Evidence Report/Technology Assessment

Number 72

Criteria for Determining Disability in 

Infants and Children: Failure to Thrive

Prepared for: 

Agency for Healthcare Research and Quality

U.S. Department of Health and Human Services

2101 East Jefferson Street

Rockville, MD 20852

www.ahrq.gov

Contract No. 290-97-0019

Prepared by:

Tufts-New England Medical Center EPC, Boston, MA

Investigators

Ellen C. Perrin, MD, MA

Cynthia H. Cole, MD, MPH

Deborah A. Frank, MD

Stephan R. Glicken, MD

Nicholas Guerina, MD

Kevin Petit, MD

Robert Sege, MD, PhD

MaryAnn V. Volpe, MD

EPC Staff

Joseph Lau, MD, Director

Caroline A. McFadden, MD, /Priscilla Chew MPH, Project Leaders

Deirdre DeVine, M Litt, Project Manager

Kimberly Miller, BA, Research Assistant

AHRQ Publication No. 03-E020

March 2003
This report may be used, in whole or in part, as the basis for development of clinical practice 

guidelines and other quality enhancement tools, or a basis for reimbursement and coverage 

policies. AHRQ or U.S. Department of Health and Human Services endorsement of such 

derivative products may not be stated or implied.

AHRQ is the lead Federal agency charged with supporting research designed to improve the 

quality of health care, reduce its cost, address patient safety and medical errors, and broaden access 

to essential services. AHRQ sponsors and conducts research that provides evidence-based 

information on health care outcomes; quality; and cost, use, and access. The information helps 

health care decisionmakers—patients and clinicians, health system leaders, and policymakers—

make more informed decisions and improve the quality of health care services.
ii

This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

specific permission of copyright holders.

Suggested Citation:

Perrin E, Frank D, Cole C, et al. Criteria for Determining Disability in Infants and Children: 

Failure to Thrive. Evidence Report/Technology Assessment No. 72 (Prepared by Tufts-New 

England Medical Center Evidence-based Practice Center under Contract No. 290-97-0019). 

AHRQ Publication No. 03-E020. Rockville, MD: Agency for Healthcare Research and Quality. 

March 2003.
iii

Preface

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

Practice Centers (EPCs), sponsors the development of evidence reports and technology 

assessments to assist public- and private-sector organizations in their efforts to improve the 

quality of health care in the United States. The reports and assessments provide organizations 

with comprehensive, science-based information on common, costly medical conditions and new 

health care technologies. The EPCs systematically review the relevant scientific literature on 

topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to 

developing their reports and assessments.

To bring the broadest range of experts into the development of evidence reports and health 

technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality improvement projects throughout the Nation. The 

reports undergo peer review prior to their release. 

AHRQ expects that the EPC evidence reports and technology assessments will inform 

individual health plans, providers, and purchasers as well as the health care system as a whole by 

providing important information to help improve health care quality.

We welcome written comments on this evidence report. They may be sent to: Director, 

Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality, 

6010 Executive Blvd., Suite 300, Rockville, MD 20852.

Carolyn M. Clancy, M.D.

Director

Agency for Healthcare Research and Quality

Jean Slutsky, P.A., M.S.P.H.

Acting Director, Center for Practice and 

 Technology Assessment 

Agency for Healthcare Research and Quality

The authors of this report are responsible for its content. Statements in the report 

should not be construed as endorsement by the Agency for Healthcare Research and 

Quality or the U.S. Department of Health and Human Services of a particular drug, 

device, test, treatment, or other clinical service.
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v

Structured Abstract

Objectives. The evidence report provides a systematic review of the scientific evidence to 

answer the question of whether children, defined by investigators as failing to thrive or grow 

adequately, have a concurrent ‘disability’, or will have one within 6 months. The population of 

interest includes children age 18 years or younger, both male and female, of all racial, ethnic and 

socioeconomic groupings. 

Search Strategy. Systematic searches were performed for relevant articles in MEDLINE® from 

1966 through December 2000, with updates through September 2001. Additional studies were 

identified from other databases, reference lists of review and primary articles, and from domain 

experts. Since disability is not a specific medical condition that can readily be searched for, 

many studies with related concepts (i.e. medically definable impairments that are related to 

disability) were reviewed to identify potentially relevant studies. Search terms were textwords: 

failure to thrive, failure to grow, growth retardation, childhood malnutrition, protein-calorie 

malnutrition, starvation and psychosocial dwarfism

Selection Criteria. Eligibility criteria for study inclusion included: 1) published articles 

including at least one disability related outcome; 2) cross-sectional or longitudinal studies; 3) 

studies with at least two arms, one of which had a non-failure to thrive or healthy control group 

[added to control for potential confounders for any particular statistically significant outcome or 

covariate]; 4) studies conducted in either developed or developing countries. Studies of sample 

size of less than 10 subjects per arm, or those concerned primarily with particular diagnoses and 

conditions were excluded, as were studies published only as abstracts. Investigators’ own 

definitions of failure to thrive were retained despite their resulting variability in inclusion criteria 

across studies.

Main Results. Including studies found from other sources, a total of 10,966 English language 

citations were identified. A total of 275 original studies were retrieved for careful evaluation. 

Detailed examination of these articles identified 52 publications comprising 43 studies that met 

inclusion criteria. Detailed data extraction was performed on these 43 studies.

Persistent disorders of growth. Overall these studies comparing children who were thriving 

with those who were undernourished in both developed and developing countries show that 

children with FTT have poorer growth in weight, height, and head growth, and that this poorer 

growth is often long-standing despite appropriate interventions. Earlier intervention leads to 

potentially better long-term outcome.

Associations of FTT with immunologic/infectious outcomes. The evidence that children with 

FTT have significantly greater susceptibility to infection is strong, with significant immunologic 

dysfunction and clinical infectious complications seen consistently across a variety of conditions. 

The laboratory markers of immunologic dysfunction were apparent in children with moderate 

severity. Only one study demonstrated improvement following immunologic intervention. 

Severe complications were most prevalent among the most severely malnourished children.
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Disabilities related to child behavior associated with Failure to Thrive. The evidence 

identified by the search showed that children with failure to thrive concurrently exhibited a 

variety of behavioral disorders as well as at follow-up. The behavioral problems ranged from 

eating disorders, increased negative and decreased positive affective expression, to lower scores 

in communication and mood.

Developmental disorders associated with Failure to Thrive. FTT is associated consistently 

with depressed developmental test scores. In both clinical and epidemiological samples, FTT is 

associated on average with roughly 2/3 of a standard deviation decrease in developmental test 

scores. As a result, a greater proportion of children who are failing to thrive than children in a 

reference population will score in the supplemental security income (SSI) qualifying range for 

developmental delay.

Evidence that Failure to Thrive (FTT) is associated with other psychosocial and family 

factors. Compared to well-nourished peers, children with FTT were more likely to have had 

neonatal problems (jaundice, possible sepsis, and poor feeding, and family problems). There 

were no differences however in the incidence of prematurity, LBW, or maternal pregnancy 

complications.

Conclusions. The findings emphasize the importance of early and intensive intervention for 

children with poor growth velocity (FTT) so as to prevent permanent growth retardation. The 

evidence also supports the value of identification of children with growth failure as a marker for 

chronic and multiple acute infections. Children with a history of FTT were found to have 

clinically and statistically significant behavioral deficits and consistently depressed scores in 

cognitive, neurological, and psychomotor development. The increased risks for secondary 

disability generally persist in spite of intervention.

In summary, there is persuasive evidence that failure to thrive is associated with a range of 

organic and psychosocial difficulties and significant disability. Primary categories of 

associations include the child’s age, socioeconomic factors (lower income, lower maternal 

education, less enriched family environment/interactions); neonatal morbidity; acute illnesses 

and hospitalizations; and neurological/anatomical abnormalities.
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Contents

Summary........................................................................................................................................ 1

Evidence Report

Chapter 1. Introduction............................................................................................................... 13

Definitions............................................................................................................................. 13

Causes and Effects of FTT.................................................................................................... 14

Association of FTT with Immunological Functioning.......................................................... 15

Association of FTT with Neurological Functioning.............................................................. 15

Growth Abnormalities........................................................................................................... 16

Other Associated Health Problems........................................................................................

 Summary.............................................................................................................................

16

16

Chapter 2. Methodology............................................................................................................. 17

Key Question Addressed in the Evidence Report................................................................ 17

Search Strategies.................................................................................................................... 18

Study Selection...................................................................................................................... 18

Covariates/ Outcomes Considered........................................................................................ 18

Data Abstraction.................................................................................................................... 19

Reporting the Evidence......................................................................................................... 19

Evidence Tables..................................................................................................................... 20

Summary Tables.................................................................................................................... 21

Summarizing the Evidence of Individual Studies................................................................. 21

 Study Quality................................................................................................................... 21

 Applicability.................................................................................................................... 21

 Results............................................................................................................................. 22

Study size......................................................................................................................... 22

Chapter 3. Results....................................................................................................................... 23

Persistent Disorders of Growth Following Diagnosis of Failure to Thrive........................... 23

 Findings from Industrialized Nations.............................................................................. 23

 Findings from the Developing World.............................................................................. 25

 Summary.......................................................................................................................... 26

Associations of FTT With Immunologic/Infectious Outcomes............................................ 26

 Evidence of Immunologic Dysfunction in Failure to Thrive.......................................... 27

 Clinical Infections in Failure to Thrive........................................................................... 28

Child Behavior Problems Associated With Failure to Thrive............................................... 30
viii

Evidence of Concurrent Feeding-Related Behavior Problems Associated With 

FTT.................................................................................................................................. 31

Evidence Suggesting Concurrent Behavioral Problems Associated With 

FTT.................................................................................................................................. 32

Evidence Regarding Behavior Problems Detected in Follow-up.................................... 33

Developmental Disorders Associated With Failure to Thrive............................................... 36

 Developed Countries....................................................................................................... 36

 Developing Countries...................................................................................................... 42

 Evidence that Failure to Thrive (FTT) is associated With Other Clinical, Psychosocial 

and Family Factors.................................................................................... 46

Chapter 4. Conclusions............................................................................................................... 49

Overview............................................................................................................................... 49

Persistent Disorders of Growth.............................................................................................. 49

Association of FTT with Immunologic/Infectious Outcomes............................................... 50

Behavior Difficulties Associated with Failure to Thrive....................................................... 50

Developmental Disorders Associated with Failure to Thrive............................................... 50

Evidence that Failure to Thrive is Associated with Other Clinical, Psychosocial and 

Family Factors................................................................................................................ 51

Chapter 5. Future Research........................................................................................................ 53

References and Bibliography....................................................................................................... 55

