Introduction

The purpose of this study was to conduct a

systematic review of the scientific-medical

literature to identify, appraise, and synthesize the

human evidence for the effects of omega-3 fatty

acids on child and maternal health. The review

was requested and funded by the Office of

Dietary Supplements, National Institutes of

Health. It was undertaken as part of a

consortium involving three Evidence-based

Practice Centers (EPCs), which investigated the

value of omega-3 fatty acid supplementation

across eleven health/disease areas. The three

EPCs are Southern California-RAND, Tufts-New

England Medical Center, and the University of

Ottawa. To ensure consistency of approach, the

three EPCs collaborated on selected methodologic

elements, including literature search strategies,

rating of evidence, and data table design.

It has been posited that the accretion of

omega-3 fatty acids within the maternal biological

system has the potential to influence both

maternal health during pregnancy and fetal

health. Likewise, it has been hypothesized that

their accumulation within the post-delivery child’s

biological system can affect its development and

health. Birth weight is the most important factor

affecting neonatal morbidity and mortality, and is

thus an outcome worth monitoring.1 Moreover,

premature infants are at risk of injury to every

organ system in the newborn period. Of greatest

concern for infants who survive are the risks of

developing permanent neurocognitive deficits that

impact their lifelong health and functional

capacity.2-5

Results of studies conducted on residents of the

Faroe Islands6,7 suggest that marine diets, which

contain omega-3 fatty acids, increase birth weight

either by prolonging pregnancy8 or by increasing

the fetal growth rate.9,10 Additionally, it has been

hypothesized that marine oils may lower risks of

certain complications of pregnancy, in particular

preterm delivery, intrauterine growth retardation,

preeclampsia, and gestational hypertension,11

given that some of omega-3 fatty acids’ presumed

mechanisms of action overlap with those of

aspirin.12-14

Docosahexaenoic acid (DHA) and arachidonic

acid (AA) have been identified as important

structural components of the highly specialized

membrane lipids of the human central nervous

system, with phospholipids of brain gray matter

containing high proportions of DHA.15-17 DHA

has also been observed to be the major long-chain

polyunsaturated fatty acid (LC PUFA) in the

outer segments of the retina’s rods and cones.15

Based on observational studies, it has been

shown that human milk fed infants have

improved neurocognitive development compared

to formula fed infants; it was hypothesized that

one of the contributing factors may be the

availability of long-chain derivatives of linoleic

acid (LA) and alpha-linolenic acid (ALA) that is

present only in human milk.18,19 This difference

in fatty acids intake is reflected in lower

erythrocyte membrane phospholipid DHA in

Evidence Report/Technology Assessment

Number 118

Effects of Omega-3 Fatty Acids on Child and

Maternal Health

Summary

Authors: Lewin GA, Schachter HM, Yuen D, Merchant P, Mamaladze V, Tsertsvadze A, et al.

Agency for Healthcare Research and Quality

Advancing Excellence in Health Care • www.ahrq.gov

Agency for Healthcare Research and Quality Evidence-Based

Practice
2

infants fed formula.18 Until the recent availability of infant

formula with added omega-3 LC PUFAs, standard infant

formula was devoid of these fatty acids. 

The likely significance of omega-3 fatty acids for child health

is therefore suggested by the observations that (a) the human

brain and retina each contain considerable amounts of omega-3

fatty acids; (b) the children delivered at term receive an

important supply of omega-3 fatty acids, especially in the third

trimester of pregnancy; and (c) due to a shortened gestational

period, a child delivered prematurely receives less exposure to

omega-3 fatty acids content than does the term child. Not

surprisingly, the observation concerning preterm infants has

afforded considerable empirical study of the impact of omega-3

fatty acids on the health of such infants.

Key Questions 

The questions are organized by type of population (i.e.,

maternal/pregnancy versus child) and type of outcome data

(i.e., clinical/pregnancy versus clinical/child-developmental).

Maternal population, pregnancy outcomes/biomarkers

associations:

• What is the evidence that intake of omega-3 fatty acids

influences

- duration of gestation?

