyunsaturated fatty acid profiles of lactating and nonlactating 

women. Am J Clin Nutr. 2001 Jun;73(6):1074-9. PMID: 11382662.

32. Peng Y, Zhou T, Wang Q, et al. Fatty acid composition of diet, cord blood and breast milk in 

Chinese mothers with different dietary habits. Prostaglandins Leukotrienes & Essential Fatty 

Acids. 2009 Nov-Dec;81(5-6):325-30. PMID: 19709866.
B-31

33. Sabel KG, Lundqvist-Persson C, Bona E, et al. Fatty acid patterns early after premature 

birth, simultaneously analysed in mothers' food, breast milk and serum phospholipids of mothers 

and infants. Lipids Health Dis. 2009;8:20. PMID: 19515230.

34. Sala-Vila A, Campoy C, Castellote AI, et al. Influence of dietary source of docosahexaenoic 

and arachidonic acids on their incorporation into membrane phospholipids of red blood cells in 

term infants. Prostaglandins Leukotrienes & Essential Fatty Acids. 2006 Feb;74(2):143-8. 

PMID: 16326086.

35. Sanjurjo P, Ruiz-Sanz JI, Jimeno P, et al. Supplementation with docosahexaenoic acid in the 

last trimester of pregnancy: maternal-fetal biochemical findings. J Perinat Med. 2004;32(2):132-

6. PMID: 15085888.

36. Smithers LG, Gibson RA, McPhee A, et al. Effect of two doses of docosahexaenoic acid 

(DHA) in the diet of preterm infants on infant fatty acid status: results from the DINO trial. 

Prostaglandins Leukotrienes & Essential Fatty Acids. 2008 Sep-Nov;79(3-5):141-6. PMID: 

18951004.

37. Stark KD, Beblo S, Murthy M, et al. Comparison of bloodstream fatty acid composition 

from African-American women at gestation, delivery, and postpartum. J Lipid Res. 2005 

Mar;46(3):516-25. PMID: 15604519.

38. Valentine CJ, Morrow G, Pennell M, et al. Randomized controlled trial of docosahexaenoic 

acid supplementation in midwestern U.S. human milk donors. Breastfeeding Medicine: The 

Official Journal of the Academy of Breastfeeding Medicine. 2013 Feb;8(1):86-91. PMID: 

22568471.

39. Vlaardingerbroek H, Hornstra G. Essential fatty acids in erythrocyte phospholipids during 

pregnancy and at delivery in mothers and their neonates: comparison with plasma phospholipids. 

Prostaglandins Leukotrienes & Essential Fatty Acids. 2004 Dec;71(6):363-74. PMID: 15519495.

Duplicate data - N=24

1. Denburg JA, Hatfield HM, Cyr MM, et al. Fish oil supplementation in pregnancy modifies 

neonatal progenitors at birth in infants at risk of atopy. Pediatr Res. 2005 Feb;57(2):276-81. 

PMID: 15585690.

2. Drover J, Hoffman DR, Castañeda YS, et al. Three randomized controlled trials of early longchain polyunsaturated fatty acid supplementation on means-end problem solving in 9-montholds. Child Dev. 2009 Sep-Oct, 2009;80(5):1376-84. PMID: 2009-16643-006.

3. Drover JR, Felius J, Hoffman DR, et al. A randomized trial of DHA intake during infancy: 

School readiness and receptive vocabulary at 2–3 5 years of age. Early Hum Dev. 2012 Nov, 

2012;88(11):885-91. PMID: 2012-26775-008.

4. Duley L. Pre-eclampsia, eclampsia, and hypertension. Clin Evid. 2008PMID: 19445808.
B-32

5. Hernandez E, Barraza-Villarreal A, Escamilla-Nunez MC, et al. Prenatal determinants of cord 

blood total immunoglobulin E levels in Mexican newborns. Allergy Asthma Proc. 2013 SepOct;34(5):e27-34. PMID: 23998234.

6. Lee HS, Barraza-Villarreal A, Biessy C, et al. Dietary supplementation with polyunsaturated 

fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and 

growth of infants. Physiol Genomics. 2014 Dec 1;46(23):851-7. PMID: 25293351.

7. Lumia M, Luukkainen P, Kaila M, et al. Maternal dietary fat and fatty acid intake during 

lactation and the risk of asthma in the offspring. Acta Paediatr. 2012 Aug, 2012;101(8):e337-

e43. PMID: 2012-18797-028.

8. Makrides M. DHA supplementation during the perinatal period and neurodevelopment: Do 

some babies benefit more than others? Prostaglandins Leukotrienes & Essential Fatty Acids. 

2013 Jan;88(1):87-90. PMID: 22698951.

9. Makrides M, Neumann MA, Gibson RA. Perinatal characteristics may influence the outcome 

of visual acuity. Lipids. 2001 Sep;36(9):897-900. PMID: 11724461.

10. Markhus MW, Skotheim S, Graff IE, et al. Low omega-3 index in pregnancy is a possible 

biological risk factor for postpartum depression. PLoS One. 2013 Jul 3, 2013;8(7):ArtID e67617. 

PMID: 2013-25674-001.

11. Mattes E, McCarthy S, Gong G, et al. Maternal mood scores in mid-pregnancy are related to 

aspects of neonatal immune function. Brain Behav Immun. 2009 Mar;23(3):380-8. PMID: 

19150495.

12. Mattes E, McCarthy S, Gong G, et al. Maternal mood scores in mid-pregnancy are related to 

aspects of neonatal immune function. Brain Behav Immun. 2009 Mar, 2009;23(3):380-8. PMID: 

2009-03076-012.

13. Mihrshahi S, Peat JK, Marks GB, et al. Eighteen-month outcomes of house dust mite 

avoidance and dietary fatty acid modification in the Childhood Asthma Prevention Study 

(CAPS).[Erratum appears in J Allergy Clin Immunol. 2003 Apr;111(4):735]. J Allergy Clin 

Immunol. 2003 Jan;111(1):162-8. PMID: 12532113.

14. Miyake Y, Sasaki S, Yokoyama T, et al. Risk of postpartum depression in relation to dietary 

fish and fat intake in Japan: the Osaka Maternal and Child Health Study. Psychol Med. 2006 

Dec;36(12):1727-35. PMID: 16938145.

15. Olsen SF, Osterdal ML, Salvig JD, et al. Duration of pregnancy in relation to fish oil 

supplementation and habitual fish intake: a randomised clinical trial with fish oil. Eur J Clin 

Nutr. 2007 Aug;61(8):976-85. PMID: 17299499.
B-33

16. Owen C, Rees A-M, Parker G. The role of fatty acids in the development and treatment of 

mood disorders. Current Opinion in Psychiatry. 2008 Jan, 2008;21(1):19-24. PMID: 2007-

19007-004.

17. Simmer K. Long-chain polyunsaturated fatty acid supplementation in infants born at term. 

Cochrane Database of Systematic Reviews. 2000(2):CD000376. PMID: 10796352.

18. Simmer K. Long-chain polyunsaturated fatty acid supplementation in preterm infants. 

Cochrane Database of Systematic Reviews. 2000(2):CD000375. PMID: 10796351.

19. Simmer K. Long-chain polyunsaturated fatty acid supplementation in infants born at term. 

Cochrane Database of Systematic Reviews. 2001(4):CD000376. PMID: 11687076.

20. Simmer K, Patole S. Longchain polyunsaturated fatty acid supplementation in preterm 

infants. Cochrane Database of Systematic Reviews. 2004(1):CD000375. PMID: 14973956.

21. Simmer K, Patole SK, Rao SC. Long-chain polyunsaturated fatty acid supplementation in 

infants born at term. Cochrane Database of Systematic Reviews. 2008(1):CD000376. PMID: 

18253974.

22. Simmer K, Schulzke SM, Patole S. Long-chain polyunsaturated fatty acid supplementation 

in preterm infants. Cochrane Database of Systematic Reviews. 2008(1):CD000375. PMID: 

18253973.

23. van de Lagemaat M, Rotteveel J, Muskiet FA, et al. Post term dietary-induced changes in 

DHA and AA status relate to gains in weight, length, and head circumference in preterm infants. 

Prostaglandins Leukotrienes & Essential Fatty Acids. 2011 Dec;85(6):311-6. PMID: 21995887.

24. van Goor SA, Dijck-Brouwer DA, Erwich JJ, et al. The influence of supplemental 

docosahexaenoic and arachidonic acids during pregnancy and lactation on neurodevelopment at 

eighteen months. Prostaglandins Leukotrienes & Essential Fatty Acids. 2011 May-Jun;84(5-

6):139-46. PMID: 21316208.

No interventions of interest - N=7

1. Almqvist C, Garden F, Xuan W, et al. Omega-3 and omega-6 fatty acid exposure from early 

life does not affect atopy and asthma at age 5 years. J Allergy Clin Immunol. 2007 

Jun;119(6):1438-44. PMID: 17379291.

2. Ashorn P, Alho L, Ashorn U, et al. Supplementation of Maternal Diets during Pregnancy and 

for 6 Months Postpartum and Infant Diets Thereafter with Small-Quantity Lipid-Based Nutrient 

Supplements Does Not Promote Child Growth by 18 Months of Age in Rural Malawi: A 

Randomized Controlled Trial. J Nutr. 2015 Jun;145(6):1345-53. PMID: 25926413.
B-34

3. Ashorn P, Alho L, Ashorn U, et al. The impact of lipid-based nutrient supplement provision 

to pregnant women on newborn size in rural Malawi: A randomized controlled trial. Am J Clin 

Nutr; 2015. p. 387-97.

4. Burks W, Jones SM, Berseth CL, et al. Hypoallergenicity and effects on growth and tolerance 

of a new amino acid-based formula with docosahexaenoic acid and arachidonic acid. J Pediatr. 

2008 Aug;153(2):266-71. PMID: 18534230.

5. Gibson RA, Barclay D, Marshall H, et al. Safety of supplementing infant formula with longchain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised 

controlled trial. Br J Nutr. 2009 Jun;101(11):1706-13. PMID: 19134240.

6. Mardones F, Urrutia MT, Villarroel L, et al. Effects of a dairy product fortified with multiple 

micronutrients and omega-3 fatty acids on birth weight and gestation duration in pregnant 

Chilean women. Public Health Nutr. 2008 Jan;11(1):30-40. PMID: 17565762.

7. van der Merwe LF, Moore SE, Fulford AJ, et al. Long-chain PUFA supplementation in rural 

African infants: a randomized controlled trial of effects on gut integrity, growth, and cognitive 

development. Am J Clin Nutr. 2013 Jan;97(1):45-57. PMID: 23221579.

Non-Systematic Review Background - N=58

1. Batchelor JM, Grindlay DJ, Williams HC. What's new in atopic eczema? An analysis of 

systematic reviews published in 2008 and 2009. Clin Exp Dermatol. 2010 Dec;35(8):823-7; quiz 

7-8. PMID: 20649899.

2. Borja-Hart NL, Marino J. Role of omega-3 Fatty acids for prevention or treatment of perinatal 

depression. Pharmacotherapy:The Journal of Human Pharmacology & Drug Therapy. 2010 

Feb;30(2):210-6. PMID: 20099994.

3. Carvajal JA. Docosahexaenoic acid supplementation early in pregnancy may prevent deep 

placentation disorders. BioMed Research International. 2014;2014:526895. PMID: 25019084.

4. Casper RC. Nutrients, neurodevelopment, and mood. Current Psychiatry Reports. 2004 

Dec;6(6):425-9. PMID: 15538990.

5. Cheatham CL, Colombo J, Carlson SE. N-3 fatty acids and cognitive and visual acuity 

development: methodologic and conceptual considerations. Am J Clin Nutr. 2006 Jun;83(6 

Suppl):1458S-66S. PMID: 16841855.

6. Ciaccio CE, Girdhar M. Effect of maternal omega3 fatty acid supplementation on infant 

allergy. Ann Allergy Asthma Immunol. 2014 Mar;112(3):191-4. PMID: 24565593.

7. Cohen JT, Bellinger DC, Connor WE, et al. A quantitative analysis of prenatal intake of n-3 

polyunsaturated fatty acids and cognitive development. Am J Prev Med. 2005 Nov;29(4):366-74. 

PMID: 16242603.
B-35

8. Decsi T. Effects of supplementing LCPUFA to the diet of pregnant women: data from RCT. 

Adv Exp Med Biol. 2009;646:65-9. PMID: 19536664.

9. Decsi T, Koletzko B. N-3 fatty acids and pregnancy outcomes. Curr Opin Clin Nutr Metab 

Care. 2005 Mar;8(2):161-6. PMID: 15716794.

10. Duchen K, Bjorksten B. Polyunsaturated n-3 fatty acids and the development of atopic 

disease. Lipids. 2001 Sep;36(9):1033-42. PMID: 11724455.

11. EFSA NDA Panel (EFSA Panel on Dietetic Products NaA. Scientific Opinion on health 

benefits of seafood (fish and shellfish) consumption in relation to health risks associated with 

exposure to methylmercury. EFSA Journal. 2014;12(7):1-80.

12. Facchinetti F, Fazzio M, Venturini P. Polyunsaturated fatty acids and risk of preterm 

delivery. Eur Rev Med Pharmacol Sci. 2005 Jan-Feb;9(1):41-8. PMID: 15850143.

13. Fleith M, Clandinin MT. Dietary PUFA for preterm and term infants: review of clinical 

studies. Crit Rev Food Sci Nutr. 2005;45(3):205-29. PMID: 16048149.

14. Forsyth JS, Carlson SE. Long-chain polyunsaturated fatty acids in infant nutrition: effects on 

infant development. Curr Opin Clin Nutr Metab Care. 2001 Mar;4(2):123-6. PMID: 11224656.

15. Grieger JA, Clifton VL. A review of the impact of dietary intakes in human pregnancy on 

infant birthweight. Nutrients. 2015 Jan;7(1):153-78. PMID: 25551251.

16. Hadders-Algra M. The role of long-chain polyunsaturated fatty acids (LCPUFA) in growth 

and development. Adv Exp Med Biol. 2005;569:80-94. PMID: 16137111.

17. Hadders-Algra M. Prenatal and early postnatal supplementation with long-chain 

polyunsaturated fatty acids: neurodevelopmental considerations. Am J Clin Nutr. 2011 Dec;94(6 

Suppl):1874S-9S. PMID: 21525202.

18. Hadders-Algra M, Bouwstra H, van Goor SA, et al. Prenatal and early postnatal fatty acid 

status and neurodevelopmental outcome. J Perinat Med. 2007;35 Suppl 1:S28-34. PMID: 

17302538.

19. Hoffman DR, Boettcher JA, Diersen-Schade DA. Toward optimizing vision and cognition in 

term infants by dietary docosahexaenoic and arachidonic acid supplementation: a review of 

randomized controlled trials. Prostaglandins Leukotrienes & Essential Fatty Acids. 2009 AugSep;81(2-3):151-8. PMID: 19505812.

20. Hosli I, Zanetti-Daellenbach R, Holzgreve W, et al. Role of omega 3-fatty acids and 

multivitamins in gestation. J Perinat Med. 2007;35 Suppl 1:S19-24. PMID: 17302536.
B-36

21. Jensen CL, Lapillonne A. Docosahexaenoic acid and lactation. Prostaglandins Leukotrienes 

& Essential Fatty Acids. 2009 Aug-Sep;81(2-3):175-8. PMID: 19632101.

22. Kim DR, Epperson CN, Weiss AR, et al. Pharmacotherapy of postpartum depression: an 

update. Expert Opin Pharmacother. 2014 Jun;15(9):1223-34. PMID: 24773410.

23. Koletzko B, Boey CC, Campoy C, et al. Current information and Asian perspectives on 

long-chain polyunsaturated fatty acids in pregnancy, lactation, and infancy: systematic review 

and practice recommendations from an early nutrition academy workshop. Ann Nutr Metab. 

2014;65(1):49-80. PMID: 25227906.

24. Koletzko B, Cetin I, Brenna JT, et al. Dietary fat intakes for pregnant and lactating women. 

Br J Nutr. 2007 Nov;98(5):873-7. PMID: 17688705.

25. Koren G. Polyunsaturated fatty acids and fetal brain development. Can Fam Physician. 

2015;61:41-2.

26. Lapillonne A, Carlson SE. Polyunsaturated fatty acids and infant growth. Lipids. 2001 

Sep;36(9):901-11. PMID: 11724462.

27. Larque E, Demmelmair H, Koletzko B. Perinatal supply and metabolism of long-chain 

polyunsaturated fatty acids: importance for the early development of the nervous system. Ann N 

Y Acad Sci. 2002 Jun;967:299-310. PMID: 12079857.

28. Makrides M. Is there a dietary requirement for DHA in pregnancy? Prostaglandins 

Leukotrienes & Essential Fatty Acids. 2009 Aug-Sep;81(2-3):171-4. PMID: 19500960.

29. Makrides M, Anderson A, Gibson RA. Early influences of nutrition on fetal growth. Nestle 

Nutr Inst Workshop Ser. 2013;71:1-9. PMID: 23502134.

30. Makrides M, Smithers LG, Gibson RA. Role of long-chain polyunsaturated fatty acids in 

neurodevelopment and growth. Nestle Nutrition Workshop Series. Paediatric Programme. 

2010;65:123-33; discussion 33-6. PMID: 20139678.

31. Marini A, Vegni C, Gangi S, et al. Influence of different types of post-discharge feeding on 

somatic growth, cognitive development and their correlation in very low birthweight preterm 

infants. Acta Paediatrica Supplement. 2003 Sep;91(441):18-33. PMID: 14599038.

32. Meldrum SJ, Smith MA, Prescott SL, et al. Achieving definitive results in long-chain 

polyunsaturated fatty acid supplementation trials of term infants: factors for consideration. Nutr 

Rev. 2011 Apr;69(4):205-14. PMID: 21457265.

33. Michaelsen KF, Larnkjaer A, Lauritzen L, et al. Science base of complementary feeding 

practice in infancy. Curr Opin Clin Nutr Metab Care. 2010 May;13(3):277-83. PMID: 20397319.
B-37

34. Morse N. Health benefits of maternal supplementation with docosahexaenoic acid, folic 

acid, vitamin D and iodine during pregnancy and lactation for foetal and infant brain 

development and function. Lipid Technology. 2015;27(2).

35. Morse NL. Benefits of docosahexaenoic acid, folic acid, vitamin D and iodine on foetal and 

infant brain development and function following maternal supplementation during pregnancy 

and lactation. Nutrients. 2012 Jul;4(7):799-840. PMID: 22852064.

36. Mozurkewich EL, Klemens C. Omega-3 fatty acids and pregnancy: current implications for 

practice. Curr Opin Obstet Gynecol. 2012 Mar;24(2):72-7. PMID: 22327736.

37. Oh R. Practical applications of fish oil (Omega-3 fatty acids) in primary care. J Am Board 

Fam Pract. 2005 Jan-Feb;18(1):28-36. PMID: 15709061.

38. Olsen SF. Is supplementation with marine omega-3 fatty acids during pregnancy a useful 

tool in the prevention of preterm birth? Clin Obstet Gynecol. 2004 Dec;47(4):768-74; discussion 

881-2. PMID: 15596931.

39. Olsen SF, Secher NJ. A possible preventive effect of low-dose fish oil on early delivery and 

pre-eclampsia: indications from a 50-year-old controlled trial. Br J Nutr. 1990 

11/1990;64(3):599-609.

40. Owen C, Rees AM, Parker G. The role of fatty acids in the development and treatment of 

mood disorders. Current Opinion in Psychiatry. 2008 Jan;21(1):19-24. PMID: 18281836.

41. Protzko J, Aronson J, Blair C. How to make a young child smarter: Evidence from the 

Database of Raising Intelligence. Perspect Psychol Sci. 2013 Jan, 2013;8(1):25-40. PMID: 2013-

01782-002.

42. Ramakrishnan U, Imhoff-Kunsch B, DiGirolamo AM. Role of docosahexaenoic acid in 

maternal and child mental health. Am J Clin Nutr. 2009 Mar;89(3):958S-62S. PMID: 19176728.

43. Richardson AJ. Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. 

Int Rev Psychiatry. 2006 Apr, 2006;18(2):155-72. PMID: 2006-07941-009.

44. Riediger ND, Othman RA, Suh M, et al. A systemic review of the roles of n-3 fatty acids in 

health and disease. J Am Diet Assoc. 2009 Apr;109(4):668-79. PMID: 19328262.

45. Schuchardt JP, Huss M, Stauss-Grabo M, et al. Significance of long-chain polyunsaturated 

fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr. 2010 

Feb;169(2):149-64. PMID: 19672626.

46. Secher NJ. Does fish oil prevent preterm birth? J Perinat Med. 2007;35 Suppl 1:S25-7. 

PMID: 17302537.
B-38

47. Shams K, Grindlay DJ, Williams HC. What's new in atopic eczema? An analysis of 

systematic reviews published in 2009-2010. Clin Exp Dermatol. 2011 Aug;36(6):573-7; quiz 7-

8. PMID: 21718344.

48. Shapiro GD, Fraser WD, Séguin JR. Emerging risk factors for postpartum depression: 

Serotonin transporter genotype an omega-3 fatty acid status. The Canadian Journal of Psychiatry 

/ La Revue canadienne de psychiatrie. 2012 Nov, 2012;57(11):704-12. PMID: 2012-34727-008.

49. Shoji H, Koletzko B. Oxidative stress and antioxidant protection in the perinatal period. Curr 

Opin Clin Nutr Metab Care. 2007 May;10(3):324-8. PMID: 17414502.

50. Sinn N. Nutritional and dietary influences on attention deficit hyperactivity disorder. Nutr 

Rev. 2008 Oct;66(10):558-68. PMID: 18826452.

51. Sinn N, Milte C, Howe PR. Oiling the brain: a review of randomized controlled trials of 

omega-3 fatty acids in psychopathology across the lifespan. Nutrients. 2010 Feb;2(2):128-70. 

PMID: 22254013.

52. Szajewska H, Makrides M. Is early nutrition related to short-term health and long-term 

outcome? Ann Nutr Metab. 2011;58 Suppl 1:38-48. PMID: 21701166.

53. Tai EK, Wang XB, Chen ZY. An update on adding docosahexaenoic acid (DHA) and 

arachidonic acid (AA) to baby formula. Food Funct. 2013 Dec;4(12):1767-75. PMID: 24150114.

54. Torley D, Futamura M, Williams HC, et al. What's new in atopic eczema? An analysis of 

systematic reviews published in 2010-11. Clin Exp Dermatol. 2013 Jul;38(5):449-56. PMID: 

23750610.

55. Uauy R, Hoffman DR. Essential fat requirements of preterm infants. Am J Clin Nutr. 2000 

Jan;71(1 Suppl):245S-50S. PMID: 10617979.

56. Villar J, Merialdi M, Gulmezoglu AM, et al. Nutritional interventions during pregnancy for 

the prevention or treatment of maternal morbidity and preterm delivery: an overview of 

randomized controlled trials. J Nutr. 2003 May;133(5 Suppl 2):1606S-25S. PMID: 12730475.

57. Willatts P, Forsyth JS. The role of long-chain polyunsaturated fatty acids in infant cognitive 

development. Prostaglandins Leukotrienes & Essential Fatty Acids. 2000 Jul-Aug;63(1-2):95-

100. PMID: 10970720.

58. Wroble M, Mash C, Williams L, et al. Should long chain polyunsaturated fatty acids be 

added to infant formula to promote development? J Appl Dev Psychol. 2002 Jan-Feb, 

2002;23(1):99-112. PMID: 2002-02435-004.

Systematic reviews - N=44

1. Anandan C, Nurmatov U, Sheikh A. Omega 3 and 6 oils for primary prevention of allergic 

disease: systematic review and meta-analysis. Allergy. 2009 Jun;64(6):840-8. PMID: 19392990.
B-39

2. Beyerlein A, Hadders-Algra M, Kennedy K, et al. Infant formula supplementation with longchain polyunsaturated fatty acids has no effect on Bayley developmental scores at 18 months of 

age--IPD meta-analysis of 4 large clinical trials. J Pediatr Gastroenterol Nutr. 2010 Jan;50(1):79-

84. PMID: 19881391.

3. Campoy C, Escolano-Margarit MV, Anjos T, et al. Omega 3 fatty acids on child growth, 

visual acuity and neurodevelopment. Br J Nutr. 2012 Jun;107 Suppl 2:S85-106. PMID: 

22591907.

4. Chen B, Ji X, Zhang L, et al. Fish Oil Supplementation does not Reduce Risks of Gestational 

Diabetes Mellitus, Pregnancy-Induced Hypertension, or Pre-Eclampsia: A Meta-Analysis of 

Randomized Controlled Trials. Med Sci Monit. 2015;21:2322-30. PMID: 26256041.

5. Delgado-Noguera MF, Calvache JA, Bonfill Cosp X. Supplementation with long chain 

polyunsaturated fatty acids (LCPUFA) to breastfeeding mothers for improving child growth and 

development. Cochrane Database of Systematic Reviews. 2010(12):CD007901. PMID: 

21154388.

6. Delgado-Noguera MF, Calvache JA, Bonfill Cosp X, et al. Supplementation with long chain 

polyunsaturated fatty acids (LCPUFA) to breastfeeding mothers for improving child growth and 

development. Cochrane Database of Systematic Reviews. 2015;7:CD007901. PMID: 26171898.

7. Dennis CL. Preventing postpartum depression part I: a review of biological interventions. 

Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie. 2004 Jul;49(7):467-75. 

PMID: 15362251.

8. Dennis C-LE. Preventing Postpartum Depression Part I: A Review of Biological 

Interventions. The Canadian Journal of Psychiatry / La Revue canadienne de psychiatrie. 2004 

Jul, 2004;49(7)PMID: 2004-18785-008.

9. Duley L. Pre-eclampsia, eclampsia, and hypertension. Clin Evid. 2011PMID: 21718554.

10. Dunlop AL, Kramer MR, Hogue CJ, et al. Racial disparities in preterm birth: an overview of 

the potential role of nutrient deficiencies. Acta Obstet Gynecol Scand. 2011 Dec;90(12):1332-41. 

PMID: 21910693.

11. Eilander A, Hundscheid DC, Osendarp SJ, et al. Effects of n-3 long chain polyunsaturated 

fatty acid supplementation on visual and cognitive development throughout childhood: a review 

of human studies. Prostaglandins Leukotrienes & Essential Fatty Acids. 2007 Apr;76(4):189-

203. PMID: 17376662.

12. Gibson RA, Chen W, Makrides M. Randomized trials with polyunsaturated fatty acid 

interventions in preterm and term infants: functional and clinical outcomes. Lipids. 2001 

Sep;36(9):873-83. PMID: 11724459.
B-40

13. Gunaratne AW, Makrides M, Collins CT. Maternal prenatal and/or postnatal n-3 long chain 

polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early 

childhood. Cochrane Database of Systematic Reviews. 2015;7:CD010085. PMID: 26197477.

14. Honest H, Forbes CA, Duree KH, et al. Screening to prevent spontaneous preterm birth: 

systematic reviews of accuracy and effectiveness literature with economic modelling. Health 

Technology Assessment (Winchester, England). 2009 Sep;13(43):1-627. PMID: 19796569.

15. Horvath A, Koletzko B, Szajewska H. Effect of supplementation of women in high-risk 

pregnancies with long-chain polyunsaturated fatty acids on pregnancy outcomes and growth 

measures at birth: a meta-analysis of randomized controlled trials. Br J Nutr. 2007 

Aug;98(2):253-9. PMID: 17419889.

16. Imhoff-Kunsch B, Briggs V, Goldenberg T, et al. Effect of n-3 long-chain polyunsaturated 

fatty acid intake during pregnancy on maternal, infant, and child health outcomes: a systematic 

review. Paediatr Perinat Epidemiol. 2012 Jul;26 Suppl 1:91-107. PMID: 22742604.

17. Jans LA, Giltay EJ, Van der Does AJ. The efficacy of n-3 fatty acids DHA and EPA (fish 

oil) for perinatal depression. Br J Nutr. 2010 Dec;104(11):1577-85. PMID: 21078211.

18. Jiao J, Li Q, Chu J, et al. Effect of n-3 PUFA supplementation on cognitive function 

throughout the life span from infancy to old age: a systematic review and meta-analysis of 

randomized controlled trials. Am J Clin Nutr. 2014;100:1422-36.

19. Klemens CM, Berman DR, Mozurkewich EL. The effect of perinatal omega-3 fatty acid 

supplementation on inflammatory markers and allergic diseases: a systematic review. BJOG. 

2011 Jul;118(8):916-25. PMID: 21658192.

20. Leung BM, Wiens KP, Kaplan BJ. Does prenatal micronutrient supplementation improve 

children's mental development? A systematic review. BMC Pregnancy Childbirth. 2011;11:12. 

PMID: 21291560.

21. Lo A, Sienna J, Mamak E, et al. The effects of maternal supplementation of polyunsaturated 

Fatty acids on visual, neurobehavioural, and developmental outcomes of the child: a systematic 

review of the randomized trials. Obstet Gynecol Int. 2012;2012:591531. PMID: 22315616.

22. Makrides M, Duley L, Olsen SF. Marine oil, and other prostaglandin precursor, 

supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth 

restriction. Cochrane Database of Systematic Reviews. 2006(3):CD003402. PMID: 16856006.

23. Makrides M, Gibson RA, Udell T, et al. Supplementation of infant formula with long-chain 

polyunsaturated fatty acids does not influence the growth of term infants. Am J Clin Nutr. 2005 

May;81(5):1094-101. PMID: 15883434.

24. Martinez-Victoria E, Yago MD. Omega 3 polyunsaturated fatty acids and body weight. Br J 

Nutr. 2012 Jun;107 Suppl 2:S107-16. PMID: 22591885.
B-41

25. Miller BJ, Murray L, Beckmann MM, et al. Dietary supplements for preventing postnatal 

depression. Cochrane Database of Systematic Reviews. 2013;10:CD009104. PMID: 24158923.

26. Ortega RM, Rodriguez-Rodriguez E, Lopez-Sobaler AM. Effects of omega 3 fatty acids 

supplementation in behavior and non-neurodegenerative neuropsychiatric disorders. Br J Nutr. 

2012 Jun;107 Suppl 2:S261-70. PMID: 22591900.

27. Previti G, Pawlby S, Chowdhury S, et al. Neurodevelopmental outcome for offspring of 

women treated for antenatal depression: a systematic review. Archives of Women's Mental 

Health. 2014 Dec;17(6):471-83. PMID: 25212663.

28. Qawasmi A, Landeros-Weisenberger A, Bloch MH. Meta-analysis of LCPUFA 

supplementation of infant formula and visual acuity. Pediatrics. 2013 Jan;131(1):e262-72. 

PMID: 23248232.

29. Qawasmi A, Landeros-Weisenberger A, Leckman JF, et al. Meta-analysis of long-chain 

polyunsaturated fatty acid supplementation of formula and infant cognition. Pediatrics. 2012 

Jun;129(6):1141-9. PMID: 22641753.

30. Rosenfeld E, Beyerlein A, Hadders-Algra M, et al. IPD meta-analysis shows no effect of 

LC-PUFA supplementation on infant growth at 18 months. Acta Paediatr. 2009 Jan;98(1):91-7. 

PMID: 18691337.

31. Saccone G, Berghella V. Omega-3 supplementation to prevent recurrent preterm birth: a 

systematic review and metaanalysis of randomized controlled trials. Am J Obstet Gynecol. 2015 

Aug;213(2):135-40. PMID: 25757636.

32. Saccone G, Berghella V. Omega-3 long chain polyunsaturated fatty acids to prevent preterm 

birth: a systematic review and meta-analysis. Obstet Gynecol. 2015 Mar;125(3):663-72. PMID: 

25730231.

33. Salvig JD, Lamont RF. Evidence regarding an effect of marine n-3 fatty acids on preterm 

birth: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2011 Aug;90(8):825-

38. PMID: 21535434.

34. SanGiovanni JP, Berkey CS, Dwyer JT, et al. Dietary essential fatty acids, long-chain 

polyunsaturated fatty acids, and visual resolution acuity in healthy fullterm infants: a systematic 

review. Early Hum Dev. 2000 Mar;57(3):165-88. PMID: 10742608.

35. Schachter HM, Reisman J, Tran K, et al. Health effects of omega-3 fatty acids on asthma. 

Evidence Report: Technology Assessment (Summary). 2004 Mar(91):1-7. PMID: 15133885.

36. Schulzke SM, Patole SK, Simmer K. Long-chain polyunsaturated fatty acid supplementation 

in preterm infants. Cochrane Database of Systematic Reviews. 2011(2):CD000375. PMID: 

21328248.
B-42

37. Simmer K, Patole SK, Rao SC. Long-chain polyunsaturated fatty acid supplementation in 

infants born at term. Cochrane Database of Systematic Reviews. 2011(12):CD000376. PMID: 

22161363.

38. Smithers LG, Gibson RA, McPhee A, et al. Effect of long-chain polyunsaturated fatty acid 

supplementation of preterm infants on disease risk and neurodevelopment: a systematic review 

of randomized controlled trials. Am J Clin Nutr. 2008 Apr;87(4):912-20. PMID: 18400714.

39. Szajewska H, Horvath A, Koletzko B. Effect of n-3 long-chain polyunsaturated fatty acid 

supplementation of women with low-risk pregnancies on pregnancy outcomes and growth 

measures at birth: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2006 

Jun;83(6):1337-44. PMID: 16762945.

40. Udell T, Gibson RA, Makrides M, et al. The effect of alpha-linolenic acid and linoleic acid 

on the growth and development of formula-fed infants: a systematic review and meta-analysis of 

randomized controlled trials. Lipids. 2005 Jan;40(1):1-11. PMID: 15825825.

41. Wojcicki JM, Heyman MB. Maternal omega-3 fatty acid supplementation and risk for 

perinatal maternal depression. J Matern Fetal Neonatal Med. 2011 May;24(5):680-6. PMID: 

20925595.

42. Wright K, Coverston C, Tiedeman M, et al. Formula supplemented with docosahexaenoic 

acid (DHA) and arachidonic acid (ARA): a critical review of the research. Journal for Specialists 

in Pediatric Nursing: JSPN. 2006 Apr;11(2):100-12; discussion 12-3. PMID: 16635189.

43. Yang H, Xun P, He K. Fish and fish oil intake in relation to risk of asthma: a systematic 

review and meta-analysis. PLoS ONE [Electronic Resource]. 2013;8(11):e80048. PMID: 

24265794.

44. Zhang P, Lavoie PM, Lacaze-Masmonteil T, et al. Omega-3 long-chain polyunsaturated 

fatty acids for extremely preterm infants: a systematic review. Pediatrics. 2014 Jul;134(1):120-

34. PMID: 24913791.

Observational studies with less than a sample size of 250 - N=33

1. Barman M, Johansson S, Hesselmar B, et al. High levels of both n-3 and n-6 long-chain 

polyunsaturated fatty acids in cord serum phospholipids predict allergy development. PLoS ONE 

[Electronic Resource]. 2013;8(7):e67920. PMID: 23874467.

2. Birberg-Thornberg U, Karlsson T, Gustafsson PA, et al. Nutrition and theory of mind--The 

role of polyunsaturated fatty acids (PUFA) in the development of theory of mind. Prostaglandins 

Leukotrienes & Essential Fatty Acids. 2006 Jul;75(1):33-41. PMID: 16750357.
B-43

3. Birch EE, Khoury JC, Berseth CL, et al. The impact of early nutrition on incidence of allergic 

manifestations and common respiratory illnesses in children. J Pediatr. 2010 Jun;156(6):902-6, 

6.e1. PMID: 20227721.

4. Boucher O, Burden MJ, Muckle G, et al. Neurophysiologic and neurobehavioral evidence of 

beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age. Am J 

Clin Nutr. 2011 May;93(5):1025-37. PMID: 21389181.

5. Browne JC, Scott KM, Silvers KM. Fish consumption in pregnancy and omega-3 status after 

birth are not associated with postnatal depression. J Affect Disord. 2006 Feb;90(2-3):131-9. 

PMID: 16325262.

6. Cheruku SR, Montgomery-Downs HE, Farkas SL, et al. Higher maternal plasma 

docosahexaenoic acid during pregnancy is associated with more mature neonatal sleep-state 

patterning. Am J Clin Nutr. 2002 September;76(3):608-13. PMID: 2002303115 MEDLINE 

PMID 12198007 (http://www.ncbi.nlm.nih.gov/pubmed/12198007).

7. Colombo J, Kannass KN, Shaddy DJ, et al. Maternal DHA and the development of attention 

in infancy and toddlerhood. Child Dev. 2004 Jul-Aug;75(4):1254-67. PMID: 15260876.

8. da Rocha CM, Kac G. High dietary ratio of omega-6 to omega-3 polyunsaturated acids during 

pregnancy and prevalence of post-partum depression. Matern Child Nutr. 2012 Jan;8(1):36-48. 

PMID: 22136220.

9. De Vriese SR, Matthys C, De Henauw S, et al. Maternal and umbilical fatty acid status in 

relation to maternal diet. Prostaglandins Leukotrienes & Essential Fatty Acids. 2002 

Dec;67(6):389-96. PMID: 12468259.

10. Gale CR, Marriott LD, Martyn CN, et al. Breastfeeding, the use of docosahexaenoic acidfortified formulas in infancy and neuropsychological function in childhood. Arch Dis Child. 

2010 Mar;95(3):174-9. PMID: 20133326.

11. Gustafsson PA, Duchen K, Birberg U, et al. Breastfeeding, very long polyunsaturated fatty 

acids (PUFA) and IQ at 6 1/2 years of age. Acta Paediatr. 2004 Oct;93(10):1280-7. PMID: 

15499945.

12. Jacobson JL, Jacobson SW, Muckle G, et al. Beneficial effects of a polyunsaturated fatty 

acid on infant development: evidence from the inuit of arctic Quebec. J Pediatr. 2008 

Mar;152(3):356-64. PMID: 18280840.

13. Kannass KN, Colombo J, Carlson SE. Maternal DHA levels and toddler free-play attention. 

Dev Neuropsychol. 2009;34(2):159-74. PMID: 19267293.

14. Lowe AJ, Thien FC, Stoney RM, et al. Associations between fatty acids in colostrum and 

breast milk and risk of allergic disease. Clin Exp Allergy. 2008 Nov;38(11):1745-51. PMID: 

18702657.
B-44

15. Lundqvist-Persson C, Lau G, Nordin P, et al. Early behaviour and development in breast-fed 

premature infants are influenced by omega-6 and omega-3 fatty acid status. Early Hum Dev. 

2010 Jul;86(7):407-12. PMID: 20646880.

16. Magnusardottir AR, Steingrimsdottir L, Thorgeirsdottir H, et al. Red blood cell n-3 

polyunsaturated fatty acids in first trimester of pregnancy are inversely associated with placental 

weight. Acta Obstet Gynecol Scand. 2009;88(1):91-7. PMID: 19140046.

17. Markhus MW, Skotheim S, Graff IE, et al. Low omega-3 index in pregnancy is a possible 

biological risk factor for postpartum depression. PLoS ONE [Electronic Resource]. 

2013;8(7):e67617. PMID: 23844041.

18. Montes R, Chisaguano AM, Castellote AI, et al. Fatty-acid composition of maternal and 

umbilical cord plasma and early childhood atopic eczema in a Spanish cohort. Eur J Clin Nutr. 

2013 Jun;67(6):658-63. PMID: 23549201.

19. Oddy WH, Pal S, Kusel MM, et al. Atopy, eczema and breast milk fatty acids in a high-risk 

cohort of children followed from birth to 5 yr. Pediatr Allergy Immunol. 2006 Feb;17(1):4-10. 

PMID: 16426248.

20. Olsen SF, Hansen HS, Jensen B, et al. Pregnancy duration and the ratio of long-chain n-3 

fatty acids to arachidonic acid in erythrocytes from Faroese women. J Intern Med. 1989 

1989;225(731 Suppl):185-9.

21. Olsen SF, Hansen HS, Secher NJ, et al. Gestation length and birth weight in relation to 

intake of marine n-3 fatty acids. Br J Nutr. 1995 3/1995;73(3):397-404.

22. Parra-Cabrera S, Moreno-Macias H, Mendez-Ramirez I, et al. Maternal dietary omega fatty 

acid intake and auditory brainstem-evoked potentials in Mexican infants born at term: cluster 

analysis. Early Hum Dev. 2008 Jan;84(1):51-7. PMID: 17434694.

23. Pedersen L, Lauritzen L, Brasholt M, et al. Polyunsaturated fatty acid content of mother's 

milk is associated with childhood body composition. Pediatr Res. 2012 Dec;72(6):631-6. PMID: 

23007033.

24. Pittaluga E, Vernal P, Llanos A, et al. Benefits of supplemented preterm formulas on insulin 

sensitivity and body composition after discharge from the neonatal intensive care unit. J Pediatr. 

2011 Dec;159(6):926-32.e2. PMID: 21784447.

25. Rees A, Sirois S, Wearden A. Maternal docosahexaenoic acid intake levels during 

pregnancy and infant performance on a novel object search task at 22 months. Child 

Development S2- Child Development: Abstracts & Bibliography. 2014 Nov-Dec, 

2014;85(6):2131-9. PMID: 2014-33557-001.
B-45

26. Rzehak P, Koletzko S, Koletzko B, et al. Growth of infants fed formula rich in canola oil 

(low erucic acid rapeseed oil). Clin Nutr. 2011 Jun;30(3):339-45. PMID: 21130544.

27. Soto-Ramirez N, Karmaus W, Zhang H, et al. Fatty acids in breast milk associated with 

asthma-like symptoms and atopy in infancy: a longitudinal study. J Asthma. 2012 

Nov;49(9):926-34. PMID: 22991928.

28. Stokes-Riner A, Thurston SW, Myers GJ, et al. A longitudinal analysis of prenatal exposure 

to methylmercury and fatty acids in the Seychelles. Neurotoxicol Teratol. 2011 MarApr;33(2):325-8. PMID: 21145963.

29. Stoney RM, Woods RK, Hosking CS, et al. Maternal breast milk long-chain n-3 fatty acids 

are associated with increased risk of atopy in breastfed infants.[Erratum appears in Clin Exp 

Allergy. 2007 Dec;37(12):1895; PMID: 18028101]. Clin Exp Allergy. 2004 Feb;34(2):194-200. 

PMID: 14987297.

30. Strain JJ, Davidson PW, Bonham MP, et al. Associations of maternal long-chain 

polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child 

Development Nutrition Study.[Erratum appears in Neurotoxicology. 2011 Dec;32(6):990]. 

Neurotoxicology. 2008 Sep;29(5):776-82. PMID: 18590765.

31. Tanaka K, Kon N, Ohkawa N, et al. Does breastfeeding in the neonatal period influence the 

cognitive function of very-low-birth-weight infants at 5 years of age? Brain Dev. 2009 Apr, 

2009;31(4):288-93. PMID: 2009-02659-007.

32. Toro-Ramos T. The relationship between maternal body composition and diet with fetal 

development in low-income women in Brazil. Dissertation Abstracts International: Section B: 

The Sciences and Engineering. 2013 2013;73(7-B(E))PMID: 2013-99020-220.

33. Zornoza-Moreno M, Fuentes-Hernandez S, Carrion V, et al. Is low docosahexaenoic acid 

associated with disturbed rhythms and neurodevelopment in offsprings of diabetic mothers? Eur 

J Clin Nutr. 2014 Aug;68(8):931-7. PMID: 24918123.

No numerical data - N=1

1. Lumia M, Luukkainen P, Kaila M, et al. Maternal dietary fat and fatty acid intake during 

lactation and the risk of asthma in the offspring. Acta Paediatrica. 2012 Aug;101(8):e337-43. 

PMID: 22578184.
C-1

Appendix C. Evidence Table for Randomized Controlled Trials
C-2

Table C1. Evidence table for randomized controlled trials

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Agostoni et al., 2009139

Study name: NR

Study dates: Enrollment 

occurred May and June 

2005; 1-year follow-up

Study design: Trial 

randomized parallel

Location: Italy

Funding source / 

conflict: Manufacturer 

supplied product

Study Population: 

Healthy infants

Infants enrolled 1160 

Infants withdrawals 69 

Infants completers 1091

Mother age: 32 years 

(4.5 years) NR

Infant age: intervention 

began 1 day after 

discharge (NA) NA

Race of Mother: White 

European (100%)

Inclusion Criteria: 

weight at birth 2500 g 

or more, gestational 

age between 37 and 

42 completed weeks, 

single birth, absence 

of neonatal or birth 

abnormalities, Apgar 

score 7 or higher at 5 

min, and white 

parents.

Exclusion Criteria: 

presence of neonatal 

diseases requiring 

hospitalization for 7 

days or more; 

involvement of 

neonate in another 

clinical study; 

unknown father; and 

parents unable to 

understand the 

protocol requirements, 

to fill out the infant’s 

diary, or to understand 

and speak the Italian 

language adequately.

Start time: Infants 1 day after discharge from 

birth hospital

Duration: Infants 1 year

Arm 1: placebo

Description: oral liquid

Manufacturer: Humana Italia SpA

Active ingredients: 400 IU vitamin D3

Viability: Parents were advised to store the 

bottles in a dry and fresh environment.

Dose: 1 mL once per day

Blinding: Intervention and placebo preparations 

were identical in aroma, taste, and texture

Total N-3: 0

Arm 2: Human Italia SpA

Active ingredients: 400 IU vitamin D3

Viability: Parents were advised to store the 

bottles in a dry and fresh environment.

Dose: 1 mL once per day

DHA: 20 mg DHA/ml

Outcome domain: Neurological 

development

Outcome: age achieving gross motor: 

hands-and-knees crawling (weeks) 

(Primary)

Follow-up time: varies

Arm 1: Sample size 476; mean 39.4; SD 

(6.2)

Arm 2: Sample size 482; mean 38.9; SD 

(6.4)

Outcome: age achieving gross motor: 

sitting without support (weeks) (Primary)

Follow-up time: varies

Arm 1: Sample size 542; mean 28.3; SD 

(4.2)

Arm 2: Sample size 551; mean 26.8; SD 

(4.2)

Outcome: age achieving gross motor: 

standing alone (weeks) (Primary)

Follow-up time: varies

Arm 1: Sample size 542; mean 50.1; SD 

(8.1)

Arm 2: Sample size 549; mean 49.2; SD 

(7.6)

Outcome: age achieving gross motor: 

walking alone (weeks) (Primary)

Follow-up time: varies

Arm 1: Sample size 542; mean 55.8; SD 

(6.7)

Arm 2: Sample size 549; mean 54.9; SD 

(6.8)

Almaas et al., 2015126

Study name: Unnamed 

Study Population: 

Preterm infants Low 

birth weight infants

Inclusion Criteria: Very 

low birth weight infants 

(birth weight <1500 g)

Start time: Infants (intervention began when the 

infant received most of his nutrients enterally: 

>100ml human milk/kg body weight/day

Outcome domain: Cognitive development

Outcome: Weschler Abbreviated Scale of 

Intelligence: Full Scale IQ (Secondary)
C-3

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Trial D

Study dates: 2003-2014

Study design: Trial 

randomized parallel

Location: Norway

Funding source / 

conflict: Government, 

None

Study follow-up: 8 years

Original, same study, or 

follow-up studies: 

Henriksen, 20008107; 

Ane, 2011125

Infants enrolled 129 

Infants completers 98

Mother age: Median: 

Intervention: 31 years 

Control: 32 years 28-35 

years

Infant age: Median 

Gestational age: 

Control: 28.9 weeks 

Intervention: 28.4 weeks 

Gestational age: 26.6-

30.9 weeks

Race of Mother: NR

Exclusion Criteria: 

Major congenital 

abnormalities and 

cerebral hemorrhage

Duration: Infants Until discharge or bottle of 

study oil was empty (average 63 days of age)

Arm 1: Control

Description: Study oil: soy oil and medium 

chain triglycerides

Active ingredients: 127mg linolenic acid/100 ml 

milk(27.1% total fatty acids)

Dose: 0.5 ml study oil/100 ml human milk

Blinding: Study oils packed in numbered bottles 

in hospital pharmacy

Maternal conditions

Infant conditions

ALA: 16mg/100 ml milk; 3.4% total fatty acids

Current smoker 15%

Low birth weight 100%

Other conditions 1 Small for gestational age: 

30%

Arm 2: Intervention

Description: DHA and AA-containing oil

Manufacturer: Martek Biosciences

Active ingredients: 88mg/100 ml linoleic acid 

per 100 ml milk (18.8%)

Dose: 0.5 ml study oil per 100 ml milk, ad lib

Maternal conditions

Infant conditions

DHA: 32mg/100ml milk (6.9%)

AA: 31 mg/100 ml milk (6.7% total fatty acids

Current smoker 19%

Low birth weight 100%

Other conditions 1 Small for gestational age: 

29%

Follow-up time: 8 years

Arm 1: Sample size 52; mean 93.9; SD 

(10)

Arm 2: Sample size 45; mean 92.7; SD 

(8.8)

Outcome: Weschler Abbreviated Scale of 

Intelligence: Verbal IQ (Secondary)

Follow-up time: 8 years

Arm 1: Sample size 52; mean 90.3; SD 

(12.5)

Arm 2: Sample size 45; mean 88.8; SD 

(10.3)

Outcome: Weschler Abbreviated Scale of 

Intelligence: performance IQ (Secondary)

Follow-up time: 8 years

Arm 1: Sample size 52; mean 95.9; SD 

(14.4)

Arm 2: Sample size 45; mean 95.0; SD 

(12.6)

Ane C. Westerberg et Study Population: Inclusion Criteria: All Start time: Infants at start of enteral feeding Outcome domain: Cognitive development
C-4

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

al., 2011125

Study name: Unnamed 

Trial D

Study dates: Enrollment: 

December 2003 and 

October 2005

Study design: Trial 

randomized parallel

Location: Norway

Funding source / 

conflict: Multiple 

foundations and 

Societies, Manufacturer 

supplied product

Study follow-up: 20 

months

Preterm infants

Infants enrolled 141 

Infants completers 92

Mother age: 

Intervention: 30.8 years 

Control: 31.7 years 

(Intervention: 4.9 years 

Control: 5.0 years) 28-

35 years

Infant age: Mean 

Gestational age: 

Intervention: 28.7 weeks 

Control: 28.9 weeks 

(Intervention: 2.9 weeks 

Control: 2.7 weeks) 

Gestational age: 26.6-

30.9 weeks

Race of Mother: NR

Baseline biomarker 

information: DHA: 

intervention[64.2 (23.5) 

mg/mL] and control 

group [61.3 (18.7)mg / 

mL], AA: 

intervention[205.6 (52.8) 

mg/mL] and control 

group [199.6 (48.7)mg / 

mL],

VLBW infants 

(<1500g) born 

between December 

2003 and November 

2005 at RikshospitaletRadiumhospitalet 

Medical Center, 

Akershus University 

Hospital, Buskerud 

Hospital, and Vestfold 

Hospital in Norway

Exclusion Criteria: 

Major congenital 

abnormalities or 

cerebral hemorrhage 

(grade 3 or 4) as 

determined through 

ultrasonography

Duration: Infants until discharge or until the 

study oil bottle was empty (mean duration of 

supplementation was 63 days)

Arm 1: Placebo

Description: Soy oil

Active ingredients: 127mg linolenic acid/100 ml 

milk(27.1% total fatty acids)

Dose: 0.5 ml study oil/100 ml human milk

Blinding: Study oils packed in numbered bottles 

in hospital pharmacy

ALA: 16mg/100 ml milk; 3.4% total fatty acids

Arm 2: DHA + AA group

Description: DHA and AA-containing oil

Manufacturer: Martek

Active ingredients: 88mg/100 ml linoleic acid 

per 100 ml milk (18.8%)

Dose: 0.5 ml study oil per 100 ml milk, ad lib

Maternal conditions

ALA: 11mg/100 ml milk; 3.4% total fatty acids

DHA: 32mg/100ml milk (6.9%)

AA: 31 mg/100 ml milk (6.7% total fatty acids

Current smoker 22% during pregnancy

Outcome: Bayley Mental Development 

Index (MDI) (Secondary)

Follow-up time: 20 months

Arm 1: Sample size 42; mean 82.9; SD 

(13.3)

Arm 2: Sample size 40; mean 83.5; SD 

(10.5)

Atwell et al., 2013119 Study Population: 

Preterm infants

Inclusion Criteria: 

Infants were eligible if 

Start time: Infants birth Outcome domain: respiratory illness

Outcome: one or more hospitalizations for 
C-5

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: DINO

Study dates: 2001-2005

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Multiple foundations and 

Societies, Manufacturer 

supplied product, Some 

authors serve on

scientific advisory 

boards for corporations

Study follow-up: 18 

months corrected age

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Collins, 2015120

Infants enrolled 657 

Infants completers 648

Infant age: birth

Race of Mother: White 

European (90.5%) Other 

race/ethnicity (9.5%)

born before 33 weeks’ 

gestation

Exclusion Criteria: 

Infants in other trials of 

fatty acid 

supplementation, or 

with major congenital 

or chromosomal 

abnormalities, or 

maternal 

contraindication for 

tuna oil ingestion 

(allergy or 

coagulopathy) were 

excluded.

Duration: Infants to 40 weeks’ postmenstrual 

age (term)

Arm 1: Standard DHA

Description: Placebo/control group (soy oil)

Dose: 6 soy oil capsules/ daily

Blinding: capsules given to breastfeeding 

mothers or added to formula

DHA: 0.35% in preterm formula

Arm 2: High DHA

Description: DHA maternal supplements or 

supplemented preterm formula

Dose: 6 tuna oil capsules daily

DHA: 900 mg in capsules or 1% infant formula

lower respiratory conditions (Secondary) 

Follow-up time: 18 months

Arm 1: 82/335 (24.48%)

Arm 2: 72/322 (22.36%)

Bergmann et al., 201252

Study name: NR

Study dates: 2000-2009

Study design: Trial 

Study Population: 

Healthy infants

Pregnant enrolled 144 

Pregnant completers 

115

Inclusion Criteria: 

Healthy pregnant 

Caucasian women 

who were at least 18 

years and willing to 

breastfeed for at least 

3 months were 

Start time: Pregnant 21 weeks gestation

Duration: Pregnant 21 weeks until 3 months 

after delivery

Arm 1: Vitamins and minerals ("basic")

Description: Control 1

Outcome domain: growth

Outcome: BMI (kg/m2) (Secondary)

Follow-up time: 6 yrs

Arm 1: Sample size 74; mean 15.5; SD 

(1.3)

Arm 2: Sample size 41; mean 15.7; SD 

(1.5)
C-6

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

randomized parallel

Location: Germany

Funding source / 

conflict: NR, None,

Manufacturer supplied 

product

Study follow-up: 6 years

Original, same study, or 

follow-up studies: 

Bergmann, 201241

Infants enrolled 123 

Infants completers 115

Pregnant age: 30.9 

years (4.89)

Infant age: 21 weeks 

gestation

Race of Mother: White 

European (100)

Baseline biomarker 

information: In previous 

study, see refid 2803

enrolled at 21 weeks 

of gestation

Exclusion Criteria: 

Mothers: increased 

risk of premature 

delivery or multiple 

pregnancy, allergy to 

cow milk protein, 

lactose intolerance, 

diabetes, smoking, 

consumption of 

alcohol (>20 g/week), 

or participation in 

another study Infants: 

Premature at birth 

(<37 weeks’ 

gestation), had any 

major malformations, 

or were hospitalized 

for more than one 

week

Manufacturer: Nestle

Arm 2: Basic supplements plus a prebiotic 

fructooligosaccharide (FOS)

Description: Control 2

Manufacturer: Nestle

Arm 3: Basic supplements, FOS, and fish oil

Description: Intervention

Manufacturer: Nestle

DHA: 200 mg

EPA: 60 mg

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 6 yrs

Arm 1: Sample size 74; mean 52.7; SD 

(1.3)

Arm 2: Sample size 41; mean 52.5; SD 

(1.6)

Outcome: height (cm) (Secondary)

Follow-up time: 6 yrs

Arm 1: Sample size 74; mean 119.6; SD 

(4.6)

Arm 2: Sample size 41; mean 119.2; SD 

(5.3)

Outcome: weight (kg) (Secondary)

Follow-up time: 6 yrs

Arm 1: Sample size 74; mean 22.3; SD 

(2.9)

Arm 2: Sample size 41; mean 22.4; SD

(3.1)

Birch et al., 2005111

Study name: NR

Study dates: Not 

reported

Study design: Trial 

randomized parallel

Location: US

Funding source / 

Study Population: 

Healthy infants

Infants enrolled 103 

Infants completers 86

Pregnant age: 31 years 

(4 years)

Infant age: 3.6 

_x0004_days (1.3 days) 

1-5 days

Inclusion Criteria: All 

were born at 37– 40 

wk after conception. 

Only singleton births 

with birth weight 

appropriate for 

gestational age

Exclusion Criteria: 

Family history of milk 

protein allergy, genetic 

or familial eye disease, 

vegetarian or vegan 

Start time: Infants 1-5 days

Duration: Infants 52 wks

Arm 1: Control

Description: Commercial infant formula

Brand name: Enfamil with Iron

Manufacturer: Mead Johnson Nutritionals, 

Evansville, IN

Active ingredients: Linoleic acid-8.48g/L 

(14.6%); 14.7 g protein/L, 37.5 g fat/L, 69.0 g 

carbohydrate/L

Blinding: Each diet was masked by 2 color and 

Outcome domain: Visual function

Reason results are not reported: data only 

reported on graph

Outcome: (Primary)

Outcome domain: growth

Reason results are not reported: data only 

reported on graph

Outcome: (Secondary)
C-7

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

conflict: Government, 

Manufacturer supplied 

product

Race of Mother: NR maternal dietary 

patterns, maternal 

metabolic disease or 

infection, jaundice, 

perinatal asphyxia, 

meconium aspiration, 

or any perinatal event 

that resulted in 

placement of the infant 

in the neonatal 

intensive care unit.

2 number codes, for a total of 4 possible diet 

assignments. The randomization schedule had 

random-length blocks (block length varied from 

6 to 12) and was provided in individual sealed 

envelopes to the study site.

ALA: 1.5% of total fatty acids

Arm 2: LCPUFA-supplemented formula

Description: Commercial formula 

supplemented with LCPUFA

Brand name: Enfamil with Iron plus DHASCO 

and ARASCO

Manufacturer: Formula: Mead Johnson; 

DHA+ARA: Martek Biosciences

Active ingredients: 15% linoleic acid,14.7 g /L 

protein, 37.5 g /L fat, 69.0 g /L carbohydrate

ALA: 1.5% of total fatty acids

DHA: 0.36% of total fatty acids

AA: 0.72% of total fatty acids

Birch et al., 2007146

Study name: Birch

Study dates: 1993-1999

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

Study Population: 

Healthy infants, 

Pregnant women whose 

unborn children were at 

high risk of developing 

asthma

Infants enrolled 

79+40BF Infants 

completers 52+32BF

Infant age: birth (0-5 

days)

Race of Mother: NR

Inclusion Criteria: All 

participants were born 

at 37 to 40 weeks 

postmenstrual age. 

Only singleton births 

with birthweights 

appropriate for 

gestational age

Exclusion Criteria: 

family history of milkprotein allergy, genetic 

or familial eye disease 

(e.g. hereditary retinal 

disease, strabismus), 

vegetarian or vegan 

Start time: Infants birth (0-5 days)

Duration: Infants 17 weeks

Arm 1: Control

Description: standard infant formula without 

added n-3 FA

Brand name: Enfamil with Iron

Manufacturer: Mead Johnson Nutritionals

Active ingredients: linoleic acid: 15% of total 

fats

ALA: 1.5% of total fats

Arm 2: DHA

Description: infant formula fortified with DHA

Brand name: Enfamil with Iron, supplemented 

Outcome domain: Cognitive development

Outcome: Wechsler Preschool and 

Primary Scale of Intelligence: Full-Scale 

IQ (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 101.0; SE 

(2.6)

Arm 2: Sample size 16; mean 105.9; SE 

(3.9)

Arm 3: Sample size 32; mean 107.5; SE 

(3.1)

Outcome: Wechsler Preschool and 

Primary Scale of Intelligence: 

Performance IQ (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 104.2; SE 
C-8

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 4 years maternal dietary 

patterns, maternal 

metabolic disease, 

anemia, or infection, 

presence of a 

congenital 

malformation or 

infection, jaundice, 

perinatal asphyxia, 

meconium aspiration, 

and any perinatal 

event which resulted in 

placement of the infant 

in the neonatal 

intensive care unit

with DHASCO

Manufacturer: Formula: Mead Johnson; DHA: 

Martek Biosciences

Active ingredients: linoleic acid: 15% of total 

fats

ALA: 1.5%

DHA: 0.36%

Arm 3: DHA+ARA

Description: infant formula fortified with DHA 

and ARA

Brand name: Enfamil with Iron, fortified with 

DHASCO and ARASCO

Manufacturer: Formula: Mead-Johnson; DHA, 

ARA: Martek Biosciences

Active ingredients: linoleic acid 15%

ALA: 1.5%

DHA: 0.36%

AA: 0.72%

(2.7)

Arm 2: Sample size 16; mean 108.1; SE 

(3.8)

Arm 3: Sample size 32; mean 108.6; SE 

(3.3)

Outcome: Wechsler Preschool and 

Primary Scale of Intelligence: Verbal IQ 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 98.8; SE 

(2.6)

Arm 2: Sample size 16; mean 102.7; SE 

(4.1)

Arm 3: Sample size 32; mean 104.5; SE 

(2.9)

Outcome domain: Visual function

Outcome: Visual acuity Left Eye (log 

minimum angle of resolution in minutes of 

arc) (Primary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 0.05; SE 

(0.016)

Arm 2: Sample size 16; mean 0.02; SE 

(0.018)

Arm 3: Sample size 17; mean 0.03; SE 

(0.017)

Outcome: Visual acuity Right Eye (log 

minimum angle of resolution in minutes of 

arc) (Primary)

Follow-up time: 4 years

Arm 1: Sample size 19; mean 0.08; SE 

(0.022)

Arm 2: Sample size 16; mean 0.02; SE 

(0.019)

Arm 3: Sample size 17; mean 0.03; SE 
C-9

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(0.017)

Birch et al., 2010121

Study name: Diamond

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: US

Funding source /

conflict: Industry, Some 

authors employed by 

industry (companies that 

make the supplements)

Original, same study, or 

follow-up studies: 

Drover, 2011122; Drover. 

2012123; Colombo, 

2013124; Currie, 2015115

Study Population: 

Healthy infants

Infants enrolled 343 

Infants completers 244

Pregnant age: NR

Mother age: NR

Infant age: 1-9 days

Race of Mother: NR

Inclusion Criteria: 

Healthy term formulafed, singleton-birth 

infants born in any of 5 

hospitals

Exclusion Criteria: 

Infants who had 

received human milk 

within 24 h of 

randomization or who 

had diseases or 

congenital 

abnormalities likely to 

interfere with normal 

growth and 

development or with 

the normal maturation 

of visual or cognitive 

function, poor formula 

intake, or known or 

suspected intolerance 

to cow milk infant 

formula were excluded 

from the study. Also 

excluded were infants 

born to mothers with 

chronic illness, such 

as HIV disease, renal 

or hepatic disease, 

type 1 or type 2 

diabetes, alcoholism, 

or substance abuse

Start time: Infants 4-9 days of age

Duration: Infants 12 months

Arm 1: Control

Brand name: Enfamil with IRon

Manufacturer: Mead-Johnson Nutrition, 

Evansville IN

Arm 2: 0.32% DHA

Brand name: Enfamil LIPIL

Manufacturer: Mead-Johnson; DHA and ARA 

from algal and fungal oils manufactured by 

Martek Biosciences

Dose: not specified

Blinding: not specified

DHA: 0.32% or 17mg/100kcal

AA: 0.64% FA or 34mg/100kcal

Arm 3: 0.64% DHA

Brand name: not specified

Manufacturer: not specified

DHA: 34mg/100kg

AA: 0.64% FA or 34mg/100kcal

Arm 4: 0.96% DHA

Brand name: not specified

Manufacturer: not specified

DHA: 51mg/100kg

AA: 0.64% FA or 34mg/100kcal

Outcome domain: Visual function

Reason results are not reported: data only 

reported on graph

Outcome: (Primary)

Bouwstra et al., 200362 Study Population: Inclusion Criteria: Start time: Infants Birth Outcome domain: Neurological 
C-10

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: Groningen 

LCPUFA study

Study dates: 1997-1999

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / 

conflict: Industry

Study follow-up: 3 

months

Original, same study, or 

follow-up studies: 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; van Goor, 

201036; Goor, 201166

Healthy infants

Infants enrolled 472 

Infants completers 397

Mother age: 31 (5) NR

Infant age: Gestational 

age 39.6 wk (1.3) NR

Race of Mother: White 

European (100)

healthy term infants

Exclusion Criteria: 

infants who had a 

congenital disorder 

that interfered with 

adequate functioning 

in daily life, infants 

from multiple births, 

infants whose mothers 

did not have mastery 

of the Dutch language 

or suffered from 

significant illness or 

disability, adopted and 

foster infants, and 

formula-fed infants 

who had received 

human milk for >5 d.

Duration: Infants 2 months

Arm 1: Control formula

Description: Standard formula with no 

supplemental LCPUFA

Brand name: Nutrilon premium

Manufacturer: Zoetermeer, Netherlands

Active ingredients: linoleic acid (11mol%); ALA 

1.27 mol%

Dose: ad lib

Blinding: not reported

Maternal conditions

Current smoker 32% during pregnancy

Maternal abuse of alcohol/psychotropic drugs 

Alcohol USE during pregnancy 10%

Arm 2: LCPUFA formula

Description: LCPUFA formula fortified with n-3s 

and n-6s

Brand name: NR

Maternal conditions

DHA: 0.30% (by wt)

AA: h 0.45% (by wt)

Current smoker 32% smoked during pregnancy

Maternal abuse of alcohol/psychotropic drugs 

13% used alcohol during pregnancy

Arm 3: breastfed group

Description: breastfed, no formula, not 

randomized here - used as reference group

Maternal conditions

Current smoker 28% smoked during pregnancy

Maternal abuse of alcohol/psychotropic drugs 

38% consumed alcohol during pregnancy

development

Outcome: mildly abnormal general 

movements (Primary)

Follow-up time: 3 months

Arm 1: 41/131 (31.0%)

Arm 2: 23/119 (19.0%)

Outcome: normal-optimal general 

movements (Primary)

Follow-up time: 3 months

Arm 1: 28/131 (21.0%)

Arm 2: 21/119 (18.0%)
C-11

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Bouwstra et al., 200563

Study name: Groningen 

LCPUFA study

Study dates: 1997-2002

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / 

conflict: Industry

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; de 

Jong, 201064; de Jong, 

201265; van Goor, 

201036; Goor, 201166

Study Population: 

Healthy infants

Infants enrolled 472 

Infants completers 446

Mother age: 31 years (5 

years) NR

Infant age: birth

Race of Mother: White 

European (100%)

Inclusion Criteria: 

healthy term infants

Exclusion Criteria: 

infants who had a 

congenital disorder 

that interfered with 

adequate functioning 

in daily life, infants 

from multiple births, 

infants whose mothers 

did not have mastery 

of the Dutch language 

or suffered from 

significant illness or 

disability, adopted and 

foster infants, and 

formula-fed infants 

who had received 

human milk for >5 d.

Start time: Infants Birth

Duration: Infants 2 months

Arm 1: Control group

Description: Standard formula

Brand name: Nutrilon premium

Manufacturer: Zoetermeer, Netherlands

Active ingredients: linoleic acid (11mol%); ALA 

1.27 mol%

Dose: ad lib

Maternal conditions

Current smoker 31% during pregnancy

Maternal abuse of alcohol/psychotropic drugs 

Alcohol USE during pregnancy 8%

Arm 2: LCPUFA formula

Description: LCPUFA formula

Dose: ad lib

Maternal conditions

DHA: 0.30% DHA

AA: 0.45% AA

Current smoker 31% during pregnancy

Maternal abuse of alcohol/psychotropic drugs 

9% used alcohol during pregnancy

Arm 3: breast feeding group

Description: breast fed, no formula

Maternal conditions

Current smoker 19% smoked during pregnancy

Maternal abuse of alcohol/psychotropic drugs 

24% used alcohol during pregnancy

Outcome domain: Cognitive development

Outcome: Bayley Scales of Infant 

Development (Mental Development Index) 

(Secondary)

Follow-up time: 18 months

Arm 1: Sample size 155; mean 105.4; SD 

(15)

Arm 2: Sample size 135; mean 102.7; SD 

(15.4)

Outcome domain: Neurological 

development

Outcome: Bayley PDI (Secondary)

Follow-up time: 18 months

Arm 1: Sample size 169; mean 100.9; SD 

(13.6)

Arm 2: Sample size 146; mean 99.4; SD 

(13.4)

Outcome: neurological optimality score 

(Secondary)

Follow-up time: 18 months

Arm 1: Sample size 169; median 52.0; 5, 

95 percentile

Arm 2: Sample size 146; median 52.0; 5, 

95 percentile

Outcome: number of children with minor 

neurological dysfunction (Secondary)

Follow-up time: 18 months

Arm 1: 8/169 (5.0%)

Arm 2: 10/146 (7.0%)

Brew et al., 2015165

Study name: CAPS

Study Population: 

Healthy infants

Inclusion Criteria: 

parent or an older 

sibling had a history of 

Start time: Infants Birth

Duration: Infants 8 years

Outcome domain: Cognitive development

Outcome: National Assessment Program 

Literacy and Numeracy (NAPLAN): 
C-12

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: September 

1997 to 1999-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source /

conflict: Government

Study follow-up: 3, 5, 7, 

and 9 years of school

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; 

Toelle, 2010169

Infants enrolled 616 

Infants completers 239

Pregnant age: 29.8 

(4.90)

Infant age: NR

Race of Mother: NR 

(NR)

Baseline biomarker 

information: Total n-3 

PUFA 

(DHA+EPA+DPA+ALA) 

as % of total fatty acids 

at 4 ages (on a bar 

chart): 18 months: 

Intervention 72% 

Controls: 48% 3 years 

Intervention 64% 

Controls: 46% 5 years 

Intervention 62% 

Controls: 50% 8 years: 

Intervention 50% 

Controls: 45%

Baseline Omega-3 

intake: 500 mg of tuna 

fish oil, daily, which 

comprised 37% 

LCPUFA (including 135 

mg of DHA and 32 mg 

of EPA per capsule) and 

6% omega-6 PUFA 

(linoleic acid, 

asthma or recurrent 

wheezing, and that the 

child was born at 436 

weeks of gestation

Exclusion Criteria: NR

Arm 1: Intervention

Description: d 500 mg of tuna fish oil 37% 

LCPUFA

Manufacturer: Nu-Mega Industries Pty Ltd, 

Brisbane, Australia

DHA: 135 mg

EPA: 32 mg

AA: 6% of omega 3PUFA (linoleic acid, 

arachidonic acid, docosapentaenoic acid)

Arm 2: Control

Description: a daily Sunola oil capsule

Manufacturer: Nu-Mega Industries

ALA: 0.3%

numeracy score (difference in NAPLAN 

units) (Secondary)

Follow-up time: 10-11 years

239; difference in means -13.7; 95% CI

Follow-up time: 12-13 years

239; difference in means -11.7; 95% CI

Follow-up time: 14-15 years

239; difference in means -24.1; 95% CI

Follow-up time: 8-9 years

239; difference in means -25.4; 95% CI

Outcome: National Assessment Program 

Literacy and Numeracy (NAPLAN): 

reading score (difference in NAPLAN 

units) (Secondary)

Follow-up time: 10-11 years

239; difference in means -3.2; 95% CI

Follow-up time: 12-13 years

239; difference in means -7.0; 95% CI

Follow-up time: 14-15 years

239; difference in means -19.9; 95% CI

Follow-up time: 8-9 years

239; difference in means -27.03; 95% CI
C-13

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

arachidonic acid and 

docosapentaenoic acid)

Campoy et al., 2011141

Study name: NR

Study dates: NR, <2011

Study design: Trial 

randomized factorial 

design

Location: Germany, 

Spain, Hungary

Funding source / 

conflict: Government, 

None

Study follow-up: 6.5 

years

Original, same study, or 

follow-up studies: 

Escolano-Margarit, 

2011130

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 315 

Pregnant completers 

154

Pregnant age: 31 years 

(NR)

Race of Mother: White 

European (99%)

Baseline biomarker 

information: From 

Krauss, 2007 mean 

DHA Placebo group 

5.95 Fish oil group 5.75 

5-MHTF (folic acid) 

group 5.68 Fish oil + 5-

MHTF group 5.89 

mean EPA Placebo 

group 0.28 Fish oil 

group 0.18 5-MHTF 

(folic acid) group 0.17 

Fish oil + 5-MHTF group 

0.22

Inclusion Criteria: 

health pregnant 

women, singleton 

pregnancy, gestation 

20 week at enrollment, 

body weight between 

50 and 92 kg at study 

entry, and intention to 

deliver in one of the 

obstetrical centers

Exclusion Criteria: 

serious chronic illness 

(e.g., diabetes, 

hepatitis, or chronic 

enteric disease), use 

of FO supplements 

since the beginning of 

pregnancy or folate or 

vitamin B-12 

supplements after 

gestation week 16

Start time: Pregnant 22 weeks gestation Infants 

22 weeks gestation

Duration: Pregnant until birth Infants until birth

Arm 1: placebo

Description: milk-based supplement

Brand name: Blemil Plus

Manufacturer: Ordesa Laboratorios, Barcelona, 

Spain)

Active ingredients: vitamins and minerals in 

amounts meeting the recommended intakes 

during the second half of pregnancy for

European women

Dose: one daily dose of 15 g

Blinding: supplements were not distinguishable 

with respect to the appearance of the sachets 

or to their contents

Maternal conditions

Current smoker during pregnancy 8.9%

Arm 2: fish oil

Description: fish oil in milk-based supplement

Manufacturer: Pronova Biocare, Lysaker, 

Norway

Active ingredients: vitamins and minerals in 

amounts meeting the recommended intakes 

during the second half of pregnancy for 

European women

Dose: one 15 g dose

Maternal conditions

DHA: 500 mg

EPA: 100 mg

Outcome domain: Cognitive development

Outcome: Kauffman Assessment Battery 

for Children: Mental Processing 

Composite (Secondary)

Follow-up time: 6.5 years

Arm 1: Sample size 45; median 110.0; 

IQR (14.5)

Arm 2: Sample size 37; median 110.0; 

IQR (11)

Arm 3: Sample size 35; median 108.0; 

IQR (12)

Arm 4: Sample size 37; median 108.0; 

IQR (10.5)

Outcome: Kauffman Assessment Battery 

for Children: Sequential Processing Scale 

(Secondary)

Follow-up time: 6.5 years

Arm 1: Sample size 45; median 106.0; 

IQR (19)

Arm 2: Sample size 37; median 108.0; 

IQR (12)

Arm 3: Sample size 35; median 104.0; 

IQR (14)

Arm 4: Sample size 37; median 104.0; 

IQR (17)

Outcome: Kauffman Assessment Battery 

for Children: Simultaneous Processing 

Scale (Secondary)

Follow-up time: 6.5 years

Arm 1: Sample size 45; median 112.0; 

IQR (11.5)

Arm 2: Sample size 37; median 112.0; 

IQR (10.5)
C-14

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Current smoker during pregnancy 18.9%

Arm 3: folic acid

Description: 400 ug 5-MTHF

Manufacturer: BASF, Ludwigshafen, Germany

Active ingredients: vitamins and minerals in 

amounts meeting the recommended intakes 

during the second half of pregnancy for 

European women

Dose: one 15 g dose

Maternal conditions

Current smoker during pregnancy 17.1%

Arm 4: folic acid + fish oil

Description: 400 _x0001_g 5-MTHF +fish oil

Manufacturer: BASF, Ludwigshafen, Germany

Active ingredients: vitamins and minerals in 

amounts meeting the recommended intakes 

during the second half of pregnancy for 

European women

Dose: one 15 g dose

Maternal conditions

DHA: 500 mg

EPA: 100 mg

Current smoker during pregnancy 18.9%

Arm 3: Sample size 35; median 109.0; 

IQR (14)

Arm 4: Sample size 37; median 110.0; 

IQR (10.5)

Carlson et al., 1996160

Study name: NR

Study dates: NR 

(<1995)

Study design: Trial 

randomized parallel

Study Population: 

Preterm infants

Infants enrolled 59 

Infants completers 27

Infant age: 3 days (NR) 

2 to 5 days

Race of Mother: NR 

Inclusion Criteria: 

infants weighing 

between 747 and 1275 

g at birth who 

achieved full enteral 

feeding of 418 kJ (100 

kcal)/kg/d by 6 wk of 

age and tolerated 

enteral feeding 

thereafter

Start time: Infants 3 days after birth

Duration: Infants 2 months

Arm 1: Placebo

Description: standard formula

Brand name: Similac Special Care

Manufacturer: Ross Products Division, Abbott 

Laboratories

Infant conditions

Outcome domain: Cognitive development

Outcome: Fagan Test of Intelligence: 

time/look (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 1.3; SD 

(0.1)

Arm 2: Sample size 15; mean 1.13; SD 

(0.07)

Outcome: Fagan Test of Intelligence: 

looks to familiar (number) (Secondary)
C-15

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: US

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

Study follow-up: 12 

months

(100)

Exclusion Criteria: 

intraventricular or 

periventricular 

hemorrhage > grade 2, 

a history of maternal 

cocaine or alcohol 

abuse, congenital 

anomalies likely to 

affect long-term 

growth and 

development, or 

intrauterine growth 

retardation defined as 

a weight for 

gestational age below 

the 5th percentile

ALA: 2.4 g / 100 g

Other dose 1: linolenic acid 21.2 g/ 100 g

Pre-term birth 100%

Other conditions 1 bronchopulmonarydysplasia 

(BPD) or chronic lung disease of %

Arm 2: DHA supplement

Description: formula supplemented with DHA 

from marine oil

Brand name: Similac Special Care (plus marine 

oil)

Manufacturer: Ross Products Division, Abbott 

Laboratories

Infant conditions

ALA: 2.4 g / 100 g

DHA: 0.20 g / 100g

EPA: 0.06 g / 100 g

Other dose 1: linolenic acid 21.2 g/ 100 g

Pre-term birth 100%

Other conditions 1 bronchopulmonarydysplasia 

(BPD) or chronic lung disease of- %

Follow-up time: 12 months

Arm 1: Sample size 12; mean 17.5; SD 

(1.4)

Arm 2: Sample size 15; mean 21.5; SD 

(1.3)

Outcome: Fagan Test of Intelligence: 

looks to novel (number) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 22.9; SD 

(1.5)

Arm 2: Sample size 15; mean 25.3; SD 

(1.6)

Outcome: Fagan Test of Intelligence: 

novel time (% of total) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 64.0; SD 

(1.9)

Arm 2: Sample size 15; mean 59.7; SD 

(1.7)

Outcome: Fagan Test of Intelligence: time 

to familiar (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 16.9; SD (1)

Arm 2: Sample size 15; mean 19.3; SD 

(0.9)

Outcome: Fagan Test of Intelligence: time 

to novel (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 33.1; SD 

(1.4)

Arm 2: Sample size 15; mean 31.5; SD 

(1.5)

Outcome: Fagan Test of Intelligence: 

time/familiar look (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 1.04; SD 
C-16

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(0.11)

Arm 2: Sample size 15; mean 0.95; SD 

(0.08)

Outcome: Fagan Test of Intelligence: 

time/novel look (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 1.49; SD 

(0.09)

Arm 2: Sample size 15; mean 1.28; SD 

(0.06)

Outcome: Fagan Test of Intelligence: total 

looks (number) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 40.4; SD 

(2.7)

Arm 2: Sample size 15; mean 46.8; SD 

(2.7)

Outcome: Fagan Test of Intelligence: total 

time (seconds) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 12; mean 50.0; SD 

(1.6)

Arm 2: Sample size 15; mean 50.8; SD 

(1.7)

Carlson et al., 201331

Study name: NR

Study dates: 2006.01-

2011.10

Study design: Trial 

randomized parallel

Location: US

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 350 

Pregnant withdrawals 

49 Pregnant completers 

301

Pregnant age: placebo: 

24.8; DHA: 25.3 

Inclusion Criteria: 

English speaking, 

between 8 and 20 wk 

of gestation, between 

16 and 35.99 y of age, 

and planning to deliver 

at a hospital in the 

Kansas City 

metropolitan area

Exclusion Criteria: 

Start time: Pregnant 99.6/102.9 day

Duration: Pregnant enrollment to birth

Arm 1: Placebo

Description: half soybean and half coin oil

Manufacturer: DSM Nutritional Products)

Active ingredients: a-linolenic acid

Dose: 3 *capsule 200/day

Blinding: both DHA and placebo capsules were 

orange flavored

Outcome domain: Birth weight

Outcome: birth weight (g) (Primary)

Follow-up time: birth

Arm 1: Sample size 147; mean 3187.0; 

SD (602)

Arm 2: Sample size 154; mean 3359.0; 

SD (524)

Outcome domain: Gestational 

hypertension preeclampsia eclampsia

Outcome: preeclampsia (Secondary)
C-17

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

(placebo 4.7; DHA 4.9)

Race of Mother: Black 

(46%;37%) Non-black 

(54%; 63%)

Baseline biomarker 

information: RBCphospholipid-DHA 

(placebo group 4.3 +-

1.3; 4.3 +- 1.1)

Baseline Omega-3 

intake: Voluntary DHA 

intake from supplement 

(placebo group 15%, 

DHA group 9%)

carrying more than 

one fetus, had 

preexisting diabetes 

mellitus or systolic 

blood pressure $140 

mm Hg at enrollment, 

or had any serious 

health condition likely 

to affect the prenatal 

or postnatal growth 

and development of 

their offspring, 

including cancer, 

lupus, hepatitis, 

HIV/AIDS, or a 

diagnosed alcohol or 

chemical dependency, 

or if the initial 

screening based on 

their self-reported 

weight and height 

suggested a BMI (in 

kg/m2 >=40).

Arm 2: DHA

Description: marine algae-oil source of DHA

Manufacturer: DHASCO; DSM Nutritional 

Products, formerly Martek Biosciences)

Dose: 200 mg capsule, 3 times a day

DHA: 200mg/capsule * 3

Follow-up time: during pregnancy

Arm 1: 2/147 (1.3%)

Arm 2: 2/154 (1.3%)

Outcome domain: LBW

Outcome: birthweight <1500g (Secondary)

Follow-up time: birth

Arm 1: 5/147 (3.4%)

Arm 2: 0/154 (0.0%)

Outcome: birthweight <2500g (Secondary)

Follow-up time: birth

Arm 1: 13/147 (9.0%)

Arm 2: 6/154 (3.9%)

Outcome domain: duration of gestation

Outcome: gestational age (days) (Primary)

Follow-up time: birth

Arm 1: Sample size 147; mean 272.8; SD 

(17)

Arm 2: Sample size 154; mean 275.7; SD 

(11.2)

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 13/147 (8.8%)

Arm 2: 12/154 (7.8%)

Cheatham et al., 2011129

Study name: Danish 

National Birth CohortLactating Women

Study dates: 1998-2007

Study design: 

Study Population: 

Healthy infants

Pregnant enrolled 150 

Pregnant completers 98

Infants enrolled 98 

Infants completers 92

Inclusion Criteria: 

Described in Ref. 26 

All the children who 

participated in the 9 

month follow-up visit 

(n = 149) were invited 

to participate in the 7 

year follow-up study.

Start time: Pregnant birth

Duration: Pregnant 9 months

Arm 1: Fish oil

Manufacturer: m BASF Health and Nutrition 

A/S, Ballerup, Denmark

DHA: 0.62 g

EPA: 0.79 g

Outcome domain: Cognitive development

Outcome: Stroop scores (Secondary)

Follow-up time: 7.5 years

Arm 1: Sample size 28; mean -0.21; SD 

(0.1)

Arm 2: Sample size 35; mean -0.23; SD 

(0.14)

Outcome: Woodcock Johnson Test: 

Standardized speed of processing 
C-18

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Observational 

prospective

Location: Denmark

Funding source / 

conflict: Government

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Lauritzen, 2004127; 

Lauritzen, 2005102; 

Lauritzen, 2005128

Infant age: 7.5

Race of Mother: NR 

(100)

Exclusion Criteria: 

Living outside Zealand

Total N-3: 1.5 g/d LCPUFA

Arm 2: Olive oil

Manufacturer: m BASF Health and Nutrition 

A/S, Ballerup, Denmark

(Secondary)

Follow-up time: 7.5 years

Arm 1: Sample size 27; mean 1.02; SD 

(0.26)

Arm 2: Sample size 36; mean 0.96; SD 

(0.26)

Clandinin et al., 2005108

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Canada

Funding source / 

conflict: Industry

Study Population: 

Preterm infants

Infants enrolled 361 

preterm+105 term 

breastfed Infants 

completers 179 preterm 

and 76/105 term 

breastfed

Infant age: 30.6 weeks 

postmenstrual age 24-

36 weeks postmenstrual 

age

Race of Mother: NR 

(100)

Inclusion Criteria: 

Phase I: gestational 

age <35 weeks PMA 

and received <10 total 

days of enteral 

feedings of >30 mL/kg 

per day. Infants initially 

fed human milk were 

not enrolled unless 

formula was started 

within 10 days after 

completing the first 

day of human milk 

feeding Phase II: 

completion of phase I 

and >=80% enteral 

intake from study 

formula during 

hospitalization and 

100% of caloric intake 

Start time: Infants 10 days of age

Duration: Infants 118 weeks

Arm 1: Control

Description: Non-supplemented premature, 

discharge, and term formula

Dose: Ad lib

Blinding: Not reported

Infant conditions

Pre-term birth 119 (100%)

Arm 2: Algal-DHA

Description: supplemented premature infant 

formula supplemented with DHA from algal oil

Manufacturer: Martek Biosciences

Dose: ad lib

DHA: 17mg/100kcal (0.33% by weight)

EPA: 0.1% by weight

AA: 34mg/100kcal (0.67% by weight)

Outcome domain: Cognitive development

Outcome: Bayley Scale of Infant 

Development II (Mental developmental 

index) (Unspecified)

Follow-up time: 118 weeks

Arm 1: Sample size 54; mean 77.0; SE (2)

Arm 2: Sample size 44; mean 83.0; SE (2)

Arm 3: Sample size 60; mean 87.0; SE (2)

Arm 4: Sample size 58; mean 98.0; SE (2)

Outcome domain: Neurological 

development

Outcome: Bayley Scale of Infant 

Development II (Physical developmental 

index) (Unspecified)

Follow-up time: 118 weeks

Arm 1: Sample size 54; mean 83.0; SE (2)

Arm 2: Sample size 46; mean 88.0; SE (2)

Arm 3: Sample size 59; mean 88.0; SE (2)

Arm 4: Sample size 59; mean 98.0; SE (2)
C-19

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

from study formula at 

completion of phase 1. 

Birth weight<1500g

Exclusion Criteria: 

congenital 

abnormalities of the 

gastrointestinal tract, 

hepatitis, hepatic or 

biliary pathology, 

necrotizing 

enterocolitis confirmed 

before enrollment, or 

history of underlying 

disease or congenital 

malformation likely to 

interfere with 

evaluation

Arm 3: Fish-DHA

Description: Premature infant formula 

supplemented with DHA from tuna fish oil

Manufacturer: Martek Biosciences

Dose: ad lib

DHA: 17mg DHA/100 kcal

AA: 34mg/100 kcal

Arm 4: Reference

Description: Breast fed term infants

Outcome domain: growth

Reason results are not reported: data only 

reported on graph

Outcome: (Unspecified)

Collins et al., 2011105

Study name: DINO

Study dates: 2001-2007

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

Study follow-up: 18 

Study Population: 

Preterm infants 

Postpartum women 

Breast-feeding women

Pregnant enrolled 545

Infants enrolled 657 

Infants completers 598

Pregnant age: high DHA 

group 29.9; standard 

DHA group 30.2 (high 

DHA group 5.8; 

standard DHA group 

5.4)

Inclusion Criteria: 

infant born <33 weeks 

gestation

Exclusion Criteria: 

Infants were excluded 

if they had major 

congenital or 

chromosomal 

abnormalities; were a 

multiple birth where 

not all live births were 

eligible; were in other 

trials of fatty acid 

supplementation or 

had a lactating mother 

where tuna oil was 

Start time: Infants birth

Duration: NR

Arm 1: standard DHA

Description: placebo soya oil capsules for 

lactating women and/or standard pre-term 

formula

Manufacturer: Capsule: Clover Corporation; 

Formula: Mead Johnson Nutritionals and 

Nutricia Australasia

Dose: 6*500mg placebo soya oil capsules

Blinding: All capsules were similar in size, 

shape and colour. Formula was packaged by 

colour code. Parents, clinicians and all 

research personnel were blinded to the 

participant’s study group

Outcome domain: growth

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 12 months

Arm 1: Sample size 231; mean 46.2; SD 

(1.8)

Arm 2: Sample size 225; mean 46.1; SD 

(1.8)

Follow-up time: 18 months

Arm 1: Sample size 305; mean 47.8; SD 

(1.7)

Arm 2: Sample size 282; mean 47.8; SD 

(1.8)

Follow-up time: 4 months

Arm 1: Sample size 312; mean 41.8; SD 

(1.7)

Arm 2: Sample size 289; mean 41.6; SD 
C-20

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

months

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Atwell, 

2013119; Collins, 2015120

Infant age: 4 day high 

DHA 3-6; standard 2-5

Race of Mother: NR 

(100)

contraindicated 

(bleeding disorders, 

anticoagulants).

Arm 2: High DHA

Description: tuna oil capsules or DHA pre-term 

formula

Manufacturer: Capsule: Clover Corporation; 

Formula: Mead Johnson Nutritionals and 

Nutricia Australasia

Dose: six 500 mg DHA-rich tuna oil capsules 

per day

(1.7)

Outcome: length (cm) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 239; mean 74.1; SD 

(3.7)

Arm 2: Sample size 226; mean 74.3; SD 

(3.6)

Follow-up time: 18 months

Arm 1: Sample size 306; mean 81.2; SD 

(3.9)

Arm 2: Sample size 286; mean 81.9; SD 

(4)

Follow-up time: 4 months

Arm 1: Sample size 311; mean 61.2; SD 

(3.4)

Arm 2: Sample size 294; mean 61.3; SD 

(3.2)

Outcome: weight (g) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 240; mean 9195.0; 

SD (1410)

Arm 2: Sample size 231; mean 9317.0; 

SD (1455)

Follow-up time: 18 months

Arm 1: Sample size 306; mean 10775.; 

SD (1520)

Arm 2: Sample size 292; mean 11029.; 

SD (1764)

Follow-up time: 4 months

Arm 1: Sample size 316; mean 6203.0; 

SD (1059)

Arm 2: Sample size 299; mean 6218.0; 

SD (1013)

Collins et al., 2015120 Study Population: 

Preterm infants

Inclusion Criteria: 

infants born at <33 

Start time: Infants within 5 days of 1st enteral 

feeding

Outcome domain: ADHD

Outcome: ADHD Conners 3 Al-parent: 
C-21

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: DINO

Study dates: 2001-2013

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Industry, 

Government

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Infants enrolled 657 

Infants completers 604

Infant age: median 30 

weeks gestational age 

28-31 weeks

Race of Mother: NR 

(100)

weeks’ gestation from 

five Australian tertiary 

hospitals between 

2001 and 2005

Exclusion Criteria: a 

major congenital or 

chromosomal 

abnormality, multiple 

birth in which not all 

live-born infants were 

eligible, enrollment in 

other trials of fatty acid 

supplementation, or if 

fish oil was 

contraindicated in the 

lactating mother

Duration: Infants to expected due date

Arm 1: standard DHA

Description: DHA supplementation of infant 

formula or breastfeeding mothers to achieve 

DHA concentrations of term formula fed infants

DHA: ___20 mg/kg/ day of DHA

Arm 2: High DHA

Description: DHA supplementation of infant 

formula or breastfeeding mothers to achieve 

DHA concentration of breastmilk

DHA: ___50 mg/kg/ day of DHA

ADHD t score (total score) (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 64.4; SD 

(18.7)

Arm 2: Sample size 291; mean 65.6; SD 

(18.5)

Outcome: number with ADHD (parent 

reported) (Secondary)

Follow-up time: 7 years

Arm 1: 7/298 (2.3%)

Arm 2: 9/285 (3.16%)

Outcome domain: Autism

Outcome: number with autism spectrum 

disorder

Follow-up time: 7 years

Arm 1: 9/298 (3.0%)

Arm 2: 10/285 (3.5%)

Outcome domain: Cognitive development

Outcome: Weschler Abbreviated Scale of 

Intelligence: Full Scale IQ (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 98.5; SD 

(14.9)

Arm 2: Sample size 291; mean 98.3; SD 

(14)

Outcome: Weschler Abbreviated Scale of 

Intelligence: Performance IQ (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 98.5; SD 

(13.6)

Arm 2: Sample size 291; mean 98.5; SD 

(14.5)

Outcome: Weschler Abbreviated Scale of 

Intelligence: Verbal IQ (Secondary)
C

-22

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 7 years

Arm 1: Sample size 313; mean 98.8; SD 

(15.8)

Arm 2: Sample size 291; mean 98.0; SD 

(14.2)

Outcome domain: Neurological 

development

Outcome: Rey Auditory Verbal Learning 

Test: Delayed recall raw score 

(Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 7.2; SD (3)

Arm 2: Sample size 291; mean 7.3; SD 

(3.5)

Outcome: Rey Auditory Verbal Learning 

Test: Delayed recognition correct words 

(Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 13.1; SD 

(3)

Arm 2: Sample size 291; mean 13.3; SD 

(2.6)

Outcome: Rey Auditory Verbal Learning 

Test: Total (trials 1-5) correct words 

(Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 34.8; SD 

(10.8)

Arm 2: Sample size 291; mean 34.4; SD 

(12.1)

Outcome: Rey Auditory Verbal Learning 

Test: Total intrusions (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 2.5; SD (4)

Arm 2: Sample size 291; mean 2.1; SD 
C

-23

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(3.5)

Outcome: Rey Auditory Verbal Learning Test: Total repetitions (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 3.7; SD 

(4.1)

Arm 2: Sample size 291; mean 4.0; SD 

(4.5)

Outcome: Rey Auditory Verbal Learning 

Test: Trial 1 correct words (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 4.3; SD (2)

Arm 2: Sample size 291; mean 4.4; SD (2)

Outcome domain: Visual function

Outcome: Test of visual perception skills: 

figure ground standard score (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 9.6; SD 

(4.3)

Arm 2: Sample size 291; mean 9.4; SD 

(3.8)

Outcome: Test of visual perception skills: 

visual closure standard score (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 8.0; SD 

(3.7)

Arm 2: Sample size 291; mean 7.6; SD 

(3.6)

Outcome: Test of visual perception skills: 

visual discrimination standard score 

(Secondary)

Follow-up time: 7 years

Arm 1: Sample size 313; mean 8.1; SD 

(3.6)

Arm 2: Sample size 291; mean 8.1; SD 
C-24

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(3.1)

Colombo et al., 2013124

Study name: Diamond

Study dates: 09/03/03-

09/25/05

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry, 

Government, 

Manufacturer supplied 

product

Study follow-up: 18 

months-6 years

Original, same study, or 

follow-up studies: Birch, 

2010121; Drover, 

2011122; Drover. 

2012123; Currie, 2015115

Study Population: 

Healthy infants

Infants enrolled 159 

Infants completers 81

Pregnant age: 24.1 (5.1)

Race of Mother: White 

European (34.9) Black 

(63.9) Other 

race/ethnicity (1.2)

Inclusion Criteria: 

Healthy, full term 

formula-fed singleton 

infants, 37-42 weeks 

gestation, 2490-4200 

g birth weight, born in 

Kansas City between 

9/3/03 and 9/25/05

Exclusion Criteria: 

Receipt of human milk 

within 24 h of 

randomization; 

maternal and newborn 

health conditions 

known to interfere with 

normal growth and 

development (e.g., 

intrauterine growth 

restriction) or with 

normal cognitive 

function (e.g., 

congenital anomalies 

or established genetic 

diagnoses associated 

with intellectual 

disability), poor 

formula intake, or 

intolerance to cow milk 

infant formula; 

mothers with 

physician-documented 

chronic illness (e.g., 

HIV, renal or hepatic 

Start time: Infants Birth

Duration: Infants 12 months

Arm 1: 0.00%

Description: Control, no DHA or AA

Blinding: NR

Arm 2: 0.32%

Description: 0.32% DHA

DHA: 17mg/100 kcal

AA: 34 mg/100 kcal

Arm 3: 0.64%

DHA: 34mg/100 kcal

AA: 34 mg/100 kcal

Arm 4: 0.96%

DHA: 51mg/100 kcal

AA: 34 mg/100 kcal

Outcome domain: Cognitive development

Outcome: Macarthur-Bates 

Communicative Development Inventory

Follow-up time: 18 months

Arm 1: Sample size 18; mean 71.0; SEM 

(20)

Arm 2: Sample size 21; mean 55.0; SEM 

(15)

Arm 3: Sample size 18; mean 97.0; SEM 

(20)

Arm 4: Sample size 24; mean 73.0; SEM 

(15)

Outcome: Weschler Primary Preschool 

Test of Intelligence: Full Scale IQ 

(Secondary)

Follow-up time: 6 year

66; mean 96.2; SE (2)

Arm 1: Sample size 18; mean 90.5; SE (3)

Outcome domain: Neurological 

development

Outcome: Bayley PDI (Secondary)

Follow-up time: 18 months

Arm 1: Sample size 18; mean 99.0; SEM 

(5)

Arm 2: Sample size 21; mean 97.0; SEM 

(5)

Arm 3: Sample size 18; mean 97.0; SEM 

(5)

Arm 4: Sample size 24; mean 98.0; SEM 

(5)
C-25

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

disease, type 1 or type 

2 diabetes, alcoholism, 

or substance abuse)

Courville et al., 201138

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry, 

Government

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 47 

Pregnant withdrawals 0 

Pregnant completers 47

Pregnant age: NR (NR) 

NR

Race of Mother: White 

European (8.5) Black 

(10.6) Asian (4.3) 

Minority (Puerto 

Rican/Latino 66%; 

African - other 8.5%; 

Other or mixed ethnicity 

= 2%)

Baseline Omega-3 

intake: Dietary DHA 

intake (mg/d), not 

including the 

intervention food, from 

24 h dietary recalls: 

DHA-FF 67+-7 (SD); 

Placebo 87+-10 (SD), 

P=0.059

Inclusion Criteria: 

Healthy pregnant 

women, midpregnancy (20–24 

weeks)

Exclusion Criteria: 

parity .5; history of 

chronic hypertension; 

hyperlipidemia; renal 

or liver disease; heart 

disease; thyroid 

disorder; multiple 

gestations; having 

been pregnant or 

lactating in the 

previous 2 years.