Evidence Tables

Evidence Table 1. Studies associating anthropometrics to Failure to Thrive cases 

compared to healthy control group in developed countries................... 61

Evidence Table 2. Studies associating anthropometrics with malnourished patients 

compared to well-nourished control subjects in developing countries... 67

Evidence Table 3. Studies associating immunologic response or infectious diseases with 

Failure to Thrive patients compared to healthy control subjects in 

developed countries................................................................................. 74

Evidence Table 4. Studies associating immunologic response or infectious diseases with 

malnourished patients compared to well-nourished control subjects 

in developing countries........................................................................... 77

Evidence Table 5. Studies associating behavioral problems with Failure to Thrive 

patients compared to healthy control subjects in developed countries... 83

Evidence Table 6. Study associating behavioral problems with malnourished patients 

compared to healthy control subjects in developing country.................. 96

Evidence Table 7. Studies associating cognitive & neurological development with 

Failure to Thrive patients compared to healthy control subjects in 

developed countries................................................................................. 97
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Evidence Table 8. Studies associating cognitive & neurological development with 

malnourished patients compared to well-nourished control subjects 

in developing countries........................................................................... 109

Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive 

patients compared to healthy control subjects in developed countries... 116

Evidence Table 10. Studies associating other correlates / outcomes with malnourished 

patients compared to well nourished control subjects in developing

countries.................................................................................................. 129

Appendixes

Appendix A. Literature Search Strategies............................................................................. 135

Appendix B. Data Abstraction Form..................................................................................... 139

Appendix C. Acknowledgements.......................................................................................... 145

Appendix D. Acronyms/Abbreviations................................................................................. 149

Tables 

Table 1. Outcomes and covariates studied........................................................................... 19

Table 2. Studies of persistent anthropometric abnormalities following diagnosis of 

Failure to Thrive in developed countries .............................................................. 24

Table 3. Studies of persistent anthropometrics abnormalities in malnourished cases in 

developing countries.................................................................................. 25

Table 4. Studies with associations of immunologic dysfunction or infectious diseases to 

Failure to Thrive and healthy comparison groups in developed countries............ 29

Table 5. Studies with associations of immunologic dysfunction or infectious diseases 

and malnourished cases compared to well-nourished controls in developing 

countries..................................................................................... 30

Table 6. Studies with association of behavioral correlates to Failure to Thrive compared 

to healthy comparison groups in developed and developing countries................. 34

Table 7. Studies with association of cognitive and neurological development to Failure 

to Thrive compared to healthy comparison groups in developed countries.......... 41

Table 8. Studies with association cognitive and neurological development and 

malnourished cases compared to well-nourished controls in developing 

countries ................................................................................................................ 45
Overview

The Social Security Administration (SSA)

requested that the Agency for Healthcare

Research and Quality (AHRQ), through its

Evidence-based Practice Center (EPC) program,

provide a systematic review of the scientific

evidence on whether children, defined by

investigators as failing to thrive or grow

adequately, have a concurrent disability, or will

have one within 6 months. The population of

interest includes children age 18 years or

younger, both male and female, of all racial,

ethnic, and socioeconomic groupings. 

The evidence report was prepared to assist

SSA in updating its Listing of Impairments and

revising its disability policy, as may be

appropriate. 

Causes of Failure to Thrive

The underlying cause of failure to thrive

(FTT) is always insufficient usable nutrition.

This may occur when sufficient nutrients are

not available to the child as a result of social or

environmental causes that prevent parents from

obtaining, preparing, or offering age-appropriate

foods to the child. This growth failure often

includes concurrent and potentially persistent

disability. This syndrome of under-nutrition,

previously termed “non-organic FTT” is

recognized as a multifaceted disease. Because of

this, the world’s literature on the disabilities of

poorly nourished children in developing as well

as developed countries becomes relevant to the

discussion of disability arising from FTT even in

the United States.

In addition, almost any serious pediatric

illness can result in FTT. There are three basic

mechanisms for this phenomenon: 

1) insufficient nutrition is available to the child

because of the child’s inability to feed properly,

e.g., severe neurological dysfunction,

gastroesophageal reflux, cleft palate; 2) nutrition

is adequate but inadequately absorbed and/or

utilized (malabsorption syndromes); or 3) the

disease process creates added metabolic

requirements, e.g., asthma, cardiac failure,

thyroiditis. It is not uncommon for FTT to be

the first clue to an active disease process which

has not yet manifested itself in specific

symptomatology.

Whatever its multidimensional causes, FTT

affects growing children in many important

ways. Severe malnutrition has been shown to

cause permanent damage to various parts of the

brain and central nervous system, leading to a

range of disabilities manifested by aberrant

behavioral, cognitive, language, and motor

development. In addition, FTT is closely linked

with infectious disease. Children who are

undernourished (of which FTT is an indicator)

consistently have been found to have significant

and profound changes in cell-mediated

immunity, complement levels, and opsonization

that lead to susceptibility to various infections.

FTT is also associated with disabilities in cardiac

functioning, gastrointestinal conditions,

persistently small stature, and other

physiological derangements.

Reporting the Evidence

The key question posed by SSA was refined

by the EPC Evidence Review Team and

technical experts to review the association of five

categories of disability with failure to thrive.

Key Question: Among children defined by

investigators as failing to thrive or grow

adequately, what evidence exists that they

have, or will have within 6 months, a

concurrent disability?

Evidence Report/Technology Assessment

Number 72

Criteria for Determining Disability in Infants and Children:

Failure to Thrive

Summary

Agency for Healthcare Research and Quality

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service
The following associations between FTT and disability were

investigated:

• Persistent disorders of growth following FTT

• Association of FTT with immunologic/infectious

outcomes

• Child behavior associated with FTT

• Developmental disorders associated with FFT

• Association of FTT with other psychosocial and family

factors

Methodology

Definition of Failure to Thrive

Most clinicians make a diagnosis of FTT when a child’s

growth in weight and/or in height fails to increase as expected

for his or her age. Operationally this is frequently defined as a

crossing of two or more standard percentile lines in a standard

growth chart. Other clinicians use a definition of FTT that

can be assessed without access to growth charts, or that can be

assessed at a single point in time. These definitions include

children who are persistently at or below the third or fifth

percentile for weight, or less than the 80th percentile of

median weight-for-height. 

Other definitions used commonly in the professional

literature include height-for-weight <3rd percentile; weightfor-age less than 3rd or 5th percentile or less than 80 percent

of mean for age; weight-for-height <10th percentile; and

weight-for-age less than 2 standard deviations below the mean

for age. Because of inconsistent definitions it is hard to make

comparisons among the various investigative approaches to

this syndrome.

Current SSA guidelines consider FTT to be present when

there is a fall in weight to below the 3rd percentile or to less

than 75 percent of median weight-for-height or age in

children under 2-years old. There must be no underlying

medical disorder, and growth failure should last, or be

expected to last, for at least 12 months. 

Earlier research attempted to distinguish FTT that resulted

from a known organic disease process from the more common

circumstance in which the specific cause for the growth failure

is unknown. This distinction is no longer considered useful.

Instead, current data suggest that organic and non-organic

causes and effects are intertwined in most affected children.

This review therefore will not use the terms organic or nonorganic FTT.

Literature Search 

Disability is not a specific medical condition that can

readily be searched for. Thus, we had to look at many studies

with related concepts (i.e., medically definable impairments

that are related to disability) to identify potentially relevant

studies.

The main search consisted of a MEDLINE® search from

1966 through December 2000. A broadly sensitive, rather

than specific, search strategy was employed to identify relevant

studies. The search strategy used the following textwords:

failure to thrive, failure to grow, growth retardation, childhood

malnutrition, protein-calorie malnutrition, starvation and

psychosocial dwarfism. Development of the search strategies

was an iterative process that included input from domain

experts. Keywords from known relevant studies were used to

refine and focus the final search strategies used. Results were

limited to studies in age-group under 18 and English language

only. Various investigators defined the population of interest

differently. We accepted whatever definition the investigator

had used to identify children who were not growing as

expected. We also inspected references from retrieved primary

studies and relevant reviews, and consulted with technical

experts and colleagues in order to identify additional studies.

Study Selection

Including studies found from other sources, a total of

10,486 English-language citations were identified in the initial

search. An updated MEDLINE® search using the same

search strategy was conducted in September 2001 which

resulted in additional 480 abstracts.

Titles and abstracts were manually screened by physician

members of the EPC and pediatricians to identify potentially

relevant articles. Inclusion criteria for article selection were as

follows: 1) published articles including at least one disabilityrelated outcome; 2) cross-sectional or longitudinal studies; 3)

studies with at least two arms, one of which had a non-FTT

or healthy control group; and 4) studies conducted in either

developed or developing countries. The third inclusion criteria

was added to control for potential confounders for any

particular statistically significant outcome or covariate. Studies

of sample size of less than 10 subjects per arm, or those

concerned primarily with particular diagnoses and conditions

were excluded, as were studies published only as abstracts.

The mechanisms of undernutrition have been well-studied

in developing countries. In addition, the associations of

undernutrition and various outcomes such as cognitive and

neurological development and infections are clearly delineated

in these conditions. Because undernutrition as applied to

developed countries may not be understood or studied as

extensively, studies in developing countries were included to

help correlate associations made.

Summarizing the Literature

A total of 275 original studies were retrieved for careful

evaluation. Detailed examination of these articles identified 52

publications comprising 43 studies that met the inclusion

criteria. Detailed data extraction was performed on these 43

studies. Their overall methodologic quality will be described

individually below.

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Findings

Persistent Disorders of Growth Following

Failure to Thrive

Findings From Industrialized Nations. Seven studies

compared anthropometric data of FTT patients with healthy

comparison groups in developed countries. Most studies were

performed in the United States or the United Kingdom, with

one study from Israel. The majority of the studies were

prospective-longitudinal, and two of the studies were

ambidirectional blinded studies. Six out of seven of these

studies show a statistically significant association between FTT

and sub-optimal weight-for-height and weight-for-age. This

growth retardation for the most part persists despite adequate

correction of malnutrition. The clinical significance of this

degree of growth retardation is not clear.

Findings From the Developing World. Seven studies

compared anthropometric data of FTT patients with wellnourished control groups in developing countries. The studies

in developing countries mainly compared children with

marasmus and kwashiokor to healthy controls, mostly from

outpatient settings, and six of the seven studies found similar

associations. One study looked primarily at the effect of home

visits on Jamaican children with FTT and found that height

for age remained low in the FTT group, even with the

intervention. The addition of more adequate nutritional

supplementation to such children would be anticipated to aid

in these improvements in outcome. Two other studies also

showed significant differences in body fat and arm muscle

composition in the FTT groups compared to controls; in one

of the studies, the decreased body fat and muscle mass had a

negative impact on physical performance.