- incidence of preeclampsia, eclampsia or gestational

hypertension?

- incidence of births of human infants small for

gestational age (SGA)?

Child population, growth patterns, neurological, visual or

cognitive developmental outcomes/biomarkers

associations:

• What is the evidence that maternal intake of omega-3

fatty acids

- during pregnancy influences any of the clinical

outcomes in term or preterm human infants?

- within maternal breast milk, infant formula, both

and/or other sources (i.e., diet) influences any of the

clinical outcomes in term or preterm human infants?

• What is the evidence that term or preterm human infants’

clinical outcomes are associated with the omega-3 or

omega-6/omega-3 fatty acids content of

- maternal or fetal biomarkers during pregnancy?

- child biomarkers?

Adverse effects:

• What is the evidence for the risk, in pregnant or

breastfeeding women, term or preterm human infants, of

short- and long-term adverse events related to their intake

of omega-3 fatty acids during pregnancy or after birth?

Methods

A Technical Expert Panel (TEP) consisting of six members

was convened to provide advisory support to the project,

including refining the questions and highlighting key variables

requiring consideration in the evidence synthesis.

Study Identification

Several electronic databases were searched: MEDLINE®,

PreMEDLINE®, EMBASE, the Cochrane Library including

the Cochrane Central Register of Controlled Trials, and CAB

Health. Searches were not restricted by language of publication,

publication type, or study design, except with respect to the

MeSH term “dietary fats,” which was limited by study design

to increase its specificity. Search elements included scientific

terms, with acronyms, as well as generic and trade names

relating to the exposure and its sources (e.g., eicosapentaenoic

acid [EPA], omega-3 fatty acids, infant formula) and relevant

population terms (e.g., gestational hypertension). Reference

lists of included studies, book chapters, and narrative or

systematic reviews retrieved after having passed the first level of

relevance screening were manually searched to identify

additional unique references. Through contact with content

experts, attempts were made to identify both published and

unpublished studies. A final set of 2,049 unique references was

identified and posted to an internet-based software system for

review.

Studies were considered relevant if they described live,

otherwise “healthy” human populations of any age. The

generic term “child” was used to refer to infants (less than 12

months of age), toddlers, and children up to 18 years old.

Excluded were studies whose biomarker data were solely

obtained from aborted fetuses and which did not distinguish

between data obtained from term and preterm births. 

Interventional/exposure studies had to specifically investigate

foods or supplements known to contain omega-3 fatty acids of

any type, from any source, any serving size or dose, delivered in

any fashion and for any length of time. No restrictions were

placed on the types or doses of pre- or on-study

cointerventions. While omega-6 fatty acids appear to play a key

role in health and development, and their possible co-influence

on outcomes is thus assessed in our review, studies exclusively

investigating their impact on health outcomes were excluded. 

If at least two randomized controlled trials (RCTs) were

identified, no other types of design were required. Yet, if

insufficient numbers of RCTs were retrieved, non-RCT (i.e.,

controlled clinical trials, without random allocation) and
observational studies (i.e., cohort, case-control, or crosssectional studies) were included. Descriptive study designs

were also excluded.

Any and all child developmental outcomes reflecting the

four categories of the developmental arc were considered

relevant. As markers of omega-3 fatty acids metabolism, the

following fatty acids compositions or concentrations, from any

source (e.g., red blood cell [RBC] membranes, plasma

phospholipids) were considered relevant: EPA, DHA, AA/EPA,

AA/DHA, AA/EPA+DHA. 

Two initial levels of screening for relevance, and two

reviewers per level, were employed (directed at bibliographic

records, then full articles). A screening identified and excluded

uncontrolled studies. Calibration exercises preceded each step

of the screening process. The reasons for the unsuitability of

excluded studies were noted according to a modified

QUOROM format.20 Disagreements were resolved by

consensus and, when necessary, third-party intervention. 