Start time: Pregnant 20-24 wk of gestation

Duration: Pregnant until birth

Arm 1: Placebo

Description: placebo bars (

Manufacturer: Nestec Limited (Vevey, 

Switzerland)

Dose: 5 placebo bars per week

Blinding: NR

Arm 2: DHA-FF

Description: DHA cereal-based bars

Manufacturer: Nestec Limited (Vevey, 

Switzerland)

Dose: 5DHA cereal-based bars per week

DHA: 241 mg/d

EPA: 30.1 mg/d

Outcome domain: Birth weight

Outcome: birth weight (kg) (Unspecified)

Follow-up time: birth

Arm 1: Sample size 25; mean 3.19; SD 

(0.44)

Arm 2: Sample size 22; mean 3.33; SD 

(0.46)

Outcome domain: duration of gestation

Outcome: gestational age (weeks) 

(Unspecified)

Follow-up time: birth

Arm 1: Sample size 25; mean 39.4; SD 

(1.2)

Arm 2: Sample size 22; mean 39.9; SD 

(1.1)

Currie et al., 2015115

Study name: Diamond

Study Population: 

Healthy infants

Inclusion Criteria: 

Healthy, singleton, 

term (37–42 weeks 

Start time: Infants birth

Duration: Infants 12 months

Outcome domain: growth

Outcome: BMI (Secondary)

Follow-up time: 2-6 years
C-26

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: 2003-2011

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry, 

Government, 

Manufacturer supplied 

product

Study follow-up: 6 years

Original, same study, or 

follow-up studies: Birch, 

2010121; Drover, 

2011122; Drover. 

2012123; Colombo, 

2013124

Infants enrolled 159 

Infants completers 92

Mother age: 22.9 y (4.1 

y)

Race of Mother: White 

European (NR) Black 

(59-87%) Asian (NR) 

Hispanic (0-9%) Inuit 

Eskimo (NR) Other 

race/ethnicity (NR) Nonblack (13-41%)

gestation), formula-fed 

infants were eligible 

for the study if they 

weighed between 

2490 and 4550 g at 

birth. All were born 

between September 

2003 and October 

2005. Only one child 

per family could 

participate.

Exclusion Criteria: 

Infants were excluded 

if they were older than 

9 days, had received 

human breast milk 

within 24 h of 

randomization or if 

there were newborn 

health conditions 

known to interfere with 

normal growth and 

development or 

cognitive function 

(e.g., intrauterine 

growth restriction, 

congenital anomalies 

or established genetic 

disorders associated 

with intellectual 

disability). Infants were 

also excluded if they 

previously 

demonstrated any 

evidence of cows' milk 

Arm 1: Placebo

Manufacturer: Mead Johnson Nutrition

Blinding: eight colored labeling scheme and 

provided to participants by courier

Arm 2: DHA < ARA

Description: 0.32% DHA 0.64% ARA

Manufacturer: Mead Johnson Nutrition

DHA: 0.32%

AA: 0.64%

Arm 3: DHA = ARA

Description: 0.64% DHA 0.64% ARA

Manufacturer: Mead Johnson Nutrition

DHA: 0.64%

AA: 0.64%

Arm 4: DHA > ARA

Description: 0.96% DHA 0.64% ARA

Manufacturer: Mead Johnson Nutrition

DHA: 0.96%

AA: 0.64%

Arm 1: Sample size 15; mean 16.6; SE 

(0.4)

Arm 2: Sample size 54; mean 16.9; SE 

(0.4)

Outcome: BMI-for-age percentile 

(Secondary)

Follow-up time: 2-6 years

Arm 1: Sample size 15; mean 61.2; SE 

(4.8)

Arm 2: Sample size 54; mean 67.8; SE 

(3.2)

Outcome: Length-for-age percentile 

(Secondary)

Follow-up time: 2-6 years

Arm 1: Sample size 15; mean 46.5; SE 

(4.6)

Arm 2: Sample size 54; mean 59.1; SE 

(3.5)

Follow-up time: birth-18 months

Arm 1: Sample size 15; mean 53.1; SE 

(3.7)

Arm 2: Sample size 54; mean 61.8; SE 

(2.4)

Outcome: Weight-for-age percentile 

(Secondary)

Follow-up time: 2-6 years

Arm 1: Sample size 15; mean 49.8; SE 

(12)

Arm 2: Sample size 54; mean 68.0; SE 

(10.8)

Follow-up time: birth-18 months

Arm 1: Sample size 15; mean 50.0; SE 

(3.8)

Arm 2: Sample size 54; mean 54.5; SE 

(2.6)
C-27

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

formula intolerance or 

if born to mothers with 

physician-documented 

chronic illness (e.g., 

HIV, renal or hepatic 

disease, type 1 or 2 

diabetes, alcoholism 

or other substance 

abuse).

D'Vaz et al., 2012142

Study name: IFOS

Study dates: 2005-2009

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Multiple foundations and 

Societies, None, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Meldrum, 2012140

Study Population: 

Pregnant women with 

allergies

Infants enrolled 420 

Infants completers 323

Pregnant age: Placebo: 

33.2 Fish Oil: 32.5 

(Placebo: 4.2 Fish Oil: 

4.8)

Infant age: Term (39.3 

weeks gestation)

Race of Mother: NR 

(100)

Inclusion Criteria: 

Maternal: Pregnant 

History of doctor 

diagnosed asthma or 

allergic rhinitis Skin 

prick positive to at 

least one allergen

Exclusion Criteria: 

Maternal: Smoking 

Auto-immune disease 

Pre-existing medical 

conditions other than 

asthma High-risk 

pregnancy Seafood 

allergy Fish eaten 

more than three times 

per week Fish oil 

supplementation 

already taken (in 

excess of 1000 mg per

day) Exclusion from 

data analysis criteria 

due to protocol 

deviations: Pre-term 

delivery (gestation <36 

Start time: Infants Birth

Duration: Infants 6 months

Arm 1: Placebo

Description: Olive oil

Manufacturer: Ocean Nutrition, Ltd

Dose: 650 mg olive oil

Blinding: Randomization was completed by 

external staff via computer software using an 

unpredictable allocation sequence, stratified 

according to maternal and paternal atopic 

history and parity. Mothers and study 

personnel were unaware of the group 

allocation.

Maternal conditions

Maternal allergies 100

Arm 2: Fish oil group

Manufacturer: Ocean Nutrition Ltd.

Purity Data: fatty acid composition remained 

unchanged over the study period

Dose: 1 capsule contents, to be administered 

orally, prior to feeding in the morning

Maternal conditions

DHA: 280 mg

Outcome domain: allergies

Outcome: allergic disease (any of IgE 

mediated food allergy, eczema or asthma) 

(Primary)

Follow-up time: 12 months

Arm 1: 66/167 (39.52%)

Arm 2: 59/156 (37.82%)

Outcome: food allergy (Primary)

Follow-up time: 12 months

Arm 1: 25/167 (14.97%)

Arm 2: 19/156 (12.18%)

Outcome domain: atopic dermatitis

Outcome: eczema (Primary)

Follow-up time: 12 months

Arm 1: 68/167 (40.72%)

Arm 2: 61/156 (39.1%)

Outcome domain: respiratory illness

Outcome: asthma (Primary)

Follow-up time: 12 months

Arm 1: 0/167 (0.0%)

Arm 2: 0/156 (0.0%)

Outcome: persistent cough (Primary)

Follow-up time: 12 months

Arm 1: 38/167 (22.75%)
C-28

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

weeks) Infant with 

congenital 

abnormalities or 

significant disease not 

related to intervention

EPA: 110 mg

Maternal allergies 100

Arm 2: 42/156 (26.92%)

Follow-up time: 6 months

Arm 1: 27/167 (16.17%)

Arm 2: 19/156 (12.18%)

Outcome: recurrent wheeze (Primary)

Follow-up time: 12 months

Arm 1: 16/167 (9.58%)

Arm 2: 21/156 (13.46%)

Follow-up time: 6 months

Arm 1: 27/167 (16.17%)

Arm 2: 23/156 (14.74%)

Doornbos et al., 200990

Study name: NR

Study dates: Not 

reported

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / 

conflict: Industry

Study follow-up: 3 

months/12 weeks 

postpartum

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 182 

Pregnant withdrawals 

63 Pregnant completers 

119

Pregnant age: NR (NR) 

NR

Race of Mother: NR 

(100)

Baseline biomarker 

information: Placebo 

group: DHA- 4.44 (3.00–

6.92); AA-12.91 (9.95–

14.95) DHA group: 

DHA- 5.51 (3.98–8.20); 

AA-12.13 (9.63–15.22) 

DHA+AA group: DHA5.57 (2.48–8.32); AAInclusion Criteria: 

women with first or 

second, singleton 

pregnancies

Exclusion Criteria: 

women with a 

vegetarian or vegan 

diet or gestational 

diabetes and preterm 

delivery (<37 weeks)

Start time: Pregnant 16.5 (14-20) week of 

pregnancy

Duration: Pregnant till 3 months after delivery

Arm 1: Control group

Description: Placebo-soybean oil

Arm 2: DHA group

Brand name: NR

Manufacturer: NR

DHA: 220mg

Arm 3: DHA + AA group

Brand name: NR

Manufacturer: NR

DHA: 220 mg

AA: 220mg

Outcome domain: Ante or postnatal 

depression

Outcome: Edinburgh Postnatal 

Depression Scale (EPDS) (Secondary)

Follow-up time: 36 weeks pregnant

Arm 1: Sample size 34; median 4.0; IQR

Arm 2: Sample size 40; median 4.0; IQR

Arm 3: Sample size 37; median 6.0; IQR

Follow-up time: 6 weeks post-partum

Arm 1: Sample size 32; median 5.0; IQR

Arm 2: Sample size 38; median 4.0; IQR

Arm 3: Sample size 30; median 5.0; IQR
C-29

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

13.60 (11.17–15.52)

Drover et al., 2011122

Study name: Diamond

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: Birch, 

2010121; Drover. 

2012123; Colombo, 

2013124; Currie, 2015115

Study Population: 

Healthy infants

Infants enrolled 181 

Infants withdrawals 64 

Infants completers 117

Infant age: 18.1 month 

(0.2)

Race of Mother: White 

European (70%) 

Minority (30%)

Inclusion Criteria: 

Children who had 

enrolled in the initial 

phase of the 

DIAMOND study at the 

Dallas site, and had 

completed the 12-

month feeding protocol 

and the 12-month 

primary outcome visit 

(141 children)

Exclusion Criteria: 

Infants who had 

diseases or congenital 

abnormalities known 

to affect growth, 

development, visual or 

cognitive maturation, 

or who had poor 

formula intake did not 

participate in the 

study. Infants were 

also excluded if they 

had received human 

milk within 24 h of 

randomization, or if 

they were born to 

mothers with chronic 

illness such as HIV 

disease, renal or 

hepatic disease, type 

1 or type 2 diabetes, 

alcoholism, or 

Start time: Infants birth (1 9 days)

Duration: Infants 1 year

Arm 1: No DHA (Control)

Description: Cow's milk-based infant formula 

without DHA or ARA

Brand name: Enfamil® with iron

Manufacturer: Mead Johnson & Co, Evansville, 

IN

Blinding: After obtaining signed assent from a 

parent, the study coordinator opened the next 

sequentially-numbered opaque sealed 

envelope to determine the code of the study 

formula to be assigned to that infant. All 

recruiting personnel, parents or guardians, 

study monitors, researchers, and pediatricians 

were masked to the infant's assigned formula.

Arm 2: 0.32% DHA

Description: 0.32% fatty acids from DHA & 

0.64% ARA

Brand name: Enfamil LIPIL®)

Manufacturer: Enfamil LIPIL®

DHA: 17mg/100 kcal, 0.32% DHA with 0.32% 

fatty acids from DHA

AA: 34mg/100 kcal, 0.64% ARA

Arm 3: 0.64% DHA

Description: 0.64% DHA & 0.64% ARA

Brand name: Enfamil LIPIL

Manufacturer: Mead Johnson Nutrition

DHA: 34 mg/100 kcal

AA: 34mg/100 kcal, 0.64% ARA

Outcome domain: Cognitive development

Outcome: Bayley Scale of Infant 

Development II (Mental developmental 

index) (Secondary)

Follow-up time: 18 months

Arm 1: Sample size 28; mean 98.4; SD 

(13.1)

Arm 2: Sample size 29; mean 105.2; SD 

(10.7)

Arm 3: Sample size 32; mean 104.2; SD 

(9.8)

Arm 4: Sample size 28; mean 102.6; SD 

(11.9)
C-30

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

substance abuse

Arm 4: 0.96% DHA

Description: 0.96% DHA & 0.64% ARA

Brand name: Enfamil LIPIL

Manufacturer: Mead Johnson Nutrition

DHA: 54 mg/100 kcal; 0.96% DHA

AA: 34 mg/100 kcal; 0.64% ARA

Drover et al., 2012123

Study name: Diamond

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry

Study follow-up: 3.5 

years

Original, same study, or 

follow-up studies: Birch, 

2010121; Drover, 

2011122; Colombo, 

2013124; Currie, 2015115

Study Population: 

Healthy infants

Infants enrolled 343 

Infants completers 88

Pregnant age: 31 years 

(4 years)

Infant age: <= 9 days 1 

to 9 days

Race of Mother: NR 

(100)

Inclusion Criteria: 

Healthy term 

singleton-birth infants 

born in any of 5 

hospitals

Exclusion Criteria: 

Infants who had 

diseases or congenital 

abnormalities known 

to affect growth, 

development, visual or 

cognitive maturation, 

Infants were also 

excluded if they had 

received human milk 

within 24 h of 

randomization, or if 

they were born to 

mothers with chronic 

illness such as HIV 

disease, renal or 

hepatic disease, type 

1 or type 2 diabetes, 

alcoholism, or 

substance abuse

Start time: Infants <=9 days after birth

Duration: Infants 12 months

Arm 1: Control group

Description: Standard infant formula

Brand name: Enfamil with Iron

Manufacturer: Mead-Johnson Nutrition, 

Evansville IN

Arm 2: 0.32% DHA formula

Brand name: Enfamil LIPIL®

Manufacturer: Mead-Johnson; DHA and ARA 

from algal and fungal oils manufactured by 

Martek Biosciences

DHA: 0.32% or 17mg/100kcal

AA: 0.64% FA or 34mg/100kcal

Arm 3: 0.64% DHA formula

Brand name: NR

Manufacturer: NR

DHA: 34mg/100kg

AA: 0.64% FA or 34mg/100kcal

Arm 4: 0.96% DHA formula

Brand name: NR

Manufacturer: NR

DHA: 51mg/100kg

Outcome domain: Cognitive development

Outcome: School Readiness Composite 

(SRC) (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 19; mean 9.79; SD 

(2.42)

Arm 2: Sample size 23; mean 10.3; SD 

(1.92)

Arm 3: Sample size 27; mean 10.63; SD 

(2.75)

Arm 4: Sample size 24; mean 10.79; SD 

(2.62)
C-31

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

AA: 0.64% FA or 34mg/100kcal

Dunstan et al., 200350

Study name: Dunstan

Study dates: 1999-2001

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government

Study follow-up: 1 year

Original, same study, or 

follow-up studies: 

Dunstan, 200844; 

Meldrum, 201551

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 98 

Pregnant withdrawals 

15 Pregnant completers 

83

Pregnant age: NR (NR) 

NR

Race of Mother: NR 

(100)

Inclusion Criteria: All 

women had a history 

of physiciandiagnosed allergic 

rhinitis and/or asthma 

and 1 or more positive 

skin prick tests to 

common allergens 

(house dust mite; 

grass pollens; molds; 

and cat, dog, and 

cockroach extracts)

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked; if they had 

other medical 

problems, complicated 

pregnancies, or 

seafood allergy; or if 

their normal dietary 

intake exceeded 2 

meals of fish per 

week.

Start time: Pregnant 20 weeks of gestation

Duration: Pregnant till delivery

Arm 1: Placebo group

Description: 46 women allocated and received 

placebo-olive oil

Manufacturer: Pan Laboratories, Moorebank, 

NSW, Australia

Active ingredients: 66.6% n-9 oleic acid

Dose: 4 (1-g) capsules of olive oil per day

Blinding: Randomization and allocation of 

capsules occurred at a different center 

separate from the recruitment of participants. 

Capsules were administered to the participants 

by someone separate from those doing the 

allocation. The capsules in the 2 groups were 

image-matched.

Total N-3: <1% n-3 PUFAs

Arm 2: Fish oil group

Description: 52 women were randomized to 

receive fish oil

Manufacturer: Ocean Nutrition, Halifax, Nova 

Scotia, Canada

Dose: 4 (1g) fish oil capsules per day 

_x001E__x0007__x0005__x0015__x0013__x0

007_ _x001E__x0013__x000F_

DHA: 56.0%

EPA: 27.7%

Total N-3: 3.7 g

Outcome domain: allergies

Outcome: food allergy (Secondary)

Follow-up time: 1 year

Arm 1: 5/43 (11.63%)

Arm 2: 3/40 (7.5%)

Outcome domain: atopic dermatitis

Outcome: atopic dermatitis (Secondary)

Follow-up time: 1 year

Arm 1: 13/43 (30.23%)

Arm 2: 18/40 (45.0%)

Outcome domain: respiratory illness

Outcome: asthma (Secondary)

Follow-up time: 1 year

Arm 1: 6/43 (13.95%)

Arm 2: 2/40 (5.0%)

Outcome: chronic cough (Secondary)

Follow-up time: 1 year

Arm 1: 11/43 (25.58%)

Arm 2: 5/40 (12.5%)

Outcome: recurrent wheeze (Secondary)

Follow-up time: 1 year

Arm 1: 12/43 (27.91%)

Arm 2: 10/40 (25.0%)

Dunstan et al., 200844

Study name: Dunstan

Study Population: 

Healthy infants 

Pregnant women with 

Inclusion Criteria: 

Healthy term infants of 

pregnant women 

Start time: Pregnant 20 weeks gestation

Duration: Pregnant to term

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth
C-32

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: 2000-2003

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Multiple 

foundations and 

Societies

Original, same study, or 

follow-up studies: 

Dunstan, 200350; 

Meldrum, 201551

allergies

Pregnant enrolled 98 

Pregnant completers 83

Infants enrolled 83 

Infants withdrawals 11

(7 FO, 4 control) Infants 

completers 72

Pregnant age: Fish oil: 

30.9 Control: 32.6 (Fish 

oil: 3.7 Control: 3.6)

Infant age: Term (mean 

gestational period 275 

days)

Race of Mother: NR 

(NR)

Baseline biomarker 

information: Cord blood 

erythrocyte (as % total 

fatty acids) 20:4n-6 14.9 

(1.4) 17.6 (1.0) ,0.001 

20:5n-3 1.3 (0.5) 0.4 

(0.3) ,0.001 22:3n-6 2.8 

(0.5) 3.9 (0.5) ,0.001 

22:4n-6 0.8 (0.2) 1.5 

(0.3) ,0.001 22:5n-3 6.3 

(0.8) 6.0 (0.5) 0.037 

22:6n-3 10.3 (1.1) 7.4 

(0.9) ,0.001 Total n-6 

PUFAs* 25.0 (1.8) 29.6 

(1.1) ,0.001 Total n-3 

enrolled in RCT of 

gestational 

supplementation

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked, had medical 

problems, a 

complicated 

pregnancy, seafood 

allergy, or if their 

normal dietary intake 

exceeded two meals 

of fish per week. 

Children were 

excluded from the 

study if they were born 

before 36 weeks’ 

gestation or with major 

disease (to avoid the 

confounding effects on 

immune response) or 

if cord blood was not 

collected

Arm 1: Control

Description: olive oil placebo

Blinding: capsules image matched

Maternal conditions

Current smoker 0%

Maternal allergies 100%

Arm 2: Fish oil

Description: same

Manufacturer: Ocean Nutrition, Halifax Nova 

Scotia

Active ingredients: 3-4mg/g vitamin E

Viability: none reported

Dose: 4 1-gm capsules fish oil per day

Maternal conditions

DHA: 2.2

EPA: 1.1

Other dose 1: fish oil supplying 2,2g/d DHA 

and 1.1g/day EPA

Current smoker 0%

Maternal allergies 100%

Arm 1: Sample size 39; mean 3434.0; SD 

(377)

Arm 2: Sample size 33; mean 3508.0; SD 

(353)

Outcome domain: Cognitive development

Outcome: Griffith Mental Development 

Scales: Eye and hand coordination 

(Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 108.0; SD 

(11.3)

Arm 2: Sample size 33; mean 114.0; SD 

(10.2)

Outcome: Griffith Mental Development 

Scales: Performance (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 115.8; SD 

(13.7)

Arm 2: Sample size 33; mean 120.9; SD 

(12.7)

Outcome: Griffith Mental Development 

Scales: Practical reasoning (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 113.6; SD 

(15)

Arm 2: Sample size 33; mean 114.3; SD 

(14.5)

Outcome: Griffith Mental Development 

Scales: Speech and hearing (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 109.6; SD 

(14.9)

Arm 2: Sample size 33; mean 112.0; SD 

(15)

Outcome: Griffith Mental Development 
C

-33

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

PUFAs{ 17.9 (1.9) 13.7 

(1.3) ,0.001 Total n-3 to 

n-6{ 0.8 (0.1) 0.5 (0.1) 

,0.001

Scales: General quotient score 

(Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 110.5; SD 

(10.6)

Arm 2: Sample size 33; mean 114.2; SD 

(9.8)

Outcome: Griffith Mental Development 

Scales: Personal social (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 109.4; SD 

(11.5)

Arm 2: Sample size 33; mean 112.4; SD 

(11.9)

Outcome: Griffith Mental Development 

Scales: Locomotor (Secondary)

Follow-up time: 2.5 years

Arm 1: Sample size 39; mean 107.9; SD 

(12.6)

Arm 2: Sample size 33; mean 112.5; SD 

(12.2)

Outcome domain: duration of gestation

Outcome: gestational age (days) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 39; mean 274.5; SD 

(8)

Arm 2: Sample size 33; mean 276.0; SD 

(8)

Outcome domain: growth

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 30 months

Arm 1: Sample size 36; mean 49.8; SD 
C-34

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(1.7)

Arm 2: Sample size 28; mean 49.4; SD 

(1.6)

Outcome: length (cm) (Secondary)

Follow-up time: 30 months

Arm 1: Sample size 36; mean 93.3; SD 

(4.6)

Arm 2: Sample size 28; mean 93.8; SD 

(3.8)

Outcome: weight (kg) (Secondary)

Follow-up time: 30 months

Arm 1: Sample size 36; mean 14.1; SD (2)

Arm 2: Sample size 28; mean 14.5; SD (2)

Escamilla-Nunez et al., 

201459

Study name: POSGRAD

Study dates: 2005-2009

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / 

conflict: Government

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Stein, 201233; ImhoffStudy Population: 

Pregnant women with 

allergies

Pregnant enrolled 1,040 

Pregnant completers 

973

Pregnant age: 26.3 (4.8) 

18-35

Race of Mother: 

Hispanic (100% 

Mexican)

Baseline Omega-3 

intake: DHA median 

(25th, 75th percentile), 

mg/d: 55(37, 99)

Inclusion Criteria: 

Maternal age 18 - 35 

years, recruited 

between 18 and 22 

weeks of gestation. 

Willingness to 

breastfeed exclusively 

or predominantly 

during at least the first 

3 months of life of the 

newborn and with the 

intention to live in their 

area of residence for 

at least 2 years after 

delivery

Exclusion Criteria: 

High-risk pregnancies 

(pregnancy 

complications, 

including premature 

placental abruption, 

Start time: Pregnant 18-22 weeks gestation

Duration: Pregnant to term

Arm 1: Placebo

Description: olive oil capsule

Dose: 2 capsules per day

Arm 2: DHA

Description: Algal DHA

Manufacturer: Martek Biosciences

Dose: 2 capsules of 200mg each

DHA: 200 mg algal DHA/capsule

Outcome domain: respiratory illness

Outcome: breathing difficulty (number of 

episodes)

Follow-up time: 18 months

Arm 1: 48/440

Arm 2: 47/429

Outcome: cough (number of episodes)

Follow-up time: 18 months

Arm 1: 1151/440

Arm 2: 1178/429

Outcome: phlegm with congestion and/or 

nasal discharge, fever with phlegm and 

congestion and/or nasal discharge, or 

wheezing with fever (Primary)

Follow-up time: 18 months

Arm 1: 49/440 (11.11%)

Arm 2: 48/429 (11.11%)

Outcome: wheezing (number of episodes)

Follow-up time: 18 months

Arm 1: 262/440

Arm 2: 252/429
C-35

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Kunsch, 201158; 

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561

preeclampsia, 

pregnancy-induced 

hypertension, severe 

bleeding episode in 

pregnancy or lipid 

absorption disorders; 

Regular consumption 

of fish oil or DHA 

supplements; Chronic 

use of certain 

medications (e.g., 

drugs for epilepsy)

Escolano-Margarit et al., 

2011130

Study name: NUHEAL

Study dates: 2001-2008

Study design: Trial 

randomized parallel

Location: Germany, 

Spain, Hungary

Funding source / 

conflict: Manufacturer 

supplied product

Study follow-up: 5.5 

years

Original, same study, or 

follow-up studies: 

Campoy, 2011141.

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 315 

Pregnant completers 

157

Infants enrolled 315 

Infants completers 148

Pregnant age: 31 (NR) 

18 to 41

Race of Mother: NR 

(100)

Baseline biomarker 

information: For 

newborns mean plasma 

DHA Placebo group 

_x0007_6.9 Fish oil 

group 7.8 5-MHTF (folic 

Inclusion Criteria: 

singleton pregnancy, 

gestation 20 week at 

enrollment, and 

intention to deliver in 

one of the obstetrical 

centers

Exclusion Criteria: 

serious chronic illness 

(e.g., diabetes, 

hepatitis, or chronic 

enteric disease), use 

of FO supplements 

since the beginning of 

pregnancy or folate or 

vitamin B-12 

supplements after 

gestation week 16

Start time: Pregnant week 22 of pregnancy 

Infants NA

Duration: Pregnant until birth

Arm 1: placebo

Description: milk-based supplement

Brand name: Blemil Plus

Manufacturer: Ordesa Laboratorios, Barcelona, 

Spain)

Active ingredients: vitamins and minerals in 

amounts meeting the recommended intakes 

during the second half of pregnancy for 

European women

Dose: one daily dose of 15 g

Blinding: supplements were not distinguishable 

with respect to the appearance of the sachets 

or to their contents

Arm 2: fish oil

Description: fish oil in milk-based supplement

Manufacturer: Pronova Biocare, Lysaker, 

Norway

Outcome domain: Neurological 

development

Outcome: number considered normal on 

Hempel exam (Secondary)

Follow-up time: 5.5 years

Arm 1: 81/87 (93.0%)

Arm 2: 74/80 (93.0%)

Outcome: number considered normal on 

Towen exam (Secondary)

Follow-up time: 5.5 years

Arm 1: 48/69 (70.0%)

Arm 2: 55/79 (70.0%)
C-36

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

acid) group 6.2 

_x0007_Fish oil + 5-

MHTF group 

_x0007_7.0 mean 

plasma AA Placebo 

group 17.6 Fish oil 

group 16.8 5-MHTF 

(folic acid) group 17.3 

_x0007_Fish oil + 5-

MHTF group 16.4

Active ingredients: vitamins and minerals in 

amounts meeting the recommended intakes 

during the second half of pregnancy for 

European women

Dose: one daily dose of 15 g

DHA: 500 mg

EPA: 100 mg

Arm 3: folic acid

Description: 400 _x0001_g 5-MTHF

Manufacturer: BASF, Ludwigshafen, Germany

Active ingredients: vitamins and minerals in 

amounts meeting the recommended intakes 

during the second half of pregnancy for 

European women

Dose: one dose of 15 g

Arm 4: folic acid + fish oil

Description: fish oil + 400 _x0001_g 5-MTHF

Manufacturer: BASF, Ludwigshafen, Germany

Active ingredients: vitamins and minerals in 

amounts meeting the recommended intakes 

during the second half of pregnancy for 

European women

Dose: one dose of 15 g

DHA: 500 mg

EPA: 100 mg

Fang et al., 2005137

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Study Population: 

Preterm infants

Infants enrolled 28 

Infants withdrawals 1 

Infants completers 27

Infant age: 1 week 

Inclusion Criteria: (1) A 

gestational age at birth 

between 30 and 37 

weeks; (2) Normal 

fundus oculi; (3) 

Recruitment prior to 

commencement of 

feeding

Start time: Infants 1 week after birth

Duration: Infants 24 weeks

Arm 1: placebo

Description: infant formula based on the 

composition of human milk

Brand name: Neoangelac

Outcome domain: Cognitive development

Outcome: Bayley Mental Development 

Index (Primary)

Follow-up time: 1 year

Arm 1: Sample size 11; mean 90.5; SD 

(6.9)

Arm 2: Sample size 16; mean 98.7; SD (8)

Follow-up time: 6 months
C-37

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Location: Taiwan

Funding source / 

conflict: Manufacturer 

supplied product

(mean gestation age 33 

weeks) (0.5 week) NA

Race of Mother: NR 

(100)

Exclusion Criteria: (1) 

Breast feeding; (2) A 

maternal history of 

infection, diabetes 

mellitus, gestational 

diabetes mellitus, 

cocaine or alcohol 

abuse, systemic 

diseases or if 

intrauterine growth 

retardation had been 

diagnosed during 

pregnancy; (3) Major 

congenital 

abnormality; (4) 

Severe intraventricular 

hemorrhage > grade 2; 

(5) Cystic 

periventricular 

leukomalacia; (6) 

Retinopathy of 

prematurity stage 2; 

(7) Bronchopulmonary 

dysplasia on 

radiographs or oxygen 

usage 28 days; (8) 

Body weight less than 

the third percentile; (9) 

Surgical intervention 

for necrotizing 

enterocolitis (10) 

Mechanical ventilation 

after achieving enteral 

intake > 110 kcal/kg 

per day; (11) A 5-min 

Manufacturer: Multipower Enterprise 

Corporation

Dose: Babies were given more than 110 

kcal/kg per day during the first 4 months and 

more than 70 kcal/kg per day from 4 to 6 

months

N-6 N-3: 10:1 linoleic:linolenic

Arm 2: Neoangelac Plus

Description: Neoangelac supplemented with 

Omega 3

Brand name: Neoangelac Plus

Manufacturer: Multipower Enterprise 

Corporation

Dose: Babies were given more than 110 

kcal/kg per day during the first 4 months and 

more than 70 kcal/kg per day from 4 to 6 

months

DHA: 0.05%

AA: 0.10%

Arm 1: Sample size 11; mean 91.7; SD 

(10.4)

Arm 2: Sample size 16; mean 96.1; SD 

(8.6)

Outcome domain: Neurological 

development

Outcome: Bayley psychomotor 

development index (Primary)

Follow-up time: 12 months

Arm 1: Sample size 11; mean 86.7; SD 

(11.1)

Arm 2: Sample size 16; mean 98.0; SD 

(5.8)

Follow-up time: 6 months

Arm 1: Sample size 11; mean 95.4; SD 

(13.2)

Arm 2: Sample size 16; mean 102.2; SD 

(10.5)

Outcome domain: Visual function

Outcome: Hiding Heidi Analysis <100% 

(Primary)

Follow-up time: 4 months

Arm 1: 2/11 (18.0%)

Arm 2: 5/16 (31.0%)

Follow-up time: 6 months

Arm 1: 10/11 (91.0%)

Arm 2: 16/16 (100.0%)

Outcome: Lea grating acuity card 1 or 2 

cycles per degree (Primary)

Follow-up time: 4 months

Arm 1: 8/11 (72.0%)

Arm 2: 16/16 (100.0%)

Outcome: Lea grating acuity card 2 or4 

cycles per degree (Primary)
C-38

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Apgar score < 7; (12) 

Administration of blood 

transfusion, blood 

products, or parenteral 

lipids with DHA or AA.

Follow-up time: 6 months

Arm 1: 8/11 (73.0%)

Arm 2: 15/16 (94.0%)

Outcome: Visual evoked potential (log 

minimum angle of resolution in minutes of 

arc) (Primary)

Follow-up time: 4 months

Arm 1: Sample size 10; mean 0.36; SD 

(0.34)

Arm 2: Sample size 14; mean 0.19; SD 

(0.27)

Follow-up time: 6 months

Arm 1: Sample size 10; mean 0.13; SD 

(0.22)

Arm 2: Sample size 13; mean 0.1; SD 

(0.17)

Field et al., 2008112

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Canada

Funding source / 

conflict: Industry

Study Population: 

Healthy infants

Infants enrolled 30 

Infants completers 30

Infant age: 2 weeks 7 to 

14 days

Race of Mother: NR 

(100)

Inclusion Criteria: 

Inclusion criteria for all 

infants stipulated that 

by age 14 d infants 

were receiving 100 % 

of their intake by 

mouth from human 

milk or commercial 

infant formula and that 

infants were healthy 

with birth weight, 

length and head 

circumference 

between the 10th and 

90th percentile for 

gestational age, 

according to the 

National Center for 

Health Statistics 

Start time: Infants no later than 14 days

Duration: NR

Arm 1: Formula (unsuppl)

Description: Placebo/control formula

Brand name: S-26

Manufacturer: Wyeth Nutrition

ALA: 2.3% by weight

Arm 2: Formula + LCP

Description: LCP supplemented formula

Brand name: S-26 Gold

Manufacturer: Wyeth Nutrition

Active ingredients: arachidonic acid - see 

below

ALA: 1.9%

DHA: 0.20%

AA: 0.34%

Outcome domain: growth

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 6 wk

Arm 1: Sample size 14; mean 38.6; SD 

(1.1)

Arm 2: Sample size 16; mean 38.4; SD 

(1.4)

Arm 3: Sample size 16; mean 38.9; SD 

(1.2)

Outcome: length (cm) (Secondary)

Follow-up time: 6 wk

Arm 1: Sample size 14; mean 56.0; SD (2)

Arm 2: Sample size 16; mean 56.0; SD (2)

Arm 3: Sample size 16; mean 58.0; SD (3)

Outcome: weight (g) (Secondary)

Follow-up time: 6 wk

Arm 1: Sample size 14; mean 4901.0; SD 

(590)
C-39

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

growth charts14.

Exclusion Criteria: 

Infants with major 

congenital 

malformations, 

documented systemic 

or congenital infection, 

significant neonatal 

morbidity, diagnosed 

maternal autoimmune 

disorders, acute illness 

precluding oral 

feedings, or conditions 

requiring infant 

feedings other than 

standard formula or 

human milk were 

excluded from the 

study. None of the 

infants had received 

corticosteroids, 

erythrocyte or plasma 

transfusions, or 

intravenous lipid 

emulsions before 

entering the study

Arm 3: Breastfed comparison

Description: Breastfed group, not randomized

Arm 2: Sample size 16; mean 5076.0; SD 

(646)

Arm 3: Sample size 16; mean 5045.0; SD 

(516)

Fleddermann et al., 

2014113

Study name: BeMIM 

(Belgrade-Munch Infant 

Milk Trial)

Study dates: Jan 2010 

Study Population: 

Healthy infants

Infants enrolled 207 

Infants completers 164

Mother age: Control: 

30.6 Intervention: 30.7 

Inclusion Criteria: 

Eligible infants had to 

be born apparently 

healthy from singleton 

pregnancies after 37-

41 weeks of gestation, 

with a birth weight 

between the 3rd and 

Start time: Infants within 28 days

Duration: Infants until 120 days

Arm 1: Control Formula (CF)

Description: Placebo/control formula

Manufacturer: HiPP GmbH & Co. Vertrieb KG 

(Pfaffenhofen, Germany)

Outcome domain: growth

Outcome: head circumference gain 

(g/day) (Secondary)

Follow-up time: about 92 days

Arm 1: Sample size 82; mean 0.05; SD 

(0.01)

Arm 2: Sample size 82; mean 0.05; SD 

(0.01)
C-40

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

to May 2011

Study design: Trial 

randomized parallel

Location: Serbia

Funding source / 

conflict: Industry

Breastfed: 30.1 (Control: 

5.5 Intervention: 5.5 

Breastfed: 4.7)

Infant age: Gestation 

(weeks) Control: 39.2 

Intervention: 39.2 

Breastfed: 39.2 

(Gestation (weeks) 

Control: 1.1 

Intervention: 1.0 

Breastfed: 1.1) until 28 

days

Race of Mother: NR 

(100%)

97th weight-for-age 

percentile according to 

the EURO-Growth 

charts.

Exclusion Criteria: 

Infants with 

malformations, 

congenital heart 

defects, congenital 

vascular diseases, 

severe diseases of 

gastrointestinal tract, 

kidney, liver, central 

nervous system, or 

metabolic disease.

Blinding: 600g cartons and labeled by random 

numbers. The products were packed in 

identical white boxes and labeled with the 

same product name.

ALA: 0.1g/100mL

Arm 2: Intervention Formula (IF)

Manufacturer: HiPP GmbH & Co. Vertrieb KG 

(Pfaffenhofen, Germany)

ALA: 0.1g/100mL

DHA: 7.2g/100mL

AA: 7.2g/100mL

Arm 3: Breastfed

Description: Breastfeeding reference group

Outcome: length gain (g/day) (Secondary)

Follow-up time: about 92 days

Arm 1: Sample size 82; mean 0.1; SD 

(0.02)

Arm 2: Sample size 82; mean 0.11; SD 

(0.02)

Outcome: weight gain (g/day) (Primary)

Follow-up time: about 92 days

Arm 1: Sample size 82; mean 28.3; SD 

(6.5)

Arm 2: Sample size 82; mean 30.2; SD 

(6.3)

Furuhjelm et al., 2009173

Study name: NR

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: Sweden

Funding source / 

conflict: Industry, 

Multiple foundations and 

Societies

Study follow-up: 1 year

Original, same study, or 

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 145 

Pregnant withdrawals 

28 Pregnant completers 

117

Infants enrolled 145 

Infants withdrawals 28 

Infants completers 117

Mother age: 

Intervention: 31.1 years 

(at delivery) Placebo: 

31.7 years (at delivery) 

(Intervention: 4.1 years 

(at delivery) Placebo: 

Inclusion Criteria: a 

family history of past 

of current allergic 

symptoms in at least 

one parent or older 

child.

Exclusion Criteria: 

Mothers with an 

allergy to soy or fish or 

undergoing treatment 

with anticoagulants or 

commercial w-3 fatty 

acid supplements

Start time: Pregnant 25 weeks of gestation

Duration: Pregnant 15 weeks (i.e., until 

delivery)

Arm 1: Placebo

Description: 75 women received soy oil as 

placebo

Manufacturer: Pharma Nord

Active ingredients: w-6 PUFA LA (58%, 2.5 g / 

day), a small amount (6%, 0.28 g / day) of the 

w-3 PUFA LNA and 36 mg a-tocopherol

Viability: alpha-tocopherol was given as an 

antioxidant, a necessary ingredient according 

to the standard procedure of the manufacturer 

to assure the durability of the oil.

Dose: nine soy oil capsules a day

N-6 N-3: 9

Outcome domain: allergies

Outcome: Food Allergy (Primary)

Follow-up time: 12 months

Arm 1: 10/65 (15.38%)

Arm 2: 1/52 (1.92%)

Outcome domain: atopic dermatitis

Outcome: IgE associated eczema 

(Primary)

Follow-up time: 12 months

Arm 1: 15/63 (23.81%)

Arm 2: 4/52 (7.69%)

Follow-up time: 6 months

Arm 1: 13/65 (20.0%)

Arm 2: 4/52 (7.69%)
C-41

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

follow-up studies: 

Furuhjelm, 2011172

3.9 years (at delivery)) 

NR

Race of Mother: NR 

(100)

Baseline biomarker 

information: Treatment -

mean(sd) mol % EPA1.3 (0.8) DHA- 5.5 

(1.1) AA- 9.2 (1.7) 

AA/EPA- 9.1 (4.3) 

Placebo - mean(sd) mol 

% EPA- 1.2 (0.6) DHA5.4 (1.2) AA- 8.6 (1.5) 

AA/EPA- 8.6 (4.0)

Baseline Omega-3 

intake: DHA - 0.2g/day 

EPA- 0.1g/day

Arm 2: w3 group

Description: 70 women are randomized into 

this group

Brand name: Bio Marin capsules

Manufacturer: Pharma Nord, Vejle, Denmark

Active ingredients: 23 mg alpha-tocopherol

Viability: alpha-tocopherol was given as an 

antioxidant, a necessary ingredient according 

to the standard procedure of the manufacturer 

to assure the durability of the oil.

Dose: nine 500-mg capsules, once daily

DHA: 1.1g

EPA: 1.6g

N-6 N-3: <0.1

Furuhjelm et al., 2011172

Study name: NR

Study dates: 2003-2007

Study design: Trial 

randomized parallel

Location: Sweden

Funding source / 

conflict: Industry, 

Multiple foundations and 

Societies

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 145 

Pregnant withdrawals 

28 Pregnant completers 

117

Infants enrolled 145 

Infants withdrawals 28 

Infants completers 117

Pregnant age: NR (NR) 

NR

Inclusion Criteria: 

family history of 

current or previous 

allergic symptoms, i.e. 

bronchial asthma, 

eczema, allergic food 

reactions, itching and 

running eyes and nose 

at exposure to pollen, 

pets or other known 

allergens.

Exclusion Criteria: 

Allergy to soya or fish, 

treatment with 

Start time: Pregnant 25 weeks of gestation

Duration: Pregnant 15 weeks (i.e., until 

delivery)

Arm 1: Placebo

Description: soya bean oil

Manufacturer: Pharma Nord, Vejle, Denmark

Active ingredients: 58% linoleic acid (LA), 2.5 

g/day

Viability: the antioxidant a-tocopherol (placebo: 

36 mg/day) to assure the stability of the oil

Dose: nine capsules a day

Blinding: The mothers, as well as the staff 

handling clinical and laboratory follow-up, were 

Outcome domain: allergies

Outcome: any food reactions (Primary)

Follow-up time: 2 years

Arm 1: 16/65 (24.62%)

Arm 2: 6/54 (11.11%)

Outcome domain: atopic dermatitis

Outcome: any eczema (Primary)

Follow-up time: 2 years

Arm 1: 21/65 (32.31%)

Arm 2: 11/54 (20.37%)

Outcome domain: respiratory illness

Outcome: any asthma (Primary)

Follow-up time: 2 years
C-42

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study follow-up: 2 years

Original, same study, or 

follow-up studies: 

Furuhjelm, 2009173

Race of Mother: NR 

(100)

anticoagulants or 

omega-3 fatty acid 

supplements.

blinded to group allocation, and the mothers 

were identified by their study number only.

ALA: 6%, 0.28 g/day

Arm 2: w-3 group

Description: w-3 fatty acids

Viability: the antioxidant a-tocopherol (w-3 

group: 28 mg/day) to assure the stability of the 

oil

Dose: nine capsules a day

DHA: 25% DHA, 1.1 g/day

EPA: 35% EPA, 1.6 g/day

Arm 1: 8/65 (12.31%)

Arm 2: 7/54 (12.96%)

Outcome: any rhinoconjunctivitis (Primary)

Follow-up time: 2 years

Arm 1: 2/65 (3.08%)

Arm 2: 2/54 (3.7%)

Gonzalez-Casanova et 

al., 201560

Study name: POSGRAD

Study dates: 2005-2012

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / 

conflict: Government, 

None

Study follow-up: 60 

months

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Stein, 201233; ImhoffStudy Population: 

Healthy infants Preterm 

infants

Pregnant enrolled 1040 

Pregnant completers 

968

Infants enrolled 973 

Infants completers 802

Pregnant age: 26.3 y 

(4.7 y)

Infant age: 20.5 weeks 

gestation (2.0)

Race of Mother: NR 

(100)

Inclusion Criteria: 

Pregnant women 18–

35 y of age, in week 

18–22 of gestation, 

and planned to deliver 

at the hospital, 

breastfeed for >3 mo, 

and reside in the area 

for >2 y after delivery

Exclusion Criteria: NR

Start time: Pregnant 18-22 weeks gestation

Duration: Pregnant 18-22 weeks gestation until 

delivery

Arm 1: Placebo

Description: Soy and corn placebo

Dose: 2 200 mg capsules/day

Blinding: Soy-corn placebo of similar taste and 

appearance

Arm 2: DHA (algal)

Dose: 2 200 mg capsules/day

DHA: 400mg

Outcome domain: growth

Outcome: bmi-for-age z score (Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean 0.1; SD 

(1.1)

Arm 2: Sample size 403; mean 0.1; SD 

(1.1)

Outcome: height (cm) (Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean 108.4; SD 

(4.5)

Arm 2: Sample size 403; mean 108.3; SD 

(4.4)

Outcome: height-for-age z-score (Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean -0.4; SD 

(0.9)

Arm 2: Sample size 403; mean -0.4; SD 

(0.9)

Outcome: weight (kg) (Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean 18.4; SD 

(3)
C-43

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Kunsch, 201158; 

Escamilla-Nunez, 

201459; Ramakrishnan, 

201561

Arm 2: Sample size 403; mean 18.3; SD 

(3)

Outcome: weight-for-age z-score 

(Primary)

Follow-up time: 5 years

Arm 1: Sample size 399; mean -0.1; SD 

(1.1)

Arm 2: Sample size 403; mean -0.2; SD 

(1.1)

Goor et al., 201166

Study name: Groningen 

LCPUFA study

Study dates: 2004-2009

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / 

conflict: Industry

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; van Goor, 

201036

Study Population: 

Healthy infants

Pregnant enrolled 119

Infants enrolled 119 

Infants completers 114

Pregnant age: Placebo: 

32.7 DHA: 32.5 

DHA+AA: 32.9 

(Placebo: 5.1 DHA: 4.4 

DHA+AA: 4.8)

Infant age: 18 months

Race of Mother: NR

(100)

Inclusion Criteria: 

women with a first or 

second low-risk 

singleton pregnancy, 

between the 14th and 

20th weeks of 

pregnancy

Exclusion Criteria: 

women with 

vegetarian or vegan 

diets; women with 

diabetes mellitus; birth 

complications

Start time: Pregnant 14th-20th week pregnancy 

Lactating 3 months after delivery Mothers 3 

months after delivery Infants NR

Duration: Pregnant NR Lactating 33-39 weeks 

Mothers 33-39 weeks Infants NR

Arm 1: placebo

Description: Soy bean oil

Brand name: none

Arm 2: DHA

Description: DHA plus soy bean oil

Brand name: Marinol D40

Manufacturer: Lipid Nutrition B.V., 

Wormerveer, The Netherlands; AA:

Dose: 1 capsule DHA and 1 capsule soy bean 

oil once a day

ALA: 32 mg/d

DHA: 220 mg/d

EPA: 34 mg/d

Arm 3: DHA+AA

Description: DHA plus AA

Brand name: AA: no brand name

Manufacturer: Wuhan Alking Bioengeneering 

Outcome domain: Birth weight

Outcome: birth weight (g) (Unspecified)

Follow-up time: birth

Arm 1: Sample size 34; mean 3576.0; SD 

(551)

Arm 2: Sample size 41; mean 3592.0; SD 

(465)

Arm 3: Sample size 39; mean 3652.0; SD 

(377)

Outcome domain: Cognitive development

Outcome: Bayley Scale of Infant 

Development (Mental developmental 

index) (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 115.2; SD 

(11.6)

Arm 2: Sample size 41; mean 113.7; SD 

(13)

Outcome domain: Neurological 

development

Outcome: Bayley psychomotor 

development index (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 91.7; SD 
C-44

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Co. Ltd., Wuhan, China

Dose: 2 capsules once a day

ALA: 7 mg/d

DHA: 220 mg/d

EPA: 36 mg/d

AA: 220 mg per capsule

(8.3)

Arm 2: Sample size 41; mean 95.8; SD 

(11.4)

Arm 3: Sample size 39; mean 92.4; SD 

(8.8)

Outcome: fluency score (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; median 10.0; 

range

Arm 2: Sample size 41; median 9.0; range

Arm 3: Sample size 39; median 10.0; 

range

Outcome: neurological optimality score 

(Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; median 47.5; 

range

Arm 2: Sample size 41; median 46.0; 

range

Arm 3: Sample size 39; median 48.0; 

range

Outcome: prevalence of complex minor 

neurological dysfunction (Unspecified)

Follow-up time: 18 months

Arm 1: 5/34 (14.7%)

Arm 2: 3/41 (7.3%)

Arm 3: 5/39 (12.8%)

Outcome: prevalence of normal 

neurological condition (Unspecified)

Follow-up time: 18 months

Arm 1: 20/34 (58.8%)

Arm 2: 24/41 (58.5%)

Arm 3: 28/39 (71.8%)

Outcome: prevalence of simple minor 

neurological dysfunction (Unspecified)

Follow-up time: 18 months
C-45

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: 9/34 (26.5%)

Arm 2: 14/41 (34.1%)

Arm 3: 6/39 (15.4%)

Outcome domain: growth

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 47.8; SD 

(1.5)

Arm 2: Sample size 41; mean 47.6; SD 

(1.1)

Arm 3: Sample size 39; mean 47.5; SD 

(1.4)

Outcome: length (cm) (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 84.0; SD 

(3.8)

Arm 2: Sample size 41; mean 82.8; SD 

(4.7)

Arm 3: Sample size 39; mean 83.6; SD 

(2.9)

Outcome: weight (kg) (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 34; mean 11.5; SD 

(1.1)

Arm 2: Sample size 41; mean 11.3; SD 

(1.4)

Arm 3: Sample size 39; mean 11.5; SD 

(1.3)

Groh-Wargo et al., 

2005106

Study name: NR

Study Population: 

Preterm infants

Infants enrolled 60 

Infants withdrawals 3 

Inclusion Criteria: 

Preterm infants with 

birth weights from 750 

to 1800 g and GA at 

birth <33 wk were 

Start time: Infants first enteral formula feeding

Duration: Infants 24 kcal/fl oz formula until 40 

wk corrected age; 22 kcal/fl oz formula from 40 

wk CA to 1 year CA

Outcome domain: growth

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 12 months (corrected age)

Arm 1: Sample size 14; mean 46.2; SE 
C-46

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: Sept 1997 

- Sept 1998

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry, 

Government

Infants completers 57

Infant age: GA= 30 

weeks (0.5) NR

Race of Mother: NR

recruited between 

September 1997 and 

September 1998 from 

the neonatal intensive 

care unit. No 

restrictions on the type 

of feeding before study 

entry.

Exclusion Criteria: 

Congenital 

abnormalities that 

could affect growth or 

development, major 

surgery, periventricular 

hemorrhage greater 

than grade II (Papile 

classification), 

asphyxia resulting in 

severe and permanent 

neurologic damage, 

treatment with 

extracorporeal 

membrane 

oxygenation, maternal 

incapacity (including 

substance abuse), or 

uncontrolled systemic 

infection at the time of 

enrollment.

Arm 1: Control

Description: Control formula without DHA or 

ARA

Brand name: Similac Special Care to 40 wk 

GA; and NeoSure until 1 year

ALA: 2.4 g/100 g (to 40 wk GA); 2.4 g/100 g (to 

1 year)

DHA: 0

EPA: 0

AA: 0

Arm 2: DHA+ARA (FF)

Description: DHA or ARA from fish/fungal oil

Brand name: Similac Special Care to 40 wk 

GA; and NeoSure until 1 year

ALA: 2.6 g/100 g (to 40 wk GA); 2.4 g/100 g (to 

1 year)

DHA: 0.27 g/100 g (to 40 wk GA); 0.16 g/100 g 

(to 1 yr)

EPA: 0.08 g/100 g (to 40 wk GA); 0 (to 1 yr)

AA: 0.43 g/100 g (to 40 wk GA); 0 (to 1 yr)

Arm 3: DHA+ARA (EF)

Description: DHA or ARA from egg-derived 

triglyceride and fish oil

Brand name: Similac Special Care to 40 wk 

GA; and NeoSure until 1 year

ALA: 2.5 g/100 g (to 40 wk GA); 2.4 g/100 g (to 

1 year)

DHA: 0.24 g/100 g (to 40 wk GA); 0.15 g/100 g 

(to 1 yr)

EPA: 0

AA: 0.41 g/100 g

(0.4)

Arm 2: Sample size 14; mean 46.0; SE 

(0.4)

Arm 3: Sample size 13; mean 46.2; SE 

(0.4)

Follow-up time: 35 weeks (corrected age)

Arm 1: Sample size 18; mean 30.8; SE 

(0.2)

Arm 2: Sample size 17; mean 30.6; SE 

(0.5)

Arm 3: Sample size 18; mean 30.3; SE 

(0.4)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 14; mean 41.9; SE 

(0.4)

Arm 2: Sample size 16; mean 41.1; SE 

(0.6)

Arm 3: Sample size 14; mean 42.0; SE 

(0.3)

Follow-up time: 40 weeks (corrected age)

Arm 1: Sample size 18; mean 25.4; SE 

(0.3)

Arm 2: Sample size 18; mean 34.5; SE 

(0.5)

Arm 3: Sample size 17; mean 35.0; SE 

(0.3)

Outcome: length (cm) (Secondary)

Follow-up time: 12 months (corrected age)

Arm 1: Sample size 14; mean 73.9; SE 

(0.9)

Arm 2: Sample size 14; mean 75.2; SE 

(0.9)

Arm 3: Sample size 13; mean 76.3; SE 

(0.8)

Follow-up time: 35 weeks (corrected age)

Arm 1: Sample size 18; mean 42.5; SE 
C

-47

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(0.5)

Arm 2: Sample size 17; mean 42.7; SE 

(0.7)

Arm 3: Sample size 18; mean 42.7; SE 

(0.5)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 14; mean 61.8; SE 

(0.7)

Arm 2: Sample size 16; mean 60.9; SE 

(0.6)

Arm 3: Sample size 14; mean 62.8; SE 

(0.7)

Follow-up time: 40 weeks (corrected age)

Arm 1: Sample size 18; mean 48.0; SE 

(0.7)

Arm 2: Sample size 18; mean 48.2; SE 

(0.7)

Arm 3: Sample size 17; mean 48.1; SE 

(0.5)

Outcome: weight (g) (Secondary)

Follow-up time: 12 months (corrected age)

Arm 1: Sample size 14; mean 9343.0; SE 

(307)

Arm 2: Sample size 14; mean 8977.0; SE 

(293)

Arm 3: Sample size 13; mean 9505.0; SE 

(243)

Follow-up time: 35 weeks (corrected age)

Arm 1: Sample size 18; mean 1916.0; SE 

(73)

Arm 2: Sample size 17; mean 1871.0; SE 

(118)

Arm 3: Sample size 18; mean 1874.0; SE 

(85)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 14; mean 6524.0; SE 
C-48

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(220)

Arm 2: Sample size 16; mean 6454.0; SE 

(212)

Arm 3: Sample size 14; mean 6432.0; SE 

(217)

Follow-up time: 40 weeks (corrected age)

Arm 1: Sample size 18; mean 3280.0; SE 

(135)

Arm 2: Sample size 18; mean 3147.0; SE 

(149)

Arm 3: Sample size 17; mean 3136.0; SE 

(105)

Gustafson et al., 201374

Study name: NR

Study dates: May 2009 -

July 2011

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 67 

Pregnant withdrawals 

12 Pregnant completers 

52

Infants enrolled 44 

Infants completers 41

Pregnant age: placebo 

25.6+; DHA 25.5 

(placebo 4.8; DHA 4.3)

Race of Mother: White 

European (46.3) Black 

(37.3) Asian (3) 

Hispanic (13.4)

Baseline biomarker 

information: plasma 

Inclusion Criteria: 

between 16–35.9 

years of age and 

carrying a singleton 

pregnancy between 

the 12th and 20th 

week of gestation

Exclusion Criteria: any 

serious health 

condition likely to 

affect the growth and 

development of the 

fetus or health of the 

mother including 

cancer, lupus, 

hepatitis, diabetes 

mellitus (Type1, Type 

2 or gestational) or 

HIV/AIDS at baseline 

or fetal cardiac 

structural or 

conduction defects. 

Start time: Pregnant 12-20 week gestation 

Infants birth

Duration: Pregnant till birth

Arm 1: Placebo

Description: g 50% soy and 50% corn oil

Manufacturer: Martek Biosciences, now DSM 

Nutritional Products

Dose: 3 capsule a day each 500 mg

Blinding: Only members of the investigational 

pharmacy knew the subject allocation. 

Participants and all members of the 

investigational team were blinded to the 

intervention assignment. Participants were 

allocated to either group based on the simple 

randomization procedure using random 

numbers generated by SAS. All capsules were 

the same color, size, weight and the oils were 

orange-flavored to prevent investigator or 

subject bias.

Arm 2: algal oil as a source of DHA (200 mg of 

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 24; mean 3435.5; SD 

(404.8)

Arm 2: Sample size 22; mean 3416.8; SD 

(552.9)

Outcome domain: Cognitive development

Outcome: Neonatal Behavior Assessment: 

state organization (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 13.5; SD 

(13.89)

Arm 2: Sample size 15; mean 15.13; SD 

(8.02)

Outcome: Neonatal Behavior Assessment: 

autonomic (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 14.83; SD 

(16.9)

Arm 2: Sample size 15; mean 18.13; SD 

(14.48)
C-49

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

DHA (wt% TFA) placebo 

group: 3.91 (3.15-4.21); 

DHA group: 3.94(3.39-

4.72) RBC DHA 

(wt%TFA) placebo 

group 4.30(3.99-5.03); 

DHA group 4.50 (3.73-

5.44)

Women who selfreported illicit drug use 

or alcohol use during 

pregnancy and those 

with hypertension or 

BMI Z40 were 

excluded. Women who 

were taking more than 

200 mg/day DHA in 

prenatal vitamins or 

over the counter 

supplements were 

excluded from 

participation

DHA per capsule for a total of 600 mg 

DHA/day)

Dose: 3 capsule of 200mg DHA total 600 mg

DHA: 200 mg * 3

Outcome: Neonatal Behavior Assessment: 

motor (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 23.08; SD 

(11.4)

Arm 2: Sample size 15; mean 26.07; SD 

(18.13)

Outcome: Neonatal Behavior Assessment: 

reflexes (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 21.92; SD 

(14.45)

Arm 2: Sample size 15; mean 22.6; SD 

(14.33)

Outcome: Neonatal Behavior Assessment: 

state regulation (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 16.42; SD 

(20.02)

Arm 2: Sample size 15; mean 16.93; SD 

(20.06)

Outcome: Neonatal Behavior Assessment: 

habituation (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 9.92; SD 

(9.28)

Arm 2: Sample size 15; mean 8.47; SD 

(9.26)

Outcome: Neonatal Behavior Assessment: 

orienting (Primary)

Follow-up time: 1-14 days post-partum

Arm 1: Sample size 12; mean 19.75; SD 

(15.45)

Arm 2: Sample size 15; mean 23.4; SD 

(18.32)
C-50

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Harper et al., 201029

Study name: NR

Study dates: 01. 2005 -

10. 2006

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Klebanoff, 201149

Study Population: At risk 

for preterm labor

Pregnant enrolled 852 

Pregnant withdrawals 0 

Pregnant completers 

852

Pregnant age: n3: 28 

placebo 27 n3 23-32; 

placebo 24-32

Race of Mother: White 

European (n3: 56.5; 

placebo 57.7) Black (n3: 

34.1; placebo 34.9) 

Asian (n3: 3, placebo 

1.2) Hispanic (n3: 14.7; 

placebo 13.6) Other 

race/ethnicity (NR)

Inclusion Criteria: a 

documented history of 

at least one prior 

singleton preterm 

delivery between 20 

0/7 and 36 6/7 weeks 

of gestation after 

spontaneous preterm 

labor or premature 

rupture of the 

membranes, and a 

current singleton 

pregnancy between 16 

and 21 6/7 weeks of 

gestation

Exclusion Criteria: 

evidence of a major 

fetal anomaly, intake 

of a fish oil 

supplement in excess 

of 500 mg per week at 

any time during the 

preceding month, 

allergy to fish, 

anticoagulation 

therapy, hypertension, 

White’s classification 

D or higher diabetes, 

drug or alcohol abuse, 

seizure disorder, 

uncontrolled thyroid 

disease, clotting 

disorder, current or 

planned cerclage, or a 

Start time: Pregnant 16-22 week gestation age

Duration: Pregnant 36 weeks of gestation

Arm 1: placebo

Description: inert mineral oil

Manufacturer: Eminent Services, Frederick, 

MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: four capsules of matching oil containing 

a minute amount of inert mineral oil

Blinding: Boxes containing a woman’s entire 

supply of capsules in blister packs were 

sequentially numbered according to the 

predetermined randomization sequence, and 

on enrollment a woman was assigned the next 

number in sequence. Study group assignment 

was not known by study participants, their 

health care providers, or the research 

personnel

Arm 2: Eminent Services, Frederick, MD

Active ingredients: 10 IU vitamin E per capsule, 

injections of 17_x0001_-hydroxyprogesterone 

caproate

Dose: in 4 capsules total 2000 mg of n3

DHA: 800 mg

EPA: 1200 mg

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 418; median 2923.0; 

IQR

Arm 2: Sample size 434; median 2990.0; 

IQR

Outcome domain: Gestational 

hypertension preeclampsia eclampsia

Outcome: preeclampsia or gestational 

hypertension (Secondary)

Follow-up time: during pregnancy

Arm 1: 20/418 (4.8%)

Arm 2: 20/434 (4.6%)

Outcome domain: Infants born small 

gestational age

Outcome: SGA less than 10th percentile 

(Secondary)

Follow-up time: birth

Arm 1: 41/410 (10.0%)

Arm 2: 35/427 (8.2%)

Outcome domain: LBW

Outcome: birthweight <1500g (Secondary)

Follow-up time: birth

Arm 1: 29/410 (7.1%)

Arm 2: 26/427 (6.1%)

Outcome: birthweight <2500g

Follow-up time: birth

Arm 1: 112/410 (27.3%)

Arm 2: 94/427 (22.0%)

Outcome domain: duration of gestation
C-51

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

plan to deliver either 

elsewhere or before 

37 weeks of gestation

Outcome: gestational age (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 418; mean 37.4; 

range

Arm 2: Sample size 434; mean 37.7; 

range

Outcome: incidence of premature birth 

(Primary)

Follow-up time: birth

Arm 1: 174/418 (41.6%)

Arm 2: 164/434 (37.8%)

Hauner et al., 201237

Study name: INFAT

Study dates: July 14 

2006 - may 22 2009

Study design: Trial 

randomized parallel

Location: Germany

Funding source / 

conflict: Industry, 

Government, Multiple 

foundations and 

Societies

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 208 

Pregnant withdrawals 

38 Pregnant completers 

170

Infants enrolled 188 

Infants withdrawals 18 

Infants completers 170

Pregnant age: 31.9 (4.9) 

18-43

Race of Mother: NR 

(NR)

Baseline biomarker 

information: Maternal 

fatty acid profile in 

RBCs at 15th wk: EPA, 

Inclusion Criteria: 

healthy pregnant 

women before the 

15th wk of gestation, 

between 18 and 43 y 

of age, pre-pregnancy 

BMI (in kg/m2) 

between 18 and 30, 

willingness to 

implement the dietary 

recommendations, 

sufficient German 

language skills.

Exclusion Criteria: 

high-risk pregnancy 

(multiple pregnancy, 

rhesus incompatibility, 

hepatitis B infection, or 

parity .4); 

hypertension; chronic 

diseases (e.g., 

diabetes) or 

Start time: Pregnant 15th wk of gestation

Duration: Pregnant to 4 mo postpartum

Arm 1: Control

Description: brief semi structured counseling 

on a healthy balanced diet according to the 

guidelines of the German Nutrition Society and 

were explicitly asked to refrain from taking fish 

oil or DHA supplements

N-6 N-3: 2.80 +- 1.17 (SD) at 32nd wk of 

gestation

AA: 10.15 +- 3.89 SD) at 32nd wk of gestation

Arm 2: Intervention

Description: Fish-oil supplement + nutritional 

counseling (to normalize the consumption of 

AA

Brand name: Marinol D-40

Manufacturer: Lipid Nutrition

DHA: 1020 mg

EPA: 180 mg

N-6 N-3: 1.54 +- 0.63 (SD) at 32nd wk of 

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 96; mean 3357.0; SD 

(557)

Arm 2: Sample size 92; mean 3534.0; SD 

(465)

Outcome domain: Infants born small 

gestational age

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 4/96 (4.2%)

Arm 2: 3/92 (3.3%)

Outcome domain: duration of gestation

Outcome: gestational age (days) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 96; mean 275.1; SD 

(11.4)

Arm 2: Sample size 92; mean 279.9; SD 
C-52

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

DHA, AA, and n-6:n-3 

LCUFA ratio (reported in 

Table 2 by intervention 

and control groups). No 

significant differences 

between groups.

Baseline Omega-3 

intake: 7-d dietary 

records completed by 

participants at the 15th 

(baseline) and 32nd wk 

of gestation but only 

dietary intake at 32nd 

we of gestation was 

reported (in Table 2). At 

week 32 of gestation, 

the dietary n-6:n-3 

PUFA ratio was .5:1 in 

the intervention group 

compared with :1 in the 

control group, as 

originally intended.

gastrointestinal 

disorders 

accompanied by 

maldigestion, 

malabsorption, or 

elevated energy and 

nutritional 

requirements (e.g., 

gluten enteropathy); 

known metabolic 

defects (e.g., 

phenylketonuria); 

psychiatric diseases; 

hyperemesis 

gravidarum; 

supplementation with 

n–3 LCPUFAs before 

randomization; and 

alcohol abuse and 

smoking.

gestation

AA: 8.82 +- 2.84 (SD) at 32nd wk of gestation

Other dose 1: Vit E 9 mg

(8.5)

Outcome domain: growth

Outcome: bmi (kg/m2) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 83; mean 16.7; SD 

(1.4)

Arm 2: Sample size 87; mean 16.9; SD 

(1.5)

Follow-up time: 4 months

Arm 1: Sample size 87; mean 16.2; SD 

(1.3)

Arm 2: Sample size 87; mean 16.5; SD 

(1.4)

Follow-up time: 6 weeks

Arm 1: Sample size 91; mean 15.3; SD 

(1.2)

Arm 2: Sample size 89; mean 15.2; SD 

(1.4)

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 12 months

Arm 1: Sample size 83; mean 46.1; SD 

(1.5)

Arm 2: Sample size 87; mean 46.5; SD 

(1.6)

Follow-up time: 4 months

Arm 1: Sample size 87; mean 41.0; SD 

(1.3)

Arm 2: Sample size 87; mean 41.2; SD 

(1.3)

Follow-up time: 6 weeks

Arm 1: Sample size 90; mean 38.8; SD 

(1.2)

Arm 2: Sample size 89; mean 38.4; SD 

(1.1)
C-53

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Outcome: length (cm) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 83; mean 74.9; SD 

(2.8)

Arm 2: Sample size 87; mean 75.5; SD 

(2.4)

Follow-up time: 4 months

Arm 1: Sample size 87; mean 62.4; SD 

(2.2)

Arm 2: Sample size 88; mean 62.6; SD (2)

Follow-up time: 6 weeks

Arm 1: Sample size 91; mean 55.6; SD 

(2.6)

Arm 2: Sample size 89; mean 56.0; SD (2)

Outcome: weight (g) (Secondary)

Follow-up time: 12 months

Arm 1: Sample size 83; mean 9379.0; SD 

(1035)

Arm 2: Sample size 87; mean 9650.0; SD 

(1025)

Follow-up time: 4 months

Arm 1: Sample size 87; mean 6303.0; SD 

(724)

Arm 2: Sample size 87; mean 6476.0; SD 

(679)

Follow-up time: 6 weeks

Arm 1: Sample size 91; mean 4736.0; SD 

(625)

Arm 2: Sample size 89; mean 4793.0; SD 

(606)

Helland et al., 200876

Study name: NR

Study dates: 1994-2003

Study Population: 

Healthy infants Healthy 

pregnant women 

Breast-feeding women

Inclusion Criteria: 

Healthy nulliparous or 

primiparous women, 

aged 19-35 with single 

pregnancies

Start time: Pregnant week 18 of pregnancy

Duration: NR

Arm 1: Cod oil

Outcome domain: Birth weight

Outcome: birth weight (g) (Primary)

Follow-up time: birth

Arm 1: Sample size 61; mean 3518.0; SD 

(560)
C-54

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: Norway

Funding source / 

conflict: Industry, 

Government, Multiple 

foundations and 

Societies

Study follow-up: 7 years

Original, same study, or 

follow-up studies: 

Helland, 200186 and 

Helland, 200387 and 

which are both included 

in the original report

Infants enrolled 262 

Infants completers 143

Pregnant age: cod oil 

28.6 n=175 corn oil 27.6 

n=166 (cod oil 3.4; corn 

oil 3.2)

Race of Mother: NR 

(100)

Baseline biomarker 

information: from id 

10331 cod(n148) corn 

(n137) n-3 cod: 73.7 

(30.0) corn 52.0 

(14.9)*** 20:5n-3 cod: 

10.8 (7.6) corn: 2.5 

(1.8)*** 22:5n-3 cod: 5.0 

(2.6) corn: 2.9 (1.3)*** 

22:6n-3 cod: 55.8 (20.6) 

corn: 45.3 (12.8)***

Baseline Omega-3 

intake: from 10331 cod 

n147 corn n159 18:3 n3: cod: 1.3 (0.5) corn: 

1.2 (0.5) 20:5 n-3 cod: 

0.2 (0.2) corn:0.2 (0.2) 

22:5 n-3 cod: 0.05 

(0.03) corn: 0.05 (0.03) 

22:6 n-3 cod: 0.3 (0.3) 

corn: 0.3 (0.3)

Exclusion Criteria: 

Unhealthy neonates

Manufacturer: Peter Moller, Avd Orkla ASA, 

Oslo, Norway

Active ingredients: Vit 1: 117 ug/mL, Vit D3: 1 

ug/mL, vit E: 1.4 mg/mL

Viability: frozen at _x0003_ 70 ° C under 

nitrogen. Before storage, the samples were 

sonicated and ethylenediaminetetraacetic acid 

and butylated hydroxytoluene were added to a 

final concentration of 1.85 mg/mL and 75 

_x0003_ g/mL, respectively

DHA: 1183mg/10 mL

EPA: 803 mg/10mL

Total N-3: 2494 mg/10mL

Arm 2: corn oil

Active ingredients: Vit 1: 117 ug/mL, Vit D3: 1 

ug/mL, vit E: 1.4 mg/mL

Viability: frozen at _x0003_ 70 ° C under 

nitrogen. Before storage, the samples were 

sonicated and ethylenediaminetetraacetic acid 

and butylated hydroxytoluene were added 

to a final concentration of 1.85 mg/mL 

and 75 _x0003_ g/mL, respectively

ALA: 92 mg/10mL

Arm 2: Sample size 82; mean 3613.0; SD 

(458)

Outcome domain: Cognitive development

Outcome: Kaufman Assessment Battery 

for Children (K-ABC): mental processing 

composite (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 28; mean 102.0

Arm 2: Sample size 30; mean 107.0

Follow-up time: 7 years

Arm 1: Sample size 28; mean 108.0

Arm 2: Sample size 30; mean 110.0

Outcome: Kaufman Assessment Battery 

for Children (K-ABC): non-verbal abilities 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 28; mean 102.0

Arm 2: Sample size 30; mean 107.0

Follow-up time: 7 years

Arm 1: Sample size 28; mean 112.0

Arm 2: Sample size 30; mean 112.0

Outcome: Kaufman Assessment Battery 

for Children (K-ABC): sequential 

processing (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 28; mean 107.0

Arm 2: Sample size 30; mean 109.0

Follow-up time: 7 years

Arm 1: Sample size 28; mean 105.0

Arm 2: Sample size 30; mean 107.0

Outcome: Kaufman Assessment Battery 

for Children (K-ABC): simultaneous 

processing (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 28; mean 98.0
C-55

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 30; mean 102.0

Follow-up time: 7 years

Arm 1: Sample size 28; mean 110.0

Arm 2: Sample size 30; mean 110.0

Outcome domain: growth

Outcome: bmi (kg/m2) (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 61; mean 16.3; SD 

(1.7)

Arm 2: Sample size 82; mean 16.4; SD 

(1.7)

Outcome: length (cm) (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 61; mean 128.6; SD 

(5)

Arm 2: Sample size 82; mean 127.5; SD 

(5.5)

Outcome: weight (kg) (Secondary)

Follow-up time: 7 years

Arm 1: Sample size 61; mean 27.0; SD 

(4.1)

Arm 2: Sample size 82; mean 26.8; SD 

(4.1)

Henriksen et al., 2008107

Study name: Unnamed 

Trial D

Study dates: 2003-2006

Study design: Trial 

randomized parallel

Location: Norway

Study Population: 

Preterm infants

Infants enrolled 141 

Infants completers 129

Mother age: Median: 

Intervention: 31 years 

Control: 32 years 28-35 

years

Inclusion Criteria: All 

VLBW infants 

(<1500g) born 

between December 

2003 and November 

2005 at RikshospitaletRadiumhospitalet 

Medical Center, 

Akershus University 

Hospital, Buskerud 

Hospital, and Vestfold 

Start time: Infants (intervention began when the 

infant received most of his nutrients enterally: 

>100ml human milk/kg body weight/day

Duration: Infants Until discharge or bottle of 

study oil was empty (average 63 days of age)

Arm 1: Control

Description: Study oil: soy oil and medium 

chain triglycerides

Active ingredients: 127mg linolenic acid/100 ml 

Outcome domain: Cognitive development

Outcome: Ages and Stages: 

Communication

Follow-up time: 6 months

Arm 1: Sample size 55; mean 46.6; SD 

(9.1)

Arm 2: Sample size 50; mean 45.4; SD 

(7.9)

Outcome: Ages and Stages: Fine motor

Follow-up time: 6 months

Arm 1: Sample size 55; mean 45.8; SD 
C-56

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / 

conflict: Multiple 

foundations and 

Societies, Manufacturer 

supplied product

Study follow-up: 6 

months

Original, same study, or 

follow-up studies: Ane, 

2011125; Almaas, 

2015126

Infant age: Median 

Gestational age: 

Control: 28.9 weeks 

Intervention: 28.4 weeks 

Gestational age: 26.6-

30.9 weeks

Race of Mother: White 

European (Intervention: 

79%; Control 84%)

Hospital in Norway

Exclusion Criteria: 

Major congenital 

abnormalities or 

cerebral hemorrhage 

(grade 3 or 4, as 

determined through 

ultrasonography)

milk(27.1% total fatty acids)

Dose: 0.5 ml study oil/100 ml human milk

Blinding: Study oils packed in numbered bottles 

in hospital pharmacy

ALA: 16mg/100 ml milk; 3.4% total fatty acids

Arm 2: Intervention

Description: DHA and AA-containing oil

Manufacturer: Martek Biosciences

Active ingredients: 88mg/100 ml linoleic acid 

per 100 ml milk (18.8%)

Dose: 0.5 ml study oil per 100 ml milk, ad lib

Maternal conditions

Infant conditions

DHA: 32mg/100ml milk (6.9%)

AA: 31 mg/100 ml milk (6.7% total fatty acids

Current smoker 22% during pregnancy

Low birth weight 100% (median 1090 g)

(14.3)

Arm 2: Sample size 50; mean 45.2; SD 

(10.7)

Outcome: Ages and Stages: Gross motor

Follow-up time: 6 months

Arm 1: Sample size 55; mean 30.9; SD 

(11.1)

Arm 2: Sample size 50; mean 33.3; SD 

(11.5)

Outcome: Ages and Stages: Personalsocial

Follow-up time: 6 months

Arm 1: Sample size 55; mean 42.2; SD 

(12.3)

Arm 2: Sample size 50; mean 43.2; SD 

(12.8)

Outcome: Ages and Stages: Problemsolving

Follow-up time: 6 months

Arm 1: Sample size 55; mean 49.5; SD 

(9.5)

Arm 2: Sample size 50; mean 53.4; SD (7)

Outcome: Ages and Stages: Total

Follow-up time: 6 months

Arm 1: Sample size 55; mean 215.0; SD 

(39)

Arm 2: Sample size 50; mean 221.0; SD 

(32)

Outcome domain: growth

Outcome: head circumference (mm/day)

(Secondary)

Follow-up time: day 65

Arm 1: Sample size 50; mean 1.0; SD 

(0.4)

Arm 2: Sample size 50; mean 1.2; SD 
C-57

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(0.7)

Hoffman et al., 2008114

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry, 

Manufacturer supplied 

product

Study Population: 

Healthy infants

Infants enrolled 244 

Infants withdrawals 3 

Infants completers 241

Infant age: 14 days

Race of Mother: NR

Inclusion Criteria: 12–

16 days of age, had a 

minimum birth weight 

of 2,500 g, and solely 

received formula at 

least 24 h prior to 

randomization

Exclusion Criteria: 

history of underlying 

disease or 

malformation that 

could interfere with 

growth and 

development; largefor-gestational-age 

infants whose mothers 

were diabetic; 

breastfeeding within 

24 h prior to 

randomization; 

evidence of formula 

intolerance or poor 

intake at time of 

randomization; weight 

at randomization less 

than 98% of birth 

weight; enlarged liver 

or spleen; or plans to 

move outside of the 

study area within the 

study time frame (120 

days)

Start time: Infants 14 day

Duration: NR

Arm 1: Control

Description: soy formula without 

supplementation

Brand name: Enfamil ProSobee1, Mead 

Johnson & Company, Evansville, IN

Blinding: Aside from the addition of DHA and 

ARA, the formulas were identical in all other 

respects.

Arm 2: DHA + ARA

Description: soy formula supplemented with a 

minimum 17 mg DHA/100kcal from algal oil 

and 34 mg ARA/100kcal from fungal oil

Brand name: Enfamil ProSobee1 LIPIL1, Mead 

Johnson & Company, Evansville, IN)

DHA: 0.3%

AA: 0.6%

Outcome domain: growth

Outcome: head circumference (cm/day) 

(Secondary)

Follow-up time: 14-120d

Arm 1: Sample size 86; mean gain 0.05; 

SE (0.001)

Arm 2: Sample size 93; mean gain 0.05; 

SE (0.001)

Outcome: length (cm/day) (Secondary)

Follow-up time: 14-120d

Arm 1: Sample size 86; mean change 0.1; 

SE (0.002)

Arm 2: Sample size 93; mean change 0.1; 

SE (0.002)

Outcome: weight (g/day) (Secondary)

Follow-up time: 14-120d

Arm 1: Sample size 86; mean change 

27.8; SE (0.8)

Arm 2: Sample size 93; mean change 

27.3; SE (0.7)

Imhoff-Kunsch et al., Study Population: Inclusion Criteria: Start time: Pregnant 18 to 22 weeks gestation Outcome domain: respiratory illness
C-58

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

201158

Study name: POSGRAD

Study dates: February 

2005 - February 2007

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / 

conflict: Government, 

March of Dimes

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Stein, 201233; EscamillaNunez, 201459; 

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561

Healthy pregnant 

women

Pregnant enrolled 1094 

Pregnant completers 

851

Infants enrolled 851 

Infants completers 834

Pregnant age: DHA: 

26.3 Placebo:20.5 

(DHA: 4.9 Placebo: 1.9)

Race of Mother: NR 

(100%)

Women were 

considered for 

inclusion in the study if 

they were in gestation 

week 18 to 22, were 

aged 18 to 35 years, 

planned to deliver at 

the IMSS General 

Hospital in 

Cuernavaca, planned 

to predominantly 

breastfeed for at least 

3 months, and planned 

to live in the area for 2 

years after delivery

Exclusion Criteria: 

Exclusion criteria 

included (1) high-risk 

pregnancy, (2) lipid 

metabolism/absorption 

disorders, (3) regular 

intake of fish oil or 

DHA supplements, or 

(4) chronic use of 

certain medications.

Duration: Pregnant until parturition

Arm 1: Placebo

Description: Placebo/control corn and soy oil 

capsule

Dose: 2 capsules daily

Blinding: The placebo capsules, which were 

similar in appearance and taste to the DHA 

capsules, contained a corn and soy oil blend 

with no added antioxidants....All participants 

and members of the study team were blinded 

to the treatment scheme throughout the 

intervention period of the study. Data were 

unblinded for the analytical study team after the 

last infant in the study was born and had 

reached the age of 6 months.

Arm 2: DHA

Description: DHA capsule

Manufacturer: Martek Biosciences Corporation, 

Columbia, MD

Dose: 2 capsules daily

DHA: 200mg/ capsule

Outcome: cold (any of cough, phlegm, 

nasal congestion, nasal secretion) 

(Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 190/427 (44.6%)

Arm 2: 159/422 (37.6%)

Follow-up time: 3 months

Arm 1: 185/419 (44.1%)

Arm 2: 157/415 (37.8%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 193/414 (46.6%)

Arm 2: 194/420 (46.2%)

Outcome: cough (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 47/427 (11.0%)

Arm 2: 40/422 (9.5%)

Follow-up time: 3 months

Arm 1: 100/419 (23.9%)

Arm 2: 80/415 (19.3%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 136/414 (32.9%)

Arm 2: 139/420 (33.1%)

Outcome: difficulty breathing (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 10/427 (2.3%)

Arm 2: 10/422 (2.4%)

Follow-up time: 3 months

Arm 1: 10/419 (2.4%)

Arm 2: 12/415 (2.9%)

Follow-up time: 6 months (preceding 15 

days)
C

-59

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: 7/414 (1.7%)

Arm 2: 6/420 (1.4%)

Outcome: nasal congestion (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 140/427 (32.8%)

Arm 2: 119/422 (28.2%)

Follow-up time: 3 months

Arm 1: 119/419 (28.4%)

Arm 2: 104/415 (25.1%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 116/414 (28.0%)

Arm 2: 124/420 (29.6%)

Outcome: nasal secretion (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 46/427 (10.8%)

Arm 2: 30/422 (7.1%)

Follow-up time: 3 months

Arm 1: 72/419 (17.2%)

Arm 2: 62/415 (14.9%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 122/414 (29.5%)

Arm 2: 118/420 (28.2%)

Outcome: phlegm (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 82/427 (19.2%)

Arm 2: 71/422 (16.8%)

Follow-up time: 3 months

Arm 1: 78/419 (18.6%)

Arm 2: 81/415 (19.5%)

Follow-up time: 6 months (preceding 15 

days)
C-60

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: 100/414 (24.2%)

Arm 2: 100/420 (23.9%)

Outcome: wheezing (Secondary)

Follow-up time: 1 month (preceding 15 

days)

Arm 1: 30/427 (7.0%)

Arm 2: 35/422 (8.3%)

Follow-up time: 3 months

Arm 1: 34/419 (8.1%)

Arm 2: 29/415 (7.0%)

Follow-up time: 6 months (preceding 15 

days)

Arm 1: 45/414 (10.9%)

Arm 2: 50/420 (11.9%)

Innis et al., 2008145

Study name: NR

Study dates: NR, <2008

Study design: Trial 

randomized parallel

Location: Canada

Funding source / 

conflict: Government, 

None, Manufacturer 

supplied product

Study follow-up: 60 days

Study Population: 

Healthy pregnant 

women

Pregnant enrolled NR 

Pregnant completers 

135

Infants enrolled 135 

Infants completers 134

Pregnant age: 33 years 

(0. 4 years)

Infant age: 14 to 16 

weeks gestation

Race of Mother: White 

European (72%)

Baseline biomarker 

Inclusion Criteria: 14 –

16 wk gestation, not 

taking any lipid 

supplement, no 

complications likely to 

affect maternal or fetal 

metabolism or fetal 

development, 

expected to deliver 

one full-term infant

Exclusion Criteria: NR

Start time: Pregnant 16 weeks gestation Infants 

16 weeks gestation

Duration: Pregnant to birth Infants to birth

Arm 1: placebo

Description: corn oil / soybean oil capsule

Manufacturer: Martek Biosciences, Columbia, 

MD)

Dose: 2 capsules

Blinding: identical capsules, containing an 

orange flavor to assist in further blinding

Maternal conditions

ALA: 40 mg

Other dose 1: LA 265 mg

Current smoker 2/67

Arm 2: DHA supplement

Description: capsule containing 200 mg DHA

Manufacturer: Martek Biosciences, Columbia, 

MD)

Outcome domain: Visual function

Outcome: Teller Acuity Card procedure 

(visual acuity) (cyc/deg) (Secondary)

Follow-up time: 60 days

Arm 1: Sample size 68; mean 2.42; SD 

(0.63)

Arm 2: Sample size 67; mean 2.6; SD

(0.5)
C-61

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

information: 16 week 

gestation baseline 

values for both groups 

similar. Reported 

graphically, so 

approximations. 22:6n3: 7 %wt of total FA 

22:5n-3: 4 %wt of total 

FA 20:5n-3: 1 %wt of 

total FA 18:3n-3: 0.4 

%wt of total FA

Baseline Omega-3 

intake: For mothers, at 

assignment: Linoleic 

acid (g) median 13.5 

range 2.52–43 Alpha 

Linolenic acid (g) 

median 1.48 range 

0.46–9.21 Arachidonic 

acid (mg) median 90 

range 20–360 EPA (mg) 

median 70 range 10–

280 DHA (mg) median 

110 range 10–760

Dose: 2 capsules

Maternal conditions

DHA: 200 mg/g

Current smoker 0/68

Isaacs et al., 201199

Study name: Unnamed 

Trial A

Study dates: 

Recruitment of infants 

from 1995 through 1997 

with 10-year follow-up

Study Population: 

Preterm infants

Infants enrolled 238 

Infants completers 107

Infant age: birth (at < 35 

weeks gestation) NA

Race of Mother: NR 

Inclusion Criteria: birth 

weight of < 2000 g, 

and gestational age of 

< 35 weeks

Exclusion Criteria: 

congenital 

malformations

Start time: Infants at hospital discharge

Duration: Infants 9 months

Arm 1: control

Description: control formula

Active ingredients: protein, minerals, vitamins 

A, E, K, D

DHA: 0

EPA: 0

Outcome domain: ADHD

Outcome: Test of Everyday Attention for 

Children: Attention scaled score 

(Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 8.3; SD 

(2.6)

Arm 2: Sample size 50; mean 8.2; SD 

(2.5)

Outcome: Test of Everyday Attention for 
C-62

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: UK

Funding source / 

conflict: Industry, 

Government, Some 

authors have received 

research funding from 

infant formula 

manufacturers

Study follow-up: 10 

years

Original, same study, or 

follow-up studies: 

Fewtrell, 2002158 is the 

original study; Llorente, 

200398 reports postpartum depression

(NR) AA: 0

Other dose 1: C18:2, n-6, linoleic acid 11.5 g / 

100g fat

Other dose 2: C18:3, n-3, alpha_x0004_-

linolenic acid 1.6 g / 100g fat

Arm 2: Omega 3 supplemented formula

Description: LCPUFA-Supplemented Formula

Active ingredients: protein, minerals, vitamins 

A, E, K, D

Infant conditions

DHA: 0.5 g / 100g fat

EPA: 0.1 g/ 100g fat

AA: 0.04 g / 100g fat

Other dose 1: C18:2, n-6, linoleic acid 12.3 g / 

100g fat

Other dose 2: C18:3, n-6, gamma-linoleic acid 

0.9 g / 100g fat

Other dose 3: C18:3, n-3, _x0004_alphalinolenic acid 1.5 g / 100g fat

Pre-term birth 100%

Low birth weight 100%

Children: Creature counting scale score 

(Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 9.6; SD 

(2.1)

Arm 2: Sample size 50; mean 10.0; SD 

(2.7)

Outcome: Test of Everyday Attention for 

Children: Dual-task decrement scaled 

score (Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 7.3; SD 

(2.8)

Arm 2: Sample size 50; mean 7.6; SD 

(2.5)

Outcome: Test of Everyday Attention for 

Children: Opposite Worlds different scaled 

score (Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 8.4; SD 

(2.8)

Arm 2: Sample size 50; mean 8.9; SD 

(3.5)

Outcome: Test of Everyday Attention for 

Children: Score! Scale scored 

(Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 7.8; SD 

(3.4)

Arm 2: Sample size 50; mean 7.7; SD 

(3.4)

Outcome domain: Cognitive development

Outcome: Wechsler Abbreviated Scale of 

Intelligence: FSIQ (Secondary)

Follow-up time: 10 years
C-63

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 57; mean 92.7; SD 

(12.3)

Arm 2: Sample size 50; mean 95.1; SD 

(13.2)

Outcome: Wechsler Abbreviated Scale of 

Intelligence: Performance IQ (Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 94.5; SD 

(14.1)

Arm 2: Sample size 50; mean 94.2; SD 

(12.7)

Outcome: Wechsler Abbreviated Scale of 

Intelligence: VIQ (Secondary)

Follow-up time: 10 years

Arm 1: Sample size 57; mean 92.6; SD 

(12.6)

Arm 2: Sample size 50; mean 96.7; SD 

(13.2)

Jensen et al., 2005136

Study name: Unnamed 

Trial B

Study dates: <2004

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry, 

Government

Original, same study, or 

Study Population: 

Breast-feeding women

Lactating enrolled 227 

Lactating completers 

174

Infants enrolled 230 

Infants completers 177

Lactating enrolled 227 

Lactating completers 

174

Lactating age: 31.5 

years (5 years) 18-40

Inclusion Criteria: 

maternal age between 

18 and 40 y, infant 

gestational age >=37 

wk, infant birth weight 

between 2500 and 

4200 g

Exclusion Criteria: 

chronic maternal 

disorders, major 

congenital anomalies, 

obvious 

gastrointestinal or 

metabolic disorders of 

the infant

Start time: Lactating 5 days after delivery 

Infants 5 days after birth

Duration: Lactating 4 months Infants 4 months

Arm 1: placebo

Description: capsule containing corn & soy oil

Manufacturer: Martek Biosciences

Purity Data: 15% saturated fatty acids, 23.5% 

monounsaturated fatty acids, 56.3% linoleic 

acid (18: 2n_x0001_6), and 3.9% _x0001_-

linolenic acid (18:3n_x0001_3)

Dose: 1 capsule

Blinding: identical capsules

ALA: 56.3% linoleic acid (18: 2n_x0001_6), 

3.9% _x0001_-linolenic acid (18:3n_x0001_3)

Total N-3: 57.2%

Outcome domain: Neurological 

development

Outcome: Bayley Physical Developmental 

Index (Primary)

Follow-up time: 30 months

Arm 1: Sample size 65; mean 108.4; SD 

(13.8)

Arm 2: Sample size 68; mean 116.8; SD 

(15.2)

Outcome: Clinical Linguistic and Auditory 

Milestone Scale (CLAMS) (Secondary)

Follow-up time: 30 months

Arm 1: Sample size 72; mean 106.6; SD 

(14.9)

Arm 2: Sample size 75; mean 106.8; SD 

(15.2)

Follow-up time: 12 months
C-64

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

follow-up studies: 

Jensen, 2010135

Infant age: birth (NA) 

NA

Race of Mother: NR

Arm 2: DHA algal triacylglycerol (DHASCO)

Description: DHA capsule

Brand name: DHASCO

Manufacturer: Martek Biosciences

Purity Data: 44%saturatedfattyacids, 13.6% 

monounsaturated fatty acids, 0.8% linoleic acid 

(18:2n _x0001_ 6), and 41.7% DHA (22:6n-3) 

by weight

Dose: 1 capsule

ALA: 0.8% (18:2n-6)

DHA: 200 mg, 41.7% (22:6n-3)

Total N-3: 42.5%

Arm 1: Sample size 76; mean 102.5; SD 

(13.2)

Arm 2: Sample size 86; mean 100.6; SD 

(14.6)

Outcome: Clinical adaptive test 

development quotient (CAT DQ) 

(Secondary)

Follow-up time: 30 months

Arm 1: Sample size 72; mean 98.3; SD 

(8.7)

Arm 2: Sample size 75; mean 98.1; SD (9)

Follow-up time: 12 months

Arm 1: Sample size 76; mean 110.0; SD 

(10.8)

Arm 2: Sample size 86; mean 109.0; SD 

(10)

Outcome: Gesell Gross Motor 

development quotient (DQ) (Secondary)

Follow-up time: 30 months

Arm 1: Sample size 72; mean 102.4; SD 

(10.2)

Arm 2: Sample size 75; mean 100.8; SD 

(11.4)

Follow-up time: 12 months

Arm 1: Sample size 76; mean 99.5; SD 

(13.3)

Arm 2: Sample size 86; mean 101.8; SD

(13.8)

Outcome domain: Visual function

Outcome: Sweep VEP (cyc/deg) 

(Secondary)

Follow-up time: 4 months

Arm 1: Sample size 79; mean 9.4; SD 

(0.21)

Arm 2: Sample size 81; mean 9.4; SD 
C

-65

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(0.23)

Outcome: Teller Acuity Card procedure 

(cyc/deg) (Secondary)

Follow-up time: 4 months

Arm 1: Sample size 77; mean 5.3; SD 

(0.56)

Arm 2: Sample size 70; mean 5.6; SD 

(0.71)

Follow-up time: 8 months

Arm 1: Sample size 73; mean 13.5; SD 

(0.57)

Arm 2: Sample size 74; mean 12.3; SD 

(0.53)

Outcome: Visual evoked potential 

amplitude (mV) (Secondary)

Follow-up time: 4 months

Arm 1: Sample size 82; mean 33.3; SD 

(12.4)

Arm 2: Sample size 86; mean 28.9; SD 

(12.1)

Follow-up time: 8 months

Arm 1: Sample size 74; mean 27.9; SD 

(11)

Arm 2: Sample size 79; mean 24.3; SD 

(8.9)

Outcome: Visual evoked potential latency 

(ms) (Secondary)

Follow-up time: 4 months

Arm 1: Sample size 82; mean 123.9; SD 

(10.6)

Arm 2: Sample size 86; mean 124.8; SD 

(11.7)

Follow-up time: 8 months

Arm 1: Sample size 74; mean 115.3; SD 

(10.5)

Arm 2: Sample size 79; mean 115.1; SD 
C-66

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(8.1)

Jensen et al., 2010135

Study name: Unnamed 

Trial B

Study dates: NR 

(<2010)

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry, 

Government

Study follow-up: 5 years

Original, same study, or 

follow-up studies: 

Jensen, 2005136

Study Population: 

Breast-feeding women

Lactating enrolled 227

Infants enrolled 230 

Infants completers 119

Lactating enrolled 227

Lactating age: 31.5 

years (5 years) 18 to 40

Infant age: birth (NA) 

NA

Race of Mother: NR 

(NR)

Inclusion Criteria: 

maternal age between 

18 and 40 y, infant 

gestational age >=37 

wk, infant birth weight 

between 2500 and 

4200 g

Exclusion Criteria: 

chronic maternal 

disorders, major 

congenital anomalies, 

obvious 

gastrointestinal or 

metabolic disorders of 

the infant

Start time: Infants birth

Duration: Infants 4 months

Arm 1: placebo

Description: capsule containing corn & soy oil

Manufacturer: Martek Biosciences

Purity Data: 50:50 mixture of soy and corn oils 

consisting, by weight, of 15% saturated fatty 

acids, 23.5% monounsaturated fatty acids, 

56.3% linoleic acid (18:2 n-6) and 3.9% alinolenic acid (18:3 n-3)

Dose: 1 capsule

Blinding: capsules were identical

ALA: 3.9%

Arm 2: omega 3 capsule

Description: high-DHA algal triglyceride 

capsule

Brand name: DHASCO

Manufacturer: Martek

Purity Data: by weight, 44% saturated fatty 

acids, 13.6% monounsaturated fatty acids, 

0.8% linoleic acid (18:2n-6) and 41.7% DHA 

(22:6n-3)

Dose: 1 capsule

DHA: 200 mg

Outcome domain: Cognitive development

Outcome: Wechsler Primary and 

Preschool Scale of Intelligence - Revised : 

Vocabulary Subset (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 12.9; SD 

(2.4)

Arm 2: Sample size 60; mean 12.3; SD 

(2.8)

Outcome: Wechsler Primary and 

Preschool Scale of Intelligence - Revised : 

Animal Pegs Subset (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 12.2; SD 

(1.8)

Arm 2: Sample size 60; mean 12.1; SD 

(2.4)

Outcome: Wechsler Primary and 

Preschool Scale of Intelligence - Revised : 

Block Design Subset (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 11.1; SD 

(2.2)

Arm 2: Sample size 60; mean 11.3; SD 

(2.1)

Outcome: Wechsler Primary and 

Preschool Scale of Intelligence - Revised : 

Information Subset (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 11.2; SD 

(2.6)

Arm 2: Sample size 60; mean 10.8; SD 

(2.6)
C

-67

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Outcome domain: Neurological 

development

Outcome: Development test of Visual-

Motor Integration (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 11.8; SD 

(1.8)

Arm 2: Sample size 57; mean 11.6; SD 

(1.9)

Outcome: Kaufman Assessment Battery 

for Children: hand movement (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 9.02; SD 

(2.84)

Arm 2: Sample size 59; mean 8.39; SD 

(2.55)

Outcome: McCarthy (leg coordination) 

(Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 10.7; SD 

(1.9)

Arm 2: Sample size 59; mean 10.6; SD 

(1.5)

Outcome: Purdue pegboard test 

(dominant hand) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 9.8; SD 

(2.7)

Arm 2: Sample size 59; mean 9.6; SD 

(1.7)

Outcome: Purdue pegboard test (non-

dominant hand) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 8.9; SD 

(2.7)

Arm 2: Sample size 59; mean 8.9; SD 
C

-68

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(1.6)

Outcome domain: Visual function

Reason results are not reported: 

intervention first 4 months

Outcome: VEP Latency (30' check sizes) 

(ms) (Secondary)

Follow-up time: 5 years

Arm 2: Sample size 60; mean 110.0; SD 

(8.1)

Outcome domain: Visual function

Reason results are not reported: 

intervention first 4 months; same trial as 

3433 (later fu)

Outcome: Bailey Lovie Acuity - left eye 

(number of letters correct) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 57; mean 52.1; SD 

(4.9)

Arm 2: Sample size 60; mean 53.1; SD 

(4.7)

Outcome: Bailey Lovie Acuity - right eye 

(number of letters correct) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 58; mean 51.6; SD 

(5.6)

Arm 2: Sample size 60; mean 52.6; SD 

(4.6)

Outcome: Sweep VEP acuity (cyc/deg) 

(Secondary)

Follow-up time: 5 years

Arm 1: Sample size 55; mean 11.8; SD 

(0.3)

Arm 2: Sample size 56; mean 11.9; SD 

(0.3)
C-69

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Outcome: VEP Amplitude (mV) 

(Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 45.3; SD 

(18)

Arm 2: Sample size 60; mean 39.6; SD 

(13.7)

Outcome: VEP Latency (30' check sizes) 

(ms) (Secondary)

Follow-up time: 5 years

Arm 1: Sample size 56; mean 108.0; SD 

(6.5)

Judge et al., 200739

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Industry, 

Government, None

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 29 

Pregnant completers 29

Pregnant age: 23.75 

years (.4 years) NR

Race of Mother: NR 

(100%)

Inclusion Criteria: 

women aged 18 –35 y 

who were at 20 wk of 

gestation

Exclusion Criteria: 

Women with a history 

of drug or alcohol 

addiction, 

hypertension, 

smoking, 

hyperlipidemia, renal 

disease, liver disease, 

diabetes, or 

psychiatric disorder

Start time: Pregnant 24 weeks gestation

Duration: Pregnant until birth

Arm 1: placebo

Description: cereal based placebo bars

Manufacturer: Nestec

Active ingredients: 18 g carbohydrates, 1.3 

grams protein, 92 calories, 1.7 g fat

Viability: NR

Dose: 5 bars per week

Blinding: NR

Arm 2: DHA supplemented cereal bars

Manufacturer: Nestec

Active ingredients: 18 g carbohydrates, 1.3 

grams protein, 92 calories, 1.7 g fat

Viability: NR

Dose: 5 bars per week. DHA-containing cereal 

based bars [1.7 g total fat, 300 mg DHA as loweicosapentaenoic oil (EPA) fish oil; EPA:DHA 

1:8 per bar

DHA: mg/d

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 15; mean 3222.0; SD 

(363)

Arm 2: Sample size 14; mean 3465.0; SD 

(406)

Outcome domain: duration of gestation

Outcome: gestational age (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 15; mean 39.0; SD (1)

Arm 2: Sample size 14; mean 39.9; SD 

(0.8)
C-70

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

EPA: .75 mg (calculated based on EPA:DHA 

ratio)

EPA-DHA: 1:8

Judge et al., 201240

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Multiple 

foundations and 

Societies

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 48

Pregnant age: 

Treatment group: 23.93 

Placebo: 23.86 

(Treatment group: 4.32 

Placebo: 4.53)

Race of Mother: White 

European (Treatment: 

11.1%, Placebo: 0%) 

Black (Treatment: 

18.5%, Placebo: 4.8%) 

Asian (Treatment: 3.7%, 

Placebo: 0%) Hispanic 

(Treatment: 59.3%, 

Placebo: 80.9%) NR 

(Treatment: 7.4%, 3 

(14.3%))

Baseline biomarker 

information: Maternal 

plasma phospholipid 

(PL) fatty acids (FA): 

2.85 +/- .87 % in 

treatment group and 

2.95 +/- .91% in placebo 

group. Infant RBC PL 

Inclusion Criteria: The 

women were either 

primiparous or had not 

been pregnant for the 

past 2 years.