Overall these studies comparing children who were thriving

with those who were undernourished in both developed and

developing countries show that children with FTT have

poorer weight, height, and head growth, and that this poorer

growth is often long-standing despite appropriate

interventions. Earlier intervention leads to potentially better

long-term outcomes. The fact that children who fail to thrive

have poorer head growth is not surprising considering that

human brain growth is tremendous in the early childhood

years and insults during this time may impact permanently on

developmental and intellectual outcome. These findings

emphasize the importance of early and intensive intervention

for children with, or at risk for, FTT so as to prevent

permanent growth retardation.

Association of Failure to Thrive With

Immunologic/Infectious Outcomes

A total of eight controlled studies were identified for review;

four of these focused primarily upon aspects of immune

function while four examined clinical infections among FTT

children. Studies carried out in developing countries have

variable generalizability for outcomes and policies in the

United States.

Of the studies, seven were prospective cross-sectional studies

and one study was retrospective. Only two studies were

longitudinal; all others were cross-sectional. The principal

source of potential bias involved the selection of controls. One

study included adults as well as children in the controls;

additionally, there were only controls (no FTT patients)

entered from the children in an urban study center. The FTT

and control groups in one study were from different hospitals

serving different social-economic status (SES) populations; in

another study controls included children with “nutritional

growth retardation,” likely comparable to the United States

FTT population. 

Studies comparing children who were thriving with those

who were undernourished in both developed and developing

countries show that children with FTT have such factors as

significantly decreased chemotactic response to bacterial

endotoxin as well as phagocytosis of zymogen particles;

significantly lower percentages of rosette forming cells (a

sensitive marker of cellular immune function); and reduced

Candida killing ability. Studies comparing the same cohort of

children also show that children with FTT have significantly

greater evidence both clinically and in the laboratory of

susceptibility to infection. These findings emphasize the

importance of identifying children who are failing to grow

normally since their growth failure may be a marker for a

variety of chronic and multiple acute infections that would

otherwise be hard to identify. In addition, treatment of FTT

provides an opportunity to prevent the far more destructive

consequences and costs associated with chronic infectious

conditions in children.

Child Behavior Associated With Failure to

Thrive

Fifteen studies examined the relationship between FTT and

behavioral disorders. Evidence will be presented in three areas.

Evidence of Concurrent Feeding-Related Behavior

Problems Associated With Failure to Thrive. Four studies

noted concurrent feeding disorders in children diagnosed with

FTT. Behavior problems were more common in children with

FTT, even beyond those children who were known to be

failing to grow on the basis of neurological or other organic

damage or disease. Children had such factors as increased

negative affect and decreased positive affect during feeding

compared to controls, with no difference in non-feeding

situations. Severity of malnutrition, but not presence of

organic disease, was associated with affective outcomes. Also,

parents reported more feeding problems during infancy for the

FTT cases, and described their children as uninterested or

poor eaters.

Evidence Suggesting Other Concurrent Behavioral

Problems. Four studies examined behavior problems that were

either diagnosed concurrently with diagnosis or within the

ensuing weeks or months. These behavior problems were

3
related to evidence of insecure attachment, and problems with

communication and with mood/affect. The FTT groups

scored significantly lower than controls on reports describing

affect and communication skills, matched for such factors as

age, sex, and race.

Evidence Regarding Behavior Problems Detected in

Followup After a Diagnosis of Failure to Thrive. Seven

studies evaluated children with FTT for behavioral disorders.

When compared to the controls, the index groups had

significantly more family problems, poor psychological

development, or behavioral deficits as measured by a variety of

behavioral screening questionnaires or checklists used in the

studies. 

Developmental Disorders Associated With

Failure to Thrive

FTT is consistently associated with evidence of neurologic

disabilities. Insufficient intake of both macro- and

micronutrients exerts diverse functional and structural effects

on the nervous system, with effects particularly likely to persist

if they occur during the vulnerable periods of most rapid

development. Since FTT most often occurs in early life,

during the period of most rapid postnatal brain development,

developmental concomitants and lasting sequelae are to be

expected. In addition, FTT appears to heighten developmental

vulnerability to other adverse environmental factors. In

addition, subtle neurologic deficits may interfere with the

normal progression of feeding skills, even in the absence of

clinically evident palsies. They contribute to FTT by

interfering with the child’s ability to take in adequate

nutrients. We present data from three domains.

Oral Motor and Other Neurologic Findings

Five prospective, epidemiologic, and observational studies

consistently noted increased rates of feeding difficulties in

children with FTT with some investigators also noting

clinically poorly specified “neurologic” findings other than in

feeding skills. Since these studies are often based on parental

report, it is difficult to disaggregate true subtle neurologic

(either oral motor or sensory) deficits in feeding from parental

perceptions and from learned behaviors. However, delays in

acquisition of mature feeding skills are a consistent finding in

every study where they have been assessed.

Developmental/Cognitive Impairments

Concurrent With the Identification of Failure to

Thrive

Historically, developmental delay was considered by some

authors as one of the criteria necessary for a diagnosis of FTT

in addition to growth failure. It is only in recent decades that

children have been labeled as FTT on the basis of weight gain

alone. Thus many older studies do not include children who

are failing to thrive but developing normally. In addition it is

difficult to mask testers to the differences in size between

acutely underweight FTT children and normally growing

comparison children of the same age. Therefore some

experimenter effect cannot be ruled out in the studies

summarized below. 

There are three United States studies, two based on

hospitalized children and the other on a sample not

hospitalized but drawn from an outpatient inner city clinic

(Mackner, Starr, Jr., and Black, 1997). In all three studies, the

average Bayley Mental Development Index (MDI) scores were

strikingly and significantly lower in children who had been

identified with FTT compared to the control groups.

Two studies from the United Kingdom reported similar

findings. Infants with FTT had scores that were significantly

lower than controls on both the Bayley MDI (98.2 vs.108.5)

and Psychomotor Development Index (PDI) (96.7 vs. 103.6).

At 36 months, the Stanford Binet IQ scores were lower for

children with FTT, 84.7 vs. 89.9 for non-FTT, p < 0.007.

Developmental/Cognitive Function in Later

Childhood Among Survivors of Early Failure to

Thrive

Four studies evaluated developmental/cognitive function in

later childhood among survivors of early FTT. Three of the

four were United Kingdom studies and one was a United

States study. Two were ambidirectional longitudinal studies,

one prospective longitudinal, and the fourth, an

ambidirectional cross-sectional study. Two were of high quality,

and two of low quality. In one study, children with a history of

FTT were found to have clinically and statistically significant

cognitive deficits. The remaining three studies found that

FTT was associated with decreased cognitive, motor, or

neurological measures compared to controls. 

Summary

At the time of identification, FTT is associated with lower

than expected developmental test scores, especially in clinically

identified hospitalized children. However, even in samples

identified epidemiologically rather than by clinicians, FTT is

associated on average with roughly two-thirds of a standard

deviation decrease in developmental test scores, so that many

more FTT children will score in the Supplemental Security

Income qualifying range of developmental delay than children

in a reference population.

Association of Failure to Thrive With Other

Psychosocial and Family Factors

Thirteen studies assessed diverse risks associated with FTT.

These studies were from developed countries (eight from the

United States, four from the United Kingdom, and one from

Israel) and populations were highly comparable. Five studies

were prospective longitudinal, three were prospective crosssectional, two each were retrospective longitudinal or

ambidirectional cross-sectional, and one, ambidirectional

longitudinal.

4
5

There is persuasive evidence that FTT is associated with a

variety of other difficulties that may themselves secondarily

predict or cause significant disability. Categories of associations

include socioeconomic factors (lower income, lower maternal

education, less enriched family environment/interactions);

neonatal morbidity; acute illnesses and hospitalizations;

neurological/anatomical abnormalities; family dysfunction;

and abuse/neglect. Clearly these factors may precede the

infant’s FTT and/or occur subsequent to it. These variables are

almost certainly multiply interrelated and the directions of

causation impossible to describe in a linear fashion (for

example, poverty may be one factor that leads to malnutrition,

which increases the risk of illness/disability, which leads to

increased poverty).

Future Research

The studies comprising this report, though insufficient in

number and variable in their methodologic quality and their

potential biases, were of sufficient validity to provide

significant information regarding the association of FTT with

disability. The variety and long-term nature of the disabilities

associated with FTT have major impact on the child, the

family, and society.

Notwithstanding this, it may well be that the most

significant finding of this review was the paucity of

information available on the subject. Much remains to be

learned regarding the extent and specifics of these associations

and disabilities. Even more remains to be determined as to the

optimal management of these patients.

The following recommendations for future research address

specific problematic issues and limitations identified from

review of existing research:

• One of the central problems in interpreting these studies

was the heterogeneity of definitions of FTT. This

variability in case definition makes it unclear how well

the population at risk is being identified at present.

Future research should apply a uniform definition of

FTT. This would serve to facilitate comparison and

perhaps even allow a meta-analysis of studies. It would

also define more clearly the true prevalence of FTT.

• Within the definition of FTT, provisions should be made

for categorization based upon 1) severity and 2) longevity

or duration of growth failure. The data currently available

indicate that both of these factors are strong predictors

not only for the risk of associated disabilities but for

potential response to therapy as well. Refining the

classification of the FTT population in this way would

facilitate identification of the relative risk of disability for

an individual FTT child. It would also help in the

evaluation of intervention studies.

• Although it is clear that the degree of disability increases

with increasing severity of growth failure, this is an

imprecise correlation especially in children with mild to

moderate FTT. Since the majority of FTT that is seen in

the United States tends not to be the most severe forms

of marasmus and kwashiorkor, future research should

specifically target those children with mild to moderate

growth failure.

• Similarly, more research needs to be conducted in the

United States or in developed countries with comparable

social-economic structures and health care systems.

• Special emphasis should be given to outcomes focusing

on neurodevelopmental and cognitive disorders. The data

presented in this report indicate that this is likely one of

the areas of strongest impact of FTT and certainly one

with the greatest relevance for long-term disability.

Specifically, very few studies have focused on the issue of

FTT and brain growth during the immediate postneonatal period and early infancy. This is one of the most

critical periods for dendritic arborization, axonal

myelination, and the development of cognitive functions.

More studies are needed in this area.

• Further study is also needed on the association of FTT

with general health outcomes because of their potential

impact on the health care system. Beyond the risk to the

individual child, the data linking FTT to increased risk

of infections and poorer general health may have

important implications at a broader level. Such data may

help us understand the true “cost” of FTT and prove

useful in evaluating intervention strategies.