Data Abstraction

Following a calibration exercise involving two studies, eleven

reviewers independently abstracted the contents of included

studies using an electronic data abstraction form. A second

reviewer then verified these data. Data abstracted included the

characteristics of the report (e.g., publication status), study

(e.g., sample size), population (e.g., preterm versus term status),

intervention/exposure (e.g., omega-3 fatty acids types), and

comparator(s), cointerventions (e.g., omega-6 fatty acids use),

withdrawals and dropouts, including reasons, clinical outcomes,

fatty acids content of biomarkers, and adverse events.

Data Synthesis

A summary table provided a question-specific overview of

included studies’ relevant data, which is presented in greater

detail in evidence tables. A question-specific summary matrix

described each study in terms of its quality and applicability

ratings. Question-specific qualitative syntheses of the evidence

were derived. Meta-analysis was performed if the following

criteria were met: at least two RCTs, same population

characteristics (mean age, health status, gender), same cointerventions, same intervention based on the type of omega-3

fatty acids supplemented (DHA+AA vs. DHA vs. DHA+EPA,

etc.) regardless of the daily dose in the child population, same

comparator based on source of placebo (e.g., olive oil,

unsupplemented formula), outcomes relevant to respond to the

key-questions: percentage (n) of premature deliveries, incidence

of gestational hypertension (GHT), pre-eclampsia or eclampsia,

incidence of IUGR or SGA infants, weight, length, and head

circumference of infants (means), neurological and cognitive

development measured by validated scales (e.g., Bayley’s

Developmental Scale score), and visual acuity or visual function

of infants measured by appropriate tests (Teller’s Card test,

etc.).

Results

Literature Search

Of the 2,049 records entered into the initial screening for

relevance, 1,579 were excluded. Of the 191 reports that made

it to this level of screening, 74 were excluded. Hence, in total,

117 reports, describing 89 unique studies, were deemed

relevant for the systematic review, with 20 studies each

described by more than one report and three reports describing

more than one unique study. There were 63 randomized

controlled trials (RCTs) and 26 observational studies across all

the key questions. Only one study required translation from

German to English.21 No studies were identified across all the

child outcomes (i.e., growth patterns, neurocognitive

development, and visual function) regarding the influence of

the intake of omega-3 fatty acids from sources other than

human milk, or infant formula, as well as the association

between omega-3 or omega-6/omega-3 fatty acids content of

fetal biomarkers and any of the clinical outcomes. Synopses of

evidence are presented according to the clinical outcomes by

population.

Safety Issues

Overall, omega-3 fatty acids supplementation in pregnant

women, breastfeeding mothers, and preterm and term infants,

was very well tolerated and did not generate any serious adverse

events across the included RCTs. The safety data was reported

in 21 RCTs. In pregnant women, the adverse events related to

the omega-3 fatty acids intake were mild and transient, with

nausea and gastrointestinal discomfort being the most

commonly reported.22,23 For both term and preterm

populations, change in number of stools and flatulence were

the most common adverse events related to the omega-3

supplemented formulas. However, most of the serious harms

were related to the fact that the infants were premature with

low birth weights, which increases the occurrence of necrotizing

enterocolitis (NEC), bleeding problems, infections and

respiratory failure, among others in the case of preterm

infants.24-43 None of the withdrawals were due to the

interventional formula.