Exclusion Criteria: 

parity greater than 5, 

history of chronic 

hypertension, 

hyperlipidemia, renal, 

liver or heart disease, 

thyroid disorder, 

multiple gestations or 

pregnancy induced 

complications 

including 

hypertension, 

preeclampsia or 

preterm labor, 

smoking and 

psychiatric disorders. 

Women who were 

treated during labor 

with analgesics such 

as Stadol (butorphanol 

tartrate), that may 

cause infant 

respiratory distress 

were also excluded. In 

addition, infants born 

preterm and infants 

Start time: Pregnant 24 weeks gestation

Duration: Pregnant until delivery

Arm 1: Placebo

Description: Control group

Manufacturer: Nestec, S.A., Switzerland

Blinding: The total macronutrient content was 

the same in both the DHA and placebo bars 

with respect to carbohydrate, protein and fat, 

how- ever, the DHA bars contained fish oil (300 

mg DHA) and the placebo bars contained corn 

oil.

Arm 2: DHA

Description: Intervention group

Manufacturer: Nestec, S.A., Switzerland

Dose: average of 5 bars weekly

DHA: 300 mg

EPA-DHA: 8:1 ratio of DHA to EPA

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 21; mean 3224.62; 

SD (431.25)

Arm 2: Sample size 27; mean 3394.7; SD 

(430)

Outcome domain: Neurological 

development

Outcome: Infant sleep: Active Sleep (AS, 

%) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 51.81; SD 

(10.43)

Arm 2: Sample size 27; mean 49.39; SD 

(10.32)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 51.7; SD 

(11.13)

Arm 2: Sample size 24; mean 51.57; SD 

(14.54)

Outcome: Infant sleep: Active–Quiet 

Sleep Transition (AQST, %) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 0.53; SD 

(0.23)

Arm 2: Sample size 27; mean 0.59; SD 

(0.37)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 0.41; SD 

(0.27)
C

-71

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

FA: 7.55 +/- 1.61% in 

treatment group and 

7.07 +/- 1.25% in 

placebo group.

with less than 4 h of 

crib time in the first 

and second days 

postpartum were 

excluded from the 

analyses.

Arm 2: Sample size 24; mean 0.47; SD 

(0.3)

Outcome: Infant sleep: Arousals in AS 

(Ar/AS) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 20.41; SD 

(4.39)

Arm 2: Sample size 27; mean 17.41; SD 

(4.71)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 24.67; SD 

(6.82)

Arm 2: Sample size 24; mean 24.04; SD 

(7.04)

Outcome: Infant sleep: Arousals in QS 

(Ar/QS) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 5.89; SD 

(6.01)

Arm 2: Sample size 27; mean 2.7; SD 

(2.65)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 5.44; SD 

(4.07)

Arm 2: Sample size 24; mean 3.55; SD 

(3.98)

Outcome: Infant sleep: Mean Sleep 

Period (LSP, min) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 185.95; SD 

(79.75)

Arm 2: Sample size 27; mean 228.19; SD 

(104.89)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 202.6; SD 

(123.18)
C

-72

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 24; mean 190.75; SD 

(102.75)

Outcome: Infant sleep: Mean Sleep 

Period (MSP, min) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 46.09; SD 

(17.6)

Arm 2: Sample size 27; mean 48.03; SD 

(17.55)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 48.85; SD 

(29.99)

Arm 2: Sample size 24; mean 48.67; SD 

(21.18)

Outcome: Infant sleep: Wakefulness (W, 

%) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 27.59; SD 

(11.54)

Arm 2: Sample size 27; mean 29.57; SD 

(13.56)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 28.95; SD 

(12.14)

Arm 2: Sample size 24; mean 30.71; SD 

(18.92)

Outcome: Infant sleep: quiet sleep 

(QS,%) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 15.14; SD 

(4.26)

Arm 2: Sample size 27; mean 15.88; SD 

(5.1)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 13.7; SD 

(4.76)
C

-73

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 24; mean 12.7; SD 

(5.85)

Outcome: Infant sleep: Active sleep bout 

length (ASBL, min) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 28.93; SD 

(9.67)

Arm 2: Sample size 27; mean 29.0; SD 

(7.07)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 29.81; SD 

(12.5)

Arm 2: Sample size 24; mean 30.48; SD 

(9.14)

Outcome: Infant sleep: Active/Quiet Sleep Ratio(AS:QS) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 3.83; SD 

(2.15)

Arm 2: Sample size 27; mean 3.38; SD 

(1.1)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 4.56; SD 

(3.13)

Arm 2: Sample size 24; mean 4.46; SD 

(2.14)

Outcome: Infant sleep: Quiet sleep bout 

length (QSBL, min) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 21.81; SD 

(4.93)

Arm 2: Sample size 27; mean 22.74; SD 

(5.73)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 20.59; SD 

(4.98)
C-74

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 24; mean 18.75; SD 

(6.86)

Outcome: Infant sleep: Sleep–Wake 

Transition (T, %) (Secondary)

Follow-up time: 1 day after birth

Arm 1: Sample size 19; mean 4.92; SD 

(1.48)

Arm 2: Sample size 27; mean 4.57; SD 

(1.33)

Follow-up time: 2 days after birth

Arm 1: Sample size 15; mean 5.23; SD 

(1.88)

Arm 2: Sample size 24; mean 4.5; SD 

(1.39)

Outcome domain: duration of gestation

Outcome: gestational age (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 21; mean 39.19; SD 

(1.17)

Arm 2: Sample size 27; mean 39.72; SD 

(1.2)

Judge et al., 201491

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: US

Funding source / 

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 73 

Pregnant completers 42

Pregnant age: 18-35

Race of Mother: NR 

(100)

Inclusion Criteria: No 

other births in the 

previous two years; 20 

weeks pregnant; and 

18-35 years of age.

Exclusion Criteria: with 

a self-reported 

significant medical 

history (i.e., currently 

being treated for 

depression/psychiatric 

Start time: Pregnant 24 weeks gestation

Duration: Pregnant 24 weeks gestation until 

delivery

Arm 1: Placebo

Description: corn oil capsule

Dose: 1 capsule, 5 days/week

Blinding: Identical package and only ID 

information

Arm 2: DHA group

Outcome domain: Ante or postnatal 

depression

Outcome: Postpartum Depression 

Screening Scale (PDSS) total score 

(Primary)

Follow-up time: 2 weeks

Arm 1: Sample size 22; mean 53.86; SD 

(15.25)

Arm 2: Sample size 20; mean 47.65; SD 

(12.96)

Follow-up time: 3 months

Arm 1: Sample size 22; mean 42.63; SD 
C-75

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

conflict: Multiple 

foundations and 

Societies, None

Original, same study, or 

follow-up studies: none

illness, addiction 

problems, 

hyperlipidemia, 

hypertension, renal 

disease, liver disease, 

or diabetes).

Description: 300mg DHA fish oil capsule

Dose: 1 capsule, 5 days/week

DHA: 300mg

(9.52)

Arm 2: Sample size 20; mean 45.28; SD 

(12.25)

Follow-up time: 6 months

Arm 1: Sample size 22; mean 48.42; SD 

(17.18)

Arm 2: Sample size 20; mean 45.55; SD 

(13.5)

Follow-up time: 6 weeks

Arm 1: Sample size 22; mean 47.4; SD 

(12.42)

Arm 2: Sample size 20; mean 47.61; SD 

(14.31)

Knudsen et al., 200645

Study name: Danish 

National Birth CohortPregnant Women

Study dates: 2001-

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / 

conflict: Multiple 

foundations and 

Societies

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 3098 

Pregnant withdrawals 

1033 Pregnant 

completers 2065

Pregnant age: Group 

01: 28.4 years 

Group 03: 28.7 years 

Group 07: 28.4 years 

Group 14: 28.9 years 

Group 28: 28.8 years 

Group C18: 28.8 years 

Group CG: 28.5 years

Race of Mother: NR

Baseline biomarker 

information: Level of 

Inclusion Criteria: Low 

dietary intake of fish 

(lowest 20% of fish 

consumption), no use 

of fish oil capsules in 

pregnancy, gestational 

age 17-27 weeks.

Exclusion Criteria: NR

Start time: Pregnant 17-27 weeks gestation

Duration: Pregnant until delivery

Arm 1: CG

Description: control group ( flax oi)

Blinding: The women in the control group were 

allocated to any treatment and were not 

contacted at all.

ALA: 2.2 g/d

Arm 2: 01

Description: Treatment Group 1

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, 

Denmark

Active ingredients: 13.4 mg D-alpha-tocopherol 

per gram

Dose: 1 0.5 g three times per week

DHA: 22%

EPA: 32%

Total N-3: 0.1 g per day

Outcome domain: duration of gestation

Outcome: gestational age (days) (Primary)

Follow-up time: birth

Arm 1: Sample size 748; mean 280.6; SD 

(11.7)

Arm 2: Sample size 229; mean 281.5; SD 

(12.6)

Arm 3: Sample size 224; mean 279.7; SD 

(12)

Arm 4: Sample size 222; mean 280.5; SD 

(12.6)

Arm 5: Sample size 212; mean 280.6; SD 

(12.6)

Arm 6: Sample size 187; mean 279.6; SD 

(14.8)

Arm 7: Sample size 176; mean 280.7; SD 

(12.8)
C-76

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

EPA, DHA, and AA in 

erythrocyte 

phospholipids assessed 

in a subsample of 

women in the 6 

treatment groups

Baseline Omega-3 

intake: EPA, DHA, 

EPA+DHA, ALA, AA

Arm 3: 03

Description: Treatment group 2

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, 

Denmark

Active ingredients: 13.4 mg D- alphatocopherol per gram

Dose: 1 0.5 g capsule per day

Total N-3: 0.3 g per day

Arm 4: 07

Description: Treatment group 3

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, 

Denmark

Active ingredients: 13.4 mg D- alphatocopherol per gram

Dose: 1 1 g capsule per day

DHA: 22%

EPA: 32%

Total N-3: 0.7 g per day

Arm 5: 14

Description: Treatment group 4

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, 

Denmark

Active ingredients: 13.4 mg D- alphatocopherol per gram

Dose: 2 1g capsules per day

DHA: 22%

EPA: 32%

Total N-3: 1.4 g per day

Arm 6: 28
C-77

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Description: Treatment group 5

Brand name: Futura Fish Oil

Manufacturer: Dansk Droge A/S, Ishoej, 

Denmark

Active ingredients: 13.4 mg Dalpha-tocopherol 

per gram

Dose: 4 g per day

DHA: 22%

EPA: 32%

Total N-3: 2.8g per day

Arm 7: c18

Description: Treatment group 6 - flax oil

Brand name: Prima FlaxTM

Manufacturer: Bioriginal Food & Science Corp., 

Saskatoon, Canada

Dose: 4 1-g capsules of flax oil

ALA: 2.2g per day

Lagemaat et al., 2011109

Study name: NR

Study dates: 2003 -

2006

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / 

conflict: Industry

Study Population: 

Preterm infants Low 

birth weight infants

Infants enrolled 152 

Infants completers 139

Infant age: Gestational 

age (week) PDF: 30.5 

TF: 30.5 HM: 30.0 

(PDF: 1.4 TF: 1.4 HM: 

1.6)

Race of Mother: NR 

(100)

Baseline biomarker 

Inclusion Criteria: 

infants born at 

gestational ages of 32 

weeks or less and/or 

with birth weights of 

1500 g or less

Exclusion Criteria: NR

Start time: Infants at term

Duration: Infants 6 months

Arm 1: Term Formula (TF)

Description: Placebo/control formula

Brand name: Friso 1 normal

Manufacturer: FrieslandCampina, Leeuwarden, 

The Netherlands

Blinding: NR

ALA: 63mg / 100ml

DHA: 7mg / 100ml

AA: 7mg/ 100ml

Arm 2: PDF

Description: Post-discharge formula (LCPUFA 

enriched)

Outcome domain: growth

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: term age

Arm 1: Sample size 41; mean 35.8; SD 

(1.5)

Arm 2: Sample size 52; mean 35.9; SD 

(1.2)

Arm 3: Sample size 46; mean 35.6; SD 

(1.5)

Outcome: length (cm) (Unspecified)

Follow-up time: term age

Arm 1: Sample size 41; mean 48.7; SD 

(2.1)

Arm 2: Sample size 52; mean 48.7; SD 

(2.3)

Arm 3: Sample size 46; mean 48.2; SD 
C-78

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

information: Baseline (at 

term) Mean(SD) AA 

PDF: 13.74 (0.89) TF: 

13.86 (0.93) HM: 14.06 

(1.17) DHA PDF: 4.71 

(0.70) TF: 4.59 (0.76) 

HM: 4.08 (0.55) EPA 

PDF: 0.34 (0.05) TF: 

0.32 (0.06) HM: 0.33 

(0.13) DHA/AA ratio 

PDF: 0.34 (0.05) TF: 

0.33 (0.06) HM: 0.29 

(0.04)

Brand name: Friso 1 premature

Manufacturer: Friesland Foods

ALA: 59mg/ 100ml

DHA: 14mg/ 100ml

EPA: 3.9mg/ 100ml

AA: 14mg/ 100ml

Arm 3: HM

Description: Human milk

(2.5)

Outcome: weight (g) (Unspecified)

Follow-up time: term age

Arm 1: Sample size 41; mean 3193.0; SD 

(489)

Arm 2: Sample size 52; mean 3137.0; SD 

(511)

Arm 3: Sample size 46; mean 3138.0; SD 

(513)

Lauritzen et al., 2004127

Study name: Danish 

National Birth CohortLactating Women

Study dates: December 

1998 to November 1999

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / 

conflict: Industry, 

Government

Study follow-up: 2 and 4 

months

Original, same study, or 

Study Population: 

Breast-feeding mothers 

with lower than average 

fish intake

Infants enrolled 175 

Infants completers 149

Pregnant age: Olive oil 

30.2 Fish oil 29.6 High 

fish 31.9 (Olive oil ± 4.1 

Fish oil ± 4.3 High fish ± 

4.1)

Infant age: 40.1 weeks 

gestation (birth) (1.2 

weeks)

Race of Mother: NR

(100)

Baseline Omega-3 

Inclusion Criteria: 

pregnant Danish 

women living in the 

greater Copenhagen 

area who had a fish 

intake below the 50th 

percentile of the 

DNBC population; an 

uncomplicated 

pregnancy, prepregnancy body mass 

index (BMI) < 30 

kg/m2 , and an 

absence of metabolic 

disorders; intention to 

breast-feed for at least 

4 mon at the time of 

recruiting; newborns 

had to be healthy (no 

admission to a 

neonatal department), 

term (37–43 wks of 

Start time: NR

Duration: NR

Arm 1: Placebo

Blinding: Intervention fish oil was deodorized

Arm 2: FO Intervention

Description: Fish oil powder baked into cookies

Other dose 1: 17 g/d of deodorized 

microencapsulated FO powder, containing 4.5 

g of FO and 1.5 g of n-3 LCPUF

Outcome domain: Visual function

Outcome: swept visual evoked potential 

(SWEEP-VEP) (Primary)

Follow-up time: 2 months

Arm 1: Sample size 46; mean 0.84; SD 

(0.08)

Arm 2: Sample size 42; mean 0.84; SD 

(0.09)

Follow-up time: 4 months

Arm 1: Sample size 45; mean 0.64; SD 

(0.09)

Arm 2: Sample size 52; mean 0.62; SD 

(0.08)
C-79

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

follow-up studies: 

Lauritzen, 2005102; 

Lauritzen, 2005128; 

Cheatham, 2011129;

intake: Habitual n-3 

LCPUFA intake (g/d) 

Olive oil: 0.3 ± 0.3 Fish 

oil: 0.3 ± 0.3 High fish: 

1.1 ± 0.6

gestation), singleton 

infants with normal 

weight for gestation 

(20) and an Apgar 

score >7 at 5 min after 

delivery. Willingness to 

start on the 

supplements within 2 

wks after birth; no use 

of other types of oil 

supplements

Exclusion Criteria: BMI 

>= 30 kg/m2...

Lauritzen et al., 2005102

Study name: Danish 

National Birth CohortLactating Women

Study dates: 

Recruitment: April 1999-

February 2000 Followup 2.5 years

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / 

conflict: Industry, 

Government

Study follow-up: 2.5 

Study Population: 

Breast-feeding women

Infants enrolled 100 

Infants completers 72

Mother age: High fish: 

31.9 Fish oil: 29.6 Olive 

oil: 30.2 (High fish: 4.1 

Fish oil: 4.3 Olive oil: 

4.1)

Race of Mother: NR 

(100%)

Inclusion Criteria: 

Pregnant women who 

were recruited for the 

Danish National Birth 

Cohort (DNBC) (16), 

all from the greater 

Copenhagen area, 

who were in their 

eighth month of 

gestation and had a 

fish intake below the 

median (0.40 g/d n3LCPUFA) ... (554 

women with a fish 

intake in the upper 

quartile (0.82 g/d n3LCPUFA) were 

invited to participate in 

the study as a high 

fish intake reference 

group); uncomplicated 

Start time: Lactating within 2 weeks of delivery

Duration: Lactating 4 months

Arm 1: Olive oil

Description: Control group receiving olive oil 

supplement

Dose: 2 muesli bars daily; or 4 1000-mg 

capsules

Blinding: Investigators and families were 

blinded to the randomization throughout the 

first year of life of the infants. Fish oil as well as 

olive oil supplements were given as 

microencapsulated oils concealed in two 

muesli bars (produced by Halo Foods Ltd., 

Tywyn Gwynedd, Wales, UK) daily for the first 

4 mo of lactation.

Arm 2: Fish oil

Description: Intervention group receiving fish oil 

supplement

Outcome domain: growth

Outcome: bmi (kg/m2) (Secondary)

Follow-up time: 2 months

Arm 1: Sample size 51; mean 15.93; SD 

(1.37)

Arm 2: Sample size 52; mean 15.74; SD 

(1.24)

Arm 3: Sample size 50; mean 15.63; SD 

(1.36)

Follow-up time: 2.5 years

Arm 1: Sample size 28; mean 15.86; SD 

(1.21)

Arm 2: Sample size 42; mean 16.51; SD 

(1.08)

Arm 3: Sample size 29; mean 16.11; SD 

(1.08)

Follow-up time: 4 months

Arm 1: Sample size 46; mean 17.04; SD 

(1.7)

Arm 2: Sample size 52; mean 16.93; SD 

(1.23)
C-80

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

years

Original, same study, or 

follow-up studies: 

Lauritzen, 2004127; 

Lauritzen, 2005128; 

Cheatham, 2011129;

pregnancy; body mass 

index (BMI) <30 

kg/m2; no metabolic 

disorders; intention to 

breastfeed for at least 

4 mo.; willingness to 

begin supplement 

within 2 weeks of birth. 

Newborns had to be 

healthy (no admission 

to a neonatal 

department), term 

(37– 43 wk of 

gestation), singleton 

infants with normal 

weight for gestation 

(17) and an Apgar 

score 7 at 5 min after 

delivery.

Exclusion Criteria: NR

Manufacturer: BASF Health and Nutrition A/S, 

Ballerup, Denmark

Dose: 2 muesli bars providing 0.62g EPA and 

0.79g DHA; or fish oil capsules providing 0.36g 

EPA and 0.99g DHA

DHA: 0.79g/d

EPA: 0.62g/d

Total N-3: 1.5g/d

Arm 3: High fish

Description: Group with high fish intake as 

reference group

Arm 3: Sample size 49; mean 16.57; SD 

(1.66)

Follow-up time: 9 months

Arm 1: Sample size 47; mean 17.64; SD 

(1.52)

Arm 2: Sample size 53; mean 17.91; SD 

(1.24)

Arm 3: Sample size 48; mean 17.27; SD 

(1.39)

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 1 week

Arm 1: Sample size 56; mean 35.72; SD 

(1.53)

Arm 2: Sample size 54; mean 36.11; SD 

(1.25)

Arm 3: Sample size 51; mean 36.18; SD 

(1.59)

Follow-up time: 2 months

Arm 1: Sample size 50; mean 39.28; SD 

(1.16)

Arm 2: Sample size 50; mean 39.7; SD 

(1.22)

Arm 3: Sample size 47; mean 39.68; SD 

(1.27)

Follow-up time: 2.5 years

Arm 1: Sample size 30; mean 49.74; SD 

(1.34)

Arm 2: Sample size 41; mean 50.42; SD 

(1.2)

Arm 3: Sample size 29; mean 50.62; SD 

(1.23)

Follow-up time: 4 months

Arm 1: Sample size 46; mean 41.84; SD 

(1.12)

Arm 2: Sample size 45; mean 42.17; SD 
C

-81

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(1.16)

Arm 3: Sample size 45; mean 42.4; SD 

(1.38)

Follow-up time: 9 months

Arm 1: Sample size 45; mean 45.29; SD 

(1.4)

Arm 2: Sample size 52; mean 45.85; SD 

(1.53)

Arm 3: Sample size 42; mean 45.81; SD 

(1.36)

Outcome: length (cm) (Secondary)

Follow-up time: 2 months

Arm 1: Sample size 51; median 58.7; 10th, 

90th percentile

Arm 2: Sample size 52; median 58.8; 10th, 

90th percentile

Arm 3: Sample size 50; median 59.1; 10th, 

90th percentile

Follow-up time: 2.5 years

Arm 1: Sample size 28; mean 92.65; SD 

(3.04)

Arm 2: Sample size 42; mean 92.58; SD 

(3.14)

Arm 3: Sample size 29; mean 93.74; SD 

(2.93)

Follow-up time: 4 months

Arm 1: Sample size 46; mean 64.02; SD 

(2.16)

Arm 2: Sample size 52; mean 64.21; SD 

(2.08)

Arm 3: Sample size 50; mean 64.7; SD 

(1.71)

Follow-up time: 9 months

Arm 1: Sample size 47; mean 72.15; SD 

(2.04)

Arm 2: Sample size 53; mean 72.66; SD 
C-82

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(2.35)

Arm 3: Sample size 48; mean 72.75; SD 

(2.01)

Outcome: weight (kg) (Secondary)

Follow-up time: 2 months

Arm 1: Sample size 51; mean 5.4; 10th, 

90th percentile

Arm 2: Sample size 53; median 5.5; 10th, 

90th percentile

Arm 3: Sample size 50; median 5.3; 10th, 

90th percentile

Follow-up time: 2.5 years

Arm 1: Sample size 30; mean 13.71; SD 

(1.26)

Arm 2: Sample size 42; mean 14.16; SD 

(1.26)

Arm 3: Sample size 29; mean 14.18; SD 

(1.43)

Follow-up time: 4 months

Arm 1: Sample size 47; mean 7.0; SD 

(0.85)

Arm 2: Sample size 53; mean 7.0; SD 

(0.73)

Arm 3: Sample size 49; mean 6.93; SD 

(0.67)

Follow-up time: 9 months

Arm 1: Sample size 47; mean 9.19; SD 

(0.94)

Arm 2: Sample size 53; mean 9.47; SD 

(0.94)

Arm 3: Sample size 48; mean 9.15; SD 

(0.9)

Lauritzen et al., 2005128

Study name: Danish 

Study Population: 

Healthy infants Breastfeeding women

Inclusion Criteria: 

pregnant women with 

a fish intake below the 

Start time: Lactating 9 days after birth Infants 9 

days after birth

Outcome domain: Cognitive development

Outcome: Infant Planning Test (problem 

solving) (Secondary)
C-83

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

National Birth CohortLactating Women

Study dates: Enrolled in 

1999

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / 

conflict: Industry, 

Government

Study follow-up: 9 

months, 1 year, 2 years

Original, same study, or 

follow-up studies: 

Lauritzen, 2004127; 

Lauritzen, 2005102; 

Cheatham, 2011129;

Lactating enrolled 122 

Lactating completers 89

Infants enrolled 122 

Infants completers 89

Lactating enrolled 122 

Lactating completers 89

Pregnant age: NR (NR) 

NR

Infant age: 9 days (3 

days) NA

Race of Mother: NR 

(100%)

Baseline Omega-3 

intake: < 0.4 g n-3 

LCPUFA/d

population median (< 

0.4 g n-3 LCPUFA·d–

1), uncomplicated 

pregnancy, a normal 

pre-pregnancy body 

mass index (< 30 

kg·m–2), no metabolic 

disorders, an intention 

to breastfeed for at 

least four months. 

Newborns had to be 

healthy, singleton, 

term infants with 

normal weight for 

gestation [33] and an 

Apgar score > 7 five 

minutes after delivery.

Exclusion Criteria: NR

Duration: Lactating 4 months Infants 4 months

Arm 1: placebo group

Description: olive oil in muesli bars, cookies, or 

capsules

Manufacturer: BASF

Dose: one bar/cookie/capsule containing 4.5 g 

olive oil

Blinding: identical bars/cookies/capsules

Arm 2: fish oil

Description: fish oil in muesli bars, cookies, or 

capsules

Manufacturer: BASF

Dose: one bar/cookie/capsule containing 4.5 g 

fish oil

DHA: 0.9 g

Total N-3: Other FA (not DHA): 0.6 g

Arm 3: high n-3 reference group

Description: top quartile fish intake at baseline

Dose: no supplementation, high fish intake

Total N-3: > 0.8 n-3 LCPUFA/d

Follow-up time: 9 months

Arm 1: Sample size 38; mean 4.3; SD 

(3.6)

Arm 2: Sample size 48; mean 4.5; SD 

(3.1)

Arm 3: Sample size 42; mean 4.5; SD 

(3.3)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: late gestures (Secondary)

Follow-up time: 1 year

Arm 1: Sample size 37; mean 15.0; SD (7)

Arm 2: Sample size 52; mean 14.0; SD (6)

Arm 3: Sample size 42; mean 16.0; SD (7)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: number of irregular words 

(Secondary)

Follow-up time: 2 years

Arm 1: Sample size 31; median 3.0; IQR

Arm 2: Sample size 40; median 3.0; IQR

Arm 3: Sample size 40; median 4.0; IQR

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: number of over regularized 

words (Secondary)

Follow-up time: 2 years

Arm 1: Sample size 31; median 1.0; IQR

Arm 2: Sample size 40; median 1.0; IQR

Arm 3: Sample size 40; median 1.0; IQR

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: early gestures (Secondary)

Follow-up time: 1 year

Arm 1: Sample size 37; median 11.0; IQR

Arm 2: Sample size 52; median 11.0; IQR
C

-84

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 3: Sample size 42; median 12.0; IQR

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: percent starting to talk 

(Secondary)

Follow-up time: 1 year

Arm 1: 6/37 (16.0%)

Arm 2: 6/52 (12.0%)

Arm 3: 7/42 (17.0%)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: phrases understood 

(Secondary)

Follow-up time: 1 year

Arm 1: Sample size 37; mean 11.0; SD (6)

Arm 2: Sample size 52; mean 11.0; SD (5)

Arm 3: Sample size 42; mean 11.0; SD (5)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: talk about abstract 

(Secondary)

Follow-up time: 2 years

Arm 1: 29/31 (94.0%)

Arm 2: 30/40 (75.0%)

Arm 3: 38/40 (95.0%)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: use grammar (Secondary)

Follow-up time: 2 years

Arm 1: 10/31 (32.0%)

Arm 2: 10/40 (25.0%)

Arm 3: 16/40 (40.0%)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: vocabulary comprehension 

(Secondary)
C-85

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 1 year

Arm 1: Sample size 37; mean 71.0; SD 

(45)

Arm 2: Sample size 52; mean 54.0; SD 

(37)

Arm 3: Sample size 42; mean 65.0; SD 

(40)

Outcome: MacArthur Communicative 

Development Inventory Linguistic 

Development: vocabulary production 

(Secondary)

Follow-up time: 1 year

Arm 1: Sample size 37; median 5.0; IQR

Arm 2: Sample size 52; median 3.0; IQR

Arm 3: Sample size 42; median 5.0; IQR

Follow-up time: 2 years

Arm 1: Sample size 31; mean 297.0; SD 

(147)

Arm 2: Sample size 40; mean 242.0; SD 

(170)

Arm 3: Sample size 40; mean 312.0; SD 

(146)

Linnamaa et al., 201079

Study name: NR

Study dates: 2004-2008

Study design: Trial 

randomized parallel

Location: Finland

Funding source / 

conflict: Government, 

Study Population: 

Healthy infants Healthy 

pregnant women

Infants enrolled 314 

Infants withdrawals 137 

Infants completers 177

Mother age: NR (NR) 

NR

Race of Mother: NR 

(NR)

Inclusion Criteria: All 

pregnant mothers <16 

weeks of gestation

Exclusion Criteria: 

Sick children and 

those born 

prematurely who 

required more 

intensive care (n=8)

Start time: Pregnant 8th to 16th weeks of 

pregnancy and then continued Infants when 

exclusive breastfeeding ended

Duration: Pregnant until the end of the 

exclusive breastfeeding period Infants until 2 

years of age

Arm 1: Controls

Description: Olive oil

Manufacturer: Santagata Luigi s.r.l., Genova, 

Italia

Dose: 3 g/day for mothers, 1 mL/day for infants

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 129; mean 3599.0; 

SD (468)

Arm 2: Sample size 112; mean 3595.0; 

SD (461)

Outcome domain: allergies

Outcome: positive egg skin test 

(Secondary)

Follow-up time: 12 months

Arm 1: 18/104 (17.31%)
C-86

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Multiple foundations and 

Societies

Blinding: NR "double-blind"

ALA: 0

DHA: 0

EPA: 0

EPA-DHA: 0

AA: 0

Total N-3: 0

Other dose 1: LA (18:2n-6): 9 weight% of total

Arm 2: Intervention

Description: Blackcurrant seed oil

Manufacturer: Aromtech Ltd, Tornio, Finland

Dose: 3 g/day for mothers, 1 mL/day for infants

ALA: 14 weight% of total

DHA: 0

EPA: 0

EPA-DHA: 0

AA: 0

Total N-3: 17 weight% of total

Other dose 1: SDA: 3 weight% of total

Arm 2: 14/98 (14.29%)

Follow-up time: 24 months

Arm 1: 7/87 (8.05%)

Arm 2: 4/79 (5.06%)

Follow-up time: 3 months

Arm 1: 1/126 (0.79%)

Arm 2: 1/112 (0.89%)

Outcome domain: atopic dermatitis

Outcome: atopic dermatitis (Primary)

Follow-up time: 12 months

Arm 1: 52/110 (47.27%)

Arm 2: 33/100 (33.0%)

Follow-up time: 24 months

Arm 1: 10/92 (11.11%)

Arm 2: 9/85 (11.11%)

Follow-up time: 3 months

Arm 1: 14/129 (11.11%)

Arm 2: 12/112 (11.11%)

Llorente et al., 200398

Study name: Unnamed 

Trial A

Study dates: <2002

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Government, 

Manufacturer supplied 

Study Population: 

Breast-feeding women

Lactating enrolled 138 

Lactating completers 

101

Lactating enrolled 138 

Lactating completers 

101

Lactating age: 31.5 

years (4.5 years) 18 - 42

Race of Mother: White 

Inclusion Criteria: 

pregnant women who 

were 18 to 42 years 

old and planned to 

breast feed for at least 

4 months

Exclusion Criteria: 

those with chronic 

medical conditions, or 

taking dietary 

supplements other 

than vitamins, or 

smokers, or who had 

been pregnant >5 

Start time: Lactating birth

Duration: Lactating 4 months

Arm 1: placebo

Description: placebo capsule

Manufacturer: Martek Biosciences Corporation, 

Columbia, MD

Dose: 1 capsule

Blinding: capsules were identical in 

appearance

Arm 2: omega 3 capsule

Description: algae-derived triglyceride capsule

Brand name: DHASCO

Outcome domain: Ante or postnatal 

depression

Outcome: Beck Depression Inventory 

(BDI) (Unspecified)

Follow-up time: 2 months

Arm 1: Sample size 45; mean 4.4; SD 

(4.2)

Arm 2: Sample size 44; mean 5.5; SD 

(4.3)

Follow-up time: 3 weeks

Arm 1: Sample size 45; mean 6.3; SD 

(4.7)

Arm 2: Sample size 44; mean 7.1; SD 

(5.7)

Follow-up time: 4 months
C-87

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

product

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Isaacs, 201199

European (82%) Black 

(14%) Hispanic (2.3%) 

Other race/ethnicity 

(1.6%)

Baseline biomarker 

information: Placebo 

group Total saturated 

49.7 ± 2.3 Total 

monounsaturated 12.2 ± 

1.9 Total __6 33.7 ± 2.2 

Total __3 4.37 ± 0.91 

Intervention group Total 

saturated 49.3 ± 2.7 

Total monounsaturated 

12.3 ± 1.3 Total __6 

34.2 ± 2.0 Total __3 

4.14 ± 0.89

times Manufacturer: Martek Biosciences Corporation, 

Columbia, MD

Dose: 1 capsule

DHA: 200 mg

Arm 1: Sample size 45; mean 4.8; SD 

(5.9)

Arm 2: Sample size 44; mean 5.8; SD 

(5.2)

Outcome: Edinburgh Postnatal 

Depression Scale (EPDS) (Unspecified)

Follow-up time: 18 months

Arm 1: Sample size 32; mean 6.3; SD 

(4.1)

Arm 2: Sample size 31; mean 6.3; SD 

(5.2)

Outcome: responder: BDI<10 

(Unspecified)

Follow-up time: at either 2, 4 or 18 months

Arm 1: 36/45 (79.0%)

Arm 2: 33/44 (76.0%)

Outcome: responder: BDI<20 

(Unspecified)

Follow-up time: at either 2, 4 or 18 months

Arm 1: 43/45 (95.5%)

Arm 2: 40/44 (91.1%)

Lucia Bergmann et al., 

200741

Study name: NR

Study dates: 2000-2002

Study design: Trial 

randomized parallel

Location: Germany

Funding source / 

conflict: NR

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 144 

Pregnant withdrawals 

51 Pregnant completers 

69

Pregnant age: 31 (DHA 

4.69; control 4.89)

Infant age: DHA 39.1; 

control 39.5 weeks 

Inclusion Criteria: at 

least 18 years of age 

and willing to 

breastfeed for at least 

three months were 

enrolled at 21 weeks’ 

gestation during the 

period October 2000 

to August 2002

Exclusion Criteria: 

increased risk of 

premature delivery or 

multiple pregnancy, 

Start time: Pregnant 21th week

Duration: Pregnant 37th week

Arm 1: Vitamins and minerals

Manufacturer: Nestle ́ (Vevey, Switzerland)

Arm 2: Prebiotic

Description: basic supplement plus the 

prebiotic, fructooligosaccharide (FOS) (4.5 g)

Manufacturer: Nestle ́ (Vevey, Switzerland)

Active ingredients: fructooligosaccharide (FOS) 

(4.5 g)

Outcome domain: Birth weight

Outcome: birth weight (g) (Unspecified)

Follow-up time: birth

Arm 1: Sample size 74; mean 3548.0; SD 

(469.3)

Arm 3: Sample size 43; mean 3427.0; SD 

(493.6)

Outcome domain: duration of gestation

Outcome: gestational age (weeks) 

(Unspecified)

Follow-up time: birth

Arm 1: Sample size 74; mean 39.5; SD 

(1.38)
C-88

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Original, same study, or 

follow-up studies: Lucia, 

200752

(DHA 1.64; control 1.38)

Race of Mother: White 

European (100)

Baseline biomarker 

information: DHA % of 

all identified fatty acid in 

RBC: Vitamin: 5.76 +-

2.45 (47); DHA: 

Prebiotic:5.94+-2.37(48) 

DHA: DHA: 5.69+-

2.40(47) ARA Vitamin: 

14.01+-4.04(47) ARA 

Prebiotic 14.82+-

3.60(48) ARA DHA: 

14.18+-4.32(47) EPA 

Vitamin: 0.72+-0.32(47) 

EPA Prebiotic: 0.78+-

0.38(48) EPA DHA: 

0.79+-0.41(47)

allergy to cow milk 

protein, lactose 

intolerance, diabetes, 

smoking, consumption 

of alcohol ()20 

g/week), or 

participation in another 

study. Infants 

excluded if they were 

premature at birth (<37 

week gestation, or had 

any major 

malformations or 

hospitalized for more 

than one week.

Arm 3: DHA

Description: basic supplement with FOS and 

DHA (200 mg)

Manufacturer: Nestle ́ (Vevey, Switzerland)

Dose: 200 mg DHA prepared from fish oil 

(assuming that some EPA but dose was not 

reported)

DHA: 200 mg

EPA: NR

Arm 3: Sample size 43; mean 39.1; SD 

(1.64)

Outcome domain: growth

Outcome: bmi (kg/m2) (Unspecified)

Follow-up time: 1 month

Arm 1: Sample size 74; mean 14.2; SE 

(0.37)

Arm 3: Sample size 43; mean 14.06; SE 

(0.4)

Follow-up time: 21 months

Arm 1: Sample size 74; mean 15.46; SE 

(0.32)

Arm 3: Sample size 43; mean 14.7; SE 

(0.36)

Follow-up time: 3 months

Arm 1: Sample size 74; mean 15.58; SE 

(0.38)

Arm 3: Sample size 43; mean 16.14; SE 

(0.44)

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: 1 month

Arm 1: Sample size 74; mean 37.4; SE 

(0.41)

Arm 3: Sample size 43; mean 37.1; SE 

(0.44)

Follow-up time: 21 months

Arm 1: Sample size 74; mean 47.7; SE 

(0.36)

Arm 3: Sample size 43; mean 48.4; SE 

(0.4)

Follow-up time: 3 months

Arm 1: Sample size 74; mean 40.6; SE 

(0.43)

Arm 3: Sample size 43; mean 40.6; SE
C-89

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(0.5)

Outcome: length (cm) (Unspecified)

Follow-up time: 1 month

Arm 1: Sample size 74; mean 55.6; SE 

(0.64)

Arm 3: Sample size 43; mean 56.3; SE 

(0.69)

Follow-up time: 21 months

Arm 1: Sample size 74; mean 85.4; SE 

(0.56)

Arm 3: Sample size 43; mean 85.5; SE 

(0.62)

Follow-up time: 3 months

Arm 1: Sample size 74; mean 61.9; SE 

(0.65)

Arm 3: Sample size 43; mean 61.7; SE 

(0.76)

Outcome: weight (kg) (Unspecified)

Follow-up time: 1 month

Arm 1: Sample size 74; mean 4.45; SE 

(0.226)

Arm 3: Sample size 43; mean 4.52; SE 

(0.244)

Follow-up time: 21 months

Arm 1: Sample size 74; mean 11.35; SE 

(0.197)

Arm 3: Sample size 43; mean 10.75; SE 

(0.22)

Follow-up time: 3 months

Arm 1: Sample size 74; mean 6.03; SE 

(0.23)

Arm 3: Sample size 43; mean 6.19; SE 

(0.269)

Makrides et al., 2009116 Study Population: 

Preterm infants BreastInclusion Criteria: infants born at < 33 wk 

Start time: Infants 4 days after birth Outcome domain: Cognitive development

Outcome: Bayley Scale of Infant 
C-90

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: DINO

Study dates: Enrollment 

April 2001 to October 

2005

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Multiple foundations and 

Societies, Manufacturer 

supplied product, Some 

authors serve on 

scientific advisory 

boards for corporations, 

Some authors have 

received research 

funding from infant 

formula manufacturers

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

feeding women

Pregnant enrolled 545

Infants enrolled 657 

Infants completers 614

Lactating age: 30 years 

(5.5 years) NR

Infant age: 4 days after 

birth (29 weeks 

gestation) 2 to 6 days 

after birth

Race of Mother: White 

European (90%)

of gestation

Exclusion Criteria: 

Infants born with major 

congenital or 

chromosomal 

abnormalities, 

lactating women for 

whom tuna oil was 

contraindicated(wome

n with bleeding 

disorders or taking 

anticoagulants)

Duration: Infants until infants reached their 

"expected" date of delivery

Arm 1: Placebo

Description: Soy oil capsules or regular 

preterm formula

Manufacturer: Clover Corporation

Dose: six 500-mg soy oil capsules

Blinding: all capsules were similar in size, 

shape, and color

Maternal conditions

Infant conditions

Current smoker 25.1% during pregnancy

Pre-term birth 100%

Low birth weight 44.5%

Other conditions 1 SGA 18.6%

Arm 2: tuna oil capsules

Description: DHA-rich tuna oil capsules or highDHA formula

Manufacturer: Clover Corporation

Dose: 6 500 mg capsules

Maternal conditions

Infant conditions

DHA: Capsules: Intended to achieve breast 

milk concentration of 1.0%.Formula: 1.0%

AA: Capsules: not intended to alter AA levels. 

Formula: 0.6%

Current smoker 25.6% during pregnancy

Pre-term birth 100%

Low birth weight 45.7%

Other conditions 1 SGA 18.9%

Development (Mental developmental 

index) (Primary)

Follow-up time: 18 months

Arm 1: Sample size 335; mean 93.0; SD 

(17.3)

Arm 2: Sample size 322; mean 94.9; SD 

(14.5)

Outcome domain: Neurological 

development

Outcome: Bayley psychomotor 

development index (Secondary)

Follow-up time: 18 months

Arm 1: Sample size 335; mean 92.1; SD 

(16.3)

Arm 2: Sample size 322; mean 93.1; SD 

(16.1)

Makrides et al., 201035 Study Population: Inclusion Criteria: with Start time: Pregnant < 21 week's gestation Outcome domain: Ante or postnatal 
C-91

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: DOMInO

Study dates: 2005-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Smithers, 201153; 

Palmer, 201254; Zhou, 

201255; Palmer, 201356; 

Makrides, 2014 57

Healthy pregnant 

women

Pregnant enrolled 2399 

Pregnant withdrawals 1

Infants enrolled 605 

Infants withdrawals 32 

Infants completers 726

Pregnant age: 28.9 

(DHA5.7___ control5.6)

Race of Mother: NR 

(NR)

singleton pregnancies 

at less than 21 weeks’ 

gestation were 

approached by study 

research assistants 

while attending routine 

antenatal 

appointments

Exclusion Criteria: 

already taking a 

prenatal supplement 

with DHA, their fetus 

had a known major 

abnormality, they had 

a bleeding disorder in 

which tuna oil was

contraindicated, were 

taking anticoagulant 

therapy, had a 

documented history of 

drug or alcohol abuse, 

were participating in 

another fatty acid trial, 

were unable to give 

written informed 

consent, or if English 

was not the main 

language spoken at 

home

Duration: NR

Arm 1: vegetable oil capsules

Description: a blend of 3 non-genetically 

modified oils (rapeseed, sunflower, and palm) 

in equal proportions

Manufacturer: Efamol, Surrey, England.

Dose: 3* 500mg capsule / day

Blinding: All capsules were similar in size, 

shape, and color

Arm 2: DHA

Description: DHA-rich fish oil concentrate

Manufacturer: ; Incromega 500 TG, Croda 

Chemicals, East Yorkshire, England

Dose: 500mg capsule *3/day

DHA: 800mg

EPA: 100mg

depression

Outcome: % with Edinburgh Postnatal 

Depression Scale (EPDS) > 12 (Primary)

Follow-up time: 6 months

Arm 1: 138/1202 (11.5%)

Arm 2: 117/1197 (9.74%)

Follow-up time: 6 weeks

Arm 1: 131/1202 (10.88%)

Arm 2: 115/1197 (9.61%)

Outcome domain: Birth weight

Reason results are not reported: duplicate 

data of id 4404

Outcome: (Secondary)

Outcome domain: Cognitive development

Outcome: Bayley Scale of Infant 

Development III (Cognitive Component) 

(Primary)

Follow-up time: 18 months

Arm 1: Sample size 375; weighted mean 

101.75; SD (12.56)

Arm 2: Sample size 351; weighted mean 

101.81; SD (11.05)

Outcome domain: LBW

Reason results are not reported: duplicate 

data of id 4404

Outcome domain: duration of gestation

Outcome: gestational age (days) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 1202; median 281.0; 

IQR

Arm 2: Sample size 1197; median 282.0; 
C-92

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

IQR

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 88/1202 (7.34%)

Arm 2: 67/1197 (5.6%)

Makrides et al., 201457

Study name: DOMInO

Study dates: October 

31, 2005 to September 

25, 2012

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Manufacturer supplied 

product, Some authors 

have received research 

funding from infant 

formula manufacturers

Original, same study, or 

follow-up studies: 

Makrides, 2010 35

Smithers, 201153; 

Palmer, 201254; Zhou, 

201255; Palmer, 201356

Study Population: 

Healthy pregnant 

women

Infants enrolled 726 

Infants completers 646

Race of Mother: NR 

(100)

Inclusion Criteria: 

Women with singleton 

pregnancies at less 

than 21 weeks' 

gestation

Exclusion Criteria: 

Already taking a 

prenatal supplement 

with DHA, fetus had a 

known major 

abnormality, had a 

bleeding disorder in 

which tuna oil was 

contraindicated, were 

taking anticoagulant 

therapy, had a 

documented history of 

drug or alcohol abuse, 

were participating in 

another fatty acid trial, 

were unable to give 

written informed

consent, or if English 

was not the main 

language spoken at 

home

Start time: Pregnant <21 weeks gestation

Duration: Pregnant <21 weeks gestation until 

birth

Arm 1: Placebo

Description: rapeseed, sunflower, and palm oil 

capsules

Manufacturer: Enfamol

Dose: 3 500mg capsules/day

Blinding: similar in size, shape, and color

Arm 2: DHA supplement

Description: DHA-rich fish oil capsules

Manufacturer: Enfamol

Dose: 3 500mg capsules/day

DHA: 800 mg/d

EPA: 100 mg/day

Outcome domain: ADHD

Outcome: hyperactivity disorder

Follow-up time: 4 years

Arm 1: 0/333 (0.0%)

Arm 2: 0/313 (0.0%)

Outcome domain: Autism

Outcome: diagnosis of autism

Follow-up time: 4 years

Arm 1: 4/333 (1.2%)

Arm 2: 2/313 (0.64%)

Outcome domain: Cognitive development

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Emergent 

Meta-Cognition Index (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Emotional 

Control Scale (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Flexibility 

Index (Secondary)

Follow-up time: 4 years
C

-93

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Global 

Executive Composite score (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Inhibition 

Scale (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Inhibitory 

Self-Control Index (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313 Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: 

Plan/Organize Scale (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Shift Scale 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Behavior Rating Inventory of 

Executive Function-Preschool: Working 

Memory Scale (Secondary)

Follow-up time: 4 years
C-94

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: CELF-P2 Core Language Score 

(Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Day-night stroop (measure of 

efficiency) (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Outcome: Differential Ability Scales, 

second edition (DAS II) score: General 

Conceptual Ability Score (Secondary)

Follow-up time: 4 years

Arm 1: Sample size 333

Arm 2: Sample size 313

Malcolm et al., 2003100

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: NR

Funding source / 

conflict: NR

Study Population: NR

Pregnant enrolled 100 

Pregnant withdrawals 

37 Pregnant completers 

63

Infants enrolled 60 

Infants withdrawals 5 

Infants completers 55

Infant age: 279.6 (8.5)

Race of Mother: NR 

(NR)

Baseline biomarker 

Inclusion Criteria: d 

women who were 

expected to deliver 

their infants at term 

and planned to feed 

them on breast and/or 

formula milk

Exclusion Criteria: 

diabetes, twin 

pregnancies, preeclampsic toxaemia, a 

past history of 

abruption or 

postpartum 

hemorrhage, allergy to 

fish products, a 

Start time: Pregnant week 15 Infants birth

Duration: Pregnant birth

Arm 1: Placebo

Description: contained 323 mg sunflower oil 

with high levels of oleic acid and was free of 

any significant amounts of LCPUFAs or their 

precursors

Manufacturer: R P Scherer Limited (Swindon, 

Wiltshire, UK)

Dose: 323 mg per capsule * 2

Blinding: e identical in appearance and could 

not be identified on the basis of scent or taste

Total N-3: 0

Arm 2: DHA

Outcome domain: Visual function

Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: N1 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 18; mean 58.1; SD 

(21.4)

Arm 2: Sample size 19; mean 54.7; SD 

(16.2)

Follow-up time: 66 weeks (corrected age)

Arm 1: Sample size 24; mean 57.3; SD 

(10.7)

Arm 2: Sample size 23; mean 61.5; SD 

(5.4)

Follow-up time: birth

Arm 1: Sample size 4; mean 74.8; SD 

(16.8)
C-95

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

information: Only 

reported: "The fish oil 

and placebo groups did 

not differ in maternal 

RBC and plasma fatty 

acid composition at 

enrollment"

thrombophilic 

tendency, or who were 

receiving drugs that 

affect thrombocyte 

function (non-steroidal 

anti-inflammatories)

Description: f a blended fish oil, Marinol D40, 

and contained 100 mg DHA in 323 mg oil per 

capsule

Manufacturer: R P Scherer Limited (Swindon, 

Wiltshire, UK)

Dose: 323 mg capsule * 2

DHA: 200 mg

EPA: .64 mg (estimated based on the FA 

composition)

Arm 2: Sample size 5; mean 62.2; SD 

(3.8)

Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: N2 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 28; mean 112.8; SD 

(46.5)

Arm 2: Sample size 24; mean 128.9; SD 

(47.9)

Follow-up time: 66 weeks (corrected age)

Arm 1: Sample size 26; mean 122.1; SD 

(33.7)

Arm 2: Sample size 25; mean 128.5; SD 

(30.3)

Follow-up time: birth

Arm 1: Sample size 22; mean 149.9; SD 

(28)

Arm 2: Sample size 27; mean 153.5; SD 

(28.9)

Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: N3 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 20; mean 277.3; SD 

(49.4)

Arm 2: Sample size 14; mean 241.8; SD 

(49.8)

Follow-up time: 66 weeks (corrected age)

Arm 1: Sample size 15; mean 209.2; SD 

(38.2)

Arm 2: Sample size 11; mean 228.9; SD 

(55.9)

Follow-up time: birth

Arm 1: Sample size 27; mean 298.4; SD 

(52.8)
C

-96

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 26; mean 292.2; SD 

(58.2)

Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: P1 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 22; mean 84.2; SD 

(22.5)

Arm 2: Sample size 23; mean 80.3; SD 

(21.1)

Follow-up time: 66 weeks (corrected age)

Arm 1: Sample size 26; mean 76.5; SD 

(19.5)

Arm 2: Sample size 25; mean 80.1; SD 

(15.8)

Follow-up time: birth

Arm 1: Sample size 5; mean 107.8; SD 

(11.8)

Arm 2: Sample size 9; mean 101.0; SD 

(13.6) Outcome: Peak latencies of major 

components of the transient flash visual 

evoked potential waveform: P2 (Primary)

Follow-up time: 50 weeks (corrected age)

Arm 1: Sample size 26; mean 162.5; SD 

(26.5)

Arm 2: Sample size 21; mean 164.2; SD 

(29.9)

Follow-up time: 66 weeks (corrected age)

Arm 1: Sample size 19; mean 152.5; SD 

(43.6)

Arm 2: Sample size 12; mean 150.6; SD 

(33)

Follow-up time: birth

Arm 1: Sample size 27; mean 201.8; SD 

(33.3)
C

-97

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 28; mean 201.9; SD 

(28.4)

Outcome domain: growth

Outcome: head circumference (cm) 

(Secondary)

Follow-up time: 50 weeks PCA 

(postconceptional age)

Arm 1: Sample size 27; mean 40.1; SD 

(2.3)

Arm 2: Sample size 28; mean 39.9; SD 

(1.5)

Follow-up time: 66 weeks (post 

conceptional age)

Arm 1: Sample size 27; mean 44.1; SD 

(1.7)

Arm 2: Sample size 28; mean 43.8; SD 

(2.4)

Outcome: length (cm) (Secondary)

Follow-up time: 50 weeks PCA 

(postconceptional age)

Arm 1: Sample size 27; mean 60.5; SD 

(2.9)

Arm 2: Sample size 28; mean 60.0; SD 

(2.6)

Follow-up time: 66 weeks (post 

conceptional age)

Arm 1: Sample size 27; mean 69.1; SD 

(3.2)

Arm 2: Sample size 28; mean 68.5; SD 

(2.6)

Outcome: weight (g) (Secondary)

Follow-up time: 50 weeks PCA 

(postconceptional age)

Arm 1: Sample size 27; mean 5995.7; SD 

(827.9)
C-98

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 28; mean 5894.4; SD 

(662.3)

Follow-up time: 66 weeks (post 

conceptional age)

Arm 1: Sample size 27; mean 8626.7; SD 

(208.2)

Arm 2: Sample size 28; mean 8263.7; SD 

(999.4)

Manley et al., 2011118

Study name: DINO

Study dates: 2001-2007

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Multiple foundations and 

Societies, Manufacturer 

supplied product, Some 

authors serve on 

scientific advisory 

boards for corporations

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Study Population: 

Preterm infants Breastfeeding women

Infants enrolled 657 

Infants completers 614

Lactating age: 

Intervention: 29.9 (5.8) 

Placebo: 30.2 (5.4)

Infant age: 4 days 

(median)

Race of Mother: NR 

(100%)

Inclusion Criteria: 

Infants born before 33 

weeks’ gestation, 

within 5 days of the 

infant commencing 

any enteral feedings.

Exclusion Criteria: 

major congenital or 

chromosomal 

abnormalities, from a 

multiple birth in which 

not all live-born infants 

were eligible, enrolled 

in other trials of fatty 

acid supplementation, 

or mother with 

contraindication to fish 

oil

Start time: Infants Within 5 days (or less) of 

starting enteral feeding

Duration: Infants NR

Arm 1: Standard DHA diet

Description: Soy bean oil

Manufacturer: Clover Corporation

Dose: 6 capsules per day

Maternal conditions

Infant conditions

Current smoker 25% during pregnancy

Other maternal conditions 

1arm_1_maternal_conditions_other1

Other maternal conditions 10 Birth by Csection: 69%

Pre-term birth 100%

Low birth weight 18.6%

Arm 2: High DHA

Description: Tuna fish oil

Manufacturer: Clover Corporation

Dose: 6 500-mg DHA-rich tuna oil capsules per 

day

Maternal conditions

Infant conditions

DHA: DHA to achieve a breast milk 

Outcome domain: allergies

Outcome: hay fever (Secondary)

Follow-up time: 12 months

Arm 1: 13/249 (5.22%)

Arm 2: 5/232 (2.16%)

Follow-up time: 12 or 18 months

Arm 1: 21/244 (8.61%)

Arm 2: 8/231 (3.46%)

Follow-up time: 18 months

Arm 1: 10/311 (3.22%)

Arm 2: 7/292 (2.4%)

Outcome domain: atopic dermatitis

Outcome: eczema (Secondary)

Follow-up time: 12 months

Arm 1: 40/249 (16.06%)

Arm 2: 29/232 (12.5%)

Follow-up time: 12 or 18 months

Arm 1: 67/248 (27.02%)

Arm 2: 61/236 (25.85%)

Follow-up time: 18 months

Arm 1: 51/311 (16.4%)

Arm 2: 48/292 (16.44%)

Outcome domain: respiratory illness

Outcome: asthma (Secondary)

Follow-up time: 12 months
C-99

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Smithers, 2010117; 

Collins, 2011105; Atwell, 

2013119; Collins, 2015120

concentration that was 1% of total fatty acids

Other dose 1: If supplementary formula was 

required, infants were given a high- DHA 

preterm formula (approximately 1.0%DHAand 

0.6% AA).

Current smoker 25% during pregnancy

Other maternal conditions 

1arm_2_maternal_conditions_other1

Other maternal conditions 10 Birth by Csection: 68.3%

Pre-term birth 100%

Low birth weight 18.9%

Arm 1: 25/249 (10.04%)

Arm 2: 18/232 (7.76%)

Follow-up time: 12 or 18 months

Arm 1: 53/252 (21.03%)

Arm 2: 47/237 (19.83%)

Follow-up time: 18 months

Arm 1: 46/311 (14.79%)

Arm 2: 41/292 (14.04%)

Marks et al., 2006168

Study name: CAPS

Study dates: 1997-2004

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Multiple foundations and 

Societies

Study follow-up: 5 years

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; 

Brew, 2015165; Toelle, 

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 616 

Pregnant withdrawals 

100 Pregnant 

completers 516

Infants completers 516

Race of Mother: NR

Inclusion Criteria: 

pregnant women 

whose unborn children 

were at increased risk 

of developing asthma 

because 1 or more 

parents or siblings had 

asthma or wheezing

Exclusion Criteria: with 

a pet cat at home, 

strict vegetarians, 

women with a nonsingleton pregnancy, 

and infants born 

earlier than 36 weeks 

of gestation. Infants 

had birth weights less 

than 2.5 kg, significant 

congenital 

malformations, or 

other significant 

neonatal disease.

Start time: Infants from the time the child 

started bottle-feeding, or to solid foods from 

age 6 months

Duration: NR

Arm 1: Diet control

Description: polyunsaturated oils and spreads, 

containing 40% w6 FA, and sunola oil capsules

Manufacturer: Crisco-Meadow Lea Foods Inc., 

Sydney, Australia

Blinding: The approach to blinding participants 

and research staff is described in this article’s 

Online Repository at www.jacionline.org.

Arm 2: Active

Description: canola-based oils and spreads, 

which are low in n-6 fatty acids, and tuna oil 

capsules, which contain n-3 fatty acids.

Outcome domain: allergies

Outcome: any atopy (from skin prick test) 

(Secondary)

Follow-up time: 5 years

Arm 1: 108/249 (43.37%)

Arm 2: 109/267 (40.82%)

Outcome: rhinitis (Secondary)

Follow-up time: 5 years

Arm 1: 102/249 (40.96%)

Arm 2: 111/267 (41.57%)

Outcome domain: atopic dermatitis

Outcome: current eczema (Secondary)

Follow-up time: 5 years

Arm 1: 59/249 (23.69%)

Arm 2: 54/267 (20.22%)

Outcome domain: respiratory illness

Outcome: cough without cold (Secondary)

Follow-up time: 5 years

Arm 1: 36/249 (14.46%)

Arm 2: 55/267 (20.6%)

Outcome: frequent wheeze (Secondary)
C-100

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

2010169 Follow-up time: 5 years

Arm 1: 4/249 (1.61%)

Arm 2: 5/267 (1.87%)

Outcome: probable current asthma 

(Primary)

Follow-up time: 5 years

Arm 1: 51/249 (20.48%)

Arm 2: 62/267 (23.22%)

Meldrum et al., 2012140

Study name: Infant 

FishOil Supplementation 

Study (IFOS)

Study dates: 

Recruitment from June 

2005 through October 

2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

None, Manufacturer 

supplied product

Original, same study, or 

follow-up studies: D'Vaz, 

2012142

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 420

Infants enrolled 420 

Infants completers 287

Mother age: NR (NR) 

NR

Infant age: Birth (NA) 

NA

Race of Mother: NR

Baseline biomarker 

information: Cord blood 

data Fish oil group LA, 

linoleic acid 3.71 ALA, 

a-linolenic acid 0·496 

EPA 0·334 DHA 7·36 

DPA 0·700 AA, 

arachidonic acid 15·76 

Olive oil group LA, 

linoleic acid 3.81 ALA, 

Inclusion Criteria: 

allergic pregnant 

women were recruited 

as their infants are at a 

higher risk of 

developing allergic 

disease. Maternal 

atopy was defined by 

at least one positive 

skin prick test to at 

least one of a defined 

panel of allergens.

Exclusion Criteria: 

maternal smoking, a 

pre-existing medical 

condition or high-risk 

pregnancy, more than 

three fish meals 

consumed per week or 

fish oil intake during 

pregnancy in excess 

of 1000 mg/d, preterm 

delivery, and infants 

with significant 

congenital 

abnormalities or 

Start time: Infants birth

Duration: Infants 6 months

Arm 1: placebo

Description: olive oil capsule

Manufacturer: Ocean Nutrition, Canada

Active ingredients: 66·6 % n-9 oleic acid

Viability: he composition was regularly tested 

by an independent laboratory during the trial

Dose: one 650 mg capsule

Blinding: image and scent matched

Arm 2: fish oil capsules

Manufacturer: Ocean Nutrition, Canada

Viability: he composition was regularly tested 

by an independent laboratory during the trial.

Dose: one 650 mg capsule

DHA: 280 mg

EPA: 110 mg

Outcome domain: Cognitive development

Outcome: Bayley Scales of Infant and 

Toddler Development (BSID-III) 

Composite Scores Cognitive (Primary)

Follow-up time: 18 months

Arm 1: Sample size 149; mean 105.28; 

SD (19.9)

Arm 2: Sample size 138; mean 107.65; 

SD (11.6)

Outcome: Bayley Scales of Infant and 

Toddler Development (BSID-III) Standard 

Scores Cognitive (Primary)

Follow-up time: 18 months

Arm 1: Sample size 149; mean 11.43; SD 

(2.3)

Arm 2: Sample size 138; mean 11.55; SD 

(2.2)

Outcome: Macarthur-Bates 

Communicative Development Inventory 

raw score: early gestures (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 9.56; SD 

(3.14)

Arm 2: Sample size 62; mean 10.29; SD 

(3.5)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 13.62; SD 
C

-101

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

a-linolenic acid 0·513 

EPA 0·308 DHA 7·44 

DPA 0·673 AA, 

arachidonic acid 15·54

Baseline Omega-3 

intake: From maternal 

food questionnaire, 

while pregnant Fish oil 

group LA, linoleic acid 

10·59 ALA, a-linolenic 

acid 0·87 EPA 0·07 

DHA 0·09 AA, 

arachidonic acid 0·87 

Olive oil group LA, 

linoleic acid 9·90 ALA, a-linolenic acid 0·89 

EPA 0.06 DHA 0·08 

AA, arachidonic acid 

0·84

medical conditions. (7.7)

Arm 2: Sample size 77; mean 14.09; SD 

(2.3)

Outcome: Macarthur-Bates 

Communicative Development Inventory 

raw score: later gestures (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 11.26; SD 

(7.5)

Arm 2: Sample size 62; mean 15.16; SD 

(8.3)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 28.08; SD 

(7.7)

Arm 2: Sample size 77; mean 30.81; SD 

(7.6)

Outcome: Macarthur-Bates 

Communicative Development Inventory 

raw score: phrases understood (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 13.6; SD 

(5.8)

Arm 2: Sample size 62; mean 13.34; SD 

(6.7)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 23.5; SD 

(5.1)

Arm 2: Sample size 77; mean 24.06; SD 

(4.7)

Outcome: Macarthur-Bates 

Communicative Development Inventory 

raw score: total gestures (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 20.76; SD 

(10.1)

Arm 2: Sample size 62; mean 25.47; SD 
C

-102

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(10.9)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 41.48; SD 

(9.3)

Arm 2: Sample size 77; mean 44.75; SD 

(9)

Outcome: Macarthur-Bates 

Communicative Development Inventory 

raw score: words spoken (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 5.52; SD 

(8.7)

Arm 2: Sample size 62; mean 6.11; SD 

(7.5)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 58.5; SD 

(63.5)

Arm 2: Sample size 77; mean 49.16; SD 

(55.8)

Outcome: Macarthur-Bates 

Communicative Development Inventory 

raw score: words understood (Primary)

Follow-up time: 12 months

Arm 1: Sample size 66; mean 61.42; SD 

(52.2)

Arm 2: Sample size 62; mean 68.3; SD 

(47.6)

Follow-up time: 18 months

Arm 1: Sample size 84; mean 190.43; SD 

(94.5)

Arm 2: Sample size 77; mean 199.09; SD 

(83.7)

Outcome domain: Neurological 

development

Outcome: Categorical Child Behavior 
C-103

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Checklist: Sleep problems - number with tscore>59 (Primary)

Follow-up time: 18 months

Arm 1: 56/144 (39.0%)

Arm 2: 54/125 (43.5%)

Meldrum et al., 201551

Study name: Dunstan

Study dates: 10/2012-

12/2013 for 12-year 

follow-up

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Multiple 

foundations and 

Societies, None

Study follow-up: 12 

years

Original, same study, or 

follow-up studies: 

Dunstan, 200350; 

Dunstan, 200844;

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 98 

Pregnant completers 82

Infants enrolled 82 

Infants completers 50

Pregnant age: Fish oil 

30.9 Control 32.6 (Fish 

oil: 3.7 Control: 3.6)

Infant age: NR (NR)

Race of Mother: NR 

(100)

Inclusion Criteria: 

Pregnant women with 

allergies

Exclusion Criteria: 

Women were ineligible 

for the study if they 

smoked, had medical 

problems, a 

complicated 

pregnancy, seafood 

allergy, or if their 

normal dietary intake 

exceeded two meals 

of fish per week. 

Children were 

excluded from the 

study if they were born 

before 36 weeks’ 

gestation or with major 

disease (to avoid the 

confounding effects on 

immune response) or 

if cord blood was not 

collected

Start time: Pregnant 20 weeks gestation

Duration: Pregnant to birth

Arm 1: Placebo

Description: Olive oil capsules

Manufacturer: Pan Laboratories

Dose: 4 1g capsules per day

Blinding: Randomisation and allocation of 

capsules was carried out in a blinded manner, 

and capsules in the two groups were image 

matched

Arm 2: Fish oil

Manufacturer: Ocean Nutrition

Active ingredients: 3–4 mg/g oil a-tocopherol 

(vitamin E)

Dose: 4 1g capsules per day

DHA: 2.2g

EPA: 1.1g

Outcome domain: Cognitive development

Outcome: Wechsler Intelligence Scale for 

Children IV (Secondary)

Follow-up time: 12 years

Arm 1: Sample size 25; mean 107.6; SD 

(9.9)

Arm 2: Sample size 25; mean 108.6; SD 

(12.2)

Outcome domain: Neurological 

development

Outcome: Beery-Buktenica Development 

Test of Visual-Motor Integration (TVMI) 

(Secondary)

Follow-up time: 12 years

Arm 1: Sample size 23; mean 103.2; SD 

(9.9)

Arm 2: Sample size 24; mean 104.4; SD 

(9)

Mihrshahi et al., 2003166

Study name: CAPS

Study dates: 1997-2002

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 616 

Inclusion Criteria: At 

least one parent or 

sibling with symptoms 

of asthma as 

assessed by screening 

Start time: Infants initiation of bottle feeding or 

6 months of age

Duration: Infants NR

Outcome domain: allergies

Outcome: any atopy

Follow-up time: 18 months

Arm 1: 58/275 (21.1%)

Arm 2: 51/279 (18.2%)
C-104

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Multiple foundations and 

Societies, Manufacturer 

supplied product

Study follow-up: 18 

months

Original, same study, or 

follow-up studies: 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; 

Brew, 2015165 Toelle, 

2010169

(all 4 arms) Pregnant 

withdrawals 62 

Pregnant completers 

554

Pregnant age: 28.5 (5.3)

Race of Mother: NR 

(96.9%) Other 

race/ethnicity 

(Aboriginal 3.1%)

questionnaire, 

Reasonable fluency in 

English, Telephone at 

home, Reside within 

30 km from center of 

recruitment

Exclusion Criteria: Pet 

cat at home, Families 

on strict vegetarian 

diet, Multiple births, 

Babies born earlier 

than 36 weeks 

gestation, with 

congenital 

malformations or other 

serious disease, or 

requiring major 

surgery or 

hospitalization for 

greater than 1 week

Arm 1: Diet Control/HDM control or intervention

Brand name: Sunola oil

Manufacturer: Clover Corporation

Arm 2: Dietary intervention/HDM control or 

intervention

Description: 500mg n-3 rich tuna fish oil 

supplement

Manufacturer: Clover Corporation

DHA: 76-128 mg

EPA: 18-30 mg

Other dose 1: based on age and fluid intake

Outcome domain: atopic dermatitis

Outcome: eczema or dermatitis (Primary)

Follow-up time: 18 months

Arm 1: 77/275 (28.1%)

Arm 2: 85/279 (30.5%)

Outcome domain: respiratory illness

Outcome: asthma (Primary)

Follow-up time: 18 months

Arm 1: 34/275 (12.5%)

Arm 2: 41/279 (14.7%)

Outcome: wheeze ever (Primary)

Follow-up time: 18 months

Arm 1: 145/275 (52.6%)

Arm 2: 119/279 (42.8%)

Miles et al., 201178

Study name: SiPS

Study dates: NR

Study design: Trial 

randomized parallel

Location: UK

Funding source / 

conflict: Government, 

Some authors employed 

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 123 

Pregnant completers 

101

Pregnant age: Salmon: 

29.5 Control: 28.4 

(Salmon 0.5 Control: 

0.6)

Race of Mother: NR 

Inclusion Criteria: age 

18–40 y; ,19 wk 

gestation; healthy, 

uncomplicated 

singleton pregnancy; 

infant at risk of atopy 

(one or more firstdegree relatives of the 

baby affected by 

atopy, asthma, or 

allergy by self-report); 

consuming <2 portions 

of oily fish/mo 

(excluding canned 

Start time: Pregnant Week 20

Duration: Pregnant Week 20 until Term 

(delivery)

Arm 1: Control

Description: No added fish

DHA: 16 mg/d in diet

EPA: 10 mg/d in diet

EPA-DHA: 24 mg/d in diet

Arm 2: Salmon

Description: 2 portions salmon per week

DHA: 326 mg/d

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 54; mean 3425.0; SE 

(82)

Arm 2: Sample size 53; mean 3449.0; SE 

(72)
C-105

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

by industry (companies 

that make the 

supplements)

Original, same study, or 

follow-up studies: 

Noakes, 201288

(100%) tuna); not using fish-oil 

supplements currently 

or in the previous 3 mo

Exclusion Criteria: age 

<18 or >40 y; .19 wk 

gestation; no firstdegree relatives of the 

infant affected by 

atopy, asthma, or 

allergy; consuming >2 

portions of oily fish/mo 

(excluding canned 

tuna); use of fish-oil 

supplements within 

previous 3 mo; 

participation in another 

research study; known 

diabetic; or presence 

of any autoimmune 

disease, learning 

disability, terminal 

illness, or mental 

health problems

EPA: 162 mg/d

EPA-DHA: 491 mg/d

Min et al., 201443

Study name: NR

Study dates: Jan 2008 -

Dec 2011

Study design: Trial

randomized parallel

Location: UK

Study Population: 

Healthy pregnant 

women, Pregnant 

women with type 2 

diabetes

Pregnant enrolled 85 

Pregnant completers 59

Pregnant age: 29 18-44

Inclusion Criteria: 

Pregnant women of 

17–45 years old with 

singleton pregnancies 

with either pre-existing 

Type 2 diabetes or 

without any known 

medical condition 

(uncomplicated 

pregnancy group)

Start time: Pregnant average: 9.9-12.1 weeks 

gestation (range: 4.3-15.9 weeks gestation)

Duration: Pregnant until delivery; average: 26.5 

weeks for placebo arm; 28.4 weeks for the fish 

oil arm

Arm 1: Placebo, healthy women

Description: high oleic acid sunflower oil

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: oleic acid, 82.6%; vitamin E 

Outcome domain: LBW

Outcome: birthweight <1500g (Secondary)

Follow-up time: birth

Arm 1: 0/27 (0.0%)

Arm 2: 1/32 (3.1%)

Outcome: birthweight <2500g (Secondary)

Follow-up time: birth

Arm 1: 3/27 (11.1%)

Arm 2: 4/32 (12.5%)

Outcome domain: duration of gestation
C-106

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / 

conflict: Industry, 

Government, Multiple 

foundations and 

Societies, Manufacturer 

supplied product

Original, same study, or 

follow-up studies: none

Infant age: 11.0-12.1 

weeks gestation 6.0-

15.9 weeks gestation

Race of Mother: White 

European (22.3%) Black 

(28.2%) Asian (40.0%) 

Other race/ethnicity 

(9.4%)

Exclusion Criteria: 

Women planning to 

receive tocolytic or 

corticosteroid therapy. 

Note that pregnant 

women with preexisting Type 2 

diabetes were 

excluded from this 

systematic review.

(d- a tocopherol) NR%

Dose: 2x 750 mg capsules/day

Blinding: identical oblong soft gelatin capsule

Maternal conditions

Current smoker 0%

Arm 2: Fish oil, healthy women

Description: HA-enriched fish oil

Brand name: Mumomega

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: vitamin E (d- a tocopherol) 

NR%

Dose: 2 750 mg capsules/day

Maternal conditions

DHA: 43.7% (600 mg/d)

EPA: 7.5% (estimated to be 103 mg/d)

Current smoker 13.3%

Arm 3: Placebo, diabetic women

Description: igh oleic acid sunflower oil

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: oleic acid, 82.6%; vitamin E 

(d- a tocopherol) NR%

Dose: 2 750 mg capsules/day

Maternal conditions

Current smoker 0%

Other maternal conditions 

1arm_3_maternal_conditions_other1

Other maternal conditions 10 Type 2 diabetes: 

100%

Arm 4: Fish oil, diabetic women

Description: HA-enriched fish oil

Brand name: Mumomega

Manufacturer: Equazen/Vifor Pharma Ltd.

Active ingredients: vitamin E (d- a tocopherol) 

Outcome: gestational age birth (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 27; median 39.3; 

range

Arm 2: Sample size 32; median 39.3; 

range

Outcome: preterm birth (Secondary)

Follow-up time: birth

Arm 1: 3/27 (11.1%)

Arm 2: 3/32 (9.4%)
C-107

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

NR%

Dose: 2 750 mg capsules/day

Blinding: identical oblong soft gelatin capsule

Maternal conditions

DHA: 43.7%

EPA: 7.5%

Current smoker 4.9%

Other maternal conditions 

1arm_4_maternal_conditions_other1

Other maternal conditions 10 Type 2 diabetes: 

100%

Mozurkewich et al., 

201342

Study name: NR

Study dates: Oct 2008 -

May 2011

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 126 

Pregnant withdrawals 8 

Pregnant completers 

118

Pregnant age: EPA 

29.9; DHA 30.6; placebo 

30.4 (EPA 5.0; DHA 4.5; 

placebo 5.9)

Race of Mother: White 

European (85%; 76%; 

83%) Black (10%; 11%; 

5%) Asian (3%; 3%; 

2%) Hispanic (0%; 11%; 

7%) Inuit Eskimo (0%; 

0%; 2%) Pacific Islander 

(NR)

Baseline biomarker 

Inclusion Criteria: past 

history of depression, 

an EPDS score 9-19 

(at risk for depression 

or mildly depressed), 

singleton gestation, a 

maternal age of 18 

years or older, and a 

gestational age of 12-

20 weeks

Exclusion Criteria: had 

a history of a bleeding 

disorder, thrombophilia 

requiring 

anticoagulation, 

multiple gestation, 

bipolar disorder, 

current major 

depressive disorder, 

current substance 

abuse, lifetime 

substance 

dependence, or 

Start time: Pregnant 12-20 week gestation

Duration: Pregnant assuming till birth

Arm 1: Control/Placebo

Description: 98% soy oil and 1% each of lemon 

and fish oil

Manufacturer: Nordic Naturals Corporation in 

Watsonville, CA

Viability: centrifuged before separation into the 

6 aliquots and were stored at 70 degrees C.

Dose: 2 large and 4 small placebo capsules

Blinding: The placebos were formulated to be 

identical in appearance to both the EPA- and 

DHA-rich supplements

Arm 2: EPA-rich fish oil

Description: an approximate 4:1 ratio of EPA to 

DHA (1060 mg EPA plus 274 mg DHA)

Brand name: ProEPAXtra, Nordic Naturals

Viability: centrifuged before separation into the 

6 aliquots and were stored at 70 degrees C.

Dose: 2 large EPA capsule and 4 small 

placebo

Outcome domain: Ante or postnatal 

depression

Outcome: Beck Depression Inventory 

(BDI) (Primary)

Follow-up time: 26-28 weeks

Arm 1: Sample size 41; mean 6.3; SD 

(3.9)

Arm 2: Sample size 39; mean 8.7; SD 

(4.2)

Arm 3: Sample size 38; mean 7.0; SD 

(4.6)

Follow-up time: 34-36 weeks

Arm 1: Sample size 41; mean 7.4; SD 

(5.5)

Arm 2: Sample size 39; mean 8.2; SD 

(5.7)

Arm 3: Sample size 38; mean 6.9; SD 

(6.3)

Follow-up time: 6-8 weeks post-partum

Arm 1: Sample size 41; mean 5.9; SD 

(6.1)

Arm 2: Sample size 39; mean 6.6; SD 

(5.2)

Arm 3: Sample size 38; mean 5.7; SD 
C-108

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

information: EPA group: 

EPA 0.29+-0.18; DHA 

4.24+-2.30; total n3 FA: 

22.10+-3.72 DHA group: 

EPA 0.31+-0.24; DHA 

4.66+-2.29; total n3 FA 

36.41+-9.71 placebo: 

EPA .34+-0.22; DHA

3.85+-1.77; omega3 fa 

322.86+-5.02

schizophrenia. Women 

were also ineligible if 

they were currently 

taking omega-3 fatty 

acid supplements or 

antidepressant 

medications or eating 

more than 2 fish meals 

per week.

DHA: 274 mg

EPA: 1060 mg

Arm 3: DHA-rich fish oil

Description: DHA and EPA in an approximate 

4:1 ratio o (900 mg DHA plus 180 mg EPA)

Brand name: ProDHA, Nordic Naturals

Viability: centrifuged before separation into the 

6 aliquots and were stored at 70 degrees C.

Dose: 2 large placebo oil and 4 small DHA rich

DHA: 900 mg

EPA: 180 mg

(4.8)

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 40; mean 3309.0; SD 

(555)

Arm 2: Sample size 40; mean 3402.0; SD 

(550)

Arm 3: Sample size 38; mean 3774.0; SD 

(438)

Outcome domain: Gestational 

hypertension preeclampsia eclampsia

Outcome: gestational hypertension or 

preeclampsia (Secondary)

Follow-up time: during pregnancy

Arm 1: 5/41 (12.0%)

Arm 2: 8/39 (21.0%)

Arm 3: 2/38 (5.0%)

Outcome domain: duration of gestation

Outcome: gestational age (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 41; mean 39.1; SD 

(1.5)

Arm 2: Sample size 39; mean 39.1; SD 

(1.5)

Arm 3: Sample size 38; mean 40.4; SD 

(0.9)

Mulder et al., 201475

Study name: NR

Study Population: 

Healthy pregnant 

women

Inclusion Criteria: at 

least 16 wk gestation, 

not taking any lipid or 

fatty acid supplement, 

Start time: Pregnant 16 weeks gestation

Duration: Pregnant Until birth

Outcome domain: Birth weight

Outcome: birth weight (g) (Unspecified)

Follow-up time: birth

Arm 1: Sample size 111; mean 3497.0; 
C-109

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: 2004 to 

2008

Study design: Trial 

randomized parallel

Location: Canada

Funding source / 

conflict: Government

Study follow-up: 18 

months

Pregnant enrolled 271 

Pregnant completers 

200

Pregnant age: 33 years 

(4 years) NR

Race of Mother: White 

European (73%) Other 

race/ethnicity (27%)

Baseline biomarker 

information: maternal 

RBC 

Phusphatidylethanolami

ne DHA: placebo group 

6.25 (1.60) g/ 100g DHA 

group 6.36 (1.62) g/ 

100g

Baseline Omega-3 

intake: median (2.5 to 

97.5th percentile range) 

intake: placebo group 

80.0 (0.00-334) mg/day, 

DHA group 90.0 (6.00-

472) mg/d

and were expected to 

deliver one infant at 

full-term gestation, 

with no maternal or 

fetal complications

Exclusion Criteria: NR

Arm 1: placebo

Description: corn and soybean oil supplement

Manufacturer: Martek Biosciences

Blinding: supplements were identical in 

appearance, contained an orange flavour mask

Arm 2: DHA supplement

Description: algal oil DHA supplement

Manufacturer: Martek Biosciences

DHA: 400 mg

SD (479)

Arm 2: Sample size 104; mean 3494.0; 

SD (400)

Outcome domain: Cognitive development

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

cognitive (Unspecified)

Follow-up time: 18 months

Arm 1: 18/80 (23.1%)

Arm 2: 15/74 (20.0%)

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

expressive language (Unspecified)

Follow-up time: 18 months

Arm 1: 19/80 (24.1%)

Arm 2: 28/74 (37.5%)

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

receptive language (Unspecified)

Follow-up time: 18 months

Arm 1: 16/80 (20.5%)

Arm 2: 27/74 (36.5%)

Outcome: Number in highest quartile of 

Infant MacArthur Communicative 

Development Inventory: words produced 

(Unspecified)

Follow-up time: 14 months

Arm 1: 13/81 (16.0%)

Arm 2: 26/78 (33.3%)

Follow-up time: 18 months

Arm 1: 12/61 (19.1%)

Arm 2: 27/73 (37.3%)

Outcome: Number in highest quartile of 

Infant MacArthur Communicative 

Development Inventory: words understood 
C

-110

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(Unspecified)

Follow-up time: 14 months

Arm 1: 12/81 (14.8%)

Arm 2: 28/78 (35.9%)

Follow-up time: 18 months

Arm 1: 11/61 (18.8%)

Arm 2: 27/73 (37.3%)

Outcome: Number in highest quartile of 

Toddler MacArthur Communicative 

Development Inventory: words produced 

(Unspecified)

Follow-up time: 18 months

Arm 1: 10/61 (17.1%)

Arm 2: 26/73 (35.0%)

Outcome domain: Neurological 

development

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

fine motor (Unspecified)

Follow-up time: 18 months

Arm 1: 20/80 (25.6%)

Arm 2: 22/74 (30.1%)

Outcome: Number in highest quartile of 

Bayley Scales of Infant Development III: 

gross motor (Unspecified)

Follow-up time: 18 months

Arm 1: 21/80 (26.6%)

Arm 2: 22/74 (29.7%)

Outcome domain: Visual function

Outcome: number with visual acuity>==13 

cycles/degree (Unspecified)

Follow-up time: 12 months

Arm 1: 20/95 (21.1%)

Arm 2: 20/81 (24.7%)
C

-111

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Outcome: number with visual acuity>==3.3 

cycles/degree (Unspecified)

Follow-up time: 2 months

Arm 1: 8/94 (8.51%)

Arm 2: 17/90 (18.9%)

Outcome domain: growth

Outcome: length-for-age z score 

(Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 94; mean 0.44; SD 

(1.11)

Arm 2: Sample size 84; mean 0.11; SD 

(1.06)

Follow-up time: 18 months

Arm 1: Sample size 82; mean 0.41; SD 

(1.14)

Arm 2: Sample size 76; mean 0.16; SD 

(1.11)

Follow-up time: 2 months

Arm 1: Sample size 102; mean 0.29; SD 

(1.08)

Arm 2: Sample size 92; mean 0.17; SD 

(1.04)

Follow-up time: 6 months

Arm 1: Sample size 101; mean 0.25; SD 

(1.06)

Arm 2: Sample size 95; mean 0.17; SD 

(1.04)

Follow-up time: 9 months

Arm 1: Sample size 95; mean 0.22; SD 

(1.08)

Arm 2: Sample size 88; mean -0.06; SD 

(1.05)

Outcome: weight-for-age z score 

(Unspecified)
C

-112

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 12 months

Arm 1: Sample size 94; mean 0.15; SD 

(1.02)

Arm 2: Sample size 81; mean 0.12; SD 

(1.05)

Follow-up time: 18 months

Arm 1: Sample size 70; mean 0.27; SD 

(0.99)

Arm 2: Sample size 74; mean 0.21; SD 

(1.04)

Follow-up time: 2 months

Arm 1: Sample size 101; mean 0.06; SD 

(1.08)

Arm 2: Sample size 90; mean -0.19; SD 

(1.08)

Follow-up time: 6 months

Arm 1: Sample size 101; mean 0.1; SD 

(1.01)

Arm 2: Sample size 95; mean -0.06; SD 

(1.11)

Follow-up time: 9 months

Arm 1: Sample size 94; mean 0.03; SD 

(0.99)

Arm 2: Sample size 87; mean 0.04; SD 

(1.11)

Outcome: weight-for-length z score 

(Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 93; mean -0.04; SD 

(0.99)

Arm 2: Sample size 81; mean 0.14; SD 

(1.09)

Follow-up time: 18 months

Arm 1: Sample size 70; mean 0.14; SD 

(1.05)

Arm 2: Sample size 74; mean 0.14; SD 
C-113

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(1.05)

Follow-up time: 2 months

Arm 1: Sample size 101; mean -0.16; SD 

(1.08)

Arm 2: Sample size 90; mean -0.42; SD 

(1.2)

Follow-up time: 6 months

Arm 1: Sample size 101; mean 0.04; SD 

(1.04)

Arm 2: Sample size 95; mean -0.11; SD 

(1.02)

Follow-up time: 9 months

Arm 1: Sample size 94; mean -0.04; SD 

(0.99)

Arm 2: Sample size 87; mean 0.17; SD 

(1.05)

Noakes et al., 201288

Study name: SiPS

Study dates: Not 

reported

Study design: Trial 

randomized parallel

Location: UK

Funding source / 

conflict: Government, 

None

Original, same study, or 

follow-up studies: Miles, 

201178

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 123 

Pregnant withdrawals 

37 Pregnant completers 

86

Pregnant age: 

Mean(SEM)(n):Control 

group -28.4 (0.6)(61); 

Salmon group- 29.5(0.5) 

(62) (NR) 18-40 years

Race of Mother: NR 

(100)

Inclusion Criteria: age 

18–40 y; >19 wk 

gestation; healthy 

uncomplicated 

singleton pregnancy; 

infant at risk of atopy 

(one or more firstdegree relatives of the 

infant affected by 

atopy, asthma or 

allergy by self-report); 

consumption of < 2 

portions oily fish per 

month, excluding 

tinned tuna; and no 

use of fish-oil 

supplements currently 

or in the previous 3 

months.

Start time: Pregnant 20 weeks of gestation

Duration: Pregnant until birth

Arm 1: Control group

Description: Women in the control group (n = 

61) were asked to continue their habitual diet

Blinding: Researchers responsible for 

assessing outcome measures (both laboratory 

and clinical) remained blinded to the groups

Arm 2: Salmon group

Description: Women in the salmon group (n = 

62) were asked to incorporate 2 portions of 

farmed salmon (150 g/portion) into their diet 

per week

Active ingredients: 30.5 g protein, 16.4 g fat,4.1 

mg alpha-tocopherol, 1.6 mg gammatocopherol, 6 micro-g vitamin A, 14 micro-g 

Outcome domain: atopic dermatitis

Outcome: atopic dermatitis (Primary)

Follow-up time: 6 months

Arm 1: 12/48 (25.0%)

Arm 2: 7/38 (18.42%)

Outcome domain: respiratory illness

Outcome: chest infection (Secondary)

Follow-up time: 6 months

Arm 1: 1/46 (2.17%)

Arm 2: 3/37 (8.11%)

Outcome: pneumonia/bronchiolitis 

(Secondary)

Follow-up time: 6 months

Arm 1: 1/46 (2.17%)

Arm 2: 1/37 (2.7%)

Outcome: wheeze (Secondary)

Follow-up time: 6 months

Arm 1: 11/46 (23.91%)
C-114

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Exclusion Criteria: age 

<18 or >40 y; <19 wk 

gestation; no firstdegree relatives of the 

infant affected by 

atopy, asthma, or 

allergy; consumption 

of >2 portions oily fish 

per month, excluding 

tinned tuna; use of 

fish-oil supplements 

within the previous 3 

mo; participation in 

another research 

study; known diabetes; 

presence of any 

autoimmune disease; 

learning disability; 

terminal illness; and 

mental health 

problems.

vitamin D3, and 43 micro-g Selenium

Dose: two 150-g portions per week

DHA: 1.16 g per portion

EPA: 0.57g per portion

EPA-DHA: 1.73 per portion

Total N-3: 3.56g per portion

Other dose 1: Docosapentaenoic acid-0.35g

Arm 2: 7/37 (18.92%)

Olsen et al., 2008187

Study name: NR

Study dates: 1989-2006

Study design: Trial 

randomized parallel

Location: Denmark

Funding source / 

conflict: Multiple 

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 533

Infants enrolled 531 

Infants completers 522

Pregnant age: Fish oil: 

29.4 Olive oil: 29.7 No 

oil: 29.1 (Fish oil: (4.4) 

Olive oil: (4.3) No oil: 

Inclusion Criteria: 

Women seen in the 

main midwife clinic in 

Aarhus Denmark at 

week 30 gestation

Exclusion Criteria: 

History of placental 

abruption in a previous 

pregnancy or a serious 

bleeding episode in 

the current pregnancy; 

multiple pregnancies; 

Start time: Pregnant 30 weeks gestation

Duration: Pregnant to term

Arm 1: Control

Description: Olive oil

Active ingredients: 72% oleic acid

Dose: 4 one gram capsules

Blinding: Gelatin capsules were coloured, and 

the capsules and their boxes looked identical.

ALA: 12%

Arm 2: Fish oil

Outcome domain: respiratory illness

Outcome: asthma (all types) (Secondary)

Follow-up time: 16 years

Arm 1: 11/136 (8.09%)

Arm 2: 8/263 (3.04%)

Arm 3: 3/129 (2.33%)

Outcome: asthma (allergic) (Secondary)

Follow-up time: 16 years

Arm 1: 8/136 (5.88%)

Arm 2: 2/263 (0.76%)

Arm 3: 0/129 (0.0%)
C-115

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

foundations and 

Societies

Study follow-up: 16 

years

(4.1)) NR

Race of Mother: NR 

(100)

allergy to fish; regular 

use of fish oil 

prostaglandin 

inhibitors

Brand name: Pikasol Fish Oil

Manufacturer: Lube Limited

Active ingredients: 2mg tocopherol/ml

Dose: 4 1-gm capsules

EPA: 32%

EPA-DHA: 23%

Total N-3: 2.7g marine n-3PUFA/day

Arm 3: No oil

Description: no intervention at all

Palmer et al., 201254

Study name: DOMInO

Study dates: 2006-2009

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Industry, 

Government, 

Manufacturer supplied 

product

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; Zhou, 

201255; Palmer, 201356; 

Makrides, 2014 57

Study Population: 

Pregnant women with 

allergies

Pregnant enrolled 706 

Pregnant withdrawals 

25 Pregnant completers 

681

Infants enrolled 706 

Infants withdrawals 25 

Infants completers 681

Pregnant age: 

Treatment: 29.6 

Placebo: 29.5 

(Treatment: 5.7 

Placebo: 5.6) NR

Race of Mother: NR 

(100)

Inclusion Criteria: 

Included if the unborn 

baby had a mother, 

father, or sibling with a 

history of any 

medically diagnosed 

allergic disease 

(asthma, allergic 

rhinitis, eczema) and 

they were enrolled 

from the Women’s and 

Children’s Hospital or 

Flinders Medical 

Centre in Adelaide.

Exclusion Criteria: NR

Start time: Pregnant 21 weeks of gestation 

Infants 21 weeks of gestation

Duration: Pregnant until delivery Infants till 

delivery

Arm 1: Placebo

Description: 338 women assigned to control 

supplements-vegetable oil capsules

Dose: three 500 mg vegetable oil capsules

daily

Blinding: All capsules were similar in size, 

shape, and colour. Neither the women nor the 

research staff was aware of the treatment 

allocated.

Arm 2: n-3 LCPUFA group

Description: 368 women assigned to fish oil 

concentrate

Brand name: Incromega 500 TG

Manufacturer: Croda Chemicals, East 

Yorkshire, UK

Dose: e three 500 mg capsules daily

DHA: 800mg

EPA: 100mg

Outcome domain: allergies

Outcome: food allergy with sensitization 

(Primary)

Follow-up time: 1 year

Arm 1: 11/338 (3.25%)

Arm 2: 11/368 (2.99%)

Outcome domain: atopic dermatitis

Outcome: eczema with sensitization 

(Primary)

Follow-up time: 1 year

Arm 1: 39/338 (11.54%)

Arm 2: 26/368 (7.07%)

Outcome domain: respiratory illness

Outcome: respiratory tract infection 

(Secondary)

Follow-up time: 1 year

Arm 1: 66/338 (19.53%)

Arm 2: 65/368 (17.66%)
C-116

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Palmer et al., 201356

Study name: DOMInO

Study dates: 2006-2011 

(allergy follow-up to 

Domino study)

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Industry, 

Government, Some 

authors serve on 

scientific advisory 

boards for corporations

Study follow-up: 3 years

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; 

Palmer, 201254; Zhou, 

201255

Study Population: 

Children with family 

history of allergy

Pregnant enrolled 706 

Pregnant completers 

638

Infants enrolled 706 

Infants completers 638

Pregnant age: DHA: 

28.9 Control: 28.9 

(DHA: 5.7) Control: 5.6)

Infant age: Birth

Race of Mother: NR 

(100)

Inclusion Criteria: 

Women whose infants 

had a parent or sibling 

with a history of any 

medically diagnosed 

allergic disease 

(asthma, allergic 

rhinitis, eczema)

Exclusion Criteria: 

Already taking a 

prenatal supplement 

with DHA Fetus had a 

known major 

abnormality, Bleeding 

disorder in which tuna 

oil was 

contraindicated, 

Taking anticoagulant 

therapy A 

documented history of 

drug or alcohol abuse, 

Participating in 

another fatty acid trial, 

Unable to give written 

informed consent, or 

English was not the 

main language spoken 

at home

Start time: Pregnant <21 weeks gestation

Duration: Pregnant to term

Arm 1: Control

Description: vegetable oil

Dose: 3 500-mg vegetable oil capsules per day

Blinding: This was a double-blinded study; all 

capsules were similar in size, shape and colour

Arm 2: Fish oil

Brand name: Incromega 500 TG,

Manufacturer: Croda Chemicals, East 

Yorkshire, England

Dose: 3 500-mg capsules per day

DHA: 800 mg per day

EPA: 100 mg per day

Outcome domain: allergies

Outcome: allergic rhinitis (Primary)

Follow-up time: 3 years

Arm 1: 20/338 (5.92%)

Arm 2: 18/368 (4.89%)

Outcome: food allergy (Primary)

Follow-up time: 3 years

Arm 1: 14/338 (4.14%)

Arm 2: 18/368 (4.89%)

Outcome domain: atopic dermatitis

Outcome: eczema (Primary)

Follow-up time: 3 years

Arm 1: 64/338 (18.93%)

Arm 2: 15/368 (4.08%)

Outcome domain: respiratory illness

Outcome: asthma (Primary)

Follow-up time: 3 years

Arm 1: 5/338 (1.48%)

Arm 2: 6/368 (1.63%)

Peat et al., 2004167

Study name: CAPS

Study dates: 2000-2003

Study Population: 

Pregnant women whose 

unborn children were at 

high risk of developing 

asthma

Inclusion Criteria: at 

least 1 parent or 

sibling with current 

asthma or frequent 

wheeze as assessed

by screening 

Start time: Infants 6 months of age

Duration: Infants NR

Arm 1: Placebo group

Description: The control group received 

Outcome domain: atopic dermatitis

Outcome: any eczema (Secondary)

Follow-up time: 3 years

Arm 1: 81/259 (31.3%)

Arm 2: 74/267 (27.7%)
C-117

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study design: Trial 

randomized factorial 

design

Location: Australia

Funding source / 

conflict: Industry, 

Government

Study follow-up: 3 years

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2006168; 

Brew, 2015165 Toelle, 

2010169

Pregnant enrolled 616 

Pregnant withdrawals 

90 Pregnant completers 

526

Pregnant age: Placebo: 

29.1 Diet: 28.6 

(Placebo: 5.0 Diet: 5.3) 

NR

Race of Mother: NR 

(100)

questionnaire, fluency 

in English, a telephone 

at home, and 

residence within 30 km 

of the recruitment 

center.