• In order to better define the true nature and extent of the

disabilities associated with FTT, more studies are needed

that prospectively follow children for a sufficient duration

to capture the more complex disabilities that may result

from FTT.

A consistent finding among the studies reviewed was the

ineffectiveness of existing intervention programs. Although

strictly beyond the focus of this report, much work still needs

to be done on developing effective treatment programs for

children with FTT. Unfortunately, the optimal intervention

will yet require better definition of the complex physical,

medical, cognitive, and psychosocial problems associated with

FTT.

Availability of the Full Report

The full evidence report from which this summary was

taken was prepared for AHRQ by Tufts-New England Medical

Center Evidence-based Practice Center under Contract No.

290-97-0019. It is expected to be available in spring 2003.

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. 72, Criteria for

Determining Disability in Infants and Children: Failure to

Thrive. Internet users will be able to access the report online

through AHRQ’s Web site at www.ahrq.gov.
AHRQ Pub. No. 03-E019

March 2003

ISSN 1530-440X
Evidence Report

13

Chapter 1. Introduction

The Social Security Administration (SSA) of the Department of Health and Human Services 

requested that the Agency for Healthcare Research and Quality, through its Evidence-based Practice 

Center (EPC) program produce an evidence report on the failure to thrive (FTT) syndrome. The 

purpose of this initiative is to assess evidence relating to the relationship between FTT and disability.

This is one of three reports requested by SSA in the broader topic of “Criteria for Determining 

Disability in Infants and Children.” The evidence reports are prepared to assist the SSA in updating its 

Listing of Impairments, and revising its disability policy, as may be appropriate. 

The syndrome of failure to thrive (FTT) is variously defined but in general terms it describes children 

who fail to maintain normal age and sex-adjusted growth parameters. FTT is not a diagnosis, but a 

syndrome that results from many different medical, social, or environmental processes. Children may fail 

to grow because they receive insufficient nutrients to sustain their caloric needs; because they fail to 

absorb and/or utilize the nutrients they take in; or because their caloric needs are excessive and thus the 

usual amount of nutrition is still insufficient for them to grow normally.

FTT sometimes reflects a systemic health condition or it may be a marker for some undiagnosed 

physiological derangement. In addition, FTT may itself exacerbate other unrelated conditions; and it can 

cause a variety of new health problems. We will address these various ramifications of growth failure in 

turn.

Definitions

Current SSA guidelines consider FTT to be present when there is a fall in weight to below the 3rd

percentile or to less than 75% of median weight-for-height or age in children under two years old. There 

must be no underlying medical disorder, and growth failure should last, or be expected to last, for at 

least twelve months. These guidelines are to be updated and the purpose of this review of the literature 

was to generate an evidence base to assist the SSA in revising its disability policy with regard to children 

who are failing to thrive.

Most clinicians make a diagnosis of FTT when children’s growth in weight and/or in height fails to 

increase as expected for their age. Operationally this is frequently defined as a crossing of two or more 

standard percentile lines in a standard growth chart. Other clinicians use a definition of FTT that can be 

assessed without access to growth charts, or that can be assessed at a single point in time. These 

definitions include children who are persistently at or below the third or fifth percentile for weight, or less 

than 80 percent of median weight-for-height or weight-for-age.

Other definitions are used commonly in the professional literature such as height-for-weight <3rd

percentile; weight-for-age less than 3rd or 5th percentile or less than 80 percent of median for age; 

weight-for-height <10th percentile; and weight-for-age more than 2 standard deviations below the mean 

for age. Because of inconsistent definitions it is hard to make comparisons among the various 

investigative approaches to this syndrome.

Earlier research attempted to distinguish FTT that resulted from a known organic disease process 

from the more common circumstance in which the specific cause for the growth failure is unknown. This 

distinction is no longer considered useful. Instead, current data suggest that organic and non-organic 
14

causes and effects are intertwined in most affected children. Therefore, this review will not use the terms 

organic or non-organic FTT. Parenthetically, the SSA definition is a reflection of an outdated 

conceptual model and should be reconsidered. It does not reflect the current thinking, which is that 

failure to thrive is a complex interaction of medical, nutritional developmental, and social factors which 

all can contribute to disability.

Depending on the definition used and demographics of the population sampled, the reported 

prevalence of FTT ranges from 1.3% to 20. 9% (Reilly and Skuse, 1994). Previous reports have 

estimated its prevalence among hospitalized children to be from 1 to 5% (Zenel, Jr., 1997). It is difficult 

to estimate the true prevalence of FTT due to the variety of diagnostic criteria used to identify it, and 

because most children are not hospitalized.

Cross sectional data from the developing world suggest that weight for age is a potent predictor of 

mortality, while height for age, which reflects duration of insult, correlates with developmental outcome 

(Wright, Ashenburg, and Whitaker, 1994). Further research is needed to define which criteria are the 

best predictors of medical and cognitive sequelae of FTT in the United States.

Causes and Effects of FTT

The underlying cause of FTT is always insufficient usable nutrition. This may occur when sufficient 

nutrients are not available to the child as a result of social or environmental causes that prevent parents 

from obtaining, preparing, or offering age-appropriate foods to the child. This growth failure often 

includes concurrent and potentially persistent disability. This syndrome of under-nutrition, previously 

termed “non-organic FTT” is recognized as a multifaceted disease. Because of this, the world's literature 

on the disabilities of poorly nourished children in developing as well as developed countries becomes 

relevant to the discussion of disability arising from FTT even in the USA.

In addition, almost any serious pediatric illness can result in FTT. There are three basic mechanisms 

for this phenomenon: (1) insufficient nutrition is available to the child because of the child's inability to 

feed properly, e.g. severe neurological dysfunction, gastroesophageal reflux; cleft palate; (2) nutrition is 

adequate but inadequately absorbed and/or utilized (malabsorption syndromes); or (3) the disease 

process creates added metabolic requirements, e.g. asthma, cardiac failure, thyroiditis. It is not 

uncommon for FTT to be the first clue to an active disease process, which has not yet manifested itself 

in specific symptomatology. 

Whatever its multidimensional causes, FTT affects growing children in many important ways. Severe 

malnutrition has been shown to cause permanent structural aberrations in the central nervous system. 

Even mild malnutrition not sufficient to cause dramatic growth failure has been associated with 

aberrations in neural transmitters and CNS functions with the detectable impairments reflected in a range 

of disabilities. In addition, FTT is closely linked with infectious disease. Children who are 

undernourished (of which FTT is an indicator) consistently have been found to have significant and 

profound changes in cell-mediated immunity, complement levels, and opsonization (vi) that lead to 

susceptibility to various infections. FTT is associated with persistently small stature. Severe FTT are 

associated with multiple physiological derangement in cardiovascular and gastrointestinal functioning.

The review that follows attempts to determine the value of the symptom complex of FTT as a 

marker for basic physiological derangements that might otherwise be either undetectable or non-
15

existent. That is, we are interested in how often a child’s failure to grow occurs prior to or coincident 

with another potentially disabling childhood condition. We do not consider the co-occurrence of FTT 

with known chronic health conditions that are already regarded as disabling e.g. cystic fibrosis, 

congenital heart disease, or celiac disease, although undernutrition is known to exacerbate the severity 

and course of these and other pediatric health conditions. The question that directed this review is: 

Among children defined by investigators as failing to thrive or to grow adequately, what evidence exists 

that they have a concurrent disability, or will have one within six months. The definition of disability used 

for this investigation is an operational one; “the presence of a medically determinable physical or mental 

impairment that causes marked and severe functional limitations and that is expected to last for 12 

months or more”.

Association of FTT with Immunological Functioning

Malnutrition severe enough to produce growth failure also impairs immuno-competence, particularly 

cell-mediated immunity, and diminishes production of complement and secretory IgA. Recurring otitis 

media, gastrointestinal and respiratory infections are more common among children who fail to thrive 

than among well-nourished children of the same age.

Children who are not thriving are often trapped in an infection-malnutrition cycle. With each illness, 

the child's appetite and nutrient intake decrease while nutrient requirements increase as a result of fever, 

diarrhea, and vomiting. In settings in which nutrient intake is already marginal, even when the child is 

well, cumulative nutritional deficits occur, leaving the child increasingly vulnerable to more severe and 

prolonged infections and even less adequate growth. Even in developed countries, malnourished 

children succumb more often than thriving children to fulminating infections. The more common 

syndrome of recurrent low-grade infections interferes with both physiologic and psychological processes 

of childhood.

Association of FTT with Neurological Functioning

Insufficient nutrition is associated with perturbations of neurotransmitters and impaired exploration 

and learning, even before growth is affected. By the time a child has experienced under-nutrition for a 

long enough period to be identified as “failing to thrive” there have been many “silent” episodes of 

impaired learning and interaction which cumulatively produces lasting disabilities in cognition and social 

behavior. Evidence from developing countries of the dire effects of protein-calorie malnutrition on 

intelligence and social behavior have shed light on the mechanisms that result in impairments at even far 

less extreme levels of malnutrition, such as those found in the US with alarmingly high prevalence.

These mechanisms account for the most significant persistent physiological derangement that is 

associated with FTT, namely that of central nervous system function. The majority of available data 

documents both delayed development and disordered behavior and affect in children at the time of 

diagnosis of FTT/malnutrition. This is particularly true of children who come to medical attention 

because of their growth failure, but also to a lesser extent of children identified only in epidemiologic 

surveys. The majority of studies of clinically diagnosed cases of FTT show reproducible developmental 

impairments. Various aspects of school achievement, memory, and attentional functions seem to suffer 
16

lasting impairment. The effects on the CNS are both structural with impaired myelinization and dendritic 

arborization, and functional in terms of altered neurotransmitter synthesis.

Growth Abnormalities

Growth failure is the most obvious and persistent symptom and sequelae of FTT. Depending on the 

age of the child when growth failure occurred and the length of time it existed before it was corrected, 

short stature almost always persists even after the child is once again adequately nourished.

Other Associated Health Problems

Elevated lead levels correlate with impaired growth, even in the 5 to 35 mg/dl range. Here too, a 

negative cycle develops. Nutritional deficiencies of iron and calcium enhance the absorption of lead and 

other heavy metals. As lead levels rise, constipation, abdominal pain, and anorexia occur, leading to 

even less adequate dietary intake. In a recent study, 16% of children with FTT had lead levels high 

enough to warrant chelation.