Pregnancy Outcomes

Duration of gestation-intake during pregnancy: Fifteen

poor quality RCTs addressed this question.11,44-51,59 Seven trials

included otherwise healthy pregnant women,52-58 the remaining

eight studies included a high-risk population of pregnant

3
4

women. Ten studies did not find a significant difference

between intervention groups in the duration of gestation

measured as mean of gestational age at delivery.22,23,53-58 Four

poor quality studies observed that the omega-3 fatty acids

group had a significantly greater duration of gestation after

treatment compared with the unsupplemented group.22,52

Omega-3 fatty acids did not have a significant effect on the

proportion of premature deliveries in ten studies.11,23,52,55,59 Fish

consumption in the background diet was used as a covariate in

only one trial.52 Other covariates used to control the results

were: the compliance with the intervention,52 current smoking

status,23,55 maternal BMI, and number of prior pregnancies.55

The only variable that had an impact on the results was the

smoking status in Smuts et al.’s study.55 The duration of

gestation was significantly longer in the high-DHA group in

the nonsmokers.55

Meta-analysis of the incidence of premature deliveries was

performed from eight RCTs that used capsules containing

DHA+EPA (OR: 0.88 [95% CI: 0.62-1.25]),11,44,49 and two

trials using high DHA eggs (OR: 0.53 [95% CI: 0.13-2.29])47,50

or control group. There is inconsistent evidence of the use of

omega-3 fatty acids supplements during the second or third

trimester of pregnancy to reduce the incidence of premature

pregnancies in high- and low-risk populations. Nevertheless,

the overall effect does not show a significant difference between

study arms.

Duration of gestation-maternal biomarkers: Nothing

conclusive can be drawn from four studies that assessed this

association.55,60-62

Incidence of gestational hypertension (GHT),

preeclampsia, or eclampsia-intake during pregnancy: Of

eight RCTs with a quality score approaching good internal

validity,22,23,52,63,64 six trials compared the use of fish oil

supplements containing DHA and EPA with placebo. The

population included healthy or high-risk pregnant women (i.e.,

twin pregnancy).22,23,63,64 The incidence of GHT in these

populations, after the use of omega-3 fatty acids or placebo did

not differ in six studies.22,23,52,59,63 Regarding the incidence of

preeclampsia (hypertension, edema, and proteinuria), six

studies showed that compared with placebo, supplementation

with omega-3 fatty acids did not have a significant

effect.22,23,55,59,63 Meta-analysis of the incidence of gestational

hypertension from two studies revealed a nonsignificant

difference between groups (OR: 1.07, CI 95%: 0.75; 1.51).22,23

These findings were not adjusted for the potential covariates or

confounders, such as background diet, grade of risk for GHT

or preeclampsia in the current pregnancy, smoking status, and

age.

Incidence of preeclampsia-eclampsia or gestational

hypertension-maternal biomarkers: Five observational studies

were identified,21,65-68 of which four selected preeclamptic

women and normal pregnant women as controls.21,66-68 The

results are very inconsistent across the studies. 

Incidence of SGA infants- intake during pregnancy:

Fourteen poor quality score RCTs showed that in the majority

of the studies, the mean birth weight was not influenced by the

intervention. None of the trials adjusted their results for the

maternal background diet, which can be an important effect

modifier. 

Meta-analysis of the birth weight (mean) was combined in

two studies that were comparable in terms of type of

intervention and population (weight mean difference: -61.51,

CI 95%: -256.21; 133.18) showing a nonsignificantly

difference between groups.23 The incidence of infants with

IUGR showed a nonsignificant effect (OR: 1.14, CI 95%:

0.79; 1.64)22,23,59 of supplementation during pregnancy. 

Incidence of SGA infants-maternal biomarker: Six

studies addressed this question.58,60,61,69-71 de Groot et al.’s RCT

found a significantly positive correlation between the maternal

plasma and RBC DHA content and birth weight; however, this

relationship was nonsignificant when measured at delivery.58

Two observational studies found that the women with IUGR

fetuses had a significantly lower content of LA (omega-6) in the

plasma.69,71 The content of DHA, EPA, AA, total omega-3 and

omega-6 fatty acids, however, did not show a constant pattern

across the studies. Two observational studies did not observe a

correlation between maternal plasma biomarkers and birth

weight,61,69 consistent with the result in the RCT.58

Growth Pattern Outcomes

Maternal intake during pregnancy: One good quality

RCT addressed this question,54 showing no statistical difference

between infants (n=590 enrolled, 341 completers) from

mothers that were taking the supplementation with omega-3

and omega-6, or omega-6 fatty acids predominantly, on the

weight, length, and head circumference (HC) from birth to 12

months of age.54

Maternal breast milk: One good quality RCT evaluating

omega-3 supplementation in Norwegian mothers,54 one poor

quality RCT,72 and two observational studies were identified.73,74

Both RCTs showed no apparent effects of breast milk, with

maternal intake of omega-3 (DHA) or omega-6 fatty acids

(AA), on the growth patterns at any time point.54,72 The single

prospective cohort of Swedish mother/term infant pairs

showed a positive correlation between the maternal mother’s

breast milk content of AA/DHA and the infant’s rate of

increase of HC at 1 and 3 months of age.74 A cross-sectional
study from Africa showed that the differences in weight-for-age