Exclusion Criteria: a 

pet cat at home, a 

vegetarian diet, 

multiple births, and 

less than 36 weeks 

gestation.

placebo supplement capsules of Sunola oil 

containing 83% monounsaturated oils (Clover 

Corp) and were provided with widely used 

soybean-based polyunsaturated oils and 

margarines high in omega-6 fatty acids for use 

in all food preparation

Manufacturer: Clover Corp; Goodman Fielder

Blinding: The research team responsible for 

recruitment was blind to the methods of 

randomization until recruitment was complete. 

The research nurses and research assistants 

who undertook the outcome assessments, 

laboratory analyses, and statistical analyses 

were blind to the group allocation of the 

participants.

Arm 2: Active intervention group

Description: tuna fish oil capsules

Manufacturer: Clover Corp; Goodman Fielder

Dose: 500 mg tuna fish oil capsules daily

Total N-3: 184 mg

Outcome domain: respiratory illness

Outcome: any asthma (Primary)

Follow-up time: 3 years

Arm 1: 108/259 (41.7%)

Arm 2: 107/267 (40.07%)

Outcome: any cough (Primary)

Follow-up time: 3 years

Arm 1: 157/259 (60.62%)

Arm 2: 132/267 (49.44%)

Outcome: any wheeze (Secondary)

Follow-up time: 3 years

Arm 1: 108/259 (41.7%)

Arm 2: 107/267 (40.07%)

Pietrantoni et al., 201430

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Italy

Funding source / 

conflict: Government

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 300 

Pregnant completers 

255

Pregnant age: DHA 

30.86 +-4.18/placebo 

group 29.92+-4.8

Race of Mother: NR 

(NR)

Inclusion Criteria: 

Caucasians 22 to 35 

yrs, 8 week gestational 

age, single pregnancy, 

BMI between 18.5 and 

25.0kg/m2, habitual 

fish consumption 

(twice a week at least), 

high school or 

university degree, 

average 

socioeconomic status, 

absence of uterine 

abnormalities (fibroids,

Start time: Pregnant 8th weeks

Duration: Pregnant 8th week to delivery

Arm 1: Placebo

Description: Olive oil

Arm 2: DHA group

Description: DHA capsule

Dose: 2* 100mg capsule

DHA: 100mg * 2 capsule

Outcome domain: duration of gestation

Outcome: preterm-premature rupture of 

membranes (Unspecified)

Follow-up time: birth

Arm 1: 4/126 (3.2%)

Arm 2: 1/129 (0.8%)
C-118

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

cervical incompetence, 

uterine malformations 

etc.)

Exclusion Criteria: 

smoking, substance 

abuse including 

alcohol, allergy to fish 

or derivates, diabetes, 

hypertension, 

metabolic, 

cardiovascular, renal, 

psychiatric, neurologic, 

throbophilic, thyroid or 

autoimmune diseases, 

previous pregnancy 

complications 

(miscarriage, preterm 

or operative delivery), 

previous uterine 

surgery, recurrent 

genito-urinary 

infections

Ramakrishnan et al., 

201032

Study name: POSGRAD

Study dates: Feb 2005 -

Feb 2007

Study design: Trial 

randomized parallel

Location: Mexico

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 1,094 

Pregnant withdrawals 

67 Pregnant completers 

973 (for birthweight)

Pregnant age: 26.2 

(controls) 26.3 (DHA) 

(4.6 (controls) 4.8 

Inclusion Criteria: 18-

35 yrs. of age, in 

gestation weeks 18-

22, planned to deliver 

at the IMSS General 

Hospital in 

Cuernavaca, 

exclusively or 

predominantly 

breastfeed for at least 

3 months, liver in the 

area for at least 2 

Start time: Pregnant at study entry

Duration: Pregnant mid pregnancy (18-22 

weeks gestation) until delivery

Arm 1: Controls

Description: Placebo containing olive oil

Manufacturer: Martek Biosciences

Dose: 1 capsule, twice a day

Blinding: Identical tablets

Arm 2: DHA

Outcome domain: Birth weight

Outcome: birth weight (g) (Primary)

Follow-up time: birth

Arm 1: Sample size 486; mean 3202.0; 

SD (472)

Arm 2: Sample size 487; mean 3207.2; 

SD (449.4)

Outcome domain: LBW

Outcome: birthweight <2500g (Secondary)

Follow-up time: birth

Arm 1: 27/486 (5.6%)
C-119

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Funding source / 

conflict: Government, 

March of Dimes

Original, same study, or 

follow-up studies: Stein, 

201233; Imhoff-Kunsch, 

201158; EscamillaNunez, 201459; 

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561; Stein, 201134

(DHA))

Race of Mother: 

Hispanic (NR)

Baseline Omega-3 

intake: mg/day for all: 

LA: 17,846 in controls, 

17,645 in DHA AA: 137 

in controls, 140 in DHA 

ALA: 1,488 in controls, 

1,477 in DHA EPA: 18 

in controls, 18 in DHA 

DHA: 54 in controls, 56 

in DHA

years after delivery.

Exclusion Criteria: 

high-risk pregnancy; 

lipid metabolism or 

absorption disorders, 

regular intake of fish

oil or DHA 

supplements; chronic 

use of certain 

medications (e.g., 

medications for 

epilepsy).

Description: Intervention

Manufacturer: Martek Biosciences

Dose: 1 capsule twice a day

DHA: 400 mg/d, 200 mg/dl derived from algal 

source

Arm 2: 27/487 (5.5%)

Outcome domain: duration of gestation

Outcome: gestational age (weeks) 

(Primary)

Follow-up time: birth

Arm 1: Sample size 486; mean 39.1; SD 

(1.7)

Arm 2: Sample size 487; mean 39.0; SD 

(1.9)

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 40/486 (8.3%)

Arm 2: 49/487 (10.1%)

Ramakrishnan et al., 

201561

Study name: POSGRAD

Study dates: 2005-2009

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / 

conflict: Government, 

None, March of Dimes

Study follow-up: 18 

months

Original, same study, or 

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 1094 

Pregnant completers 

968

Infants enrolled 973 

Infants completers 730

Pregnant age: Placebo: 

26.3 Intervention: 26.5 

(Placebo: 4.6 

Intervention: 4.9)

Infant age: Placebo: 

20.5 weeks gestation 

Intervention: 20.6 weeks 

gestation (Placebo: 2.1 

Inclusion Criteria: 

Women who were in 

gestation week 18–22, 

age 18–35 years, 

planned to deliver at 

the IMSS General 

Hospital and to remain 

in the area for the next 

2 years, and planned 

predominant 

breastfeeding for at 

least 3 months

Exclusion Criteria: 

High risk pregnancy, 

had any lipid 

metabolism/absorption 

conditions, regularly 

took DHA or fish oil 

supplements, or used 

Start time: Pregnant 18-22 weeks gestation

Duration: Pregnant 18-22 weeks gestation until 

delivery

Arm 1: Control

Description: Corn and soy oils with no added 

antioxidants

Dose: 2 capsules/day

Blinding: Similar in appearance and taste to the 

DHA capsules

Arm 2: Intervention

Description: Algal-sourced DHA capsule

Manufacturer: Martek Biosciences

Dose: 2 capsules/day

DHA: 200 mg * 2 = 400 mg/d

Outcome domain: Cognitive development

Outcome: Bayley Mental Development 

Index (Primary)

Follow-up time: 18 months

Arm 1: Sample size 365; mean 95.2; SD 

(9.3)

Arm 2: Sample size 365; mean 94.3; SD 

(10.7)

Outcome domain: Infants born small 

gestational age

Outcome: IUGR (Secondary)

Follow-up time: birth

Arm 1: 36/365 (9.9%)

Arm 2: 39/365 (10.7%)

Outcome domain: Neurological 

development

Outcome: Bayley PDI (Primary)

Follow-up time: 18 months
C-120

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

follow-up studies: 

Ramakrishnan, 201032; 

Stein, 201233; ImhoffKunsch, 201158; 

Escamilla-Nunez, 

201459; GonzalezCasanova, 201560; 

Ramakrishnan, 201561

weeks Intervention: 2.0 

weeks)

Race of Mother: NR 

(NR)

Baseline Omega-3 

intake: From original 

study ref 3364 mg/day 

for all: LA: 17,846 in 

controls, 17,645 in DHA 

AA: 137 in controls, 140 

in DHA ALA: 1,488 in 

controls, 1,477 in DHA 

EPA: 18 in controls, 18 

in DHA DHA: 54 in 

controls, 56 in DHA

certain chronic 

medications (such as 

antiepileptic drugs)

Arm 1: Sample size 365; mean 93.3; SD 

(9.8)

Arm 2: Sample size 365; mean 93.0; SD 

(8.9)

Sala-Vila et al., 2004110

Study name: NR

Study dates: NR

Study design: Trial 

randomized parallel

Location: Spain

Funding source / 

conflict: Multiple 

foundations and 

Societies, Manufacturer 

supplied product

Study Population: 

Healthy infants

Infants enrolled 35 

Infants completers 35

Pregnant age: 28.3

Infant age: NR

Race of Mother: NR 

(100)

Inclusion Criteria: fullterm infants (37–42 wk 

gestation), of 

appropriate weight-forgestation-age

Exclusion Criteria: NR

Start time: Infants birth

Duration: Infants 3 mo

Arm 1: Human Milk (HM)

Description: breast milk with composition of 

protein carbohydrate fat ash

Arm 2: E-PL formula

Description: E-PL formula provided 10% of its 

fat from egg PLs

Brand name: Ovotin 120, Lucas Meyer

DHA: 1.25%

AA: 1.9%

Arm 3: S-TG formula

Description: single-cell (SC)-TG formula 

provided _x0004_0.3 and 0.5% of its fat from 

Outcome domain: growth

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: 3 months

Arm 1: Sample size 11; mean 41.86; SE 

(1.78)

Arm 2: Sample size 12; mean 42.01; SE 

(1.46)

Arm 3: Sample size 12; mean 43.98; SE 

(1.38)

Outcome: length (cm) (Unspecified)

Follow-up time: 3 months

Arm 1: Sample size 11; mean 60.5; SE 

(6.31)

Arm 2: Sample size 12; mean 61.08; SE 

(5.31)

Arm 3: Sample size 12; mean 60.98; SE 

(3.98)
C-121

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

TGs synthesized by single cells of algal and 

fungal microorganisms

Manufacturer: Martek Biosciences

DHA: 0.1g/100g; 0.3% of 40-45% DHASCO

AA: 0.4g/100g, 0.5% of 38-44% ARASCO

Outcome: weight (g) (Unspecified)

Follow-up time: 3 months

Arm 1: Sample size 11; mean 6460.1; SE 

(630.6)

Arm 2: Sample size 12; mean 6640.8; SE 

(741)

Arm 3: Sample size 12; mean 6491.9; SE 

(906.1)

Smithers et al., 2008104

Study name: DINO

Study dates: 2001-2004

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Manufacturer 

supplied product

Study follow-up: 2 

months, 4 months

Original, same study, or 

follow-up studies: 

Makrides, 2009116; 

Smithers, 2010117; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Study Population: 

Preterm infants

Lactating enrolled 

unclear

Infants enrolled 143 

Infants completers 125

Lactating enrolled 

unclear

Mother age: Control: 31 

Treatment: 29 (Control: 

6 Treatment: 6)

Infant age: 5 days 

(control) (mean 

gestational age at birth 

29.4 weeks) 6 days 

(Treatment) (3)

Race of Mother: NR 

(NR)

Baseline Omega-3 

intake: Intervention 

Inclusion Criteria: 

infants born_x0001_33 

wk gestation at the 

Women’s and 

Children’s Hospital of 

the Child, Youth, and 

Women’s Health 

Service, Adelaide, 

Australia, between 

April 2001 and 

September 2003

Exclusion Criteria: 

Infants with major 

congenital or 

chromosomal 

abnormalities, 

lactating mothers for 

whom tuna oil was 

contraindicated 

(women with bloodthinning disorders or 

currently taking 

anticoagulants)

Start time: Lactating approximately 5 days after 

birth Infants approximately 5 days after birth

Duration: Lactating to estimated due date 

Infants to estimated due date

Arm 1: Control group

Description: Placebo capsules and/or formula

Active ingredients: Linoleic acid 53.4% of fatty 

acids

Dose: 6 500-mg capsules per day to mothers

Blinding: The soy and tuna oil capsules were 

identical in size, color, and shape

ALA: 5.9% of total fatty acids

Arm 2: Treatment

Description: DHA supplemented breastfeeding 

mothers and/or formula

Active ingredients: Linoleic acid 2.7% of fatty 

acids

Dose: 6 capsules or formula ad lib

ALA: 0.4% total FA

DHA: 29.5% total FA

EPA: 6.5% total FA

AA: 1.8% total FA

Outcome domain: Visual function

Outcome: Visual evoked potential acuity 

(cyc/deg) (Primary)

Follow-up time: 2 months (corrected age)

Arm 1: Sample size 61; mean 5.6; SD 

(2.4)

Arm 2: Sample size 54; mean 5.6; SD 

(2.4)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 51; mean 8.2; SD 

(1.8)

Arm 2: Sample size 44; mean 9.6; SD 

(3.7)

Outcome: Visual evoked potential latency: 

48 min of arc (ms) (Secondary)

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 67; mean 138.0; SD 

(23)

Arm 2: Sample size 58; mean 135.0; SD 

(23)

Outcome: Visual evoked potential latency: 

69 min of arc (ms) (Secondary)

Follow-up time: 2 months (corrected age)

Arm 1: Sample size 66; mean 200.0; SD 

(29)

Arm 2: Sample size 58; mean 193.0; SD 

(27)
C-122

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

begun at birth: see 

below

Follow-up time: 4 months (corrected age)

Arm 1: Sample size 67; mean 131.0; SD 

(21)

Arm 2: Sample size 58; mean 129.0; SD 

(20)

Outcome: Visual evoked potential latency: 

96 min of arc (ms) (Secondary)

Follow-up time: 2 months (corrected age)

Arm 1: Sample size 66; mean 188.0; SD 

(27)

Arm 2: Sample size 58; mean 182.0; SD 

(24)

Outcome domain: growth

Reason results are not reported: duplicate 

data of id 8885

Outcome: (Secondary)

Smithers et al., 2010117

Study name: DINO

Study dates: April 2001 

through September 

2003

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Multiple foundations and 

Societies, Manufacturer 

supplied product, Some 

Study Population: 

Preterm infants

Lactating enrolled 545

Infants enrolled 657 

Infants completers 614

Lactating enrolled 545

Lactating age: 30 years 

(5.5 years) NR

Infant age: 4 days after 

birth (29 weeks 

gestation) 2 to 6 days 

after birth

Inclusion Criteria: 

infants born at < 33 wk 

of gestation

Exclusion Criteria: 

Infants born with major 

congenital or 

chromosomal 

abnormalities or born 

to lactating women for 

whom tuna oil was 

contraindicated 

(women with bleeding 

disorders or taking 

anticoagulants)

Start time: Lactating 4 days after birth Infants 4 

days after birth

Duration: Lactating until infants reached their 

"expected" date of delivery. Infants until infants 

reached their "expected" date of delivery

Arm 1: Placebo

Description: Soy oil capsules or standard 

preterm formula if not breastfeeding

Manufacturer: Clover Corporation

Dose: six 500-mg soy oil capsules

Blinding: all capsules were similar in size, 

shape, and color

DHA: Formula: 0.35%

AA: Formula: 0.6%

Total N-3: Capsules: did not change FA 

content of breastmilk

Outcome domain: Cognitive development

Outcome: MacArthur Communicative 

Development Inventory (MCDI) vocabulary 

production score (Secondary)

Follow-up time: 26 months CA

Arm 1: Sample size 67; mean 316.0; SD 

(192)

Arm 2: Sample size 60; mean 308.0; SD 

(179)
C-123

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

authors serve on 

scientific advisory 

boards for corporations, 

Some authors have 

received research 

funding from infant 

formula manufacturers

Study follow-up: 3-5 

years

Original, same study, or 

follow-up studies: 

Smithers, 2008104; 

Makrides, 2009116; 

Manley, 2011118; Collins, 

2011105; Atwell, 2013119; 

Collins, 2015120

Race of Mother: White 

European (90%) Arm 2: DHA

Description: DHA-rich tuna oil capsules or highDHA formula

Manufacturer: Clover Corporation

Dose: six 500 mg capsules per day

DHA: Capsules: Achieved breast milk 

concentration of 1.0%. Formula: 1.0%

AA: Capsules: Did not change AA in breastmilk. Formula 0.6%

Other dose 1: DHA-rich tuna oil capsules to 

achieve a breast milk DHA concentration that 

was approximately 1% of total fatty acids 

without altering the naturally occurring 

concentration of arachidonic acid (AA) in breast 

milk

Smithers et al., 201153

Study name: DOMInO

Study dates: Enrollment 

from June 2007 to 

August 2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Manufacturer supplied 

product, Some authors 

Study Population: 

Healthy infants Healthy

pregnant women

Infants enrolled 185 

Infants completers 182

Pregnant age: Tx = 29.5 

years, Placebo = 28.7 

years (Tx = 5.5 years, 

Placebo = 5.4 years) NR

Infant age: (NA) NA

Race of Mother: NR 

(NR)

Inclusion Criteria: 

singleton pregnancies 

at less than 21 weeks’ 

gestation

Exclusion Criteria: 

already taking a 

prenatal supplement 

with DHA, fetus had a 

known major 

abnormality, mother 

had a bleeding 

disorder in which tuna 

oil was 

contraindicated, 

taking anticoagulant 

therapy, history of 

Start time: Pregnant 18 to 21 weeks gestation

Duration: Pregnant until birth

Arm 1: placebo

Description: vegetable oil capsule

Manufacturer: Efamol

Dose: 3 500 mg capsules

Blinding: similar in size, shape, and color

Arm 2: Omega 3 supplement

Description: fish oil capsule

Brand name: Incromega

Manufacturer: Croda Chemicals

Dose: 3 500 mg capsules

DHA: 800/3 mg

EPA: 100/3 mg

Outcome domain: Visual function

Outcome: VEP Latency: 20 min of arc 

(ms) (Secondary)

Follow-up time: 4 months

Arm 1: Sample size 93; mean 133.0; SD 

(14)

Arm 2: Sample size 89; mean 133.0; SD 

(15)

Outcome: VEP Latency: 48 min of arc 

(ms) (Secondary)

Follow-up time: 4 months

Arm 1: Sample size 93; mean 121.0; SD 

(12)

Arm 2: Sample size 89; mean 121.0; SD 

(10)

Outcome: VEP Latency: 69 min of arc 

(ms) (Secondary)
C-124

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

serve on scientific 

advisory boards for 

corporations, Some 

authors have received 

research funding from 

infant formula 

manufacturers

Study follow-up: 4 

months

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Palmer, 201254; Zhou, 

201255; Palmer, 2013

56; 

Makrides, 2014 57

drug or alcohol abuse, 

participating in another 

fatty acid trial, unable 

to give written 

informed consent, or 

English was not the 

main language spoken 

at home

Follow-up time: 4 months

Arm 1: Sample size 93; mean 116.0; SD 

(9)

Arm 2: Sample size 89; mean 115.0; SD 

(8)

Outcome: VEP acuity (adjusted) (cyc/deg) 

(Primary)

Follow-up time: 4 months

Arm 1: Sample size 93; mean 8.55; SD 

(1.97)

Arm 2: Sample size 89; mean 8.37; SD 

(1.97)

Outcome: VEP acuity (unadjusted) 

(cyc/deg) (Primary)

Follow-up time: 4 months

Arm 1: Sample size 93; mean 8.55; SD 

(1.86)

Arm 2: Sample size 89; mean 8.37; SD 

(2.11)

Stein et al., 201134

Study name: POSGRAD

Study dates: 02. 2005-

02.2007

Study design: Trial 

randomized parallel

Location: Mexico

Funding source / 

conflict: Government, 

Multiple foundations and 

Societies

Study Population: 

Healthy infants

Pregnant enrolled 1094 

Pregnant completers 

973

Pregnant age: placebo 

26.3; DHA 26.4 

(placebo 4.6; DHA 4.9)

Infant age: 39.1 

(placebo 1.6; DHA 1.8)

Race of Mother: NR

Inclusion Criteria: 

women were 18–35 y, 

were in gestation wk 

18–22, and planned to 

deliver at the IMSS 

General Hospital in 

Cuernavaca, 

exclusively or 

predominantly breastfeed for at least 3 mo, 

and to live in the area 

for at least 2 y after 

delivery

Exclusion Criteria: NR

Start time: Pregnant 18-22 Gestational week 

Infants birth

Duration: Pregnant birth

Arm 1: Placebo

Description: Olive oil

Manufacturer: Martek Biosciences

Dose: 2 capsules olive oil

Blinding: Similar in appearance and taste to 

DHA capsules

Arm 2: DHA

Description: algal DHA capsules

Manufacturer: Martek Biosciences

Dose: 2 capsules * 200mg

Outcome domain: Birth weight

Outcome: birth weight (g) (Primary)

Follow-up time: birth

Arm 1: Sample size 370; mean 3220.0; 

SD (475)

Arm 2: Sample size 369; mean 3242.0; 

SD (441)

Outcome domain: Infants born small 

gestational age

Outcome: IUGR (intrauterine growth 

retardation); birth weight for gestational 

age < 10th percentile (Secondary)

Follow-up time: birth

Arm 1: 38/368 (10.3%)

Arm 2: 39/369 (10.6%)
C

-125

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Original, same study, or 

follow-up studies: Stein, 

201233; Imhoff-Kunsch, 

201158; Escamilla-

Nunez, 201459; 

Gonzalez-Casanova, 

201560; Ramakrishnan, 

201561; Ramakrishnan, 

201132

DHA: 400 mg

Outcome domain: LBW

Outcome: birthweight <2500g (Secondary)

Follow-up time: birth

Arm 1: 20/370 (5.4%)

Arm 2: 16/369 (4.3%)

Outcome domain: duration of gestation

Outcome: gestational age (weeks) 

(Primary)

Follow-up time: birth

Arm 1: Sample size 368; mean 39.1; SD 

(1.6)

Arm 2: Sample size 369; mean 39.1; SD 

(1.8)

Outcome: incidence of premature birth 

(Secondary)

Follow-up time: birth

Arm 1: 30/368 (8.2%)

Arm 2: 33/369 (8.9%)

Outcome domain: growth

Outcome: head circumference (cm) 

(Primary)

Follow-up time: 18 months

Arm 1: Sample size 370; mean 47.0; SD 

(1.4)

Arm 2: Sample size 369; mean 47.0; SD 

(1.5)

Outcome: length (cm) (Primary)

Follow-up time: 18 months

Arm 1: Sample size 370; mean 79.5; SD 

(2.8)

Arm 2: Sample size 369; mean 79.6; SD 

(2.8)

Outcome: weight (kg) (Primary)
C-126

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Follow-up time: 18 months

Arm 1: Sample size 370; mean 10.4; SD 

(1.2)

Arm 2: Sample size 369; mean 10.4; SD 

(1.1)

Stein et al., 201233

Study name: POSGRAD

Study dates: Feb 2005-

Feb 2007

Study design: Trial 

randomized parallel

Location: NR

Funding source / 

conflict: Government

Original, same study, or 

follow-up studies: 

Ramakrishnan, 201032; 

Imhoff-Kunsch, 201158; 

Escamilla-Nunez, 

201459; GonzalezCasanova, 201560; 

Ramakrishnan, 201561

Study Population: 

Healthy infants Healthy 

pregnant women

Pregnant enrolled 1094 

Pregnant withdrawals 

63 Pregnant completers 

900

Pregnant age: 26.3 (4.6-

4.8)

Infant age: 39.1 (1.7-

1.8)

Race of Mother: NR 

(NR)

Inclusion Criteria: 

Singleton live births 

without congenital 

anomalies

Exclusion Criteria: 

3364: high risk 

pregnancy, (history 

and prevalence of 

pregnancy 

complications, 

including abruptio 

placentae, 

preeclampsia, 

pregnancy-induced 

hypertension, any 

serious bleeding 

episode in the current 

pregnancy, and 

physician referral); 

lipid metabolism or 

absorption disorders, 

regular intake of fish 

oil or DHA 

supplement, or chronic 

use of certain 

medication(e.g.. 

epilepsy medications)

Start time: Pregnant 18-22 wk

Duration: Pregnant to birth

Arm 1: Placebo

Description: A mixture of corn and soy oil

Manufacturer: Martek Biosciences

Blinding: "Participants and members of the 

study team were unaware of the treatment 

scheme throughout the intervention period of 

the study"

Arm 2: DHA

Description: DHA 400 mg/d

Manufacturer: Martek Biosciences

Dose: 2 capsule per day

DHA: 2*200mg

Outcome domain: LBW

Outcome: birthweight <2500g (Primary)

Follow-up time: birth

Arm 1: 24/452 (5.3%)

Arm 2: 17/448 (3.8%)

Outcome domain: Neurological 

development

Outcome: auditory evoked responses: 

latency 1 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 1.63; SD 

(0.14)

Arm 2: Sample size 372; mean 1.62; SD 

(0.16)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 1.58; SD 

(0.15)

Arm 2: Sample size 330; mean 1.58; SD 

(0.15)

Outcome: auditory evoked responses: 

latency 1-3 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 2.57; SD 

(0.36)

Arm 2: Sample size 372; mean 2.56; SD 

(0.27)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 2.44; SD 

(0.28)
C

-127

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 330; mean 2.45; SD 

(0.28)

Outcome: auditory evoked responses: 

latency 1-5 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 4.93; SD 

(0.36)

Arm 2: Sample size 372; mean 4.91; SD 

(0.39)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 4.75; SD 

(0.39)

Arm 2: Sample size 330; mean 4.72; SD 

(0.39)

Outcome: auditory evoked responses: 

latency 3 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 4.19; SD 

(0.33)

Arm 2: Sample size 372; mean 4.18; SD 

(0.32)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 4.02; SD 

(0.32)

Arm 2: Sample size 330; mean 4.03; SD 

(0.33)

Outcome: auditory evoked responses: 

latency 3-5 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 2.37; SD 

(0.3)

Arm 2: Sample size 372; mean 2.37; SD 

(0.34)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 2.31; SD 

(0.35)
C

-128

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 2: Sample size 330; mean 2.28; SD 

(0.33)

Outcome: auditory evoked responses: 

latency 5 (ms) (Primary)

Follow-up time: 1 month

Arm 1: Sample size 377; mean 6.55; SD 

(0.42)

Arm 2: Sample size 372; mean 6.52; SD 

(0.48)

Follow-up time: 3 months

Arm 1: Sample size 334; mean 6.33; SD 

(0.4)

Arm 2: Sample size 330; mean 6.29; SD 

(0.42)

Outcome domain: Visual function

Outcome: Visual evoked potential: 

Amplitude P (mV) (Primary)

Follow-up time: 3 months

Arm 1: Sample size 342; mean 8.14; SD 

(6.04)

Arm 2: Sample size 337; mean 7.75; SD 

(5.97)

Follow-up time: 6 months

Arm 1: Sample size 342; mean 11.3; SD 

(6.9)

Arm 2: Sample size 337; mean 11.2; SD 

(7.2)

Outcome: Visual evoked potential: 

Latency N1 (ms) (Primary)

Follow-up time: 3 months

Arm 1: Sample size 342; mean 93.9; SD 

(17.1)

Arm 2: Sample size 337; mean 94.2; SD 

(16.3)

Follow-up time: 6 months
C-129

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 342; mean 91.9; SD 

(15.1)

Arm 2: Sample size 337; mean 90.5; SD 

(14.6)

Outcome: Visual evoked potential: 

Latency N3 (ms) (Primary)

Follow-up time: 3 months

Arm 1: Sample size 342; mean 157.1; SD 

(24.1)

Arm 2: Sample size 337; mean 154.8; SD 

(23.8)

Follow-up time: 6 months

Arm 1: Sample size 342; mean 154.9; SD 

(20.2)

Arm 2: Sample size 337; mean 154.2; SD 

(19.9)

Outcome: Visual evoked potential: 

Latency P1 (ms) (Primary)

Follow-up time: 3 months

Arm 1: Sample size 342; mean 126.3; SD 

(18.3)

Arm 2: Sample size 337; mean 125.8; SD 

(17.5)

Follow-up time: 6 months

Arm 1: Sample size 342; mean 123.5; SD 

(14.3)

Arm 2: Sample size 337; mean 122.7; SD 

(14.6)

Outcome domain: duration of gestation

Reason results are not reported: duplicate 

data of id 3364

Outcome: (Primary)

Toelle et al., 2010169 Study Population: 

Healthy infants

Inclusion Criteria: 

Pregnant women 

Start time: Infants birth Outcome domain: allergies

Outcome: atopy (Primary)
C-130

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: CAPS

Study dates: 1997-2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

Study follow-up: 8 years

Original, same study, or 

follow-up studies: 

Mihrshahi, 2003166; 

Mihrshahi, 2004167; 

Mihrshahi, 2006168; 

Brew, 2015165

Pregnant enrolled 616 

Pregnant completers

Infants enrolled 616 

Infants completers 450

Pregnant age: 28.5 

years (5.3 years)

Race of Mother: NR 

(NR)

whose unborn children 

were at high risk of 

developing asthma 

because of a family 

history (at least one 

parent or sibling with 

symptoms of asthma 

as assessed by 

screening 

questionnaire), 

reasonable fluency in 

English, telephone at 

home, reside within 30 

km from center of 

recruitment

Exclusion Criteria: Pet 

cat at home, families 

on strict vegetarian 

diet, multiple births, 

babies born earlier 

than 36 weeks 

gestation, birth weight 

below 2.5 kg, babies 

requiring surgery, 

babies requiring 

hospitalization for 

more than 1 week, 

babies with significant 

neonatal disease, 

babies with congenital 

malformations

Duration: Infants 5 years

Arm 1: Control

Description: Low-n3 capsules and cooking oils

Brand name: Sunola

Active ingredients: Capsules: 7% n-6 FA, 82% 

monounsaturated FA, 9% saturated FA, and 

1.7% minor FA; cooking oils: 40% n-6 FA, 

20% n-9 FA

Dose: Designed to maintain the current n-3 to 

n-6 ingested FA ratio in the general population 

(1:15 to 1:20)

Blinding: Similar appearance

Total N-3: Capsules: 0.3%; cooking oil: 1.2%

Arm 2: Omega 3 supplementation

Description: High n-3 FA capsules and cooking 

oils

Active ingredients: Capsules: 6% n-6 

polyunsaturated FA, 24% monounsaturated 

FA, 28% saturated FA, and 5% minor FA; 

cooking oil: 6% n-6 FA, 40% n-9 FA

Blinding: Similar appearance

N-6 N-3: 5:1

Total N-3: Capsules: 37%; cooking oil: 6%

Follow-up time: 8 yrs

Arm 1: 99/220 (45.0%)

Arm 2: 104/230 (45.1%)

Outcome: rhinitis (Secondary)

Follow-up time: 8 yrs

Arm 1: 65/220 (29.6%)

Arm 2: 70/230 (30.4%)

Outcome domain: atopic dermatitis

Outcome: eczema (Secondary)

Follow-up time: 8 yrs

Arm 1: 31/220 (14.2%)

Arm 2: 35/230 (15.3%)

Outcome domain: respiratory illness

Outcome: asthma (Primary)

Follow-up time: 8 yrs

Arm 1: 44/220 (20.0%)

Arm 2: 57/230 (24.8%)

Outcome: wheeze (Primary)

Follow-up time: 8 yrs

Arm 1: 51/220 (23.2%)

Arm 2: 73/230 (31.7%)

Tofail et al., 200677

Study name: NR

Study Population: 

Healthy infants Healthy 

pregnant women

Inclusion Criteria: 

seems as if all 

pregnant women at 25 

Start time: Pregnant 25 weeks gestation

Duration: Pregnant until birth

Outcome domain: Birth weight

Outcome: birth weight (kg) (Unspecified)

Follow-up time: birth
C-131

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study dates: Enrollment 

January to March 2000

Study design: Trial 

randomized parallel

Location: Bangladesh

Funding source / 

conflict: Government

Study follow-up: 10 

months

Pregnant enrolled 400 

Pregnant completers 

151

Pregnant age: 22.7 

years (4.35 years) NR

Race of Mother: Asian 

(100%)

weeks gestation were 

enrolled, no inclusion 

criteria specified

Exclusion Criteria: NR

Arm 1: placebo

Description: soy oil capsule

Dose: 4 one gram capsules per day

Blinding: capsules were identical in 

appearance

Other dose 1: LNA 0.27 g

Other dose 2: linoleic acid 2.25 g

Arm 2: DHA supplement

Description: fish oil capsules

Dose: 4 one gram capsules per day

DHA: 1.2 g

EPA: 1.8 g

Arm 1: Sample size 124; mean 2.7; SD 

(0.4)

Arm 2: Sample size 125; mean 2.7; SD 

(0.4)

Outcome domain: Cognitive development

Outcome: Bayley Scale of Infant 

Development (Mental developmental 

index) (Unspecified)

Follow-up time: 10 months

Arm 1: Sample size 124; mean 101.5; SD 

(7.8)

Arm 2: Sample size 125; mean 102.5; SD 

(8)

Outcome domain: Neurological 

development

Outcome: Bayley Scale of Infant 

Development (Psychomotor 

developmental index) (Unspecified)

Follow-up time: 10 months

Arm 1: Sample size 124; mean 100.5; SD 

(10.1)

Arm 2: Sample size 125; mean 101.7; SD 

(10.9)

Outcome domain: growth

Outcome: head circumference (cm) 

(Unspecified)

Follow-up time: 10 months

Arm 1: Sample size 124; mean 43.2; SD 

(1.4)

Arm 2: Sample size 125; mean 43.0; SD 

(1.4)

Unay et al., 2004138 Study Population: Inclusion Criteria: Start time: Infants week 1 Outcome domain: Neurological 
C-132

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Study name: NR

Study dates: 2000-2001

Study design: Trial 

randomized parallel

Location: Turkey

Funding source / 

conflict: NR

Healthy infants

Infants enrolled 54 

Infants completers 44

Infant age: NR (term)

Race of Mother: NR 

(NR)

healthy, full term 

newborns of 

appropriate size for 

gestational age, who 

were not going to be 

breast fed because 

that was the mother’s 

wish or because of 

maternal illness or 

medication 

incompatible with 

breast feeding just 

after birth

Exclusion Criteria: 

Perinatal asphyxia, 

central nervous 

system infection, 

congenital 

malformation, or 

significant 

hyperbilirubinaemia

Duration: Infants 16 weeks

Arm 1: Formula B

Description: Infant formula without added DHA

Brand name: Nutrilon I

Manufacturer: NV Nutricia Netherlands

Active ingredients: Linoleic acid 11.2gm/100gm 

fat

ALA: 2.2g/100g fat

AA: Trace

Arm 2: Formula A

Description: DHA-containing formula

Brand name: Farley's First MIlk

Manufacturer: HJ Heinz UK

Blinding: not reported

ALA: 1.2g/100gm

DHA: 0.5g/100gm

AA: Trace

Arm 3: Human milk

Description: Breast milk

Active ingredients: Linoleic acid: 10.85 

gm/100gm fat

ALA: 1.03gm/100g fat

DHA: 0.25 gm/100gm fat

AA: 0.46 gm/100g fat

development

Outcome: brainstem auditory evoked 

potentials: interpeak latency I-III 

(Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.25; SD (0.14)

Arm 2: Sample size 22; mean decrease 

0.34; SD (0.16)

Outcome: brainstem auditory evoked 

potentials: interpeak latency I-V 

(Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.33; SD (0.16)

Arm 2: Sample size 22; mean decrease 

0.47; SD (0.2)

Outcome: brainstem auditory evoked 

potentials: interpeak latency III-V 

(Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.08; SD (0.07)

Arm 2: Sample size 22; mean decrease 

0.14; SD (0.1)

Outcome: brainstem auditory evoked 

potentials: wave I (Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.27; SD (0.14)

Arm 2: Sample size 22; mean decrease 

0.35; SD (0.13)

Outcome: brainstem auditory evoked 

potentials: wave III (Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 
C-133

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

0.52; SD (0.15)

Arm 2: Sample size 22; mean decrease 

0.69; SD (0.16)

Outcome: brainstem auditory evoked 

potentials: wave V (Unspecified)

Follow-up time: 16 weeks

Arm 1: Sample size 22; mean decrease 

0.6; SD (0.11)

Arm 2: Sample size 22; mean decrease 

0.83; SD (0.18)

Werkman et al., 1996154

Study name: NR

Study dates: 1987-1990

Study design: Trial 

randomized parallel

Location: US

Funding source / 

conflict: Government, 

Manufacturer supplied 

product

Study follow-up: 12 

months

Study Population: 

Preterm infants

Infants enrolled 67

Infants completers 64

Mother age: 23 y (6 y)

Infant age: Born at 29 

wks gestation (2 wks)

Race of Mother: NR 

(100)

Inclusion Criteria: 

Preterm infants 

weighing between 748 

and 1398 g at birth. 

They were eligible for 

this study when they 

had tolerated enteral 

intakes > 462 kJ/kg 

body weight/day for 5-

7 days

Exclusion Criteria: 

Need for mechanical 

ventilation at that time, 

intraventricular 

hemorrhage > grade 2, 

retinopathy of 

prematurity > stage 2, 

surgery for necrotizing 

enterocolitis, a weight 

less than the fifth 

percentile for 

gestational age, and a 

history of maternal 

substance abuse

Start time: Infants 25 days

Duration: Infants 25 days - 9 months

Arm 1: Placebo term and pre-term infant 

formulas

Active ingredients: n-6: 19.1-33.2% of total FA

Dose: Formula remained the infants' major 

source of nutrients and energy through at least 

9 mo past expected term, but other foods were 

gradually added to the diet beginning at -4 mon 

past term

Blinding: NR

Total N-3: Preterm: 3% of total FA; term: 4.8% 

of total FA

Arm 2: DHA-supplemented term and pre-term 

infant formulas

Description: Marine oil replaced fat blend in 

commercial formulas

Brand name: Similac

Manufacturer: Ross Products Division

Active ingredients: 18.7-32.6% of total FA

Dose: Formula remained the infants' major 

source of nutrients and energy through at least 

Outcome domain: Cognitive development

Outcome: Fagan Test of Intelligence: 

average time/look (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 1.18; SD 

(0.05)

Arm 2: Sample size 33; mean 1.11; SD 

(0.05)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 1.75; SD 

(0.06)

Arm 2: Sample size 33; mean 1.62; SD 

(0.06)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 1.3; SD 

(0.06)

Arm 2: Sample size 33; mean 1.13; SD 

(0.05)

Outcome: Fagan Test of Intelligence: 

looks to familiar (number) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 18.8; SD 

(0.8)

Arm 2: Sample size 33; mean 21.7; SD 

(0.8)
C-134

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

9 mo past expected term, but other foods were 

gradually added to the diet beginning at -4 mon 

past term

ALA: Preterm: 3.1% of total FA; Term: 4.9% of 

total FA

DHA: 0.2% of total FA

EPA: 0.3% of total FA

Other dose 1: Preterm: 3.6% of total FA; term: 

5.4% of total FA

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 18.8; SD (1)

Arm 2: Sample size 33; mean 22.1; SD (1)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 18.2; SD 

(0.9)

Arm 2: Sample size 33; mean 21.4; SD 

(0.9)

Outcome: Fagan Test of Intelligence: 

looks to novel (number) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 23.6; SD 

(0.8)

Arm 2: Sample size 33; mean 26.0; SD 

(0.8)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 22.2; SD (1)

Arm 2: Sample size 33; mean 26.0; SD (1)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 22.1; SD 

(0.9)

Arm 2: Sample size 33; mean 25.2; SD 

(0.8)

Outcome: Fagan Test of Intelligence: 

novel time (% of total) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 64.6; SD 

(1.2)

Arm 2: Sample size 33; mean 60.5; SD 

(1.3)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 60.4; SD 

(1.4)

Arm 2: Sample size 33; mean 59.8; SD 

(1.3)

Follow-up time: 9 months
C

-135

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 1: Sample size 34; mean 62.2; SD 

(1.2)

Arm 2: Sample size 33; mean 62.2; SD 

(1.2)

Outcome: Fagan Test of Intelligence: time 

to familiar (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 16.3; SD 

(0.8)

Arm 2: Sample size 33; mean 19.3; SD 

(0.9)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 26.6; SD 

(1.1)

Arm 2: Sample size 33; mean 26.6; SD 

(1.1)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 18.2; SD (1)

Arm 2: Sample size 33; mean 18.3; SD 

(0.9)

Outcome: Fagan Test of Intelligence: time 

to novel (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 32.6; SD 

(1.2)

Arm 2: Sample size 33; mean 31.9; SD 

(1.2)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 45.3; SD 

(1.5)

Arm 2: Sample size 33; mean 45.9; SD 

(1.5)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 32.9; SD 

(1.3)

Arm 2: Sample size 33; mean 32.6; SD 
C

-136

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(1.3)

Outcome: Fagan Test of Intelligence: 

time/familiar look (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 0.85; SD 

(0.05)

Arm 2: Sample size 33; mean 0.91; SD 

(0.05)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 1.42; SD 

(0.06)

Arm 2: Sample size 33; mean 1.31; SD 

(0.06)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 1.04; SD 

(0.06)

Arm 2: Sample size 33; mean 0.91; SD 

(0.05)

Outcome: Fagan Test of Intelligence: 

time/novel look (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 1.43; SD 

(0.07)

Arm 2: Sample size 33; mean 1.27; SD 

(0.07)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 2.03; SD 

(0.09)

Arm 2: Sample size 33; mean 1.88; SD 

(0.08)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 1.51; SD 

(0.08)

Arm 2: Sample size 33; mean 1.33; SD 

(0.07)

Outcome: Fagan Test of Intelligence: total 
C

-137

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

looks (number) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 42.4; SD 

(1.3)

Arm 2: Sample size 33; mean 47.7; SD 

(1.4)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 41.0; SD 

(1.7)

Arm 2: Sample size 33; mean 48.2; SD 

(1.7)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 40.3; SD 

(1.5)

Arm 2: Sample size 33; mean 47.0; SD 

(1.5)

Outcome: Fagan Test of Intelligence: total 

time (seconds) (Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 48.9; SD 

(1.4)

Arm 2: Sample size 33; mean 51.2; SD 

(1.4)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 72.0; SD 

(1.8)

Arm 2: Sample size 33; mean 72.6; SD 

(1.7)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 51.1; SD 

(1.6)

Arm 2: Sample size 33; mean 50.9; SD 

(1.5)

Outcome domain: Visual function

Outcome: number of total looks 
C-138

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

(Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 38.4; SD 

(1.6)

Arm 2: Sample size 33; mean 38.9; SD 

(1.7)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 52.6; SD 

(2.1)

Arm 2: Sample size 33; mean 56.3; SD (2)

Follow-up time: 9 months

Arm 1: Sample size 34; mean 39.1; SD 

(1.8)

Arm 2: Sample size 33; mean 42.0; SD 

(1.8)

Outcome: time/total looks (seconds) 

(Unspecified)

Follow-up time: 12 months

Arm 1: Sample size 34; mean 1.39; SD 

(0.06)

Arm 2: Sample size 33; mean 1.34; SD 

(0.06)

Follow-up time: 6.5 months

Arm 1: Sample size 34; mean 2.01; SD 

(0.08)

Arm 2: Sample size 33; mean 1.84; SD 

(0.07)

Follow-up time: 9 month

Willatts et al., 2013170

Study name: NR

Study dates: 1992

Study design: Trial 

Study Population: 

Healthy infants

Infants enrolled 237 

Infants completers 147

Infant age: birth

Inclusion Criteria: 

Healthy term 

singletons, 37-42 

weeks gestation, 

2500-4000g 

birthweight

Start time: Infants Birth to 1 week

Duration: Infants 4 months

Arm 1: Non-LC-PUFA

Description: Control formula lacking LCPUFA

Manufacturer: Milupa GmbH

Outcome domain: Cognitive development

Outcome: Wechsler Preschool and 

Primary Scale of Intelligence: Full-Scale 

IQ (Secondary)

Follow-up time: 6 year

Arm 1: Sample size 76; mean 100.9; SD 

(16.2)
C-139

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

randomized parallel

Location: Italy, UK, 

Belgium

Funding source / 

conflict: Industry

Study follow-up: 6 years

Race of Mother: NR 

(100)

Exclusion Criteria: NR Viability: g/100 g fat

Dose: NR

Blinding: NR

ALA: 0.7

DHA: 0

AA: <0.10

Arm 2: LC-PUFA formula

Manufacturer: Milupa GmbH

Dose: NR

ALA: 0.62 g/100g fat

DHA: 0.21 g/100g fat

AA: 0.35 g/100g fat

Arm 2: Sample size 71; mean 98.0; SD 

(14.8)

Outcome: Wechsler Preschool and 

Primary Scale of Intelligence: 

Performance IQ (Secondary)

Follow-up time: 6 year

Arm 1: Sample size 76; mean 101.3; SD 

(15.5)

Arm 2: Sample size 71; mean 99.6; SD 

(13.6)

Outcome: Wechsler Preschool and 

Primary Scale of Intelligence: Verbal IQ 

(Secondary)

Follow-up time: 6 year

Arm 1: Sample size 76; mean 100.2; SD 

(16.4)

Arm 2: Sample size 71; mean 97.3; SD 

(17.5)

Zhou et al., 201255

Study name: DOMInO

Study dates: 10. 2005 -

01. 2008

Study design: Trial 

randomized parallel

Location: Australia

Funding source / 

conflict: Government, 

Multiple foundations and 

Societies, Manufacturer 

supplied product

Study Population: 

Healthy pregnant 

women

Pregnant enrolled 2399

Race of Mother: White 

European (88%;88%) 

Asian (7%;8%) Inuit 

Eskimo (2%;1%) Other 

race/ethnicity (NR)

Inclusion Criteria: NR

Exclusion Criteria: If 

already taking a 

dietary supplement 

containing DHA, their 

fetus had a known 

major abnormality, 

they had a bleeding 

disorder for which fish 

oil was 

contraindicated, they 

were receiving 

anticoagulant therapy, 

they had a 

documented history of 

drug or alcohol abuse, 

Start time: Pregnant medium gestational age 

19 weeks

Duration: Pregnant birth

Arm 1: control

Description: 500-mg vegetable oil capsules

Dose: 3*500mg 3 non-genetically modified oils 

(rapeseed, sunflower, and palm) in equal 

proportions

Blinding: All capsules were similar in size, 

shape, and color

Arm 2: DHA

Description: DHA-rich fish oil

Manufacturer: Incromega 500 TG; Croda 

Chemicals

Outcome domain: Birth weight

Outcome: birth weight (g) (Secondary)

Follow-up time: birth

Arm 1: Sample size 1202; mean 3407.0; 

SD (576)

Arm 2: Sample size 1197; mean 3475.0; 

SD (564)

Outcome domain: Gestational 

hypertension preeclampsia eclampsia

Outcome: preeclampsia (Secondary)

Follow-up time: during pregnancy

Arm 1: 58/1202 (4.85%)

Arm 2: 60/1197 (4.97%)

Outcome: pregnancy induced 

hypertension (Secondary)

Follow-up time: during pregnancy
C-140

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Original, same study, or 

follow-up studies: 

Makrides, 201035; 

Smithers, 201153; 

Palmer, 201254; Palmer, 

201356; Makrides, 2014 

57

they were participating 

in another fatty acid 

trial, or English was 

not the main language 

spoken at home

Dose: 3*500mg capsule

DHA: 800 mg

EPA: 100 mg

Arm 1: 107/1202 (8.88%)

Arm 2: 98/1197 (8.18%)

Outcome domain: Infants born small 

gestational age

Outcome: SGA for weight (Secondary)

Follow-up time: birth

Arm 1: 82/1202 (6.83%)

Arm 2: 73/1197 (6.13%)

Outcome domain: LBW

Outcome: birthweight <2500g (Secondary)

Follow-up time: birth

Arm 1: 63/1202 (5.27%)

Arm 2: 41/1197 (3.41%)

de Jong et al., 201064

Study name: Groningen 

LCPUFA study

Study dates: 1997-2008

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / 

conflict: Government

Study follow-up: 9 years

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Study Population: 

Healthy infants

Infants enrolled 474 

Infants completers 341

Infant age: Gestational 

age 39.6 wk (1.3 weeks) 

NR

Race of Mother: White 

European (100)

Inclusion Criteria: 

healthy term infants

Exclusion Criteria: 

Infants who had a 

congenital disorder 

that interfered with 

adequate functioning 

in daily life, infants 

from multiple births, 

infants whose mothers 

did not have mastery 

of the Dutch language 

or suffered from 

significant illness or 

disability, adopted and 

foster infants, and 

formula-fed infants 

who had received 

human milk for >5 d.

Start time: Infants birth

Duration: NR

Arm 1: control group

Description: standard formula

Manufacturer: Zoetermeer, Netherlands

Active ingredients: linoleic acid (11mol%); ALA 

1.27 mol%

Blinding: NR

Arm 2: Omega 3 group

Description: LCPUFA formula

Brand name: Nutrilon Premium

Manufacturer: Nutricia, Zoetermeer, The 

Netherlands

Dose: NR

DHA: 0·30 % (by weight)

AA: 0·45 % (by weight)

Outcome domain: Neurological 

development

Outcome: Touwen examination: 

neurologically normal (Unspecified)

Follow-up time: 9 years

Arm 1: 56/123 (46.0%)

Arm 2: 44/91 (48.0%)
C-141

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Bouwstra, 200563; de 

Jong, 201265; van Goor, 

201036; Goor, 201166

Arm 3: Breast fed group

Description: Breast feeding only - no formula
C-142

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

de Jong et al., 201265

Study name: Groningen 

LCPUFA study

Study dates: Enrollment 

from February 1997 

through October 1999, 

follow-up 9 years later

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / 

conflict: Industry, 

Government, Some 

authors have received 

research funding from 

infant formula 

manufacturers

Study follow-up: 9 years

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; van Goor, 

201036; Goor, 201166

Study Population: 

Healthy infants

Infants enrolled 314 

Infants completers 214

Mother age: 31 years (5 

years) NR

Infant age: birth (NA) 

NA

Race of Mother: White 

European (100%)

Inclusion Criteria: 

healthy infants

Exclusion Criteria: 

infants who had a 

congenital disorder 

that interfered with 

adequate functioning 

in daily life, infants 

from multiple births, 

infants whose mothers 

did not have mastery 

of the Dutch language 

or suffered from 

significant illness or 

disability, adopted and 

foster infants, and 

formula-fed infants 

who had received 

human milk for >5 d.

Start time: Infants birth

Duration: Infants 2 months

Arm 1: Control formula

Description: Standard formula with no 

supplemental LCPUFA

Brand name: Nutrilon premium

Manufacturer: Nutricia, Zoetermeer, 

Netherlands

Active ingredients: linoleic acid (11mol%); ALA 

1.27 mol%

Blinding: NR

Maternal conditions

Current smoker 23% during pregnancy

Other maternal conditions 

1arm_1_maternal_conditions_other1

Other maternal conditions 10 maternal 

hypertension 17%

Arm 2: Omega 3 supplemented formula

Description: LCPUFA formula

Manufacturer: Nutricia, Zoetermeer, 

Netherlands

Active ingredients: linoleic acid (11mol%); ALA 

1.30 mol%

Maternal conditions

DHA: 0.30% by weight

AA: 0.45% by weight

Current smoker 32% during pregnancy

Other maternal conditions 

1arm_2_maternal_conditions_other1

Other maternal conditions 10 maternal 

hypertension 12%

Outcome domain: Cognitive development

Reason results are not reported: No 

usable data.

Outcome: (Secondary)
C-143

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Arm 3: breastfeeding comparison group

Maternal conditions

Current smoker 10% during pregnancy

Other maternal conditions 

1arm_3_maternal_conditions_other1

Other maternal conditions 10 maternal 

hypertension 9%

van Goor et al., 201036

Study name: Groningen 

LCPUFA study

Study dates: Enrollment 

from December 2004 

until December 2006

Study design: Trial 

randomized parallel

Location: Netherlands

Funding source / 

conflict: Industry, 

Government

Study follow-up: 12 

weeks

Original, same study, or 

follow-up studies: 

Bouwstra, 200362; 

Bouwstra, 200563; de 

Jong, 201064; de Jong, 

201265; Goor, 201166

Study Population: 

Healthy pregnant 

women Breast-feeding 

women

Pregnant enrolled 183 

Pregnant completers 

125

Infants completers 119

Pregnant age: 32 years 

(5 years)

Infant age: 14 to 20 

weeks gestation

Race of Mother: NR 

(100)

Inclusion Criteria: 

healthy women with a 

first or second low-risk 

singleton pregnancy

Exclusion Criteria: 

women with 

vegetarian or vegan 

diets and women with 

diabetes mellitus

Start time: Pregnant 14 to 20 weeks gestation 

Infants 14 to 20 weeks gestation

Duration: Pregnant until 3 months after delivery 

Infants until 3 months of age

Arm 1: placebo

Description: soybean oil capsule

Manufacturer: Wuhan Alking Bioengineering

Active ingredients: standard dose vitamins and 

minerals

Dose: 2 capsules

Maternal conditions

ALA: 60 mg

DHA: 0

EPA: 0

AA: 0

Other dose 1: LA 535 mg

Current smoker 2%

Arm 2: DHA group

Description: DHA fish oil capsule

Manufacturer: Wuhan Alking Bioengineering

Active ingredients: standard dose vitamins and 

minerals

Dose: 2 capsules

Maternal conditions

ALA: 32 mg

Outcome domain: Neurological 

development

Outcome: general movements: number 

definitely abnormal (Secondary)

Follow-up time: 12 weeks

Arm 1: 0/36 (0.0%)

Arm 2: 1/42 (2.38%)

Arm 3: 0/41 (0.0%)

Follow-up time: 2 weeks

Arm 1: 1/36 (2.78%)

Arm 2: 0/42 (0.0%)

Arm 3: 0/41 (0.0%)

Outcome: general movements: number 

mildly abnormal (Secondary)

Follow-up time: 12 weeks

Arm 1: 11/36 (30.56%)

Arm 2: 25/42 (59.52%)

Arm 3: 14/41 (34.15%)

Follow-up time: 2 weeks

Arm 1: 11/36 (30.56%)

Arm 2: 20/42 (47.62%)

Arm 3: 15/41 (36.59%)

Outcome: general movements: number 

normal optimal (Secondary)

Follow-up time: 12 weeks

Arm 1: 2/36 (5.56%)

Arm 2: 0/42 (0.0%)

Arm 3: 1/41 (2.44%)
C-144

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

DHA: 220 mg

EPA: 34 mg

AA: 15 mg

Other dose 2: LA 274 mg

Current smoker 2%

Arm 3: DHA + AA group

Description: DHA + AA capsule

Brand name: Marinol D40

Manufacturer: Lipid Nutrition B.V., 

Wormerveer, The Netherlands

Active ingredients: standard dose vitamins and 

minerals

Dose: 2 capsules

Maternal conditions

ALA: 7 mg

DHA: 220 mg

EPA: 36 mg

AA: 220 mg

Other dose 2: LA 46 mg

Current smoker 3%

Follow-up time: 2 weeks

Arm 1: 1/36 (2.78%)

Arm 2: 0/42 (0.0%)

Arm 3: 1/41 (2.44%)

Outcome: general movements: number 

normal suboptimal (Secondary)

Follow-up time: 12 weeks

Arm 1: 23/36 (63.89%)

Arm 2: 16/42 (38.1%)

Arm 3: 26/41 (63.41%)

Follow-up time: 2 weeks

Arm 1: 19/36 (52.78%)

Arm 2: 17/42 (40.48%)

Arm 3: 22/41 (53.66%)

Outcome: neonatal neurological 

classification: number definitely abnormal 

(Secondary)

Follow-up time: 2 weeks

Arm 1: 0/36 (0.0%)

Arm 2: 0/42 (0.0%)

Arm 3: 0/41 (0.0%)

Outcome: neonatal neurological 

classification: number mildly abnormal 

(Secondary)

Follow-up time: 2 weeks

Arm 1: 7/36 (19.44%)

Arm 2: 6/42 (14.29%)

Arm 3: 8/41 (19.51%)

Outcome: neonatal neurological 

classification: number normal (Secondary)

Follow-up time: 2 weeks

Arm 1: 28/36 (77.78%)

Arm 2: 35/42 (83.33%)

Arm 3: 33/41 (80.49%)

Outcome domain: duration of gestation
C-145

Author, Year,

Study,

Location,

Funding Source,

Follow-up

Population and 

participant information

Inclusion and 

Exclusion Criteria

Start time,

Duration,

Arms Results

Outcome: gestational age birth (weeks) 

(Secondary)

Follow-up time: birth

Arm 1: Sample size 36; mean 40.2; SD (1)

Arm 2: Sample size 42; mean 40.2; SD 

(1.1)

Arm 3: Sample size 41; mean 40.2; SD 

(1.1)
Appendix D. Evidence Table for Observational Studies
D-2

Table D1. Evidence table for observational studies

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Badart-Smook, et al., 199747

Study dates: NR

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: NR

Study Population: Healthy infants Healthy pregnant women

Pregnant enrolled 610 Pregnant withdrawals 240 Pregnant 

completers 370

Pregnant age: 29 (4)

Race of Mother: White European (100)

Inclusion Criteria: White race, intention to give birth to the baby in 

one of the three hospitals involved in the study

Exclusion Criteria: Women with diastolic blood pressure of 90mm or 

higher, women suffering from any metabolic, cardiovascular, 

neurological, or renal disorder

Adjustments: Maternal(pregnancy) 

body weight, height, age, smoking 

habits, education, parity, and sex of 

the infant were included in each 

multiple regression model as possible 

confounding factors; except for the 

regression equation with gestational 

age as a dependent variable, 

gestational age at birth was also 

added as a confounder

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Badart-Smook 

199747

Birth weight

N Total: 370

Sum of n-3 PUFAs+AA

n-3 Measure: FFQ

Length of gestation

N Total: 370

Sum of n-3 PUFAs+AA

n-3 Measure: FFQ
D-3

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Bakker, et al., 2003163

Study name: Maastricht Essential Fatty Acid Birth (MEFAB) 

Cohort

Study dates: Recruitment December 1990 to January 1994

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Government

Follow-up: 7 years

Original, same study, or follow-up studies: Bakker, 2009134

and two articles in original report: Ghys, 2002 and Al, 1995

Study Population: Healthy infants

Infants enrolled 750 Infants withdrawals 444 Infants 

completers 306

Pregnant age: 29.8 (4.1)

Infant age: birth

Race of Mother: White European (100)

Inclusion Criteria: 750 Caucasian children, 7 y old, born between 

December 1990 and January 1994 in the course of an earlier study 

on maternal and neonatal LCPUFA status and pregnancy outcome

Exclusion Criteria: Not reported

Adjustments: Social class, maternal 

intelligence, parenting skills, maternal 

smoking and drinking habits during 

pregnancy, breastfeeding duration, 

and the child’s sex, birth order and 

birthweight

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Bakker 2003163 Cognitive function K-ABC Mental 7 years AA

n-3 Measure: Umbilical plasma

n-3 Units: %wt/wt

All Coefficient

Estimate: -0.223

95% CI(-1.051,-0.605)

Cognitive function K-ABC Mental

N Total: 306

7 years DHA

n-3 Measure: Umbilical plasma

n-3 Units: % wt/wt

All Coefficient

Estimate: -0.517

95% CI(-1.471, -0.437)

Cognitive function K-ABC Sequential 7 years AA

n-3 Measure: Umbilical plasma

All Coefficient

Estimate: 0.035

95% CI(-0.886, -0.956)

Cognitive function K-ABC Sequential 7 years DHA

n-3 Measure: Umbilical plasma

All Coefficient

Estimate: -0.072

95% CI(-1.104, – 0.960)

Cognitive function K-ABC Simultaneous 7 years AA

n-3 Measure: Umbilical plasma

All Coefficient

Estimate: -0.34

95% CI(-1.156, 0.476)

Cognitive function K-ABC Simultaneous 7 years DHA

n-3 Measure: Umbilical plasma

All Coefficient

Estimate: -0.61

95% CI(-1.557, -0.337)
D-4

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Bakker, et al., 2009134

Study dates: 12/90-1/94

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Government

Follow-up: 7 years

Original, same study, or follow-up studies: Bakker, 200380 and 

two articles in original report: Ghys, 2002 and Al, 1995

Study Population: Healthy infants

Infants enrolled 750 Infants withdrawals 444 Infants 

completers 306

Pregnant age: 29.8 (4.1)

Infant age: gestational age: boys: 39.8; girls 40.0 (boys 1.7; 

girls 1.4)

Race of Mother: White European (100)

Inclusion Criteria: 750 Caucasian children of 7 y old, born between 

December 1990 and January 1994 in the course of an earlier study 

on maternal and neonatal LCPUFA status and pregnancy outcome

Exclusion Criteria: Not reported

Adjustments: Gender, cognitive 

function, gestational age, age at 

measurement

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Bakker 2009134 Maastricht Motor test quality score

N Total: 306

7 years AA

n-3 Measure: Umbilical plasma

n-3 Units: %wt/wt

Coefficient P value: P=0.052

Maastricht Motor test quality score

N Total: 306

7 years DHA

n-3 Measure: Umbilical plasma

n-3 Units: %wt/wt

Coefficient P value: P=0.01

Maastricht Motor test quantity score

N Total: 306

7 years AA

n-3 Measure: Umbilical plasma

n-3 Units: %wt/wt

Coefficient P value: P=0.78

Maastricht Motor test quantity score

N Total: 306

7 years DHA

n-3 Measure: Umbilical plasma

n-3 Units: %wt/wt

Coefficient P value: P=0.30

Maastricht Motor test total score

N Total: 306

7 years AA

n-3 Measure: Umbilical plasma

n-3 Units: %wt/wt

Coefficient P value: P=0.069

Maastricht Motor test total score

N Total: 306

7 years DHA

n-3 Measure: Umbilical plasma

n-3 Units: %wt/wt

Coefficient P value: P=0.01
D-5

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Bernard, et al., 201389

Study name: EDEN

Study dates: Recruitment 2003 to 2005

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Follow-up: 2 and 3 years

Original, same study, or follow-up studies: Drouillet, 200980

Study Population: Healthy pregnant women

Pregnant enrolled 2,002 Pregnant completers 1,882

Infants enrolled 1.882 Infants completers 1,510

Pregnant age: 29.2 years (at conception) (4.8 years) NR

Infant age: < 24 weeks gestation (NR) NR

Race of Mother: NR (100)

Inclusion Criteria: < 24 weeks amenorrhea

Exclusion Criteria: multiple pregnancies, known diabetes before 

pregnancy, illiteracy, and intention to move outside the region in the 

next 3 years

Adjustments: Center, child gender & 

age, gestational age, maternal age, 

obesity, energy intake, tobacco & 

alcohol consumption, parental 

education & income, first born, main 

daytime caregiver, and frequency of 

maternal stimulations

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Bernard, 201389 Ages and Stages Questionnaire - Breastfed children

N Total: 786

3 years (LC)PUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.19

95% CI(-0.76, 0.38)

P value: 0.51

Ages and Stages Questionnaire - Breastfed children

N Total: 786

3 years AA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.09

95% CI(-29.53, 29.35)

P value: 1

Ages and Stages Questionnaire - Breastfed children

N Total: 786

3 years ALA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 3.29

95% CI(-8.41, 14.99)

P value: 0.58

Ages and Stages Questionnaire - Breastfed children

N Total: 786

3 years DHA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 7.48

95% CI(-10.51, 25.47)

P value: 0.42

Ages and Stages Questionnaire - Breastfed children

N Total: 786

3 years EPA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 15.28

95% CI(-18.63, 49.19)

P value: 0.38

Ages and Stages Questionnaire - Breastfed children

N Total: 786

3 years LA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.23

95% CI(-0.82, 0.36)

P value: 0.45

Ages and Stages Questionnaire - Breastfed children

N Total: 786

3 years n-3 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 3.61

95% CI(-4.17, 11.39)

P value: 0.36

Ages and Stages Questionnaire - Breastfed children

N Total: 786

3 years n-6 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.22

95% CI(-0.81, 0.37)

P value: 0.45

Ages and Stages Questionnaire - Breastfed children

N Total: 786

3 years n-6:n-3

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.63

95% CI(-1.39, 0.13)

P value: 0.11
D-6

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Ages and Stages Questionnaire - Never-breastfed 

children

N Total: 270

3 years (LC)PUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.33

95% CI(-2.58, -0.08)

P value: 0.04

Ages and Stages Questionnaire - Never-breastfed 

children

N Total: 270

3 years AA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -104.25

95% CI(-162.11, -46.39)

P value: 0.001

Ages and Stages Questionnaire - Never-breastfed 

children

N Total: 270

3 years ALA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.39

95% CI(-31.22, 26.44)

P value: 0.87

Ages and Stages Questionnaire - Never-breastfed 

children

N Total: 270

3 years DHA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.77

95% CI(-49.10, 45.56)

P value: 0.94

Ages and Stages Questionnaire - Never-breastfed 

children

N Total: 270

3 years EPA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 24.51

95% CI(-60.08, 109.10)

P value: 0.57

Ages and Stages Questionnaire - Never-breastfed 

children

N Total: 270

3 years LA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.34

95% CI(-2.65, -0.03)

P value: 0.05

Ages and Stages Questionnaire - Never-breastfed 

children

N Total: 270

3 years n-3 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.43

95% CI(-21.52, 16.66)

P value: 0.8

Ages and Stages Questionnaire - Never-breastfed 

children

N Total: 270

3 years n-6 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.37

95% CI(-2.68, -0.06)

P value: 0.04

Ages and Stages Questionnaire - Never-breastfed 

children

N Total: 270

3 years n-6:n-3

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.52

95% CI(-3.01, -0.03)

P value: 0.05

Communicative Development Inventory - Neverbreastfed children

N Total: 309

3 years (LC)PUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.13

95% CI(-2.21, -0.05)

P value: 0.04

Communicative Development Inventory - Neverbreastfed children

N Total: 309

3 years AA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -33.93

95% CI(-83.64, 15.78)

P value: 0.18

Communicative Development Inventory - Neverbreastfed children

N Total: 309

3 years ALA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 13.84

95% CI(-10.21, 37.89)

P value: 0.26

Communicative Development Inventory - Neverbreastfed children

N Total: 309

3 years DHA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 6.14

95% CI(-32.79, 45.07)

P value: 0.76

Communicative Development Inventory - Neverbreastfed children

N Total: 309

3 years EPA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 13.98

95% CI(-57.56, 85.52)

P value: 0.7

Communicative Development Inventory - Neverbreastfed children

N Total: 309

3 years LA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.23

95% CI(-2.37, -0.09)

P value: 0.03

Communicative Development Inventory - Neverbreastfed children

N Total: 309

3 years n-3 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 7.02

95% CI(-9.13, 23.17)

P value: 0.39
D-7

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Communicative Development Inventory - Neverbreastfed children

N Total: 309

3 years n-6 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.24

95% CI(-2.36, -0.12)

P value: 0.03

Communicative Development Inventory - Neverbreastfed children

N Total: 309

3 years n-6:n-3

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.13

95% CI(-3.40, -0.86)

P value: 0.001

Communicative Development Inventory -Breastfed 

children

N Total: 901

3 years (LC)PUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 0.23

95% CI(-0.34, 0.80)

P value: 0.43

Communicative Development Inventory -Breastfed 

children

N Total: 901

3 years AA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 6.29

95% CI(-22.56, 35.14)

P value: 0.67

Communicative Development Inventory -Breastfed 

children

N Total: 901

3 years ALA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.77

95% CI(-14.65, 9.11)

P value: 0.65

Communicative Development Inventory -Breastfed 

children

N Total: 901

3 years DHA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -3.63

95% CI(-21.72, 14.46)

P value: 0.69

Communicative Development Inventory -Breastfed 

children

N Total: 901

3 years EPA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -8.55

95% CI(-42.77, 25.67)

P value: 0.62

Communicative Development Inventory -Breastfed 

children

N Total: 901

3 years LA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 0.25

95% CI(-0.34, 0.84)

P value: 0.4

Communicative Development Inventory -Breastfed 

children

N Total: 901

3 years n-3 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.23

95% CI(-10.07, 5.61)

P value: 0.58

Communicative Development Inventory -Breastfed 

children

N Total: 901

3 years n-6 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 0.25

95% CI(-0.34, 0.84)

P value: 0.4

Communicative Development Inventory -Breastfed 

children

N Total: 901

3 years n-6:n-3

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 0.38

95% CI(-0.40, 1.16)

P value: 0.34

Motor ability

N Total: 257

3 years (LC)PUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.17

95% CI(-0.6924, 1.0324)

Motor ability

N Total: 257

3 years AA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 5.07

95% CI(3.8744, 6.2656)

Motor ability

N Total: 257

3 years ALA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.3

95% CI(-2.8288, 0.2288)

Motor ability

N Total: 257

3 years DHA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -4.35

95% CI(-5.526, -3.174)
D-8

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Motor ability

N Total: 257

3 years EPA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -10.55

95% CI(-11.4908, -9.6092)

Motor ability

N Total: 257

3 years LA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.17

95% CI(-0.6924, 1.0324)

Motor ability

N Total: 257

3 years n-3 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.72

95% CI(-2.896, -0.544)

Motor ability

N Total: 257

3 years n-6 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.17

95% CI(-0.6728, 1.0128)

Motor ability

N Total: 257

3 years n-6:n-3

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.49

95% CI(0.3724, 0.6076)

Motor ability

N Total: 746

3 years (LC)PUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.1

95% CI(-0.1156, 0.3156)

Motor ability

N Total: 746

3 years AA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -7.67

95% CI(-19.3124, 3.9724)

Motor ability

N Total: 746

3 years ALA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.29

95% CI(-4.4336, 5.0136)

Motor ability

N Total: 746

3 years DHA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -3.26

95% CI(-10.5316, 4.0116)

Motor ability

N Total: 746

3 years EPA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -9.8

95% CI(-23.5004, 3.9004)

Motor ability

N Total: 746

3 years LA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.12

95% CI(-0.1152, 0.3552)

Motor ability

N Total: 746

3 years n-3 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.11

95% CI(-4.2264, 2.0064)
D-9

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Motor ability

N Total: 746

3 years n-6 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.12

95% CI(-0.1152, 0.3552)

Motor ability

N Total: 746

3 years n-6:n-3

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.3

95% CI(-0.0136, 0.6136)

Neurological development

N Total: 270

3 years AA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -104.25

95% CI(-162.1092, -

46.3908)

Neurological development

N Total: 270

3 years AA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -104.25

95% CI(-162.1092, -

46.3908)

Neurological development

N Total: 270

3 years ALA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.39

95% CI(-31.2216, 

26.4416)

Neurological development

N Total: 270

3 years ALA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -2.39

95% CI(-31.2216, 

26.4416)

Neurological development

N Total: 270

3 years DHA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.77

95% CI(-49.104, 45.564)

Neurological development

N Total: 270

3 years DHA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.77

95% CI(-49.104, 45.564)

Neurological development

N Total: 270

3 years EPA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 24.51

95% CI(-60.0836, 

109.1036)

Neurological development

N Total: 270

3 years EPA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 24.51

95% CI(-60.0836, 

109.1036)

Neurological development

N Total: 270

3 years LA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.34

95% CI(-2.6532, -

0.0267999999999999)

Neurological development

N Total: 270

3 years LA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.34

95% CI(-2.6532, -

0.0267999999999999)
D-10

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Neurological development

N Total: 270

3 years LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.33

95% CI(-2.5844, -

0.0756000000000001)

Neurological development

N Total: 270

3 years LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.33

95% CI(-2.5844, -

0.0756000000000001)

Neurological development

N Total: 270

3 years n-3 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.43

95% CI(-21.5204, 

16.6604)

Neurological development

N Total: 270

3 years n-3 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -2.43

95% CI(-21.5204, 

16.6604)

Neurological development

N Total: 270

3 years n-6 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.37

95% CI(-2.6832, -0.0568)

Neurological development

N Total: 270

3 years n-6 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.37

95% CI(-2.6832, -0.0568)

Neurological development

N Total: 270

3 years n-6:n-3

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.52

95% CI(-3.0096, -0.0304)

Neurological development

N Total: 270

3 years n-6:n-3

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.52

95% CI(-3.0096, -0.0304)

Neurological development

N Total: 309

2 years AA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -33.93

95% CI(-83.6356, 

15.7756)

Neurological development

N Total: 309

2 years AA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -33.93

95% CI(-83.6356, 

15.7756)

Neurological development

N Total: 309

2 years ALA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 13.84

95% CI(-10.2092, 

37.8892)

Neurological development

N Total: 309

2 years ALA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 13.84

95% CI(-10.2092, 

37.8892)

Neurological development

N Total: 309

2 years DHA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 6.14

95% CI(-32.7856, 

45.0656)
D-11

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Neurological development

N Total: 309

2 years DHA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 6.14

95% CI(-32.7856, 

45.0656)

Neurological development

N Total: 309

2 years EPA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 13.98

95% CI(-57.56, 85.52)

Neurological development

N Total: 309

2 years EPA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 13.98

95% CI(-57.56, 85.52)

Neurological development

N Total: 309

2 years LA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.23

95% CI(-2.3668, -

0.0932000000000002)

Neurological development

N Total: 309

2 years LA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.23

95% CI(-2.3668, -

0.0932000000000002)

Neurological development

N Total: 309

2 years LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.13

95% CI(-2.208, -

0.0519999999999998)

Neurological development

N Total: 309

2 years LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.13

95% CI(-2.208, -

0.0519999999999998)

Neurological development

N Total: 309

2 years n-3 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 7.02

95% CI(-9.1304, 23.1704)

Neurological development

N Total: 309

2 years n-3 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 7.02

95% CI(-9.1304, 23.1704)

Neurological development

N Total: 309

2 years n-6 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -1.24

95% CI(-2.3572, -0.1228)

Neurological development

N Total: 309

2 years n-6 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -1.24

95% CI(-2.3572, -0.1228)

Neurological development

N Total: 309

2 years n-6:n-3

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.13

95% CI(-3.404, -0.856)

Neurological development

N Total: 309

2 years n-6:n-3

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -2.13

95% CI(-3.404, -0.856)
D-12

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Neurological development

N Total: 786

3 years AA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.09

95% CI(-29.5292, 

29.3492)

Neurological development

N Total: 786

3 years AA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -0.09

95% CI(-29.5292, 

29.3492)

Neurological development

N Total: 786

3 years ALA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 3.29

95% CI(-8.4112, 14.9912)

Neurological development

N Total: 786

3 years ALA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 3.29

95% CI(-8.4112, 14.9912)

Neurological development

N Total: 786

3 years DHA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 7.48

95% CI(-10.5128, 

25.4728)

Neurological development

N Total: 786

3 years DHA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 7.48

95% CI(-10.5128, 

25.4728)

Neurological development

N Total: 786

3 years EPA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 15.28

95% CI(-18.628, 49.188)

Neurological development

N Total: 786

3 years EPA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 15.28

95% CI(-18.628, 49.188)

Neurological development

N Total: 786

3 years LA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.23

95% CI(-0.818, 0.358)

Neurological development

N Total: 786

3 years LA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -0.23

95% CI(-0.818, 0.358)

Neurological development

N Total: 786

3 years LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.19

95% CI(-0.7584, 0.3784)

Neurological development

N Total: 786

3 years LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -0.19

95% CI(-0.7584, 0.3784)

Neurological development

N Total: 786

3 years n-3 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 3.61

95% CI(-4.1712, 11.3912)
D-13

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Neurological development

N Total: 786

3 years n-3 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 3.61

95% CI(-4.1712, 11.3912)

Neurological development

N Total: 786

3 years n-6 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.22

95% CI(-0.808, 0.368)

Neurological development

N Total: 786

3 years n-6 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -0.22

95% CI(-0.808, 0.368)

Neurological development

N Total: 786

3 years n-6:n-3

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -0.63

95% CI(-1.3944, 0.1344)

Neurological development

N Total: 786

3 years n-6:n-3

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -0.63

95% CI(-1.3944, 0.1344)

Neurological development

N Total: 901

2 years AA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 6.29

95% CI(-22.5612, 

35.1412)

Neurological development

N Total: 901

2 years AA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 6.29

95% CI(-22.5612, 

35.1412)

Neurological development

N Total: 901

2 years ALA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.77

95% CI(-14.6476, 9.1076)

Neurological development

N Total: 901

2 years ALA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -2.77

95% CI(-14.6476, 9.1076)

Neurological development

N Total: 901

2 years DHA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -3.63

95% CI(-21.7208, 

14.4608)

Neurological development

N Total: 901

2 years DHA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -3.63

95% CI(-21.7208, 

14.4608)

Neurological development

N Total: 901

2 years EPA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -8.55

95% CI(-42.7716, 

25.6716)

Neurological development

N Total: 901

2 years EPA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -8.55

95% CI(-42.7716, 

25.6716)
D-14

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Neurological development

N Total: 901

2 years LA

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 0.25

95% CI(-0.338, 0.838)

Neurological development

N Total: 901

2 years LA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.25

95% CI(-0.338, 0.838)

Neurological development

N Total: 901

2 years LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 0.23

95% CI(-0.3384, 0.7984)

Neurological development

N Total: 901

2 years LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.23

95% CI(-0.3384, 0.7984)

Neurological development

N Total: 901

2 years n-3 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: -2.23

95% CI(-10.07, 5.61)

Neurological development

N Total: 901

2 years n-3 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: -2.23

95% CI(-10.07, 5.61)

Neurological development

N Total: 901

2 years n-6 LCPUFAs

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 0.25

95% CI(-0.338, 0.838)

Neurological development

N Total: 901

2 years n-6 LCPUFAs

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.25

95% CI(-0.338, 0.838)

Neurological development

N Total: 901

2 years n-6:n-3

n-3 Measure: FFQ

n-3 Units: g/d

Coefficient

Estimate: 0.38

95% CI(-0.404, 1.164)

Neurological development

N Total: 901

2 years n-6:n-3

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: g/d

All Coefficient

Estimate: 0.38

95% CI(-0.404, 1.164)
D-15

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Bouwstra, et al., 2006133

Study dates: 1997-1999

Study design: NR

Location: Netherlands

Funding source / conflict: Industry

Follow-up: 3 months

Original, same study, or follow-up studies: Bouwstra, 200362

Study Population: Healthy infants

Infants enrolled 317 Infants completers 269

Pregnant age: 30 (4.3)

Infant age: 3 months (NR)

Race of Mother: White European (100)

Inclusion Criteria: All infants were born at 37–42 wk of gestation, 

had a native West European origin, and were born between 

February 1997 and October 1999.

Exclusion Criteria: children with a congenital disorder interfering 

with adequate functioning in daily life, children from multiple births, 

children whose mother did not master the Dutch language or had 

significant illness or disability, and adopted and fostered children

Adjustments: Type of postnatal 

feeding and potential confounders 

such as the postnatal age of the infant 

at GM assessment, paternal smoking, 

and the total Obstetric Optimality 

Score

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Bouwstra 2003133 General movement (mildly abnormal)

N Total: 269

3 months AA

n-3 Measure: umbilical artery

All Standardized coefficients

Estimate: 0.81

95% CI(0.68, 0.98)

General movement (mildly abnormal)

N Total: 269

3 months DHA deficiency index

n-3 Measure: umbilical artery

All Standardized coefficients

Estimate: 2

95% CI(0.73, 5.2)

General movement (mildly abnormal)

N Total: 269

3 months DHA

n-3 Measure: umbilical artery

All Standardized coefficients

Estimate: 0.74

95% CI(0.48, 1.1)
D-16

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Brantsaeter, et al., 201281

Study name: Norwegian Mother and Child Cohort Study 

(MoBa)

Study dates: 2002-2009

Study design: Observational prospective

Location: Norway

Funding source / conflict: Government

Study Population: Healthy infants Healthy pregnant women

Pregnant enrolled 76218 Pregnant completers 62099

Race of Mother: NR

Inclusion Criteria: first participation for women with multiple 

participation in MoBa and women with singleton births.

Exclusion Criteria: participants with a pregnancy duration <28 

weeks or >42 weeks (n=628), if the birth weight of the baby 

had not been recorded or if the birth weight was, <600 g ( n = 

35). We also excluded participants who had not given birth to a 

live baby ( n 153). Lastly, we excluded women having improbable 

energy intakes, i.e. energy intake , >4·5 MJ or .<20 MJ ( n 1063)

Adjustments: Adjusted for maternal 

age, height, pre-pregnant BMI, parity, 

pregnancy duration, maternal 

education, smoking status, mother 

tongue other than Norwegian and total 

energy intake, and with intakes of 

seafood/seafood items and 

supplementary n-3 mutually adjusted

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Brantsaeter 201281 Birth weight

N Total: 61387

n-3 supplement

n-3 Measure: FFQ

n-3 Units: g/day

0 (No)

N Quantile: NR

N Cases: NR

Birth weight

N Total: 61387

n-3 supplement

n-3 Measure: FFQ

n-3 Units: g/day

0.40 - 6.9

N Quantile: NR

N Cases: NR

0.74

95% CI(-7.6, 9.07)

Birth weight

N Total: 61387

n-3 supplement

n-3 Measure: FFQ

n-3 Units: g/day

< 0.39

N Quantile: NR

N Cases: NR

-2.03

95% CI(-10.4, 6.29)

Birth weight

N Total: 61387

n-3 supplement

n-3 Measure: FFQ

n-3 Units: g/day

Per g increase

N Quantile: NR

N Cases: NR

Coefficient

Estimate: 0.53

95% CI(-3.25, 4.31)
D-17

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Chong, et al., 201595

Study dates: 2009-2010

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Follow-up: 3 months postpartum

Study Population: Healthy pregnant women Postpartum 

women

Pregnant enrolled 997 Pregnant completers 698

Pregnant age: NR (NR)

Race of Mother: Asian (100)

Inclusion Criteria: Within range of 18-50 years, recruited from 2 

major public maternity units in NUH and KKH. Were Singaporean 

citizens or permanent resident of Chinese, Malay, Indian ethnicity 

with parents of homogeneous ethnic background, with the intention 

to deliver in the two hospitals and residing in Singapore for next 5 

years and willing to donate birth tissues including cord, placenta, 

cord blood at delivery

Exclusion Criteria: pre-existing health conditions such as type 1 

diabetes, depression, or mental health related disorders selfreported during recruitment

Adjustments: Adjusted for ethnicity, 

parity, education level, marital status, 

maternal body mass index at 26-28 

week's gestation, maternal age, 

employment status, obstetric and 

neonatal complications, smoking 

status and smoke exposure before 

and during pregnancy, alcohol 

consumption before and during 

pregnancy, history of abortion, 

miscarriage, stillbirth, exercise 

frequency, and reported fish oil 

supplementation

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Chong 201595 Antenatal and Postpartum Depression

N Total: 698

26- 28 wk Log plasma AA:DHA ratio

n-3 Measure: Maternal

All

N Quantile: na

N Cases: na

OR

Estimate: 1.05

95% CI(0.08, 13.44)

Antenatal and Postpartum Depression

N Total: 698

26- 28 wk Log plasma AA:DPA ratio

n-3 Measure: Maternal

All

N Quantile: na

N Cases: na

OR

Estimate: 1.65

95% CI(0.12, 23.39)

Antenatal and Postpartum Depression

N Total: 698

26- 28 wk Log plasma AA:EPA ratio

n-3 Measure: Maternal

All

N Quantile: na

N Cases: na

OR

Estimate: 1.38

95% CI(0.31, 6.18)

Antenatal and Postpartum Depression

N Total: 698

26- 28 wk Log plasma total omega-3

n-3 Measure: Maternal

n-3 Units: ug/ml

All

N Quantile: na

N Cases: na

OR

Estimate: 1.4

95% CI(0.29, 6.73)

Antenatal and Postpartum Depression

N Total: 698

3 month 

postpartum

Log plasma AA:DHA ratio

n-3 Measure: Maternal

All

N Quantile: na

N Cases: na

OR

Estimate: 0.74

95% CI(0.08, 6.69)

Antenatal and Postpartum Depression

N Total: 698

3 month 

postpartum

Log plasma AA:DPA ratio

n-3 Measure: Maternal

All

N Quantile: na

N Cases: na

OR

Estimate: 3.81

95% CI(0.39, 37.06)

Antenatal and Postpartum Depression

N Total: 698

3 month 

postpartum

Log plasma AA:EPA ratio

n-3 Measure: Maternal

All

N Quantile: na

N Cases: na

OR

Estimate: 0.54

95% CI(0.16, 1.85)

Antenatal and Postpartum Depression

N Total: 698

3 month 

postpartum

Log plasma total omega-4

n-3 Measure: Maternal

n-3 Units: ug/ml

All

N Quantile: na

N Cases: na

OR

Estimate: 1.48

95% CI(0.40, 5055)
D-18

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Clausen, et al., 200168

Study dates: 12/94-8/96

Study design: Observational prospective

Location: Norway

Funding source / conflict: NR

Study Population: Healthy pregnant women

Pregnant enrolled 3,771 Pregnant completers 3,133

Pregnant age: 29.8 (4.5)

Race of Mother: White European (100)

Inclusion Criteria: Caucasian women seen at Aker University 

Hospital for prenatal care and who agreed to undergo ultrasound at 

their first prenatal visit and who completed a FFQ

Exclusion Criteria: Pregestational diabetes, abortion, twin or triplet 

pregnancies, patients who give birth at other hospitals, missing 

records, loss to follow-up

Adjustments: Age, smoking (yes or 

no), BMI (<=20, 20-25, 25-30, >30), 

systolic blood pressure before 20 

weeks’ gestation, and nullipara (yes or 

no)

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Clausen 200168 Preeclampsia

N Total: 3133

n-3 fatty acids

n-3 Measure: FFQ

n-3 Units: Energy %

T1 <=0.9

N Cases: 39

OR

Preeclampsia

N Total: 3133

n-3 fatty acids

n-3 Measure: FFQ

n-3 Units: Energy %

T2 0.9 - 1.6

N Cases: 35

OR

Estimate: 1.4

95% CI(0.9, 2.3)

Preeclampsia

N Total: 3133

n-3 fatty acids

n-3 Measure: FFQ

n-3 Units: Energy %

T3 >1.6

N Cases: 11

OR

Estimate: 1.9

95% CI(0.9, 3.8)

Preeclampsia

N Total: 3133

n-6 fatty acids

n-3 Measure: FFQ

n-3 Units: Energy %

T1 <=3.8

N Cases: 34

OR

Preeclampsia

N Total: 3133

n-6 fatty acids

n-3 Measure: FFQ

n-3 Units: Energy %

T2 3.8 - 5.8

N Cases: 38

OR

Estimate: 1.5

95% CI(0.9, 2.4)

Preeclampsia

N Total: 3133

n-6 fatty acids

n-3 Measure: FFQ

n-3 Units: Energy %

T3 >5.8

N Cases: 13

OR

Estimate: 2.2

95% CI(1.1, 4.4)
D-19

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Dirix, et al., 200984

Study name: Maastricht Essential Fatty Acid Birth (MEFAB) 

Cohort

Study dates: 1990-1997

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Government

Study Population: Healthy infants Healthy pregnant women

Pregnant enrolled 1238 Pregnant completers 782

Infants enrolled 1238 Infants completers 782

Pregnant age: 29.0 26.2-31.7

Infant age: 40.1 wk 39.3-41.0

Race of Mother: White European (100)

Inclusion Criteria: gestational age of <16 weeks at study entry, 

singleton pregnancy, Caucasian race, diastolic blood pressure, 90 

mmHg and the absence of any metabolic, cardiovascular, 

neurological or renal disorder at the time of recruitment

Exclusion Criteria: excluded if infants were born preterm 

(gestational age < 37 weeks,), mothers had diabetes or 

developed pregnancy-induced hypertension, mothers had 

reported specific health problems in the past (e.g. diabetes 

mellitus, hypertension and heart, kidney, liver, gall bladder or 

thyroid gland disorders, one or both parents were nonCaucasians or values for any of the afore-mentioned 

exclusion criteria were missing. The mother – infant pairs 

were also excluded if fatty acid analyses were not reported or 

values were missing for birth weight, birth length and head 

circumference

Adjustments: Infant sex, gestational 

age, maternal height

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Dirix 200984 Birth weight

N Total: 782

DHA @ 16 weeks

n-3 Measure: Maternal plasma phospholipids

n-3 Units: per %, w/w plasma phospholipids 

increase

N Quantile: 665

N Cases: NR

Coefficient

Estimate: 52.1

95% CI(20.4, 83.8)

Birth weight

N Total: 782

DHA @ 22 weeks

n-3 Measure: Maternal plasma phospholipids

n-3 Units: per %, w/w plasma phospholipids 

increase

N Quantile: 623

N Cases: NR

Coefficient

Estimate: 31.18

95% CI(-4.301, 66.67)

Birth weight

N Total: 782

DHA @ 32 weeks

n-3 Measure: Maternal plasma phospholipids

n-3 Units: per %, w/w plasma phospholipids 

increase

N Quantile: 644

N Cases: NR

Coefficient

Estimate: 33.08

95% CI(-5.699, 71.86)

Birth weight

N Total: 782

DHA @ delivery

n-3 Measure: Maternal plasma phospholipids

n-3 Units: per %, w/w plasma phospholipids 

increase

N Quantile: 608

N Cases: NR

Coefficient

Estimate: 3.423

95% CI(-34.95, 41.8)
D-20

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Drouillet, et al., 200980

Study name: EDEN

Study dates: February 2003 - September 2003

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government, Multiple 

foundations and Societies

Original, same study, or follow-up studies: Bernard, 201389

Study Population: Healthy pregnant women

Pregnant enrolled 2002 Pregnant completers 1446

Pregnant age: 29.2 (4.8)

Race of Mother: NR

Inclusion Criteria: NR

Exclusion Criteria: twin pregnancies, known diabetes before 

pregnancy, not being able to speak and read French, and 

planned moving away from the region

Adjustments: Centre, mother's age 

and height, smoking habits, parity, 

gestational age, newborn's sex, delay 

between birth and anthropometric 

measures, and BMI

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Drouillet 200980 Birth weight

N Total: 1446

Increase of 1 SD of the intake consumed per d

n-3 Measure: FFQ

n-3 Units: n-3 FA (% PUFA intake)

Coefficient

Estimate: 6.4

95% CI(NR)

P value: P=0.54
D-21

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Guxens, et al., 2011144

Study name: INMA

Study dates: Recruitment: July 2004 to July 2006 Follow-up: 

14 months

Study design: Observational prospective

Location: Spain

Funding source / conflict: Government, Multiple foundations 

and Societies

Follow-up: 14 months

Original, same study, or follow-up studies: Julvez, 2014143

Study Population: Healthy infants Breast-feeding women

Pregnant enrolled 657 Pregnant completers 622

Lactating enrolled 622 Lactating completers 582

Infants enrolled 622 Infants completers 582 (319 with 

LCPUFA data)

Lactating enrolled 622 Lactating completers 582

Lactating age: 31.6 years (4.2 years)

Infant age: 2 to 5 days postpartum

Race of Mother: NR (NR)

Inclusion Criteria: age older than 16 years, intent to deliver at the 

reference hospital, singleton pregnancy

Exclusion Criteria: no problems of communication, no assisted 

conception

Adjustments: Child's age, maternal 

and paternal: education, social class, 

attachment to child, mental health; 

maternal age, maternal alcohol use 

during pregnancy, use of gas stove, 

child age of food introduction

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Guxens, 2011144 Cognitive Development

N Total: 504

14 months ALA

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

High versus low levels 

dichotomized at median

Coefficient

Estimate: 1.25

95% CI(-1.43, 3.93)

Cognitive Development

N Total: 504

14 months ALA

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

Sample divided into only 2 

groups - High vs Low levels

Coefficient

Estimate: 1.25

95% CI(-1.43, 3.93)

Cognitive Development

N Total: 504

14 months DHA

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

High versus low levels 

dichotomized at median

Coefficient

Estimate: 0.58

95% CI(-2.08, 3.23)

Cognitive Development

N Total: 504

14 months DHA

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

Sample divided into only 2 

groups - High vs Low levels

Coefficient

Estimate: 0.58

95% CI(-2.08, 3.23)

Cognitive Development

N Total: 504

14 months DPA

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

High versus low levels 

dichotomized at median

Coefficient

Estimate: 1.35

95% CI(-1.39, 4.08)

Cognitive Development

N Total: 504

14 months DPA

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

Sample divided into only 2 

groups - High vs Low levels

Coefficient

Estimate: 1.35

95% CI(-1.39, 4.08)

Cognitive Development

N Total: 504

14 months EPA

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

High versus low levels 

dichotomized at median

Coefficient

Estimate: 0.63

95% CI(-2.18, 3.44)

Cognitive Development

N Total: 504

14 months EPA

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

Sample divided into only 2 

groups - High vs Low levels

Coefficient

Estimate: 0.63

95% CI(-2.18, 3.44)
D-22

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Cognitive Development

N Total: 504

14 months Total n-3

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

High versus low levels 

dichotomized at median

Coefficient

Estimate: 1.76

95% CI(-0.88, 4.4)

Cognitive Development

N Total: 504

14 months Total n-3

n-3 Measure: Biomarker (colostrum)

n-3 Units: weight (%)

Sample divided into only 2 

groups - High vs Low levels

Coefficient

Estimate: 1.76

95% CI(-0.88, 4.4)
D-23

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Jordi Julvez, et al., 2014143

Study name: INMA

Study dates: Enrollment conducted July 2004 to July 2006 

Follow-up: 4 years

Study design: Observational prospective

Location: Spain

Funding source / conflict: Government, Multiple foundations 

and Societies

Follow-up: 4 years

Original, same study, or follow-up studies: Guxens, 2011144

Study Population: Breast-feeding women

Pregnant enrolled 657 Pregnant completers 622

Lactating enrolled 622 Lactating completers 582

Infants enrolled 622 Infants completers 434

Lactating enrolled 622 Lactating completers 582

Lactating age: 31.6 years (4.2 years)

Infant age: 2 to 5 days after birth

Race of Mother: NR (NR)

Inclusion Criteria: age older than 16 years, intent to deliver at the 

reference hospital, singleton pregnancy

Exclusion Criteria: no problems with communication, no assisted 

conception

Adjustments: Test conditions, child 

age & sex, parental age, parity, 

alcohol consumption and smoking 

during pregnancy, day care 

attendance, country of birth, maternal 

education, social class, mental health, 

attachment to child, and perceptive 

performance IQ at 14 months, 

maternal psych symptoms, verbal IQ 

at 4 years, pollutant exposure during 

pregnancy.

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Julvez, 2013143 Neuropsychological development

N Total: 434

4 years Total n-3 fatty acids

n-3 Measure: Biomarker (colostrum)

n-3 Units: NR

Tertile 2 vs. Tertile 1 Coefficient

Estimate: 0.5

95% CI(-2.9, 3.9)

Neuropsychological development

N Total: 434

4 years Total n-3 fatty acids

n-3 Measure: Biomarker (colostrum)

n-3 Units: NR

Tertile 2 vs. Tertile 2 Coefficient

Estimate: 1.8

95% CI(-1.7, 5.4)
D-24

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Keim, et al., 2012162

Study name: Pregnancy, Infection and Nutrition Study

Study dates: Recruitment between January 2001 and June 

2005 Follow-up: 1 year

Study design: Observational prospective

Location: US

Funding source / conflict: Government

Follow-up: 12 months

Study Population: Healthy infants Breast-feeding women

Pregnant enrolled 1,169 Pregnant completers 689

Infants enrolled 408 Infants completers 358

Pregnant age: NR

Infant age: 20 weeks gestation NA

Race of Mother: White European (79.1%) Other race/ethnicity 

(21.0)

Inclusion Criteria: health women at less than 20 weeks of 

pregnancy

Exclusion Criteria: pregnant with multiple fetuses, unable to 

communicate in English, under age 16 years, no access to a 

telephone, intention to go elsewhere for future care or delivery

Adjustments: Laboratory, infant sex, 

race, parity, maternal smoking, 

education, breastfeeding status and 

preterm status

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Keim, 2012162 Mullen Scales of Early Learning - composite score

N Total: 266

12 months AA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: 0.9

95% CI(-1.5, 3.4)

Mullen Scales of Early Learning - composite score

N Total: 266

12 months DHA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: -0.5

95% CI(-2.7, 1.7)

Mullen Scales of Early Learning - expressive language 

scale

N Total: 266

12 months AA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: 0.7

95% CI(-0.9, 2.3)

Mullen Scales of Early Learning - expressive language 

scale

N Total: 266

12 months DHA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: -0.6

95% CI(-2.1, 0.8)

Mullen Scales of Early Learning - fine motor scale

N Total: 266

12 months AA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: 0

95% CI(-2, 2)

Mullen Scales of Early Learning - fine motor scale

N Total: 266

12 months DHA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: 0.2

95% CI(-1.7, 2)

Mullen Scales of Early Learning - gross motor scale

N Total: 266

12 months AA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: 1.2

95% CI(-1.1, 3.4)
D-25

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Mullen Scales of Early Learning - gross motor scale

N Total: 266

12 months DHA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: 1.1

95% CI(-0.9, 3.1)

Mullen Scales of Early Learning - receptive language 

scale

N Total: 266

12 months AA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: 0.3

95% CI(-1.2, 1.7)

Mullen Scales of Early Learning - receptive language 

scale

N Total: 266

12 months DHA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: -0.1

95% CI(-1.4, 1.2)

Mullen Scales of Early Learning - visual reception scale

N Total: 266

12 months AA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: 0.7

95% CI(-1.3, 2.8)

Mullen Scales of Early Learning - visual reception scale

N Total: 266

12 months DHA

n-3 Measure: breast milk and formula

n-3 Units: a change in fatty acid concentration of 

1.0%.