Summary

Some of the disabilities created and/or maintained by malnutrition/FTT are restored with nutritional 

rehabilitation, such as immune, gastrointestinal, and cardiac function, and weight for height. On the other 

hand, other disabilities are permanent; there are persistent impairments in stature, cognition, attention, 

and behavior.
17

Chapter 2. Methodology

This evidence report is based on a systematic review of the literature. Several teleconferences 

were held with the science partner representatives from the Social Security Administration 

(SSA), the American Academy of Pediatrics (AAP), the internal technical experts from the EPC, 

and a representative of the Disability Law Center to refine and address the key question 

formulated by SSA. A comprehensive search of the medical literature was conducted to identify 

the evidence available to address the questions.

Detailed information about each study used in the systematic review was abstracted. The 

results are presented as detailed evidence tables. Information directly pertinent to answer each 

aspect of the key question is presented in summary tables with the Results chapter (Chapter 3).

Key Question Addressed in the Evidence Report

Current SSA guidelines consider FTT to be present when there is a fall in weight to below 

the 3rd percentile or to less than 75% of median weight-for-height or age in children under two 

years old. There must be no underlying medical disorder, and growth failure should last, or be 

expected to last, for at least twelve months. Disability is defined as the presence of a ‘medically 

determinable physical or mental impairment’ that causes ‘marked and severe functional 

limitations’ and that is expected to last for twelve months or more. In turn, a ‘medically 

determinable impairment’ is ‘an impairment that results from anatomical, physiological, or 

psychological abnormalities which can be demonstrated by medical evidence consisting of signs, 

symptoms and laboratory findings’ (Disability evaluation under Social Security. Social Security 

Administration, 1999)

SSA Functional limitations may occur in any of six areas of functioning: 1) acquiring and 

using information; 2) Attending and completing tasks; 3) Interaction with others; 4) Moving 

about and manipulating objects; 5) caring for oneself; and 6) health and physical well-being. 

Marked limitation in two areas or extreme limitation in one suffices to establish disability. These 

guidelines are to be updated and the purpose of this study question was to generate an evidence 

base to assist the SSA in revising its disability policy.

Following a series of teleconferences, science partners and EPC technical experts arrived at a 

consensus on the main study question as outlined below:

• Among children defined by investigators as failing to thrive or grow adequately, what 

evidence exists that they have a concurrent disability (or will have one within six months)?

For the purposes of this question, the SSA definition of disability was applied; however, the 

definition of FTT was expanded to include growth failure in children older than two years, with 

failure to grow at the expected rate, without reference to specific percentile height and weight 

cutoffs or underlying medical conditions. Duration of disability was to be at least six months.
18

Search Strategies

Disability is not a specific medical condition that can readily be searched for. Thus, we had 

to look at many studies with related concepts (i.e. medically definable impairments that are 

related to disability) to identify potentially relevant studies.

The main search consisted of a MEDLINE® search from 1966 through December 2000. A 

broadly sensitive, rather than specific search strategy was employed to identify relevant studies. 

The search strategy used the following textwords: failure to thrive, failure to grow, growth 

retardation, childhood malnutrition, protein-calorie malnutrition, starvation and psychosocial 

dwarfism. Results were limited to studies in age group under 18 and English language only. We 

also inspected references from retrieved primary studies, relevant reviews, and consulted with 

technical experts and colleague s in order to identify additional studies.

A total of 10,486 abstracts were identified in the initial search. An updated MEDLINE® 

search using the same search strategy was conducted in September 2001, which resulted in 

additional 480 abstracts.

Study Selection

Physician members of the EPC and pediatricians manually screened titles and abstracts to 

identify potentially relevant articles. Inclusion criteria for article selection were as follows: 1) 

published articles including at least one disability-related outcome; 2) cross-sectional or 

longitudinal studies; 3) studies with at least two arms, one of which had a non-failure to thrive or 

healthy control group; 4) studies conducted in either developed or developing countries. Studies 

of sample size of less than 10 subjects per arm or those concerned primarily with particular 

diagnoses and conditions were excluded, as were studies published only as abstracts. The third 

inclusion criterion was added to control for potential confounders for any particular statistically 

significant outcome or covariate.

The mechanisms of undernutrition have been well studied in developing countries. In 

addition, the associations of undernutrition and various outcomes such as cognitive and 

neurological development, and infections are clearly delineated in these conditions. Because 

undernutrition as applied to developed countries may not be understood or studied as 

extensively, studies in developing countries were included to help correlate associations made.

Covariates / Outcomes Considered

Disability-related concepts include mental or physical impairment that results from 

anatomical, physiological, or psychological abnormalities that can be shown by medically 

acceptable clinical and laboratory diagnostic techniques. A physical or mental impairment must 

be established by medical evidence consisting of signs, symptoms, and laboratory findings. The 

rational is to relate FTT with physical or mental impairment. There are factors that in turn may 

cause or modify the severity of the impairments. Listed below are factors or correlates explored 

in this evidence report.
19

Table 1. Outcomes and covariates studied

Outcomes

Social/behavioral functioning

Infectious illnesses

Cognitive development

Neurological development

Anthropometric, measurements

Covariates

Perinatal –

Tobacco

Alcohol

Cocaine

Infection

Prematurity

LBW

Demographic –

Education

Income

Health coverage

Maternal IQ

Quality of HOME 

 Environment

Age

Gender

Organic illness –

Congenital defects

Pulmonary

Cardiovascular

Gastrointestinal

Kidney

Neurological

Immunologic

Infectious

Endocrine

Data Abstraction

The data abstraction form was developed as part of an iterative process involving the 

methodologic and domain experts. The form was designed to capture data from primary articles 

including study setting, demographic data on the study subjects as well as data on the family 

social-economic status (SES), inclusion/exclusion criteria, number of subjects, study design, 

funding source, relevant measurements and outcomes evaluated, statistical methodology, results, 

potential biases, and study quality.

As part of the data abstraction form development, domain experts performed data abstraction 

after a training period. Each pediatrician tested the form with two different articles and each 

article was extracted at least twice by different pediatricians. Because of the variation of data 

reporting by the primary articles, this process also served to validate the forms.

Data abstraction of each study was performed in duplicate, once by the pediatrician and once 

by an EPC methodologic staff. Discrepancies were resolved in a conference or by a third 

reviewer.

Reporting the Evidence

The evidence we found for the FTT is summarized in two complementary forms. The 

evidence tables provide detailed information about the feature of study design and results of all 

the studies reviewed. A narrative and tabular summary of the strength and quality of the evidence 

of each study are provided for each main outcome. In addition, the country in which the study 

was conducted was divided between two sets of tables categorized by developed and developing 
20

countries. This is for the purpose of generalizability as conditions are more severe in developing 

countries and may not apply to the FTT populations in the United States. However, the outcomes 

can provide a parallel comparison to measure the strength of association.

Evidence Tables

Evidence tables were constructed for five different categories and grouped between 

developed and developing countries. The categories include cognitive & neurological 

development, behavioral problems, immunologic response or infectious diseases, 

anthropometrics, and other correlates/outcomes. They are presented under the Evidence Tables 

section of this evidence report:

 Evidence Tables in the Report

Table Number Table Content

Evidence Table 1 Studies associating anthropometrics with Failure to Thrive patients

compared to healthy control subjects in developed countries

Evidence Table 2 Studies associating anthropometrics with malnourished patients compared to 

well-nourished control subjects in developing countries

Evidence Table 3 Studies associating immunologic response or infectious diseases

with Failure to Thrive patients compared to healthy control subjects in developed 

countries

Evidence Table 4 Studies associating immunologic response or infectious diseases with 

malnourished patients compared to well-nourished control subjects in developing 

countries

Evidence Table 5 Studies associating behavioral problems with Failure to Thrive patients compared 

to healthy control subjects in developed countries

Evidence Table 6 Studies associating behavioral problems with malnourished patients compared to 

healthy control subjects in developing countries

Evidence Table 7 Studies associating cognitive & neurological development with Failure to Thrive 

patients compared to healthy control subjects in developed countries

Evidence Table 8 Studies associating cognitive & neurological development with malnourished

patients compared to well-nourished control subjects in developing countries

Evidence Table 9 Studies associating other correlates / outcomes with Failure to Thrive patients 

compared to healthy control subjects in developed countries (miscellaneous )

Evidence Table 10

Studies associating other correlates / outcomes with malnourished patients 

compared to well-nourished control subjects in developing countries 

(miscellaneous)
21

Summary Tables

Summary tables were created to describe studies reviewed for each main topic. The tables 

describe the strength of the evidence according to six dimensions: study size, age at follow-up, 

duration of follow-up, study sample applicability, strength of association, and methodological 

quality. The study data on follow-up duration and age at enrollment were presented in a 

heterogeneous manner that required reporting of follow-up data to be approximated in some 

cases. When possible, follow-up time was calculated from the age of diagnoses of FTT or 

malnutrition. The summary tables are presented in Chapter 3 of this evidence report.

Summarizing the Evidence of Individual Studies 

In order to answer the key questions, it was necessary to assess the strength of the available 

evidence. There is no current standard approach to assess the methodological quality and the 

reliability of these studies. In this report, we used the evidence-grading scheme described below.

Study Quality

Methodological quality (or internal validity) refers to the design, conduct, and reporting of 

the clinical study. Because studies with a variety of design types were evaluated, a three-level 

classification of study quality, used in previous reports, was modified:

=Least bias: Results are valid. A study that mostly adheres to the commonly held concepts 

of high quality, including the following: a formal study; prospective design, clear 

description of the population and setting; proper measurement techniques; appropriate 

statistical and analytic methods; no reporting errors; no obvious bias.

£ Susceptible to some bias, but not sufficient to invalidate the results. A study that does not 

meet all the criteria of category A. It has some deficiencies but none likely to cause major 

bias.

° Significant bias that may invalidate the results. A study with serious errors in design or 

reporting. These studies may have large amounts of missing information or discrepancies 

in reporting. 

Applicability

Applicability (also known as generalizability or external validity) addresses the issue of 

whether the study population is sufficiently broad so that the results can be generalized to the 

population of interest at large. The study population is typically defined by the inclusion and 

exclusion criteria. The target population was defined to include patients with non-organic failure 

to thrive, except for studies that included a small subset of FTT deriving from possible or 

definite organic etiology. A designation for applicability was assigned to each article, according 

to a three-level scale. 
22

ÇÇÇ Patients enrolled in the trial represent a broad spectrum of the population (high 

degree of applicability). Typically this would be a large study, although a large 

study in itself does not guarantee a high degree of generalizability.

ÇÇ The study included only a narrow/restricted study population, but the result is 

relevant to similar types of patient population (restricted applicability). Typically 

this would be a small study, but may also be a large study of a very homogeneous 

population.

Ç Studied outlier population that is not immediately relevant to the study question 

(very limited direct applicability or not applicable), or where the study reported 

only limited information.