and weight-for-height z-scores and weight gain (g) were

significantly lower in infants from Ouagadougou (low omega-3

fatty acids intake) compared with infants from Brazzaville (high

omega-3 intake).73

Formula intake, preterm infants: Twenty RCTs of poor

quality were identified,25-32,34,75-85 of which eighteen failed to find

an effect of the omega-3 supplementation in preterm formulas

on the growth parameters at any time point.25-30,32,34,75-84 The

outcomes measured were the mean (SD) and gain in weight,

length, and HC and the normalized z-score of weight. Two

trials found that the omega-3 fatty acids supplemented group

had a significantly lower weight from 6 to 18 months.31,85 The

results of the meta-analysis performed on the mean weight and

length measured at 4 months, from studies that compared the

use of formula supplemented with DHA+AA with control,

showed that the overall effect was nonstatistically significant

(weight: WMD: 0.04, CI 95%: -0.30; 0.38; length: WMD:

0.09, CI 95%: -0.62; 0.80).28,29

Formula intake, term infants: Eighteen good quality

RCTs were identified.35-43,86-93 The effects on the growth

outcomes were nonstatistically different between study arms.

Yet, some inconsistent differences were found across five trials

at certain timepoints and subgroup of patients.94-98 Metaanalysis demonstrated a nonstatistically significant overall effect

of formulas containing DHA+AA compared with control

formula at 4 or 12 months of age for the growth parameters 

(4 months: weight: WMD: -0.06, CI 95%: -0.45; 0.34;

length: WMD: -0.33, CI 95%: -1.07; 0.40; 12 months:

weight: WMD: -0.33, CI 95%: -0.87; 0.21; length: WMD: -

0.37, CI 95%: -1.26; 0.51; HC: WMD: 0.14, CI 95%: -0.83;

1.12) or DHA (4 months: weight: WMD: -0.12, CI 95%: -

0.44; 0.20; length: WMD: -0.43, CI 95%: -1.20; 0.34; HC:

WMD: 0.04, CI 95%: -0.37; 0.46. 12 months: weight:

WMD: -0.33, CI 95%: -0.87; 0.21; length: WMD: -0.71, CI

95%: -2.18; 0.76; HC: WMD: -0.04, CI 95%: -0.45; 0.38)

36,39 Only four trials adjusted the results for potential

confounders, such as gender, maternal education, parental

socioeconomic status and center, failing to find any change in

the results.39,41,43,88

Child biomarkers: Five were RCTs in preterm

infants,25,28,29,76,85 and five RCTs39,43,87,88,99 and a prospective single

cohort

100 in term infants. 

There is a negative correlation between weight and the

plasma or RBC content of DHA, and a positive correlation

between weight and the content of AA in plasma or RBC.

However, not all of the studies found this association. The

content of omega-6 fatty acids (AA) as a biomarker may be

related to weight gain in infants. The content of DHA seems

to be inversely related to weight gain, yet no significant clinical

outcomes were detected. 

Neurological Development Outcomes

Maternal intake during pregnancy: Helland et al. failed

to find a significant difference between groups in maturity as

evaluated from the EEGs, neither at day 1 of life nor at 

3 months of age.54

Maternal breast milk: Two studies, one RCT101 and one

single prospective cohort design102 showed that maternal breast

milk may not have an influence on the neurological outcome,

measured with the PDI scale of the Bayley’s Index.