Coefficient

Estimate: -0.1

95% CI(-2, 1.8)
D-26

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Klebanoff, et al., 201149

Study dates: Jan 2005- Oct 2006

Study design: Observational prospective

Location: US

Funding source / conflict: Government

Original, same study, or follow-up studies: Harper, 201029

Study Population: Healthy pregnant women

Pregnant enrolled 852 Pregnant completers 852

Pregnant age: <1/month, 27.1 (5.6) 0.5-3 per week, 28.0 (5.6) 

>3 per week, 27.3 (5.7) (<1/month, 27.1 (5.6) 0.5-3 per week, 

28.0 (5.6) >3 per week, 27.3 (5.7))

Race of Mother: NR

Inclusion Criteria: at least one prior singleton preterm delivery 

between 20 0/7 and 36 6/7 weeks of gestation after spontaneous 

preterm labor or premature rupture of the membranes, and a 

current singleton pregnancy between 16 and 21 6/7 weeks of 

gestation

Exclusion Criteria: evidence of a major fetal anomaly, intake of a 

fish oil supplement in excess of 500 mg per week at any time 

during the preceding month, allergy to fish, anticoagulation therapy, 

hypertension, White’s classification D or higher diabetes, drug or 

alcohol abuse, seizure disorder, uncontrolled thyroid disease, 

clotting disorder, current or planned cerclage, or a plan to deliver 

either elsewhere or before 37 weeks of gestation

Adjustments: Study center, number of 

previous preterm births, gestation of 

earliest prior spontaneous preterm 

birth, receipt of omega-3 versus 

placebo supplement, smoking, age,

education, body mass index and 

ethnicity

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Klebanoff 201149 Preterm birth

N Total: 852

Erythrocyte DHA + EPA

n-3 Measure: Maternal red blood cells

n-3 Units: % of total fatty acids

Q1 <3.052 -

N Cases: 176

OR

Preterm birth

N Total: 852

Erythrocyte DHA + EPA

n-3 Measure: Maternal red blood cells

n-3 Units: % of total fatty acids

Q2 3.052 - 3.719

N Cases: 175

OR

Estimate: 0.59

95% CI(0.37, 0.94)

Preterm birth

N Total: 852

Erythrocyte DHA + EPA

n-3 Measure: Maternal red blood cells

n-3 Units: % of total fatty acids

Q3 3.723 - 4.426

N Cases: 175

OR

Estimate: 0.84

95% CI(0.53, 1.32)

Preterm birth

N Total: 852

Erythrocyte DHA + EPA

n-3 Measure: Maternal red blood cells

n-3 Units: % of total fatty acids

Q4 >4.426

N Cases: 175

OR

Estimate: 0.71

95% CI(0.45, 1.15)
D-27

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Leung, et al., 201394

Study name: Alberta Pregnancy Outcomes and Nutrition 

(APrON) study

Study dates: %n

Study design: Observational prospective

Location: Canada

Funding source / conflict: NR

Study Population: Healthy pregnant women

Pregnant enrolled 600 Pregnant withdrawals 125 Pregnant 

completers 475

Pregnant age: 31.2 not depressed 31.6 depressed (4.16 not 

depressed 4.7 depressed) not reported

Race of Mother: White European (87%) Other race/ethnicity 

(13%)

Inclusion Criteria: at least 16 years old with gestational age =27 

weeks. Women must be in the first (T1) or second (T2) trimester

Exclusion Criteria: Any woman who was 28 weeks or beyond, NonEnglish speakers, known drug and alcohol abusers, and those 

planning to move out of the region within 6 months

Adjustments: Born in Canada, prenatal 

and postnatal social support, prenatal 

EPDS, selenium

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Leung 201394 PPD

N Total: 475

Biomarkers N Cases: 59 OR

Estimate: 1

95% CI(0.99, 1)
D-28

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Lim, et al., 201571

Study dates: 2009-2012

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Study Population: Healthy pregnant women

Pregnant enrolled 1162 Pregnant completers 751

Infants completers

Pregnant age: 1st tertile 29.9 2nd tertile 30.0 3rd tertile 31.7 _ 

(1st tertile 5. 2 2nd tertile 5.2, 3rd tertile 4.8)

Race of Mother: Asian (100)

Inclusion Criteria: Healthy women in early pregnancy at one of 3 

tertiary care hospitals in Singapore

Exclusion Criteria: receiving chemotherapy, taking psychotropic 

drugs, or having type 1 diabetes

Adjustments: Adjusted for age, 

ethnicity, education, exercise, alcohol 

intake, smoking status, BMI, and 

height at the 26th to the 28th week of 

gestation, gestational diabetes, and 

heart rate, fish oil supplementation

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Lim 201571 Gestational hypertension

N Total: 751

26-28 weeks AA

n-3 Measure: Biomarker (maternal plasma)

n-3 Units: 1% increase in % total FA

All

N Quantile: NR

N Cases: 28

OR

Estimate: 1.07

95% CI(0.95, 1.22)

Gestational hypertension

N Total: 751

26-28 weeks Total n-3 PUFAs

n-3 Measure: Biomarker (maternal plasma)

n-3 Units: 1% increase in % total FA

All

N Quantile: NR

N Cases: 28

OR

Estimate: 0.76

95% CI(0.60, 0.97)

Gestational hypertension

N Total: 751

26-28 weeks n-3 LCPUFA

n-3 Measure: Biomarker (maternal plasma)

n-3 Units: 1% increase in % total FA

All

N Quantile: NR

N Cases: 28

OR

Estimate: 0.77

95% CI(0.60, 0.98)
D-29

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Lumia, et al., 2011188

Study name: Finnish Type 1 Diabetes Prediction and 

Prevention Nutrition Study

Study dates: 1997-2004

Study design: NR

Location: Finland

Funding source / conflict: Industry, Government, Multiple 

foundations and Societies, None

Follow-up: 5 years

Study Population: NR

Infants enrolled 2908 Infants completers 2679

Pregnant age: 14.8% <25 years at birth 35.4% 25-29 years 

30.4% 30-34 years 19.5% =35 years

Race of Mother: White European (100%)

Inclusion Criteria: infants at three university hospitals in Finland 

(Turku, Tampere and Oulu) whose cord blood was screened for 

HLA-conferred genetic susceptibility to type 1 diabetes (HLADQB1) and were found to have high or moderate genetic risk of 

type 1 diabetes

Exclusion Criteria: Severe congenital malformations or diseases, 

parents of non-Caucasian origin or parents who did not have a 

working knowledge of Finnish, Swedish or English

Adjustments: Maternal age, mode of 

delivery, duration of gestation, number 

of earlier deliveries, birth weight, sex 

of the child, area of birth, maternal 

smoking during pregnancy, parental 

asthma or allergic rhinitis, maternal 

vocational education, pets at home, 

farming, contact with cow stable 

during the first year of life and the 

duration of total breastfeeding

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Lumia 2011188 Asthma

N Total: 2679

5 years AA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q1 - <0.06

N Quantile: NR

N Cases: NR

RR

Estimate: 0.52

95% CI(0.32, 0.84)

P value: 0.025

Asthma

N Total: 2679

5 years AA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q2,Q3 0.06- 0.11

N Quantile: NR

N Cases: NR

RR

Asthma

N Total: 2679

5 years AA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q4 >0.11-

N Quantile: NR

N Cases: NR

RR

Estimate: 0.77

95% CI(0.51, 1.17)

Asthma

N Total: 2679

5 years ALA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q1 - <1.83

N Quantile: NR

N Cases: NR

RR

Estimate: 1.7

95% CI(1.14, 2.53)

P value: 0.022

Asthma

N Total: 2679

5 years ALA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q2,Q3 1.83- 3.18

N Quantile: NR

N Cases: NR

RR

Asthma

N Total: 2679

5 years ALA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q4 >3.18-

N Quantile: NR

N Cases: NR

RR

Estimate: 1.06

95% CI(0.68, 1.65)

Asthma

N Total: 2679

5 years DHA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q1 - <0.10

N Quantile: NR

N Cases: NR

RR

Estimate: 0.8

95% CI(0.52, 1.23)

P value: 0.467

Asthma

N Total: 2679

5 years DHA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q2,Q3 0.1- 0.32

N Quantile: NR

N Cases: NR

RR

Asthma

N Total: 2679

5 years DHA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q4 >0.32-

N Quantile: NR

N Cases: NR

RR

Estimate: 0.83

95% CI(0.53, 1.29)
D-30

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Asthma

N Total: 2679

5 years EPA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q1 - <0.04

N Quantile: NR

N Cases: NR

RR

Estimate: 1.09

95% CI(0.72, 1.65)

P value: 0.604

Asthma

N Total: 2679

5 years EPA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q2,Q3 0.04- 1.13

N Quantile: NR

N Cases: NR

RR

Asthma

N Total: 2679

5 years EPA

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q4 >1.13-

N Quantile: NR

N Cases: NR

RR

Estimate: 0.84

95% CI(0.54, 1.31)

Asthma

N Total: 2679

5 years n-3 PUFAs

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q1 - <2.24

N Quantile: NR

N Cases: NR

RR

Estimate: 1.66

95% CI(1.11, 2.48)

P value: 0.036

Asthma

N Total: 2679

5 years n-3 PUFAs

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q2,Q3 2.24- 3.84

N Quantile: NR

N Cases: NR

RR

Asthma

N Total: 2679

5 years n-3 PUFAs

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q4 >3.84-

N Quantile: NR

N Cases: NR

RR

Estimate: 1.09

95% CI(0.7, 1.7)

Asthma

N Total: 2679

5 years n-6/n-3 PUFAs

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q1 - <3.07

N Quantile: NR

N Cases: NR

RR

Estimate: 0.95

95% CI(0.62, 1.46)

P value: 0.835

Asthma

N Total: 2679

5 years n-6/n-3 PUFAs

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q2,Q3 3.07- 3.82

N Quantile: NR

N Cases: NR

RR

Asthma

N Total: 2679

5 years n-6/n-3 PUFAs

n-3 Measure: Maternal FFQ

n-3 Units: g/d

Q4 >3.82-

N Quantile: NR

N Cases: NR

RR

Estimate: 1.1

95% CI(0.72, 1.68)
D-31

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Lyall, et al., 2013171

Study name: Nurses Health Study

Study dates: Births 1991 to 2007

Study design: NR

Location: US

Funding source / conflict: Government

Study Population: Healthy pregnant women

Pregnant enrolled 18,045 Pregnant completers 5,884

Pregnant age: Q1 34.7y Q4 33.7 y NR

Infant age: birth

Race of Mother: White European (Q1: 96%; Q4: 98%) Other 

race/ethnicity (Q1 4%; Q4 2%)

Inclusion Criteria: female nurses who were 25–42 years of age in 

1989, with index births between 1991 (the year of first collection of 

dietary information) and 2007; women reported a child with ASD 

either in 2005 or 2009 not both, if 1) the reason for non-reporting on 

the other questionnaire was on participation in that questionnaire 

year; 2) the nurse confirmed the diagnosis in a previous substudy; 

or 3) for women reporting on the 2009 questionnaire only, the child 

was born after 2000 (in which case, the child might have been too 

young for report of diagnosis by the 2005 questionnaire mailing)

Exclusion Criteria: Women reporting competing diagnoses (fragile 

X syndrome, Rett Syndrome, tuberous sclerosis, Down syndrome, 

trisomy 18; in a previous sub-study were not included.. women 

without food frequency questionnaire data or without autism 

diagnosis info on child

Adjustments: Adjusted for total energy 

intake, maternal age, child’s year of 

birth, income level, race, body mass 

index, and pre-pregnancy smoking 

status. Removal of adjustment for 

smoking did not affect results. 

Additional adjustment for child birth 

order, maternal physical activity level, 

spouse’s education level, or 

multivitamin use, or for trans-fat in 

PUFA model, did not materially alter 

estimates

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Lyall, 2013171 Autism Spectrum Disorders

N Total: 17728

Total LCPUFA

n-3 Measure: FFQ

Q1 7.8 RR P value: P<0.008

Autism Spectrum Disorders

N Total: 17728

Total LCPUFA

n-3 Measure: FFQ

Q2 9.5 RR

Estimate: 0.97

95% CI(0.73, 1.3)

Autism Spectrum Disorders

N Total: 17728

Total LCPUFA

n-3 Measure: FFQ

Q3 11 RR

Estimate: 0.82

95% CI(0.82, 1.11)

Autism Spectrum Disorders

N Total: 17728

Total LCPUFA

n-3 Measure: FFQ

Q4 13.4 RR

Estimate: 0.67

95% CI(0.49, 0.92)
D-32

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Miyake, et al., 2009182

Study name: Osaka maternal and child health study

Study dates: 2002-2003

Study design: Observational prospective

Location: Japan

Funding source / conflict: Government, None

Study Population: Healthy infants

Pregnant enrolled 1,002 Pregnant completers 763

Infants enrolled 1,002 Infants completers 763

Pregnant age: 30.0 (4.0)

Race of Mother: NR (100)

Inclusion Criteria: pregnant women living in Neyagawa City, Osaka 

Prefecture or the surrounding cities

Exclusion Criteria: Not reported

Adjustments: Maternal age, gestation 

at baseline, residential municipality, 

family income, maternal and paternal 

education, maternal and paternal 

history of asthma, atopic eczema and 

allergic rhinitis, maternal intake of 

vitamins D and E during pregnancy, 

changes in maternal diet in the 

previous 1 month, season when data 

at baseline were collected, maternal 

smoking during pregnancy, baby’s 

older siblings, baby’s sex, baby’s birth 

weight, household smoking in the 

same room as the infant, 

breastfeeding duration and time of 

delivery before the third survey

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Miyake 2009182 Eczema

N Total: 763

16-24 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 1.3

N Quantile: NR

N Cases: 35

OR P value: 0.06

Eczema

N Total: 763

16-24 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 1.6

N Quantile: NR

N Cases: 33

OR

Estimate: 1.28

95% CI(0.71, 2.29)

Eczema

N Total: 763

16-24 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 1.9

N Quantile: NR

N Cases: 35

OR

Estimate: 1.69

95% CI(0.91, 3.13)

Eczema

N Total: 763

16-24 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 2.3

N Quantile: NR

N Cases: 39

OR

Estimate: 1.79

95% CI(0.93, 3.5)

Eczema

N Total: 763

16-24 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.15

N Quantile: NR

N Cases: 40

OR P value: 0.57

Eczema

N Total: 763

16-24 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.24

N Quantile: NR

N Cases: 40

OR

Estimate: 1.5

95% CI(0.76, 3.02)

Eczema

N Total: 763

16-24 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.32

N Quantile: NR

N Cases: 32

OR

Estimate: 1.11

95% CI(0.49, 2.54)

Eczema

N Total: 763

16-24 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.46

N Quantile: NR

N Cases: 30

OR

Estimate: 0.86

95% CI(0.33, 2.28)

Eczema

N Total: 763

16-24 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.08

N Quantile: NR

N Cases: 39

OR P value: 0.95
D-33

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 763

16-24 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.13

N Quantile: NR

N Cases: 36

OR

Estimate: 0.99

95% CI(0.51, 1.89)

Eczema

N Total: 763

16-24 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.18

N Quantile: NR

N Cases: 33

OR

Estimate: 1.12

95% CI(0.52, 2.45)

Eczema

N Total: 763

16-24 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.28

N Quantile: NR

N Cases: 34

OR

Estimate: 0.98

95% CI(0.39, 2.5)

Eczema

N Total: 763

16-24 months n-3 PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 1.7

N Quantile: NR

N Cases: 35

OR P value: 0.2

Eczema

N Total: 763

16-24 months n-3 PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 2.2

N Quantile: NR

N Cases: 38

OR

Estimate: 1.72

95% CI(0.95, 3.13)

Eczema

N Total: 763

16-24 months n-3 PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 2.5

N Quantile: NR

N Cases: 33

OR

Estimate: 1.63

95% CI(0.83, 3.22)

Eczema

N Total: 763

16-24 months n-3 PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 3

N Quantile: NR

N Cases: 36

OR

Estimate: 1.74

95% CI(0.82, 3.73)

Eczema

N Total: 763

16-24 months n-3/n-6

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.17

N Quantile: NR

N Cases: 31

OR P value: 0.18

Eczema

N Total: 763

16-24 months n-3/n-7

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.19

N Quantile: NR

N Cases: 33

OR

Estimate: 1.24

95% CI(0.68, 2.28)

Eczema

N Total: 763

16-24 months n-3/n-8

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.21

N Quantile: NR

N Cases: 46

OR

Estimate: 2.13

95% CI(1.17, 3.96)

Eczema

N Total: 763

16-24 months n-3/n-9

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.24

N Quantile: NR

N Cases: 32

OR

Estimate: 1.32

95% CI(0.65, 2.71)

Wheeze

N Total: 763

16-24 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 1.3

N Quantile: NR

N Cases: 53

OR P value: 0.08

Wheeze

N Total: 763

16-24 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 1.6

N Quantile: NR

N Cases: 38

OR

Estimate: 0.63

95% CI(0.37, 1.07)

Wheeze

N Total: 763

16-24 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 1.9

N Quantile: NR

N Cases: 45

OR

Estimate: 0.78

95% CI(0.45, 1.35)

Wheeze

N Total: 763

16-24 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 2.3

N Quantile: NR

N Cases: 33

OR

Wheeze

N Total: 763

16-24 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.15

N Quantile: NR

N Cases: 55

OR P value: 0.14
D-34

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Wheeze

N Total: 763

16-24 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.24

N Quantile: NR

N Cases: 29

OR

Estimate: 0.41

95% CI(0.2, 0.81)

Wheeze

N Total: 763

16-24 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.32

N Quantile: NR

N Cases: 50

OR

Estimate: 0.72

95% CI(0.33, 1.57)

Wheeze

N Total: 763

16-24 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.46

N Quantile: NR

N Cases: 35

OR

Wheeze

N Total: 763

16-24 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.08

N Quantile: NR

N Cases: 48

OR P value: 0.58

Wheeze

N Total: 763

16-24 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.13

N Quantile: NR

N Cases: 39

OR

Estimate: 0.77

95% CI(0.42, 1.41)

Wheeze

N Total: 763

16-24 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.18

N Quantile: NR

N Cases: 38

OR

Estimate: 0.76

95% CI(0.37, 1.58)

Wheeze

N Total: 763

16-24 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.28

N Quantile: NR

N Cases: 44

OR

Estimate: 0.76

95% CI(0.33, 1.8)

Wheeze

N Total: 763

16-24 months n-3 PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 1.7

N Quantile: NR

N Cases: 53

OR P value: 0.13

Wheeze

N Total: 763

16-24 months n-3 PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 2.2

N Quantile: NR

N Cases: 38

OR

Estimate: 0.57

95% CI(0.33, 0.99)

Wheeze

N Total: 763

16-24 months n-3 PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 2.5

N Quantile: NR

N Cases: 42

OR

Estimate: 0.66

95% CI(0.36, 1.22)

Wheeze

N Total: 763

16-24 months n-3 PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 3

N Quantile: NR

N Cases: 36

OR

Estimate: 0.53

95% CI(0.26, 1.08)

Wheeze

N Total: 763

16-24 months n-3/n-6

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.17

N Quantile: NR

N Cases: 46

OR P value: 0.38

Wheeze

N Total: 763

16-24 months n-3/n-7

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.19

N Quantile: NR

N Cases: 44

OR

Estimate: 0.88

95% CI(0.52, 1.51)

Wheeze

N Total: 763

16-24 months n-3/n-8

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.21

N Quantile: NR

N Cases: 37

OR

Estimate: 0.69

95% CI(0.39, 1.23)

Wheeze

N Total: 763

16-24 months n-3/n-9

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.24

N Quantile: NR

N Cases: 42

OR

Estimate: 0.81

95% CI(0.42, 1.55)
D-35

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Miyake, et al., 2013183

Study name: Kyushu Okinawa Maternal and Child Health 

Study

Study dates: 2007-2010

Study design: Observational prospective

Location: Japan

Funding source / conflict: Industry, Government, Multiple 

foundations and Societies

Follow-up: 23-29 months

Study Population: Healthy infants

Pregnant enrolled 1757 Pregnant completers 1354

Infants enrolled 1757 Infants completers 1354

Pregnant age: 31.5 (4.1)

Race of Mother: NR (100)

Inclusion Criteria: Women living in one of 7 prefectures on Kyushu 

Island who became pregnant from 2007-2008

Exclusion Criteria: Failure to complete the study surveys

Adjustments: Maternal age, gestation 

at baseline, residential municipality, 

family income, maternal and paternal 

education, maternal and paternal 

history of asthma, atopic eczema and 

allergic rhinitis, maternal intake of 

vitamins D and E during pregnancy, 

changes in maternal diet in the 

previous 1 month, season when data 

at baseline were collected, maternal 

smoking during pregnancy, baby’s 

older siblings, baby’s sex, baby’s birth 

weight, household smoking in the 

same room as the infant, 

breastfeeding duration and time of 

delivery before the third survey

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Miyake 2013183 Eczema

N Total: 763

23-29 months AA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.09

N Quantile: NR

N Cases: 56

OR

Eczema

N Total: 763

23-29 months AA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.12

N Quantile: NR

N Cases: 61

OR

Estimate: 1.08

95% CI(0.72, 1.63)

Eczema

N Total: 763

23-29 months AA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.14

N Quantile: NR

N Cases: 61

OR

Estimate: 1.07

95% CI(0.71, 1.6)

Eczema

N Total: 763

23-29 months AA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.18

N Quantile: NR

N Cases: 51

OR

Estimate: 0.87

95% CI(0.57, 1.33)

Eczema

N Total: 763

23-29 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 1.2

N Quantile: NR

N Cases: 61

OR

Eczema

N Total: 763

23-29 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 1.5

N Quantile: NR

N Cases: 52

OR

Estimate: 0.82

95% CI(0.54, 1.24)

Eczema

N Total: 763

23-29 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 1.8

N Quantile: NR

N Cases: 61

OR

Estimate: 0.97

95% CI(0.65, 1.45)

Eczema

N Total: 763

23-29 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 2.2

N Quantile: NR

N Cases: 55

OR

Estimate: 0.86

95% CI(0.57, 1.29)

Eczema

N Total: 763

23-29 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.15

N Quantile: NR

N Cases: 45

OR
D-36

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 763

23-29 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.23

N Quantile: NR

N Cases: 64

OR

Estimate: 1.51

95% CI(0.99, 2.32)

Eczema

N Total: 763

23-29 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.3

N Quantile: NR

N Cases: 58

OR

Estimate: 1.35

95% CI(0.88, 2.08)

Eczema

N Total: 763

23-29 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.45

N Quantile: NR

N Cases: 62

OR

Estimate: 1.45

95% CI(0.95, 2.24)

Eczema

N Total: 763

23-29 months EPA+DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.22

N Quantile: NR

N Cases: 48

OR

Eczema

N Total: 763

23-29 months EPA+DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.35

N Quantile: NR

N Cases: 62

OR

Estimate: 1.35

95% CI(0.89, 2.06)

Eczema

N Total: 763

23-29 months EPA+DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.47

N Quantile: NR

N Cases: 55

OR

Estimate: 1.18

95% CI(0.77, 1.82)

Eczema

N Total: 763

23-29 months EPA+DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.73

N Quantile: NR

N Cases: 64

OR

Estimate: 1.42

95% CI(0.93, 2.17)

Eczema

N Total: 763

23-29 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.07

N Quantile: NR

N Cases: 54

OR

Eczema

N Total: 763

23-29 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.13

N Quantile: NR

N Cases: 56

OR

Estimate: 1.03

95% CI(0.68, 1.57)

Eczema

N Total: 763

23-29 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.17

N Quantile: NR

N Cases: 55

OR

Eczema

N Total: 763

23-29 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.28

N Quantile: NR

N Cases: 64

OR

Estimate: 1.21

95% CI(0.8, 1.83)

Eczema

N Total: 763

23-29 months n-3-PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 1.6

N Quantile: NR

N Cases: 56

OR

Eczema

N Total: 763

23-29 months n-3-PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 2.1

N Quantile: NR

N Cases: 53

OR

Estimate: 0.93

95% CI(0.61, 1.41)

Eczema

N Total: 763

23-29 months n-3-PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 2.4

N Quantile: NR

N Cases: 68

OR

Estimate: 1.21

95% CI(0.81, 1.81)

Eczema

N Total: 763

23-29 months n-3-PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 2.9

N Quantile: NR

N Cases: 52

OR

Estimate: 0.89

95% CI(0.58, 1.35)

Eczema

N Total: 763

23-29 months n-3:n-6

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.17

N Quantile: NR

N Cases: 50

OR
D-37

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 763

23-29 months n-3:n-7

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.19

N Quantile: NR

N Cases: 59

OR

Estimate: 1.21

95% CI(0.8, 1.85)

Eczema

N Total: 763

23-29 months n-3:n-8

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.21

N Quantile: NR

N Cases: 57

OR

Estimate: 1.14

95% CI(0.75, 1.76)

Eczema

N Total: 763

23-29 months n-3:n-9

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.25

N Quantile: NR

N Cases: 63

OR

Estimate: 1.28

95% CI(0.84, 1.95)

Wheeze

N Total: 763

23-29 months AA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.09

N Quantile: NR

N Cases: 91

OR

Wheeze

N Total: 763

23-29 months AA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.12

N Quantile: NR

N Cases: 99

OR

Estimate: 1.12

95% CI(0.79, 1.59)

Wheeze

N Total: 763

23-29 months AA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.14

N Quantile: NR

N Cases: 92

OR

Estimate: 1.04

95% CI(0.74, 1.48)

Wheeze

N Total: 763

23-29 months AA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.18

N Quantile: NR

N Cases: 91

OR

Estimate: 0.95

95% CI(0.66, 1.34)

Wheeze

N Total: 763

23-29 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 1.2

N Quantile: NR

N Cases: 91

OR

Wheeze

N Total: 763

23-29 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 1.5

N Quantile: NR

N Cases: 92

OR

Estimate: 1.02

95% CI(0.72, 1.44)

Wheeze

N Total: 763

23-29 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 1.8

N Quantile: NR

N Cases: 97

OR

Estimate: 1.06

95% CI(0.75, 1.5)

Wheeze

N Total: 763

23-29 months ALA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 2.2

N Quantile: NR

N Cases: 93

OR

Estimate: 0.96

95% CI(0.68, 1.36)

Wheeze

N Total: 763

23-29 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.15

N Quantile: NR

N Cases: 98

OR

Wheeze

N Total: 763

23-29 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.23

N Quantile: NR

N Cases: 107

OR

Estimate: 1.14

95% CI(0.81, 1.6)

Wheeze

N Total: 763

23-29 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.3

N Quantile: NR

N Cases: 86

OR

Estimate: 0.82

95% CI(0.58, 1.17)

Wheeze

N Total: 763

23-29 months DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.45

N Quantile: NR

N Cases: 82

OR

Estimate: 0.77

95% CI(0.54, 1.1)

Wheeze

N Total: 763

23-29 months EPA+DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.22

N Quantile: NR

N Cases: 100

OR
D-38

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Wheeze

N Total: 763

23-29 months EPA+DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.35

N Quantile: NR

N Cases: 103

OR

Estimate: 1.07

95% CI(0.76, 1.51)

Wheeze

N Total: 763

23-29 months EPA+DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.47

N Quantile: NR

N Cases: 93

OR

Estimate: 0.87

95% CI(0.62, 1.25)

Wheeze

N Total: 763

23-29 months EPA+DHA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.73

N Quantile: NR

N Cases: 77

OR

Estimate: 0.7

95% CI(0.49, 1.003)

Wheeze

N Total: 763

23-29 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.07

N Quantile: NR

N Cases: 100

OR

Wheeze

N Total: 763

23-29 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.13

N Quantile: NR

N Cases: 109

OR

Estimate: 1.19

95% CI(0.84, 1.67)

Wheeze

N Total: 763

23-29 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.17

N Quantile: NR

N Cases: 86

OR

Estimate: 0.79

95% CI(0.55, 1.13)

Wheeze

N Total: 763

23-29 months EPA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.28

N Quantile: NR

N Cases: 78

OR

Estimate: 0.73

95% CI(0.5, 1.04)

Wheeze

N Total: 763

23-29 months n-3-PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 1.6

N Quantile: NR

N Cases: 95

OR

Wheeze

N Total: 763

23-29 months n-3-PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 2.1

N Quantile: NR

N Cases: 99

OR

Estimate: 1.05

95% CI(0.75, 1.49)

Wheeze

N Total: 763

23-29 months n-3-PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 2.4

N Quantile: NR

N Cases: 96

OR

Estimate: 0.97

95% CI(0.69, 1.38)

Wheeze

N Total: 763

23-29 months n-3-PUFA

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 2.9

N Quantile: NR

N Cases: 83

OR

Estimate: 0.79

95% CI(0.55, 1.12)

Wheeze

N Total: 763

23-29 months n-3:n-6

n-3 Measure: FFQ

n-3 Units: median, g/d

Q1 0.17

N Quantile: NR

N Cases: 90

OR

Wheeze

N Total: 763

23-29 months n-3:n-7

n-3 Measure: FFQ

n-3 Units: median, g/d

Q2 0.19

N Quantile: NR

N Cases: 104

OR

Estimate: 1.24

95% CI(0.88, 1.75)

Wheeze

N Total: 763

23-29 months n-3:n-8

n-3 Measure: FFQ

n-3 Units: median, g/d

Q3 0.21

N Quantile: NR

N Cases: 97

OR

Estimate: 1.08

95% CI(0.76, 1.54)

Wheeze

N Total: 763

23-29 months n-3:n-9

n-3 Measure: FFQ

n-3 Units: median, g/d

Q4 0.25

N Quantile: NR

N Cases: 82

OR

Estimate: 0.85

95% CI(0.59, 1.22)
D-39

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Mohanty, et al., 201585

Study dates: 1996-2008

Study design: Observational prospective

Location: US

Funding source / conflict: Government

Study Population: Healthy infants Healthy pregnant women

Pregnant completers 534

Race of Mother: White European (88)

Inclusion Criteria: initiated prenatal care at or before 20 weeks 

gestation, were aged = 18 years, able to speak and read English, 

planned to carry the pregnancy to term, and to deliver at either of 

the two hospitals

Exclusion Criteria: multi-fetal pregnancies, implausible total energy 

intake of <500 or >3500 kcal/day, pregnancies complicated by fetal 

demise (after 20 weeks of gestation), missing labor and delivery 

information, missing information on fetal growth indices, missing 

seafood intake information

Adjustments: Adjusted for maternal 

age (years), non-Hispanic white race, 

post high-school education, unmarried 

marital status, pre-pregnancy body 

mass index (indicator variables: 18.5-

24.9, 25-29.9, =30 kg/m2), total 

energy (kcal/day), current recreational 

physical activity, current smoking, 

current alcohol intake, nulliparity, 

intake of red/processed meats 

(servings/day), male infant sex.

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Mohanty 201585 Birth weight

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q1 2.28-4.49

N Quantile: 133

Mean difference

Birth weight

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q2 4.49-5.25

N Quantile: 134

Mean difference

Estimate: -59

95% CI(-207.5, 89.6)

Birth weight

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q3 5.26-6.07

N Quantile: 133

Mean difference

Estimate: 49.6

95% CI(-100.9, 200.1)

Birth weight

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q4 6.07-9.55

N Quantile: 134

Mean difference

Estimate: -39.4

95% CI(-194.5, 115.7)

Head circumference

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q1 2.28-4.49

N Quantile: 133

Mean difference

Head circumference

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q2 4.49-5.25

N Quantile: 134

Mean difference

Estimate: 0.3

95% CI(-0.3, 0.9)

Head circumference

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q3 5.26-6.07

N Quantile: 133

Mean difference

Estimate: 0.5

95% CI(-0.1, 1.1)

Head circumference

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q4 6.07-9.55

N Quantile: 134

Mean difference

Estimate: 0.2

95% CI(-0.4, 0.9)

Length

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q1 2.28-4.49

N Quantile: 133

Mean difference

Length

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q2 4.49-5.25

N Quantile: 134

Mean difference

Estimate: -0.1

95% CI(-0.9, 0.6)
D-40

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Length

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q3 5.26-6.07

N Quantile: 133

Mean difference

Estimate: -0.1

95% CI(-0.9, 0.6)

Length

N Total: 534

Erythrocyte DHA + EPA

n-3 Measure: Maternal

n-3 Units: % total fatty acids

Q4 6.07-9.55

N Quantile: 134

Mean difference

Estimate: 0

95% CI(-0.9, 0.8)
D-41

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Molto-Puigmarti, et al., 201448

Study name: KOALA Birth Cohort Study

Study dates: 2000-2002

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Multiple foundations and Societies

Study Population: Healthy pregnant women

Pregnant enrolled 2669 Pregnant completers 1516

Infants enrolled 2669 Infants completers 1515

Pregnant age: years (.7yrs)

Race of Mother: NR (100)

Inclusion Criteria: nr, Described in Ref 37

Exclusion Criteria: nr

Adjustments: Adjusted for child 

gender, study recruitment group, 

maternal education, parity, maternal 

smoking status during pregnancy, 

maternal alcohol use in pregnancy, 

and maternal age at delivery

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Molto-Puigmarti 

201448

Birth weight

N Total: 2606

DHA

n-3 Measure: Maternal

n-3 Units: mg/d

All

N Quantile: na

N Cases: na

Coefficient

Estimate: 0.16

95% CI(0.008, 0.313)

Pregnancy duration

N Total: 2606

DHA

n-3 Measure: Maternal

n-3 Units: mg/d

All

N Quantile: na

N Cases: na

Coefficient

Estimate: 0.004

95% CI(0.001, 0.007)
D-42

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Morales, et al., 2012184

Study name: INfancia y Medio Ambiente (INMA) Project

Study dates: 2004-2007

Study design: Observational prospective

Location: Spain

Funding source / conflict: Government

Follow-up: 14 months

Study Population: Healthy infants Healthy pregnant women

Pregnant enrolled 622 Pregnant completers 580

Infants enrolled 622 Infants completers 580

Mother age: 31.6 (4.2)

Race of Mother: NR (100)

Inclusion Criteria: to be resident in the study area, to be at least 16 

years old, to have a singleton pregnancy, to not have followed any 

programme of assisted reproduction, to wish to deliver in the 

reference hospital, and to have no communication problems

Exclusion Criteria: NR

Adjustments: Child gender, maternal 

social class, siblings at birth, maternal 

smoking in pregnancy, and DDE levels 

in cord blood for wheezing outcome

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Morales 2012184 Wheezing

N Total: 197

6 &14 months AA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 1.34

95% CI(0.44, 4.06)

Wheezing

N Total: 197

6 &14 months ALA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 1.57

95% CI(0.42, 5.84)

Wheezing

N Total: 197

6 &14 months All n-3

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 1.08

95% CI(0.37, 3.18)

Wheezing

N Total: 197

6 &14 months DHA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 0.91

95% CI(0.31, 2.67)

Wheezing

N Total: 197

6 &14 months EPA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 0.56

95% CI(0.15, 2.08)

Wheezing

N Total: 269

7-14 months AA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 1.36

95% CI(0.69, 2.65)

Wheezing

N Total: 269

7-14 months ALA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 0.82

95% CI(0.4, 1.69)
D-43

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Wheezing

N Total: 269

7-14 months All n-3

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 0.72

95% CI(0.36, 1.44)

Wheezing

N Total: 269

7-14 months DHA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 0.94

95% CI(0.48, 1.86)

Wheezing

N Total: 269

7-14 months EPA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 0.58

95% CI(0.27, 1.24)

Wheezing

N Total: 272

0-6 months AA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 1.19

95% CI(0.51, 2.76)

Wheezing

N Total: 272

0-6 months ALA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 1.54

95% CI(0.62, 3.78)

Wheezing

N Total: 272

0-6 months All n-3

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 1.35

95% CI(0.58, 3.13)

Wheezing

N Total: 272

0-6 months DHA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 0.91

95% CI(0.41, 2.03)

Wheezing

N Total: 272

0-6 months EPA

n-3 Measure: Colostrum fatty acid concentration

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total fatty acids

Highest vs. lowest tertile odds 

ratios

N Quantile: NR

OR

Estimate: 2.24

95% CI(0.76, 6.55)
D-44

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Much, et al., 2013101

Study name: INFAT

Study dates: Recruitment: 2006-2009 Follow-up: 1 year

Study design: Observational prospective

Location: Germany

Funding source / conflict: Industry, Government, Some 

authors employed by industry (companies that make the 

supplements)

Follow-up: 1 year

Original, same study, or follow-up studies: Hauner, 201237

Study Population: Healthy infants Breast-feeding women

Pregnant enrolled 208

Lactating enrolled 152 at 6 weeks/120 at 4 months

Infants enrolled 56 at 4 months/31 at 12 months

Lactating enrolled 152 at 6 weeks/120 at 4 months

Pregnant age: Intervention: 31.9 Control: 31.6 (Intervention: 

4.9 Control: 4.5)

Race of Mother: NR (NR)

Inclusion Criteria: Gestational age =15th wk of gestation, between 

18 and 43 y of age, pre-pregnancy BMI (in kg/m2) between 18 and 

30, willingness to implement the dietary recommendations, 

sufficient German language skills, and written informed consent

Exclusion Criteria: High-risk pregnancy (multiple pregnancy, rhesus 

incompatibility, hepatitis B infection, or parity >4); hypertension; 

chronic diseases (e.g., diabetes) or gastrointestinal disorders 

accompanied by maldigestion, malabsorption, or elevated energy 

and nutritional requirements (e.g., gluten enteropathy); known 

metabolic defects (e.g., phenylketonuria); psychiatric diseases; 

hyperemesis gravidarum; supplementation with n–3 LCPUFAs 

before randomization; and alcohol abuse and smoking

Adjustments: Gestational age, parity, 

infant sex, group, ponderal index at 

birth, breastfeeding status of infants at 

6 wk, 4 mo, and 1 yr.

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Much 2013101 BMI at 1 yr

N Total: 117

1 y DHA

n-3 Measure: Breast milk at 4 mo postpartum

n-3 Units: % wt

Coefficient

Estimate: 0.86

95% CI(0.11, 1.62)

Length at 1 yr

N Total: 117

1 y EPA

n-3 Measure: Breast milk at 4 mo postpartum

n-3 Units: % wt

Coefficient

Estimate: -12.43

95% CI(-20.36, -4.231)

Length at 4 mo

N Total: 119

4 mo EPA

n-3 Measure: Breast milk at 4 mo postpartum

n-3 Units: % wt

Coefficient

Estimate: -7.85

95% CI(-14.94, -0.73)
D-45

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Much, et al., 201383

Study name: INFAT

Study dates: >2009-<2013

Study design: Observational prospective

Location: Germany

Funding source / conflict: Industry, Government, Some 

authors employed by industry (companies that make the 

supplements), Multiple foundations and Societies, None

Study Population: Healthy infants Breast-feeding women

Pregnant enrolled 208

Infants completers 187

Race of Mother: NR (NR)

Inclusion Criteria: Healthy pregnant women at 14th week of 

gestation

Exclusion Criteria: None reported

Adjustments: Pregnancy duration, 

group, parity, and sex

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Much 2013 83 Birth weight

N Total: 187

DHA at 32 wks gestation

n-3 Measure: Maternal red blood cells

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 24.38

95% CI(0.42, 48.33)

Birth weight

N Total: 187

n-3 LCPUFA at 32 wks gestation

n-3 Measure: Maternal red blood cells

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 20.38

95% CI(2.78, 37.99)

Much 201383 BMI

N Total: 169

12 mo DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: -0.04

95% CI(-0.11, 0.04)

BMI

N Total: 169

12 mo n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: -0.02

95% CI(-0.08, 0.04)

BMI

N Total: 172

4 mo DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.04

95% CI(-0.04, 0.12)

BMI

N Total: 172

4 mo n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.03

95% CI(-0.03, 0.09)

BMI

N Total: 177

6 wks DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.05

95% CI(-0.02, 0.12)

BMI

N Total: 177

6 wks n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.04

95% CI(-0.01, 0.09)
D-46

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

BMI

N Total: 187

Birth DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.04

95% CI(-0.03, 0.1)

BMI

N Total: 187

Birth n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.03

95% CI(-0.02, 0.08)

Head circumference

N Total: 169

12 mo DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.01

95% CI(-0.08, 0.22)

Head circumference

N Total: 169

12 mo n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.01

95% CI(-0.05, 0.08)

Head circumference

N Total: 172

4 mo DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.02

95% CI(-0.04, 0.09)

Head circumference

N Total: 172

4 mo n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.03

95% CI(-0.02, 0.08)

Head circumference

N Total: 177

6 wks DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.02

95% CI(-0.04, 0.1)

Head circumference

N Total: 177

6 wks n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.02

95% CI(-0.02, 0.07)

Head circumference

N Total: 187

Birth DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.07

95% CI(0, 0.14)

Head circumference

N Total: 187

Birth n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.06

95% CI(0.01, 0.12)

Length

N Total: 169

12 mo DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.07

95% CI(-0.08, 0.22)

Length

N Total: 169

12 mo n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.04

95% CI(-0.07, 0.15)
D-47

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Length

N Total: 172

4 mo DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.03

95% CI(-0.09, 0.15)

Length

N Total: 172

4 mo n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.02

95% CI(-0.07, 0.11)

Length

N Total: 177

6 wks DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.05

95% CI(-0.07, 0.18)

Length

N Total: 177

6 wks n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.05

95% CI(-0.04, 0.15)

Length

N Total: 187

Birth DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.12

95% CI(-0.01, 0.24)

Length

N Total: 187

Birth n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 0.1

95% CI(0.01, 0.19)

Weight

N Total: 169

12 mo DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: -0.99

95% CI(-58.1, 56.12)

Weight

N Total: 169

12 mo n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 1.4

95% CI(-40.7, 43.5)

Weight

N Total: 172

4 mo DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 19.72

95% CI(-19.25, 58.69)

Weight

N Total: 172

4 mo n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 15.17

95% CI(-13.49, 43.84)

Weight

N Total: 177

6 wks DHA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 24.16

95% CI(-8.96, 57.29)

Weight

N Total: 177

6 wks n-3 LCPUFA

n-3 Measure: Maternal red blood cells at 32 wks 

gestation

n-3 Units: per unit increase in % of total FA

Coefficient

Estimate: 21.53

95% CI(-2.81, 45.86)
D-48

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Muthayya, et al., 200972

Study dates: Jan 2002- Mar 2006

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Study Population: Healthy pregnant women

Pregnant enrolled 829 Pregnant completers 676

Pregnant age: group 1, 23 group 2, 23 group 3, 23 total, 24 

group 1, 21-26 group 2, 21-27 group 3, 23-29 total: 21-27

Race of Mother: Asian (Indian, 100%)

Inclusion Criteria: pregnant women aged 17–40 years and at <20 

weeks of gestation, registered for antenatal screening at the 

Department of Obstetrics and Gynecology at St John’s Medical 

College Hospital,

Exclusion Criteria: Women with multiple pregnancies, those with a 

clinical diagnosis of chronic illness such as diabetes mellitus, 

hypertension, heart disease and thyroid disease, those who tested 

positive for HbSAg/HIV/VDRL infection or who anticipated moving 

out of the city before delivery were excluded

Adjustments: Adjusted for maternal 

age, maternal education, parity, 

maternal weight/maternal weight gain 

per week and gestational age

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Muthayya 200972 Low birth weight

N Total: 419

EPA @ 3rd trimester

n-3 Measure: FFQ

n-3 Units: mg/day

T1 0.28

N Cases: 133

AOR

Estimate: 2.75

95% CI(1.26, 6.02)

Low birth weight

N Total: 419

EPA @ 3rd trimester

n-3 Measure: FFQ

n-3 Units: mg/day

T2 3.03

N Cases: 148

AOR

Estimate: 2.54

95% CI(1.17, 5.5)

Low birth weight

N Total: 419

EPA @ 3rd trimester

n-3 Measure: FFQ

n-3 Units: mg/day

T3 9.53

N Cases: 138

AOR

Low birth weight

N Total: 675

EPA @ 1st trimester

n-3 Measure: FFQ

n-3 Units: mg/day

T1 0.24

N Cases: 225

AOR

Estimate: 1.61

95% CI(0.92, 2.8)

Low birth weight

N Total: 675

EPA @ 1st trimester

n-3 Measure: FFQ

n-3 Units: mg/day

T2 2.1

N Cases: 224

AOR

Estimate: 1.05

95% CI(0.59, 1.9)

Low birth weight

N Total: 675

EPA @ 1st trimester

n-3 Measure: FFQ

n-3 Units: mg/day

T3 9.37

N Cases: 226

AOR
D-49

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Newson, et al., 2004176

Study name: Avon Longitudinal Study of Parents and 

Children (ALSPAC)

Study dates: Recruitment: April 1, 1991 to December 31, 

1992 Follow-up: 42 months

Study design: Observational prospective

Location: UK

Funding source / conflict: Government, Multiple foundations 

and Societies

Follow-up: 42 months

Original, same study, or follow-up studies: Golding et al., 

2001 (ALSPAC)

Study Population: Healthy infants

Pregnant enrolled 4136

Infants enrolled 4202 Infants completers 1762

Infant age: Prenatal

Race of Mother: NR (100%)

Inclusion Criteria: Pregnant women with expected date of delivery 

between April 1, 1991, and December 31, 1992, and place of 

residence within the 3 Bristol-based health districts of the former 

county of Avon, United Kingdom

Exclusion Criteria: NR for enrollment. Exclusion for analysis: 

multiple pregnancies or in small missing value categories for 

various confounders.

Adjustments: Child’s sex, gestational 

age at birth, and birth weight, and for 

the mother’s age, education level, 

housing tenure, parity, ethnicity, and 

smoking in pregnancy (for variable 

categories see Table EI in the 

Journal’s Online Repository at 

http://www.mosby.com/jaci), as well as 

maternal atopic disease (asthma, 

eczema, rhinoconjunctivitis), child’s 

head circumference at birth ( < 33 cm, 

33-34.99 cm, 35-36.99 cm, 37+ cm, 

unknown), child’s crown to heel length 

at birth ( < 48 cm, 48-50.99 cm, 51-

53.99 cm, 54+ cm, unknown), 

mother’s body mass index (from prepregnancy self-reported weight and 

height; < 18.5 kg/m2 , 18.5-24.99 

kg/m2 , 25-29.99 kg/m2 , 30+ kg/m2 , 

unknown), breast-feeding

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Newson 2004176 Eczema

N Total: 1238

30 months 18:3 n-3 ALA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1

95% CI(0.9, 1.11)

Eczema

N Total: 1238

30 months 20:4 n-6 AA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.08

95% CI(0.93, 1.25)

Eczema

N Total: 1238

30 months 20:5 n-3 EPA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 0.95

95% CI(0.86, 1.06)

Eczema

N Total: 1238

30 months 22:6 n-3 DHA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1

95% CI(0.91, 1.1)

Eczema

N Total: 1238

30 months AA: EPA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.14

95% CI(1, 1.31)

Eczema

N Total: 2945

30 months 18:3 n-3 ALA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1

95% CI(0.91, 1.09)

Eczema

N Total: 2945

30 months 20:4 n-6 AA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 0.98

95% CI(0.88, 1.1)

Eczema

N Total: 2945

30 months 20:5 n-3 EPA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.03

95% CI(0.94, 1.12)
D-50

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 2945

30 months 22:6 n-3 DHA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.02

95% CI(0.94, 1.12)

Eczema

N Total: 2945

30 months AA: EPA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 0.95

95% CI(0.85, 1.05)

Wheezing

N Total: 1191

42 months 18:3 n-3 ALA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 0.99

95% CI(0.85, 1.15)

Wheezing

N Total: 1191

42 months 20:4 n-6 AA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.05

95% CI(0.86, 1.27)

Wheezing

N Total: 1191

42 months 20:5 n-3 EPA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.01

95% CI(0.87, 1.17)

Wheezing

N Total: 1191

42 months 22:6 n-3 DHA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.05

95% CI(0.93, 1.19)

Wheezing

N Total: 1191

42 months AA: EPA

n-3 Measure: Cord blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.01

95% CI(0.85, 1.21)

Wheezing

N Total: 2764

42 months 18:3 n-3 ALA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.03

95% CI(0.91, 1.16)

Wheezing

N Total: 2764

42 months 20:4 n-6 AA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.02

95% CI(0.86, 1.2)

Wheezing

N Total: 2764

42 months 20:5 n-3 EPA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 0.94

95% CI(0.84, 1.06)

Wheezing

N Total: 2764

42 months 22:6 n-3 DHA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 0.99

95% CI(0.86, 1.13)

Wheezing

N Total: 2764

42 months AA: EPA

n-3 Measure: Maternal blood

n-3 Units: % of total RBC membrane phospholipid

All Per doubling OR

Estimate: 1.11

95% CI(0.95, 1.3)
D-51

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Notenboom, et al., 2011179

Study name: KOALA Birth Cohort Study

Study dates: Recruitment from October 2000 onwards and 

Follow-up: 6-7 years

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government, Multiple 

foundations and Societies

Follow-up: 3 - 84 months

Study Population: Healthy infants Healthy pregnant women

Infants enrolled 1275 Infants completers 1253 (samples for 

815)

Mother age: 32.6 (3.8)

Race of Mother: White European (Dutch 96.3%)

Inclusion Criteria: Conventional participants: participation in 

ongoing study of pelvic girdle pain Alternative participants: 

frequented locations associated with organic diet and similar 

lifestyles Subsample: participants recruited from January 2002 

onwards who consented to biosampling.

Exclusion Criteria: Current multiple pregnancy n=9 Prematurity 

n=15 Perinatal infant death n=2 Down syndrome n=4 No response 

after birth n=51

Adjustments: Adjusted for recruitment 

group, maternal age, maternal 

ethnicity, maternal education level, 

maternal smoking during pregnancy, 

parental history of atopy, term of 

gestation, season of birth, gender, 

birth weight, mode of delivery, 

exposure to environmental tobacco, 

presence of older siblings and sibling 

atopy, breastfeeding, child day care, 

and pets at home

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Notenboom 2011179 Allergic rhinoconjunctivitis

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -6.46

N Quantile: 192

N Cases: 13

OR

Allergic rhinoconjunctivitis

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 6.47-7.15

N Quantile: 199

N Cases: 14

OR

Estimate: 1.04

95% CI(0.47, 2.27)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 7.16-7.85

N Quantile: 190

N Cases: 15

OR

Estimate: 1.17

95% CI(0.54, 2.53)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 7.86-8.6

N Quantile: 199

N Cases: 12

OR

Estimate: 0.87

95% CI(0.39, 1.197)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 8.61-

N Quantile: 171

N Cases: 15

OR

Estimate: 1.3

95% CI(0.59, 2.83)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -60.72

N Quantile: 176

N Cases: 14

OR

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 60.73-72.35

N Quantile: 189

N Cases: 16

OR

Estimate: 1.07

95% CI(0.51, 2.26)
D-52

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 72.36-82.29

N Quantile: 191

N Cases: 8

OR

Estimate: 0.51

95% CI(0.21, 1.25)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 83.3-102.69

N Quantile: 205

N Cases: 15

OR

Estimate: 0.92

95% CI(0.43, 2)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 102.7-

N Quantile: 190

N Cases: 16

OR

Estimate: 1.09

95% CI(0.51, 2.31)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -1.91

N Quantile: 195

N Cases: 8

OR

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 1.92-2.24

N Quantile: 194

N Cases: 14

OR

Estimate: 1.81

95% CI(0.74, 4.41)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 2.25-2.52

N Quantile: 187

N Cases: 18

OR

Estimate: 2.48

95% CI(1.05, 5.85)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 2.53-2.84

N Quantile: 183

N Cases: 12

OR

Estimate: 1.62

95% CI(0.64, 4.06)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 2.85-

N Quantile: 192

N Cases: 17

OR

Estimate: 2.24

95% CI(0.94, 5.34)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -3.93

N Quantile: 195

N Cases: 19

OR

Allergic rhinoconjunctivitis

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 3.94-4.44

N Quantile: 185

N Cases: 10

OR

Estimate: 0.53

95% CI(0.24, 1.17)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 4.45-4.93

N Quantile: 182

N Cases: 16

OR

Estimate: 0.89

95% CI(0.44, 1.79)
D-53

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Allergic rhinoconjunctivitis

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 4.94-5.64

N Quantile: 191

N Cases: 16

OR

Estimate: 0.85

95% CI(0.42, 1.71)

Allergic rhinoconjunctivitis

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 5.65-

N Quantile: 198

N Cases: 8

OR

Estimate: 0.4

95% CI(0.17, 0.92)

Allergic sensitization

N Total: 768

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -6.46

N Quantile: 156

N Cases: 45

OR

Allergic sensitization

N Total: 768

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 6.47-7.15

N Quantile: 159

N Cases: 42

OR

Estimate: 0.81

95% CI(0.48, 1.34)

Allergic sensitization

N Total: 768

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 7.16-7.85

N Quantile: 159

N Cases: 52

OR

Estimate: 1.15

95% CI(0.7, 1.9)

Allergic sensitization

N Total: 768

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 7.86-8.6

N Quantile: 153

N Cases: 41

OR

Estimate: 0.86

95% CI(0.51, 1.46)

Allergic sensitization

N Total: 768

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 8.61-

N Quantile: 141

N Cases: 33

OR

Estimate: 0.69

95% CI(0.39, 1.23)

Allergic sensitization

N Total: 768

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -60.72

N Quantile: 152

N Cases: 44

OR

Allergic sensitization

N Total: 768

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 60.73-72.35

N Quantile: 158

N Cases: 42

OR

Estimate: 0.88

95% CI(0.53, 1.49)

Allergic sensitization

N Total: 768

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 72.36-82.29

N Quantile: 152

N Cases: 41

OR

Estimate: 0.96

95% CI(0.57, 1.62)

Allergic sensitization

N Total: 768

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 83.3-102.69

N Quantile: 151

N Cases: 47

OR

Estimate: 1.1

95% CI(0.65, 1.85)

Allergic sensitization

N Total: 768

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 102.7-

N Quantile: 155

N Cases: 39

OR

Estimate: 0.82

95% CI(0.48, 1.4)
D-54

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Allergic sensitization

N Total: 768

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -1.91

N Quantile: 143

N Cases: 40

OR

Allergic sensitization

N Total: 768

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 1.92-2.24

N Quantile: 150

N Cases: 42

OR

Estimate: 1.01

95% CI(0.59, 1.72)

Allergic sensitization

N Total: 768

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 2.25-2.52

N Quantile: 155

N Cases: 44

OR

Estimate: 1.03

95% CI(0.6, 1.76)

Allergic sensitization

N Total: 768

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 2.53-2.84

N Quantile: 167

N Cases: 44

OR

Estimate: 0.92

95% CI(0.53, 1.6)

Allergic sensitization

N Total: 768

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 2.85-

N Quantile: 153

N Cases: 43

OR

Estimate: 1.04

95% CI(0.6, 1.8)

Allergic sensitization

N Total: 768

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -3.93

N Quantile: 169

N Cases: 51

OR

Allergic sensitization

N Total: 768

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 3.94-4.44

N Quantile: 146

N Cases: 39

OR

Estimate: 0.79

95% CI(0.47, 1.33)

Allergic sensitization

N Total: 768

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 4.45-4.93

N Quantile: 154

N Cases: 43

OR

Estimate: 0.83

95% CI(0.5, 1.4)

Allergic sensitization

N Total: 768

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 4.94-5.64

N Quantile: 159

N Cases: 38

OR

Estimate: 0.73

95% CI(0.44, 1.24)

Allergic sensitization

N Total: 768

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 5.65-

N Quantile: 140

N Cases: 42

OR

Estimate: 0.94

95% CI(0.56, 1.6)

Asthma

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -6.46

N Quantile: NR

N Cases: NR

OR
D-55

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Asthma

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 6.47-7.15

N Quantile: NR

N Cases: NR

OR

Estimate: 1.69

95% CI(0.7, 4.1)

Asthma

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 7.16-7.85

N Quantile: NR

N Cases: NR

OR

Estimate: 1.29

95% CI(0.52, 3.2)

Asthma

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 7.86-8.6

N Quantile: NR

N Cases: NR

OR

Estimate: 0.82

95% CI(0.31, 2.15)

Asthma

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 8.61-

N Quantile: NR

N Cases: NR

OR

Estimate: 1.7

95% CI(0.67, 4.33)

Asthma

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -60.72

N Quantile: NR

N Cases: NR

OR

Asthma

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 60.73-72.35

N Quantile: NR

N Cases: NR

OR

Estimate: 1.14

95% CI(0.51, 2.55)

Asthma

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 72.36-82.29

N Quantile: NR

N Cases: NR

OR

Estimate: 0.55

95% CI(0.21, 1.45)

Asthma

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 83.3-102.69

N Quantile: NR

N Cases: NR

OR

Estimate: 1.08

95% CI(0.47, 2.49)

Asthma

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 102.7-

N Quantile: NR

N Cases: NR

OR

Estimate: 0.6

95% CI(0.23, 1.56)

Asthma

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -1.91

N Quantile: NR

N Cases: NR

OR

Asthma

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 1.92-2.24

N Quantile: NR

N Cases: NR

OR

Estimate: 1.12

95% CI(0.43, 2.89)

Asthma

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 2.25-2.52

N Quantile: NR

N Cases: NR

OR

Estimate: 1.47

95% CI(0.56, 3.85)
D-56

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Asthma

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 2.53-2.84

N Quantile: NR

N Cases: NR

OR

Estimate: 2.07

95% CI(0.82, 5.24)

Asthma

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 2.85-

N Quantile: NR

N Cases: NR

OR

Estimate: 1.87

95% CI(0.76, 4.63)

Asthma

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -3.93

N Quantile: NR

N Cases: NR

OR

Asthma

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 3.94-4.44

N Quantile: NR

N Cases: NR

OR

Estimate: 1.85

95% CI(0.83, 4.12)

Asthma

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 4.45-4.93

N Quantile: NR

N Cases: NR

OR

Estimate: 1.12

95% CI(0.45, 2.71)

Asthma

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 4.94-5.64

N Quantile: NR

N Cases: NR

OR

Estimate: 0.92

95% CI(0.37, 2.29)

Asthma

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma

phospholipids

n-3 Units: wt%

Q5 5.65-

N Quantile: NR

N Cases: NR

OR

Estimate: 0.85

95% CI(0.34, 2.16)

Atopic dermatitis

N Total: 807

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -6.46

N Quantile: 161

N Cases: 20

OR

Atopic dermatitis

N Total: 807

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 6.47-7.15

N Quantile: 166

N Cases: 23

OR

Estimate: 1.15

95% CI(0.59, 2.28)

Atopic dermatitis

N Total: 807

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 7.16-7.85

N Quantile: 166

N Cases: 24

OR

Estimate: 1.24

95% CI(0.63, 2.44)

Atopic dermatitis

N Total: 807

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 7.86-8.6

N Quantile: 162

N Cases: 26

OR

Estimate: 1.35

95% CI(0.79, 2.65)

Atopic dermatitis

N Total: 807

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 8.61-

N Quantile: 152

N Cases: 18

OR

Estimate: 0.94

95% CI(0.44, 1.98)
D-57

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Atopic dermatitis

N Total: 807

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -60.72

N Quantile: 159

N Cases: 18

OR

Atopic dermatitis

N Total: 807

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 60.73-72.35

N Quantile: 163

N Cases: 18

OR

Estimate: 0.89

95% CI(0.43, 1.85)

Atopic dermatitis

N Total: 807

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 72.36-82.29

N Quantile: 156

N Cases: 24

OR

Estimate: 1.63

95% CI(0.81, 3.27)

Atopic dermatitis

N Total: 807

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 83.3-102.69

N Quantile: 161

N Cases: 31

OR

Estimate: 2.17

95% CI(1.1, 4.27)

Atopic dermatitis

N Total: 807

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 102.7-

N Quantile: 168

N Cases: 20

OR

Estimate: 1.16

95% CI(0.56, 2.39)

Atopic dermatitis

N Total: 807

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -1.91

N Quantile: 155

N Cases: 23

OR

Atopic dermatitis

N Total: 807

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 1.92-2.24

N Quantile: 154

N Cases: 21

OR

Estimate: 0.94

95% CI(0.49, 1.83)

Atopic dermatitis

N Total: 807

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 2.25-2.52

N Quantile: 162

N Cases: 24

OR

Estimate: 1.21

95% CI(0.63, 2.35)

Atopic dermatitis

N Total: 807

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 2.53-2.84

N Quantile: 175

N Cases: 22

OR

Estimate: 0.98

95% CI(0.49, 2)

Atopic dermatitis

N Total: 807

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 2.85-

N Quantile: 162

N Cases: 21

OR

Estimate: 0.9

95% CI(0.45, 1.81)

Atopic dermatitis

N Total: 807

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -3.93

N Quantile: 174

N Cases: 22

OR
D-58

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Atopic dermatitis

N Total: 807

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 3.94-4.44

N Quantile: 155

N Cases: 24

OR

Estimate: 1.24

95% CI(0.64, 2.42)

Atopic dermatitis

N Total: 807

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 4.45-4.93

N Quantile: 163

N Cases: 24

OR

Estimate: 1.1

95% CI(0.56, 2.17)

Atopic dermatitis

N Total: 807

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 4.94-5.64

N Quantile: 164

N Cases: 21

OR

Estimate: 1

95% CI(0.5, 1.98)

Atopic dermatitis

N Total: 807

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 5.65-

N Quantile: 151

N Cases: 20

OR

Estimate: 0.92

95% CI(0.46, 1.86)

Eczema

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -6.46

N Quantile: NR

N Cases: NR

OR

Eczema

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 6.47-7.15

N Quantile: NR

N Cases: NR

OR

Estimate: 0.94

95% CI(0.67, 1.31)

Eczema

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 7.16-7.85

N Quantile: NR

N Cases: NR

OR

Estimate: 1.03

95% CI(0.73, 1.44)

Eczema

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 7.86-8.6

N Quantile: NR

N Cases: NR

OR

Estimate: 0.77

95% CI(0.55, 1.09)

Eczema

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 8.61-

N Quantile: NR

N Cases: NR

OR

Estimate: 0.81

95% CI(0.56, 1.15)

Eczema

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -60.72

N Quantile: NR

N Cases: NR

OR

Eczema

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 60.73-72.35

N Quantile: NR

N Cases: NR

OR

Estimate: 1.04

95% CI(0.73, 1.47)

Eczema

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 72.36-82.29

N Quantile: NR

N Cases: NR

OR

Estimate: 1.12

95% CI(0.8, 1.57)
D-59

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 83.3-102.69

N Quantile: NR

N Cases: NR

OR

Estimate: 0.83

95% CI(0.58, 1.19)

Eczema

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 102.7-

N Quantile: NR

N Cases: NR

OR

Estimate: 0.94

95% CI(0.66, 1.34)

Eczema

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -1.91

N Quantile: NR

N Cases: NR

OR

Eczema

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 1.92-2.24

N Quantile: NR

N Cases: NR

OR

Estimate: 0.72

95% CI(0.51, 1)

Eczema

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 2.25-2.52

N Quantile: NR

N Cases: NR

OR

Estimate: 0.68

95% CI(0.49, 0.96)

Eczema

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 2.53-2.84

N Quantile: NR

N Cases: NR

OR

Estimate: 0.7

95% CI(0.49, 0.98)

Eczema

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 2.85-

N Quantile: NR

N Cases: NR

OR

Estimate: 0.6

95% CI(0.42, 0.87)

Eczema

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -3.93

N Quantile: NR

N Cases: NR

OR

Eczema

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 3.94-4.44

N Quantile: NR

N Cases: NR

OR

Estimate: 1.21

95% CI(0.85, 1.73)

Eczema

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 4.45-4.93

N Quantile: NR

N Cases: NR

OR

Estimate: 1.02

95% CI(0.71, 1.47)

Eczema

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 4.94-5.64

N Quantile: NR

N Cases: NR

OR

Estimate: 1.3

95% CI(0.91, 1.85)
D-60

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 5.65-

N Quantile: NR

N Cases: NR

OR

Estimate: 1.29

95% CI(0.91, 1.83)

High total IgE

N Total: 776

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -6.46

N Quantile: 158

N Cases: 57

OR

High total IgE

N Total: 776

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 6.47-7.15

N Quantile: 159

N Cases: 44

OR

Estimate: 0.69

95% CI(0.42, 1.15)

High total IgE

N Total: 776

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 7.16-7.85

N Quantile: 162

N Cases: 67

OR

Estimate: 1.29

95% CI(0.8, 2.09)

High total IgE

N Total: 776

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 7.86-8.6

N Quantile: 153

N Cases: 49

OR

Estimate: 0.83

95% CI(0.5, 1.37)

High total IgE

N Total: 776

24 months AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 8.61-

N Quantile: 144

N Cases: 39

OR

Estimate: 0.72

95% CI(0.42, 1.24)

High total IgE

N Total: 776

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -60.72

N Quantile: 152

N Cases: 47

OR

High total IgE

N Total: 776

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 60.73-72.35

N Quantile: 158

N Cases: 43

OR

Estimate: 0.82

95% CI(0.5, 1.41)

High total IgE

N Total: 776

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 72.36-82.29

N Quantile: 154

N Cases: 51

OR

Estimate: 1.04

95% CI(0.63, 1.72)

High total IgE

N Total: 776

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 83.3-102.69

N Quantile: 153

N Cases: 63

OR

Estimate: 1.42

95% CI(0.86, 2.35)

High total IgE

N Total: 776

24 months Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 102.7-

N Quantile: 159

N Cases: 52

OR

Estimate: 0.88

95% CI(0.53, 1.47)

High total IgE

N Total: 776

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -1.91

N Quantile: 147

N Cases: 51

OR
D-61

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

High total IgE

N Total: 776

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 1.92-2.24

N Quantile: 150

N Cases: 46

OR

Estimate: 0.83

95% CI(0.5, 1.39)

High total IgE

N Total: 776

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 2.25-2.52

N Quantile: 155

N Cases: 53

OR

Estimate: 0.97

95% CI(0.58, 1.61)

High total IgE

N Total: 776

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 2.53-2.84

N Quantile: 169

N Cases: 50

OR

Estimate: 0.84

95% CI(0.5, 1.42)

High total IgE

N Total: 776

24 months Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 2.85-

N Quantile: 155

N Cases: 56

OR

Estimate: 1.02

95% CI(0.61, 1.71)

High total IgE

N Total: 776

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -3.93

N Quantile: 169

N Cases: 63

OR

High total IgE

N Total: 776

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 3.94-4.44

N Quantile: 149

N Cases: 44

OR

Estimate: 0.74

95% CI(0.45, 1.22)

High total IgE

N Total: 776

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 4.45-4.93

N Quantile: 156

N Cases: 54

OR

Estimate: 0.93

95% CI(0.57, 1.52)

High total IgE

N Total: 776

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 4.94-5.64

N Quantile: 159

N Cases: 48

OR

Estimate: 0.79

95% CI(0.48, 1.3)

High total IgE

N Total: 776

24 months n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 5.65-

N Quantile: 143

N Cases: 47

OR

Estimate: 0.88

95% CI(0.53, 1.46)

Wheeze

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -6.46

N Quantile: NR

N Cases: NR

OR

Wheeze

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 6.47-7.15

N Quantile: NR

N Cases: NR

OR

Estimate: 1.23

95% CI(0.87, 1.73)
D-62

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Wheeze

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 7.16-7.85

N Quantile: NR

N Cases: NR

OR

Estimate: 1.08

95% CI(0.78, 1.5)

Wheeze

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 7.86-8.6

N Quantile: NR

N Cases: NR

OR

Estimate: 1.08

95% CI(0.78, 1.49)

Wheeze

N Total: 951

6-7 years AA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 8.61-

N Quantile: NR

N Cases: NR

OR

Estimate: 1.03

95% CI(0.74, 1.44)

Wheeze

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -60.72

N Quantile: NR

N Cases: NR

OR

Wheeze

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 60.73-72.35

N Quantile: NR

N Cases: NR

OR

Estimate: 1.04

95% CI(0.76, 1.42)

Wheeze

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 72.36-82.29

N Quantile: NR

N Cases: NR

OR

Estimate: 0.87

95% CI(0.64, 1.19)

Wheeze

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 83.3-102.69

N Quantile: NR

N Cases: NR

OR

Estimate: 0.9

95% CI(0.66, 1.23)

Wheeze

N Total: 951

6-7 years Ratio LA to ALA

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 102.7-

N Quantile: NR

N Cases: NR

OR

Estimate: 0.91

95% CI(0.68, 1.23)

Wheeze

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -1.91

N Quantile: NR

N Cases: NR

OR

Wheeze

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 1.92-2.24

N Quantile: NR

N Cases: NR

OR

Estimate: 0.88

95% CI(0.63, 1.23)

Wheeze

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 2.25-2.52

N Quantile: NR

N Cases: NR

OR

Estimate: 1.03

95% CI(0.75, 1.42)
D-63

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Wheeze

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 2.53-2.84

N Quantile: NR

N Cases: NR

OR

Estimate: 0.83

95% CI(0.59, 1.18)

Wheeze

N Total: 951

6-7 years Ratio n-6 LCPs (LGLA and AA) to n-3 LCPs 

(EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 2.85-

N Quantile: NR

N Cases: NR

OR

Estimate: 0.97

95% CI(0.7, 1.35)

Wheeze

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q1 -3.93

N Quantile: NR

N Cases: NR

OR

Wheeze

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q2 3.94-4.44

N Quantile: NR

N Cases: NR

OR

Estimate: 0.96

95% CI(0.7, 1.31)

Wheeze

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q3 4.45-4.93

N Quantile: NR

N Cases: NR

OR

Estimate: 1.12

95% CI(0.82, 1.53)

Wheeze

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q4 4.94-5.64

N Quantile: NR

N Cases: NR

OR

Estimate: 1.15

95% CI(0.85, 1.57)

Wheeze

N Total: 951

6-7 years n-3 LCPs (EPA, DPA n-3, DHA)

n-3 Measure: maternal venous plasma 

phospholipids

n-3 Units: wt%

Q5 5.65-

N Quantile: NR

N Cases: NR

OR

Estimate: 0.98

95% CI(0.7, 1.37)
D-64

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Nwaru, et al., 2012180

Study name: Finnish Type 1 Diabetes Prediction and 

Prevention Nutrition Study

Study dates: Infants recruited between 20 October 1997 and 

29 February 2004; Follow-up to 5 years of age

Study design: Observational prospective

Location: Finland

Funding source / conflict: Government, Multiple foundations 

and Societies

Follow-up: 5 years

Study Population: NR

Pregnant enrolled NR Pregnant completers 3523

Infants enrolled 3253 Infants completers 2441

Infant age: birth

Race of Mother: White European (100%)

Inclusion Criteria: Newborn infants with human leucocyte antigen 

(HLA)- conferred susceptibility to type 1 diabetes recruited from 

three university hospitals in Finland

Exclusion Criteria: Infants with severe systemic disease or 

anomalies, or both parents non-Caucasian

Adjustments: Sex of child, hospital of 

birth, duration of gestation, maternal 

age at delivery, maternal basic 

education, maternal smoking during 

pregnancy, mode of delivery, number 

of siblings at the time of the child’s 

birth, parental asthma, parental 

allergic rhinitis, pets at home by 1 year 

of age. A second adjusted model was 

computed for the FA in which 

potentially confounding nutrients, 

vitamin C, Zn, Se, vitamin D and 

vitamin E were included as additional 

covariates

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Nwaru 2012180 Allergic rhinitis

N Total: 2441

5 years ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 -4.45

N Quantile: NR

N Cases: NR

OR

Estimate: 1.01

95% CI(0.79, 1.29)

Allergic rhinitis

N Total: 2441

5 years ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 4.45-6.4

N Quantile: NR

N Cases: NR

OR

Allergic rhinitis

N Total: 2441

5 years ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 6.4-8.9

N Quantile: NR

N Cases: NR

OR

Estimate: 0.74

95% CI(0.56, 0.99)

Allergic rhinitis

N Total: 2441

5 years DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 -0.19

N Quantile: NR

N Cases: NR

OR

Estimate: 0.94

95% CI(0.72, 1.22)

Allergic rhinitis

N Total: 2441

5 years DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 0.19-0.6

N Quantile: NR

N Cases: NR

OR

Allergic rhinitis

N Total: 2441

5 years DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 0.6-3.5

N Quantile: NR

N Cases: NR

OR

Estimate: 0.93

95% CI(0.72, 1.21)

Allergic rhinitis

N Total: 2441

5 years EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 -0.07

N Quantile: NR

N Cases: NR

OR

Estimate: 0.99

95% CI(0.76, 1.29)

Allergic rhinitis

N Total: 2441

5 years EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 0.07-0.23

N Quantile: NR

N Cases: NR

OR

Allergic rhinitis

N Total: 2441

5 years EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 0.23-1.25

N Quantile: NR

N Cases: NR

OR

Estimate: 0.99

95% CI(0.76, 1.28)
D-65

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Allergic rhinitis

N Total: 2441

5 years Ratio of n-6 to n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 NR-NR

N Quantile: NR

N Cases: NR

OR

Estimate: 1.09

95% CI(0.84, 1.43)

Allergic rhinitis

N Total: 2441

5 years Ratio of n-6 to n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 NR-NR

N Quantile: NR

N Cases: NR

OR

Allergic rhinitis

N Total: 2441

5 years Ratio of n-6 to n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 NR-NR

N Quantile: NR

N Cases: NR

OR

Estimate: 1.35

95% CI(1.05, 1.73)

Allergic rhinitis

N Total: 2441

5 years n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 -5.55

N Quantile: NR

N Cases: NR

OR

Estimate: 0.89

95% CI(0.69, 1.15)

Allergic rhinitis

N Total: 2441

5 years n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 5.55-7.34

N Quantile: NR

N Cases: NR

OR

Allergic rhinitis

N Total: 2441

5 years n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 7.35-11.28

N Quantile: NR

N Cases: NR

OR

Estimate: 0.82

95% CI(0.63, 1.08)

Atopic eczema

N Total: 2441

5 years ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 -4.45

N Quantile: NR

N Cases: NR

OR

Estimate: 1.05

95% CI(0.86, 1.3)

Atopic eczema

N Total: 2441

5 years ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 4.45-6.4

N Quantile: NR

N Cases: NR

OR

Atopic eczema

N Total: 2441

5 years ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 6.4-8.9

N Quantile: NR

N Cases: NR

OR

Estimate: 0.99

95% CI(0.8, 1.23)

Atopic eczema

N Total: 2441

5 years DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 -0.19

N Quantile: NR

N Cases: NR

OR

Estimate: 1.18

95% CI(0.95, 1.46)

Atopic eczema

N Total: 2441

5 years DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 0.19-0.6

N Quantile: NR

N Cases: NR

OR

Atopic eczema

N Total: 2441

5 years DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 0.6-3.5

N Quantile: NR

N Cases: NR

OR

Estimate: 0.98

95% CI(0.79, 1.2)

Atopic eczema

N Total: 2441

5 years EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 -0.07

N Quantile: NR

N Cases: NR

OR

Estimate: 1.07

95% CI(0.86, 1.33)

Atopic eczema

N Total: 2441

5 years EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 0.07-0.23

N Quantile: NR

N Cases: NR

OR

Atopic eczema

N Total: 2441

5 years EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 0.23-1.25

N Quantile: NR

N Cases: NR

OR

Estimate: 0.94

95% CI(0.76, 1.16)

Atopic eczema

N Total: 2441

5 years Ratio of n-6 to n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 NR-NR

N Quantile: NR

N Cases: NR

OR

Estimate: 0.99

95% CI(0.8, 1.22)
D-66

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Atopic eczema

N Total: 2441

5 years Ratio of n-6 to n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 NR-NR

N Quantile: NR

N Cases: NR

OR

Atopic eczema

N Total: 2441

5 years Ratio of n-6 to n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 NR-NR

N Quantile: NR

N Cases: NR

OR

Estimate: 1.01

95% CI(0.82, 1.24)

Atopic eczema

N Total: 2441

5 years n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 -5.55

N Quantile: NR

N Cases: NR

OR

Estimate: 1.03

95% CI(0.84, 1.27)

Atopic eczema

N Total: 2441

5 years n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 & Q3 5.55-7.34

N Quantile: NR

N Cases: NR

OR

Atopic eczema

N Total: 2441

5 years n-3 PUFA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 7.35-11.28

N Quantile: NR

N Cases: NR

OR

Estimate: 0.93

95% CI(0.75, 1.14)
D-67

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Oken, et al., 200446

Study name: Project Viva

Study dates: 1999-2002

Study design: Observational prospective

Location: US

Funding source / conflict: Government, Multiple foundations 

and Societies

Study Population: Healthy infants Healthy pregnant women

Pregnant enrolled 2109 Pregnant completers 2109

Pregnant age: 14-<20, 3% 20-<25, 6% 25-<30, 21% 30-<35, 

42% 35=<40, 23% >=40, 4% (14-44)

Race of Mother: White European (66) Black (16) Asian (6) 

Hispanic (7) Other race/ethnicity (4)

Inclusion Criteria: delivered a live infant, and completed at least one 

dietary questionnaire

Exclusion Criteria: taking cod liver or fish oil supplement

Adjustments: Enrollment site, infant 

sex, and maternal age, height, 

intrapartum weight gain, prepregnancy BMI, race/ethnicity, 

smoking during pregnancy, education, 

and gravidity

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Oken 200446 Birth weight

N Total: 1663

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q1 0.02

N Quantile: 416

N Cases: NR

50

95% CI(-19, 119)

Birth weight

N Total: 1663

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q2 0.09

N Quantile: 416

N Cases: NR

49

95% CI(-19, 117)

Birth weight

N Total: 1663

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q3 0.18

N Quantile: 416

N Cases: NR

-23

95% CI(-92, 47)

Birth weight

N Total: 1663

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q4 0.38

N Quantile: 416

N Cases: NR

Birth weight

N Total: 1797

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q1 0.02

N Quantile: 449

N Cases: NR

94

95% CI(23, 166)

Birth weight

N Total: 1797

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q2 0.09

N Quantile: 449

N Cases: NR

35

95% CI(-36, 107)

Birth weight

N Total: 1797

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q3 0.18

N Quantile: 449

N Cases: NR

32

95% CI(-39, 103)

Birth weight

N Total: 1797

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q4 0.36

N Quantile: 449

N Cases: NR

Birth weight

N Total: 2070

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q1+Q2 0.05

N Quantile: 1035

N Cases: NR

90

95% CI(33, 147)

Birth weight

N Total: 2070

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q3 0.09

N Quantile: 518

N Cases: NR

11

95% CI(-58, 81)
D-68

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Birth weight

N Total: 2070

DHA+EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q4 0.27

N Quantile: 518

N Cases: NR

Length of gestation

N Total: 1663

DHA+EPA @ 2nd trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q1 0.02

N Quantile: 416

N Cases: NR

Q1-Q4 (difference in 

weeks)

Estimate: 0.3

95% CI(-1.4, 2.1)

Length of gestation

N Total: 1663

DHA+EPA @ 2nd trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q2 0.09

N Quantile: 416

N Cases: NR

Q2-Q4 (difference in 

weeks)

Estimate: -0.4

95% CI(-2.1, 1.3)

Length of gestation

N Total: 1663

DHA+EPA @ 2nd trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q3 0.18

N Quantile: 416

N Cases: NR

Q3-Q4 (difference in 

weeks)

Estimate: 0.3

95% CI(-1.4, 2)

Length of gestation

N Total: 1663

DHA+EPA @ 2nd trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q4 0.38

N Quantile: 416

N Cases: NR

Length of gestation

N Total: 1797

DHA+EPA @ 1st trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q1 0.02

N Quantile: 449

N Cases: NR

Q1-Q4 (difference in 

weeks)

Estimate: 0.3

95% CI(-1.3, 19)

Length of gestation

N Total: 1797

DHA+EPA @ 1st trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q1 vs. Q4 OR

Estimate: 1.1

95% CI(0.7, 1.9)

Length of gestation

N Total: 1797

DHA+EPA @ 1st trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q2 0.09

N Quantile: 449

N Cases: NR

Q2-Q4 (difference in 

weeks)

Estimate: -0.3

95% CI(-1.9, 1.3)

Length of gestation

N Total: 1797

DHA+EPA @ 1st trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q3 0.18

N Quantile: 449

N Cases: NR

Q3-Q4 (difference in 

weeks)

Estimate: 0.6

95% CI(-1, 2.2)

Length of gestation

N Total: 1797

DHA+EPA @ 1st trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q4 0.36

N Quantile: 449

N Cases: NR

Length of gestation

N Total: 2070

DHA+EPA @ 3rd trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q1+Q2 0.05

N Quantile: 1035

N Cases: NR

Q1+Q2-Q4 (difference in 

weeks)

Estimate: 0.5

95% CI(-0.7, 1.7)

Length of gestation

N Total: 2070

DHA+EPA @ 3rd trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q3 0.09

N Quantile: 518

N Cases: NR

Q3-Q4 (difference in 

weeks)

Estimate: -0.7

95% CI(-2.2, 0.8)

Length of gestation

N Total: 2070

DHA+EPA @ 3rd trimester

n-3 Measure: FFQ

n-3 Units: g/day

Q4 0.27

N Quantile: 518

N Cases: NR
D-69

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Oken, et al., 200769

Study name: Project Viva

Study dates: Recruitment 1999-2002

Study design: Observational prospective

Location: US

Funding source / conflict: Government, Multiple foundations 

and Societies

Study Population: Healthy pregnant women

Pregnant enrolled 2,128 Pregnant completers 1,718

Pregnant age: 93% were 20-40 years

Race of Mother: White European (72%) Black (12%) Hispanic 

(6%) Other race/ethnicity (10%)

Inclusion Criteria: 1st trimester pregnant women attending 1st 

prenatal visit

Exclusion Criteria: Post hoc: no live birth, no medical records, 

failure to complete dietary questionnaires, pre-existing chronic 

hypertension and no subsequent preeclampsia

Adjustments: Maternal age, prepregnancy BMI, 1st trimester sBp, 

race/ethnicity, education, parity; 

nutrients adjusted for total energy 

intake

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Oken 200769 Gestational HTN

N Total: 1718

Term AA

n-3 Measure: FFQ

n-3 Units: per 100 mg

N Quantile: NR

N Cases: 119

OR

Estimate: 1.03

95% CI(0.97, 1.1)

Gestational HTN

N Total: 1718

Term ALA

n-3 Measure: FFQ

n-3 Units: per g

N Quantile: NR

N Cases: 119

OR

Estimate: 1.14

95% CI(0.68, 1.92)

Gestational HTN

N Total: 1718

Term DHA+EPA/AA

n-3 Measure: calculated

n-3 Units: ratio

N Quantile: NR

N Cases: 119

OR

Estimate: 0.99

95% CI(0.93, 1.07)

Gestational HTN

N Total: 1718

Term DHA+EPA

n-3 Measure: FFQ

n-3 Units: per 100 mg

N Quantile: NR

N Cases: 119

OR

Estimate: 1.01

95% CI(0.95, 1.08)

Gestational HTN

N Total: 1718

Term LA

n-3 Measure: FFQ

n-3 Units: per g

N Quantile: NR

N Cases: 119

OR

Estimate: 1.01

95% CI(0.95, 1.08)

Gestational HTN

N Total: 1718

Term Total n-3

n-3 Measure: FFQ

n-3 Units: per g

N Quantile: NR

N Cases: 119

OR

Estimate: 1.13

95% CI(0.79, 1.61)

Gestational HTN

N Total: 1718

Term n-3/n-6

n-3 Measure: calculated

n-3 Units: ratio

N Quantile: NR

N Cases: 119

OR

Estimate: 1.02

95% CI(0.96, 1.08)

Preeclampsia

N Total: 1718

Term AA

n-3 Measure: FFQ

n-3 Units: per 100 mg

N Quantile: NR

N Cases: 59

OR

Estimate: 0.99

95% CI(0.91, 1.08)

Preeclampsia

N Total: 1718

Term ALA

n-3 Measure: FFQ

n-3 Units: per g

N Quantile: NR

N Cases: 59

OR

Estimate: 1.35

95% CI(0.66, 2.74)

Preeclampsia

N Total: 1718

Term DHA+EPA/AA

n-3 Measure: calculated

n-3 Units: ratio

N Quantile: NR

N Cases: 59

OR

Estimate: 0.82

95% CI(0.66, 1.01)
D-70

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Preeclampsia

N Total: 1718

Term DHA+EPA

n-3 Measure: FFQ

n-3 Units: per 100 mg

N Quantile: NR

N Cases: 59

OR

Estimate: 0.84

95% CI(0.69, 1.03)

Preeclampsia

N Total: 1718

Term LA

n-3 Measure: FFQ

n-3 Units: per g

N Quantile: NR

N Cases: 59

OR

Estimate: 0.99

95% CI(0.91, 1.08)

Preeclampsia

N Total: 1718

Term Total n-3

n-3 Measure: FFQ

n-3 Units: per g

N Quantile: NR

N Cases: 59

OR

Estimate: 1.01

95% CI(0.55, 1.85)

Preeclampsia

N Total: 1718

Term n-3/n-6

n-3 Measure: calculated

n-3 Units: ratio

N Quantile: NR

N Cases: 59

OR

Estimate: 0.99

95% CI(0.89, 1.11)
D-71

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Olafsdottir, et al., 200582

Study dates: 1999-2001

Study design: Observational prospective

Location: NR

Funding source / conflict: Government, Multiple foundations 

and Societies

Study Population: Healthy infants Healthy pregnant women

Pregnant enrolled 436 Pregnant completers 436

Pregnant age: No 27.8; Yes 29.6 (no 4.9; yes 4.6)

Race of Mother: NR

Inclusion Criteria: absence of pre-eclampsia, hypertension or 

diabetes mellitus

Exclusion Criteria: women whose personal data could not be found 

or who moved abroad before giving birth ( n 8), had a miscarriage 

or stillbirth ( n 17), twins or triplets ( n 5), a preterm birth 

hypertension/pre-eclampsia (n 62) or gestational diabetes mellitus 

(n=4)

Adjustments: Gender, gestational age, 

mother's height, BMI, hemoglobin, 

alcohol consumption in first trimester, 

parity, smoking during pregnancy, 

weight gain during pregnancy

Article Outcome, Cohort size

Follow up

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Olafsdottir 200582 Birth weight

N Total: 350

Liquid cod liver oil in first trimester (y/n)

n-3 Measure: FFQ

n-3 Units: grams

Yes vs. no

N Quantile: NR

N Cases: NR

Coefficient

Estimate: 132.1

95% CI(18.3, 246)
D-72

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Olafsdottir, et al., 200670

Study dates: 1999-2001

Study design: Observational prospective

Location: NR

Funding source / conflict: Government, Multiple foundations 

and Societies

Study Population: Healthy pregnant women

Pregnant enrolled 549 Pregnant completers 488

Pregnant age: 28 (5)

Race of Mother: White European (NR)

Inclusion Criteria: Pregnant women attending first prenatal visit at 

Center of Prenatal Care in Reykjavik from 1999-2001, who gave 

birth to full-term babies completed the study.

Exclusion Criteria: Essential hypertension, gestational diabetes, 

miscarriage/stillbirth, twins/triplets, preterm birth, loss of personal 

data, moved, missing data,

Adjustments: Weight gain during 

pregnancy, BMI X weight gain, 

smoking, parity and diastolic and 

systolic blood pressure early in 

pregnancy

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Olafsdottir 200570 Gestational hypertension or preeclampsia n-3 LCPUFAs (0.1-0.23g/d)

n-3 Units: g/d

11th-50th

N Cases: NR

OR

Gestational hypertension or preeclampsia n-3 LCPUFAs (0.24-0.87g/d)

n-3 Units: g/d

51st-90th

N Cases: NR

OR

Gestational hypertension or preeclampsia n-3 LCPUFAs (<0.9g/d)

n-3 Units: g/d

10th centile

N Cases: NR

OR

Gestational hypertension or preeclampsia n-3 LCPUFAs (>0.87g/d)

n-3 Units: g/d

>90th

N Cases: NR

OR

Gestational hypertension or preeclampsia

N Total: 488

n-3 LCPUFAs

n-3 Units: yes/no

All

N Cases: 49

OR

Estimate: 4.7

95% CI(1.8, 12.6)

Gestational hypertension

N Total: 488

Cod liver oil liquid

n-3 Measure: FFQ yes/no

n-3 Units: yes/no

All

N Cases: 30

OR

Estimate: 5.2

95% CI(1.5, 17.8)

Preeclampsia

N Total: 488

Yes/no All

N Cases: 19

OR

Estimate: 4.2

95% CI(0.8, 20.9)
D-73

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Parker, et al., 201597

Study dates: NR

Study design: Observational prospective

Location: Australia

Funding source / conflict: Government

Study Population: Healthy pregnant women Postpartum 

women

Pregnant enrolled 1232 Pregnant completers 831

Pregnant age: 31.0 (5.7)

Race of Mother: NR (100)

Inclusion Criteria: Women between 34 and37 weeks of pregnancy 

and attending an obstetric service. Participants had to be more than 

18 years of age, be proficient in English and able to provide 

informed consent

Exclusion Criteria: nr

Adjustments: Age, education level, 

income level, marital status, number of 

children, neuroticism scores, the 

presence or absence of a lifetime 

mood disorder, coffee drinking, 

cigarette smoking and alcohol intake, 

as well as stress levels during 

pregnancy

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Parker 201597 Postnatal depression measured by EPDS

N Total: 773

PUFA variables: total omega-6; total omega-3; 

omega-6/omega-3 ratio; DHA; DPA; DPE; 

EPA+DHA; AA

n-3 Measure: Maternal RBC phospholipids at 36 

weeks of pregnancy

n-3 Units: percentage of total fatty acids in 

erythrocyte phospholipids

NR

N Cases: 138

OR

Postnatal depression measured by MINIAD

N Total: 819

PUFA variables: total omega-6; total omega-3; 

omega-6/omega-3 ratio; DHA; DPA; DPE; 

EPA+DHA; AA

n-3 Measure: Maternal RBC phospholipids at 36 

weeks of pregnancy

n-3 Units: percentage of total fatty acids in 

erythrocyte phospholipids

NR

N Cases: 87

OR
D-74

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Pike, et al., 2012186

Study name: Southampton Women's Survey

Study dates: 2006-2010

Study design: Observational prospective

Location: UK

Funding source / conflict: Government, Some authors serve 

on scientific advisory boards for corporations

Follow-up: Birth to 6 years

Study Population: Healthy infants

Pregnant enrolled

Infants enrolled 1485 Infants completers 865

Pregnant age: 30.4 (3.8)

Race of Mother: NR (100)

Inclusion Criteria: mothers and children in the Southampton 

Women’s Survey

Exclusion Criteria: Infants born = 35 weeks’ gestation were 

excluded to avoid abnormal lung development associated with 

prematurity

Adjustments: Child’s age, maternal 

asthma, and paternal rhinitis for airway 

inflammation outcome

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Pike 2012186 Airway inflammation

N Total: 452

6 years AA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.108

95% CI(0.014, 0.201)

Airway inflammation

N Total: 452

6 years ALA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: -0.05

95% CI(-0.144, 0.044)

Airway inflammation

N Total: 452

6 years DHA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.095

95% CI(0.002, 0.189)

Airway inflammation

N Total: 452

6 years EPA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: -0.022

95% CI(-0.119, 0.074)

Airway inflammation

N Total: 452

6 years Total n-3 PUFAs

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.042

95% CI(-0.052, 0.135)

Airway inflammation

N Total: 452

6 years Total n-3:n-6

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.039

95% CI(-0.053, 0.131)

Atopy

N Total: 638

6 years AA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 1.1

95% CI(0.96, 1.26)
D-75

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Atopy

N Total: 638

6 years ALA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.99

95% CI(0.86, 1.14)

Atopy

N Total: 638

6 years DHA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 1

95% CI(0.87, 1.14)

Atopy

N Total: 638

6 years EPA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.94

95% CI(0.83, 1.06)

Atopy

N Total: 638

6 years Total n-3 PUFAs

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.99

95% CI(0.87, 1.13)

Atopy

N Total: 638

6 years Total n-3:n-6

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 1

95% CI(0.88, 1.14)

Lung function

N Total: 702

6 years AA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0

95% CI(-0.014, 0.015)

Lung function

N Total: 702

6 years ALA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: -0.009

95% CI(-0.024, 0.005)

Lung function

N Total: 702

6 years DHA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.008

95% CI(-0.006, 0.022)

Lung function

N Total: 702

6 years EPA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.013

95% CI(-0.001, 0.027)

Lung function

N Total: 702

6 years Total n-3 PUFAs

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.01

95% CI(-0.004, 0.024)

Lung function

N Total: 702

6 years Total n-3:n-6

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.01

95% CI(-0.004, 0.024)

Persistent/late wheeze with atopy

N Total: 861

6 years AA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 1.06

95% CI(0.82, 1.36)
D-76

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Persistent/late wheeze with atopy

N Total: 861

6 years ALA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.91

95% CI(0.7, 1.19)

Persistent/late wheeze with atopy

N Total: 861

6 years DHA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.74

95% CI(0.55, 1)

Persistent/late wheeze with atopy

N Total: 861

6 years EPA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.65

95% CI(0.43, 0.98)

Persistent/late wheeze with atopy

N Total: 861

6 years Total n-3 PUFAs

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.72

95% CI(0.54, 0.96)

Persistent/late wheeze with atopy

N Total: 861

6 years Total n-3:n-6

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.73

95% CI(0.54, 0.99)

Persistent/late wheeze without atopy

N Total: 861

6 years AA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.76

95% CI(0.6, 0.96)

Persistent/late wheeze without atopy

N Total: 861

6 years ALA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 1.17

95% CI(0.87, 1.58)

Persistent/late wheeze without atopy

N Total: 861

6 years DHA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.67

95% CI(0.49, 0.93)

Persistent/late wheeze without atopy

N Total: 861

6 years EPA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.57

95% CI(0.37, 0.89)

Persistent/late wheeze without atopy

N Total: 861

6 years Total n-3 PUFAs

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.69

95% CI(0.51, 0.95)

Persistent/late wheeze without atopy

N Total: 861

6 years Total n-3:n-6

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.73

95% CI(0.53, 0.99)

Persistent/late wheeze

N Total: 861

6 years AA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.88

95% CI(0.76, 1.02)
D-77

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Persistent/late wheeze

N Total: 861

6 years ALA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 1.09

95% CI(0.96, 1.24)

Persistent/late wheeze

N Total: 861

6 years DHA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.91

95% CI(0.76, 1.08)

Persistent/late wheeze

N Total: 861

6 years EPA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.91

95% CI(0.73, 1.14)

Persistent/late wheeze

N Total: 861

6 years Total n-3 PUFAs

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.93

95% CI(0.79, 1.11)

Persistent/late wheeze

N Total: 861

6 years Total n-3:n-6

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.94

95% CI(0.79, 1.12)

Transient wheeze

N Total: 861

6 years AA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.94

95% CI(0.88, 1.02)

Transient wheeze

N Total: 861

6 years ALA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 1.06

95% CI(0.98, 1.14)

Transient wheeze

N Total: 861

6 years DHA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.95

95% CI(0.88, 1.03)

Transient wheeze

N Total: 861

6 years EPA%

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.98

95% CI(0.92, 1.06)

Transient wheeze

N Total: 861

6 years Total n-3 PUFAs

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.97

95% CI(0.9, 1.04)

Transient wheeze

N Total: 861

6 years Total n-3:n-6

n-3 Measure: Maternal plasma 

phosphatidylcholine at 34 weeks gestation

n-3 Units: % total fatty acids

All RR

Estimate: 0.98

95% CI(0.92, 1.05)
D-78

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Saito, et al., 2010181

Study name: Osaka maternal and child health study

Study dates: Recruitment: November 2001 to March 2003 

Follow-up: 3-4 months

Study design: Observational prospective

Location: Japan

Funding source / conflict: Government

Follow-up: 3-4 months

Study Population: Healthy infants Healthy pregnant women

Pregnant completers 771

Infants completers 771

Pregnant age: 29.9 (4.0)

Race of Mother: NR (100%)

Inclusion Criteria: Pregnant women living in Neyagawa City (one of 

the 43 municipalities in Osaka Prefecture) and a few municipalities 

other than Neyagawa

Exclusion Criteria: Survey completed outside 3-5 month postpartum 

window

Adjustments: Maternal age, gestation 

at baseline, family income, maternal 

and paternal education, maternal and 

paternal history of asthma, atopic 

eczema and allergic rhinitis, mite 

allergen level from maternal 

bedclothes, vacuuming living room, 

mold in kitchen, changes in maternal 

diet in the previous 1 month, season 

when data at baseline were collected, 

baby’s older siblings, baby’s sex, 

baby’s birth weight, breastfeeding and 

bathing or showering infant.