Results

Results are represented by proportions (percents), categorical variables, mean levels for 

continuous variables, and associations between study measures and children with FTT compared 

to children without FTT. Symbols indicate the type and significance of associations between 

study measures.

or Statistically significant association, (p < .05)

Positive association

No association

Negative association or inverse relationship

Study Size

The study size is used as a measure of the weight of the evidence. Some studies have a high 

drop out rate due to lost to follow-up; we provide both the enrolled and evaluable number of 

patients, when these data are reported. A large study provides a more precise estimation of the 

treatment effect but does not automatically confer broad applicability unless the study included a 

broad spectrum of patients. Very small studies, taken individually, cannot achieve broad 

applicability. But several small studies that enrolled diverse populations, taken together, may 

have broad applicability. The study size is included as a separate dimension used to assist the 

assessment of applicability. For summarizing all studies, this would be the number of studies 

and the total number of patients in these studies.
23

Chapter 3. Results

A total of 275 original articles were reviewed, of which 52 publications comprising 43 

studies met the criteria outlined in Chapter 2 and were assembled to provide the summary of 

results that follows. For the purposes of this summary, we will present the findings in categories 

of disability that were identified. Thus some articles will appear in more than one section if the 

investigators identified more than one type of disability in their sample. Categories of disability 

presented include (1) growth; (2) infectious/immunologic disorders; (3) behavioral disorders; (4) 

disorders of development; and (5) miscellaneous conditions.

Persistent disorders of growth following diagnosis of Failure 

to Thrive

Findings from Industrialized Nations

Most studies were performed in the United States, the United Kingdom, with one study from 

Israel. Six out of seven of these studies show a statistically significant association between 

failure to thrive and a risk of continued sub-optimal weight-for-height and weight-for-age. Of 

particular concern is the finding, in the majority of these studies, that this growth retardation 

persists despite adequate correction of malnutrition (Black and Krishnakumar, 1999; Corbett, 

Drewett, and Wright, 1996; Drewett, Corbett, and Wright, 1999; Kelleher, Casey, Bradley, et al., 

1993; Mitchell, Gorrell, and Greenberg, 1980; Reif, Beler, Villa, et al., 1995). 

Mitchell, Gorrell, and Greenberg (1980) showed that weight and head circumference were 

lower in children with FTT than in healthy controls at least until age 4-5 years (FTT 10-15% 

below controls for weight, p<0.001) and 10% below controls for head circumference (p<0.05). 

This was a longitudinal study on a US population in an outpatient clinical setting. The authors 

found no differences between controls and FTT groups for age, sex, mother's age/marital status, 

household composition, or maternal employment. Neonatal problems were more common in the 

FTT group, including evaluations for sepsis, poor sucking ability, mild neonatal jaundice but 

they were not thought to be a medically significant etiology for the FTT.

In an ambidirectional blinded study from the United Kingdom by Drewett, Corbett, and 

Wright (1999), children who failed to thrive from 1 to 5 years of age were smaller and had 

smaller head circumferences than their non-FTT counterparts at school age (median weight for 

FTT of 23.8 kg, IR 21.5 to 26.8 vs. controls 27.9 kg, IR 15.3 to 17.8). Black and Krishnakumar 

(1999), in a prospective, longitudinal study in the outpatient setting, demonstrated that despite 

catch up growth, weight and height for age were of significantly slower velocity in the FTT 

group compared to non-FTT controls. In another ambidirectional-longitudinal outpatient study 

by Reif, Beler, Villa, et al. (1995), mother's education level and family issues/living conditions 

were significant (p<0.05) covariants for long term recovery of weight and height in the FTT 

group.

Similar findings were shown in the prospective, longitudinal study by Haynes, Cutler, Gray, 

et al. (1984), where weight, head circumference and length were significantly lower in the FTT 

group, both on initial evaluation and at 6 month follow-up, despite an outpatient treatment 

program that included a case worker, visiting nurse, pediatrician and infant stimulation program,

with 29/37 children not showing catch up growth in 6 months. Significantly, children diagnosed 
24

and treated within the first 6 months of life were more likely to have improved growth outcomes. 

In their conclusion, the authors emphasized the need for more aggressive identification and more 

intensive intervention to reverse the altered growth patterns in these children.

Corbett, Drewett, and Wright (1996) extended the association of FTT with poor weight, 

height and developmental outcome one step further. This study was also an outpatient-based 

longitudinal 5-year follow up study. They identified a significant difference within the failure to 

thrive group with the severity of poor growth (weight and height) correlating with poorer 

developmental outcome.

Table 2. Studies of persistent anthropometric abnormalities following diagnosis of Failure to 

Thrive in developed countries 

Author,

Year,

UI Sample N

Age (mo) at 

assessment

Follow-up 

duration 

(mo) Applicability

Internal 

validity Correlates Association

Mitchell,

1980

80166667

FTT 30

Ctrl 282 36-60 12-36 ÇÇ =

Weight(%)

Height(%)

Head circumference(%)

Haynes,

1984

84233543

FTT 50 a

Ctrl 25 ND 6 ÇÇÇ £ Weight

Kelleher, 

1993

93234174

FTT 180

Ctrl 591 12 & 24 12 & 24 ÇÇ £

Weight / age

Height / length

Head circumference

Reif,

1995

95362505

FTT 61

Ctrl 65

74.4

81.6 61.5 ÇÇÇ £

Weight(%)

Height(%)

Ideal weight(%)

Corbett,

1996

97113595

FTT 48

Ctrl 46 72-84 > 36d ÇÇÇ =

Weight(SDS)

Height(SDS)

Black,

1999

10064327

FTT 127

Ctrl 98 ND > 60d ÇÇÇ £

Weight

Height

Drewett,

1999

99284054

FTT 107b

Ctrl 117

84-96c > 60d ÇÇ £

Weight

Height

Head circumference

Ctrl, control; FTT, failure-to-thrive; MO, month; ND, no data; SDS, standard deviation score; UI, MEDLINE® unique identifier.

a

 25 FTT had Lay Health Visitor intervention.

b

 2 FTT and 9 Ctrl with definite medical condition affecting growth; 1 FTT and 2 Ctrl with possible medical condition affecting 

growth.

c

 Five were age 9 y, ND whether cases or controls.

d

 See Chapter 2 – Methods.

FTT associated with decreased anthropometric measures compared to controls, (statistically significant, p < .05).

FTT associated with decreased anthropometric measures compared to controls.

FTT not associated with difference in anthropometric measures compared to controls.
25

Findings from the Developing World

In addition to these findings from industrial nations, seven pertinent studies were identified in 

developing countries. The studies in developing countries mainly compared children with 

marasmus and kwashiokor to healthy controls, mostly from outpatient settings, (Branko 1979; 

Evans et al. 1980, Galler et al. 1985). Using ambidirectional/longitudinal and prospective 

longitudinal research design, the majority of the studies found similar associations between the 

diagnosis of FTT and long-term disorders of growth (Branko 1997; Galler et al. 1985; Alvear et 

al. 1986; Grantham-McGregor et al. 1982, 1987; Benefice 1992; Walker et al. 1996). 

Specifically, in the studies by Grantham-McGregor, Schofield, and Powell (1987) looked 

primarily at the effect of home visits on Jamaican children with FTT and found that height for 

age remained low in the FTT group, even with the intervention (p<0.001 for Height/Age 88% 

FTT, 101% control; Head Circumference/Age 91% FTT, 99% control). The addition of more 

adequate nutritional supplementation to such children would be anticipated to aid in these 

improvements in outcome. This is further supported in the study by Evans and colleagues (1980), 

where height and weight improvements (p<0.01 in treatment vs. control group) seen two years 

post nutritional intervention did not persist six to seven years after intervention. Two other 

studies also showed significant differences in body fat and arm muscle composition in the FTT 

groups compared to controls (p<0.05) (Alvear, Artaza, Vial, et al., 1986, arm fat area 73.5+/-15.3 

and 64.5 +/-16.5 in FTT groups and 91+/-24.7 and 95.7 +/-28.5 in control groups) (Benefice, 

1992, % body fat of arm muscle area 18.7+/-0.33 in FTT and 21.8 +/-0.47 in controls). In the 

study by Benefice (1992), the decreased body fat and muscle mass had a negative impact on 

physical performance.

Table 3. Studies of persistent anthropometrics abnormalities in malnourished cases in developing 

countries

Author,

Year,

UI Sample N

Age (y) at 

assessment

Follow-up 

duration (y) Applicability

Internal 

validity Correlates Association

Branko,

1979

79228898

Gpa 87

Ctrl 559

(5.5-14)

(5-14) 7.5(2.5) Ç £

Height 

Weight

Head circumference

Evans, f

1980

81008912

Gp1 14

Gp2 14

Ctrl 26b

8.9(0.5)

13(1.9)

10.7, 12

2 & 6-7 Ç = Height

Weight

g

Galler, 

1985a

85241832

Gpc 108

Ctrl 107 9-15 6-12 ÇÇ £

Height

Weight

Birth height

Birth weight

Arm fat area

Alvear,

1986

86185605 Gp 40d

Ctrl 38 4-6 4

h ÇÇ £

Bone age

Height for age

GranthamMcGregor, 

1987, 1982

82236679

87117313

Gpe 34

Ctrl 20 ~7i 6 ÇÇ =

Weight for height
26

Author,

Year,

UI Sample N

Age (y) at 

assessment

Follow-up 

duration (y) Applicability

Internal 

validity Correlates Association

Bénéfice,

1992

92296639

Gp 64

Ctrl 34 9-14 NAj ÇÇ £ Body fat

Arm muscle

Walker,

1996

97154651

Gpk 122

Ctrl 32 7.7(0.4) 4 ÇÇ = HeightWeight

Head circumference

Ctrl, control; Gp1, Marasmus; Gp2, Kwashiorkor; NA, Not applicable; UI, MEDLINE® unique identifier; Y, year.

a

 2 groups collapsed into 1: 44 with marasmus, 43 with kwashiorkor.

b

 3 control arms collapsed into 1: controls consist of 30 siblings, 30 yardmates of index cases, 90 High SES Whites.

c

 PEM Grade II – III.

d

 Cases hospitalized for PEM.

e

 2 groups with severe PEM collapsed into 1: 18 had intervention, 16 had standard care.

f

 Assessment at 2 yr post-intervention for height & weight.

g

 Assessment at 6-7 year post-intervention for height & weight.

h

 After discharge.

i

 See Chapter 2 – Methods.

j

 Cross-sectional study.

k

 5 study arms collapsed into 2: index group consists of 31 stunted cases with supplement intervention, 29 stunted 

 cases with psychosocial intervention, 30 stunted cases with both interventions; control group – nonstunted.

Index cases associated with increased anthropometric measures compared to controls, (statistically significant, p < .05).