Formula intake, preterm infants: Six good quality RCTs

were identified.28,30,31,34,82,103 For the Bayley’s PDI scale, two trials

did not observe a significant difference between the

supplemented and the control formula.31,34 Meta-analysis was

not possible for this outcome. Only Fewtrell et al. found that

there was no difference between groups in the neurological

impairment assessment at 9 and 18 months of corrected age

(CA), and in the Knobloch, Passamanick, and Sherrards’

Developmental Screening Inventory score.34 There is not

consistent evidence to suggest that the omega-3 fatty acids

supplementation of infant formula, with or without breast

milk, influences the neurological development in preterm

infants. 

Formula intake, term infants: Eight good quality RCTs,36-

39,42,43,104 of which seven failed to find a statistically significant

difference between diet groups at different follow-ups (6 to 24

months of age) in the Bayley’s PDI scale.36-39,42,43 One trial

showed a significantly better Brunet-Lézine test result in the LC

PUFAs supplemented group compared with control at 4

months of age (after exclusive formula intake) but not at 24

months.104 Meta-analysis of Bayley’s PDI score showed a

nonstatistically significant difference between groups using

formula supplemented with DHA+AA and control (WMD: -

2.80, CI 95%: -7.43; 1.82) at 12 months. 36,39,42

Maternal biomarkers: One cross-sectional study showed

that maternal DHA was negatively associated with active sleep

(AS), AS:QS (quiet sleep) and sleep-wake transition, and

positively associated with wakefulness (postpartum day 2).105

The ratio of n-6:n-3 in maternal plasma was positively

associated with AS, AS:QS and sleep-wake transition, and

negatively associated with wakefulness (day 2), suggesting a

greater CNS maturity. 

Child biomarkers: Three RCTs37,39,43 and a prospective

cohort study100 evaluated the association between the infant’s

plasma and RBC DHA content and the Bayley’s psychomotor

developmental index (PDI) score in healthy term infants. Two

RCTs found a significant positive correlation between the

5
plasma DHA and the PDI score.39,43 Two other studies

(including the observational study), did not find a significant

correlation between the PDI and the infant content of PUfatty

acids in plasma or RBC.37,100

Visual Function Outcomes

Maternal intake during pregnancy: One RCT failed to

find a significant effect of DHA supplementation during

pregnancy on the retinal sensitivity (ERG) measured at birth in

term infants.51 One cross-sectional study failed to find a

statistically significant difference in mean visual function values

between the exclusively breastfed group and the infants who

were also receiving formula.106

Maternal breast milk: Five studies found that the

correlation between the DHA content in breast milk and visual

function was not consistent with the clinical outcomes

measured in breastfed term infants of mothers who were or

were not taking supplements containing high DHA.72,101,106-108

Formula intake, preterm infants: Nine RCTs with a

quality score approaching good internal validity were

identified.25,26,28,29,76,77,82,85,103 Of five studies that measured visual

evoked potentials (VEP), two did not find a statistical

difference between feeding groups at any time point (from 1 to

12 months).82,103 Three studies found that compared with the

unsupplemented group, infants fed with LC PUFAssupplemented formula had a better or faster maturation of

visual function, in terms of significantly shorter waves in the

VEP.