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Yokoyama 2010181 Atopic eczema

N Total: 771

3-5 months ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 1.3

N Quantile: 192

N Cases: 13

OR

Atopic eczema

N Total: 771

3-5 months ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 1.6

N Quantile: 193

N Cases: 19

OR

Estimate: 1.59

95% CI(0.73, 3.57)

Atopic eczema

N Total: 771

3-5 months ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q3 1.9

N Quantile: 193

N Cases: 23

OR

Estimate: 2.26

95% CI(1.06, 5.03)

Atopic eczema

N Total: 771

3-5 months ALA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 2.3

N Quantile: 193

N Cases: 10

OR

Estimate: 0.76

95% CI(0.3, 1.87)

Atopic eczema

N Total: 771

3-5 months DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 0.15

N Quantile: 192

N Cases: 16

OR

Atopic eczema

N Total: 771

3-5 months DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 0.24

N Quantile: 193

N Cases: 14

OR

Estimate: 0.96

95% CI(0.43, 2.11)

Atopic eczema

N Total: 771

3-5 months DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q3 0.31

N Quantile: 193

N Cases: 16

OR

Estimate: 0.93

95% CI(0.42, 2.05)

Atopic eczema

N Total: 771

3-5 months DHA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 0.46

N Quantile: 193

N Cases: 19

OR

Estimate: 1.43

95% CI(0.68, 3.07)

Atopic eczema

N Total: 771

3-5 months EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 0.07

N Quantile: 192

N Cases: 13

OR
D-79

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Atopic eczema

N Total: 771

3-5 months EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 0.13

N Quantile: 193

N Cases: 20

OR

Estimate: 1.57

95% CI(0.72, 3.53)

Atopic eczema

N Total: 771

3-5 months EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q3 0.18

N Quantile: 193

N Cases: 13

OR

Estimate: 0.98

95% CI(0.41, 2.31)

Atopic eczema

N Total: 771

3-5 months EPA

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 0.27

N Quantile: 193

N Cases: 19

OR

Estimate: 1.84

95% CI(0.84, 4.15)

Atopic eczema

N Total: 771

3-5 months n-3 Polyunsaturated fatty acids

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 1.71

N Quantile: 192

N Cases: 13

OR

Atopic eczema

N Total: 771

3-5 months n-3 Polyunsaturated fatty acids

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 2.1

N Quantile: 193

N Cases: 22

OR

Estimate: 2.06

95% CI(0.97, 4.55)

Atopic eczema

N Total: 771

3-5 months n-3 Polyunsaturated fatty acids

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q3 2.5

N Quantile: 193

N Cases: 14

OR

Estimate: 1.33

95% CI(0.57, 3.11)

Atopic eczema

N Total: 771

3-5 months n-3 Polyunsaturated fatty acids

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 3

N Quantile: 193

N Cases: 16

OR

Estimate: 1.45

95% CI(0.64, 3.31)

Atopic eczema

N Total: 771

3-5 months n-3/n-6 Polyunsaturated fatty acid ratio

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q1 0.17

N Quantile: 192

N Cases: 15

OR

Atopic eczema

N Total: 771

3-5 months n-3/n-6 Polyunsaturated fatty acid ratio

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q2 0.19

N Quantile: 193

N Cases: 16

OR

Estimate: 0.95

95% CI(0.43, 2.11)

Atopic eczema

N Total: 771

3-5 months n-3/n-6 Polyunsaturated fatty acid ratio

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q3 0.21

N Quantile: 193

N Cases: 19

OR

Estimate: 1.27

95% CI(0.59, 2.78)

Atopic eczema

N Total: 771

3-5 months n-3/n-6 Polyunsaturated fatty acid ratio

n-3 Measure: Intake (FFQ)

n-3 Units: g/d

Q4 0.24

N Quantile: 193

N Cases: 15

OR

Estimate: 1.17

95% CI(0.52, 2.62)
D-80

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Sallis, et al., 201496

Study name: Avon Longitudinal Study of Parents and 

Children (ALSPAC)

Study dates: 1991-1992

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Study Population: Healthy pregnant women

Pregnant enrolled 14,541 Pregnant withdrawals 11,144 

Pregnant completers 3,397

Pregnant age: 28.9 (4.5) not reported

Race of Mother: White European (100%)

Inclusion Criteria: All women with an expected due date between 

April 1991 and December 1992 were eligible for the study. Only 

women with data available on genotype, FA levels and depressive 

symptoms during pregnancy or at 8 weeks postnatally and women 

with a self-reported ethnicity of White European were included in 

this analysis.

Exclusion Criteria: Mothers who lost a child during the neonatal 

period and those with a still birth; mothers with multiple births.

Adjustments: Social class (I/II, III or 

IV/V) and maternal age

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Sallis 201496 Antenatal depression

N Total: 2911

EPA

n-3 Measure: Maternal red blood cells

n-3 Units: % total RBC phospholipid

All

N Cases: 441

OR

Estimate: 0.97

95% CI(0.91, 1.04)

Antenatal depression

N Total: 2912

DHA

n-3 Measure: Maternal red blood cells

n-3 Units: % total RBC phospholipid

All OR

Estimate: 0.99

95% CI(0.91, 1.07)

Antenatal depression

N Total: 2912

DHA

n-3 Measure: Maternal red blood cells

n-3 Units: % total RBC phospholipid

All RD

Estimate: 0.05

95% CI(-0.09, 0.19)

Perinatal onset depression

N Total: 2377

EPA

n-3 Measure: Maternal red blood cells

n-3 Units: % total RBC phospholipid

All

N Cases: 306

OR

Estimate: 1.07

95% CI(0.99, 1.15)

Perinatal onset depression

N Total: 2378

DHA

n-3 Measure: Maternal red blood cells

n-3 Units: % total RBC phospholipid

All OR

Estimate: 1.08

95% CI(0.98, 1.19)

Perinatal onset depression

N Total: 2378

DHA

n-3 Measure: Maternal red blood cells

n-3 Units: % total RBC phospholipid

All RD

Estimate: 0.08

95% CI(-0.05, 0.22)

Postnatal depression

N Total: 2756

EPA

n-3 Measure: Maternal red blood cells

n-3 Units: % total RBC phospholipid

All

N Cases: 265

OR

Estimate: 1.04

95% CI(0.96, 1.13)

Postnatal depression

N Total: 2757

DHA

n-3 Measure: Maternal red blood cells

n-3 Units: % total RBC phospholipid

All OR

Estimate: 1.04

95% CI(0.94, 1.15)

Postnatal depression

N Total: 2757

DHA

n-3 Measure: Maternal red blood cells

n-3 Units: % total RBC phospholipid

All RD

Estimate: 0.02

95% CI(-0.08, 0.13)
D-81

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Scholtens, et al., 2009103

Study name: The Prevention and Incidence of Asthma and 

Mite Allergy (PIAMA) birth cohort study

Study dates: Recruitment: 1996-1997 Follow-up: 1 year

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government, Multiple 

foundations and Societies, None

Follow-up: 1 year

Original, same study, or follow-up studies: Study described in 

Brunekreef, 2002

Study Population: NR

Pregnant enrolled 4146

Infants enrolled 276 Infants completers 244

Infant age: Birth

Race of Mother: NR (NR)

Inclusion Criteria: Children of mothers recruited from the general 

population during pregnancy

Exclusion Criteria: None reported

Adjustments: Age of child at breastmilk collection and total breast-feeding 

duration

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Scholtens 2008103 Mean BMI gain

N Total: 244

1 y ALA (18 : 3n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.002

95% CI(0.002, -0.01)

Mean BMI gain

N Total: 244

1 y ALA (18 : 3n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.007

95% CI(0.007, -0.004)

Mean BMI gain

N Total: 244

1 y DHA (22 : 6n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.004

95% CI(0.004, -0.008)

Mean BMI gain

N Total: 244

1 y DHA (22 : 6n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.009

95% CI(0.009, -0.003)

Mean BMI gain

N Total: 244

1 y EPA (20 : 5n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.003

95% CI(-0.003, -0.015)

Mean BMI gain

N Total: 244

1 y EPA (20 : 5n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.004

95% CI(-0.004, -0.015)

Mean BMI gain

N Total: 244

1 y Total n-3 LCPUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.009

95% CI(-0.009, -0.021)

Mean BMI gain

N Total: 244

1 y Total n-3 LCPUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.01

95% CI(-0.01, -0.021)
D-82

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Mean BMI gain

N Total: 244

1 y Total n-3 PUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.001

95% CI(-0.001, -0.013)

Mean BMI gain

N Total: 244

1 y Total n-3 PUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.008

95% CI(0.008, -0.004)

Mean length gain

N Total: 244

1 y ALA (18 : 3n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.011

95% CI(-0.011, -0.029)

Mean length gain

N Total: 244

1 y ALA (18 : 3n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.01

95% CI(-0.01, -0.028)

Mean length gain

N Total: 244

1 y DHA (22 : 6n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.013

95% CI(-0.013, -0.031)

Mean length gain

N Total: 244

1 y DHA (22 : 6n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.006

95% CI(0.006, 0.024)

Mean length gain

N Total: 244

1 y EPA (20 : 5n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.007

95% CI(0.007, -0.011)

Mean length gain

N Total: 244

1 y EPA (20 : 5n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.01

95% CI(0.01, -0.008)

Mean length gain

N Total: 244

1 y Total n-3 LCPUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.009

95% CI(0.009, -0.008)

Mean length gain

N Total: 244

1 y Total n-3 LCPUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.016

95% CI(0.016, 0.001)

Mean length gain

N Total: 244

1 y Total n-3 PUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.002

95% CI(-0.002, -0.02)

Mean length gain

N Total: 244

1 y Total n-3 PUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.004

95% CI(-0.004, -0.022)

Mean weight gain

N Total: 244

1 y ALA (18 : 3n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -1.64

95% CI(-1.64, -6.596)

Mean weight gain

N Total: 244

1 y ALA (18 : 3n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.697

95% CI(0.697, -4.275)

Mean weight gain

N Total: 244

1 y DHA (22 : 6n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.606

95% CI(0.606, -4.387)

Mean weight gain

N Total: 244

1 y DHA (22 : 6n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 0.833

95% CI(0.833, -4.124)
D-83

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Mean weight gain

N Total: 244

1 y EPA (20 : 5n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 2.434

95% CI(2.434, -2.516)

Mean weight gain

N Total: 244

1 y EPA (20 : 5n-3)

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 3.187

95% CI(3.187, -1.776)

Mean weight gain

N Total: 244

1 y Total n-3 LCPUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.329

95% CI(-0.329, -5.282)

Mean weight gain

N Total: 244

1 y Total n-3 LCPUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -1.574

95% CI(-1.574, 6.532)

Mean weight gain

N Total: 244

1 y Total n-3 PUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: -0.253

95% CI(-0.253, -5.216)

Mean weight gain

N Total: 244

1 y Total n-3 PUFA

n-3 Measure: Breast milk wt%

n-3 Units: wt%

Coefficient

Estimate: 2.843

95% CI(2.843, -2.17)
D-84

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Smits, et al., 201373

Study name: Amsterdam Born Children and their 

Development (ABCD)

Study dates: Jan 2003- Mar 2004

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: None

Study Population: Healthy infants Healthy pregnant women

Pregnant enrolled 1659 Pregnant completers 1659

Infants enrolled 1659 Infants completers 1659

Pregnant age: <25 y, 5.7% 25-34 y, 61.2% >=35 y, 33.1%

Infant age: 40.0 weeks (1.2)

Race of Mother: White European (88.4)

Inclusion Criteria: NR

Exclusion Criteria: primiparous women or delivered preterm

Adjustments: Potential confounding 

factors were evaluated but none of 

them was significant confounding 

defined as changing the odds ratio by 

10%

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Smits 201573 Birth weight

N Total: 1659

DHA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q1 <3.74 -

N Quantile: NR

N Cases: NR

-118.2

95% CI(-195.032, -41.368)

Birth weight

N Total: 1659

DHA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q2 3.74 - 4.35

N Quantile: NR

N Cases: NR

-43.8

95% CI(-120.632, 33.032)

Birth weight

N Total: 1659

DHA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q3 4.35 - 4.86

N Quantile: NR

N Cases: NR

Birth weight

N Total: 1659

DHA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q4 4.88 - 5.54

N Quantile: NR

N Cases: NR

-34.4

95% CI(-111.232, 42.432)

Birth weight

N Total: 1659

DHA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q5 >=5.54 -

N Quantile: NR

N Cases: NR

-15.4

95% CI(-92.232, 61.432)

Birth weight

N Total: 1659

EPA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q1 <0.33 -

N Quantile: NR

N Cases: NR

-182.5

95% CI(-258.94, -106.06)

Birth weight

N Total: 1659

EPA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q2 0.33 - 0.46

N Quantile: NR

N Cases: NR

-66.1

95% CI(-142.54, 10.34)

Birth weight

N Total: 1659

EPA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q3 0.46 - 0.58

N Quantile: NR

N Cases: NR
D-85

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Birth weight

N Total: 1659

EPA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q4 0.58 - 0.81

N Quantile: NR

N Cases: NR

18.4

95% CI(-57.844, 94.644)

Birth weight

N Total: 1659

EPA

n-3 Measure: Maternal plasma phospholipids at 

early pregnancy

n-3 Units: mg/L

Q5 >=0.81 -

N Quantile: NR

N Cases: NR

-26.6

95% CI(-103.04, 49.84)

SGA

N Total: 1659

DHA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q1 <3.74 -

N Quantile: 332

N Cases: 44

OR

Estimate: 1.11

95% CI(0.7, 1.75)

SGA

N Total: 1659

DHA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q2 3.74 - 4.35

N Quantile: 332

N Cases: 42

OR

Estimate: 1.05

95% CI(0.66, 1.67)

SGA

N Total: 1659

DHA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q3 4.35 - 4.86

N Quantile: 332

N Cases: 40

OR

SGA

N Total: 1659

DHA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q4 4.88 - 5.54

N Quantile: 332

N Cases: 39

OR

Estimate: 0.96

95% CI(0.6, 1.54)

SGA

N Total: 1659

DHA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q5 >=5.54 -

N Quantile: 332

N Cases: 40

OR

Estimate: 0.99

95% CI(0.62, 4.59)

SGA

N Total: 1659

EPA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q1 <0.33 -

N Quantile: 332

N Cases: 42

OR

Estimate: 2.09

95% CI(1.32, 3.3)

SGA

N Total: 1659

EPA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q2 0.33 - 0.46

N Quantile: 332

N Cases: 44

OR

Estimate: 1.42

95% CI(0.88, 2.31)

SGA

N Total: 1659

EPA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q3 0.46 - 0.58

N Quantile: 332

N Cases: 32

OR

SGA

N Total: 1659

EPA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q4 0.58 - 0.81

N Quantile: 332

N Cases: 32

OR

Estimate: 0.98

95% CI(0.59, 1.64)

SGA

N Total: 1659

EPA

n-3 Measure: Biomarker

n-3 Units: mg/L

Q5 >=0.81 -

N Quantile: 332

N Cases: 36

OR

Estimate: 1.13

95% CI(0.68, 1.87)
D-86

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Standl, et al., 2014177

Study name: LISAplus

Study dates: Recruitment 1997-1999

Study design: Observational prospective

Location: Germany

Funding source / conflict: Government

Follow-up: 10 years

Study Population: Healthy infants

Infants enrolled 436 Infants completers 243

Mother age: 32.7 (3.9) NR

Infant age: Birth (NR) NR

Race of Mother: NR (100)

Inclusion Criteria: NR

Exclusion Criteria: Neonates displaying at least one of the following 

criteria: preterm birth (maturity <37 gestational weeks), low birth 

weight (<2,500 g), congenital malformation, symptomatic neonatal 

infection, antibiotic medication, hospitalization or intensive medical 

care during neonatal period. In addition, newborns from mothers 

with immune-related diseases (autoimmune disorders, diabetes, 

hepatitis B), on long-term medication or who abuse drugs and/or 

alcohol, and newborns from parents with a nationality other than 

German or who were not born in Germany, were excluded.

Adjustments: Parental education, sex, 

time of follow-up (2 yr, 6 yr or 10 yr for 

eczema; 6 yr and 10 yr for asthma, 

hay fever/allergic rhinitis and 

aeroallergen sensitization), age, 

maternal age at birth, parental atopy, 

total sum of fatty acids

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Standl 2014177 Aeroallergen sensitization

N Total: 243

10 y n-3 LC-PUFA

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 43

OR

Estimate: 1.03

95% CI(0.87, 1.23)

Aeroallergen sensitization

N Total: 243

10 y n-6/n-3 ratio

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 43

OR

Estimate: 0.82

95% CI(0.56, 1.22)

Aeroallergen sensitization

N Total: 277

6 y n-3 LC-PUFA

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 24

OR

Estimate: 1.03

95% CI(0.85, 1.25)

Aeroallergen sensitization

N Total: 277

6 y n-6/n-3 ratio

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 24

OR

Estimate: 0.94

95% CI(0.61, 1.44)

Asthma

N Total: 243

10 y n-3 LC-PUFA

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 5

OR

Estimate: 1.18

95% CI(0.79, 1.75)

Asthma

N Total: 243

10 y n-6/n-3 ratio

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 5

OR

Estimate: 0.77

95% CI(0.29, 2.04)

Asthma

N Total: 277

6 y n-3 LC-PUFA

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 3

OR

Estimate: 0.83

95% CI(0.48, 1.44)

Asthma

N Total: 277

6 y n-6/n-3 ratio

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 3

OR

Estimate: 1.75

95% CI(0.73, 4.21)

Eczema

N Total: 243

10 y n-3 LC-PUFA

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 7

OR

Estimate: 0.76

95% CI(0.52, 1.12)
D-87

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 243

10 y n-6/n-3 ratio

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 7

OR

Estimate: 1.31

95% CI(0.63, 2.71)

Eczema

N Total: 277

6 y n-3 LC-PUFA

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 14

OR

Estimate: 1.18

95% CI(0.95, 1.48)

Eczema

N Total: 277

6 y n-6/n-3 ratio

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 14

OR

Estimate: 0.75

95% CI(0.45, 1.25)

Eczema

N Total: 280

2 y n-3 LC-PUFA

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 15

OR

Estimate: 0.99

95% CI(0.78, 1.25)

Eczema

N Total: 280

2 y n-6/n-3 ratio

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 15

OR

Estimate: 0.97

95% CI(0.58, 1.63)

Hay fever or allergic rhinitis

N Total: 243

10 y n-3 LC-PUFA

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 13

OR

Estimate: 1

95% CI(0.77, 1.3)

Hay fever or allergic rhinitis

N Total: 243

10 y n-6/n-3 ratio

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 13

OR

Estimate: 0.84

95% CI(0.47, 1.51)

Hay fever or allergic rhinitis

N Total: 277

6 y n-3 LC-PUFA

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 3

OR

Estimate: 0.96

95% CI(0.6, 1.56)

Hay fever or allergic rhinitis

N Total: 277

6 y n-6/n-3 ratio

n-3 Measure: Cord blood serum fatty acids

n-3 Units: percentage of total fatty acids

All

N Cases: 3

OR

Estimate: 0.75

95% CI(0.27, 2.1)
D-88

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Steer, et al., 2013164

Study name: Avon Longitudinal Study of Parents and 

Children (ALSPAC)

Study dates: 1991-2000

Study design: Observational prospective

Location: UK

Funding source / conflict: Government

Follow-up: 8 years

Study Population: Healthy infants Healthy pregnant women

Pregnant enrolled 14,541

Infants completers 2,839

Mother age: 29.33 (4.48)

Infant age: birth

Race of Mother: White European (98.8) Black (0.6) Asian 

(0.6)

Inclusion Criteria: pregnant women with expected delivery date 

between 4/91 and 12/92 in Bristol UK

Exclusion Criteria: Not reported

Adjustments: Maternal age, education, 

ethnicity, alcohol consumption and 

smoking; partner status, housing 

tenure, crowding index, parity, preterm 

gestation (,37 wk), low birth weight 

(,2500 g), multiple births, sex, 

breastfeeding, and measures of 

adversity (in pregnancy and during the

first 2 y after birth) and child 

stimulation (both from the home 

environment and maternal interaction 

with the child)

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Steer 2013164 IQ

N Total: 2839

7 years AA

n-3 Measure: maternal erythrocyte

Highest to other 3 Coefficient

Estimate: -1.18

95% CI(-2.53, 0.18)

IQ

N Total: 2839

7 years AA

n-3 Measure: maternal erythrocyte

Lowest to other 3 Coefficient

Estimate: -1.54

95% CI(-2.91, -0.14)

IQ

N Total: 2839

7 years DHA

n-3 Measure: maternal erythrocyte

Highest to other 3 Coefficient

Estimate: -0.18

95% CI(-1.52, 1.17)

IQ

N Total: 2839

7 years DHA

n-3 Measure: maternal erythrocyte

Lowest to other 3 Coefficient

Estimate: -1.52

95% CI(-2.91, -0.14)
D-89

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Strom, et al., 200992

Study name: Danish National Birth Cohort

Study dates: 1996-2002

Study design: Observational prospective

Location: Denmark

Funding source / conflict: Government, Multiple foundations 

and Societies, Funding Affiliations trade group, March of 

Dimes

Study Population: Healthy pregnant women

Pregnant enrolled 86,453 Pregnant withdrawals 32,251 

Pregnant completers 54,202

Pregnant age: not reported (not reported) not reported

Race of Mother: NR (100%)

Inclusion Criteria: All pregnant women living in Denmark between 

1996 and 2002, who were fluent in Danish

Exclusion Criteria: NR

Adjustments: Total energy intake, prepregnant BMI, maternal age, parity, 

alcohol intake, smoking, occupation, 

education, homeownership, marital 

status, social support, and history of 

previous depression

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Strom 200992 PPD admission n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q1 9.1

N Cases: 16

OR

Estimate: 0.96

95% CI(0.51, 1.78)

PPD admission n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q2 14.1

N Cases: 16

OR

Estimate: 1.03

95% CI(0.55, 1.92)

PPD admission n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q3 18.1

N Cases: 11

OR

Estimate: 0.73

95% CI(0.36, 1.48)

PPD admission n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q4 22.2

N Cases: 19

OR

Estimate: 1.33

95% CI(0.74, 2.39)

PPD admission n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q5 27

N Cases: 17

OR

Estimate: 1.21

95% CI(0.66, 2.21)

PPD admission n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q6 32.7

N Cases: 23

OR

Estimate: 1.65

95% CI(0.95, 2.88)

PPD admission n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q7 39.6

N Cases: 18

OR

Estimate: 1.3

95% CI(0.72, 2.36)

PPD admission n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q8 48.4

N Cases: 11

OR

Estimate: 0.79

95% CI(0.39, 1.59)

PPD admission n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q9+Q10 72.8

N Cases: 28

OR
D-90

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

PPD prescription n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q1 9.1

N Cases: 110

OR

Estimate: 1.24

95% CI(0.96, 1.61)

PPD prescription n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q2 14.1

N Cases: 97

OR

Estimate: 1.17

95% CI(0.9, 1.53)

PPD prescription n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q3 18.1

N Cases: 82

OR

Estimate: 0.99

95% CI(0.75, 1.31)

PPD prescription n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q4 22.2

N Cases: 102

OR

Estimate: 1.29

95% CI(0.99, 1.68)

PPD prescription n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q5 27

N Cases: 83

OR

Estimate: 1.09

95% CI(0.83, 1.44)

PPD prescription n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q6 32.7

N Cases: 85

OR

Estimate: 1.11

95% CI(0.84, 1.46)

PPD prescription n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q7 39.6

N Cases: 80

OR

Estimate: 1.04

95% CI(0.79, 1.38)

PPD prescription n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q8 48.4

N Cases: 70

OR

Estimate: 0.89

95% CI(0.67, 1.2)

PPD prescription n-3 PUFA intake

n-3 Measure: FFQ

n-3 Units: mg/d

Q9+Q10 72.8

N Cases: 157

OR
D-91

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Sun, et al., 2010131

Study name: Danish National Birth Cohort

Study dates: Recruitment March 1996 to November 2002

Study design: Observational prospective

Location: Denmark

Funding source / conflict: Government

Follow-up: 10.8 years (median 7.8 years)

Study Population: Healthy infants

Infants enrolled 65,754 Infants completers 65754

Infant age: birth

Race of Mother: NR (NR)

Inclusion Criteria: live-born singletons whose mothers provided 

information on fish intake from food frequency questionnaire

Exclusion Criteria: children with missing information on maternal 

smoking and parity, children who died during the neonatal period, 

and children born to mothers with an unlikely high (>16,700 kJ/day) 

or low (<4200 kJ/day) intake of energy during pregnancy

Adjustments: Energy intake, sex, 

gestational age, parity, time 

breastfeeding, maternal age, SES, 

pre-pregnancy BMI, smoking status at 

recruitment, maternal history of 

epilepsy

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Sun, 2010131 Epilepsy Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: FFQ

n-3 Units: mg/day

N Quantile: 12,245

N Cases: 126

Incidence rate ratio (IRR)

Estimate: 1.33

95% CI(1.02, 1.74)

Epilepsy Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: FFQ

n-3 Units: mg/day

N Quantile: 12,318

N Cases: 97

Incidence rate ratio (IRR)

Epilepsy Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: FFQ

n-3 Units: mg/day

N Quantile: 12,332

N Cases: 104

Incidence rate ratio (IRR)

Estimate: 1.05

95% CI(0.79, 1.38)

Epilepsy Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: FFQ

n-3 Units: mg/day

N Quantile: 12,421

N Cases: 102

Incidence rate ratio (IRR)

Estimate: 1.05

95% CI(0.81, 1.41)

Epilepsy Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: FFQ

n-3 Units: mg/day

N Quantile: 4,528

N Cases: 34

Incidence rate ratio (IRR)

Estimate: 1.01

95% CI(0.68, 1.49)

Epilepsy

N Total: 65754

Up to 10.8 

years, mean 

7.8 years

Supplements during pregnancy

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: mg/day

377

N Quantile: 4,528

N Cases: 34

Incidence rate ratio (IRR)

Estimate: 1.01

95% CI(0.68, 1.49)

Epilepsy

N Total: 65754

Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: FFQ

n-3 Units: mg/day

N Quantile: 11,910

N Cases: 128

Incidence rate ratio (IRR)

Estimate: 1.28

95% CI(0.98, 1.67)

Epilepsy

N Total: 65754

Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: mg/day

Q1 117

N Quantile: 11,910

N Cases: 128

Incidence rate ratio (IRR)

Estimate: 1.28

95% CI(0.98, 1.67)

Epilepsy

N Total: 65754

Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: mg/day

Q2 207

N Quantile: 12,332

N Cases: 104

Incidence rate ratio (IRR)

Estimate: 1.05

95% CI(0.79, 1.38)
D-92

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Epilepsy

N Total: 65754

Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: mg/day

Q3 308

N Quantile: 12,318

N Cases: 97

Incidence rate ratio (IRR)

Epilepsy

N Total: 65754

Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: mg/day

Q4 451

N Quantile: 12,421

N Cases: 102

Incidence rate ratio (IRR)

Estimate: 1.05

95% CI(0.81, 1.41)

Epilepsy

N Total: 65754

Up to 10.8 

years, mean 

7.8 years

Total n-3 LCPUFA

n-3 Measure: Maternal food frequency 

questionnaire

n-3 Units: mg/day

Q5 817

N Quantile: 12,245

N Cases: 126

Incidence rate ratio (IRR)

Estimate: 1.33

95% CI(1.02, 1.74)
D-93

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Thijs, et al., 2011178

Study name: KOALA Birth Cohort Study

Study dates: 2003

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Government, None

Follow-up: 2 years

Study Population: Healthy pregnant women

Pregnant enrolled 312 Pregnant completers 304

Infants enrolled 312 Infants completers 304

Pregnant age: 33.3 (3.9) NR

Race of Mother: NR (100)

Inclusion Criteria: availability of complete baseline data from the 34 

weeks pregnancy questionnaire and availability of a breast milk 

sample.

Exclusion Criteria: NR

Adjustments: Recruitment group, 

maternal age, maternal education, 

infant’s gender, number of older 

siblings and their atopic history, 

parental atopic history, maternal 

smoking during pregnancy and/or 

smoking in presence of the infant, 

place of birth, season of breast milk 

collection, duration and exclusivity of 

breastfeeding, maternal n-3 fatty acids 

supplement use, maternal probiotic 

supplement use, maternal probiotic 

dairy use, maternal antibiotic use 

during lactation, infant’s antibiotic use, 

vaccination schedule, dampness of 

the home, pet animals in the home.

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Thijs 2011178 Allergic sensitisation

N Total: 204

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt1 0.3-0.56

N Quantile: 41

N Cases: 10

OR

Allergic sensitisation

N Total: 204

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt2 0.56-0.65

N Quantile: 44

N Cases: 13

OR

Estimate: 1.29

95% CI(0.45, 3.68)

Allergic sensitisation

N Total: 204

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt3 0.65-0.78

N Quantile: 53

N Cases: 15

OR

Estimate: 1.32

95% CI(0.47, 3.72)

Allergic sensitisation

N Total: 204

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt4 0.78-2.55

N Quantile: 66

N Cases: 13

OR

Estimate: 0.89

95% CI(0.32, 2.5)

Allergic sensitisation

N Total: 220

1 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt1 0.3-0.56

N Quantile: 49

N Cases: 8

OR

Allergic sensitisation

N Total: 220

1 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt2 0.56-0.65

N Quantile: 45

N Cases: 6

OR

Estimate: 0.8

95% CI(0.21, 3.08)
D-94

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Allergic sensitisation

N Total: 220

1 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt3 0.65-0.78

N Quantile: 58

N Cases: 9

OR

Estimate: 0.68

95% CI(0.21, 2.2)

Allergic sensitisation

N Total: 220

1 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt4 0.78-2.55

N Quantile: 68

N Cases: 5

OR

Estimate: 0.17

95% CI(0.04, 0.77)

Atopic dermatitis

N Total: 207

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: NR

All

N Cases: 31

OR

Estimate: 0.33

95% CI(0.13, 0.87)

Atopic dermatitis

N Total: 207

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt1 0.3-0.56

N Quantile: 43

N Cases: 10

OR

Atopic dermatitis

N Total: 207

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt2 0.56-0.65

N Quantile: 44

N Cases: 7

OR

Estimate: 0.83

95% CI(0.27, 2.57)

Atopic dermatitis

N Total: 207

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt3 0.65-0.78

N Quantile: 54

N Cases: 8

OR

Estimate: 0.46

95% CI(0.13, 1.59)

Atopic dermatitis

N Total: 207

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt4 0.78-2.55

N Quantile: 66

N Cases: 6

OR

Estimate: 0.34

95% CI(0.12, 0.97)

Eczema

N Total: 304

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: NR

All

N Cases: 95

OR

Estimate: 0.6

95% CI(0.37, 0.98)

Eczema

N Total: 304

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt1 0.3-0.56

N Quantile: 72

N Cases: 26

OR

Eczema

N Total: 304

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt2 0.56-0.65

N Quantile: 68

N Cases: 21

OR

Estimate: 0.8

95% CI(0.37, 1.71)
D-95

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 304

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt3 0.65-0.78

N Quantile: 74

N Cases: 24

OR

Estimate: 0.89

95% CI(0.43, 1.88)

Eczema

N Total: 304

2 y Main n-3 LCPs (EPA+DHA+DPA)

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: weight-percentage (wt%, mg/100 mg) 

of total breast milk fat

Qt4 0.78-2.55

N Quantile: 90

N Cases: 24

OR

Estimate: 0.62

95% CI(0.3, 1.29)
D-96

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Valent, et al., 2013132

Study dates: 2007-2011

Study design: Observational prospective

Location: Italy

Funding source / conflict: Government

Study Population: Healthy infants Healthy pregnant women

Pregnant enrolled 900 Pregnant completers 767

Infants enrolled 767 Infants completers 632

Pregnant age: 33.3 (4.3)

Infant age: Birth

Race of Mother: NR (100)

Inclusion Criteria: Permanent residents of the study areas for at 

least 2 years, at least 18 years of age, and had no absence from 

the study area for more than 6 weeks during pregnancy, no history 

of drug abuse, no serious health problems or complications of 

pregnancy, and no twin gestation

Exclusion Criteria: Preterm births (<37 weeks of gestational age), 

babies with congenital malformations or severe perinatal problems, 

and those with severe health problems that presented postnatally 

and potentially compromised their neurological development

Adjustments: Fish intake, fatty acids in 

maternal serum and proportion of 

PUFAs, sex, birth weight, maternal IQ, 

weight gain during pregnancy, marital 

status at delivery, SES index, number 

of children living in home, alcohol 

intake during pregnancy, 

breastfeeding history, child intake of 

fish until age 18 months, and daycare 

attendance at age 18 months

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Valent 2013132 Bayley Scales of Infant Dev., Version 3, Cognitive Scale

N Total: 606

18 months AA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.95

Bayley Scales of Infant Dev., Version 3, Cognitive Scale

N Total: 606

18 months ALA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.35

Bayley Scales of Infant Dev., Version 3, Cognitive Scale

N Total: 606

18 months DHA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.49

Bayley Scales of Infant Dev., Version 3, Cognitive Scale

N Total: 606

18 months DPA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.28

Bayley Scales of Infant Dev., Version 3, Cognitive Scale

N Total: 606

18 months EPA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.99

Bayley Scales of Infant Dev., Version 3, Cognitive Scale

N Total: 606

18 months Total n-3s

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.66

Bayley Scales of Infant Dev., Version 3, Cognitive Scale

N Total: 606

18 months n-6/n-3

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.82

Motor function

N Total: 606

18 months AA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.79

Motor function

N Total: 606

18 months ALA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.56

Motor function

N Total: 606

18 months DHA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.51
D-97

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Motor function

N Total: 606

18 months DPA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.22

Motor function

N Total: 606

18 months EPA

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.31

Motor function

N Total: 606

18 months Total n-3s

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.41

Motor function

N Total: 606

18 months n-6/n-3

n-3 Measure: Maternal prenatal serum

n-3 Units: mg/ml

All Coefficient P value: P=0.61
D-98

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Wijga, et al., 2006175

Study name: The Prevention and Incidence of Asthma and 

Mite Allergy (PIAMA) birth cohort study

Study dates: 1995-2000

Study design: Observational prospective

Location: Netherlands

Funding source / conflict: Industry, Government

Follow-up: 4 years

Study Population: NR

Pregnant enrolled 276 Pregnant withdrawals 11 Pregnant 

completers 265

Infants enrolled 276 Infants withdrawals 11 Infants 

completers 265

Pregnant age: 31.0 (3.9) NR

Race of Mother: NR (100)

Inclusion Criteria: Mothers reporting at least 1 of the following: (a 

history of) asthma, current hay fever, current allergy for pets, or 

current allergy for house dust or house dust mite were defined as 

allergic, and mothers reporting that they had none of these were 

defined as non-allergic.

Exclusion Criteria: NR

Adjustments: Sex, number of older 

siblings, maternal age, maternal 

smoking during pregnancy, and 

maternal body mass index before 

pregnancy

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Wilja 2006175 Asthma

N Total: 158

4 y AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 14

OR

Estimate: 0.74

95% CI(0.37, 1.47)

Asthma

N Total: 158

4 y ALA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 14

OR

Estimate: 0.93

95% CI(0.5, 1.35)

Asthma

N Total: 158

4 y All n-3

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 14

OR

Estimate: 0.5

95% CI(0.22, 1.13)

Asthma

N Total: 158

4 y DHA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 14

OR

Estimate: 0.39

95% CI(0.15, 0.99)

Asthma

N Total: 158

4 y EPA/AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 14

OR

Estimate: 0.79

95% CI(0.48, 1.29)

Asthma

N Total: 158

4 y EPA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 14

OR

Estimate: 0.72

95% CI(0.41, 1.26)
D-99

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Asthma

N Total: 158

4 y n-3LCP/n-6LCP

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 14

OR

Estimate: 0.39

95% CI(0.16, 1)

Eczema

N Total: 158

1 y AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 26

OR

Estimate: 0.62

95% CI(0.36, 1.01)

Eczema

N Total: 158

1 y ALA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 26

OR

Estimate: 0.67

95% CI(0.39, 1.2)

Eczema

N Total: 158

1 y All n-3

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 26

OR

Estimate: 0.74

95% CI(0.45, 1.21)

Eczema

N Total: 158

1 y DHA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 26

OR

Estimate: 0.79

95% CI(0.5, 1.23)

Eczema

N Total: 158

1 y EPA/AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 26

OR

Estimate: 1.06

95% CI(0.83, 1.37)

Eczema

N Total: 158

1 y EPA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 26

OR

Estimate: 0.9

95% CI(0.65, 1.26)

Eczema

N Total: 158

1 y n-3LCP/n-6LCP

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 26

OR

Estimate: 0.82

95% CI(0.52, 1.27)

Eczema

N Total: 158

4 y AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 27

OR

Estimate: 0.82

95% CI(0.48, 1.39)

Eczema

N Total: 158

4 y ALA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 27

OR

Estimate: 0.82

95% CI(0.5, 1.35)
D-100

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 158

4 y All n-3

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 27

OR

Estimate: 0.84

95% CI(0.54, 1.3)

Eczema

N Total: 158

4 y DHA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 27

OR

Estimate: 0.99

95% CI(0.7, 1.41)

Eczema

N Total: 158

4 y EPA/AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 27

OR

Estimate: 0.91

95% CI(0.68, 1.23)

Eczema

N Total: 158

4 y EPA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 27

OR

Estimate: 0.9

95% CI(0.65, 1.26)

Eczema

N Total: 158

4 y n-3LCP/n-6LCP

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 27

OR

Estimate: 0.81

95% CI(0.52, 1.26)

Persistent symptoms (eczema at 1 year as well as 

eczema and/or asthma at age 4 years)

N Total: 158

1 y/4 y AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 20

OR

Estimate: 0.81

95% CI(0.45, 1.48)

Persistent symptoms (eczema at 1 year as well as 

eczema and/or asthma at age 4 years)

N Total: 158

1 y/4 y ALA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 20

OR

Estimate: 0.66

95% CI(0.35, 1.25)

Persistent symptoms (eczema at 1 year as well as 

eczema and/or asthma at age 4 years)

N Total: 158

1 y/4 y All n-3

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 20

OR

Estimate: 0.53

95% CI(0.27, 1.04)

Persistent symptoms (eczema at 1 year as well as 

eczema and/or asthma at age 4 years)

N Total: 158

1 y/4 y DHA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 20

OR

Estimate: 0.67

95% CI(0.37, 1.19)

Persistent symptoms (eczema at 1 year as well as 

eczema and/or asthma at age 4 years)

N Total: 158

1 y/4 y EPA/AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 20

OR

Estimate: 0.72

95% CI(0.46, 1.14)
D-101

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Persistent symptoms (eczema at 1 year as well as 

eczema and/or asthma at age 4 years)

N Total: 158

1 y/4 y EPA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 20

OR

Estimate: 0.67

95% CI(0.41, 1.1)

Persistent symptoms (eczema at 1 year as well as 

eczema and/or asthma at age 4 years)

N Total: 158

1 y/4 y n-3LCP/n-6LCP

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 20

OR

Estimate: 0.51

95% CI(0.25, 1.03)

Sensitization and symptoms

N Total: 81

4 y AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 10

OR

Estimate: 1.23

95% CI(0.53, 2.82)

Sensitization and symptoms

N Total: 81

4 y ALA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 10

OR

Estimate: 0.7

95% CI(0.3, 1.63)

Sensitization and symptoms

N Total: 81

4 y All n-3

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 10

OR

Estimate: 0.48

95% CI(0.17, 1.31)

Sensitization and symptoms

N Total: 81

4 y DHA

n-3 Measure: Breast milk fatty acid content,

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 10

OR

Estimate: 0.78

95% CI(0.36, 1.69)

Sensitization and symptoms

N Total: 81

4 y EPA/AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 10

OR

Estimate: 0.52

95% CI(0.23, 1.18)

Sensitization and symptoms

N Total: 81

4 y EPA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 10

OR

Estimate: 0.56

95% CI(0.26, 1.22)

Sensitization and symptoms

N Total: 81

4 y n-3 LCP/n-6 LCP

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 10

OR

Estimate: 0.38

95% CI(0.12, 1.22)

Sensitization

N Total: 52

4 y AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 16

OR

Estimate: 0.62

95% CI(0.27, 1.39)
D-102

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Sensitization

N Total: 52

4 y ALA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 16

OR

Estimate: 2.43

95% CI(1.01, 5.88)

Sensitization

N Total: 52

4 y All n-3

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 16

OR

Estimate: 1.11

95% CI(0.86, 1.42)

Sensitization

N Total: 52

4 y DHA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 16

OR

Estimate: 1.1

95% CI(0.9, 1.34)

Sensitization

N Total: 52

4 y EPA/AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 16

OR

Estimate: 1.22

95% CI(0.92, 1.62)

Sensitization

N Total: 52

4 y EPA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 16

OR

Estimate: 1.13

95% CI(0.9, 1.43)

Sensitization

N Total: 52

4 y n-3LCP/n-6LCP

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 16

OR

Estimate: 1.29

95% CI(0.85, 1.95)

Sensitization

N Total: 81

4 y AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 32

OR

Estimate: 0.85

95% CI(0.5, 1.46)

Sensitization

N Total: 81

4 y ALA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 32

OR

Estimate: 0.81

95% CI(0.49, 1.35)

Sensitization

N Total: 81

4 y All n-3

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 32

OR

Estimate: 0.86

95% CI(0.52, 1.41)

Sensitization

N Total: 81

4 y DHA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 32

OR

Estimate: 0.89

95% CI(0.57, 1.38)
D-103

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Sensitization

N Total: 81

4 y EPA/AA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 32

OR

Estimate: 1.02

95% CI(0.71, 1.46)

Sensitization

N Total: 81

4 y EPA

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 32

OR

Estimate: 0.85

95% CI(0.55, 1.32)

Sensitization

N Total: 81

4 y n-3LCP/n-6LCP

n-3 Measure: Breast milk fatty acid content, 

median wt% (interquartile range)

n-3 Units: per interquartile range increase in 

breast milk FA content (wt%)

All

N Cases: 32

OR

Estimate: 1.12

95% CI(0.7, 1.77)
D-104

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Yoshihiro Miyake, et al., 200693

Study name: Osaka maternal and child health study

Study dates: 2001-2003

Study design: Observational prospective

Location: Japan

Funding source / conflict: Government, Multiple foundations 

and Societies, None

Study Population: Healthy pregnant women

Pregnant enrolled 1002 Pregnant withdrawals 137 Pregnant 

completers 865

Pregnant age: age reported in categories

Race of Mother: Asian (100%)

Inclusion Criteria: women who became pregnant in Neyagawa City, 

Osaka Prefecture, Japan

Exclusion Criteria: NR

Adjustments: Age, gestation, parity, 

cigarette smoking, family structure, 

family income, education, changes in 

diet in the previous month, season 

when data at baseline were collected, 

body mass index, time of delivery 

before the second survey, medical 

problems in pregnancy, baby’s sex 

and baby’s birthweight

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Miyake 200693 DHA

n-3 Measure: FFQ

n-3 Units: g/day

Q1 0.16 OR

DHA

n-3 Measure: FFQ

n-3 Units: g/day

Q2 0.26 OR

Estimate: 0.76

95% CI(0.44, 1.32)

DHA

n-3 Measure: FFQ

n-3 Units: g/day

Q3 0.34 OR

Estimate: 0.62

95% CI(0.34, 1.09)

DHA

n-3 Measure: FFQ

n-3 Units: g/day

Q4 0.5 OR

Estimate: 0.85

95% CI(0.49, 1.46)

EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q1 0.08 OR

EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q2 0.15 OR

Estimate: 0.93

95% CI(0.54, 1.6)

EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q3 0.21 OR

Estimate: 0.81

95% CI(0.46, 1.42)

EPA

n-3 Measure: FFQ

n-3 Units: g/day

Q4 0.32 OR

Estimate: 0.89

95% CI(0.51, 1.55)

n-3 FA

n-3 Measure: FFQ

n-3 Units: g/day

Q1 1.6 OR

n-3 FA

n-3 Measure: FFQ

n-3 Units: g/day

Q2 2.1 OR

Estimate: 0.68

95% CI(0.39, 1.18)
D-105

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

n-3 FA

n-3 Measure: FFQ

n-3 Units: g/day

Q3 2.4 OR

Estimate: 0.58

95% CI(0.33, 1.02)

n-3 FA

n-3 Measure: FFQ

n-3 Units: g/day

Q4 3 OR

Estimate: 0.9

95% CI(0.53, 1.53)
D-106

Author, Year,

Study,

Location,

Funding Source,

Follow-up Population and participant information Inclusion and Exclusion Criteria Adjustment

Yu, et al., 2015185

Study dates: Participants recruited between June 2009 and 

September 2010

Study design: Observational prospective

Location: NR

Funding source / conflict: Industry, Government

Study Population: Healthy infants Healthy pregnant women

Infants enrolled 1162 Infants completers 960

Pregnant age: NR (NR) NR

Race of Mother: NR (100%)

Inclusion Criteria: Participants were mother–child pairs in the 

Growing Up in Singapore Towards healthy Outcomes (GUSTO) 

birth cohort.

Exclusion Criteria: NR

Adjustments: In the models, we 

adjusted for maternal characteristics 

including maternal age, ethnicity, 

gravidity, education level and energy 

intake. The same was done for infant 

characteristics including sex, birth 

weight, gestational age, duration of 

breast-feeding, family history of 

allergic diseases (which includes 

allergic rhinitis, eczema and asthma in 

first-degree relatives of the children 

(i.e. father, mother and/or sibling), 

exposure to environmental tobacco 

smoking, child day care attendance 

and having a cat or dog at home up to 

18 months of age.
D-107

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Yu 2015185 Allergic sensitisation

N Total: 728

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =1.0

N Quantile: NR

N Cases: NR

OR

Allergic sensitisation

N Total: 728

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 0.11-0.18

N Quantile: NR

N Cases: NR

OR

Estimate: 0.8

95% CI(0.43, 1.49)

Allergic sensitisation

N Total: 728

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 0.19-0.27

N Quantile: NR

N Cases: NR

OR

Estimate: 0.92

95% CI(0.51, 1.68)

Allergic sensitisation

N Total: 728

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =0.28

N Quantile: NR

N Cases: NR

OR

Estimate: 0.85

95% CI(0.46, 1.55)

Allergic sensitisation

N Total: 728

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =3.60

N Quantile: NR

N Cases: NR

OR

Allergic sensitisation

N Total: 728

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 3.16-4.59

N Quantile: NR

N Cases: NR

OR

Estimate: 0.9

95% CI(0.48, 1.65)

Allergic sensitisation

N Total: 728

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 4.60-5.63

N Quantile: NR

N Cases: NR

OR

Estimate: 0.73

95% CI(0.38, 1.40)

Allergic sensitisation

N Total: 728

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =5.64

N Quantile: NR

N Cases: NR

OR

Estimate: 1.24

95% CI(0.69, 2.24)

Allergic sensitisation

N Total: 728

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =0.35

N Quantile: NR

N Cases: NR

OR

Allergic sensitisation

N Total: 728

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 0.36-0.51

N Quantile: NR

N Cases: NR

OR

Estimate: 1.12

95% CI(0.57, 2.21)

Allergic sensitisation

N Total: 728

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 0.52-0.82

N Quantile: NR

N Cases: NR

OR

Estimate: 1.26

95% CI(0.65, 2.47)

Allergic sensitisation

N Total: 728

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =0.83

N Quantile: NR

N Cases: NR

OR

Estimate: 1.82

95% CI(0.94, 3.50)

Allergic sensitisation

N Total: 728

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =5.00

N Quantile: NR

N Cases: NR

OR

Allergic sensitisation

N Total: 728

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 5.01-6.18

N Quantile: NR

N Cases: NR

OR

Estimate: 0.91

95% CI(0.48, 1.72)

Allergic sensitisation

N Total: 728

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 6.19-7.49

N Quantile: NR

N Cases: NR

OR

Estimate: 0.83

95% CI(0.43, 1.58)
D-108

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Allergic sensitisation

N Total: 728

Up to 18

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =7.50

N Quantile: NR

N Cases: NR

OR

Estimate: 1.41

95% CI(0.77, 2.58)

Allergic sensitisation

N Total: 728

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =4.52

N Quantile: NR

N Cases: NR

OR

Allergic sensitisation

N Total: 728

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 4.53-5.49

N Quantile: NR

N Cases: NR

OR

Estimate: 0.6

95% CI(0.33, 1.10)

Allergic sensitisation

N Total: 728

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 5.50-6.94

N Quantile: NR

N Cases: NR

OR

Estimate: 0.67

95% CI(0.37, 1.21)

Allergic sensitisation

N Total: 728

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =6.95

N Quantile: NR

N Cases: NR

OR

Estimate: 0.66

95% CI(0.36, 1.22)

Eczema

N Total: 833

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =1.0

N Quantile: NR

N Cases: NR

OR

Eczema

N Total: 833

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 0.11-0.18

N Quantile: NR

N Cases: NR

OR

Estimate: 0.87

95% CI(0.50, 1.51)

Eczema

N Total: 833

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 0.19-0.27

N Quantile: NR

N Cases: NR

OR

Estimate: 1.07

95% CI(0.64, 1.81)

Eczema

N Total: 833

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =0.28

N Quantile: NR

N Cases: NR

OR

Estimate: 0.87

95% CI(0.51, 1.47)

Eczema

N Total: 833

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =3.60

N Quantile: NR

N Cases: NR

OR

Eczema

N Total: 833

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 3.16-4.59

N Quantile: NR

N Cases: NR

OR

Estimate: 1.02

95% CI(0.61, 1.70)

Eczema

N Total: 833

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 4.60-5.63

N Quantile: NR

N Cases: NR

OR

Estimate: 0.61

95% CI(0.35, 1.07)

Eczema

N Total: 833

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =5.64

N Quantile: NR

N Cases: NR

OR

Estimate: 0.8

95% CI(0.47, 1.35)

Eczema

N Total: 833

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =0.35

N Quantile: NR

N Cases: NR

OR

Eczema

N Total: 833

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 0.36-0.51

N Quantile: NR

N Cases: NR

OR

Estimate: 1.14

95% CI(0.64, 2.04)
D-109

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Eczema

N Total: 833

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 0.52-0.82

N Quantile: NR

N Cases: NR

OR

Estimate: 1.07

95% CI(0.60, 1.89)

Eczema

N Total: 833

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =0.83

N Quantile: NR

N Cases: NR

OR

Estimate: 1.2

95% CI(0.68, 2.13)

Eczema

N Total: 833

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =5.00

N Quantile: NR

N Cases: NR

OR

Eczema

N Total: 833

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 5.01-6.18

N Quantile: NR

N Cases: NR

OR

Estimate: 1.02

95% CI(0.60, 1.74)

Eczema

N Total: 833

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 6.19-7.49

N Quantile: NR

N Cases: NR

OR

Estimate: 0.67

95% CI(0.38, 1.18)

Eczema

N Total: 833

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =7.50

N Quantile: NR

N Cases: NR

OR

Estimate: 0.93

95% CI(0.55, 1.60)

Eczema

N Total: 833

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 1.9-4.5

N Quantile: NR

N Cases: NR

OR

Eczema

N Total: 833

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 4.6-5.4

N Quantile: NR

N Cases: NR

OR

Estimate: 0.55

95% CI(0.32, 0.97)

Eczema

N Total: 833

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 5.5-6.9

N Quantile: NR

N Cases: NR

OR

Estimate: 1.19

95% CI(0.72, 1.97)

Eczema

N Total: 833

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 7.0-16.6

N Quantile: NR

N Cases: NR

OR

Estimate: 1.21

95% CI(0.71, 2.06)

Rhinitis

N Total: 808

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =1.0

N Quantile: NR

N Cases: NR

OR

Rhinitis

N Total: 808

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 0.11-0.18

N Quantile: NR

N Cases: NR

OR

Estimate: 1.18

95% CI(0.74, 1.89)

Rhinitis

N Total: 808

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 0.19-0.27

N Quantile: NR

N Cases: NR

OR

Estimate: 0.95

95% CI(0.59, 1.52)

Rhinitis

N Total: 808

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =0.28

N Quantile: NR

N Cases: NR

OR

Estimate: 0.86

95% CI(0.54, 1.38)

Rhinitis

N Total: 808

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =3.60

N Quantile: NR

N Cases: NR

OR
D-110

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Rhinitis

N Total: 808

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 3.16-4.59

N Quantile: NR

N Cases: NR

OR

Estimate: 1.53

95% CI(0.94, 2.50)

Rhinitis

N Total: 808

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 4.60-5.63

N Quantile: NR

N Cases: NR

OR

Estimate: 1.97

95% CI(1.22, 3.21)

Rhinitis

N Total: 808

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =5.64

N Quantile: NR

N Cases: NR

OR

Estimate: 1.42

95% CI(0.87, 2.32)

Rhinitis

N Total: 808

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =0.35

N Quantile: NR

N Cases: NR

OR

Rhinitis

N Total: 808

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 0.36-0.51

N Quantile: NR

N Cases: NR

OR

Estimate: 1.09

95% CI(0.68, 1.77)

Rhinitis

N Total: 808

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 0.52-0.82

N Quantile: NR

N Cases: NR

OR

Estimate: 1.02

95% CI(0.63, 1.66)

Rhinitis

N Total: 808

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =0.83

N Quantile: NR

N Cases: NR

OR

Estimate: 1.04

95% CI(0.64, 1.69)

Rhinitis

N Total: 808

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =5.00

N Quantile: NR

N Cases: NR

OR

Rhinitis

N Total: 808

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 5.01-6.18

N Quantile: NR

N Cases: NR

OR

Estimate: 1.56

95% CI(0.96. 2.54)

Rhinitis

N Total: 808

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 6.19-7.49

N Quantile: NR

N Cases: NR

OR

Estimate: 1.67

95% CI(1.03, 2.70)

Rhinitis

N Total: 808

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =7.50

N Quantile: NR

N Cases: NR

OR

Estimate: 1.34

95% CI(0.81. 2.21)

Rhinitis

N Total: 808

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 1.9-4.5

N Quantile: NR

N Cases: NR

OR

Rhinitis

N Total: 808

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 4.6-5.4

N Quantile: NR

N Cases: NR

OR

Estimate: 1.11

95% CI(.7, 1.75)

Rhinitis

N Total: 808

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 5.5-6.9

N Quantile: NR

N Cases: NR

OR

Estimate: 1.34

95% CI(.85, 2.11)

Rhinitis

N Total: 808

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 7.0-16.6

N Quantile: NR

N Cases: NR

OR

Estimate: 0.66

95% CI(0.40, 1.10)
D-111

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Wheezing

N Total: 859

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =1.0

N Quantile: NR

N Cases: NR

OR

Wheezing

N Total: 859

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 0.11-0.18

N Quantile: NR

N Cases: NR

OR

Estimate: 1.22

95% CI(0.61, 2.44)

Wheezing

N Total: 859

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 0.19-0.27

N Quantile: NR

N Cases: NR

OR

Estimate: 1.77

95% CI(0.91, 3.46)

Wheezing

N Total: 859

Up to 18 

months

A-linolenic acid

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =0.28

N Quantile: NR

N Cases: NR

OR

Estimate: 1.12

95% CI(0.56, 2.24)

Wheezing

N Total: 859

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =3.60

N Quantile: NR

N Cases: NR

OR

Wheezing

N Total: 859

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 3.16-4.59

N Quantile: NR

N Cases: NR

OR

Estimate: 0.95

95% CI(0.49, 1.86)

Wheezing

N Total: 859

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 4.60-5.63

N Quantile: NR

N Cases: NR

OR

Estimate: 0.98

95% CI(0.49, 1.96)

Wheezing

N Total: 859

Up to 18 

months

DHA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =5.64

N Quantile: NR

N Cases: NR

OR

Estimate: 1.15

95% CI(0.60, 2.22)

Wheezing

N Total: 859

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =0.35

N Quantile: NR

N Cases: NR

OR

Wheezing

N Total: 859

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 0.36-0.51

N Quantile: NR

N Cases: NR

OR

Estimate: 1.07

95% CI(0.52, 2.21)

Wheezing

N Total: 859

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 0.52-0.82

N Quantile: NR

N Cases: NR

OR

Estimate: 1.19

95% CI(0.60, 2.36)

Wheezing

N Total: 859

Up to 18 

months

EPA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =0.83

N Quantile: NR

N Cases: NR

OR

Estimate: 1.2

95% CI(0.60, 2.39)

Wheezing

N Total: 859

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 =5.00

N Quantile: NR

N Cases: NR

OR

Wheezing

N Total: 859

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 5.01-6.18

N Quantile: NR

N Cases: NR

OR

Estimate: 0.9

95% CI(0.45, 1.78)

Wheezing

N Total: 859

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 6.19-7.49

N Quantile: NR

N Cases: NR

OR

Estimate: 1.09

95% CI(0.56, 2.13)
D-112

Article Outcome, Cohort size

Follow up 

Time

Exposure

Intervention, n-3 measure, n-3 units Quantile

Metric, Estimate and 

CI P value

Wheezing

N Total: 859

Up to 18 

months

n-3 PUFA

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 =7.50

N Quantile: NR

N Cases: NR

OR

Estimate: 1.12

95% CI(0.57, 2.2)

Wheezing

N Total: 859

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q1 1.9-4.5

N Quantile: NR

N Cases: NR

OR

Wheezing

N Total: 859

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q2 4.6-5.4

N Quantile: NR

N Cases: NR

OR

Estimate: 0.7

95% CI(0.38, 1.30)

Wheezing

N Total: 859

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q3 5.5-6.9

N Quantile: NR

N Cases: NR

OR

Estimate: 0.64

95% CI(0.34, 1.23)

Wheezing

N Total: 859

Up to 18 

months

n-6: n-3 PUFA ratio

n-3 Measure: Maternal blood

n-3 Units: % of total plasma fatty acids

Q4 7.0-16.6

N Quantile: NR

N Cases: NR

OR

Estimate: 0.63

95% CI(0.32, 1.25)
Appendix E. Data Abstraction Tools

1. Data Abstraction Tool for RCTs

2. Data Abstraction Tool for Observational Studies

3. Modified Cochrane Risk of Bias Tool 

4. Modified Newcastle-Ottawa Quality Assessment Scale

5. McHarms Tool

E-1
1. Data Abstraction Tool

Article information

1. What is the name of this study? (e.g. DART, Physician's Health Study) Omit if name of study is not provided.

DART

Physician's Health Study

Maastricht Essential Fatty Acid Birth (MEFAB) Cohort

The DIAMOND Study (DHA Intake And Measurement Of Neural Development)

data using DIAMOND study

POSGRAD

NUHEAL

Infant Fish Oil Supplementation Study (IFOS)

Danish National Birth Cohort

Groningen LCPUFA study

DINO (Docosahexaenoic acid for the Improvement in Neurodevelopmental Outcome)

DOMINO

INFAT

BeMIM (Belgrade-Munch Infant Milk Trial)

GINI

The Docosahexaenoic Acid to Optimise Mother Infant Outcome (DOMInO)

Childhood Asthma Prevention Study

Salmon in Pregnancy Study (SiPS)

Other study names

2. Study Design

Trial: Randomized Parallel (Omega-3 vs. Control; Omega-3 XX vs. X)

Trial: Randomized Cross-over

E-2
Trial: Randomized Factorial Design

Observational: Prospective, longitudinal, comparative study

Observational: Nested Case Control

Other

Clear Response

3. Funding source

Industry funded

Government funded

Some authors employed by industry (companies that make the supplements)

Funding or affiliations not reported

Mulitple foundations and Societies

None of the authors had any personal or financial conflicts of interest

Trade group funded

March of Dimes

Manufacturer supplied product

Some authors serve on scientific advisory boards for corporations

Other funding source

4. Country in which study conducted (where subjects live) Note that this might be different than the countries where

the authors are based. Select "NR (not reported)" if it's truly unclear.

US

Canada

Denmark

Finland

Germany

Greece

Italy

E-3
Japan

Netherlands

Norway

Sweden

UK

NR (not reported)

Mexico

Australia

Taiwan

Spain

Hungary

Turkey

Bangladesh

Thailand

Serbia

Multie-center study in hospitals of 11 countries in Europe

Other

5. Study Population

Healthy infants or children

Preterm infants

Healthy pregnant women

Postpartum women

Breast-feeding women

Low birth weight infants

E-4
Pregnant mothers with allergies and their offspring

Pregnant women whose unborn children were at high risk of developing asthma

children with family history of allergy

Other

6. Inclusion criteria as defined in study

7. Exclusion criteria

II. Participant Information

1. Sample size

Pregnant

#

Enrolled/Rand

omized

# of

withdrawals

# of

completers

(largest followup)

Lactating mothers

#

Enrolled/Rand

omized

# of

withdrawals

# of

completers

(largest followup)

Mothers

#

Enrolled/Rand

omized

# of

withdrawals

# of

completers

(largest followup)

Infants

#

Enrolled/Rand

omized

# of

withdrawals

# of

completers

(largest followup)

2. Age at baseline

Mean age (Pregnant) Mean age (Lactating

mothers)

Mean age (Mothers) Mean age (Infants)

Standard Deviation

(Pregnant)

Standard Deviation

(Lactating mothers)

Standard Deviation

(Mothers)

Standard Deviation

(Infants)

E-5
Age range (Pregnant) Age range (Lactating

mothers)

Age range (Mothers) Age range (infants)

3. Race/Ethnicity (Mother)

White/European (specify %)

Black/African American/etc. (specify %)

Asian (specify %)

Hispanic (specify %)

Inuit/Eskimo (specify %)

NR (specify %)

varied by study site and experimental group (specify %)

Minority (specify %)

Other

non black

Puerto Rican/Latino

Native Hawaiian or other pacific ethnicity

Other

4. Race/Ethnicity (Infant)

White/European (specify %)

Black/African American/etc. (specify %)

Asian (specify %)

E-6
Hispanic (specify %)

Inuit/Eskimo (specify %)

Not reported (specify %)

varied by study site and experimental groups (specify %)

Non-white

Other

5. Is baseline biomarker information reported?

Yes No Clear Response

6. Is baseline Omega-3 intake reported?

Yes No Clear Response

III. Intervention information [if observational study, please stop here]

Pregnant Lactating mothers Mothers Infants

Start time of

intervention

Length

(duration) of

intervention

Longest followup time

V. Arms

How to fill out this section:

For controlled trials, Arm 1 should be the placebo/control group or lowest dose of intervention.

1. How many arms are there?

Arm 1:

Name

Description

RCT: Arm 1 (placebo or other control)

Brand name (if applicable)

Manufacturer (specify)

Purity data (specify)

Presence of other potentially active ingredients (e.g., arachidonic acid, vitamin E) (specify)

E-7
Storage conditions or other efforts to preserve product viability) (specify)

n-3 composition (e.g., grams or percent EPA, DHA per capsule) (specify)

Dose per day (e.g., 1 1gm capsule, twice a day) (specify)

If placebo, how was blinding achieved? (specify)

Maternal conditions

Infant conditions

Arm 2:

Name

Description

RCT: Arm 2 (placebo or other control)

Brand name (if applicable)

Manufacturer (specify)

Purity data (specify)

Presence of other potentially active ingredients (e.g., arachidonic acid, vitamin E) (specify)

Storage conditions or other efforts to preserve product viability) (specify)

n-3 composition (e.g., grams or percent EPA, DHA per capsule) (specify)

Dose per day (e.g., 1 1gm capsule, twice a day) (specify)

If placebo, how was blinding achieved? (specify)

Maternal conditions

Infant conditions

Arm 3:

Name

Description

RCT: Arm 3 (placebo or other control)

Brand name (if applicable)

Manufacturer (specify)

E-8
Purity data (specify)

Presence of other potentially active ingredients (e.g., arachidonic acid, vitamin E) (specify)

Storage conditions or other efforts to preserve product viability) (specify)

n-3 composition (e.g., grams or percent EPA, DHA per capsule) (specify)

Dose per day (e.g., 1 1gm capsule, twice a day) (specify)

If placebo, how was blinding achieved? (specify)

Maternal conditions

Infant conditions

Arm 4:

Name

Description

RCT: Arm 4 (placebo or other control)

Brand name (if applicable)

Manufacturer (specify)

Purity data (specify)

Presence of other potentially active ingredients (e.g., arachidonic acid, vitamin E) (specify)

Storage conditions or other efforts to preserve product viability) (specify)

n-3 composition (e.g., grams or percent EPA, DHA per capsule) (specify)

Dose per day (e.g., 1 1gm capsule, twice a day) (specify)

If placebo, how was blinding achieved? (specify)

Maternal conditions

Infant conditions

Arm 5:

Name

Description

RCT: Arm 5 (placebo or other control)

E-9
Brand name (if applicable)

Manufacturer (specify)

Purity data (specify)

Presence of other potentially active ingredients (e.g., arachidonic acid, vitamin E) (specify)

Storage conditions or other efforts to preserve product viability) (specify)

n-3 composition (e.g., grams or percent EPA, DHA per capsule) (specify)

Dose per day (e.g., 1 1gm capsule, twice a day) (specify)

If placebo, how was blinding achieved? (specify)

Maternal conditions

Infant conditions

Please indicate if there are any references from the studies reference list that we should pull (indicate the

reference number from the article)

Arm 6:

Name

Description

RCT: Arm 6 (placebo or other control)

Brand name (if applicable)

Manufacturer (specify)

Purity data (specify)

Presence of other potentially active ingredients (e.g., arachidonic acid, vitamin E) (specify)

Storage conditions or other efforts to preserve product viability) (specify)

n-3 composition (e.g., grams or percent EPA, DHA per capsule) (specify)

Dose per day (e.g., 1 1gm capsule, twice a day) (specify)

If placebo, how was blinding achieved? (specify)

E-10
Maternal conditions

Infant conditions

Arm 7:

Name

Description

RCT: Arm 7 (placebo or other control)

Brand name (if applicable)

Manufacturer (specify)

Purity data (specify)

Presence of other potentially active ingredients (e.g., arachidonic acid, vitamin E) (specify)

Storage conditions or other efforts to preserve product viability) (specify)

n-3 composition (e.g., grams or percent EPA, DHA per capsule) (specify)

Dose per day (e.g., 1 1gm capsule, twice a day) (specify)

If placebo, how was blinding achieved? (specify)

Maternal conditions

Infant conditions

E-11
2. Data Abstraction Tool for Observational Studies

I. Article information

1. What is the name of this study? (e.g. DART, Physician's Health Study) Omit if name of study is not

provided.

DART

Physician's Health Study

Maastricht Essential Fatty Acid Birth (MEFAB) Cohort

The DIAMOND Study (DHA Intake And Measurement Of Neural Development)

data using DIAMOND study

POSGRAD

NUHEAL

Infant Fish Oil Supplementation Study (IFOS)

Danish National Birth Cohort

Groningen LCPUFA study

DINO (Docosahexaenoic acid for the Improvement in Neurodevelopmental Outcome)

DOMINO

INFAT

BeMIM (Belgrade-Munch Infant Milk Trial)

GINI

The Docosahexaenoic Acid to Optimise Mother Infant Outcome (DOMInO)

Childhood Asthma Prevention Study

Salmon in Pregnancy Study (SiPS)

Project Viva

INMA

Avon Longitudinal Study of Parents and Children (ALSPAC)

E-12
Alberta Pregnancy Outcomes and Nutrition (APrON) study

Osaka maternal and child health study

Amsterdam Born Children and their Development (ABCD)

EDEN

LISAplus

The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study

KOALA Birth Cohort Study

Finnish Type 1 Diabetes Prediction and Prevention Nutrition Study

The Prevention of Allergy among Children in Trondheim study

Norwegian Mother and Child Cohort Study (MoBa)

INfancia y Medio Ambiente (INMA) Project

Pregnancy, Infection and Nutrition Study

Nurses Health Study

Kyushu Okinawa Maternal and Child Health Study

Southampton Women's Survey

Other study names

2. Study Design

Trial: Randomized Parallel (Omega-3 vs. Control; Omega-3 XX vs. X)

Trial: Randomized Cross-over

Trial: Randomized Factorial Design

Observational: Prospective, longitudinal, comparative study

Observational: Nested Case Control

Other

Clear Response

3. Funding source

Industry funded

E-13
Government funded

Some authors employed by industry (companies that make the supplements)

Funding or affiliations not reported

Mulitple foundations and Societies

None of the authors had any personal or financial conflicts of interest

Trade group funded

March of Dimes

Manufacturer supplied product

Some authors serve on scientific advisory boards for corporations

Alberta Innovates-Health Solutions

Infant formula manufacturer performed assays

Other funding source

4. Country in which study conducted (where subjects live) Note that this might be different than the

countries where the authors are based. Select "NR (not reported)" if it's truly unclear.

US

Canada

Denmark

Finland

Germany

Greece

Italy

Japan

Netherlands

Norway

Sweden

E-14
UK

NR (not reported)

Mexico

Australia

Taiwan

Spain

Hungary

Turkey

Bangladesh

Thailand

Serbia

Multie-center study in hospitals of 11 countries in Europe

Iceland

England

France

Malaysia

India

Other

5. Study Population

Healthy infants or children

Preterm infants

Healthy pregnant women

Postpartum women

Breast-feeding women

E-15
Low birth weight infants

Pregnant mothers with allergies and their offspring

Pregnant women whose unborn children were at high risk of developing asthma

children with family history of allergy

Children with allergies

Infants at risk for Diabetes 1

Pregnant mothers without allergies and their offspring

Children with a family history of asthma

Other

6. Inclusion criteria as defined in study

7. Exclusion criteria

II. Participant Information

1. Sample size

Pregnant

#

Enrolled/Rand

omized

# of

withdrawals

# of

completers

(largest followup)

Lactating mothers

#

Enrolled/Rand

omized

# of

withdrawals

# of

completers

(largest followup)

Mothers

#

Enrolled/Rand

omized

# of

withdrawals

# of

completers

(largest followup)

Infants

#

Enrolled/Rand

omized

# of

withdrawals

# of

completers

(largest followup)

2. Age at baseline

Mean age (Pregnant) Mean age (Lactating

mothers)

Mean age (Mothers) Mean age (Infants)

E-16
Standard Deviation

(Pregnant)

Standard Deviation

(Lactating mothers)

Standard Deviation

(Mothers)

Standard Deviation

(Infants)

Age range (Pregnant) Age range (Lactating

mothers)

Age range (Mothers) Age range (infants)

3. Race/Ethnicity (Mother)

White/European (specify %)

Black/African American/etc. (specify %)

Asian (specify %)

Hispanic (specify %)

Inuit/Eskimo (specify %)

NR (specify %)

varied by study site and experimental group (specify %)

Minority (specify %)

Other

non black

Puerto Rican/Latino

Native Hawaiian or other pacific ethnicity

non-western

E-17
Other

4. Race/Ethnicity (Infant)

White/European (specify %)

Black/African American/etc. (specify %)

Asian (specify %)

Hispanic (specify %)

Inuit/Eskimo (specify %)

Not reported (specify %)

varied by study site and experimental groups (specify %)

Non-white

Not relevant

Other

5. Is baseline biomarker information reported?

Yes No Clear Response

6. Is baseline Omega-3 intake reported?

Yes No Clear Response

7. Dates of study

When was the actual study conducted as opposed to when it was published

8. Medical history

9. Risk Type

10. Exposure Timing

e.g., second and third trimester, birth to age 1..

E-18
E-19
3. Modified Cochrane Risk of Bias Tool

1. Was the allocation sequence (randomization method) adequately generated

There is a LOW RISK OF BIAS if the investigators describe a random component in the sequence generation

process such as: referring to a random number table, using a computer random number generator, coin tossing,

shuffling cards or envelopes, throwing dice, drawing of lots. There is a HIGH RISK OF BIAS if the investigators

describe a non-random component in the sequence generation process, such as: sequence generated by odd or

even date of birth, date (or day) of admission, hospital or clinic record number; or allocation by judgement of the

clinician, preference of the participant, results of a laboratory test or a series of tests, or availability of the intervention.

IF HIGH RISK OF BIAS, EXPLAIN IN NOTES.

Low risk (yes)

High risk (no)

Unclear

Clear Response

High risk notes

2. Was ALLOCATION adequately concealed (prior to assignment)?

There is a LOW RISK OF BIAS if the participants and investigators enrolling participants could not foresee

assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation

(including telephone, web-based and pharmacy-controlled randomization); sequentially numbered drug containers of

identical appearance; or sequentially numbered, opaque, sealed envelopes. There is a HIGH RISK OF BIAS if

participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection

bias, such as allocation based on: using an open random allocation schedule (e.g. a list of random numbers);

assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non-opaque or

not sequentially numbered); alternation or rotation; date of birth; case record number; or other explicitly unconcealed

procedures. IF HIGH RISK OF BIAS, EXPLAIN IN NOTES.

Low risk

High risk

Unclear

Clear Response

High risk notes

3. Were PARTICIPANTS adequately BLINDED?

There is a LOW RISK OF BIAS if blinding of participants was ensured and it was unlikely that the blinding could have

been broken; or if there was no blinding or incomplete blinding, but the review authors judge that the outcome is not

likely to be influenced by lack of blinding.

E-20
Low risk

High risk

Unclear

Clear Response

High risk notes

4. Were OUTCOME ASSESSORS adequately BLINDED?

There is LOW RISK OF BIAS if the blinding of the outcome assessment was ensured and it was unlikely that the

blinding could have been broken; or if there was no or incomplete blinding, but the outcome is unlikely to be

influenced by lack of blinding (ie, lab tests--lipids--inherently low risk of bias, but not blood pressure).

Low risk

High risk

Unclear

Clear Response

High risk notes

5. If outcome assessor blinding risk of bias is different for different outcomes (eg, lipids vs. MI), choose HIGH

risk of bias and describe in Notes

Low risk

High risk

Unclear

Not applicable

Clear Response

High risk notes

6. Incomplete outcome data (ATTRITION BIAS) due to amount, nature or handling of incomplete outcome

data

E-21
There is a LOW RISK OF BIAS if there were no missing outcome data; reasons for missing outcome data were

unlikely to be related to the true outcome; missing outcome data were balanced in numbers, with similar reasons for

missing data across groups (****The percentage of withdrawals and drop-outs should not exceed 20% for short-term

follow-up [<=1 year] and 30% for long-term follow-up [>1 year] ). IF HIGH RISK OF BIAS, EXPLAIN IN NOTES.

Low risk

High risk

Unclear

Clear Response

High risk notes

7. If attrition risk of bias is different for different outcomes (eg, lipids vs. MI) or different time points (eg, 1

year vs. 5 years), choose HIGH risk of bias and describe in Notes

Low risk

High risk

Unclear

Not applicable

Clear Response

High risk notes

8. Is there evidence of SELECTIVE OUTCOME REPORTING bias (Yes/No)?

For LIPIDS, are only selected lipids/lipoproteins reported, were lipids measured at baseline and was a blood sample

taken at follow-up but follow-up lipids were not reported, were subgroup lipid outcomes omitted? For BLOOD

PRESSURE, was BP measured at baseline and was there a follow-up clinical encounter (where follow-up BP would

have been measured), but BP is not reported, were subgroup BP outcomes omitted? For CLINICAL OUTCOMES,

are all outcomes in the Methods section (all pre-specified outcomes) reported, were all components of composite

outcomes reported? DESCRIBE ISSUES IN NOTES.

Yes

No

Unclear

Clear Response

Notes

E-22
9. INTENTION-TO-TREAT analysis? (Yes/No)

YES if they state ITT and methods used were actually ITT, or ** all** participants were analyzed in the group to which

they were allocated by randomization (no cross-over). IF NO ITT, EXPLAIN IN NOTES.

Yes

No

Unclear

Clear Response

Notes

10. Group SIMILARITY AT BASELINE (**GENERAL**)

There is LOW RISK OF BIAS if groups are similar at baseline for demographic and other factors ("Table 1"). Also

LOW risk of bias if any baseline differences were adjusted for in all relevant analyses. IF HIGH RISK OF BIAS,

EXPLAIN IN NOTES.

Low risk

High risk

Unclear

Clear Response

Notes

11. Group SIMILARITY AT BASELINE (**OMEGA-3**)

There is LOW RISK OF BIAS if groups were similar (or statistical adjustments were made to account for differences)

in omega-3 intake or status (biomarkers) at baseline. There is HIGH RISK OF BIAS if groups had different omega-3

intake/status at baseline that was not accounted for. There is UNCLEAR RISK OF BIAS if baseline omega-3 status

was not reported.

Low risk

High risk

Unclear

E-23
Clear Response

Notes

12. Was there incomplete COMPLIANCE with interventions across groups?

There is LOW RISK OF BIAS if compliance with the interventions was acceptable (>=80% across intervention

duration), based on the reported actual compliance compared to protocol or increased biomarker levels were

reported during or at the end of the intervention. There is HIGH RISK OF BIAS if compliance was low (<80%) or no

change in biomarker levels were found during or at the end of the intervention. There is UNCLEAR RISK OF BIAS if

these data were not reported.

Low risk

High risk

Unclear

Clear Response

Notes

13. Additional Bias: Bias due to problems not covered elsewhere in the table.

Yes

No

Clear Response

E-24
5. Modified Newcastle-Ottawa Quality Assessment Scale

Selection

1) Representativeness of the exposed cohort

a) truly representative of the average pregnant women and children in the community

b) somewhat representative of the average pregnant women and children in the community

c) selected group of users eg nurses, volunteers

d) no description of the derivation of the cohort

2) Selection of the non exposed cohort

a) drawn from the same community as the exposed cohort

b) drawn from a different source

c) no description of the derivation of the non exposed cohort

d) N/A

3) Ascertainment of exposure

a) secure record (eg surgical records)

b) structured interview

c) written self report

d) no description

4) Demonstration that outcome of interest was not present at start of study (if relevant, which will almost never be the

case) or author's statement that a valid outcome measure was chosen.

a) yes

b) no

Clear Response

Comparability

1) Comparability of cohorts on the basis of the design or analysis

If the authors describe factors for which they adjusted or noted that cohorts were matched on important factors and

listed the factors, count that as a “yes.”

a) study controls for _____________ (select the most important factor)

b) study controls for any additional factor (This criteria could be modified to indicate specific control for a second

important factor.)

Outcome

1) Assessment of outcome

a) independent blind assessment

E-25
b) record linkage

c) self report

d) no description

2) Was follow-up long enough for outcomes to occur (e.g., 5 years or older for asthma; for other outcomes, if the

authors say why they chose a particular followup time, definitely select "yes"; otherwise use your own judgment.

a) yes (select an adequate follow up period for outcome of interest)

b) no

Clear Response

3) Adequacy of follow up of cohorts

a) complete follow up - all subjects accounted for

b) subjects lost to follow up unlikely to introduce bias - small number lost - >80% retention for ≤ 1 year followup;

>30% retention for 1-5 years followup; >40% retention for 6-10 years followup; >50% retention for 11-18 years

followup; or description provided of those lost)

c) follow up rate < 80% (select an adequate %) and no description of those lost

d) no statement

E-26
6. McHarms Tool

1. Were the harms PRE-DEFINED using standardized or precise definitions?

Harms can be defined as the totality of adverse consequences of an intervention or therapy. Harms are the opposite

of benefits, against which they are directly compared. The balance between the benefit(s) and harm(s) of an

intervention (i.e. drug or surgery) is ideally used to determine its efficacy or effectiveness.

Pre-defined indicates that the harms that were expected are explicitly defined prior to the collection of these expected

events. For example, if bleeding is listed as a harmful event, the criteria by which they determine the bleeding (i.e.

body location, type, or amount of blood loss that counts as an event, etc) should be specified.

Standardized classification of harms can be derived from any of the following:

1) reference to standard terminology or classifications of harms from a recognized external organization(s)(such as

government regulatory or health agencies. Examples of standardized terminology for harms includes, WHO-ART,

MEDra, HTA report on the Measurement and Monitoring of Surgical Adverse Events)

2) previously explicitly defined classifications of harms in the literature, or

3) based on pre-specified clinical criteria, or

4) pre-specified laboratory test (may not need to have a specific cut-off level specified in all cases)

In some instances only some of the harms identified in a study will be precisely defined. In this case, there

must be some judgement.

Yes

No

Unclear

Clear Response

2. Was the mode of harms collection specified as ACTIVE?

Active ascertainment of harms indicates that participants are asked about the occurrence of specific harms in

structured questionnaires or interviews or pre-defined laboratory or diagnostic tests and usually performed at prespecified time intervals.

Passive ascertainment of harms indicates that study participants spontaneously report (on their own initiatives) or are

allowed to report harmful events not probed with active ascertainment.

Yes

No

Unclear

Clear Response

3. Was the potential occurrence of harmful events collected at pre-specified intervals; for example, the

occurrence of post-operative complications were evaluated on a daily basis within 30 days of the surgery?

Yes

No

E-27
Unclear

Clear Response

4. Did the author(s) specify the NUMBER for each TYPE of harmful event for each study group?

For example, the study reported 3 types of harmful events (nausea, vomiting, and bleeding); for each of these events

the frequency was reported for each study group.

Yes

No

Unclear

Clear Response

5. Was the TOTAL NUMBER of participants affected by harms specified for each study arm?

Yes

No

Unclear

Clear Response

6. If the study reported that there were no serious AE's reported did they define serious AEs?

Yes

No

Unclear

N/A

Clear Response

E-28
Appendix F. Quality of Included Studies

Table F1. Quality assessment of randomized controlled trials 

Table F2. Quality assessment of cohort studies 

Table F3. Quality assessment of studies reporting harms 

F-1
Table F1. Quality assessment of randomized controlled trials 

Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

Agostoni 

C, et al, 

2009139

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No No Low risk Unclear Low risk No

Almaas, et 

al., 

2015126

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

Low risk High risk No No Low risk Low risk Unclear No

Atwell K, 

et al, 

2013119

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Unclear Low risk No

Bergmann 

et al., 

2012 52

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No No Low risk Unclear Low risk No

Birch EE, 

et al, 

2010121

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk Uncle

ar

Yes Low risk Unclear Unclear No

Birch EE, 

et al, 

2005111

Low 

risk

Low 

risk

Low 

risk

Uncle

ar

Unclear Low risk High risk No Uncl

ear

Low risk Unclear Unclear No

Birch EE, 

et al, 

2007146

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No No Unclear Unclear Low risk No

Bouwstra 

H, et al, 

200563

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Unclear Low risk Low risk No No Low risk Unclear Unclear No

Bouwstra 

H, et al, 

200362

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Unclear Low risk Low risk No No Low risk Unclear Unclear No

Brew B, et 

al., 

2015165

Uncle

ar

Low 

risk

Low 

risk

Low 

risk

Low risk High risk Unclear Uncle

ar

Yes Low risk Unclear Low risk Yes

F-2
Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

Campoy 

C, et al, 

2011141

Low

risk

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

High risk Not 

applicable

No No Low risk Low risk Unclear No

Carlson 

SE, et al, 

201331

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Carlson 

SE, et al, 

1996160

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

High risk High risk No No Low risk Unclear Unclear No

Cheatham 

CL, et al, 

2011129

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Low risk High risk Not 

applicable

Yes No Low risk Low risk Low risk No

Clandinin 

MT, et al, 

2005108

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Unclear High risk High risk No No High risk Unclear Unclear No

Collins 

CT, et al, 

2015120

Low 

risk

Low 

risk

Uncle

ar

Low 

risk

Not 

applicable

Low risk Not 

applicable

No Uncl

ear

Low risk Low risk Unclear No

Collins 

CT, et al, 

2011105

Low 

risk

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Colombo 

J, et al, 

2013124

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Unclear No Uncl

ear

Unclear Unclear Unclear No

Courville

AB, et al, 

201138

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Currie 

LM, et al, 

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

High risk Not 

applicable

No No Low risk Unclear Low risk No

F-3
Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

2015115

de Jong C, 

et al, 

201265

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

Yes No Low risk Unclear Unclear Yes

de Jong C, 

et al, 

201064

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No No Low risk Unclear Unclear No

Doornbos 

B, et al, 

200990

Uncle

ar

Uncle

ar

Uncle

ar

Uncle

ar

Unclear High risk High risk No No Low risk High risk Low risk No

Drover JR, 

et al, 

2012123

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

High risk Not 

applicable

No No Unclear Unclear Unclear No

Drover JR, 

et al, 

2011122

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

Low risk High risk No No Low risk Unclear Unclear No

Dunstan 

JA, et al, 

200350

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No No Low risk Unclear Unclear No

Dunstan 

JA, et al, 

200844

Uncle

ar

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk High risk No No Low risk Unclear Unclear Yes

D'Vaz N, 

et al, 

2012142

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk High risk Low risk No Yes Unclear Low risk Low risk No

Escamilla-

Nunez 

MC, et al, 

201459

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No No Low risk Low risk Unclear No

Escolano- Uncle Uncle Low Low Not High risk Not No No Low risk Low risk Low risk No F-4
Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

Margarit

MV, et al, 

2011130

ar ar risk risk applicable applicable

Fang PC, 

et al, 

2005137

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No No Low risk Unclear Unclear No

Field CJ, 

et al, 

2008112

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No Yes Low risk Low risk Low risk No

Fledderma

nn M, et 

al, 2014113

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Unclear High risk Low risk No Yes Low risk Unclear Unclear No

Furuhjelm 

C, et al, 

2011172

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk High risk Unclear No No Low risk Low risk Low risk No

Furuhjelm 

C, et al, 

2009173

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk High risk Unclear No Yes Low risk Low risk Low risk No

Gonzalez-

Casanova 

I, et al, 

201560

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No No Low risk Unclear Low risk No

Goor SA, 

et al, 

201166

Uncle

ar

Uncle

ar

Uncle

ar

Uncle

ar

Unclear High risk Unclear No No Low risk Unclear Unclear No

Groh-

Wargo S, 

et al, 

2005106

Low 

risk

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes High risk Low risk Low risk No F-5
Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

Gustafson 

KM, et al, 

201374

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk High risk High risk No Yes Low risk Low risk Low risk No

Harper M, 

et al, 

201029

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Hauner H, 

et al, 

201237

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Helland 

IB, et al, 

200876

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Unclear High risk Unclear No No High risk Unclear Unclear Yes

Henriksen 

C, et al, 

2008107

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

High risk High risk No No Low risk Unclear Unclear No

Hoffman 

D, et al, 

2008114

Low 

risk

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

ImhoffKunsch B, 

et al, 

201158

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Unclear Low risk No

Innis SM, 

et al, 

2008145

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

Unclear Not 

applicable

No Uncl

ear

High risk Low risk Unclear Yes

Isaacs EB, 

et al, 

201199

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

High risk Not 

applicable

No No Unclear Unclear Unclear Yes

Jensen 

CL, et al, 

2010135

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No No Low risk Unclear Unclear No

F-6
Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

Jensen 

CL, et al, 

2005136

Low 

risk

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

Low risk High risk No No Low risk Unclear Low risk No

Judge MP, 

et al, 

201491

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk High risk Not 

applicable

No No Low risk Unclear Unclear No

Judge MP, 

et al, 

201240

Low 

risk

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Judge MP, 

et al, 

200739

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Knudsen 

VK, et al, 

200645

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Lagemaat 

M, et al, 

2011109

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Unclear No

Lauritzen 

L, et al, 

2005102

Uncle

ar

Uncle

ar

Low 

risk

High 

risk

Low risk High risk Low risk No No Low risk Low risk Low risk No

Lauritzen 

L, et al, 

2004127

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No Yes Low risk Low risk Low risk No

Lauritzen 

L, et al, 

2005128

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

Yes No Low risk Unclear Low risk No

Linnamaa 

P, et al, 

201079

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk High risk Low risk No Yes Low risk Low risk Low risk No

Llorente Low Uncle Low Low Not High risk High risk No No Low risk Low risk Low risk No

F-7
Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

AM, et al, 

200398

risk ar risk risk applicable

Lucia 

Bergmann 

R, et al, 

200741

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk High risk Low risk Yes Yes Low risk Low risk Unclear No

Makrides 

M, et al, 

2009116

Low 

risk

Uncle

ar

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No Yes Low risk Unclear Low risk No

Makrides 

M, et al, 

201035

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Makrides 

M, et al, 

201457

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Unclear Low risk No

Malcolm 

CA, et al, 

2003100

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Low risk High risk Low risk No Yes Low risk Low risk Low risk No

Manley 

BJ, et al, 

2011118

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Unclear Low risk No

Marks 

GB, et al, 

2006168

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No No Low risk Unclear Unclear No

Meldrum 

SJ, et al, 

201556

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Low risk High risk High risk Uncle

ar

Yes Low risk Unclear Unclear No

Meldrum 

SJ, et al, 

2012140

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

High risk Not 

applicable

No No High risk Low risk High risk No

Mihrshahi Low Low Low Low Low risk Low risk Low risk No No Low risk Unclear Unclear No F-8
Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

S, et al, 

2003166

risk risk risk risk

Miles EA, 

et al, 

201178

Low 

risk

High 

risk

High 

risk

Low 

risk

Unclear Low risk Unclear No No Low risk Low risk Low risk No

Min Y, et 

al, 201443

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Mozurkew

ich EL, et 

al, 201342

Low 

risk

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Mulder 

KA, et al, 

201475

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

High risk Low risk No No High risk Low risk Unclear No

Noakes 

PS, et al, 

201288

Low 

risk

Uncle

ar

High 

risk

Low 

risk

Low risk High risk Not 

applicable

No No Low risk Unclear Unclear No

Olsen SF, 

et al, 

2008187

Low 

risk

Low 

risk

High 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Palmer 

DJ, et al, 

201254

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Unclear Low risk No

Palmer 

DJ, et al, 

201356

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Unclear Low risk Low risk No Yes Low risk Low risk High risk No

Peat JK, et 

al, 2004167

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Unclear Unclear No

Pietrantoni 

E, et al, 

201430

Uncle

ar

Uncle

ar

Uncle

ar

Uncle

ar

Not 

applicable

Low risk Not 

applicable

No Yes Low risk Low risk High risk No

F-9
Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

Ramakrish

nan U, et 

al, 201032

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Low risk Low risk No

Ramakrish

nan U, et 

al, 201561

Low 

risk

Low 

risk

Low 

risk

Low 

risk

High risk Unclear Not 

applicable

Yes Yes Low risk Unclear Low risk No

Sala-Vila 

A, et al, 

2004110

High 

risk

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Unclear Low risk No

Smithers 

LG, et al, 

2010117

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No Uncl

ear

Low risk Unclear Unclear No

Smithers 

LG, et al, 

201153

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

Low risk Not 

applicable

No Yes Low risk Unclear Unclear No

Smithers 

LG, et al, 

2008104

Low 

risk

Low 

risk

Low 

risk

Uncle

ar

Low risk Low risk Low risk No Yes Low risk Unclear Unclear No

Stein AD, 

et al, 

201134

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Unclear Low risk No

Stein AD, 

et al, 

201233

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk High risk High risk No Yes Low risk Low risk Low risk No

Toelle 

BG, et al, 

2010169

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Low risk Low risk Not 

applicable

No No Low risk Unclear Unclear No

Tofail F, 

et al, 

200677

Uncle

ar

Uncle

ar

Low 

risk

Low 

risk

Unclear High risk Not 

applicable

No Uncl

ear

High risk Unclear Low risk No

F-10
Author, 

year

Allocation Sequence Generated AdequatelyAllocation Treatment Adequately ConcealedParticipants Adequately BlindedOutcome Assessors BlindedOutcome Assessor Blinding is Different for Different OutcomesIncomplete outcome data (Attrition bias) due to amount, nature or handling of incomplete outcome dataAttrition risk of bias is different for different outcomes or different time pointsSelective Outcome ReportingIntention-to-treatGroup Similarity at Baseline (general)Group Similarity at Baseline (Omega-3)Incomplete Compliance with Interventions Across GroupsAdditional bias

Unay B, et 

al, 2004138

Low 

risk

Low 

risk

Low 

risk

Uncle

ar

Low risk Low risk Low risk No No Low risk Unclear Unclear No

van Goor 

SA, et al, 

201036

Uncle

ar

Uncle

ar

Low 

risk

Uncle

ar

Not 

applicable

High risk Not 

applicable

Yes No Low risk Unclear Unclear No

Werkman 

SH, et al, 

1996154

Low 

risk

Low 

risk

Uncle

ar

Low 

risk

Low risk Low risk Not 

applicable

Yes No Low risk Unclear Unclear No

Westerber

g AneC, et 

al, 2011125

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

High risk Not 

applicable

Yes Uncl

ear

Low risk Low risk Unclear No

Willatts P, 

et al, 

2013170

Low 

risk

Low 

risk

Low 

risk

Low 

risk

Not 

applicable

High risk Not 

applicable

Uncle

ar

No Low risk Unclear Unclear Yes

Zhou SJ, 

et al, 

201255

Low 

risk

Uncle

ar

Low 

risk

Low 

risk

Low risk Low risk Low risk No Yes Low risk Unclear Low risk No

F-11
Table F2. Quality assessment of cohort studies 

Author, year Representativeness of 

the exposed cohort

Selection of 

the non 

exposed 

cohort

Ascertainment 

of exposure

Outcome 

of interest 

not 

present at 

start of 

study

Comparability 

of cohorts

Assessment of 

outcome

Followup long 

enough 

to occur

Adequacy 

of follow up 

of cohorts

Badart-Smook 

A, et al, 199747

Truly representative Not applicable Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Complete 

follow-up

Bakker EC, et 

al, 2003163

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

Independent 

blind 

assessment 

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Bakker EC, et 

al, 2009134

Somewhat 

representative

Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor

Independent 

blind 

assessment 

Yes Follow up 

rate < 80% 

(select an 

adequate %) 

and no 

description 

of those lost

Bernard JY, et 

al, 201389

Somewhat 

representative

Not applicable Written self 

report

Yes Controls for 

most important 

factor and other 

factors

Independent 

blind 

assessment 

Yes Follow up 

rate < 80% 

(select an 

adequate %) 

and no 

description 

of those lost

Bouwstra H, et 

al, 2006133

Somewhat 

representative

Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor

Independent 

blind 

assessment 

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Brantsaeter AL, 

et al, 201281

Somewhat 

representative

Not applicable Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Self report Yes No 

statement

Chong MF, et 

al, 201595

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

F-12
Author, year Representativeness of 

the exposed cohort

Selection of 

the non 

exposed 

cohort

Ascertainment 

of exposure

Outcome 

of interest 

not 

present at 

start of 

study

Comparability 

of cohorts

Assessment of 

outcome

Followup long 

enough 

to occur

Adequacy 

of follow up 

of cohorts

Clausen T, et al, 

200168

Truly representative Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Independent 

blind 

assessment 

Yes Complete 

follow-up

Dirix CE, et al, 

200984

Truly representative Not applicable Secure record Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Drouillet P, et 

al, 200980

Truly representative Not applicable Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Guxens M, et 

al, 2011144

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

Independent 

blind 

assessment 

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Jordi Julvez, et 

al, 2014143

Truly representative Not applicable Secure record Yes Controls for 

most important 

factor and other 

factors

Independent 

blind 

assessment 

Yes Follow up 

rate < 80% 

(select an 

adequate %) 

and no 

description 

of those lost

Keim SA, et al, 

2012162

Somewhat 

representative

Not applicable Secure record Yes Controls for 

most important 

factor and other 

factors

Independent 

blind 

assessment 

Yes Follow up 

rate < 80% 

(select an 

adequate %) 

and no 

description 

of those lost

Klebanoff MA, 

et al, 201149

Truly representative Drawn from 

same 

community

Secure record, 

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Complete 

follow-up

Leung BM, et Truly representative Drawn from Structured Yes Controls for Self report No Subjects lost 

F-13
Author, year Representativeness of 

the exposed cohort

Selection of 

the non 

exposed 

cohort

Ascertainment 

of exposure

Outcome 

of interest 

not 

present at 

start of 

study

Comparability 

of cohorts

Assessment of 

outcome

Followup long 

enough 

to occur

Adequacy 

of follow up 

of cohorts

al, 201394 same 

community

interview most important 

factor and other 

factors

to follow up 

unlikely to 

introduce 

bias

Lim WY, et al, 

201571

Somewhat 

representative

Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

Independent 

blind 

assessment 

Yes Follow up 

rate < 80% 

(select an 

adequate %) 

and no 

description 

of those lost

Lumia M, et al, 

2011188

Truly representative Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor

Record linkage Yes Follow up 

rate < 80% 

(select an 

adequate %) 

and no 

description 

of those lost

yall K, et al, 

2013171

Selected group Not applicable Written self 

report

Yes Controls for 

most important 

factor and other 

factors

Self report Yes Follow up 

rate < 80% 

(select an 

adequate %) 

and no 

description 

of those lost

Miyake Y, et al, 

2009182

Truly representative Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Self report No Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Miyake Y, et 

al, 2013183

Somewhat 

representative

Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Self report No Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Mohanty AF, 

et al, 201585

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

Record linkage Yes Subjects lost 

to follow up 

unlikely to 

F-14
Author, year Representativeness of 

the exposed cohort

Selection of 

the non 

exposed 

cohort

Ascertainment 

of exposure

Outcome 

of interest 

not 

present at 

start of 

study

Comparability 

of cohorts

Assessment of 

outcome

Followup long 

enough 

to occur

Adequacy 

of follow up 

of cohorts

factors introduce 

bias

MoltoPuigmarti C, et 

al, 201448

Truly representative Not applicable Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Morales E, et 

al, 2012184

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

Self report No Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Much D, et al, 

2013101

No description of the 

derivation of cohort

Not applicable No description Yes Controls for 

most important 

factor

Independent 

blind 

assessment 

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Much D, et al, 

201383

No description of the 

derivation of cohort

Not applicable Secure record Yes Controls for 

most important 

factor and other 

factors

Independent 

blind 

assessment 

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Muthayya S, et 

al, 200972

Truly representative Not applicable Secure record Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Newson RB, et 

al, 2004176

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor

Independent 

blind 

assessment and 

self report

Yes No 

statement

Notenboom 

ML, et al, 

2011179

Somewhat 

representative

Not applicable Secure record Yes Controls for 

most important 

factor and other 

factors

Record linkage 

and self report

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Nwaru BI, et al, 

2012180

Truly representative Drawn from 

same 

Structured 

interview

Yes Controls for 

most important 

Self report Yes No 

statement

F-15
Author, year Representativeness of 

the exposed cohort

Selection of 

the non 

exposed 

cohort

Ascertainment 

of exposure

Outcome 

of interest 

not 

present at 

start of 

study

Comparability 

of cohorts

Assessment of 

outcome

Followup long 

enough 

to occur

Adequacy 

of follow up 

of cohorts

community factor and other 

factors

Oken E, et al, 

200446

Truly representative Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes No 

statement

Oken E, et al, 

200769

Truly representative Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Olafsdottir AS, 

et al, 200582

Truly representative Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage 

and self report

Yes Complete 

follow-up

Olafsdottir AS, 

et al, 200670

Somewhat 

representative

Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Parker G, 

Hegarty B, et 

al, 201597

Truly representative Not applicable Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Pike KC, et al, 

2012186

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important

factor

Record linkage 

and self report

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Saito K, et al, 

2010181

Somewhat 

representative

Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Self report Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Sallis H, et al, 

201496

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

Record linkage Yes No 

statement

F-16
Author, year Representativeness of 

the exposed cohort

Selection of 

the non 

exposed 

cohort

Ascertainment 

of exposure

Outcome 

of interest 

not 

present at 

start of 

study

Comparability 

of cohorts

Assessment of 

outcome

Followup long 

enough 

to occur

Adequacy 

of follow up 

of cohorts

factors

Scholtens S, et 

al, 2009103

Selected group Not applicable Secure record Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Follow up 

rate < 80% 

(select an 

adequate %) 

and no 

description 

of those lost

Smits LJ, et al, 

201373

Truly representative Not applicable Secure record Yes Controls for 

most important 

factor and other 

factors

No description Yes No 

statement

Standl M, et al, 

2014177

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

Self report Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Steer CD, et al, 

2013164

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor

Record linkage Yes No 

statement

Strom M, et al, 

200992

Truly representative Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes No 

statement

Sun Y, et al, 

2010131

Truly representative Not applicable Written self 

report

Yes Controls for 

most important 

factor and other 

factors

Record linkage Yes Complete 

follow-up

Thijs C, et al, 

2011178

Somewhat 

representative

Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

Record linkage 

and self report

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Valent F, et al, 

2013132

Somewhat 

representative

Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

No description Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

F-17
Author, year Representativeness of 

the exposed cohort

Selection of 

the non 

exposed 

cohort

Ascertainment 

of exposure

Outcome 

of interest 

not 

present at 

start of 

study

Comparability 

of cohorts

Assessment of 

outcome

Followup long 

enough 

to occur

Adequacy 

of follow up 

of cohorts

Wijga AH, et 

al, 2006175

Truly representative Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

Independent 

blind 

assessment and 

self report

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Yoshihiro 

Miyake, et al, 

200693

Truly representative Drawn from 

same 

community

Structured 

interview

Yes Controls for 

most important 

factor and other 

factors

Self report Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

Yu YM, et al, 

2015185

Somewhat 

representative

Drawn from 

same 

community

Secure record Yes Controls for 

most important 

factor and other 

factors

Record linkage 

and self report

Yes Subjects lost 

to follow up 

unlikely to 

introduce 

bias

F-18
Table F3. Quality assessment of studies reporting harms 

Author, year Were the 

harms 

predefined 

using 

standardized 

or precise 

definitions?