Index cases associated with decreased anthropometric measures compared to controls, (statistically significant, p < .05).

Index cases associated with decreased anthropometric measures compared to controls.

Index cases not associated with difference in anthropometric measures compared to controls.

Summary

Overall these studies comparing children who were thriving with those who were 

undernourished in both developed and developing countries show that children with FTT are at 

substantial risk for continued poor growth in weight, height, and head circumference, and that 

this growth disturbance is difficult to reverse despite appropriate interventions. The data also 

suggest that earlier diagnosis and intervention lead to potentially better long-term outcome. The 

fact that children who fail to thrive have poorer head growth is not surprising considering that 

human brain growth is tremendous in the early childhood years and insults during this time may 

impact permanently on developmental and intellectual outcome. These findings emphasize the 

importance of early and intensive intervention for children with or at risk for FTT so as to 

prevent permanent growth retardation.

Associations of FTT with Immunologic/Infectious Outcomes

Eight controlled studies were identified for review; four of these focused primarily upon 

aspects of immune function while four examined clinical infections among FTT children. Studies 

carried out in developing countries have variable generalizability for outcomes and policies in 

the United States. The studies conducted by Sherrod, O'Connor, Vietze, et al. (1984) in 

Tennessee, and by Carvalho Neves Forte, Martins Campos, and Carneiro Leao (1984) in Brazil 

involved infants and children with moderate degrees of malnutrition, similar to the patient 
27

population in the USA. Studies by Ferguson, Lawlor, Jr., Neumann, et al. (1974) (Ghana) and 

Friedland (1992) (South Africa) included only cases of severe malnutrition, i.e., marasmus and 

kwashiorkor. The studies of Tuck, Burke, Gracey, et al. (1979), Neumann, Lawlor, Jr., Stiehm, et 

al. (1975), and Pandey and Chakraborty (1996) included more than one group of FTT children, 

graded by severity. Patients in the moderate malnutrition categories likely represent a reasonable 

comparison to the US population of FTT patients.

Seven studies were prospective and one study was retrospective. Only three studies (Ballard 

and Neumann, 1995; Pandey and Chakraborty, 1996; Sherrod, O'Connor, Vietze, et al. 1984) 

were longitudinal; all others were cross-sectional. The principal source of potential bias involved 

the selection of controls. Tuck, Burke, Gracey, et al. (1979) included adults as well as children in 

his controls; additionally, there were only controls (no FTT patients) entered from the children in 

the urban study center. The FTT and control groups in the study by Carvalho Neves Forte, 

Martins Campos, and Carneiro Leao (1984) were from different hospitals serving different SES 

populations. Friedland’s (1992) controls included children with "nutritional growth retardation", 

likely comparable to the US FTT population; further specifics are not provided. 

Evidence of Immunologic Dysfunction in Failure to Thrive

Multiple indicators of immunologic function and dysfunction have been used to try to 

understand the effects of malnutrition on children’s response to infectious insults.

Carvalho Neves Forte, Martins Campos, and Carneiro Leao (1984) examined monocyte 

chemotaxis and phagocytosis in Brazilian children (6 months to 5 years) with moderate protein 

calorie malnutrition (PCM). Because these investigators were interested in immunologic 

functioning of children with moderate PCM rather than severe malnutrition, they recruited a 

sample of children whose weight for age was between the 25th and 40th percentile of standards 

for age. Compared to well nourished controls, patients with moderate PCM demonstrated 

significant decreases in chemotactic response to bacterial endotoxin, as well as phagocytosis of 

zymogen particles (p< .001). Serum complement levels were not different between groups, and 

the differences in chemotaxis and phagocytosis persisted whether cells were incubated with 

simple media, patient serum or pooled normal serum suggesting that the defect existed at the 

level of the cell receptor.

Ferguson, Lawlor, Jr., Neumann, et al. (1974), studied in vivo cell mediated immunity in 10 

infants (ages 12-42 months) with severe PCM in Ghana (3 with marasmus, 7 with kwahiorkor) 

compared to 10 age matched controls. Although total lymphocyte counts were similar in the two 

groups, PCM infants had significantly lower percentages of rosette forming cells (RFC), a 

sensitive marker of cellular immune function; 16.6 percent + 2.7 vs. 64.5 percent + 1.0 

(p<0.001). PCM infants also manifested a higher incidence of negative skin hypersensitivity 

responses to monilia and SK/SD; no analysis is provided regarding the significance of this trend. 

Repeat studies on five of the malnourished infants following nutritional therapy with high 

protein diet showed reversion to normal for both the skin delayed hypersensitivity response and 

the percentage of RFC's.

Tuck, Burke, Gracey, et al. (1979) studied candidacidal activity of leukocytes in three groups 

of children in Indonesia as well as both urban and rural Australia: Controls (>80 percent standard 

weight for age (SWFA)); moderate under-nutrition (60-80 percent SWFA); and marasmus (<60 

percent SWFA). Both under-nourished and marasmic children demonstrated reduced Candida 

killing ability (17.6 percent and 13.7 percent respectively) compared to controls (44.5 percent; 
28

p< .001 for comparison of each malnourished group to controls). The candidacidal activity of 

leukocytes was not improved by addition of normal serum, suggesting, as does the study by 

Carvalho Neves Forte, Martins Campos, and Carneiro Leao (1984), tha t there is a primary 

cellular defect in leukocyte function. No population demographics are provided, including the 

age of patients and controls, which makes for some difficulty in interpretation and concern about 

potential bias. Controls included both adults and children; the authors note that candidacidal 

activity is known not to be age-related, with no difference between healthy, well nourished 

children and adults. 

Neumann, Lawlor, Jr., Stiehm, et al. (1975), examined markers of immunologic dysfunction 

along with clinical correlates of infection in children ages 6 months to 6 years in Ghana. Three 

groups of children were compared: Group I, severe malnutrition (50-60 percent weight for age 

with low serum albumin); Group 2, moderate malnutrition (61-80 percent weight for age with 

normal serum albumin); and Group 3, well nourished controls (>81 percent weight for age with 

normal serum albumin). Delayed hypersensitivity skin test response to PHA, monilia and SK-SD 

were significantly decreased in both malnourished groups compared to controls. Forty-four 

percent of children with severe malnutrition and 29 percent of those with moderate malnutrition 

were non-responders to PHA, compared to only 5 percent for controls. In addition, malnourished 

responders manifested significantly smaller areas of induration. Lymphocyte response to PHA 

tested in vitro was significantly less in both malnourished groups and absolute lymphocyte 

counts were significantly lower in the severely malnourished group (all significance at p<.05). 

Immunoglobulin and complement levels, as well as antibody response to KLH (keyhole limpit 

hemocyanin) and PPS (pneumococcal polysaccharide) were similar among all three groups.

Tonsil size was reduced in Group 1 compared to Group 2 and Group 3; with 36 percent 

demonstrating trace or absent tonsil tissue compared with 5 percent of group 2 and none of the 

control group 3. Clinical infections, particularly pneumonia and fungal skin infections were more 

frequent in severely malnourished children.

Clinical Infections in Failure to Thrive

Friedland (1992) conducted a large prospective study of FTT infants (median 11 months, 

range 2-84 months) in South Africa. One thousand five hundred eighty two FTT children (792 

with kwashiorkor, 513 with marasmus, and 277 with marasmic kwashiorkor), all of whom were 

hospitalized specifically for their malnutrition, were compared to 7282 controls hospitalized for 

other reasons. Controls included both well nourished and “nutritionally growth retarded”; no 

specifics are provided regarding the percentage of the controls with nutritional growth 

retardation or the degree of growth retardation present.

Bacteremia, whether compared as total cases, or by subsets of community acquired and 

hospital acquired cases, was consistently more common among the FTT population. The overall 

incidence of bacteremia was 9.9 percent for the FTT children vs. 6.0 percent of controls 

(p<0.001). Furthermore, the mortality among bacteremic patients was also significantly greater 

among FTT cases (FTT 31 percent vs. controls 13 percent; p<0.001). Therefore, both the risk of 

bacteremia and subsequent mortality from bacteremia are significantly associated with FTT.

Sherrod, O'Connor, Vietze, et al. (1984) found a 4-fold increase in “bacterial or viral 

infections such as URI or mumps” among American infants aged 0 to 3 months with non-organic 

failure to thrive compared to controls (p<.05, Evidence Table 3). FTT was defined as weight gain 

falling below two-thirds of the Harvard fiftieth percentile growth curve.
29

Ballard and Neumann (1995) conducted a prospective cohort study of 200 children in Kenya, 

age 14-25 months. Children were followed for development of acute lower respiratory infections 

(ALRI) for up to 12 months. Symptom checklists were completed based on parental report at 

weekly visits. FTT, either low weight for age or low height for age, was a strong predictor of 

development of ALRI. Height for age < 90 percent of the median had the strongest correlation, 

with a relative risk of 4.5 vs. non-FTT (95 percent CI 1.1-17.4). The fact that height for age was 

a stronger predictor than weight for age suggests that chronicity of malnutrition has a greater 

impact upon immune function and risk of infection than does acute malnutrition.

Pandey and Chakraborty (1996) followed a cohort of 200 Indian children, documenting 

episodes of acute respiratory infections (ARI). Malnutrition was graded based on weight for age. 

The number of ARI episodes per child was significantly greater in FTT children than controls 

(6.6 episodes/year vs. 4.8 episodes /year; p<0.05). Furthermore, there was a stepwise increase 

from grade I (mild malnutrition; 5.6 episodes/year) to grade IV (severe malnutrition (7.7 

episodes/year; p<.05, chi-square) (Evidence Table 4).

In summary, studies comparing children who are thriving with those who were 

undernourished in both developed and developing countries show that children with FTT have 

significant pertubrations in immunologic function, and a corresponding increased susceptibility 

to clinical infection. These findings emphasize the importance of identifying children who are 

failing to grow normally since their growth failure may put them at additional risk for a variety 

of acute and chronic infections that might not necessarily be appreciated. In addition, treatment 

of FTT provides an opportunity to prevent the additional consequences and costs associated with 

chronic infectious conditions in children.

Table 4. Studies with associations of immunologic dysfunction or infectious diseases to Failure to

Thrive & healthy comparison groups in developed countries 

Author,

Year,

UI Sample N

Age (mo) at 

assessment

Follow-up 

duration (mo) Applicability

Internal 

validity Correlates / outcomes Association

Carvalho,

1984

85145406

FTT 20a

Ctrl 40 6-60 NAb ÇÇÇ £

Immune function

• Phagocytic 

responses

• Chemotactic 

function

• Complement levels

Sherrod,

1984

85026403

FTT 31

Ctrl 24 ND 36 ÇÇÇ £ Infections

Ctrl, control; FTT, failure-to-thrive; Mo, month; NA, not applicable; UI, Medline® unique identifier.

a

 Cases diagnosed with moderate & chronic primary protein-calorie malnutrition.

b Cross-sectional study.