25,28,77 Two studies found a significant difference between

groups in the Teller’s Acuity Card test.85 Meta-analysis of the

relevant visual outcomes comparing the studies by the type of

omega-3 fatty acids used in the supplemented formula (DHA

or DHA+AA) and control formula, and by the type of outcome

(VEP and Teller’s test of visual acuity) was done. For the VEP

visual acuity outcomes, only two studies were combined.25,28

O’Connor et al. found that the use of formulas with DHA+AA

resulted in a better VEP measurements compared with control

formula at 6 months of age yet not at 4 months.25,28

No significant effect of DHA-supplementation at 2, 4, 6, or

9 months of CA,29,76 or DHA+AA supplementation at 2, 3, 4,

or 6 months of CA was found in the visual acuity measured

with the Teller’s Card test.25,28,29,85,103

Formula intake, term infants: Thirteen RCTs, of average

good quality (Jadad: 3.61/5) were identified,36,37,39,41-43,88,89,91,93,109,110

of which five trials did not find a significant difference between

groups in the VEP at any age.36,39,41,43,89 Four trials found a

significantly better VEP in the LC PUFAs-supplemented group

compared with the control group at a number of time points,

from 1.5 to 13 months of age.37,87,91,93 The meta-analysis

performed on this outcome, by LC PUFAs content of DHA

alone (or with the addition of AA), versus control, showed that

the studies that compared DHA supplemented formula with

control formula did not have an overall significant effect at any

age.36,37,39 Conversely, in seven studies that compared the use of

DHA+AA formula with placebo, there was no difference

between groups at any age,36,37,39,87,89,91,93 with the exception of

four studies that found a significant difference at 12 months of

age.36,37,91,93

One trial that evaluated behavioral visual acuity with the

Teller’s test,110 found a significantly better acuity in the LC

PUFAs formula group compared with the control group at 2

months of age, yet not at 4, 6, 9, or 12 months. The

remaining four trials did not observe a significant difference

between groups in this outcome, at any time point.36,42,88 The

meta-analysis performed on this outcome showed that, in

studies comparing the use of DHA+AA with a control

intervention, acuity was only significantly better in the

DHA+AA group at 2 months of age,36,37,110 but not at 4, 6, 9, or

12 months of age.

Maternal biomarkers: One study measured the association

between the maternal content of biomarkers at 2 months

postpartum and the visual acuity (Teller’s Card Test) in term

infants at 2 months of age that failed to find a significant

correlation.106

Child biomarkers: Twenty-one studies assessed this

association. Of five studies in the preterm group, three were

RCTs,25,76,77 and two were cross-sectional studies.111,112 Of the 16

term infant studies, nine were RCTs,37,43,72,87-89,91,93,101 and seven

were observational studies.100,106,107,111,113-115 There was no pattern

of correlation between the infant’s biomarkers in blood and the

visual function outcomes across 21 studies that addressed this

issue.

Cognitive Development Outcomes

Maternal intake during pregnancy: One RCT addressed

this question.54 There were no differences between groups in

the novelty preference (Fagan Test of Infant Intelligence) at 6

and 9 months of age.54

Maternal breast milk: Two RCTs54,101 and one prospective

cohort

102 were identified. The study by Helland et al. was an

RCT described above,54 and Gibson et al. included mother of

term infants who intended to breastfeed.101 They were

randomized to receive five increasing doses of DHA (algal oil)

during the first 3 months postpartum. The mean Bayley’s

Mental Developmental Index (MDI) score did not differ

between groups at 1 or 2 years of age (underpowered).101

Formula intake preterm infants: Six good quality (Jadad:

4.4/5) RCTs were identified.28,30,31,34,76,103 Four of the five trials

6
did not find an effect on the Bayley’s MDI score from 3 to 24

months of age.28,31,34,116 Two studies found a significant

difference between the omega-3 fatty acids group and the

control group in the Fagan Test of Infant Intelligence.28,76

O’Connor et al. found that there was no significant differences

between groups in the Infant version of the MacArthur

Communicative Development Inventories at 9 months CA and

14 months CA.28 Meta-analysis was not possible given the

heterogeneity across the studies for each of the different

outcomes due to the intervention characteristics (meaning dose,

source of omega-3 fatty acids, duration of intervention),

cointerventions, different assessment tools, and timing of the

outcomes measures. 