Was the mode of 

harms collected 

specified as 

active?

Was the potential 

occurrence of 

harmful events 

collected at prespecified 

intervals?

Did the author(s) 

specify the NUMBER 

for each TYPE of 

harmful event for 

each study group?

Was the TOTAL 

NUMBER of 

participants 

affected by harms 

specified for each 

study arm?

If the study reported that 

there were no serious AE's 

reported did they define 

serious AEs?

Agostoni C, et al, 2009139 No No Yes Yes Yes No

Birch EE, et al, 2005111 No Unclear Unclear Yes Yes Not applicable

Birch EE, et al, 2010121 No Unclear Yes No Yes Yes

Carlson SE, et al, 201331 Yes Yes Unclear Yes Yes Not applicable

Clandinin MT, et al, 

2005108 Unclear No Unclear Yes Yes Not applicable

Dunstan JA, et al, 200350 No No No Yes Yes Not applicable

Escolano-Margarit MV, 

et al, 2011130

Unclear Unclear Unclear No Yes Not applicable

Fang PC, et al, 2005137 No No Yes No No No

Field CJ, et al, 2008112 No No No No No Not applicable

Fleddermann M, et al, 

2014113 Yes Yes Unclear Yes Yes Not applicable

Furuhjelm C, et al,

2009173 No No No Yes Yes No

Furuhjelm C, et al, 

2011172 No No No Yes No No

Harper M, et al, 201029 Yes Yes Yes Yes No Unclear

Henriksen C, et al, 

2008107 No Unclear Yes No No Not applicable

Hoffman D, et al, 2008114 Yes Unclear Yes Yes No Not applicable

Imhoff-Kunsch B, et al, 

201158 Yes Yes Yes Yes Yes Not applicable

Llorente AM, et al, 

200398 No Unclear Unclear No No No

Makrides M, et al, 

2009116 Yes Yes Unclear Yes Yes Not applicable

Makrides M, et al, 

201035 Yes Yes Yes Yes Yes Not applicable

Ramakrishnan U, et al, 

201032 Yes Yes Yes Yes Yes No

F-19
Appendix G. Strength of Evidence

Table G1. Strength of evidence for KQ1: maternal outcomes (gestational length, preterm birth, SGA/IUGR, low 

birth weight, birth weight, antenatal and/or postnatal depression)

Table G2. Strength of evidence for KQ1: maternal outcomes (gestational hypertension/preeclampsia)

Table G3. Strength of evidence for KQ2: infant and child outcomes (growth patterns)

Table G4. Strength of evidence for KQ2: infant and child outcomes (neurological development)

Table G5. Strength of evidence for KQ2: infant and child outcomes (visual function)

Table G6. Strength of evidence for KQ2: infant and child outcomes (cognitive)

Table G7. Strength of evidence for KQ2: infant and child outcomes (autism spectrum disorders)

Table G8. Strength of evidence for KQ2: infant and child outcomes (attention deficit hyperactivity disorder)

Table G9. Strength of evidence for KQ2: infant and child outcomes (atopic dermatitis, allergies, and respiratory 

illness)

Table G10. Strength of evidence for KQ3: infant and child outcomes (adverse events/serious adverse events)

G-1
Table G1. Strength of evidence for KQ1: maternal outcomes (gestational length, preterm birth, SGA/IUGR, low birth weight, birth weight, 

antenatal and/or postnatal depression)

Outcome

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Gestational 

length 

n-3 FA 

supplementation

Healthy 

pregnant 

women

Moderate RCT: 14

(original 

report); 

14

Obs intake: 

3

Obs 

biomarker

s: 1

Low RCT: 

Consistent

Obs intake: 

Consistent

Obs 

biomarkers: 

NA

All: Consistent

Precise Large 

heterogeneity 

in the metaanalysis

Original report: 

Mixed findings

Meta-analysis of 12

RCTs in update: 

WMD 0.33 (95% 

CI 0.04, 0.62) 

weeks

Gestational 

length 

DHA or DHArich fish oilHealthy 

pregnant 

women

Moderate RCT: 3 

(original 

report); 

11

Obs intake: 

1

Obs 

biomarker

s: 0

Low RCT: 

Inconsistent 

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: 

Inconsistent

Precise Large 

heterogeneity 

in the metaanalysis

Original report: 

Mixed findings

Meta-analysis of 11

RCTs in update: 

WMD 0.34 (95% 

CI 0.02, 0.67) 

weeks

Gestational 

length 

Fish oil or 

EPA+DHA

Healthy 

pregnant 

women

Low RCT: 11 

(original 

report); 2

Obs intake: 

2

Obs 

biomarker

s: 1

Low RCT: 

Consistent

Obs intake: 

Consistent

Obs 

biomarkers: 

NA

All: Consistent

Imprecise A few studies 

excluded 

preterm infants

Original report: No 

effects

No effects

Gestational 

length 

DHA+AA Healthy 

pregnant 

women

Insufficient RCT: 1

Obs intake: 

0

Obs 

biomarker

s: 0

High RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Imprecise Sparse No effects

G-2
Outcome

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Gestational 

length 

EPA+DHA vs. 

ALA

Healthy 

pregnant 

women

Insufficient RCT: 1

Obs intake: 

0

Obs 

biomarker

s: 0

Low RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Precise Sparse No differences 

between 5 

differences 

doses of fish oil 

(EPA+DHA 0.1, 

0.3, 0.7, 1.4 and 

2.8 g/d) and ALA 

control

Gestational 

length 

n-6/n-3 No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

Gestational 

length 

Other – total n-3 

FA 

Healthy 

pregnant 

women

Insufficient RCT: 0

Obs intake: 

1

Obs 

biomarker

s: 1 

(original 

report); 0

Low RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Precise Sparse No associations

Preterm 

birth

DHA or DHArich fish oilHealthy 

pregnant 

women

Low RCT: 2 

(original 

report); 5

Obs intake: 

0

Obs 

biomarker

s: 0

Low RCT: 

Consistent

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Imprecise No Obs Meta-analysis of 7

RCTs: OR 0.87

(95% CI 0.66, 

1.15)

G-3
Outcome

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Preterm 

birth

Fish oil or

EPA+DHA

At risk

pregnant 

women

Low RCT: 8 

(original 

report); 1

Obs intake: 

1

Obs 

biomarker

s: 1

Moderate RCT: 

Consistent

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: Consistent

Imprecise NA Meta-analysis of 9 

RCTs: 0.86 (95% 

CI 0.65, 1.15)

Highest and lowest 

quartiles of 

maternal 

DHA+EPA 

intake: OR 1.1 

(95% CI 0.7, 1.9)

Erythrocyte 

DHA+EPA top 3 

quartiles vs. 

lowest quartile: 

OR 1.41 (95% CI 

0.97 – 2.05)

Preterm 

birth

DHA+AA No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

Preterm 

birth

n-6/n-3 No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

SGA/

IUGR

DHA or DHArich fish oilAt risk 

pregnant 

women 

Insufficient RCT: 2

Obs intake: 

Obs 

biomarker

s: 0

Low RCT: 

Consistent

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Imprecise Sparse No effects

G-4
Outcome

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

SGA/

IUGR

Fish oil or 

EPA+DHA

At risk 

pregnant 

women

Low RCT: 3 

(original 

report); 1

Obs intake: 

1

Obs 

biomarker

s: 0

Low RCT: 

Consistent

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: Consistent

Imprecise NA Meta-analysis of 4 

RCTs: OR 1.00 

(95% CI 0.70, 

1.43)

No association 

between 

quartiles of 

DHA+EPA 

intake and risk of 

having an SGA 

birth outcome

SGA/

IUGR

DHA+AA No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

SGA/

IUGR

n-6/n-3 No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

SGA/

IUGR

Other – EPA or 

DHA

Healthy 

pregnant 

women

Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 1

Low RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Precise Sparse Lowest quintile of 

plasma EPA 

concentration 

(<0.33 mg/L) vs. 

middle quintile 

(0.46 -0.58 

mg/L): AOR 2.09 

(95% CI 1.32, 

3.30)

No associations for 

concentrations 

of plasma DHA

G-5
Outcome

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Low birth 

weight

DHA or DHArich fish oilHealthy 

pregnant 

women

Low RCT: 4

Obs intake: 

0

Obs 

biomarker

s: 0

Low RCT: 

Inconsistent

Obs intake: 

NA 

Obs 

biomarkers: 

NA

All: NA

Imprecise Moderate 

heterogeneity 

in the metaanalysis;

Meta-analysis of 4

RCTs: OR 0.72

(95% CI 0.43, 

1.11)

Low birth 

weight

Fish oil or 

EPA+DHA

At risk 

pregnant 

women 

Insufficient RCT: 1

Obs intake: 

0

Obs 

biomarker

s: 0

Low RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Precise Sparse No effects

Low birth 

weight

DHA+AA No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

Low birth 

weight

n-6/n-3 No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

Low birth 

weight

Other - EPA Healthy 

pregnant 

women

Insufficient RCT: 0

Obs intake: 

1

Obs 

biomarker

s: 0

Low RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Precise No RCT 1st tertile of EPA 

intake vs. the 

highest tertile: 

AOR 2.75 (95% 

CI 1.26, 6.02); 

and 2nd tertile of 

EPA vs. the 

highest tertile: 

AOR 2.54, (95% 

CI 1.17. 5.50)

G-6
Outcome

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Birth 

weight

n-3 FA 

supplementation

Healthy 

pregnant 

women

Moderate RCT: 14

(original 

report); 

16

Obs intake: 

6

Obs 

biomarker

s: 4

Low RCT: 

Consistent

Obs intake: 

Consistent

Obs 

biomarkers: 

NA

All: Consistent

Precise Moderate

heterogeneity 

in the metaanalysis

Original report: 

Mixed findings

Meta-analysis of 16

RCTs in update: 

WMD 74.8 (95% 

CI 12.4, 137.17) 

grams

Birth 

weight

DHA or DHArich fish oilHealthy 

Pregnant 

women

Moderate RCT: 2 

(original 

report); 

11

Obs intake: 

0

Obs 

biomarker

s: 3

Low RCT: 

Consistent

Obs intake: 

Obs 

biomarkers: 

Consistent

All: Consistent

Precise Large 

heterogeneity 

in the metaanalysis

Original report: 

mixed findings

Meta-analysis of 12

RCTs: WMD 

90.12 (95% CI 

2.62, 177.62) 

grams

Higher maternal 

blood DHA 

concentrations 

were associated 

with higher birth 

weight.

Birth 

weight

Fish oil or 

EPA+DHA

Healthy 

Pregnant 

women

Low RCT: 9 

(original 

report); 5

Obs intake: 

2

Obs 

biomarker

s: 0

Low RCT: 

Consistent

Obs intake: 

Inconsistent

Obs 

biomarkers: 

NA

All: 

Inconsistent

Precise NA Original report: 

mostly no effects

Meta-analysis of 5 

RCTs: WMD 

37.89 (95% CI -

19.53, 95.31) 

grams

Birth 

weight

DHA+AA No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

G-7
Outcome

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Birth 

weight

n-6/n-3 No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

Birth 

weight

Other - ALA Healthy 

Pregnant 

women

Insufficient RCT: 1

Obs intake: 

Obs 

biomarker

s: 0

Low RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Imprecise Sparse Black current seed 

oil (ALA 0.42 g/d; 

SDA 0.09 g/d) 

vs. placebo: No 

effects

Birth 

weight

Other - total n-3 

FA

Healthy 

Pregnant 

women

Insufficient RCT: 0

Obs intake: 

2

Obs 

biomarker

s: 0

Low RCT: NA

Obs intake: 

Consistent

Obs 

biomarkers: 

NA

All: NA

Precise Sparse; No 

RCT

No associations

Antenatal 

and/or 

Postnatal 

Depression

DHA or DHArich fish oil 

(prenatal)

Pregnant 

woman

Low RCT: 4

Obs intake: 

0

Obs 

biomarker

s: 3

Moderate RCTs: 

Consistent

Obs intake: 

NA

Obs 

biomarkers: 

Consistent

All: Consistent

Imprecise Outcome 

definitions 

were 

heterogeneous

Mostly no 

significant 

effects/associati

ons on both 

antenatal and 

postnatal 

depression 

outcomes

Antenatal 

and/or 

Postnatal 

Depression

Fish oil or 

EPA+DHA 

(prenatal)

Pregnant 

woman

Insufficient RCT: 1

Obs intake: 

1

Obs 

biomarker

s: 0

Low RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: Consistent

Imprecise Outcome 

definitions 

were 

heterogeneous

No significant 

effects/associati

ons on both 

antenatal and 

postnatal 

depression 

outcomes

Antenatal 

and/or 

Postnatal 

Depression

DHA+AA 

(prenatal)

Pregnant 

woman

Insufficient RCT: 1

Obs intake: 

0

Obs 

biomarker

s: 0

High RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Imprecise Sparse No differences in 

median EPDS 

scores at either 

week 36 of 

pregnancy or 6 

months 

postpartum

G-8
Outcome

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Antenatal 

and/or 

Postnatal 

Depression

n-6/n-3 

(prenatal)

No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

Antenatal 

and/or 

Postnatal 

Depression

Other – total n-3 

FA (prenatal)

Pregnant 

woman

Insufficient RCT: 0

Obs intake: 

2

Obs 

biomarker

s: 0 

Low RCT: NA

Obs intake: 

Consistent

Obs 

biomarkers: 

NA

All: NA

Precise No RCTs; 

Outcome 

definitions 

were 

heterogeneous

No associations 

and no 

significant doseresponse 

relationship

Postnatal 

Depression

DHA or DHArich fish oil 

(postnatal)

Lactating 

women

Insufficient RCT: 1

Obs intake: 

0

Obs 

biomarker

s: 0

Moderate RCT: NA

Obs intake: 

NA

Obs 

biomarkers: 

NA

All: NA

Imprecise Sparse No significant 

effects any of 

the time points 

(3 weeks, 2 

months, 4 

months, or 18 

months 

postpartum)

Postnatal 

Depression

Fish oil or 

EPA+DHA 

(postnatal)

No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

Postnatal 

Depression

DHA+AA 

(postnatal)

No studies Insufficient RCT: 

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

Postnatal 

Depression

n-6/n-3 

(postnatal)

No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

G-9
Outcome

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Postnatal 

Depression

Other – total n-3 

FA (postnatal)

No studies Insufficient RCT: 0

Obs intake: 

0

Obs 

biomarker

s: 0

NA NA NA No data NA

G-10
Table G2. Strength of evidence for KQ1: maternal outcomes (gestational hypertension/preeclampsia)

Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision

Other 

Issues Finding

DHA Pregnant 

women not 

at risk for 

poor 

pregnancy 

outcomes

Low RCT: 3

Obs intake: 0

Obs 

biomarkers:

0

Cochrane 

11,12,13/13

RCT: Inconsistent 

Obs intake: NA

Obs biomarkers: 

NA 

All: NA

RCT: Precise

Obs intake: NA

Obs biomarker: 

NA

All 

interventions 

had very low 

levels EPA

RCT: OR 

0.94[0.66, 1.34], 

I

2

=0% (n=2,818)

Obs intake: NA

Obs biomarkers: 

NA

DHA+EPA Healthy 

pregnant 

women

Insufficient RCT: 0

Obs intake: 1

Obs 

biomarkers:

NewcastleOttawa Low 

RoB

RCT: NA 

Obs intake: NA

Obs biomarkers: 

NA 

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

Only 1 

cohort study

RCT: NA

Obs intake: 

nonsignificant 

decrease in risk

Obs biomarkers: 

NA

Fishoil Pregnant 

women at 

risk for 

poor 

pregnancy 

outcomes

Moderate RCT: 3

Obs intake: 1 

Obs 

biomarkers:

Cochrane: 

13/13 

NewcastleOttawa: 

Low RoB

RCT: NA 

Obs intake: NA

Obs biomarkers: 

NA 

All: NA

RCT: Precise

Obs intake: NA

Obs biomarker: 

NA

At-risk 

populations

RCT: OR 1.04 

[0.76 , 1.42], I2=

0% 

Obs intake: Ushaped 

association with 

risk

Obs biomarkers: 

NA

DHA+AA No studies Insufficient RCT: 0

Obs intake: 

NA 

Obs 

biomarkers: 

NA

NA RCT: NA 

Obs intake: NA

Obs biomarkers: 

NA 

All: NA

RCT: NA

Obs intake: NA

Obs biomarker:

NA

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

n-3 FA Healthy 

pregnant 

women

Insufficient RCT: 0

Obs intake:2 

Obs 

biomarkers: 

1

NewcastleOttawa: 

Low RoB

RCT: NA 

Obs intake: 

Consistent

Obs biomarkers: 

NA (1 study)

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

precise

NA RCT: NA

Obs intake: No 

association

Obs biomarkers: 

inverse 

association

G-11
Table G3. Strength of evidence for KQ2: infant and child outcomes (growth patterns)

Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA+EPA Prenatal 

maternal 

interventi

on

Moderate RCT: 6

Obs intake: 0

Obs 

biomarkers: 

0

Cochrane:

3-9/13

RCT: Mostly 

consistent

Obs intake: NA

Obs biomarkers: 

NA

All: Mostly 

consistent

RCT: Precise

Obs intake: NA

Obs biomarker: 

NA

NA RCT: No effect, 

pooled results 

for weight at 

18 months 

0.22 [-0.62, 

0.19], length 

0.01 [-0.52, 

0.54], head 

circumf. -0.01 

[-0.28,0.27] 

DHA+AA Prenatal 

+ 

postnatal 

maternal 

interventi

on

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers: 

0 

Cochrane: 

1/13 (very 

high ROB)

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: No effect

DHA+EPA Prenatal 

+ 

postnatal 

maternal 

interventi

on

Low RCT: 4

Obs intake: 0

Obs 

biomarkers: 

0

Cochrane: 2-

10/13

RCT: Consistent

Obs intake: NA

Obs biomarkers: 

NA

All: Consistent

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

NA RCT: No effect

n-3 FAs Prenatal 

+ 

postnatal 

maternal 

interventi

on

Insufficient RCT: 0

Obs intake: 2

Obs 

biomarkers: 

0 

Observationa

l only; fair 

quality

RCT: NA

Obs intake: 

Inconsistent

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No RCTs Obs intake: 1 

study found no 

effect, 1 found 

neg. assoc. 

with n-3s and 

length at 1y

DHA+EPA Postnatal 

maternal 

interventi

on

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers: 

0

Cochrane: 

6/13

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: Greater 

BMI and head 

circumf. At 2.5 

years in fish oil 

group 

n-3 FAs Postnatal 

maternal 

interventi

on

Insufficient RCT: 0

Obs intake: 1

Obs 

biomarkers: 

0

Observationa

l only; fair 

quality

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No RCTs Obs intake: No 

effect

G-12
Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA+EPA Prenatal 

maternal 

+ 

preterm 

infant 

interventi

on

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers: 

0

Cochrane

7-9/13

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: Pos. assoc. 

with n-3s and 

length at 18 

mo.

DHA+AA Preterm 

infants

Low RCT: 3

Obs intake: 0

Obs 

biomarkers: 

0

Cochrane: 4-

9/13

RCT: Inconsistent

Obs intake: NA

Obs biomarkers: 

NA

All: Inconsistent

RCT: Imprecise

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: No effect, 

pooled results 

for weight at 4 

months -0.01 

[-0.48, 0.47, 

length -0.03 [-

0.91, 0.85]; 1 

study found 

lower fat mass 

and greater 

lean mass at 

12 mo

DHA+AA+E

PA

Preterm 

infants

Insufficient RCT: 2

Obs intake: 0

Obs 

biomarkers: 

0

Cochrane: 4-

9/13

RCT: Consistent

Obs intake: NA

Obs biomarkers: 

NA

All: Consistent

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: No effect 

on weight, 

length, head 

circumf; 1 

study found 

lower fat mass 

and greater 

lean mass at 

12 mo 

G-13
Intervention

/exposure Population SoE Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA+AA Term 

infants

Low RCT: 6

Obs intake: 0

Obs 

biomarkers: 

0 

Cochrane: 5-

9/13

RCT: Mostly 

consistent

Obs intake: NA

Obs biomarkers: 

NA

All: Mostly 

consistent 

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

NA RCT: No 

differences in 

overall weight, 

length, or 

head 

circumf.One 

study had 

higher rates of 

length gain. 

One had 

overall higher 

weight and 

stature for age 

percentiles 

from 2-6 

years, but no 

differences in 

BMI or BMIfor-age. 

Infant n-3 

FA 

biomarkers

Term 

and 

preterm 

infants

Low RCT: 0

Obs intake: 0

Obs 

biomarkers: 

3

Observationa

l only; good 

quality

RCT: NA

Obs intake: NA

Obs biomarkers: 

Inconsistent

All: Inconsistent

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

NA Obs biomarkers: 

Two studies 

found pos. 

assoc. with 

weight and 

length gain; 

one study 

found pos. 

assoc. with 

BMI at 7 yrs. 

G-14
Table G4. Strength of evidence for KQ2: infant and child outcomes (neurological development)

Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision

Other 

Issues Finding

DHA Preterm 

intervention

Low RCT: 4

Obs intake: 

Obs 

biomarkers:

4 

Cochrane

9-13/13

NOS: fairvery good

RCT: Slightly 

inconsistent

Obs intake: NA 

Obs biomarkers: 

Inconsistent

All: Consistently 

inconsistent

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA

Outcome 

measures 

vary. 1 RCT 

included 

trace EPA

RCT: No differences 

for most outcome 

measures

Obs intake: NA 

Obs biomarkers: 

Possible 

associations with 

some outcomes

DHA+EPA Preterm 

intervention

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers: 

0 

NA RCT: NA

Obs intake: NA 

Obs biomarkers: NA

All: NA 

RCT: NA

Obs intake:NA

Obs biomarker:NA 

No data RCT: NA

Obs intake: 

Obs biomarkers: 

Fish oil Preterm 

intervention

Insufficient RCT: 4

Obs intake:0 

Obs 

biomarkers: 

1

Cochrane 

6-13/13

NOS: fair

RCT: Consistent

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake:NA

Obs biomarker:NA 

Sparse RCT: No differences 

Obs intake: NA

Obs biomarkers: NA

DHA+AA Preterm 

intervention

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers:

0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA 

RCT: NA

Obs intake: 

Obs biomarker: 

No data RCT: NA

Obs intake: 

Obs biomarkers: 

n-6/n-3 Preterm 

intervention

Insufficient RCT: 0

Obs intake: 1

Obs 

biomarkers: 

1

NOS fairgoodRCT: NA

Obs intake: NA 

Obs biomarkers: NA

All: Consistent

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA

No RCT RCT: NA

Obs intake: No 

association 

Obs biomarkers: No 

association

n-3 FA Preterm 

intervention

Insufficient RCT: 0

Obs intake:2 

Obs 

biomarkers: 

5

NOS fairvery goodRCT: NA

Obs intake: 

Inconsistent 

Obs biomarkers: 

All:NA

RCT: NA

Obs intake: 

Obs biomarker: 

No RCT RCT: NA

Obs intake: 1 of 5

showed 

association for one 

outcome 

Obs biomarkers: NA

DHA Pre and 

postnatal 

intervention

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers: 

0

Cochrane: 

4/11

12/13

RCT: NA

Obs intake: NA 

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarkers: 

NA

All: NA

Sparse (1 

RCT 

reported in 2 

publications)

RCT: Increase in 

mildly abnormal 

movements cf. 

placebo

Obs intake: NA 

Obs biomarkers: NA

All: NA

G-15
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision

Other 

Issues Finding

DHA+EPA Pre and 

postnatal 

intervention

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers: 

0

NA RCT: NA

Obs intake: NA 

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarkers: 

NA

All: NA

No data RCT: NA

Obs intake: NA 

Obs biomarkers: NA

All: NA

Fish oil Pre and 

postnatal 

intervention

RCT: 0

Obs intake: 0

Obs 

biomarkers: 

0

NA RCT: NA

Obs intake: NA 

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarkers: 

NA

All: NA

No data RCT: NA

Obs intake: NA 

Obs biomarkers: NA

All: NA

DHA+AA Pre and 

postnatal 

intervention

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers: 

0

Cochrane:

4/11

12/13

RCT: NA

Obs intake: NA 

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarkers: 

NA

All: NA

Sparse RCT: Decrease in 

mildly abnormal 

movements cf. 

DHA alone and 

placebo

Obs intake: NA 

Obs biomarkers: NA

All: NA

n-6/n-3 Pre and 

postnatal 

intervention

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers: 

1

Cochrane 

4/11

RCT: NA

Obs intake: NA 

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarkers: 

NA

All: NA

No RCT RCT: NA

Obs intake:NA 

Obs biomarkers: No 

association 

DHA Breast

Feeding

Mothers 

Insufficient RCT: 1 

Obs intake: 0 

Obs 

biomarkers: 

1 

Cochrane: 

7/11

8/12

RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA

No RCT RCT: Inconsistent 

effects over time 

and among tests

Obs intake: NA 

Obs biomarkers: No 

association 

DHA+EPA Breast

Feeding

Mothers

Insufficient RCT: 0 

Obs intake: 

0 

Obs 

biomarkers: 

0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA 

Obs biomarkers: NA

Fishoil Breast

Feeding

Mothers

Insufficient RCT: 0 

Obs intake:0 

Obs 

biomarkers: 

0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: NA

G-16
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision

Other 

Issues Finding

DHA+AA Breast

Feeding

Mothers

Insufficient RCT: 0 

Obs intake:0 

Obs 

biomarkers: 

0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA 

No data RCT: NA

Obs intake: NA 

Obs biomarkers: NA 

n-6/n- 3 Breast

Feeding

Mothers

Insufficient RCT: 0 

Obs intake:0 

Obs 

biomarkers: 

0 

NA RCT: NA

Obs: NA

Obs biomarkers: In 

All: 

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA 

No data RCT: NA

Obs intake: NA

Obs biomarkers: NA 

DHA Preterm 

infants

Insuffiient RCT: 0 

Obs intake: 0 

Obs 

biomarkers: 

0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake:NA 

Obs biomarkers: 

NA

No data RCT: NA

Obs intake: NA 

Obs biomarkers: NA

DHA+EPA Preterm 

infants

Insufficient RCT: 1 

Obs intake: 0 

Obs 

biomarkers: 

0 

7357 RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA

NA Sparse

DHAenriched 

tuna oil

RCT: No differences

Obs intake: NA

Obs biomarkers: NA

Fish oil Preterm 

infants

Insufficient RCT: 0 

Obs intake: 0 

Obs 

biomarkers: 

0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarkers: 

No data RCT: NA

Obs intake: NA

Obs biomarkers: NA 

DHA+AA Preterm 

infants

Insufficient RCT: 2 

Obs intake: 0 

Obs 

biomarkers: 

0 

Cochrane: 

12/13

6/13

RCT: Consistent

Obs: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarkers: 

Sparse RCT: Significantly 

higher PDI scores 

at 12, 18 months

Obs intake: NA

Obs biomarkers: NA 

n-6/n-3 Preterm 

infants

Insufficient RCT: 0 

Obs: 0

Obs 

biomarkers: 

0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA 

RCT: NA

Obs intake:NA 

Obs biomarkers: 

NA 

No data RCT: NA

Obs intake: NA 

Obs biomarkers: NA 

G-17
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision

Other 

Issues Finding

DHA Term 

Infants

Insufficient RCT: 2 

Obs intake: 0 

Obs 

biomarkers: 

Cochrane:

9/13

9/13

RCT: Inconsistent

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA 

Sparse RCT: Positive effects 

on brainstem 

maturation but 

mixed effects on 

gross motor 

control

Obs intake: NA

Obs biomarkers: NA 

DHA+EPA Term 

Infants

Insufficient RCT: 0 

Obs intake: 0 

Obs 

biomarkers: 

0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA 

RCT: NA

Obs intake: NA 

Obs 

biomarkers:NA 

No data RCT: NA

Obs intake: NA 

Obs biomarkers: NA 

Fish oil Term 

Infants

Insufficient RCT:1 

Obs intake: 0 

Obs 

biomarkers: 

0 

9/13 RCT: NA

Obs intake: NA

Obs biomarkers:NA

All:NA

NA No data RCT: No effects on 3 

indices

Obs intake: NA

Obs biomarkers: NA

DHA+AA Term 

Infants

Insufficient RCT: 2 

Obs intake: 0 

Obs 

biomarkers: 

0 

Cochrane:

9/13

6/13

RCT: NA

Obs intake: In 

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: 

Obs biomarker: 

NA

1 RCT in 3 

publications

RCT: small but 

significant effect at 

3 months not seen 

at 18 months or 9 

years in one RCT; 

and no effects on 

PDI in the other 

RCT

Obs intake: NA 

Obs biomarkers: NA

n-6/n-3 Term 

Infants

Insufficient RCT: 0 

Obs intake: 0 

Obs 

biomarkers: 

0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: 

Obs intake: NA

Obs biomarker: 

NA 

RCT: No effect

Obs intake: NA

Obs biomarkers: NA

G-18
Table G5. Strength of evidence for KQ2: infant and child outcomes (visual function)

Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA Preterm 

intervention

Low RCT: 4

Obs intake: 0

Obs 

biomarkers

: 2 

Cochrane:10/13, 

9/11, 7/11,13/13

RCT: Consistent

Obs intake: 

Inconsistent

Obs biomarkers:

Inconsistent 

All: NA

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA

2 RCTs 

included 

small amts. 

EPA; all used 

different 

outcome 

measures 

and FU times 

RCT: no effect on 

visual acuity

Obs intake: NA

Obs biomarkers: 

Inconsistent 

associations

DHA+EPA Insufficient RCT: 0

Obs intake:0 

Obs 

biomarkers

:0 

NA RCT: NA

Obs intake: 

Inconsistent

Obs biomarkers: 

NA

All: Inconsistent

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA 

Obs biomarkers: 

NA

Fish oil Insufficient RCT: 0

Obs intake: 0 

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+AA Insufficient RCT: 0

Obs intake:0 

Obs 

biomarkers

:0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

n-6/n-3 insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0 

NA RCT: NA

Obs intake: NA 

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA Breast

Feeding

mothers

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers

: 1

Cochrane 8/12 RCT: 

Inconsistent 

across time 

points

Obs intake: 

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: 

Improvement in 

one VEP 

outcome 4 and 

8 months but 

no difference at 

5 years

Obs intake: NA

Obs biomarkers: 

No association

G-19
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA+EPA Breast

Feeding

mothers

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers: 

0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake:NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

Fish oil Breast

Feeding

mothers

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers

: 1

Cochrane 12/12 RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: divergence 

between RCT 

and biomarker 

results

RCT: NA

Obs intake: 

NA;Obs. 

biomarker

Sparse data RCT: no effect 

observed on 

visual acuity at 

4 months

Obs intake: NA

Obs biomarkers: 

significant 

association of 

infant RBC 

DHA and visual 

acuity at 4 

months 

DHA+AA Breast

Feeding

mothers

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA 

Obs biomarkers: 

NA

n-6/n-3 Breast

Feeding

mothers

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers:

NA RCT: NA

Obs: NA

Obs biomarkers: 

NA

All: 

RCT: NA

Obs intake: NA

Obs biomarker: 

Precise

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

Unclear

Any n-3 FAs Preterm 

infants

VEP 4 

months

Low Pooled 

analysis of 4 

RCTs (5 

outcomes)

Study quality 

varied widely 

(Cochrane 6/11 

and 4/11, jadad 

3 and 5)

Inconsistent Precise Studies 

differed by 

intervention

WMD nonsignificant at 4 

months 

followup

WMD -0.06 

(−0.12; 0.01)

Any n-3 FAs Preterm 

infants 

VEP 6 

months

Low Pooled 

analysis of 

4 

RCTs (5 

outcomes)

Study quality 

varied widely 

(Cochrane 6/11 

and 4/11, jadad 

3 and 5)

Inconsistent Precise Studies 

differed by 

intervention

WMD nonsignificant at 6 

months 

followup

WMD -0.04[ -

0.09, 0.01

G-20
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA Preterm 

infants

Insufficient RCT: 2

Obs intake: 0

Obs 

biomarkers

: 0

Cochrane 10/13, 

8/11

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarkers: NA

Sparse

One study 

included 

small amount 

EPA

RCT: No 

differences at 

2, 4 months CA

in one study

Obs intake: NA 

Obs biomarkers: 

NA

DHA+EPA Preterm 

infants

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

NA No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

Fishoil Preterm 

infants

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarkers: NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+AA Preterm 

infants

Low RCT: 1

Obs intake: 0

Obs 

biomarkers

: 0

Cochrane 7/11 RCT: NA

Obs: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarkers: 

Unclear

Sparse RCT: 1 new study 

and 5 from 

original report 

show no 

consistent 

effect

Obs intake: NA

Obs biomarkers: 

NA

n-6/n-3 Preterm 

infants

Insufficient RCT: 0

Obs: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarkers: NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

Any n-3 FA Term 

infants 2 

month 

followup 

Behavioral

Low RCT:6 

Obs: 0

Obs 

biomarkers

: 0

Jadad 3.8 Inconsistent Precise Small effect 

size

Significant effect 

on BM 2 

months

WMD 0.07 [0.00, 

0.14] six RCTs

Any n-3 FA Term 

infants 2 

month 

followup 

VEP

Low RCT:6 

Obs: 0

Obs 

biomarkers

: 0

Jadad 4.2 

Cochrane 9/13

Inconsistent Precise Medium 

heterogeneity

Nonsignificant 

effect on VEP 

at 2 months

WMD 0.07[-0.03, 

0.17], six 

RCTs

G-21
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Any n-3 FA Term 

infants 4 

month 

followup 

Behavioral

Low RCT:6 

Obs: 0

Obs 

biomarkers

: 0

Jadad 3.8 Inconsistent Precise No new 

studies

Non-significant 

effect on BM at 4 

months WMD -

0.05 [-0.08, -

0.01], six RCTs

Any n-3 FA Term 

infants 4 

month 

followup 

VEP

Moderate RCT:8 

Obs: 0

Obs 

biomarkers

: 0

Jadad 3.8

Cochrane 7-

9/13

Inconsistent Precise Significant effect 

of n-3 FAs on 

VEP at 4 

months

WMD -0.10 (-

0.14, -0.07), 

eight RCTs

Any n-3 FA Term 

infants 12 

month 

followup 

Behavioral

Low RCT:6 

Obs: 0

Obs 

biomarkers

: 0

Jadad 3.8 Inconsistent Precise Non-significant

effect of n-3 FA 

on BM at 12 

months WMD -

0.10

(-0.14, -0.07)

six RCTs

Any n-3 FA Term 

infants 12 

month 

followup 

VEP

Moderate RCT:8 

Obs: 0

Obs 

biomarkers

: 0

Jadad 4.0

Cochrane 7-

9/13

Consistent Precise Significant effect 

of n-3 FA on 

VEP at 12 

months

WMD -0.14 

(-0.17, -0.12)

8 RCTs

DHA Term 

infants

Low RCT: 1

Obs intake: 0

Obs 

biomarkers

: 1

Cochrane 12/13 RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarkers: NA

Sparse RCT: 1 new study 

and 2 RCTs 

from original 

report suggest 

possible lasting 

benefit but 

inconsistent

Obs intake: NA

Obs biomarkers: 

NA

DHA+EPA Term 

infants

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarkers: NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

G-22
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Fishoil Term 

infants

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

:0

NA RCT: 

Obs intake: NA

Obs biomarkers: 

NA

All:NA

NA No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+AA Term 

infants

2 months 

followup

Behavioral

Low RCT: 4

Obs intake: 0

Obs 

biomarkers

: 0

Jadad 3.8 RCT: 

Inconsistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: Precise

Obs intake: NA

Obs biomarker: 

NA

No new 

studies

No significant

effect on BM at 

2 months

Obs intake: NA

Obs biomarkers: 

NA

WMD -0.07 (-

0.19, 0.04) six 

RCTs

DHA+AA Term 

infants

2 months 

followup

VEP

Low RCT: 6 Jadad 4.2

Cochrane 9/13

Inconsistent Precise One new 

study

No significant

effect on VEP 

at 2 months

WMD -0.06 

(−0.22; 0.10)

DHA+AA Term 

infants

4 months 

followup

Behavioral

Low RCT: 6 Jadad 3.8 Inconsistent Precise No new 

studies

No significant 

effect on BM at 

4 months WMD 

0.04 (0.02, 

0.10)

DHA+AA Term 

infants

4 months 

followup

VEP

Low RCT: 5 Jadad 4.3

Cochrane 7-

9/13

Inconsistent Precise Two new 

studies

Significant effect 

on VEP at 4 

months WMD

-0.10 [-0.14, -

0.07

DHA+AA Term 

infants

12 months 

followup

Behavioral

Moderate RCT: 4 Jadad 3.75 Consistent Precise No new 

studies

No significant 

effect on BM at 

12 months

WMD 0.01 (-

0.01, 0.02)

G-23
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA+AA Term 

infants

12 months 

followup

VEP

Low RCT: 6 Jadad 4.0

7-9/13

Inconsistent Precise 2 new 

studies

Significant effect 

on VEP at 12 

months

WMD -0.14 

(-0.17, -0.12)

n-6/n-3 Term 

infants

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA 

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

G-24
Table G6. Strength of evidence for KQ2: infant and child outcomes (cognitive)

Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Any n-3 FA Preterm 

infants

Moderate RCTs: 7 Medium risk 

of bias

High Imprecise Heterogeneous 

interventions

Significant 

increase in 

cognitive 

development 

(MDI scores)

WMD 2.24; 

(95% CI 0.05, 

4.43)

DHA Preterm 

Infants

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers: 

0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No studies RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+EPA Preterm 

Infants

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers: 

0

Low risk of 

bias

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: 

Imprecise

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: No effect

Obs intake: NA

Obs biomarkers: 

NA

DHA+AA Preterm 

Infants

Low RCT: at 2

Obs intake: 0

Obs 

biomarkers: 

0

1 RCT: 

Unclear 

allocation 

concealment 

and sequence

1 RCT: 

Attrition bias

RCT: 

Inconsistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: 

Imprecise

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: Mixed

Obs intake: NA

Obs biomarkers: 

NA

DHA+EPA

+AA

Preterm 

Infants

Insufficient RCT: 2

Obs intake: 0

Obs 

biomarkers: 

0

1 RCT: High 

Risk of Bias

1 RCT: 

Attrition bias

RCT: 

Inconsistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: 

Imprecise

Obs intake: NA 

Obs biomarker: 

NA

Sparse RCT: Mixed

Obs intake: NA

Obs biomarkers: 

NA

DHA Full Term 

Infants

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers: 

0

Low risk of 

bias

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: 

Imprecise

Obs intake: 

NA

Obs biomarker: 

NA

Sparse RCT: No effect

Obs intake: NA

Obs biomarkers: 

NA

G-25
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA+EPA Full Term 

Infants

Insufficient RCT: 2

Obs intake: 0

Obs 

biomarkers: 

0

1 RCT: Low 

risk of bias

1 RCT: High 

risk of bias

RCT: Consistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: 

Imprecise

Obs intake: 

Unclear

Obs biomarker: 

NA

Sparse RCT: No effect

Obs intake: 

Lower risk

Obs biomarkers: 

NA

DHA+AA Full Term 

Infants Low

RCT: 3

Obs intake: 0

Obs 

biomarkers: 

0

Low risk of 

bias

RCT: 

Inconsistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: 

Imprecise

Obs intake: NA

Obs biomarker: 

NA

Sparse, 

heterogeneous 

studies

No significant 

effect on MDI 

scores at 18-

24 months of 

age 

WMD 0.75, 95% 

CI -9.29, 

10.79

Obs intake: NA

Obs biomarkers: 

NA

DHA Pregnant 

women

Low for no 

effect

RCT: 1

Obs intake: 2

Obs 

biomarkers: 

4

Low risk of 

bias

RCT: NA

Obs intake: 

Consistent

Obs biomarkers: 

Consistent

All: Consistent

RCT: Precise

Obs intake: 

Precise

Obs 

biomarkers: 

Imprecise

RCT Outcome 

was Neonatal 

Behavior 

Assessment at 

age 14 days 

RCT: Positive 

effect

Obs intake: No 

effect

Obs biomarkers: 

No effect

DHA+EPA Pregnant 

women

Moderate 

for no 

effect

RCT: 5

Obs intake: 2

Obs 

biomarkers 

2: 

3 RCTs: Low

ROB

2 RCTs: High 

ROB

Observational:

Low ROB

RCT: Consistent

Obs intake: 

Consistent

Obs biomarkers: 

Consistent

All: Consistent

RCT: Precise

Obs intake: 

Precise

Obs 

biomarkers: 

Precise

Observational 

report results 

for DHA and

EPA levels 

separately

RCT: No effect

Obs intake: No 

effect of EPA: 

Obs biomarkers: 

No effect

DHA+AA Pregnant 

women

Moderate 

for no 

effect

RCT: 1

Obs intake: 2

Obs 

biomarkers: 

4

RCT: High 

ROB

Observational: 

Low ROB

RCT: NA

Obs: Consistent

Obs biomarkers: 

Inconsistent

All: Consistent

with one 

exception

RCT: Precise

Obs intake: 

Precise

Obs 

biomarkers: 

Imprecise

Observational 

report results 

for DHA and

AA levels 

separately

RCT: No effect

Obs intake: No 

effect

Obs biomarkers: 

effect in one 

study

n-6/n-3 Pregnant 

women

Insufficient RCT: 0

Obs intake: 1

Obs 

biomarkers: 

0

Low ROB RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: 

Imprecise

Obs: 

biomarkers: NA

Effect only in 

offspring never 

breastfed

RCT: NA

Obs intake: 

Positive effect

Obs biomarkers: 

NA

G-26
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

Other: ALA Pregnant 

women

Insufficient RCT: 0

Obs intake: 2 

Obs 

biomarkers: 

1

Low ROB RCT: NA

Obs intake: 

Consistent

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: 

Imprecise

Obs 

biomarkers: 

Precise

No RCTs RCT: NA

Obs intake: No 

effect

Obs biomarkers: 

No effect

DHA Breast 

feeding 

women

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers: 

0

NA RCT:NA 

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarkers: 

NA

No studies RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+EPA Breast 

feeding 

women

Low for no 

effect

RCT: 4

Obs intake: 0

Obs 

biomarkers: 

0

1 RCT: Low 

ROB

2 RCTs: 

Moderate 

ROB

1 RCT: High 

ROB

RCT: Consistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: Precise

Obs intake: 

Obs 

biomarkers: 

RCT: No effect

Obs intake: 

Obs biomarkers: 

DHA+AA Breast 

feeding 

women

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers: 

1

Moderate 

ROB

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: A

RCT: NA

Obs intake: NA

Obs biomarker: 

Precise

No RCTs

Observational 

report results 

for DHA and

AA levels 

separately

RCT: NA

Obs intake: NA

Obs biomarkers: 

No effect

G-27
Table G7. Strength of evidence for KQ2: infant and child outcomes (autism spectrum disorders)

Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA Preterm 

Infants (1 

RCT) 

Pregnant 

women (1 

RCT, 1 

Obs) 

Low for no 

effect

RCT: 2

Obs intake: 1

Obs 

biomarkers: 

0

2 RCTs: Low 

ROB

Obs: Low 

ROB

RCT: Consistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: Precise

Obs intake: NA

Obs biomarker: 

NA

Obs study 

authors 

advise that 

the results 

should be 

interpreted 

with caution, 

given the 

small number 

of cases

RCT: No 

association

Obs intake: 

women with 

the highest 

quartile of 

total PUFA 

intake were at 

lower risk of 

having a child 

with ASD than 

women in the 

lowest quartile

Obs biomarkers: 

NA

G-28
Table G8. Strength of evidence for KQ2: infant and child outcomes (attention deficit hyperactivity disorder)

Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision Other Issues Finding

DHA Preterm 

Infants (2 

RCTs) 

Pregnant 

women (1 

RCT) 

Low for no 

effect

RCT: 3

Obs intake: 0

Obs 

biomarkers: 

0

2 RCTs: Low 

ROB

1 RCT: High 

ROB

RCT: Consistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: Precise

Obs intake: NA

Obs biomarker: 

NA

The RCT 

reporting 

ADHD 

diagnosis at 

10 year 

follow-up had 

over 50% 

attrition

RCT: No 

association 

with attention 

outcomes or 

diagnosis of 

ADHD

Obs intake: NA

Obs biomarkers: 

NA

G-29
Table G9. Strength of evidence for KQ2: infant and child outcomes (atopic dermatitis, allergies, and respiratory illness)

Outcom

e

Intervent

ion

/exposur

e Population

SoE 

Grade

Design 

No. Studies

Study

Limitatio

ns Consistency Precision

Other 

Issues Finding

Atopic

Dermatiti

s

DHA Prenatal + 

Postnatal 

interventionpreterm and 

term infants

Low RCT:1

Obs intake: 2 

Obs 

biomarkers: 1

Cochrane: 

10/11

NOS: fair

RCT: NA

Obs intake: Consistent

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA

RCT 

compar

ed high 

DHA to 

standard 

DHA 

diet

RCT: No difference 

in risk

Obs intake: No 

significant 

association 

Obs biomarkers: 

low risk

Atopic 

Dermatiti

s

DHA+EP

A

Prenatal 

interventionpreterm and 

term infants

Low RCT: 4(2 

follow-up)

Obs intake: 6

Obs 

biomarkers:N

A

Cochrane:

9/12,5/12,

12/13, 

,12/13

NOS: 

poor-fair

RCT: Inconsistent

Obs intake: Consistent

Obs biomarkers: 

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

RCT: one study 

reported a 

significant risk 

reduction, 

remaining found 

no significant 

difference 

Obs intake: No 

association

Obs biomarkers: NA 

Atopic 

Dermatiti

s

DHA+EP

A

Postnatal 

interventionpreterm and 

term infants

Insufficie

nt

RCT: 1

Obs intake: NA

Obs 

biomarkers:N

A

Cochrane:

9/13

RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA 

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: No significant 

difference 

Obs intake: NA 

Obs biomarkers: NA 

Atopic 

Dermatiti

s

Fish oil Prenatal 

+Postnatal 

intervention

Low RCT: 3 (+2 

follow-up)

Obs intake: 0

Obs 

biomarkers: 0

Cochrane:

9/12,10/13

, 10/13

RCT: Consistent

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker:

RCT: No significant 

difference 

Obs intake: NA

Obs biomarkers: NA

G-30
Outcom

e

Intervent

ion

/exposur

e Population

SoE 

Grade

Design 

No. Studies

Study

Limitatio

ns Consistency Precision

Other 

Issues Finding

Atopic 

Dermatiti

s

n-3 FA Prenatal 

+Postnatal 

intervention

Low RCT: 1 (+2 

follow-up)

Obs intake: 7

Obs 

biomarkers:3

RCT:10-

11/13

NOS: 

poor-good

RCT: Consistent

Obs intake: Inconsistent 

Obs biomarkers: 

Consistent

All: NA

RCT: NA

Obs intake:NA 

Obs biomarker: 

NA

RCT: No significant 

difference

Obs intake: One of 

the studies found 

reduced risk, 

others found no 

significant 

association

Obs biomarkers: No 

association 

Atopic 

Dermatiti

s

n-6/n-3 Prenatal 

+Postnatal 

interventionTerm infants

Low RCT: 0

Obs intake: 5

Obs 

biomarkers: 3

NOS: 

poor-good

RCT: NA

Obs intake: Consistent

Obs biomarkers: 

Inconsistent

All: NA

RCT: NA

Obs intake:NA 

Obs biomarker: 

NA 

RCT: NA

Obs intake: No 

association 

Obs biomarkers: 

One of the studies 

found reduced 

risk, others found 

no significant 

association

Atopic 

Dermatiti

s

ALA Prenatal 

+Postnatal 

interventionTerm infants

Low RCT: 1 

Obs intake:1

Obs 

biomarkers:2 

Cochrane:

11/12

NOS: fairgood

RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs 

biomarker:NA 

Sparse RCT: Significant 

risk reduction at 

12 month followup 

Obs intake: No 

significant 

association 

Obs biomarkers: No 

significant 

association

G-31
Outcom

e

Intervent

ion

/exposur

e Population

SoE 

Grade

Design 

No. Studies

Study

Limitatio

ns Consistency Precision

Other 

Issues Finding

Allergies DHA Prenatal + 

Postnatal 

interventionpreterm and 

term infants

Low RCT: 1

Obs intake: 2

Obs 

biomarkers: 3

Cochrane:

10/11

NOS: fairgood

RCT: NA

Obs intake: Consistent

Obs biomarkers: 

Inconsistent

All: NA

RCT: NA

Obs intake: 

Obs biomarker: 

NA

Sparse RCT: No significant 

difference

Obs intake: No 

significant 

association 

Obs biomarkers: 

One of the studies 

reported low risk, 

others found no 

significant 

association

Allergies DHA+EP

A

Prenatal 

intervention

Low RCT: 3 (+2 

follow-up) 

Obs intake: 1 

Obs 

biomarkers:0 

Cochrane: 

12/13, 

9/12,11-

12/13,

NOS: fair

RCT: Inconsistent

Obs intake: NA 

Obs biomarkers: NA 

All: NA

RCT: Imprecise

Obs intake: NA 

Obs biomarker: 

NA 

RCT: Nonsignificant effect

on allergy risk at 

12 months

OR 0.54 (95% CI 

0.05, 6.2)

(3 RCTs)

Obs intake: no 

significant 

association 

Obs biomarkers: NA

Allergies DHA+EP

A

Postnatal 

intervention

Insufficie

nt

RCT: 1

Obs intake: NA

Obs 

biomarkers:N

A

Cochrane: 

9/13

RCT: NA

Obs intake: NA

Obs biomarkers: NA

All: NA 

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

Sparse RCT: No significant 

association 

Obs intake: NA 

Obs biomarkers: NA 

Allergies Fish oil Prenatal + 

Postnatal 

interventionpreterm and 

term infants

Low RCT: 3 (+2 

follow-up) 

Obs intake: NA 

Obs 

biomarkers: 

NA 

Cochrane:

9/13, 

10/13,

9/12

RCT: Inconsistent

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT:NA

Obs intake: NA 

Obs biomarker: 

NA 

RCT: No significant 

association 

Obs intake: NA

Obs biomarkers: NA

G-32
Outcom

e

Intervent

ion

/exposur

e Population

SoE 

Grade

Design 

No. Studies

Study

Limitatio

ns Consistency Precision

Other 

Issues Finding

Allergies n-3 FA Prenatal + 

Postnatal 

interventionpreterm and 

term infants

Low RCT: 0 

Obs intake:4 

Obs 

biomarkers: 4 

NOS: 

poorgood

RCT: NA

Obs intake: Inconsistent

Obs biomarkers: 

Consistent

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: one

study found 

reduced risk, 

others found no

significant 

association 

Obs biomarkers: No 

association 

Allergies n-6/n-3 Prenatal + 

Postnatal 

interventionpreterm and 

term infants

Low RCT: 0 

Obs intake: 2 

Obs 

biomarkers: 4 

NOS: 

poorgood

RCT: NA

Obs intake: Inconsistent

Obs biomarkers: 

Consistent

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarker:NA

RCT: NA

Obs intake: one 

study found a 

significant 

association, the 

other found no

significant 

association 

Obs biomarkers: No 

significant 

association 

Allergies OtherALAPrenatal + 

Postnatal 

interventionpreterm and 

term infants

Low RCT: 1 

Obs intake:2

Obs 

biomarkers:2 

Cochrane:

11/12

NOS: fairgood

RCT: NA

Obs intake: Consistent

Obs biomarkers:

Consistent

All: NA

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA 

A study 

reported 

positive 

associat

ion with 

sensitiz

ation in 

infants 

with no 

materna

l history 

of 

allergy

RCT: No significant 

difference 

Obs intake: No 

significant 

association 

Obs biomarkers: No 

significant 

association 

G-33
Outcom

e

Intervent

ion

/exposur

e Population

SoE 

Grade

Design 

No. Studies

Study

Limitatio

ns Consistency Precision

Other 

Issues Finding

Respirator

y Illness: 

Wheeze

DHA Prenatal + 

Postnatal 

interventionpreterm and 

term infants

Low RCT: 3

Obs intake: 5 

Obs 

biomarkers:4 

Cochrane:

11/13, 

10/13

NOS: 

poor-good

RCT: Inconsistent

Obs intake: Inconsistent

Obs biomarkers: 

Inconsistent

All: Inconsistent

RCT:NA

Obs intake: NA 

Obs 

biomarkers: NA

RCT: no significant 

effect on risk for 

wheeze at 12 

months 

OR 0.95 (95% CI

0.77,1.16)

(3 RCTs)

Obs intake: one 

study found a 

significant risk 

reduction, others 

found no 

significant

association 

Obs biomarkers: one 

study reported a 

significant risk 

reduction, others 

found no 

significant

association. 

Respirator

y Illness: 

Wheeze

DHA+EP

A

Prenatal 

intervention

Low RCT: 2 

Obs intake: 1 

Obs 

biomarkers: 

NA 

Cochrane:

5/12,9/12

NOS: 

poor

RCT: Consistent

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs 

biomarkers: NA

RCT: no significant 

difference

Obs intake: Reduced 

risk 

Obs biomarkers: NA

Respirator

y Illness: 

Wheeze

Fish oil Prenatal + 

Postnatal 

intervention

Low RCT: 3 (+3 

follow-up) 

Obs intake: 0 

Obs 

biomarkers:0 

Cochrane:

10/13,9/13

9/12

RCT: Consistent

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs 

biomarkers: NA 

RCT: No significant 

difference

Obs intake: NA

Obs biomarkers: NA

Respirator

y Illness: 

Wheeze

DHA+AA RCT: 0 

Obs intake: 0 

Obs 

biomarkers: 0 

RCT: NA

Obs: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarkers: 

No data RCT: NA

Obs intake: NA

Obs biomarkers: NA 

G-34
Outcom

e

Intervent

ion

/exposur

e Population

SoE 

Grade

Design 

No. Studies

Study

Limitatio

ns Consistency Precision

Other 

Issues Finding

Respirator

y Illness: 

Wheeze

n-6/n-3 Prenatal + 

Postnatal 

intervention

Low RCT:0 

Obs intake: 2 

Obs 

biomarkers:3 

NOS: 

poor- fair

RCT: NA

Obs intake: Consistent

Obs biomarkers: 

Consistent

All: NA

RCT: NA

Obs intake: NA

Obs 

biomarkers: NA 

RCT: NA

Obs intake: No 

significant 

association 

Obs biomarkers: No 

significant 

association 

Respirator

y Illness: 

Wheeze

Total n-3 

FA

Prenatal + 

Postnatal 

intervention

Low RCT: 2 

Obs intake: 3 

Obs 

biomarkers: 

4 

Cochrane: 

10/13, 

5/12

NOS: 

poorgood

RCT: Inconsistent 

Obs intake: Consistent

Obs biomarkers: 

Inconsistent

All: NA

RCT: NA 

Obs intake: NA

Obs biomarker: 

NA

One of 

the 

RCTs 

reports 

increase

d 

prevale

nce of 

wheeze 

at 8yr 

follow 

up.

RCT: 

One study reported 

significant risk 

reduction while 

the other found 

no significant 

difference

Obs intake: No 

significant 

association

Obs biomarkers: 2 

studies found

reduced risk, the 

other two found 

no significant 

association

Respirator

y Illness: 

Asthma

DHA Prenatal + 

Postnatal 

intervention

Low RCT: 3 (+3 

follow-up) 

Obs intake:2 

Obs 

biomarkers: 1 

Cochrane:

10/13,9/13

,10/13

NOS: fairgood

RCT: Consistent

Obs intake: Inconsistent

Obs biomarkers: NA

All: NA

RCT: Imprecise

Obs intake: NA

Obs 

biomarkers: NA 

RCT: nonsignificant 

summary effect

Obs intake: one

study reported a 

significant 

association risk, 

other nonsignificant 

Obs biomarkers: No 

significant 

association 

G-35
Outcom

e

Intervent

ion

/exposur

e Population

SoE 

Grade

Design 

No. Studies

Study

Limitatio

ns Consistency Precision

Other 

Issues Finding

Respirator

y Illness: 

Asthma

DHA+EP

A

Prenatal 

intervention

Low RCT: 4 

Obs intake: NA 

Obs 

biomarkers:N

A 

Cochrane:

12/13,9/12

,11/13,12/

13

RCT: Inconsistent

Obs intake: NA

Obs biomarkers: NA

All: NA

RCT: NA

Obs intake: NA 

Obs 

biomarkers:NA 

RCT: nonsignificant 

difference

Obs intake: NA 

Obs biomarkers: NA 

Respirator

y Illness: 

Asthma

Fish oil Prenatal + 

Postnatal 

intervention

Low RCT: 4 (+ 3 

follow-up) 

Obs intake: 0 

Obs 

biomarkers: 0 

Cochrane: 

10/13,9/13

,12/13, 

9/12

RCT: Inconsistent

Obs intake: NA

Obs biomarkers:NA

All: NA

RCT: NA

Obs intake: NA 

Obs 

biomarkers:NA 

RCT: No significant 

difference

Obs intake: NA

Obs biomarkers: NA

Respirator

y Illness: 

Asthma

DHA+AA RCT: 

Obs intake: 

Obs 

biomarkers: 

RCT: 

Obs intake: 

Obs biomarkers:

All: 

RCT: 

Obs intake: 

Obs biomarker: 

No data RCT: 

Obs intake: 

Obs biomarkers:

Respirator

y Illness: 

Asthma

n-6/n-3 Prenatal + 

Postnatal 

intervention

Low RCT: 0 

Obs intake: 2 

Obs 

biomarkers:2 

NOS: fairgoodRCT: NA

Obs intake: Inconsistent

Obs biomarkers: 

Consistent 

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA 

RCT: NA

Obs intake: One 

study reported 

significant risk 

reduction while 

the other found 

no significant 

association

Obs biomarkers: No 

association

G-36
Table G10. Strength of evidence for KQ2: infant and child outcomes (adverse events)

Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision

Other 

Issues Finding

DHA Pregnant 

women

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers

: 0

Fair McH RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

NA RCT: No effect 

Obs intake: NA

Obs biomarkers: 

NA

DHA+EPA Pregnant 

women

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers

:0

Mcharm 4/6 RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

RCT: NA

Obs intake: NA

Obs 

biomarker:NA 

EPA/DHA>1 RCT: risk GI 

AEs

Obs intake: 

Obs biomarkers: 

Fishoil Pregnant 

women

Insufficient RCT: 0

Obs intake: 

Obs 

biomarkers

: 

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

NA No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+AA Pregnant 

women

Low RCT: 2

Obs intake:0 

Obs 

biomarkers

: 0

Good-fair 

McH

RCT: Inconsistent

Obs intake: NA

Obs biomarkers: 

NA

RCT: NA

Obs intake: NA 

Obs biomarker: 

NA

Sparse RCT: Unclear risk 

for GI AEs

No SAEs

Obs intake:

Obs biomarkers: 

n-6/n-3 Pregnant 

women

Insufficient RCT:0 

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: 

Obs intake: 

Obs biomarkers

RCT: NA

Obs intake: 

Obs biomarker: 

Sparse RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

No studies Breast

Feeding 

women: 

maternal 

outcomes

Insufficient RCT:0 

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers

DHA Breastfed 

term 

infants

Low RCT: 2

Obs intake: 0

Obs 

biomarkers

:

Good McH RCT: Inconsistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: 

Obs biomarkers: 

NA

Sparse RCT: No 

difference in 

AEs or lower 

AEs

Obs intake: NA

Obs biomarkers: 

NA

G-37
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision

Other 

Issues Finding

DHA+EPA Breastfed 

term 

infants

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers

: 0

McHarm 

4/6

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

NA No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

Fishoil Breastfed 

term 

infants

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 1

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarkers: 

Unclear

Sparse RCT: NA

Obs intake: NA

Obs biomarkers: 

Lower risk

DHA+AA Breastfed 

term 

infants

Insufficient RCT: 1

Obs intake: 0

Obs 

biomarkers

: 

Mcharm 4/5 RCT: NA

Obs: NA

Obs biomarkers: 

NA

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

Sparse, no 

obs

RCT: No 

differences in 

AEs

Obs intake: NA

Obs biomarkers: 

n-6/n-3 Breastfed 

term 

infants

Insufficient RCT: 0

Obs: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA Preterm 

infants 

formula fed

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 1

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarkers: 

Imprecise 

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+EPA Preterm 

infants 

formula fed

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0 

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: Consistent

RCT: NA

Obs intake: 

Imprecise

Obs biomarkers: 

Imprecise

No data RCT: NA

Obs intake: No 

association

Obs biomarkers: 

Fishoil Preterm 

infants 

formula fed

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers 

0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All:NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+AA Preterm 

infants 

formula fed

Insufficient RCT: 4

Obs intake: 0

Obs 

biomarkers

: 0

Mcharm 

1,2,4/5; 3/6

RCT: Inconsistent

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No obs;

Risks 

associated 

with 

prematurity 

reported as 

AEs

RCT: No net 

effect on AEs

Obs intake: 

Obs biomarkers: 

NA

G-38
Intervention

/exposure Population

SoE 

Grade

Design 

No. Studies

Study

Limitations Consistency Precision

Other 

Issues Finding

n-6/n-3 Preterm 

infants 

formula fed

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

:0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA 

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA Term 

infants 

formula fed

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: 

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+EPA Term 

infants 

formula fed

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: 

Obs intake: NA

Obs biomarkers: 

NA

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

Fishoil Term 

infants 

formula fed

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA 

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

DHA+AA Term 

infants 

formula fed

Moderate RCT: 5

Obs intake: 0

Obs 

biomarkers

: 0

Mcharms 

0, 2, 3, 4/5; 

3/6

RCT: Inconsistent

Obs intake: NA

Obs biomarkers: 

NA 

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No obs. RCT: No 

difference or 

fewer AEs in n3 groups; no 

SAEs

Obs intake: NA

Obs biomarkers: 

NA

n-6/n-3 Term 

infants 

formula fed

Insufficient RCT: 0

Obs intake: 0

Obs 

biomarkers

: 0

NA RCT: NA

Obs intake: NA

Obs biomarkers: 

NA 

All: NA

RCT: NA

Obs intake: NA

Obs biomarker: 

NA

No data RCT: NA

Obs intake: NA

Obs biomarkers: 

NA

G-39
Appendix H. List of Included Studies From the 

Original Report

1. Agostoni C, Marangoni F, Giovannini M, et al. Prolonged breast-feeding (six months or 

more) and milk fat content at six months are associated with higher developmental scores at one 

year of age within a breast-fed population. Adv Exp Med Biol. 2001;501:137-41. PMID: 

11787675.

2. Agostoni C, Riva E, Trojan S, et al. Docosahexaenoic acid status and developmental quotient 

of healthy term infants.[comment]. Lancet. 1995 9/2/1995;346(8975):638.

3. Agostoni C, Trojan S, Bellu R, et al. Developmental quotient at 24 months and fatty acid 

composition of diet in early infancy: a follow up study. Arch Dis Child. 1997 5/1997;76(5):421-

4.

4. Agostoni C, Trojan S, Bellu R, et al. Neurodevelopmental quotient of healthy term infants at 

4 months and feeding practice: the role of long-chain polyunsaturated fatty acids. Pediatr Res. 

1995 8/1995;38(2):262-6.

5. Al MD, van Houwelingen AC, Badart-Smook A, et al. The essential fatty acid status of 

mother and child in pregnancy-induced hypertension: a prospective longitudinal study. Am J 

Obstet Gynecol. 1995 5/1995;172(5):1605-14.

6. Al MD, von Houwelingen AC, Hasaart TH, et al. The relationship between the essential fatty 

acid status of mother and child and the occurrence of pregnancy-induced hypertension. 

Intermediate results of a prospective longitudinal study. World Rev Nutr Diet. 1994 

1994;76:110-3.

7. Auestad N, Halter R, Hall RT, et al. Growth and development in term infants fed long-chain 

polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate 

study. Pediatrics. 2001 Aug;108(2):372-81. PMID: 11483802.

8. Auestad N, Montalto MB, Hall RT, et al. Visual acuity, erythrocyte fatty acid composition, 

and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. 

Ross Pediatric Lipid Study. Pediatr Res. 1997 1/1997;41(1):1-10.

9. Auestad N, Scott DT, Janowsky JS, et al. Visual, cognitive, and language assessments at 39 

months: a follow-up study of children fed formulas containing long-chain polyunsaturated fatty 

acids to 1 year of age. Pediatrics. 2003 Sep;112(3 Pt 1):e177-83. PMID: 12949309.

10. Birch DG, Birch EE, Hoffman DR, et al. Retinal development in very-low-birth-weight 

infants fed diets differing in omega-3 fatty acids. Invest Ophthalmol Vis Sci. 1992 

7/1992;33(8):2365-76.

11. Birch E, Birch D, Hoffman D, et al. Breast-feeding and optimal visual development. J 

Pediatr Ophthalmol Strabismus. 1993 1/1993;30(1):33-8.

H-1
12. Birch EE, Birch DG, Hoffman DR, et al. Dietary essential fatty acid supply and visual acuity 

development. Invest Ophthalmol Vis Sci. 1992 10/1992;33(11):3242-53.

13. Birch EE, Garfield S, Hoffman DR, et al. A randomized controlled trial of early dietary 

supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev 

Med Child Neurol. 2000 Mar;42(3):174-81. PMID: 10755457.

14. Birch EE, Hoffman DR, Castaneda YS, et al. A randomized controlled trial of long-chain 

polyunsaturated fatty acid supplementation of formula in term infants after weaning at 6 wk of 

age. Am J Clin Nutr. 2002 Mar;75(3):570-80. PMID: 11864865.

15. Birch EE, Hoffman DR, Uauy R, et al. Visual acuity and the essentiality of docosahexaenoic 

acid and arachidonic acid in the diet of term infants. Pediatr Res. 1998 Aug;44(2):201-9. PMID: 

9702915.

16. Bougle D, Denise P, Vimard F, et al. Early neurological and neuropsychological 

development of the preterm infant and polyunsaturated fatty acids supply. Clin Neurophysiol. 

1999 8/1999;110(8):1363-70.

17. Bulstra-Ramakers MT, Huisjes HJ, Visser GH. The effects of 3g eicosapentaenoic acid daily 

on recurrence of intrauterine growth retardation and pregnancy induced hypertension. Br J 

Obstet Gynaecol. 1995 2/1995;102(2):123-6.

18. Carlson SE, Cooke RJ, Rhodes PG, et al. Long-term feeding of formulas high in linolenic 

acid and marine oil to very low birth weight infants: phospholipid fatty acids. Pediatr Res. 1991 

11/1991;30(5):404-12.

19. Carlson SE, Cooke RJ, Werkman SH, et al. First year growth of preterm infants fed standard 

compared to marine oil n-3 supplemented formula. Lipids. 1992 11/1992;27(11):901-7.

20. Carlson SE, Ford AJ, Werkman SH, et al. Visual acuity and fatty acid status of term infants 

fed human milk and formulas with and without docosahexaenoate and arachidonate from egg 

yolk lecithin. Pediatr Res. 1996 5/1996;39(5):882-8.

21. Carlson SE, Rhodes PG, Rao VS, et al. Effect of fish oil supplementation on the n-3 fatty 

acid content of red blood cell membranes in preterm infants. Pediatr Res. 1987 

5/1987;21(5):507-10.

22. Carlson SE, Werkman SH. A randomized trial of visual attention of preterm infants fed 

docosahexaenoic acid until two months. Lipids. 1996 1/1996;31(1):85-90.

23. Carlson SE, Werkman SH, Cooke RJ, et al. Docosahexaenoate (DHA) and 

eicosapentaenoate (EPA) status of preterm infants: relationship to the Fagantest of Infant 

Intelligence and the Bayley Scale of Mental Development. FASEB J. 1990 1990;4:A1156.

H-2
24. Carlson SE, Werkman SH, Peeples JM, et al. Arachidonic acid status correlates with first 

year growth in preterm infants. Proc Natl Acad Sci U S A. 1993 2/1/1993;90(3):1073-7.

25. Carlson SE, Werkman SH, Rhodes PG, et al. Visual-acuity development in healthy preterm 

infants: effect of marine-oil supplementation. Am J Clin Nutr. 1993 7/1993;58(1):35-42.

26. Carlson SE, Werkman SH, Tolley EA. Effect of long-chain n-3 fatty acid supplementation 

on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia. 

Am J Clin Nutr. 1996 5/1996;63(5):687-97.

27. Cetin I, Giovannini N, Alvino G, et al. Intrauterine growth restriction is associated with 

changes in polyunsaturated fatty acid fetal-maternal relationships. Pediatr Res. 2002 1;52(5):750-

5. PMID: 2002403314 MEDLINE PMID 12409524 

(http://www.ncbi.nlm.nih.gov/pubmed/12409524).

28. Cheruku SR, Montgomery-Downs HE, Farkas SL, et al. Higher maternal plasma 

docosahexaenoic acid during pregnancy is associated with more mature neonatal sleep-state 

patterning. Am J Clin Nutr. 2002 September;76(3):608-13. PMID: 2002303115 MEDLINE 

PMID 12198007 (http://www.ncbi.nlm.nih.gov/pubmed/12198007).

29. Clandinin MT, Aerde J, Boettcher JA, et al. Growth and development of very-low-birthweight infants (VLBW) is enhanced by formulas supplemented with docosahexaenoic acid 

(DHA) and arachidonic acid (ARA). J Pediatr Gastroenterol Nutr; 2002. p. 479.

30. Clandinin MT, Aerde J, Boettcher JA, et al. Safety of formulas with docosahexaenoic acid 

(DHA) and arachidonic acid (ARA) from single-cell and marine sources for low-birth-weight 

infants (LBW). J Pediatr Gastroenterol Nutr; 2002. p. 484.

31. Craig-Schmidt MC, Carlson SE, Crocker L, et al. Plasma total phospholipid arachidonic acid 

and eicosapentaenoic acid in normal and hypertensive pregnancy. World Rev Nutr Diet. 1994 

1994;76:126-9.

32. D'Almeida A, Carter JP, Anatol A, et al. Effects of a combination of evening primrose oil 

(gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, 

and versus placebo in preventing pre-eclampsia. Women Health. 1992 1992;19(2-3):117-31.

33. de Groot RH, Adam J, Jolles J, et al. Alpha-linolenic acid supplementation during human 

pregnancy does not effect cognitive functioning. Prostaglandins Leukotrienes & Essential Fatty 

Acids. 2004 Jan;70(1):41-7. PMID: 14643178.

34. de Groot RH, Hornstra G, van Houwelingen AC, et al. Effect of alpha-linolenic acid 

supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status 

and pregnancy outcome. Am J Clin Nutr. 2004 Feb;79(2):251-60. PMID: 14749231.

35. Decsi T, Koletzko B. Growth, fatty acid composition of plasma lipid classes, and plasma 

retinol and alpha-tocopherol concentrations in full-term infants fed formula enriched with 

H-3
omega-6 and omega-3 long-chain polyunsaturated fatty acids. Acta Paediatr. 1995 

7/1995;84(7):725-32.

36. Diersen-Schade DA, Hansen JW, Harris CL, et al. Docosahexaenoic Acid plus Arachidonic 

Acid Enhance Preterm Growth. In: Riemersma R, Armstrong R, Kelly RW, Wilson R, eds. 

Essential Fatty Acids and Eicosanoids-Invited Papers from the Fourth International Congress. 

Champaign, IL, USA: AOCS Press; 1998:pp. 123–7.

37. Dunstan JA, Mori TA, Barden A, et al. Effects of n-3 polyunsaturated fatty acid 

supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition. Eur J 

Clin Nutr. 2004 Mar;58(3):429-37. PMID: 14985680.

38. Elias SL, Innis SM. Infant plasma trans, n-6, and n-3 fatty acids and conjugated linoleic 

acids are related to maternal plasma fatty acids, length of gestation, and birth weight and length. 

Am J Clin Nutr. 2001 2001;73(4):807-14. PMID: 2001116550 MEDLINE PMID 11273857 

(http://www.ncbi.nlm.nih.gov/pubmed/11273857).

39. Faldella G, Govoni M, Alessandroni R, et al. Maturation of the visual cortex in relation to 

dietary intake of polyenoic fatty acids in preterm infants. ; . . Bambini e Nutrizione. 

1995;2(3):116-20.

40. Faldella G, Govoni M, Alessandroni R, et al. Visual evoked potentials and dietary long 

chain polyunsaturated fatty acids in preterm infants. Archives of Disease in Childhood Fetal & 

Neonatal Edition. 1996 9/1996;75(2):F108-F12.

41. Fewtrell MS, Abbott RA, Kennedy K, et al. Randomized, double-blind trial of long-chain 

polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. J 

Pediatr. 2004 Apr;144(4):471-9. PMID: 15069395.

42. Fewtrell MS, Morley R, Abbott RA, et al. Double-blind, randomized trial of long-chain 

polyunsaturated fatty acid supplementation in formula fed to preterm infants. Pediatrics. 2002 

Jul;110(1 Pt 1):73-82. PMID: 12093949.

43. Field CJ, Thomson CA, Van Aerde JE, et al. Lower proportion of CD45R0+ cells and 

deficient interleukin-10 production by formula-fed infants, compared with human-fed, is 

corrected with supplementation of long-chain polyunsaturated fatty acids. J Pediatr Gastroenterol 

Nutr. 2000 Sep;31(3):291-9. PMID: 10997375.

44. Ghebremeskel K, Burns L, Costeloe K, et al. Plasma vitamin A and E in preterm babies fed 

on breast milk or formula milk with or without long-chain polyunsaturated fatty acids. Int J 

Vitam Nutr Res. 1999 /6/1999;69(2):83-91.

45. Ghys A, Bakker E, Hornstra G, et al. Red blood cell and plasma phospholipid arachidonic 

and docosahexaenoic acid levels at birth and cognitive development at 4 years of age. Early Hum 

Dev. 2002 Oct;69(1-2):83-90. PMID: 12324186.

H-4
46. Gibson RA, Neumann MA, Makrides M. Effect of increasing breast milk docosahexaenoic 

acid on plasma and erythrocyte phospholipid fatty acids and neural indices of exclusively breast 

fed infants. Eur J Clin Nutr. 1997 9/1997;51(9):578-84.

47. Gobel Y, Koletzko B, Bohles HJ, et al. Parenteral fat emulsions based on olive and soybean 

oils: a randomized clinical trial in preterm infants. J Pediatr Gastroenterol Nutr. 2003 

Aug;37(2):161-7. PMID: 12883303.

48. Groh-Wargo S, Moore JJ, Catalano P, et al. Docosahexaenoic acid (DHA) and arachidonic 

acid (AA) supplementation does not change body composition in preterm (PT) infants. Pediatr 

Res; 2002. p. 380a.

49. Guesnet P. Blood lipid concentrations of docosahexaenoic and arachidonic acids at birth 

determine their relative postnatal changes in term infants fed breast milk or formula.[comment]. 

Am J Clin Nutr. 1999 8/1999;70(2):292-8.

50. Helland IB, Saugstad OD, Smith L, et al. Similar effects on infants of n-3 and n-6 fatty acids 

supplementation to pregnant and lactating women. Pediatrics. 2001 Nov;108(5):E82. PMID: 

11694666.

51. Helland IB, Smith L, Saarem K, et al. Maternal supplementation with very-long-chain n-3 

fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics. 

2003 Jan;111(1):e39-44. PMID: 12509593.

52. Hoffman DR, Birch EE, Birch DG, et al. Fatty acid profile of buccal cheek cell 

phospholipids as an index for dietary intake of docosahexaenoic acid in preterm infants. Lipids. 

1999 4/1999;34(4):337-42.

53. Hoffman DR, Birch EE, Birch DG, et al. Impact of early dietary intake and blood lipid 

composition of long-chain polyunsaturated fatty acids on later visual development. J Pediatr 

Gastroenterol Nutr. 2000 Nov;31(5):540-53. PMID: 11144440.

54. Hoffman DR, Birch EE, Birch DG, et al. Effects of supplementation with omega 3 longchain polyunsaturated fatty acids on retinal and cortical development in premature infants. Am J 

Clin Nutr. 1993 5/1993;57(5 Suppl):807S-12S.

55. Hoffman DR, Birch EE, Castaneda YS, et al. Visual function in breast-fed term infants 

weaned to formula with or without long-chain polyunsaturates at 4 to 6 months: a randomized 

clinical trial. J Pediatr. 2003 6/2003;142(6):669-77.

56. Hofmann M, Bahlmann F, Pollow K, et al. Phospholipid and triglycerid composition in 

patients with preeclampsia compared with normal pregnancies - Deficiency of essential 

polyunsaturated fatty acids. Geburtshilfe Frauenheilkd. 1998 1998;58(9).

H-5
57. Innis SM, Adamkin DH, Hall RT, et al. Docosahexaenoic acid and arachidonic acid enhance 

growth with no adverse effects in preterm infants fed formula. J Pediatr. 2002 May;140(5):547-

54. PMID: 12032520.

58. Innis SM, Akrabawi SS, Diersen-Schade DA, et al. Visual acuity and blood lipids in term 

infants fed human milk or formulae.[erratum appears in Lipids 1997 Apr;32(4):457]. Lipids. 

1997 1/1997;32(1):63-72.

59. Innis SM, Gilley J, Werker J. Are human milk long-chain polyunsaturated fatty acids related 

to visual and neural development in breast-fed term infants? J Pediatr. 2001 Oct;139(4):532-8. 

PMID: 11598600.

60. Innis SM, Nelson CM, Rioux MF, et al. Development of visual acuity in relation to plasma 

and erythrocyte omega-6 and omega-3 fatty acids in healthy term gestation infants. Am J Clin 

Nutr. 1994 9/1994;60(3):347-52.

61. Jensen CL, Prager TC, Fraley JK, et al. Effect of dietary linoleic/alpha-linolenic acid ratio 

on growth and visual function of term infants.[comment]. J Pediatr. 1997 8/1997;131(2):200-9.

62. Jensen CL, Prager TC, Zou Y, et al. Effects of maternal docosahexaenoic acid 

supplementation on visual function and growth of breast-fed term infants. Lipids. 1999 

1999;34(Suppl):S225.

63. Jorgensen MH, Hernell O, Hughes E, et al. Is there a relation between docosahexaenoic acid 

concentration in mothers' milk and visual development in term infants? J Pediatr Gastroenterol 

Nutr. 2001 Mar;32(3):293-6. PMID: 11345178.

64. Jorgensen MH, Hernell O, Lund P, et al. Visual acuity and erythrocyte docosahexaenoic acid 

status in breast-fed and formula-fed term infants during the first four months of life. Lipids. 1996 

1/1996;31(1):99-105.

65. Jorgensen MH, Holmer G, Lund P, et al. Effect of formula supplemented with 

docosahexaenoic acid and gamma- linolenic acid on fatty acid status and visual acuity in term 

infants. J Pediatr Gastroenterol Nutr. 1998 1998;26(4):412-21.

66. Koletzko B, Edenhofer S, Lipowsky G, et al. Effects of a low birthweight infant formula 

containing human milk levels of docosahexaenoic and arachidonic acids. J Pediatr Gastroenterol 

Nutr. 1995 8/1995;21(2):200-8.

67. Koletzko B, Sauerwald U, Keicher U, et al. Fatty acid profiles, antioxidant status, and 

growth of preterm infants fed diets without or with long-chain polyunsaturated fatty acids. A 

randomized clinical trial. Eur J Nutr. 2003 Oct;42(5):243-53. PMID: 14569405.

68. Krasevec JM, Jones PJ, Cabrera-Hernandez A, et al. Maternal and infant essential fatty acid 

status in Havana, Cuba. Am J Clin Nutr. 2002 Oct;76(4):834-44. PMID: 12324298.

H-6
69. Laivuori H, Hovatta O, Viinikka L, et al. Dietary supplementation with primrose oil or fish 

oil does not change urinary excretion of prostacyclin and thromboxane metabolites in preeclamptic women. Prostaglandins Leukotrienes & Essential Fatty Acids. 1993 9/1993;49(3):691-

4.

70. Lapillonne A, Brossard N, Claris O, et al. Erythrocyte fatty acid composition in term infants 

fed human milk or a formula enriched with a low eicosapentanoic acid fish oil for 4 months. Eur 

J Pediatr. 2000 Jan-Feb;159(1-2):49-53. PMID: 10653329.

71. Lapillonne A, JC P, V C, et al. Supplementation of preterm formulas (PTF) with a low EPA 

fish oil: Effect on polyunsaturated fatty acids(PUFAS) status and growth. J Pediatr Gastroenterol 

Nutr. 1997 1997;24(4).

72. Leaf A, Gosbell A, McKenzie L, et al. Long chain polyunsaturated fatty acids and visual 

function in preterm infants. Early Hum Dev. 1996 7/5/1996;45(1-2):35-53.

73. Lim M, Antonson D, Clandinin M, et al. Formulas with docosahexaenoic acid (DHA) and 

arachidonic acid (ARA) for low-birth weight infants (LBW) are safe. Pediatr Res; 2002. p. 319a.

74. Lucas A, Stafford M, Morley R, et al. Efficacy and safety of long-chain polyunsaturated 

fatty acid supplementation of infant-formula milk: a randomised trial.[comment]. Lancet. 1999 

12/4/1999;354(9194):1948-54.

75. Makrides M, Neumann M, Simmer K, et al. Are long-chain polyunsaturated fatty acids 

essential nutrients in infancy?[comment]. Lancet. 1995 6/10/1995;345(8963):1463-8.

76. Makrides M, Neumann MA, Gibson RA. Perinatal characteristics may influence the 

outcome of visual acuity. Lipids. 2001 Sep;36(9):897-900. PMID: 11724461.

77. Makrides M, Neumann MA, Jeffrey B, et al. A randomized trial of different ratios of linoleic 

to alpha-linolenic acid in the diet of term infants: effects on visual function and growth. Am J 

Clin Nutr. 2000 Jan;71(1):120-9. PMID: 10617956.

78. Makrides M, Neumann MA, Simmer K, et al. Dietary long-chain polyunsaturated fatty acids 

do not influence growth of term infants: A randomized clinical trial. Pediatrics. 1999 

9/1999;104(3 Pt 1):468-75.

79. Makrides M, Neumann MA, Simmer K, et al. A critical appraisal of the role of dietary longchain polyunsaturated fatty acids on neural indices of term infants: a randomized, controlled 

trial. Pediatrics. 2000 Jan;105(1 Pt 1):32-8. PMID: 10617701.

80. Makrides M, Simmer K, Goggin M, et al. Erythrocyte docosahexaenoic acid correlates with 

the visual response of healthy, term infants. Pediatr Res. 1993 4/1993;33(4 Pt 1):425-7.

H-7
81. Malcolm CA, Hamilton R, McCulloch DL, et al. Scotopic electroretinogram in term infants 

born of mothers supplemented with docosahexaenoic acid during pregnancy. Invest Ophthalmol 

Vis Sci. 2003 Aug;44(8):3685-91. PMID: 12882824.

82. Martinez FE, Santos MMd, Sieber VM, et al. Growth and nitrogen balance in preterm 

infants fed formula with long chain polyunsaturated fatty acids. Nutr Res. 1999 

1999;19(10):1497-505.

83. Matorras R, Perteagudo L, Nieto A, et al. Intrauterine growth retardation and plasma fatty 

acids in the mother and the fetus. Eur J Obstet Gynecol Reprod Biol. 1994 12/1994;57(3):189-

93.

84. McClead REJ, Meng HC, Gregory SA, et al. Comparison of the clinical and biochemical 

effect of increased alpha-linolenic acid in a safflower oil intravenous fat emulsion. J Pediatr 

Gastroenterol Nutr. 1985 1985;4(2):234-9.

85. Morris G, Moorcraft J, Mountjoy A, et al. A novel infant formula milk with added longchain polyunsaturated fatty acids from single-cell sources: a study of growth, satisfaction and 

health. Eur J Clin Nutr. 2000 Dec;54(12):883-6. PMID: 11114686.

86. O'Connor DL, Hall R, Adamkin D, et al. Growth and development in preterm infants fed 

long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Pediatrics. 

2001 Aug;108(2):359-71. PMID: 11483801.

87. O'Connor DL, Jacobs J, Hall R, et al. Growth and development of premature infants fed 

predominantly human milk, predominantly premature infant formula, or a combination of human 

milk and premature formula. J Pediatr Gastroenterol Nutr. 2003 Oct;37(4):437-46. PMID: 

14508214.

88. Olsen SF, Secher NJ, Tabor A, et al. Randomised clinical trials of fish oil supplementation 

in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. BJOG. 2000 

Mar;107(3):382-95. PMID: 10740336.

89. Olsen SF, Soorensen JD, Secher NJ, et al. [Fish oil supplementation and duration of 

pregnancy. A randomized controlled trial]. [Danish]. Ugeskr Laeger. 1994 

2/28/1994;156(9):1302-7.

90. Olsen SF, Sorensen JD, Secher NJ, et al. Randomised controlled trial of effect of fish-oil 

supplementation on pregnancy duration.[comment]. Lancet. 1992 4/25/1992;339(8800):1003-7.

91. Onwude JL, Lilford RJ, Hjartardottir H, et al. A randomised double blind placebo controlled 

trial of fish oil in high risk pregnancy. Br J Obstet Gynaecol. 1995 2/1995;102(2):95-100.

92. Ponder DL, Innis SM, Benson JD, et al. Docosahexaenoic acid status of term infants fed 

breast milk or infant formula containing soy oil or corn oil. Pediatr Res. 1992 1992;32(6):683-8.

H-8
93. Reece MS, McGregor JA, Allen KG, et al. Maternal and perinatal long-chain fatty acids: 

possible roles in preterm birth.[comment]. Am J Obstet Gynecol. 1997 4/1997;176(4):907-14.

94. Rocquelin G, Tapsoba S, Kiffer J, et al. Human milk fatty acids and growth of infants in 

Brazzaville (The Congo) and Ouagadougou (Burkina Faso). Public Health Nutr. 2003 

May;6(3):241-8. PMID: 12740073.

95. Rump P, Mensink RP, Kester AD, et al. Essential fatty acid composition of plasma 

phospholipids and birth weight: a study in term neonates. Am J Clin Nutr. 2001 Apr;73(4):797-

806. PMID: 11273856.

96. Salvig JD, Olsen SF, Secher NJ. Effects of fish oil supplementation in late pregnancy on 

blood pressure: a randomised controlled trial. Br J Obstet Gynaecol. 1996 6/1996;103(6):529-33.

97. Scott DT, Janowsky JS, Carroll RE, et al. Formula supplementation with long-chain 

polyunsaturated fatty acids: are there developmental benefits? Pediatrics. 1998 

11/1998;102(5):E59.

98. Shouk TA, Omar MN, Fayed ST. Essential fatty acids profile and lipid peroxides in severe 

pre-eclampsia. Ann Clin Biochem. 1999 1/1999;36(Pt 1):62-5.

99. Smuts CM, Borod E, Peeples JM, et al. High-DHA eggs: feasibility as a means to enhance 

circulating DHA in mother and infant. Lipids. 2003 Apr;38(4):407-14. PMID: 12848286.

100. Smuts CM, Huang M, Mundy D, et al. A randomized trial of docosahexaenoic acid 

supplementation during the third trimester of pregnancy. Obstet Gynecol. 2003 Mar;101(3):469-

79. PMID: 12636950.

101. Uauy R, Hoffman DR, Birch EE, et al. Safety and efficacy of omega-3 fatty acids in the 

nutrition of very low birth weight infants: soy oil and marine oil supplementation of formula. J 

Pediatr. 1994 4/1994;124(4):612-20.

102. Uauy RD, Birch DG, Birch EE, et al. Effect of dietary omega-3 fatty acids on retinal 

function of very-low-birth-weight neonates. Pediatr Res. 1990 11/1990;28(5):485-92.

103. van Wezel-Meijler G, van der Knaap MS, Huisman J, et al. Dietary supplementation of

long-chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation. Acta 

Paediatr. 2002;91(9):942-50. PMID: 12412870.

104. Vanderhoof J, Gross S, Hegvi T, et al. A new arachidonic acid (ARA) and docosahexanoic 

acid (DHA) supplemented preterm formula: growth and safety assessment. Pediatr Res. 1997 

1997:242A , #1440.

105. Vanderhoof J, Gross S, Hegyi T. A multicenter long-term safety and efficacy trial of 

preterm formula supplemented with long-chain polyunsaturated fatty acids. J Pediatr 

Gastroenterol Nutr. 2000 Aug;31(2):121-7. PMID: 10941962.

H-9
106. Vanderhoof J, Gross S, Hegyi T, et al. Evaluation of a long-chain polyunsaturated fatty 

acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 

weeks postconceptional age. J Pediatr Gastroenterol Nutr. 1999 1999;29(3):318-26.

107. Vilbergsson G, Samsioe G, Wennergren M, et al. Essential fatty acids in pregnancies 

complicated by intrauterine growth retardation. Int J Gynaecol Obstet. 1991 12/1991;36(4):277-

86.

108. Vilbergsson G, Wennergren M, Samsioe G, et al. Essential fatty acid status is altered in 

pregnancies complicated by intrauterine growth retardation. World Rev Nutr Diet. 1994 

1994;76:105-9.

109. Voigt RG, Jensen CL, Fraley JK, et al. Relationship between omega3 long-chain 

polyunsaturated fatty acid status during early infancy and neurodevelopmental status at 1 year of 

age. J Hum Nutr Diet. 2002 Apr;15(2):111-20. PMID: 11972740.

110. Wang YP, Kay HH, Killam AP. Decreased levels of polyunsaturated fatty acids in 

preeclampsia.[comment]. Am J Obstet Gynecol. 1991 3/1991;164(3):812-8.

111. Werkman SH, Carlson SE. A randomized trial of visual attention of preterm infants fed 

docosahexaenoic acid until nine months. Lipids. 1996 1/1996;31(1):91-7.

112. Willatts P, Forsyth JS, DiModugno MK, et al. Influence of long-chain polyunsaturated 

fatty acids on infant cognitive function. Lipids. 1998;33(10):973-80.

113. Willatts P, Forsyth JS, DiModugno MK, et al. Effect of long-chain polyunsaturated fatty 

acids in infant formula on problem solving at 10 months of age. Lancet British edition. 

1998;352(9129):688-91.

114. Williams C, Birch EE, Emmett PM, et al. Stereoacuity at age 3.5 y in children born fullterm is associated with prenatal and postnatal dietary factors: a report from a population-based 

cohort study. Am J Clin Nutr. 2001 Feb;73(2):316-22. PMID: 11157330.

115. Woltil HA, van Beusekom CM, Okken-Beukens M, et al. Development of low-birthweight 

infants at 19 months of age correlates with early intake and status of long-chain polyunsaturated 

fatty acids. Prostaglandins Leukotrienes & Essential Fatty Acids. 1999 10/1999;61(4):235-41.

116. Woltil HA, van Beusekom CM, Schaafsma A, et al. Long-chain polyunsaturated fatty acid 

status and early growth of low birth weight infants. Eur J Pediatr. 1998 2/1998;157(2):146-52.

117. Xiang M, Alfven G, Blennow M, et al. Long-chain polyunsaturated fatty acids in human 

milk and brain growth during early infancy. Acta Paediatr. 2000 Feb;89(2):142-7. PMID: 

10709881.

H-10
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Miles, 2011 NR UK Healthy pregnant women 107 Salmon vs Control Trial randomized parallel birth birth weight SMD 0.042469915 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 27 DHA+ARA (EF) vs Control Trial randomized parallel 12 months (corrected age) head circumference SMD 0 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 28 DHA+ARA (FF) vs Control Trial randomized parallel 12 months (corrected age) head circumference SMD -0.133630619 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 35 DHA+ARA (FF) vs Control Trial randomized parallel 35 weeks (corrected age) head circumference SMD -0.128260076 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 36 DHA+ARA (EF) vs Control Trial randomized parallel 35 weeks (corrected age) head circumference SMD -0.372677982 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 28 DHA+ARA (EF) vs Control Trial randomized parallel 4 months (corrected age) head circumference SMD 0.075592898 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 30 DHA+ARA (FF) vs Control Trial randomized parallel 4 months (corrected age) head circumference SMD -0.393858671 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 36 DHA+ARA (FF) vs Control Trial randomized parallel 40 weeks (corrected age) head circumference SMD 5.202124119 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 35 DHA+ARA (EF) vs Control Trial randomized parallel 40 weeks (corrected age) head circumference SMD 7.646153927 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 27 DHA+ARA (EF) vs Control Trial randomized parallel 12 months (corrected age) length SMD 0.763140142 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 28 DHA+ARA (FF) vs Control Trial randomized parallel 12 months (corrected age) length SMD 0.386043996 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 36 DHA+ARA (EF) vs Control Trial randomized parallel 35 weeks (corrected age) length SMD 0.094280906 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 35 DHA+ARA (FF) vs Control Trial randomized parallel 35 weeks (corrected age) length SMD 0.079324059 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 28 DHA+ARA (EF) vs Control Trial randomized parallel 4 months (corrected age) length SMD 0.381801784 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 30 DHA+ARA (FF) vs Control Trial randomized parallel 4 months (corrected age) length SMD -0.359404892 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 35 DHA+ARA (EF) vs Control Trial randomized parallel 40 weeks (corrected age) length SMD 0.038912445 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 36 DHA+ARA (FF) vs Control Trial randomized parallel 40 weeks (corrected age) length SMD 0.067343503 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 27 DHA+ARA (EF) vs Control Trial randomized parallel 12 months (corrected age) weight SMD 0.157750756 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 28 DHA+ARA (FF) vs Control Trial randomized parallel 12 months (corrected age) weight SMD -0.325969994 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 36 DHA+ARA (EF) vs Control Trial randomized parallel 35 weeks (corrected age) weight SMD -0.124950208 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 35 DHA+ARA (FF) vs Control Trial randomized parallel 35 weeks (corrected age) weight SMD -0.111058012 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 28 DHA+ARA (EF) vs Control Trial randomized parallel 4 months (corrected age) weight SMD -0.112528399 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 30 DHA+ARA (FF) vs Control Trial randomized parallel 4 months (corrected age) weight SMD -0.083675906 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 36 DHA+ARA (FF) vs Control Trial randomized parallel 40 weeks (corrected age) weight SMD -0.220495641 Secondary

Groh-Wargo, 2005 sept 1997 - Sept 1998 US Preterm infants 35 DHA+ARA (EF) vs Control Trial randomized parallel 40 weeks (corrected age) weight SMD -0.282478869 Secondary

Sala-Vila, 2004 nr Spain Healthy infants 23

 

(HM) Trial randomized parallel 3 months head circumference SMD 0.027388405 Unspecified

Sala-Vila, 2004 nr Spain Healthy infants 23

 

Milk (HM) Trial randomized parallel 3 months head circumference SMD 0.396647155 Unspecified

Sala-Vila, 2004 nr Spain Healthy infants 23

 

Milk (HM) Trial randomized parallel 3 months length SMD 0.027344823 Unspecified

Sala-Vila, 2004 nr Spain Healthy infants 23

 

(HM) Trial randomized parallel 3 months length SMD 0.029529136 Unspecified

Sala-Vila, 2004 nr Spain Healthy infants 23

 

(HM) Trial randomized parallel 3 months weight SMD 0.076811403 Unspecified

Sala-Vila, 2004 nr Spain Healthy infants 23

 

Milk (HM) Trial randomized parallel 3 months weight SMD 0.011815406 Unspecified

Hoffman, 2008 nr US Healthy infants 179 DHA + ARA vs Control Trial randomized parallel 14-120d head circumference SMD 0 Secondary

Hoffman, 2008 nr US Healthy infants 179 DHA + ARA vs Control Trial randomized parallel 14-120d length SMD 0 Secondary

Hoffman, 2008 nr US Healthy infants 179 DHA + ARA vs Control Trial randomized parallel 14-120d weight SMD -0.07062757 Secondary

Doornbos, 2009 Not reported Netherlands Healthy pregnant women

 g p 

4.44 (3.00–6.92); 

 g p 

group Trial randomized parallel 36 weeks pregnant

g 

Depression Scale (EPDS) NC Secondary

Doornbos, 2009 Not reported Netherlands Healthy pregnant women

 

4.44 (3.00–6.92); DHA group vs Control group Trial randomized parallel 36 weeks pregnant

 

Depression Scale (EPDS) NC Secondary

Doornbos, 2009 Not reported Netherlands Healthy pregnant women

 

4.44 (3.00–6.92); 

 

group Trial randomized parallel 6 weeks post-partum

 

Depression Scale (EPDS) NC Secondary

Doornbos, 2009 Not reported Netherlands Healthy pregnant women

 g p 

4.44 (3.00–6.92); DHA group vs Control group Trial randomized parallel 6 weeks post-partum

g 

Depression Scale (EPDS) NC Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 12 weeks

 

definitely abnormal OR 0.387387395 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 12 weeks

 

definitely abnormal OR NC Secondary

van Goor, 2010

 

until December 2006 Netherlands

y p g 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 2 weeks

g 

definitely abnormal OR 3.405405521 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 2 weeks

 

definitely abnormal OR 3.486486435 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 12 weeks

 

mildly abnormal OR 0.513333321 Secondary

van Goor, 2010

 

until December 2006 Netherlands

y p g 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 12 weeks

g 

mildly abnormal OR 0.894841254 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 2 weeks

 

mildly abnormal OR 0.83518517 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 2 weeks

 

mildly abnormal OR 0.641666651 Secondary

van Goor, 2010

 

until December 2006 Netherlands

y p g 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 12 weeks

g 

normal optimal OR 0.439024389 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 12 weeks

 

normal optimal OR 0.172093019 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 2 weeks

 

normal optimal OR 0.286821693 Secondary

van Goor, 2010

 

until December 2006 Netherlands

y p g 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 2 weeks

g 

normal optimal OR 0.878048778 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 12 weeks

 

normal suboptimal OR 0.596273303 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 12 weeks

 

normal suboptimal OR 0.992576897 Secondary

van Goor, 2010

 

until December 2006 Netherlands

y p g 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 2 weeks

g 

normal suboptimal OR 0.766917288 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 2 weeks

 

normal suboptimal OR 1.016688108 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 2 weeks

 

classification: number OR NC Secondary

van Goor, 2010

 

until December 2006 Netherlands

y p g 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 2 weeks

 g 

classification: number OR NC Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 2 weeks

 

classification: number mildly OR 1.361111164 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 2 weeks

 

classification: number mildly OR 0.996527791 Secondary

van Goor, 2010

 

until December 2006 Netherlands

y p g 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel 2 weeks

 g 

classification: number normal OR 1.034843206 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel 2 weeks

 

classification: number normal OR 1.071428537 Secondary

van Goor, 2010

 

until December 2006 Netherlands

 

Breast-feeding women 78 DHA group vs placebo Trial randomized parallel birth gestational age birth SMD 0 Secondary

van Goor, 2010

 

until December 2006 Netherlands

y p g 

Breast-feeding women 77 DHA + AA group vs placebo Trial randomized parallel birth gestational age birth SMD 0 Secondary

Tofail, 2006 enrollment January to March 2000 Bangladesh

 

pregnant women 249 DHA supplement vs placebo Trial randomized parallel birth birth weight SMD 0 Unspecified

Tofail, 2006 enrollment January to March 2000 Bangladesh

 

pregnant women 249 DHA supplement vs placebo Trial randomized parallel 10 months

 

Development (Mental SMD 0.12656565 Unspecified

Tofail, 2006 enrollment January to March 2000 Bangladesh

y y 

pregnant women Trial randomized parallel

y y 

Development (Psychomotor Unspecified

Tofail, 2006 enrollment January to March 2000 Bangladesh

 

pregnant women 249 DHA supplement vs placebo Trial randomized parallel 10 months

 

Development (Psychomotor SMD 0.114185289 Unspecified

Tofail, 2006 enrollment January to March 2000 Bangladesh

 

pregnant women 249 DHA supplement vs placebo Trial randomized parallel 10 months head circumference SMD -0.142857149 Unspecified

Peat, 2004 2000-2003 Australia

g 

unborn children were at 526

 g p 

Placebo group

 

design 3 years any eczema OR 1.226132035 Secondary

Peat, 2004 2000-2003 Australia

 

unborn children were at 526

 

Placebo group

 

design 3 years any asthma OR 1.040522456 Primary

Peat, 2004 2000-2003 Australia

 

unborn children were at 526

 

Placebo group

 

design 3 years any cough OR 1.226132035 Primary

CAUSALITY TABLE
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Peat, 2004 2000-2003 Australia

 

unborn children were at 526

 

Placebo group

 

design 3 years any wheeze OR 1.040522456 Secondary

Birch, 2007 1993-1999 US

 

women whose unborn 35 DHA vs Control Trial randomized parallel 4 years

 

Primary Scale of Intelligence: SMD 0.36454019 Secondary

Birch, 2007 1993-1999 US

y g 

women whose unborn 51 DHA+ARA vs Control Trial randomized parallel 4 years

 

Primary Scale of Intelligence: SMD 0.418064356 Secondary

Birch, 2007 1993-1999 US

 

women whose unborn 35 DHA vs Control Trial randomized parallel 4 years

 

Primary Scale of Intelligence: SMD 0.290230393 Secondary

Birch, 2007 1993-1999 US

 

women whose unborn 51 DHA+ARA vs Control Trial randomized parallel 4 years

 

Primary Scale of Intelligence: SMD 0.267109424 Secondary

Birch, 2007 1993-1999 US

y g 

women whose unborn 51 DHA+ARA vs Control Trial randomized parallel 4 years

 

Primary Scale of Intelligence: SMD 0.386548072 Secondary

Birch, 2007 1993-1999 US

 

women whose unborn 35 DHA vs Control Trial randomized parallel 4 years

 

Primary Scale of Intelligence: SMD 0.281229317 Secondary

Birch, 2007 1993-1999 US

 

women whose unborn 36 DHA+ARA vs Control Trial randomized parallel 4 years Visual acuity Left Eye SMD 0.371920019 Primary

Birch, 2007 1993-1999 US

y g 

women whose unborn 35 DHA vs Control Trial randomized parallel 4 years Visual acuity Left Eye SMD 0.508636236 Primary

Birch, 2007 1993-1999 US

 

women whose unborn 35 DHA vs Control Trial randomized parallel 4 years Visual acuity Right Eye SMD 0.606300414 Primary

Birch, 2007 1993-1999 US

 

women whose unborn 36 DHA+ARA vs Control Trial randomized parallel 4 years Visual acuity Right Eye SMD 0.495647401 Primary

Birch, 2005 Not reported US Healthy infants Trial randomized parallel Primary

Birch, 2005 Not reported US Healthy infants Trial randomized parallel Secondary 

2011

 

October 2005 Norway Preterm infants intervention[64.2 Trial randomized parallel

 

Index Secondary g 

2011

 

October 2005 Norway Preterm infants 82 intervention[64.2 DHA + AA group vs Placebo Trial randomized parallel 20 months

y y p 

Index (MDI) SMD 0.049930181 Secondary

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months

 

average time/look SMD 1.399999976 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

average time/look SMD 2.166666746 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

average time/look SMD 3.073954344 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months

 

looks to familiar SMD 3.625 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

looks to familiar SMD 3.299999952 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

looks to familiar SMD 3.555555582 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months

 

looks to novel SMD 3 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

looks to novel SMD 3.799999952 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

looks to novel SMD 3.637486458 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months

 

novel time SMD 3.279394627 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

novel time SMD 0.443887442 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

novel time SMD 0 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months

 

time to familiar SMD -3.526503086 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

time to familiar SMD 0 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

time to familiar SMD -0.105032891 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months

 

time to novel SMD 0.583333314 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

time to novel SMD -0.400000006 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

time to novel SMD 0.230769232 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 12 months

g g 

time/familiar look SMD -1.199999928 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

time/familiar look SMD 1.833333373 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

time/familiar look SMD 2.350671053 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months

 

time/novel look SMD 2.285714388 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

time/novel look SMD 1.760074019 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

time/novel look SMD 2.392242908 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 12 months

 

total looks SMD 3.925470352 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

total looks SMD 4.235293865 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

total looks SMD 4.466666698 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months

 

total time SMD -1.642857194 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months

 

total time SMD -0.342566878 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months

g g 

total time SMD 0.128901288 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months number of total looks SMD 0.303032428 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months number of total looks SMD 1.803665161 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months number of total looks SMD 1.611111164 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 12 months time/total looks SMD -0.833333373 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

 

and pre-term infant formulas Trial randomized parallel 6.5 months time/total looks SMD -2.259340525 Unspecified

Werkman, 1996 1987-1990 US Preterm infants 67

pp 

and pre-term infant formulas Trial randomized parallel 9 months time/total looks SMD -1.378915668 Unspecified

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

 

time/look SMD 2.011306286 Secondary

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

 

looks to familiar SMD 2.974162817 Secondary

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

g g 

looks to novel SMD 1.541632175 Secondary

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

 

novel time SMD 2.401223183 Secondary

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

 

time to familiar SMD -2.538865328 Secondary

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

g g 

time to novel SMD 1.098263025 Secondary

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

 

time/familiar look SMD 0.953569651 Secondary

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

 

time/novel look SMD 2.811267614 Secondary

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

g g 

total looks SMD 2.370370388 Secondary

Carlson, 1996 NR (<1995) US Preterm infants 27 DHA supplement vs Placebo Trial randomized parallel 12 months

 

total time SMD -0.4828749 Secondary

2015 2005-2012 Mexico

 

infants 802 DHA (algal) vs Placebo Trial randomized parallel 5 years bmi-for-age z score SMD 0 Primary

2015 2005-2012 Mexico

y 

infants 802 DHA (algal) vs Placebo Trial randomized parallel 5 years height SMD -0.022471754 Primary

2015 2005-2012 Mexico

 

infants 802 DHA (algal) vs Placebo Trial randomized parallel 5 years height-for-age z-score SMD 0 Primary

2015 2005-2012 Mexico

 

infants 802 DHA (algal) vs Placebo Trial randomized parallel 5 years weight SMD -0.033333335 Primary

2015 2005-2012 Mexico

y 

infants 802 DHA (algal) vs Placebo Trial randomized parallel 5 years weight-for-age z-score SMD -0.090909086 Primary

Currie, 2015 2003-2011 US Healthy infants 69 DHA < ARA vs Placebo Trial randomized parallel 2-6 years BMI SMD 0.1107613 Secondary

Currie, 2015 2003-2011 US Healthy infants 69 DHA < ARA vs Placebo Trial randomized parallel 2-6 years BMI-for-age percentile SMD 0.292358667 Secondary

Currie, 2015 2003-2011 US Healthy infants 69 DHA < ARA vs Placebo Trial randomized parallel 2-6 years Length-for-age percentile SMD 0.518910348 Secondary

Currie, 2015 2003-2011 US Healthy infants 69 DHA < ARA vs Placebo Trial randomized parallel birth-18 months Length-for-age percentile SMD 0.511804104 Secondary

Currie, 2015 2003-2011 US Healthy infants 69 DHA < ARA vs Placebo Trial randomized parallel 2-6 years Weight-for-age percentile SMD 0.246899456 Secondary

Currie, 2015 2003-2011 US Healthy infants 69 DHA < ARA vs Placebo Trial randomized parallel birth-18 months Weight-for-age percentile SMD 0.246220678 Secondary
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

ADHD t score (total score) SMD -0.064502522 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 583 High DHA vs standard DHA Trial randomized parallel 7 years

 

reported) OR 0.743847847 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 583 High DHA vs standard DHA Trial randomized parallel 7 years

 p 

disorder OR 0.860738277

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

of Intelligence: Full Scale IQ SMD -0.013818421 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

of Intelligence: Performance SMD 0 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

of Intelligence: Verbal IQ SMD -0.053154435 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

Test: Delayed recall raw score SMD 0.030764695 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

Test: Delayed recognition SMD 0.071062736 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

y y g 

Test: Total (trials 1-5) correct SMD -0.034950692 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

Test: Total intrusions SMD -0.106173202 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

Test: Total repetitions SMD 0.069810607 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

y y g 

Test: Trial 1 correct words SMD 0.050000001 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

skills: figure ground standard SMD -0.049178504 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 

skills: visual closure standard SMD -0.109523952 Secondary

Collins, 2015 2001-2013 Australia Preterm infants 604 High DHA vs standard DHA Trial randomized parallel 7 years

 p p 

skills: visual discrimination SMD 0 Secondary

Brew, 2015 September 1997 to 1999-2008 Australia Healthy infants

 

fish oil, daily, 

 

(DHA+EPA+DPA+A omega-placebo Trial randomized parallel 8-9 years

 

Program Literacy and MD -25.39999962 Secondary

Brew, 2015 September 1997 to 1999-2008 Australia Healthy infants

 

fish oil, daily, 

 

(DHA+EPA+DPA+A omega-placebo Trial randomized parallel 10-11 years

 

Program Literacy and MD -13.69999981 Secondary

Brew, 2015 September 1997 to 1999-2008 Australia Healthy infants

 g 

fish oil, daily, 

 

(DHA+EPA+DPA+A omega-placebo Trial randomized parallel 12-13 years

 

Program Literacy and MD -11.69999981 Secondary

Brew, 2015 September 1997 to 1999-2008 Australia Healthy infants

 

fish oil, daily, 

 

(DHA+EPA+DPA+A omega-placebo Trial randomized parallel 14-15 years

 

Program Literacy and MD -24.10000038 Secondary

Brew, 2015 September 1997 to 1999-2008 Australia Healthy infants

 

fish oil, daily, 

 

(DHA+EPA+DPA+A omega-placebo Trial randomized parallel 14-15 years

 

Program Literacy and MD -19.89999962 Secondary

Brew, 2015 September 1997 to 1999-2008 Australia Healthy infants

 g 

fish oil, daily, 

 

(DHA+EPA+DPA+A omega-placebo Trial randomized parallel 8-9 years

 

Program Literacy and MD -27.03000069 Secondary

Brew, 2015 September 1997 to 1999-2008 Australia Healthy infants

 

fish oil, daily, 

 

(DHA+EPA+DPA+A omega-placebo Trial randomized parallel 10-11 years

 

Program Literacy and MD -3.200000048 Secondary

Brew, 2015 September 1997 to 1999-2008 Australia Healthy infants

 

fish oil, daily, 

 

(DHA+EPA+DPA+A omega-placebo Trial randomized parallel 12-13 years

 

Program Literacy and MD -7 Secondary

Min, 2014 Jan 2008 - Dec 2011 UK

y p g 

Pregnant women with type 2 59

 y 

Placebo, healthy women Trial randomized parallel birth birthweight <1500g OR 0.392857134 Secondary

Min, 2014 Jan 2008 - Dec 2011 UK

 

Pregnant women with type 2 59

 

Placebo, healthy women Trial randomized parallel birth birthweight <2500g OR 0.888888896 Secondary

Min, 2014 Jan 2008 - Dec 2011 UK

 

Pregnant women with type 2 

 

Placebo, healthy women Trial randomized parallel birth gestational age birth NC Secondary

Min, 2014 Jan 2008 - Dec 2011 UK

y p g 

Pregnant women with type 2 59

 y 

Placebo, healthy women Trial randomized parallel birth preterm birth OR 1.185185194 Secondary

Judge, 2014 US Healthy pregnant women 42 DHA group vs Placebo Trial randomized parallel 2 weeks

 

Screening Scale (PDSS) total SMD 0.437067092 Primary

Judge, 2014 US Healthy pregnant women 42 DHA group vs Placebo Trial randomized parallel 3 months

 

Screening Scale (PDSS) total SMD -0.243067458 Primary

Judge, 2014 US Healthy pregnant women 42 DHA group vs Placebo Trial randomized parallel 6 months

p p 

Screening Scale (PDSS) total SMD 0.184672386 Primary

Judge, 2014 US Healthy pregnant women 42 DHA group vs Placebo Trial randomized parallel 6 weeks

 

Screening Scale (PDSS) total SMD -0.01572898 Primary

Almaas, 2015 2003-2014 Norway

 

weight infants 97 Intervention vs Control Trial randomized parallel 8 years

 

of Intelligence: Full Scale IQ SMD -0.126807705 Secondary

Almaas, 2015 2003-2014 Norway

 

weight infants 97 Intervention vs Control Trial randomized parallel 8 years

 

of Intelligence: Verbal IQ SMD -0.130057693 Secondary

Almaas, 2015 2003-2014 Norway

 

weight infants 97 Intervention vs Control Trial randomized parallel 8 years

 

of Intelligence: performance SMD -0.066196062 Secondary

Ramakrishnan, 2015 2005-2009 Mexico Healthy pregnant women 730

 

study ref 3364 Intervention vs Control Trial randomized parallel 18 months

 

Index SMD -0.089780308 Primary

Ramakrishnan, 2015 2005-2009 Mexico Healthy pregnant women 730

 g 

study ref 3364 Intervention vs Control Trial randomized parallel birth IUGR OR 0.923076928 Secondary

Ramakrishnan, 2015 2005-2009 Mexico Healthy pregnant women 730

 

study ref 3364 Intervention vs Control Trial randomized parallel 18 months Bayley PDI SMD -0.032048468 Primary

Meldrum, 2015

 

followup Australia

 

pregnant women 50 Fish oil vs Placebo Trial randomized parallel 12 years

 

for Children IV SMD 0.090011589 Secondary

Meldrum, 2015

 y 

followup Australia

y y 

pregnant women 47 Fish oil vs Placebo Trial randomized parallel 12 years

y p 

Test of Visual-Motor SMD 0.126974538 Secondary

Willatts, 2013 1992 Italy, UK, Belgium Healthy infants 147

 

LC-PUFA Trial randomized parallel 6 years

 

Primary Scale of Intelligence- SMD -0.186616465 Secondary

Willatts, 2013 1992 Italy, UK, Belgium Healthy infants 147

 

LC-PUFA Trial randomized parallel 6 year

 

Primary Scale of Intelligence: SMD -0.186616465 Secondary

Willatts, 2013 1992 Italy, UK, Belgium Healthy infants 147

 

LC-PUFA Trial randomized parallel 6 year

 

Primary Scale of Intelligence: SMD -0.11632973 Secondary

Willatts, 2013 1992 Italy, UK, Belgium Healthy infants 147

 

LC-PUFA Trial randomized parallel 6 year

 

Primary Scale of Intelligence: SMD -0.171192899 Secondary

Colombo, 2013 09/03/03-09/25/05 US Healthy infants 39 0.32% vs 0.00% Trial randomized parallel 18 months Communicative Development SMD -0.208973438

Colombo, 2013 09/03/03-09/25/05 US Healthy infants 36 0.64% vs 0.00% Trial randomized parallel 18 months Communicative Development SMD 0.306412935

Colombo, 2013 09/03/03-09/25/05 US Healthy infants 42 0.96% vs 0.00% Trial randomized parallel 18 months Communicative Development SMD 0.025472023

Colombo, 2013 09/03/03-09/25/05 US Healthy infants 84

 

0.32-0.96% vs 0.00% Trial randomized parallel 6 year

 

Test of Intelligence: Full Scale SMD 0.365765303 Secondary

Colombo, 2013 09/03/03-09/25/05 US Healthy infants 36 0.64% vs 0.00% Trial randomized parallel 18 months Bayley PDI SMD -0.094280906 Secondary

Colombo, 2013 09/03/03-09/25/05 US Healthy infants 42 0.96% vs 0.00% Trial randomized parallel 18 months Bayley PDI SMD -0.043183353 Secondary

Colombo, 2013 09/03/03-09/25/05 US Healthy infants 39 0.32% vs 0.00% Trial randomized parallel 18 months Bayley PDI SMD -0.090301 Secondary

Colombo, 2013 09/03/03-09/25/05 US Healthy infants Trial randomized parallel Communicative Development Secondary

Dunstan, 2008 2000-2003 Australia

 

women with allergies 72

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel birth birth weight SMD 0.202062249 Secondary

Dunstan, 2008 2000-2003 Australia

 

women with allergies 72

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 2.5 years

 

Scales: Eye and hand SMD 0.554988265 Secondary

Dunstan, 2008 2000-2003 Australia

y g 

women with allergies 72

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 2.5 years

 p 

Scales: Performance SMD 0.384841085 Secondary

Dunstan, 2008 2000-2003 Australia

 

women with allergies 72

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 2.5 years

 

Scales: Practical reasoning SMD 0.047382046 Secondary

Dunstan, 2008 2000-2003 Australia

 

women with allergies 72

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 2.5 years

 

Scales: Speech and hearing SMD 0.160580263 Secondary

Dunstan, 2008 2000-2003 Australia

y g 

women with allergies 72

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 2.5 years

 p 

Scales: General quotient SMD 0.361256063 Secondary

Dunstan, 2008 2000-2003 Australia

 

women with allergies 72

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 2.5 years

 

Scales: Personal social SMD 0.256749153 Secondary

Dunstan, 2008 2000-2003 Australia

 

women with allergies 72

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 2.5 years

 

Scales:Locomotor SMD 0.370407909 Secondary

Dunstan, 2008 2000-2003 Australia

y g 

women with allergies 72

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel birth gestational age SMD 0.1875 Secondary

Dunstan, 2008 2000-2003 Australia

 

women with allergies 64

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 30 months head circumference SMD -0.24137193 Secondary

Dunstan, 2008 2000-2003 Australia

 

women with allergies 64

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 30 months length SMD 0.117093936 Secondary

Dunstan, 2008 2000-2003 Australia

y g 

women with allergies 64

 

erythrocyte (as % Fish oil vs Control Trial randomized parallel 30 months weight SMD 0.200000003 Secondary

Drover, 2011 2003-2006 US Healthy infants 57

 

(Control) Trial randomized parallel 18 months

 

Development II (Mental SMD 0.569579899 Secondary

Drover, 2011 2003-2006 US Healthy infants 60

 

(Control) Trial randomized parallel 18 months

 

Development II (Mental SMD 0.506325007 Secondary

Drover, 2011 2003-2006 US Healthy infants 56

 

(Control) Trial randomized parallel 18 months

y y 

Development II (Mental SMD 0.335613608 Secondary

Courville, 2011 nr US Healthy pregnant women 47

 

intake (mg/d), DHA-FF vs Placebo Trial randomized parallel birth birth weight SMD 0.3114959 Unspecified

Courville, 2011 nr US Healthy pregnant women 47

 

intake (mg/d), DHA-FF vs Placebo Trial randomized parallel birth gestational age SMD 0.433120996 Unspecified

Carlson, 2013 2006.01-2011.10 US Healthy pregnant women 301

y 

intake from 

ppp

DHA (placebo group DHA vs Placebo Trial randomized parallel birth birth weight SMD 0.305268943 Primary

Carlson, 2013 2006.01-2011.10 US Healthy pregnant women 301

 

intake from DHA (placebo group DHA vs Placebo Trial randomized parallel during pregnancy preeclampsia OR 1 Secondary

Carlson, 2013 2006.01-2011.10 US Healthy pregnant women 301

 

intake from DHA (placebo group DHA vs Placebo Trial randomized parallel birth birthweight <1500g OR 11.51608086 Secondary

Carlson, 2013 2006.01-2011.10 US Healthy pregnant women 301

y 

intake from 

ppp

DHA (placebo group DHA vs Placebo Trial randomized parallel birth birthweight <2500g OR 2.307692289 Secondary
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Carlson, 2013 2006.01-2011.10 US Healthy pregnant women 301

 

intake from DHA (placebo group DHA vs Placebo Trial randomized parallel birth gestational age SMD 0.202394068 Primary

Carlson, 2013 2006.01-2011.10 US Healthy pregnant women 301

 

intake from DHA (placebo group DHA vs Placebo Trial randomized parallel birth incidence of premature birth OR 1.134920597 Secondary

Birch, 2010 2003-2006 US Healthy infants Trial randomized parallel Primary

Isaacs, 2011

 

through 1997 with 10-year followup UK Preterm infants 107

 

formula vs control Trial randomized parallel 10 years

 

Children: Attention scaled SMD -0.039157018 Secondary

Isaacs, 2011

 

through 1997 with 10-year followup UK Preterm infants 107

 

formula vs control Trial randomized parallel 10 years

 

Children: Creature counting SMD 0.166753545 Secondary

Isaacs, 2011

 

through 1997 with 10-year followup UK Preterm infants 107

g pp 

formula vs control Trial randomized parallel 10 years

 y y 

Children: Dual-task SMD 0.112603858 Secondary

Isaacs, 2011

 

through 1997 with 10-year followup UK Preterm infants 107

 

formula vs control Trial randomized parallel 10 years

 

Children: Opposite Worlds SMD 0.158926487 Secondary

Isaacs, 2011

 

through 1997 with 10-year followup UK Preterm infants 107

 

formula vs control Trial randomized parallel 10 years

 

Children: Score! Scale scored SMD -0.029411763 Secondary

Isaacs, 2011

 

through 1997 with 10-year followup UK Preterm infants 107

g pp 

formula vs control Trial randomized parallel 10 years

 

of Intelligence: FSIQ SMD 0.188561812 Secondary

Isaacs, 2011

 

through 1997 with 10-year followup UK Preterm infants 107

 

formula vs control Trial randomized parallel 10 years

 

of Intelligence: Performance SMD -0.022280326 Secondary

Isaacs, 2011

 

through 1997 with 10-year followup UK Preterm infants 107

 

formula vs control Trial randomized parallel 10 years

 

of Intelligence: VIQ SMD 0.318237037 Secondary

Agostoni, 2009

 y 

2005; 1-year followup Italy Healthy infants 958 DHA vs placebo Trial randomized parallel varies

g g g 

hands-and-knees crawling SMD 0.079347178 Primary

Agostoni, 2009

 

2005; 1-year followup Italy Healthy infants 1093 DHA vs placebo Trial randomized parallel varies

 

sitting without support SMD 0.357142866 Primary

Agostoni, 2009

 

2005; 1-year followup Italy Healthy infants 1091 DHA vs placebo Trial randomized parallel varies

 

standing alone SMD 0.114615023 Primary

Agostoni, 2009

 y 

2005; 1-year followup Italy Healthy infants 1091 DHA vs placebo Trial randomized parallel varies

g g g 

walking alone SMD 0.133323327 Primary

Pietrantoni, 2014 nr Italy Healthy pregnant women 255 DHA group vs Placebo Trial randomized parallel birth

 

membranes OR 4.095238209 Unspecified

Bergmann, 2012 2000-2009 Germany Healthy infants 115

 

see refid 2803

 

prebiotic Trial randomized parallel 6 yrs BMI SMD 0.145546764 Secondary

Bergmann, 2012 2000-2009 Germany Healthy infants 115

 p y 

see refid 2803

 pp p 

prebiotic Trial randomized parallel 6 yrs head circumference SMD -0.14149338 Secondary

Bergmann, 2012 2000-2009 Germany Healthy infants 115

 

see refid 2803

 

prebiotic Trial randomized parallel 6 yrs height SMD -0.082315855 Secondary

Bergmann, 2012 2000-2009 Germany Healthy infants 115

 

see refid 2803

 

prebiotic Trial randomized parallel 6 yrs weight SMD 0.033643577 Secondary

Lucia Bergmann, 2007 2000-2002 Germany

y y 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel birth birth weight SMD -0.252969831 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel birth gestational age SMD -0.270222873 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 1 month bmi SMD -0.046814039 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

y y 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 21 months bmi SMD -0.290478349 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 3 months bmi SMD 0.178672299 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 1 month head circumference SMD -0.090714887 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

y y 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 21 months head circumference SMD 0.238690883 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 3 months head circumference SMD 0 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 1 month length SMD 0.135425761 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

y y 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 21 months length SMD 0.021943457 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 3 months length SMD -0.037192132 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 1 month weight SMD 0.035049614 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

y y 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 21 months weight SMD -0.3739416 Unspecified

Lucia Bergmann, 2007 2000-2002 Germany

 

pregnant women 117

 

identified fatty acid 

 

minerals Trial randomized parallel 3 months weight SMD 0.081977032 Unspecified

Furuhjelm, 2011 2003-2007 Sweden

 

pregnant women 119 w-3 group vs Placebo Trial randomized parallel 2 years any food reactions OR 2.215384722 Primary

Furuhjelm, 2011 2003-2007 Sweden

y y 

pregnant women 119 w-3 group vs Placebo Trial randomized parallel 2 years any eczema OR 1.586014032 Primary

Furuhjelm, 2011 2003-2007 Sweden

 

pregnant women 119 w-3 group vs Placebo Trial randomized parallel 2 years any asthma OR 0.949450553 Primary

Furuhjelm, 2011 2003-2007 Sweden

 

pregnant women 119 w-3 group vs Placebo Trial randomized parallel 2 years any rhinoconjunctivitis OR 0.830769241 Primary

Makrides, 2010 2005-2008 Australia Healthy pregnant women 2399

 g 

capsules Trial randomized parallel 6 months

 g 

Depression Scale (EPDS) > OR 1.180698156 Primary

Makrides, 2010 2005-2008 Australia Healthy pregnant women 2399

 g 

capsules Trial randomized parallel 6 weeks

 

Depression Scale (EPDS) > OR 1.132153988 Primary

Makrides, 2010 2005-2008 Australia Healthy pregnant women Trial randomized parallel Secondary

Makrides, 2010 2005-2008 Australia Healthy pregnant women 726

 g 

capsules Trial randomized parallel 18 months

y y 

Development III (Cognitive SMD 0.005061553 Primary

Makrides, 2010 2005-2008 Australia Healthy pregnant women 2399

 

capsules Trial randomized parallel birth birthweight <2500g OR 1.530193567 Secondary

Makrides, 2010 2005-2008 Australia Healthy pregnant women

 

capsules Trial randomized parallel birth gestational age NC Secondary

Makrides, 2010 2005-2008 Australia Healthy pregnant women 2399

 g 

capsules Trial randomized parallel birth incidence of premature birth OR 1.307969332 Secondary

Llorente, 2003 <2002 US Breast-feeding women 89

 

saturated 49.7 ± 2.3 omega 3 capsule vs placebo Trial randomized parallel 2 months

 

(BDI) SMD -0.258840621 Unspecified

Llorente, 2003 <2002 US Breast-feeding women 89

 

saturated 49.7 ± 2.3 omega 3 capsule vs placebo Trial randomized parallel 3 weeks

 

(BDI) SMD -0.15330784 Unspecified

Llorente, 2003 <2002 US Breast-feeding women 89

 g p 

saturated 49.7 ± 2.3 omega 3 capsule vs placebo Trial randomized parallel 4 months

 p y 

(BDI) SMD -0.179693267 Unspecified

Llorente, 2003 <2002 US Breast-feeding women 63

 

saturated 49.7 ± 2.3 omega 3 capsule vs placebo Trial randomized parallel 18 months

 

Depression Scale (EPDS) SMD 0 Unspecified

Llorente, 2003 <2002 US Breast-feeding women 89

 

saturated 49.7 ± 2.3 omega 3 capsule vs placebo Trial randomized parallel at either 2, 4 or 18 months responder: BDI<10 OR 0.962025285 Unspecified

Llorente, 2003 <2002 US Breast-feeding women 89

 g p 

saturated 49.7 ± 2.3 omega 3 capsule vs placebo Trial randomized parallel at either 2, 4 or 18 months responder: BDI<20 OR 0.953926683 Unspecified

Palmer, 2012 2006-2009 Australia

 

allergies 706

 

Placebo Trial randomized parallel 1 year food allergy with sensitization OR 1.088757396 Primary

Palmer, 2012 2006-2009 Australia

 

allergies 706

 

Placebo Trial randomized parallel 1 year eczema with sensitization OR 1.633136153 Primary

Palmer, 2012 2006-2009 Australia

g 

allergies 706

 g p 

Placebo Trial randomized parallel 1 year respiratory tract infection OR 1.105507493 Secondary

Field, 2008 NR Canada Healthy infants 30

 

Formula (unsuppl) Trial randomized parallel 6 wk head circumference SMD 0.25981921 Secondary

Field, 2008 NR Canada Healthy infants 30

 

(unsuppl) Trial randomized parallel 6 wk head circumference SMD -0.157534748 Secondary

Field, 2008 NR Canada Healthy infants 30

 

(unsuppl) Trial randomized parallel 6 wk length SMD 0 Secondary

Field, 2008 NR Canada Healthy infants 30

 

Formula (unsuppl) Trial randomized parallel 6 wk length SMD 0.773905993 Secondary

Field, 2008 NR Canada Healthy infants 30

 

(unsuppl) Trial randomized parallel 6 wk weight SMD 0.28197214 Secondary

Field, 2008 NR Canada Healthy infants 30

 p 

Formula (unsuppl) Trial randomized parallel 6 wk weight SMD 0.261061996 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 188

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel birth birth weight SMD 0.344324082 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 188

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel birth incidence of premature birth OR 1.277777791 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 188

 y 

records 

 y 

profile in RBCs at Intervention vs Control Trial randomized parallel birth gestational age SMD 0.475911558 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 170

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel 12 months bmi SMD 0.137736201 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 174

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel 4 months bmi SMD 0.222069964 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 180

 y 

records 

 y 

profile in RBCs at Intervention vs Control Trial randomized parallel 6 weeks bmi SMD -0.076762483 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 170

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel 12 months head circumference SMD 0.257732689 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 174

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel 4 months head circumference SMD 0.15384616 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 179

 y 

records 

 y 

profile in RBCs at Intervention vs Control Trial randomized parallel 6 weeks head circumference SMD -0.347412616 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 170

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel 12 months length SMD 0.230509579 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 175

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel 4 months length SMD 0.095156431 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 180

 y 

records 

 y 

profile in RBCs at Intervention vs Control Trial randomized parallel 6 weeks length SMD 0.172204271 Secondary
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 170

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel 12 months weight SMD 0.263134122 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 174

 

records 

 

profile in RBCs at Intervention vs Control Trial randomized parallel 4 months weight SMD 0.246487647 Secondary

Hauner, 2012 july 14 2006 - may 22 2009 Germany Healthy pregnant women 180

 y 

records 

 y 

profile in RBCs at Intervention vs Control Trial randomized parallel 6 weeks weight SMD 0.092580557 Secondary

Fang, 2005 NR Taiwan Preterm infants 27 Neoangelac Plus vs placebo Trial randomized parallel 1 year

 

Index SMD 1.081910968 Primary

Fang, 2005 NR Taiwan Preterm infants 27 Neoangelac Plus vs placebo Trial randomized parallel 6 months

 

Index SMD 0.470003933 Primary

Fang, 2005 NR Taiwan Preterm infants 27 Neoangelac Plus vs placebo Trial randomized parallel 12 months

y y p y 

development index SMD 1.355769992 Primary

Fang, 2005 NR Taiwan Preterm infants 27 Neoangelac Plus vs placebo Trial randomized parallel 6 months

 

development index SMD 0.583425582 Primary

Fang, 2005 NR Taiwan Preterm infants 27 Neoangelac Plus vs placebo Trial randomized parallel 4 months Hiding Heidi Analysis <100% OR 1.71875 Primary

Fang, 2005 NR Taiwan Preterm infants 27 Neoangelac Plus vs placebo Trial randomized parallel 6 months Hiding Heidi Analysis <100% OR 1.109243751 Primary

Fang, 2005 NR Taiwan Preterm infants 27 Neoangelac Plus vs placebo Trial randomized parallel 4 months

 

cycles per degree OR 1.370242238 Primary

Fang, 2005 NR Taiwan Preterm infants 27 Neoangelac Plus vs placebo Trial randomized parallel 6 months

 

cycles per degree OR 1.2890625 Primary

Fang, 2005 NR Taiwan Preterm infants 24 Neoangelac Plus vs placebo Trial randomized parallel 4 months Visual evoked potential SMD 0.565511107 Primary

Fang, 2005 NR Taiwan Preterm infants 23 Neoangelac Plus vs placebo Trial randomized parallel 6 months Visual evoked potential SMD 0.155423433 Primary

Helland, 2008 1994-2003 Norway

 

pregnant women Breast- 143

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel birth birth weight SMD 0.188516736 Primary

Helland, 2008 1994-2003 Norway

y y 

pregnant women Breast-

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 4 years

 y 

for Children (K-ABC): mental NC Secondary

Helland, 2008 1994-2003 Norway

 

pregnant women Breast-

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 7 years

 

for Children (K-ABC): mental NC Secondary

Helland, 2008 1994-2003 Norway

 

pregnant women Breast-

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 4 years

 

for Children (K-ABC): non- NC Secondary

Helland, 2008 1994-2003 Norway

y y 

pregnant women Breast-

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 7 years

 y 

for Children (K-ABC): non- NC Secondary

Helland, 2008 1994-2003 Norway

 

pregnant women Breast-

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 4 years

 y 

for Children (K-ABC): NC Secondary

Helland, 2008 1994-2003 Norway

 

pregnant women Breast-

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 7 years

 

for Children (K-ABC): NC Secondary

Helland, 2008 1994-2003 Norway

y y 

pregnant women Breast-

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 4 years

 y 

for Children (K-ABC): NC Secondary

Helland, 2008 1994-2003 Norway

 

pregnant women Breast-

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 7 years

 

for Children (K-ABC): NC Secondary

Helland, 2008 1994-2003 Norway

 

pregnant women Breast- 143

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 7 years bmi SMD 0.058823526 Secondary

Helland, 2008 1994-2003 Norway

y y 

pregnant women Breast- 143

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 7 years length SMD -0.20782125 Secondary

Helland, 2008 1994-2003 Norway

 

pregnant women Breast- 143

 

cod n147 corn 

 

cod(n148) corn corn oil vs Cod oil Trial randomized parallel 7 years weight SMD -0.04878049 Secondary

Gustafson, 2013 may 2009 - july 2011 US

 

pregnant women 46

 

TFA) placebo group: DHA vs Placebo Trial randomized parallel birth birth weight SMD -0.038860865 Secondary

Gustafson, 2013 may 2009 - july 2011 US

y y 

pregnant women 27

p ( 

TFA) placebo group: DHA vs Placebo Trial randomized parallel 1-14 days post-partum

 

Assessment: state SMD 0.148237228 Primary

Gustafson, 2013 may 2009 - july 2011 US

 

pregnant women 27

 

TFA) placebo group: DHA vs Placebo Trial randomized parallel 1-14 days post-partum

 

Assessment: autonomic SMD 0.211658597 Primary

Gustafson, 2013 may 2009 - july 2011 US

 

pregnant women 27

 

TFA) placebo group: DHA vs Placebo Trial randomized parallel 1-14 days post-partum

 

Assessment: motor SMD 0.192501962 Primary

Gustafson, 2013 may 2009 - july 2011 US

y y 

pregnant women 27

p ( 

TFA) placebo group: DHA vs Placebo Trial randomized parallel 1-14 days post-partum

 

Assessment: reflexes SMD 0.047278289 Primary

Gustafson, 2013 may 2009 - july 2011 US

 

pregnant women 27

 

TFA) placebo group: DHA vs Placebo Trial randomized parallel 1-14 days post-partum

 

Assessment: state regulation SMD 0.025446042 Primary

Gustafson, 2013 may 2009 - july 2011 US

 

pregnant women 27

 

TFA) placebo group: DHA vs Placebo Trial randomized parallel 1-14 days post-partum

 

Assessment:habituation SMD -0.156438708 Primary

Gustafson, 2013 may 2009 - july 2011 US

y y 

pregnant women 27

p ( 

TFA) placebo group: DHA vs Placebo Trial randomized parallel 1-14 days post-partum

 

Assessment:orienting SMD 0.21324341 Primary

Ramakrishnan, 2010 feb 2005 - feb 2007 Mexico Healthy pregnant women 973

 

LA: 17,846 in DHA vs Controls Trial randomized parallel birth birth weight SMD 0.011284063 Primary

Ramakrishnan, 2010 feb 2005 - feb 2007 Mexico Healthy pregnant women 973

 

LA: 17,846 in DHA vs Controls Trial randomized parallel birth birthweight <2500g OR 1.002057672 Secondary

Ramakrishnan, 2010 feb 2005 - feb 2007 Mexico Healthy pregnant women 973

g y 

LA: 17,846 in DHA vs Controls Trial randomized parallel birth gestational age SMD -0.055466857 Primary

Ramakrishnan, 2010 feb 2005 - feb 2007 Mexico Healthy pregnant women 973

 

LA: 17,846 in DHA vs Controls Trial randomized parallel birth incidence of premature birth OR 0.818006218 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women 117 omega 3 capsule vs placebo Trial randomized parallel 5 years

 

Preschool Scale of SMD -0.229631856 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women 117 omega 3 capsule vs placebo Trial randomized parallel 5 years

 y 

Preschool Scale of SMD -0.046969224 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women 117 omega 3 capsule vs placebo Trial randomized parallel 5 years

 

Preschool Scale of SMD 0.093054555 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women 117 omega 3 capsule vs placebo Trial randomized parallel 5 years

 

Preschool Scale of SMD -0.15384616 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women 113 omega 3 capsule vs placebo Trial randomized parallel 5 years

p 

Motor Integration SMD -0.108042359 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women 115 omega 3 capsule vs placebo Trial randomized parallel 5 years

 

for Children: hand movement SMD -0.233761802 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women 115 omega 3 capsule vs placebo Trial randomized parallel 5 years McCarthy (leg coordination) SMD -0.058601439 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women 116 omega 3 capsule vs placebo Trial randomized parallel 5 years

 pg 

(dominant hand) SMD -0.088986464 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women 116 omega 3 capsule vs placebo Trial randomized parallel 5 years

 

dominant hand) SMD 0 Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women Trial randomized parallel

 

(number of letters correct) Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women Trial randomized parallel

y y g y 

(number of letters correct) Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women Trial randomized parallel Sweep VEP acuity Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women Trial randomized parallel VEP Amplitude Secondary

Jensen, 2010 NR (<2010) US Breast-feeding women Trial randomized parallel

 y ( 

sizes) Secondary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 287

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 18 months

 

Toddler Development (BSID- SMD 0.144145399 Primary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 287

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 18 months

 

Toddler Development (BSID- SMD 0.05327452 Primary

Meldrum, 2012

 

through October 2008 Australia

g 

allergies 128

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 12 months Communicative Development SMD 0.219934821 Primary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 161

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 18 months Communicative Development SMD 0.081229486 Primary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 128

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 12 months Communicative Development SMD 0.493831664 Primary

Meldrum, 2012

 

through October 2008 Australia

g 

allergies 161

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 18 months Communicative Development SMD 0.356752485 Primary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 128

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 12 months Communicative Development SMD -0.041587263 Primary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 161

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 18 months Communicative Development SMD 0.113986336 Primary

Meldrum, 2012

 

through October 2008 Australia

g 

allergies 128

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 12 months Communicative Development SMD 0.448788583 Primary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 161

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 18 months Communicative Development SMD 0.357071489 Primary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 128

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 12 months Communicative Development SMD 0.072471201 Primary

Meldrum, 2012

 

through October 2008 Australia

g 

allergies 161

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 18 months Communicative Development SMD -0.155814633 Primary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 128

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 12 months Communicative Development SMD 0.137528867 Primary

Meldrum, 2012

 

through October 2008 Australia

 

allergies 161

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 18 months Communicative Development SMD 0.096759267 Primary

Meldrum, 2012

 

through October 2008 Australia

g 

allergies 269

 

food 

 

Fish oil group LA, fish oil capsul vs placebo Trial randomized parallel 18 months

g 

Checklist: Sleep problems - OR 0.896551728 Primary

de Jong, 2012

 

through October 1999, follow-up 9 Netherlands Healthy infants Trial randomized parallel Secondary

Jensen, 2005 <2004 US Breast-feeding women 133

 

(DHASCO) vs placebo Trial randomized parallel 30 months

 

Developmental Index SMD 0.577999294 Primary

Jensen, 2005 <2004 US Breast-feeding women 147

 g ygy 

(DHASCO) vs placebo Trial randomized parallel 30 months

 g 

Auditory Milestone Scale SMD 0.013285638 Secondary

Jensen, 2005 <2004 US Breast-feeding women 162

 

(DHASCO) vs placebo Trial randomized parallel 12 months

 

Auditory Milestone Scale SMD -0.136091054 Secondary

Jensen, 2005 <2004 US Breast-feeding women 147

 

(DHASCO) vs placebo Trial randomized parallel 30 months

 

development quotient (CAT SMD -0.022587707 Secondary

Jensen, 2005 <2004 US Breast-feeding women 162

 g ygy 

(DHASCO) vs placebo Trial randomized parallel 12 months

 p 

development quotient (CAT SMD -0.096314266 Secondary
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Jensen, 2005 <2004 US Breast-feeding women 147

 

(DHASCO) vs placebo Trial randomized parallel 30 months

 

development quotient (DQ) SMD -0.147750855 Secondary

Jensen, 2005 <2004 US Breast-feeding women 162

 

(DHASCO) vs placebo Trial randomized parallel 12 months

 

development quotient (DQ) SMD 0.169517517 Secondary

Jensen, 2005 <2004 US Breast-feeding women 160

 g ygy 

(DHASCO) vs placebo Trial randomized parallel 4 months Sweep VEP SMD 0 Secondary

Jensen, 2005 <2004 US Breast-feeding women 147

 

(DHASCO) vs placebo Trial randomized parallel 4 months Teller Acuity Card procedure SMD 0.47184062 Secondary

Jensen, 2005 <2004 US Breast-feeding women 147

 

(DHASCO) vs placebo Trial randomized parallel 8 months Teller Acuity Card procedure SMD -2.180923462 Secondary

Jensen, 2005 <2004 US Breast-feeding women 168

 g ygy 

(DHASCO) vs placebo Trial randomized parallel 4 months

 p 

amplitude SMD -0.359262765 Secondary

Jensen, 2005 <2004 US Breast-feeding women 153

 

(DHASCO) vs placebo Trial randomized parallel 8 months

 

amplitude SMD -0.361061066 Secondary

Jensen, 2005 <2004 US Breast-feeding women 168

 

(DHASCO) vs placebo Trial randomized parallel 4 months

 

latency SMD -0.080524042 Secondary

Jensen, 2005 <2004 US Breast-feeding women 153

 g ygy 

(DHASCO) vs placebo Trial randomized parallel 8 months

 p 

latency SMD 0.021418762 Secondary

Campoy, 2011 NR, <2011 Germany, Spain, Hungary Healthy pregnant women

 

mean DHA Placebo fish oil vs placebo

 

design 6.5 years

 

Battery for Children: Mental NC Secondary

Campoy, 2011 NR, <2011 Germany, Spain, Hungary Healthy pregnant women

 

mean DHA Placebo 

 

placebo

 

design 6.5 years

 

Battery for Children: Mental NC Secondary

Campoy, 2011 NR, <2011 Germany, Spain, Hungary Healthy pregnant women

 

mean DHA Placebo folic acid vs placebo

 

design 6.5 years

 

Battery for Children: Mental NC Secondary

Campoy, 2011 NR, <2011 Germany, Spain, Hungary Healthy pregnant women

 

mean DHA Placebo fish oil vs placebo

 

design 6.5 years

 

Battery for Children: NC Secondary

Campoy, 2011 NR, <2011 Germany, Spain, Hungary Healthy pregnant women

 

mean DHA Placebo 

 

placebo

 

design 6.5 years

 

Battery for Children: NC Secondary

Campoy, 2011 NR, <2011 Germany, Spain, Hungary Healthy pregnant women

 

mean DHA Placebo folic acid vs placebo

 

design 6.5 years

 

Battery for Children: NC Secondary

Campoy, 2011 NR, <2011 Germany, Spain, Hungary Healthy pregnant women

 

mean DHA Placebo fish oil vs placebo

 

design 6.5 years

 

Battery for Children: NC Secondary

Campoy, 2011 NR, <2011 Germany, Spain, Hungary Healthy pregnant women

 

mean DHA Placebo 

 

placebo

 

design 6.5 years

 

Battery for Children: NC Secondary

Campoy, 2011 NR, <2011 Germany, Spain, Hungary Healthy pregnant women

 

mean DHA Placebo folic acid vs placebo

 

design 6.5 years

 

Battery for Children: NC Secondary

Mihrshahi, 2003 1997-2002 Australia

 

allergies 554

 

control or intervention vs Diet Trial randomized parallel 18 months eczema or dermatitis OR 1 Primary

Mihrshahi, 2003 1997-2002 Australia

 

allergies 554

 

control or intervention vs Diet Trial randomized parallel 18 months asthma OR 1 Primary

Mihrshahi, 2003 1997-2002 Australia

g 

allergies 554

y 

control or intervention vs Diet Trial randomized parallel 18 months wheeze ever OR 1 Primary

Toelle, 2010 1997-2008 Australia Healthy infants 450

 

vs Control Trial randomized parallel 8 yrs atopy OR 0.995192289 Primary

Toelle, 2010 1997-2008 Australia Healthy infants 450

 

vs Control Trial randomized parallel 8 yrs rhinitis OR 0.97077924 Secondary

Toelle, 2010 1997-2008 Australia Healthy infants 450

g pp 

vs Control Trial randomized parallel 8 yrs eczema OR 0.925974011 Secondary

Toelle, 2010 1997-2008 Australia Healthy infants 450

 

vs Control Trial randomized parallel 8 yrs asthma OR 0.807017565 Primary

Toelle, 2010 1997-2008 Australia Healthy infants 450

 

vs Control Trial randomized parallel 8 yrs wheeze OR 0.730386078 Primary

Innis, 2008 NR, <2008 Canada Healthy pregnant women 135

 

assignment: 

 g 

baseline values for DHA supplement vs placebo Trial randomized parallel 60 days

 y p 

(visual acuity) SMD 0.316226661 Secondary

Smithers, 2010

 

2003 Australia Preterm infants 127 DHA vs Placebo Trial randomized parallel 26 months CA

 

Development Inventory SMD -0.043016009 Secondary

Knudsen, 2006 2001- Denmark Healthy pregnant women 972

 

EPA+DHA, 

 

and AA in 03 vs CG Trial randomized parallel birth gestational age SMD -0.076467894 Primary

Knudsen, 2006 2001- Denmark Healthy pregnant women 977

 

EPA+DHA, 

 

and AA in 01 vs CG Trial randomized parallel birth gestational age SMD 0.075525202 Primary

Knudsen, 2006 2001- Denmark Healthy pregnant women 960

 

EPA+DHA, 

 

and AA in 14 vs CG Trial randomized parallel birth gestational age SMD 0 Primary

Knudsen, 2006 2001- Denmark Healthy pregnant women 935

 

EPA+DHA, 

 

and AA in 28 vs CG Trial randomized parallel birth gestational age SMD -0.080774717 Primary

Knudsen, 2006 2001- Denmark Healthy pregnant women 970

 

EPA+DHA, 

 

and AA in 07 vs CG Trial randomized parallel birth gestational age SMD -0.008395271 Primary

Knudsen, 2006 2001- Denmark Healthy pregnant women 924

 

EPA+DHA, 

 

and AA in c18 vs CG Trial randomized parallel birth gestational age SMD 0.008391659 Primary

Olsen, 2008 1989-2006 Denmark Healthy pregnant women 399 Fish oil vs Control Trial randomized parallel 16 years asthma (all types) OR 2.659007311 Secondary

Olsen, 2008 1989-2006 Denmark Healthy pregnant women 265 No oil vs Control Trial randomized parallel 16 years asthma (all types) OR 3.477941275 Secondary

Olsen, 2008 1989-2006 Denmark Healthy pregnant women 399 Fish oil vs Control Trial randomized parallel 16 years asthma (allergic) OR 7.735294342 Secondary

Olsen, 2008 1989-2006 Denmark Healthy pregnant women 265 No oil vs Control Trial randomized parallel 16 years asthma (allergic) OR 16.13138771 Secondary

Cheatham, 2011 1998-2007 Denmark Healthy infants 63 Olive oil vs Fish oil Observational prospective 7.5 years Stroop scores SMD -0.161422551 Secondary

Cheatham, 2011 1998-2007 Denmark Healthy infants 63 Olive oil vs Fish oil Observational prospective 7.5 years

 

Standardized speed of SMD -0.230769232 Secondary

Furuhjelm, 2009 2003-2006 Sweden

 

pregnant women 117

 

0.2g/day EPA- 

 

mean(sd) mol % w3 group vs Placebo Trial randomized parallel 12 months Food Allergy OR 8 Primary

Furuhjelm, 2009 2003-2006 Sweden

y y 

pregnant women 115

 

0.2g/day EPA- 

 

mean(sd) mol % w3 group vs Placebo Trial randomized parallel 12 months IgE associated eczema OR 3.095238209 Primary

Furuhjelm, 2009 2003-2006 Sweden

 

pregnant women 117

 

0.2g/day EPA- 

 

mean(sd) mol % w3 group vs Placebo Trial randomized parallel 6 months IgE associated eczema OR 2.599999905 Primary

Dunstan, 2003 1999-2001 Australia

 

pregnant women 83

 

group Trial randomized parallel 1 year food allergy OR 1.550387621 Secondary

Dunstan, 2003 1999-2001 Australia

y y 

pregnant women 83

 g p 

group Trial randomized parallel 1 year atopic dermatitis OR 0.671834648 Secondary

Dunstan, 2003 1999-2001 Australia

y y 

pregnant women 83

 

group Trial randomized parallel 1 year asthma OR 2.790697575 Secondary

Dunstan, 2003 1999-2001 Australia

 

pregnant women 83

 

group Trial randomized parallel 1 year chronic cough OR 2.04651165 Secondary

Dunstan, 2003 1999-2001 Australia

y y 

pregnant women 83

 g p 

group Trial randomized parallel 1 year recurrent wheeze OR 1.116279125 Secondary

Zhou, 2012 10. 2005 - 01. 2008 Australia Healthy pregnant women 2399 DHA vs control Trial randomized parallel birth birth weight SMD 0.119289018 Secondary

Zhou, 2012 10. 2005 - 01. 2008 Australia Healthy pregnant women 2399 DHA vs control Trial randomized parallel during pregnancy preeclampsia OR 0.96264559 Secondary

Zhou, 2012 10. 2005 - 01. 2008 Australia Healthy pregnant women 2399 DHA vs control Trial randomized parallel during pregnancy

p g y 

hypertension OR 1.087294936 Secondary

Zhou, 2012 10. 2005 - 01. 2008 Australia Healthy pregnant women 2399 DHA vs control Trial randomized parallel birth SGA for weight OR 1.11861515 Secondary

Zhou, 2012 10. 2005 - 01. 2008 Australia Healthy pregnant women 2399 DHA vs control Trial randomized parallel birth birthweight <2500g OR 1.530193567 Secondary

Makrides, 2014

 p 

25, 2012 Australia Healthy pregnant women 646 DHA supplement vs Placebo Trial randomized parallel 4 years hyperactivity disorder OR NC

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women 646 DHA supplement vs Placebo Trial randomized parallel 4 years diagnosis of autism OR 0.531948865

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

Executive Function- NC Secondary

Makrides, 2014

 p 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 g y 

Executive Function- NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

Executive Function- NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

Executive Function- NC Secondary

Makrides, 2014

 p 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 g y 

Executive Function- NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

Executive Function- NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

Executive Function- NC Secondary

Makrides, 2014

 p 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 g y 

Executive Function- NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

Executive Function- NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

Score NC Secondary

Makrides, 2014

 p 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

y g p ( 

efficiency) NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

second edition (DAS II) score: NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

second edition (DAS II) score: NC Secondary

Makrides, 2014

 p 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 y 

second edition (DAS II) score: NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

second edition (DAS II) score: NC Secondary

Makrides, 2014

 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 

second edition (DAS II) score: NC Secondary

Makrides, 2014

 p 

25, 2012 Australia Healthy pregnant women DHA supplement vs Placebo Trial randomized parallel 4 years

 y 

second edition (DAS II) score: NC Secondary
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

de Jong, 2010 1997-2008 Netherlands Healthy infants 214

 

group Trial randomized parallel 9 years

 

neurologically normal OR 1.062009454 Unspecified

Clandinin, 2005 NR Canada Preterm infants 114 Fish-DHA vs Control Trial randomized parallel 118 weeks

 

Development II (Mental SMD 0.661334515 Unspecified

Clandinin, 2005 NR Canada Preterm infants 112 Reference vs Control Trial randomized parallel 118 weeks

y y 

Development II (Mental SMD 1.402211308 Unspecified

Clandinin, 2005 NR Canada Preterm infants 98 Algal-DHA vs Control Trial randomized parallel 118 weeks

 

Development II (Mental SMD 0.426311731 Unspecified

Clandinin, 2005 NR Canada Preterm infants 113 Fish-DHA vs Control Trial randomized parallel 118 weeks

 

Development II (Physical SMD 0.332264096 Unspecified

Clandinin, 2005 NR Canada Preterm infants 113 Reference vs Control Trial randomized parallel 118 weeks

y y 

Development II (Physical SMD 0.996792257 Unspecified

Clandinin, 2005 NR Canada Preterm infants 100 Algal-DHA vs Control Trial randomized parallel 118 weeks

 

Development II (Physical SMD 0.352404565 Unspecified

Clandinin, 2005 NR Canada Preterm infants Trial randomized parallel Unspecified

Stein, 2011 02. 2005- 02.2007 Mexico Healthy infants 739 DHA vs Placebo Trial randomized parallel birth birth weight SMD 0.047999464 Primary

Stein, 2011 02. 2005- 02.2007 Mexico Healthy infants 737 DHA vs Placebo Trial randomized parallel birth

 

retardation); birth weight for OR 0.977006674 Secondary

Stein, 2011 02. 2005- 02.2007 Mexico Healthy infants 739 DHA vs Placebo Trial randomized parallel birth birthweight <2500g OR 1.255813956 Secondary

Stein, 2011 02. 2005- 02.2007 Mexico Healthy infants 737 DHA vs Placebo Trial randomized parallel birth gestational age SMD 0 Primary

Stein, 2011 02. 2005- 02.2007 Mexico Healthy infants 737 DHA vs Placebo Trial randomized parallel birth incidence of premature birth OR 0.911561251 Secondary

Stein, 2011 02. 2005- 02.2007 Mexico Healthy infants 739 DHA vs Placebo Trial randomized parallel 18 months head circumference SMD 0 Primary

Stein, 2011 02. 2005- 02.2007 Mexico Healthy infants 739 DHA vs Placebo Trial randomized parallel 18 months length SMD 0.035714287 Primary

Stein, 2011 02. 2005- 02.2007 Mexico Healthy infants 739 DHA vs Placebo Trial randomized parallel 18 months weight SMD 0 Primary

Manley, 2011 2001-2007 Australia

 

feeding women 481

 

diet Trial randomized parallel 12 months hay fever OR 2.422489882 Secondary

Manley, 2011 2001-2007 Australia

 

feeding women 475

g 

diet Trial randomized parallel 12 or 18 months hay fever OR 2.485143423 Secondary

Manley, 2011 2001-2007 Australia

 

feeding women 603

 

diet Trial randomized parallel 18 months hay fever OR 1.341295362 Secondary

Manley, 2011 2001-2007 Australia

 

feeding women 481

 

diet Trial randomized parallel 12 months eczema OR 1.285140514 Secondary

Manley, 2011 2001-2007 Australia

 

feeding women 484

g 

diet Trial randomized parallel 12 or 18 months eczema OR 1.045214176 Secondary

Manley, 2011 2001-2007 Australia

 

feeding women 603

 

diet Trial randomized parallel 18 months eczema OR 0.997588396 Secondary

Manley, 2011 2001-2007 Australia

 

feeding women 481

 

diet Trial randomized parallel 12 months asthma OR 1.294065118 Secondary

Manley, 2011 2001-2007 Australia

 

feeding women 489

g 

diet Trial randomized parallel 12 or 18 months asthma OR 1.060536981 Secondary

Manley, 2011 2001-2007 Australia

 

feeding women 603

 

diet Trial randomized parallel 18 months asthma OR 1.05340755 Secondary

Smithers, 2008 2001-2004 Australia Preterm infants 115 begun at birth: Treatment vs Control group Trial randomized parallel 2 months (corrected age) Visual evoked potential acuity SMD 0 Primary

Smithers, 2008 2001-2004 Australia Preterm infants 95 begun at birth: Treatment vs Control group Trial randomized parallel 4 months (corrected age) Visual evoked potential acuity SMD 0.492770821 Primary

Smithers, 2008 2001-2004 Australia Preterm infants 125 begun at birth: Treatment vs Control group Trial randomized parallel 4 months (corrected age)

 

latency: 48 min of arc SMD 0.130434781 Secondary

Smithers, 2008 2001-2004 Australia Preterm infants 124 begun at birth: Treatment vs Control group Trial randomized parallel 2 months (corrected age)

 

latency: 69 min of arc SMD 0.249258399 Secondary

Smithers, 2008 2001-2004 Australia Preterm infants 125 begun at birth: Treatment vs Control group Trial randomized parallel 4 months (corrected age)

 p 

latency: 69 min of arc SMD 0.09735848 Secondary

Smithers, 2008 2001-2004 Australia Preterm infants 124 begun at birth: Treatment vs Control group Trial randomized parallel 2 months (corrected age)

 

latency: 96 min of arc SMD 0.233990356 Secondary

Smithers, 2008 2001-2004 Australia Preterm infants begun at birth: Trial randomized parallel Secondary

Henriksen, 2008 2003-2006 Norway Preterm infants Trial randomized parallel Ages and Stages Primary

Henriksen, 2008 2003-2006 Norway Preterm infants 105 Intervention vs Control Trial randomized parallel 6 months

g g 

Communication SMD -0.14034833

Henriksen, 2008 2003-2006 Norway Preterm infants 105 Intervention vs Control Trial randomized parallel 6 months Ages and Stages: Fine motor SMD -0.047187887

Henriksen, 2008 2003-2006 Norway Preterm infants 105 Intervention vs Control Trial randomized parallel 6 months

g g 

motor SMD 0.212538749

Henriksen, 2008 2003-2006 Norway Preterm infants 105 Intervention vs Control Trial randomized parallel 6 months

 

social SMD 0.079742588

Henriksen, 2008 2003-2006 Norway Preterm infants 105 Intervention vs Control Trial randomized parallel 6 months

 

solving SMD 0.464068025

Henriksen, 2008 2003-2006 Norway Preterm infants 105 Intervention vs Control Trial randomized parallel 6 months Ages and Stages: Total SMD 0.167406961

Henriksen, 2008 2003-2006 Norway Preterm infants 100 Intervention vs Control Trial randomized parallel day 65 head circumference SMD 0.350823224 Secondary

Noakes, 2012 Not reported UK Healthy pregnant women 86

 

group Trial randomized parallel 6 months atopic dermatitis OR 1.357142806 Primary

Noakes, 2012 Not reported UK Healthy pregnant women 83

 g p 

group Trial randomized parallel 6 months chest infection OR 0.268115938 Secondary

Noakes, 2012 Not reported UK Healthy pregnant women 83

 

group Trial randomized parallel 6 months pneumonia/bronchiolitis OR 0.804347813 Secondary

Noakes, 2012 Not reported UK Healthy pregnant women 83

 

group Trial randomized parallel 6 months wheeze OR 1.263975143 Secondary

Fleddermann, 2014 Jan 2010 to May 2011 Serbia Healthy infants 164

 ( ) 

Control Formula (CF) Trial randomized parallel days head circumference gain SMD 0 Secondary

Fleddermann, 2014 Jan 2010 to May 2011 Serbia Healthy infants 164

 

Control Formula (CF) Trial randomized parallel days length gain SMD 0.5 Secondary

Fleddermann, 2014 Jan 2010 to May 2011 Serbia Healthy infants 164

 

Control Formula (CF) Trial randomized parallel days weight gain SMD 0.29683876 Primary

Goor, 2011 2004-2009 Netherlands Healthy infants 75 DHA vs placebo Trial randomized parallel birth birth weight SMD 0.031639852 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 73 DHA+AA vs placebo Trial randomized parallel birth birth weight SMD 0.163081348 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 75 DHA vs placebo Trial randomized parallel 18 months

 

Development (Mental SMD -0.121097274 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 75 DHA vs placebo Trial randomized parallel 18 months

y y p y 

development index SMD 0.405259818 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 73 DHA+AA vs placebo Trial randomized parallel 18 months

 

development index SMD 0.081668519 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants DHA vs placebo Trial randomized parallel 18 months fluency score NC Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants DHA+AA vs placebo Trial randomized parallel 18 months fluency score NC Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants DHA+AA vs placebo Trial randomized parallel 18 months neurological optimality score NC Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants DHA vs placebo Trial randomized parallel 18 months neurological optimality score NC Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 73 DHA+AA vs placebo Trial randomized parallel 18 months

p p 

neurological dysfunction OR 1.147058845 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 75 DHA vs placebo Trial randomized parallel 18 months

 

neurological dysfunction OR 2.00980401 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 75 DHA vs placebo Trial randomized parallel 18 months

 

neurological condition OR 0.995121956 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 73 DHA+AA vs placebo Trial randomized parallel 18 months

p 

neurological condition OR 1.220512867 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 75 DHA vs placebo Trial randomized parallel 18 months

 

neurological dysfunction OR 0.775210083 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 73 DHA+AA vs placebo Trial randomized parallel 18 months

 

neurological dysfunction OR 1.720588207 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 73 DHA+AA vs placebo Trial randomized parallel 18 months head circumference SMD -0.207277015 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 75 DHA vs placebo Trial randomized parallel 18 months head circumference SMD -0.154297054 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 75 DHA vs placebo Trial randomized parallel 18 months length SMD -0.278005928 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 73 DHA+AA vs placebo Trial randomized parallel 18 months length SMD -0.119455278 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 73 DHA+AA vs placebo Trial randomized parallel 18 months weight SMD 0 Unspecified

Goor, 2011 2004-2009 Netherlands Healthy infants 75 DHA vs placebo Trial randomized parallel 18 months weight SMD -0.157088354 Unspecified

Bouwstra, 2005 1997-2002 Netherlands Healthy infants 290

 

group Trial randomized parallel 18 months

y y 

Development (Mental SMD -0.177778691 Secondary

Bouwstra, 2005 1997-2002 Netherlands Healthy infants 315

 

group Trial randomized parallel 18 months Bayley PDI SMD -0.11104764 Secondary

Bouwstra, 2005 1997-2002 Netherlands Healthy infants

 

group Trial randomized parallel 18 months neurological optimality score NC Secondary

Bouwstra, 2005 1997-2002 Netherlands Healthy infants 315

 

group Trial randomized parallel 18 months

 

neurological dysfunction OR 0.69112426 Secondary
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Bouwstra, 2003 1997-1999 Netherlands Healthy infants 250

 

formula Trial randomized parallel 3 months

 

movements OR 1.631578922 Primary

Bouwstra, 2003 1997-1999 Netherlands Healthy infants 250

 

formula Trial randomized parallel 3 months

 

movements OR 0.857142806 Primary

Judge, 2012 nr US Healthy pregnant women 48

 p 

phospholipid (PL) DHA vs Placebo Trial randomized parallel birth birth weight SMD 0.395035178 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 

(AS, %) SMD -0.233474881 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 

(AS, %) SMD -0.009735975 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 p 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 p 

Sleep Transition (AQST, %) SMD 0.187375277 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 

Sleep Transition (AQST, %) SMD 0.207601592 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 

(Ar/AS) SMD 0.654765487 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 p 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 p 

(Ar/AS) SMD 0.090548791 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 

(Ar/QS) SMD 0.733264267 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 

(Ar/QS) SMD 0.470817834 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 p 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 p p 

Period (LSP, min) SMD 0.442723185 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 

Period (LSP, min) SMD -0.10683021 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 

Period (MSP, min) SMD 0.110412516 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 p 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 p p 

Period (MSP, min) SMD -0.007233827 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 

(W, %) SMD 0.155022875 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 

(W, %) SMD 0.105503738 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 p 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 p q p 

(QS,%) SMD 0.154997826 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 

(QS,%) SMD -0.183042795 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 

length (ASBL, min) SMD -0.008501874 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 p 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 p p 

length (ASBL, min) SMD -0.063578799 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 

Sleep Ratio(AS:QS) SMD 0.278755456 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 

Sleep Ratio(AS:QS) SMD 0.039062161 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 p 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 p p 

length (QSBL, min) SMD 0.171680912 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 

length (QSBL, min) SMD -0.296015859 Secondary

Judge, 2012 nr US Healthy pregnant women 46

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 1 day after birth

 

Transition (T, %) SMD 0.251199126 Secondary

Judge, 2012 nr US Healthy pregnant women 39

 p 

phospholipid (PL) DHA vs Placebo Trial randomized parallel 2 days after birth

 p p 

Transition (T, %) SMD 0.458189279 Secondary

Judge, 2012 nr US Healthy pregnant women 48

 

phospholipid (PL) DHA vs Placebo Trial randomized parallel birth gestational age SMD 0.446485102 Secondary

Judge, 2007 US Healthy pregnant women 29 DHA vs placebo Trial randomized parallel birth birth weight SMD 0.632310689 Secondary

Judge, 2007 US Healthy pregnant women 29 DHA vs placebo Trial randomized parallel birth gestational age SMD 0.989868045 Secondary

Malcolm, 2003 NR NR 37

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 50 weeks (corrected age)

 

components of the transient SMD 0.179844633 Primary

Malcolm, 2003 NR NR 47

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 66 weeks (corrected age)

 

components of the transient SMD -0.492338538 Primary

Malcolm, 2003 NR NR 9

y p 

fish oil and placebo DHA vs Placebo Trial randomized parallel birth

 j 

components of the transient SMD 1.108460188 Primary

Malcolm, 2003 NR NR 52

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 50 weeks (corrected age)

 j 

components of the transient SMD -0.341469467 Primary

Malcolm, 2003 NR NR 51

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 66 weeks (corrected age)

 

components of the transient SMD -0.199502796 Primary

Malcolm, 2003 NR NR 49

y p 

fish oil and placebo DHA vs Placebo Trial randomized parallel birth

 j 

components of the transient SMD -0.126309648 Primary

Malcolm, 2003 NR NR 34

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 50 weeks (corrected age)

 

components of the transient SMD 0.716261685 Primary

Malcolm, 2003 NR NR 26

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 66 weeks (corrected age)

 

components of the transient SMD -0.424542576 Primary

Malcolm, 2003 NR NR 53

y p 

fish oil and placebo DHA vs Placebo Trial randomized parallel birth

 j 

components of the transient SMD 0.111686088 Primary

Malcolm, 2003 NR NR 45

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 50 weeks (corrected age)

 

components of the transient SMD 0.17894046 Primary

Malcolm, 2003 NR NR 51

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 66 weeks (corrected age)

 

components of the transient SMD -0.202426881 Primary

Malcolm, 2003 NR NR 14

y p 

fish oil and placebo DHA vs Placebo Trial randomized parallel birth

 j 

components of the transient SMD 0.521966219 Primary

Malcolm, 2003 NR NR 47

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 50 weeks (corrected age)

 

components of the transient SMD -0.060580112 Primary

Malcolm, 2003 NR NR 31

 

fish oil and placebo DHA vs Placebo Trial randomized parallel 66 weeks (corrected age)

 

components of the transient SMD 0.047604621 Primary

Malcolm, 2003 NR NR 55

y p 

fish oil and placebo DHA vs Placebo Trial randomized parallel birth

 j 

components of the transient SMD -0.003236139 Primary

Malcolm, 2003 NR NR 55

 

fish oil and placebo DHA vs Placebo Trial randomized parallel

 

(postconceptional age) head circumference SMD -0.103399284 Secondary

Malcolm, 2003 NR NR 55

 

fish oil and placebo DHA vs Placebo Trial randomized parallel

 

age) head circumference SMD -0.143804684 Secondary

Malcolm, 2003 NR NR 55

y p 

fish oil and placebo DHA vs Placebo Trial randomized parallel

 

(postconceptional age) length SMD -0.18173489 Secondary

Malcolm, 2003 NR NR 55

 

fish oil and placebo DHA vs Placebo Trial randomized parallel

 

age) length SMD -0.206196889 Secondary

Malcolm, 2003 NR NR 55

 

fish oil and placebo DHA vs Placebo Trial randomized parallel

 

(postconceptional age) weight SMD -0.135403872 Secondary

Malcolm, 2003 NR NR 55

y p 

fish oil and placebo DHA vs Placebo Trial randomized parallel

 (p p 

age) weight SMD -0.498577684 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 103 Fish oil vs Olive oil Trial randomized parallel 2 months bmi SMD -0.145485193 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 101 High fish vs Olive oil Trial randomized parallel 2 months bmi SMD -0.21977061 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 57 High fish vs Olive oil Trial randomized parallel 2.5 years bmi SMD 0.218214259 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 70 Fish oil vs Olive oil Trial randomized parallel 2.5 years bmi SMD 0.57349366 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 95 High fish vs Olive oil Trial randomized parallel 4 months bmi SMD -0.279849559 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 98 Fish oil vs Olive oil Trial randomized parallel 4 months bmi SMD -0.074872986 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 95 High fish vs Olive oil Trial randomized parallel 9 months bmi SMD -0.25416404 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 100 Fish oil vs Olive oil Trial randomized parallel 9 months bmi SMD 0.195860922 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 107 High fish vs Olive oil Trial randomized parallel 1 week head circumference SMD 0.295087546 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 110 Fish oil vs Olive oil Trial randomized parallel 1 week head circumference SMD 0.278649122 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 97 High fish vs Olive oil Trial randomized parallel 2 months head circumference SMD 0.329351515 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 100 Fish oil vs Olive oil Trial randomized parallel 2 months head circumference SMD 0.352829069 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 59 High fish vs Olive oil Trial randomized parallel 2.5 years head circumference SMD 0.683686197 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 71 Fish oil vs Olive oil Trial randomized parallel 2.5 years head circumference SMD 0.539367497 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 91 Fish oil vs Olive oil Trial randomized parallel 4 months head circumference SMD 0.2894862 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 91 High fish vs Olive oil Trial randomized parallel 4 months head circumference SMD 0.446112722 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 97 Fish oil vs Olive oil Trial randomized parallel 9 months head circumference SMD 0.380636931 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 87 High fish vs Olive oil Trial randomized parallel 9 months head circumference SMD 0.376579493 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 57 High fish vs Olive oil Trial randomized parallel 2.5 years length SMD 0.365219474 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 70 Fish oil vs Olive oil Trial randomized parallel 2.5 years length SMD -0.022575691 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 98 Fish oil vs Olive oil Trial randomized parallel 4 months length SMD 0.089712508 Secondary
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 96 High fish vs Olive oil Trial randomized parallel 4 months length SMD 0.350786001 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 100 Fish oil vs Olive oil Trial randomized parallel 9 months length SMD 0.230778441 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 95 High fish vs Olive oil Trial randomized parallel 9 months length SMD 0.296311766 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women High fish vs Olive oil Trial randomized parallel 2 months length NC Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women Fish oil vs Olive oil Trial randomized parallel 2 months length NC Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 72 Fish oil vs Olive oil Trial randomized parallel 2.5 years weight SMD 0.357142866 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 59 High fish vs Olive oil Trial randomized parallel 2.5 years weight SMD 0.349132419 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 100 Fish oil vs Olive oil Trial randomized parallel 4 months weight SMD 0 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women 96 High fish vs Olive oil Trial randomized parallel 4 months weight SMD -0.091694273 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 95 High fish vs Olive oil Trial randomized parallel 9 months weight SMD -0.04347815 Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women 100 Fish oil vs Olive oil Trial randomized parallel 9 months weight SMD 0.297872335 Secondary

Lauritzen, 2005

 p y 

2000 Follow-up 2.5 years Denmark Breast-feeding women Fish oil vs Olive oil Trial randomized parallel 2 months weight NC Secondary

Lauritzen, 2005

 

2000 Follow-up 2.5 years Denmark Breast-feeding women High fish vs Olive oil Trial randomized parallel 2 months weight NC Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 80

 

LCPUFA/d

 

placebo group Trial randomized parallel 9 months

 

solving) SMD -0.058045622 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

y 

feeding women 86

 g 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 9 months

 g (p 

solving) SMD -0.060069013 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 79

 

LCPUFA/d

 

placebo group Trial randomized parallel 1 year

 

Development Inventory SMD 0.142857149 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 89

 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 1 year

 

Development Inventory SMD -0.15545632 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

y 

feeding women

 g 

LCPUFA/d

g g p 

placebo group Trial randomized parallel 2 years

 

Development Inventory NC Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women

 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 2 years

 

Development Inventory NC Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women

 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 2 years

 

Development Inventory NC Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

y 

feeding women

 g 

LCPUFA/d

g g p 

placebo group Trial randomized parallel 2 years

 

Development Inventory NC Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women

 

LCPUFA/d

 

placebo group Trial randomized parallel 1 year

 

Development Inventory NC Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women

 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 1 year

 

Development Inventory NC Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

y 

feeding women 89

 g 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 1 year

 

Development Inventory OR 0.75 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 79

 

LCPUFA/d

 

placebo group Trial randomized parallel 1 year

 

Development Inventory OR 1.041666627 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 89

 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 1 year

 

Development Inventory SMD 0 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

y 

feeding women 79

 g 

LCPUFA/d

g g p 

placebo group Trial randomized parallel 1 year

 

Development Inventory SMD 0 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 71

 

LCPUFA/d

 

placebo group Trial randomized parallel 2 years

 

Development Inventory OR 1.010638356 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 71

 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 2 years

 

Development Inventory OR 0.797872365 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

y 

feeding women 71

 g 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 2 years

 

Development Inventory OR 0.78125 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 71

 

LCPUFA/d

 

placebo group Trial randomized parallel 2 years

 

Development Inventory OR 1.25 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 89

 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 1 year

 

Development Inventory SMD -0.419727713 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

y 

feeding women 79

 g 

LCPUFA/d

g g p 

placebo group Trial randomized parallel 1 year

 

Development Inventory SMD -0.141472399 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 71

 

LCPUFA/d

g g p 

placebo group Trial randomized parallel 2 years

 

Development Inventory SMD 0.102434091 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women 71

 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 2 years

 

Development Inventory SMD -0.342880517 Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

y 

feeding women

 g 

LCPUFA/d fish oil vs placebo group Trial randomized parallel 1 year

 

Development Inventory NC Secondary

Lauritzen, 2005 enrolled in 1999 Denmark

 

feeding women

 

LCPUFA/d

 

placebo group Trial randomized parallel 1 year

 

Development Inventory NC Secondary

Lauritzen, 2004

 

1999 Denmark

 

lower than average fish 88

 

LCPUFA FO Intervention vs Placebo Trial randomized parallel 2 months

 

(SWEEP-VEP) SMD 0 Primary

Lauritzen, 2004

 

1999 Denmark

g 

lower than average fish 97

 

LCPUFA FO Intervention vs Placebo Trial randomized parallel 4 months

p p 

(SWEEP-VEP) SMD 0.235909283 Primary

Smithers, 2011

 

August 2008 Australia

 

pregnant women 182

g pp 

placebo Trial randomized parallel 4 months VEP Latency: 20 min of arc SMD 0 Secondary

Smithers, 2011

 

August 2008 Australia

 

pregnant women 182

 

placebo Trial randomized parallel 4 months VEP Latency: 48 min of arc SMD 0 Secondary

Smithers, 2011

 

August 2008 Australia

y y 

pregnant women 182

g pp 

placebo Trial randomized parallel 4 months VEP Latency: 69 min of arc SMD 0.117291354 Secondary

Smithers, 2011

 

August 2008 Australia

 

pregnant women 182

 

placebo Trial randomized parallel 4 months VEP acuity (adjusted) SMD -0.09137056 Primary

Smithers, 2011

 

August 2008 Australia

 

pregnant women 182

 

placebo Trial randomized parallel 4 months VEP acuity (unadjusted) SMD -0.090627246 Primary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 79

 g p 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel 26-28 weeks

 p y 

(BDI) SMD -0.164675847 Primary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 80

 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel 26-28 weeks

 

(BDI) SMD -0.592749 Primary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 79

 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel 34-36 weeks

 

(BDI) SMD 0.084774867 Primary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 80

 g p 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel 34-36 weeks

 p y 

(BDI) SMD -0.142899796 Primary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 80

 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel 6-8 weeks post-partum

 

(BDI) SMD -0.123252839 Primary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 79

 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel 6-8 weeks post-partum

 

(BDI) SMD 0.036273193 Primary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 78

 g p 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel birth birth weight SMD 0.92729032 Secondary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 80

 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel birth birth weight SMD 0.168324068 Secondary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 79

 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel during pregnancy

 

preeclampsia OR 2.317073107 Secondary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 80

 g p 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel during pregnancy

g yp 

preeclampsia OR 0.594512224 Secondary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 80

 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel birth gestational age SMD 0 Secondary

Mozurkewich, 2013 Oct 2008 - may 2011 US Healthy pregnant women 79

 

0.29+-0.18; DHA 

 

Control/Placebo Trial randomized parallel birth gestational age SMD 1.041483521 Secondary

Makrides, 2009

 p 

2005 Australia

 

feeding women 657 tuna oil capsules vs Placebo Trial randomized parallel 18 months

y y 

Development (Mental SMD 0.118830428 Primary

Makrides, 2009

 

2005 Australia

 

feeding women 657 tuna oil capsules vs Placebo Trial randomized parallel 18 months

 

development index SMD 0.06171966 Secondary

Unay, 2004 2000-2001 Turkey Healthy infants 44 Formula A vs Formula B Trial randomized parallel 16 weeks

 

potentials: interpeak latency I- SMD 0.598671079 Unspecified

Unay, 2004 2000-2001 Turkey Healthy infants 44 Formula A vs Formula B Trial randomized parallel 16 weeks

 y 

potentials: interpeak latency I- SMD 0.773020685 Unspecified

Unay, 2004 2000-2001 Turkey Healthy infants 44 Formula A vs Formula B Trial randomized parallel 16 weeks

 

potentials: interpeak latency III- SMD 0.695141316 Unspecified

Unay, 2004 2000-2001 Turkey Healthy infants 44 Formula A vs Formula B Trial randomized parallel 16 weeks

 

potentials: wave I SMD 0.59218657 Unspecified

Unay, 2004 2000-2001 Turkey Healthy infants 44 Formula A vs Formula B Trial randomized parallel 16 weeks

 y 

potentials: wave III SMD 1.096204042 Unspecified

Unay, 2004 2000-2001 Turkey Healthy infants 44 Formula A vs Formula B Trial randomized parallel 16 weeks

 

potentials: wave V SMD 1.541923404 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 215

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel birth birth weight SMD -0.006778704 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 154

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months

 g q 

Bayley Scales of Infant OR 0.9009009 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 154

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months

 

Bayley Scales of Infant OR 1.593172073 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 154

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months

 

Bayley Scales of Infant OR 1.824324369 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 159

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 14 months

 g q 

Infant MacArthur OR 2.076923132 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 134

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months

 

Infant MacArthur OR 1.880136967 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 159

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 14 months

 

Infant MacArthur OR 2.423076868 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 134

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months

 g q 

Infant MacArthur OR 2.051058531 Unspecified
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 134

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months

 

Toddler MacArthur OR 2.172602654 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 154

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months

 

Bayley Scales of Infant OR 1.189189196 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 154

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months

 g q 

Bayley Scales of Infant OR 1.132561088 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 176

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 12 months

 

acuity>==13 cycles/degree OR 1.172839522 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 184

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 2 months

 

acuity>==3.3 cycles/degree OR 2.219444513 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 178

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 12 months length-for-age z score SMD -0.303669691 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 158

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months length-for-age z score SMD -0.222088635 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 194

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 2 months length-for-age z score SMD -0.113076374 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 196

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 6 months length-for-age z score SMD -0.076164596 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 183

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 9 months length-for-age z score SMD -0.262741685 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 175

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 12 months weight-for-age z score SMD -0.029014073 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 144

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months weight-for-age z score SMD -0.059054446 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 191

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 2 months weight-for-age z score SMD -0.231481478 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 196

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 6 months weight-for-age z score SMD -0.150995702 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 181

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 9 months weight-for-age z score SMD 0.009529548 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 174

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 12 months weight-for-length z score SMD 0.173458695 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 144

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 18 months weight-for-length z score SMD 0 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 191

 ( 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 2 months weight-for-length z score SMD -0.228453875 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 196

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 6 months weight-for-length z score SMD -0.1455805 Unspecified

Mulder, 2014 2004 to 2008 Canada Healthy pregnant women 181

 

97.5th 

 

Phusphatidylethanol DHA supplement vs placebo Trial randomized parallel 9 months weight-for-length z score SMD 0.206030265 Unspecified

Escamilla-Nunez, 2014 2005-2009 Mexico

g 

allergies

 

(25th, 75th Trial randomized parallel breathing difficulty Primary

Escamilla-Nunez, 2014 2005-2009 Mexico

 

allergies

 

(25th, 75th Trial randomized parallel cough Primary

Escamilla-Nunez, 2014 2005-2009 Mexico

 

allergies 869

 

(25th, 75th DHA vs Placebo Trial randomized parallel 18 months

 

and/or nasal discharge, fever OR 1 Primary

Escamilla-Nunez, 2014 2005-2009 Mexico

g 

allergies

 

(25th, 75th Trial randomized parallel wheezing Primary

Harper, 2010 01. 2005 - 10. 2006 US At risk for preterm labor DHA+EPA vs placebo Trial randomized parallel birth birth weight NC Secondary

Harper, 2010 01. 2005 - 10. 2006 US At risk for preterm labor Trial randomized parallel birthweight <2500g Secondary

Harper, 2010 01. 2005 - 10. 2006 US At risk for preterm labor 852 DHA+EPA vs placebo Trial randomized parallel during pregnancy

p p g 

hypertension OR 1.043478251 Secondary

Harper, 2010 01. 2005 - 10. 2006 US At risk for preterm labor 837 DHA+EPA vs placebo Trial randomized parallel birth SGA less than 10th percentile OR 1.220000029 Secondary

Harper, 2010 01. 2005 - 10. 2006 US At risk for preterm labor 837 DHA+EPA vs placebo Trial randomized parallel birth birthweight <1500g OR 1.161632299 Secondary

Harper, 2010 01. 2005 - 10. 2006 US At risk for preterm labor 837 DHA+EPA vs placebo Trial randomized parallel birth birthweight <2500g OR 1.240892529

Harper, 2010 01. 2005 - 10. 2006 US At risk for preterm labor DHA+EPA vs placebo Trial randomized parallel birth gestational age NC Secondary

Harper, 2010 01. 2005 - 10. 2006 US At risk for preterm labor 852 DHA+EPA vs placebo Trial randomized parallel birth incidence of premature birth OR 1.101587057 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

y y 

pregnant women 900 DHA vs Placebo Trial randomized parallel birth birthweight <2500g OR 1.394736886 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 749 DHA vs Placebo Trial randomized parallel 1 month

y p 

latency 1 SMD 0.066548586 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 664 DHA vs Placebo Trial randomized parallel 3 months

 

latency 1 SMD 0 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

y y 

pregnant women 749 DHA vs Placebo Trial randomized parallel 1 month

y p 

latency 1-3 SMD 0.031397559 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 664 DHA vs Placebo Trial randomized parallel 3 months

 

latency 1-3 SMD -0.035714287 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 749 DHA vs Placebo Trial randomized parallel 1 month

 

latency 1-5 SMD 0.05330497 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

y y 

pregnant women 664 DHA vs Placebo Trial randomized parallel 3 months

y p 

latency 1-5 SMD 0.07692308 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 749 DHA vs Placebo Trial randomized parallel 1 month

 

latency 3 SMD 0.030762423 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 664 DHA vs Placebo Trial randomized parallel 3 months

 

latency 3 SMD -0.03076845 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

y y 

pregnant women 749 DHA vs Placebo Trial randomized parallel 1 month

y p 

latency 3-5 SMD 0 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 664 DHA vs Placebo Trial randomized parallel 3 months

 

latency 3-5 SMD 0.088181496 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 749 DHA vs Placebo Trial randomized parallel 1 month

 

latency 5 SMD 0.066548586 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

y y 

pregnant women 664 DHA vs Placebo Trial randomized parallel 3 months

y p 

latency 5 SMD 0.097546339 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

y y 

pregnant women 679 DHA vs Placebo Trial randomized parallel 3 months

 

Amplitude P SMD -0.06494198 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 679 DHA vs Placebo Trial randomized parallel 6 months

 

Amplitude P SMD -0.014183416 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

y y 

pregnant women 679 DHA vs Placebo Trial randomized parallel 3 months

 p 

Latency N1 SMD -0.017955747 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 679 DHA vs Placebo Trial randomized parallel 6 months

 

Latency N1 SMD 0.094251022 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 679 DHA vs Placebo Trial randomized parallel 3 months

 

Latency N3 SMD 0.096027076 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

y y 

pregnant women 679 DHA vs Placebo Trial randomized parallel 6 months

 p 

Latency N3 SMD 0.034909811 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 679 DHA vs Placebo Trial randomized parallel 3 months

 

Latency P1 SMD 0.027921384 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

 

pregnant women 679 DHA vs Placebo Trial randomized parallel 6 months

 

Latency P1 SMD 0.055364583 Primary

Stein, 2012 Feb 2005-Feb 2007 NR

y y 

pregnant women Trial randomized parallel Primary

Lagemaat, 2011 2003 - 2006 Netherlands

 

weight infants 87

 

Mean(SD) AA PDF: HM vs Term Formula (TF) Trial randomized parallel term age head circumference SMD -0.13333334 Unspecified

Lagemaat, 2011 2003 - 2006 Netherlands

 

weight infants 93

 

Mean(SD) AA PDF: PDF vs Term Formula (TF) Trial randomized parallel term age head circumference SMD 0.074617639 Unspecified

Lagemaat, 2011 2003 - 2006 Netherlands

 

weight infants 87

 ( ) 

Mean(SD) AA PDF: HM vs Term Formula (TF) Trial randomized parallel term age length SMD -0.215482861 Unspecified

Lagemaat, 2011 2003 - 2006 Netherlands

 

weight infants 93

 

Mean(SD) AA PDF: PDF vs Term Formula (TF) Trial randomized parallel term age length SMD 0 Unspecified

Lagemaat, 2011 2003 - 2006 Netherlands

 

weight infants 87

 

Mean(SD) AA PDF: HM vs Term Formula (TF) Trial randomized parallel term age weight SMD -0.109594747 Unspecified

Lagemaat, 2011 2003 - 2006 Netherlands

 

weight infants 93

 ( ) 

Mean(SD) AA PDF: PDF vs Term Formula (TF) Trial randomized parallel term age weight SMD -0.111676455 Unspecified

D'Vaz, 2012 2005-2009 Australia

 

allergies 323 Fish oil group vs Placebo Trial randomized parallel 12 months

 

mediated food allergy, OR 1.044960976 Primary

D'Vaz, 2012 2005-2009 Australia

 

allergies 323 Fish oil group vs Placebo Trial randomized parallel 12 months food allergy OR 1.229120731 Primary

D'Vaz, 2012 2005-2009 Australia

g 

allergies 323 Fish oil group vs Placebo Trial randomized parallel 12 months eczema OR 1.041327238 Primary

D'Vaz, 2012 2005-2009 Australia

 

allergies 323 Fish oil group vs Placebo Trial randomized parallel 12 months asthma OR NC Primary

D'Vaz, 2012 2005-2009 Australia

 

allergies 323 Fish oil group vs Placebo Trial randomized parallel 12 months persistent cough OR 0.845166802 Primary

D'Vaz, 2012 2005-2009 Australia

g 

allergies 323 Fish oil group vs Placebo Trial randomized parallel 6 months persistent cough OR 1.327450395 Primary

D'Vaz, 2012 2005-2009 Australia

 

allergies 323 Fish oil group vs Placebo Trial randomized parallel 12 months recurrent wheeze OR 0.711719394 Primary

D'Vaz, 2012 2005-2009 Australia

 

allergies 323 Fish oil group vs Placebo Trial randomized parallel 6 months recurrent wheeze OR 1.096589446 Primary

Collins, 2011 2001-2007 Australia

 p 

women Breast-feeding 456 High DHA vs standard DHA Trial randomized parallel 12 months head circumference SMD -0.055555556 Secondary

Collins, 2011 2001-2007 Australia

 

women Breast-feeding 587 High DHA vs standard DHA Trial randomized parallel 18 months head circumference SMD 0 Secondary

Collins, 2011 2001-2007 Australia

 

women Breast-feeding 601 High DHA vs standard DHA Trial randomized parallel 4 months head circumference SMD -0.117647052 Secondary

Collins, 2011 2001-2007 Australia

 p 

women Breast-feeding 465 High DHA vs standard DHA Trial randomized parallel 12 months length SMD 0.054768324 Secondary
Study Study years (start date) Country Population

 

(total)

 

intake

 

(Baseline) n-3 type(s) study_design Follow-up time Outcome Effect size type (OR or SMD) Reported effect Size Outcome classification

Collins, 2011 2001-2007 Australia

 

women Breast-feeding 592 High DHA vs standard DHA Trial randomized parallel 18 months length SMD 0.177277058 Secondary

Collins, 2011 2001-2007 Australia

 

women Breast-feeding 605 High DHA vs standard DHA Trial randomized parallel 4 months length SMD 0.030263307 Secondary

Collins, 2011 2001-2007 Australia

 p 

women Breast-feeding 471 High DHA vs standard DHA Trial randomized parallel 12 months weight SMD 0.085180961 Secondary

Collins, 2011 2001-2007 Australia

 

women Breast-feeding 598 High DHA vs standard DHA Trial randomized parallel 18 months weight SMD 0.154532641 Secondary

Collins, 2011 2001-2007 Australia

 

women Breast-feeding 615 High DHA vs standard DHA Trial randomized parallel 4 months weight SMD 0.014466298 Secondary

Escolano-Margarit, 2011 2001-2008 Germany, Spain, Hungary Healthy pregnant women 167

 

plasma DHA fish oil vs placebo Trial randomized parallel 5.5 years

 

Hempel exam OR 0.993518531 Secondary

Escolano-Margarit, 2011 2001-2008 Germany, Spain, Hungary Healthy pregnant women 148

 

plasma DHA fish oil vs placebo Trial randomized parallel 5.5 years

 

Towen exam OR 1.000791192 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 849 DHA vs Placebo Trial randomized parallel 1 month (preceding 15 days)

 

nasal congestion, nasal OR 1.18617022 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 3 months

 ( y g p g 

nasal congestion, nasal OR 1.166666746 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 6 months (preceding 15 days)

 

nasal congestion, nasal OR 1.008658051 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 849 DHA vs Placebo Trial randomized parallel 1 month (preceding 15 days) cough OR 1.157894731 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 3 months cough OR 1.238341928 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 6 months (preceding 15 days) cough OR 0.993957698 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 849 DHA vs Placebo Trial randomized parallel 1 month (preceding 15 days) difficulty breathing OR 0.958333373 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 3 months difficulty breathing OR 0.827586174 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 6 months (preceding 15 days) difficulty breathing OR 1.214285731 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 849 DHA vs Placebo Trial randomized parallel 1 month (preceding 15 days) nasal congestion OR 1.163120627 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 3 months nasal congestion OR 1.131474137 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 6 months (preceding 15 days) nasal congestion OR 0.945945978 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 849 DHA vs Placebo Trial randomized parallel 1 month (preceding 15 days) nasal secretion OR 1.521126747 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 3 months nasal secretion OR 1.15436244 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 6 months (preceding 15 days) nasal secretion OR 1.046099305 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 849 DHA vs Placebo Trial randomized parallel 1 month (preceding 15 days) phlegm OR 1.142857194 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 3 months phlegm OR 0.953846157 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 6 months (preceding 15 days) phlegm OR 1.012552261 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 849 DHA vs Placebo Trial randomized parallel 1 month (preceding 15 days) wheezing OR 0.843373537 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 3 months wheezing OR 1.157142878 Secondary

Imhoff-Kunsch, 2011 February 2005 - February 2007 Mexico Healthy pregnant women 834 DHA vs Placebo Trial randomized parallel 6 months (preceding 15 days) wheezing OR 0.915966392 Secondary

Marks, 2006 1997-2004 Australia

 

allergies 516 Active vs Diet control Trial randomized parallel 5 years

 

test) OR 1.062451601 Secondary

Marks, 2006 1997-2004 Australia

g 

allergies 516 Active vs Diet control Trial randomized parallel 5 years rhinitis OR 0.985346794 Secondary

Marks, 2006 1997-2004 Australia

 

allergies 516 Active vs Diet control Trial randomized parallel 5 years current eczema OR 1.171575189 Secondary

Marks, 2006 1997-2004 Australia

 

allergies 516 Active vs Diet control Trial randomized parallel 5 years cough without cold OR 0.701861978 Secondary

Marks, 2006 1997-2004 Australia

g 

allergies 516 Active vs Diet control Trial randomized parallel 5 years frequent wheeze OR 0.857831299 Secondary

Marks, 2006 1997-2004 Australia

 

allergies 516 Active vs Diet control Trial randomized parallel 5 years probable current asthma OR 0.882044315 Primary

Palmer, 2013

 

Domino study) Australia

 

of allergy 706 Fish oil vs Control Trial randomized parallel 3 years allergic rhinitis OR 1.209730387 Primary

Palmer, 2013

 ( gy p 

Domino study) Australia

 y y 

of allergy 706 Fish oil vs Control Trial randomized parallel 3 years food allergy OR 0.846811295 Primary

Palmer, 2013

 

Domino study) Australia

 

of allergy 706 Fish oil vs Control Trial randomized parallel 3 years eczema OR 4.645364761 Primary

Palmer, 2013

 

Domino study) Australia

 

of allergy 706 Fish oil vs Control Trial randomized parallel 3 years asthma OR 0.90729785 Primary

Drover, 2012 NR US Healthy infants 42

 

Control group Trial randomized parallel 2.5 years

 p 

(SRC) SMD 0.236179456 Secondary

Drover, 2012 NR US Healthy infants 46

 

Control group Trial randomized parallel 2.5 years

 

(SRC) SMD 0.320607185 Secondary

Drover, 2012 NR US Healthy infants 43

 

Control group Trial randomized parallel 2.5 years

 

(SRC) SMD 0.394611269 Secondary

Atwell, 2013 2001-2005 Australia Preterm infants 657 High DHA vs Standard DHA Trial randomized parallel 18 months

 p 

for lower respiratory OR 1.094693184 Secondary

Linnamaa, 2010 2004-2008 Finland

 

pregnant women 241 Intervention vs Controls Trial randomized parallel birth birth weight SMD -0.008606554 Secondary

Linnamaa, 2010 2004-2008 Finland

 

pregnant women 202 Intervention vs Controls Trial randomized parallel 12 months positive egg skin test OR 1.211538434 Secondary

Linnamaa, 2010 2004-2008 Finland

y y 

pregnant women 166 Intervention vs Controls Trial randomized parallel 24 months positive egg skin test OR 1.589080453 Secondary

Linnamaa, 2010 2004-2008 Finland

y y 

pregnant women 238 Intervention vs Controls Trial randomized parallel 3 months positive egg skin test OR 0.888888896 Secondary

Linnamaa, 2010 2004-2008 Finland

 

pregnant women 210 Intervention vs Controls Trial randomized parallel 12 months atopic dermatitis OR 1.432506919 Primary

Linnamaa, 2010 2004-2008 Finland

y y 

pregnant women 177 Intervention vs Controls Trial randomized parallel 24 months atopic dermatitis OR 1 Primary

Linnamaa, 2010 2004-2008 Finland

 

pregnant women 241 Intervention vs Controls Trial randomized parallel 3 months atopic dermatitis OR 1 Primary