Formula intake term infants: Six (of eight) good quality

RCTs36-39,42,43,92 did not find a significant difference between

groups (supplemented vs. control) in the Bayley’s MDI score

from 6 to 18 months of age.36-39,42,43 Birch et al. observed that

the DHA+AA group had a significantly higher score compared

with the control group at 18 months of age.37

The Knobloch, Passamanik, and Sherrards Development

Screening Inventory test (9 months),117 and the Fagan Test of

Infant Intelligence (6 and 9 months )98 did not differ between

groups. The IQ (Stanford-Binet), Receptive Vocabulary (PPVTR), Expressive Vocabulary, and Visual-Motor Index scores, as

well as the Problem-Solving scores, did not differ between

groups in two studies.36,92

A meta-analysis using the Bayley’s MDI score at 12 months

of age showed a nonstatistical difference between groups

(DHA+AA vs. control) from three trials (WMD: -0.80, CI

95%: -3.24; 1.63).36,39,42

Child biomarkers: Four good quality RCTs and two single

prospective cohort studies100,118 showed inconsistent results.

Discussion

Studies investigating the influence of omega-3 fatty acids on

child and maternal health revealed the absence of a notable

safety profile (i.e., moderate-to-severe adverse events).

Pregnancy outcomes were either unaffected by omega-3 fatty

acids supplementation, or the results were inconclusive. Results

suggested the absence of effects with respect to the impact of

supplementation on the incidence of GHT, preeclampsia or

eclampsia, as well as on infants being born SGA. However,

regarding evaluations of the duration of gestation, some

discrepancies were observed, although most of the studies failed

to detect a statistically significant effect. Biomarker data failed

to clarify patterns in pregnancy outcome data.

Results concerning the impact of the intake of omega-3 fatty

acids on the development of infants are primarily, although not

uniformly, inconclusive. The inconsistencies in study results

may be attributable to numerous factors. 

In addition, making clear sense of the absolute or relative

effects of individual omega-3 fatty acids, or even omega-3 fatty

acids combinations, on child outcomes is complicated or

precluded by the following problem. Studies typically

employed interventions that involved various cointerventional

or background constituents (e.g., omega-6 fatty acids), yet

whose metabolic interactions with the omega-3 fatty acids were

not taken into account in interpreting the results. The

dynamic interplay among these fatty acid contents (e.g.,

competition for enzymes), and how this interplay may

influence outcomes, may differ in important ways depending

on whether DHA or olive oil is added to this combination of

cointerventional or background constituents, particularly in the

maternal population. This strategy prevented the isolation of

the exact effects relating to the omega-3 fatty acids content. It

is thus very difficult to reliably ascribe definite child outcomerelated benefits, or the absence thereof, to specific omega-3

fatty acids. Biomarker data failed to clarify patterns in child

outcome data.

Future research should likely consider investigating the

impact of specific omega-6/omega-3 fatty acids intake ratios, in

no small part to control for the possible metabolic interactions

involving these types of fatty acids. To produce results that are

applicable to the North American population, populations

consuming high omega-6/omega-3 fatty acids intake ratios

should likely be randomized into trials also exhibiting better

control of confounding variables than was observed, especially

in the present collection of studies of child outcomes.

Availability of the Full Report

The full evidence report from which this summary was taken

was prepared for the Agency for Healthcare Research and

Quality (AHRQ) by the University of Ottawa Evidence-based

Practice Center under Contract No. 290-02-0021. It is

expected to be available in August 2005. At that time, printed

copies may be obtained free of charge from the AHRQ

Publications Clearinghouse by calling 800-358-9295.

Requesters should ask for Evidence Report/Technology

Assessment No. 118, Effects of Omega-3 Fatty Acids on Child

and Maternal Health. In addition, Internet users will be able to

access the report and this summary online through AHRQ’s

Web site at www.ahrq.gov.

Suggested Citation

Lewin GA, Schachter HM, Yuen D, Merchant P,

Mamaladze V, Tsertsvadze A, et al. Effects of Omega-3 Fatty

7
8

Acids on Child and Maternal Health. Summary, Evidence

Report/Technology Assessment No. 118. (Prepared by the

University of Ottawa Evidence-based Practice Center under

Contract No. 290-02-0021.) AHRQ Publication No. 05-E025-

1. Rockville, MD: Agency for Healthcare Research and Quality.

August 2005.

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AHRQ Pub. No. 05-E025-1

August 2005

ISSN 1530-440X