FTT associated with increased incidence of infectious diseases compared to controls, (statistically significant, p < .05).

FTT not associated with increased incidence of immunologic response or infectious diseases.

FTT associated with decreased immunologic response.
30

Table 5. Studies with associations of immunologic dysfunction or infectious diseases and 

malnourished cases compared to well-nourished controls in developing countries 

Author,

Year,

UI Sample N

Age (y) at 

assessment

Follow-up 

duration (y) Applicability

Internal 

validity Correlates Association

Ferguson,

1974

75022280

Gpa 10

Ctrl 10

28.9

38.8 NAb Ç £ Rosette forming cells

Clinical infections

Parasites Neumann,

1975

75106463

Gp1c

34

Gp2 42

Ctrl 41

6 m – 6 y NAb ÇÇ £

Delayed 

hypersensitivity 

response

Tuck,

1979

79254720

Gp1d

21

Gp2 23

Ctrl 25

ND NAb ÇÇ °

Candida killing 

 Capacity

Friedland,

1992

93159117

Gpe 11

Ctrl 12

11 m

12 m NAb Ç = 

Bacteremia

Nosocomial 

 Bacteremia

Ballard,

1995

95239862

Gp1f 27

Gp2 51

Ctrl 31

2.5 - 3 1 ÇÇ = Acute lower 

 respiratory infections

Pandey,

1996

97246349

GrI-IV

115

Ctrl 85

1 - 6 1 Ç £

Acute respiratory 

 Infections

Ctrl, control; Gp, group; M, month(s); NA, Not applicable; UI, Medline® unique identifier; Y, year.

a

 Severe protein-calorie malnutrition.

b

 Cross-sectional study.

c

 Gp1 - Severely malnourished: kwashiorkor (23) & marasmus (11); Gp2 – moderately malnourished.

d Gp1 - marasmus; Gp2 – “underweight”.

e

 Kwashiorkor, maramus, marasmic kwashiorkor.

f Gp1 – Moderate & severe kwashiorkor Gp2 – Mild malnutrition.

Index cases associated with increased incidence of infectious diseases compared to controls, (statistically significant, p < 

.05).

Index cases associated with increased incidence of infectious diseases compared to controls

Index cases not associated with increased incidence of immunologic or infectious disease response.

Index cases associated with decreased immunologic response, (statistically significant, p < .05).

Child Behavior Problems Associated with Failure to Thrive

Systematic assessment of children’s behavior (usually by parent report) was a part of about 

one-third of the studies reviewed. The specific aspects of behavior assessed, and the instruments 

used to quantify these difficulties, are disparate and not easily comparable. Therefore we will 

present descriptive information summarizing the conclusions of the sixteen investigators who 

addressed behavioral difficulties as a part of their analyses. Evidence will be presented in three 

areas:
31

• concurrent feeding-related behavior problems associated with FTT

• other concurrent behavioral problems

• behavior problems detected in follow-up subsequent to the diagnosis of FTT.

Evidence of Concurrent Feeding-Related Behavior Problems 

Associated with FTT

Feeding is a critical self help skill that develops during infancy and toddlerhood. Inability to 

self-feed in toddlers or inability to be cooperative with caretaker feeding during infancy is a 

functional impairment in caring for oneself and in maintaining health and physical well-being. 

Depending on degree, disorders of feeding may result in either marked or severe functional 

limitation, thus contributing to or establishing disability.

Four controlled studies noted concurrent feeding disorders in children diagnosed with FTT. 

These studies varied in their definitions of eating disorders, and will be reviewed individually. 

One study grouped feeding behaviors with other behavior disorders, one study observed infant 

affect during feeding, one observed feeding behavior directly, and the fourth used maternal recall 

of feeding behavior. Regardless of methodology used, significant feeding-related issues were 

more frequently in infants with failure-to-thrive than in control infants.

In the first relevant study, 19 FTT children and age/sex-matched controls were evaluated 

over several weeks to determine incidence of feeding, autoerotic and self-harming behaviors by 

Pollitt and Eichler (1976). Children with mean age of 33 months were enrolled in an outpatient 

clinic. Controls were matched for age, sex, and race. Children with already-identified birth 

complications, physical disability, brain damage or "organic growth retardation" were excluded. 

Thus the group called “FTT” were those for whom no medical cause for the FTT had been 

identified. Behavior was assessed by interview and direct observations at home. Of particular 

interest/attention were the child’s response to food, mood while eating, and the presence of 

polydipsia, pica, and hiding food. Eating behavior was rated by observers on a 4-point scale 

created by the investigators. Information was collected also about autoerotic and self-harming 

behaviors. Overall, 10 children with FTT exhibited abnormal eating behavior determined over 

weekly interviews conducted for 7-11 weeks, compared to matched controls. These data 

demonstrate that eating behavior is more problematic in children with FTT, than in children 

growing normally.

Polan, Leon, Kaplan, et al. (1991) reported a small masked study of affective expression in 6-

36 month old children born appropriate for gestational age (AGA) at 35 weeks or older in US 

with (28) and without (14) FTT in feeding and non-feeding situation. The Kiddie Affect 

Inventory and Assessment, which reports four channels of emotion - facial display pattern, 

vocalization, gesture, body position and movement was used. FTT was associated with increased 

negative affect and decreased positive affect during feeding compared to controls, with no 

difference in non-feeding situations. Severity of malnutrition, but not presence of organic 

disease, was associated with affective outcomes.

A community-based cohort of children at 15 months of age was identified through medical 

records from two Israeli communities by Wilensky, Ginsberg, Altman, et al. (1996). A subgroup 

of 50 diagnosed cases of FTT was assessed along with 50 matched controls. A maternal 

questionnaire was developed to assess feeding behavior. Feeding problems included both 

behavioral (e.g. turned head from food, spits out food) and affective items (e.g. shows pleasure at 
32

meals). The results demonstrated significantly more feeding problems among FTT children 

compared with controls.

A population-based study in Newcastle, England utilized a screening program to identify 

one hundred twenty cases of FTT during the two-year enrollment period. Wright and Birks 

(2000) reported on ninety-seven FTT cases who had complete data and 28 controls identified 

from 3 general practices. FTT cases were reported to start solid foods later than controls, 3.89 

months versus 3.04 months (p = .003), as well as being delayed in starting finger foods, at 7.15 

months versus 6.14 months (p = .005). The clinical importance of these small differences is 

unclear. However, there were more parent-reported feeding problems during infancy for the FTT 

cases, 28 percent versus 2 percent for the controls (p = .022). Parents of FTT children more often 

described their children as uninterested or poor eaters (FTT 11 vs. Controls 0, p = .003).

Evidence Suggesting Concurrent Behavioral Problems Associated 

with FTT

This section reviews concurrent or nearly-concurrent behavioral problems associated with 

failure-to thrive. Four controlled studies examined behavior problems that were either diagnosed 

concurrently with diagnosis or within six months. Because each study established its own 

definition of behavioral disorder, the studies are reviewed individually rather than combined. 

Three of the four studies found an increase in attachment disorders or other early childhood 

behavior disorders in infants and toddlers with diagnosed FTT. These disorders all comprise 

functional limitations in interacting or relating to others, which may be marked or severe in 

individual cases, and would contribute to or establish disability.

Hutcheson, Black, and Starr, Jr. (1993) observed the behaviors of thirty-four children with 

FTT and matched comparison children with their mothers during feeding. The children were 

divided into two age groups, infants (age 8 – 13.4 months), and toddlers (age 13.5 – 24 months). 

Controls were matched based on age, sex and race. Parenting functioning, child functioning, and 

contextual sources of stress and support were assessed, using the Infant Characteristics 

Questionnaire. Mothers of younger children reported a greater level of difficulty in caretaking. 

No other age or group differences were found on parenting stress, informal support, life events, 

and negative affectivity.

Chatoor, Ganiban, Colin, et al. (1998) studied three groups of toddlers from various ethnic 

and economic classes based on diagnosis of infant anorexia (n=33), picky eaters (n=34), and 

healthy eaters (n=34). The study examined attachment and security level in the three groups, 

using the Ainsworth and Cassidy & Marvin attachment classification systems. Most of the 

children were evaluated as ‘secure’, but the frequency of insecure attachments was significantly 

related to diagnostic group, χ

2 = 8.0, p < .05. There was a greater frequency of insecure 

attachments in infants with anorexia compared to picky eaters, or compared to healthy eaters χ

2 

= 

6.7, p < .0 and χ

2 = 3.9, p < .05, respectively. A nine point Likert scale was used to assess the 

degree of attachment security. The infants with anorexia obtained the lowest score of 4.9 while 

picky eaters and healthy eaters scored 6.0 and 6.1 respectively. There was a main effect for the 

group, F = 5.8, p < .01, and a positive correlation between ideal weight and attachment security, r 

= 0.31, p < 01 (Evidence Table 5).

Steward, Moser, and Ryan-Wenger (2001) evaluated 14 children with FTT compared to 14 

controls matched for age, sex and race. They evaluated behavioral responsiveness of the infant 

using the Parent-Child Early Relational Assessment Scale. The FTT group scored significantly 
33

lower on the communication subscale (FTT 3.19 vs. Control 4.07). During interactions with their 

mothers, they had less visual contact, more gaze aversion, and vocalized less than controls. They 

also scored lower than controls on the mood subscale, as they were more irritable and apathetic 

(FTT 3.65 vs. Control 4.26).

Skuse, Pickles, Wolke, et al. (1994) is a population study in south London of low SES 

infants. Forty-seven FTT cases identified and matched forty-seven controls were assessed at 

approximately 15 months of age. Using the Tester’s Rating of Infant Behavior instrument, no 

significant differences were found between the groups for expression of positive affect, task 

directed behavior, and task persistence.

Evidence Regarding Behavior Problems Detected in Follow-up 

Galler, Ramsey, Solimano, et al. (1983b) compared 129 Barbadian children with FTT prior 

to 1 year old with matched controls. Assessments were conducted at age 60-132 months. 

Behavioral disorders and the presence of ADD were measured using study-specific instruments. 

Classroom behavior problems were noted more frequently in children with a history of FTT 

during infancy.

Mitchell, Gorrell, and Greenberg (1980) reviewed the medical records and prospectively 

followed a cohort of three hundred and twelve children ages two to five years from three rural 

primary care centers. A majority of families received government insurance; 70 percent were 

black. Thirty children were defined as FTT based on weight below 80 percent of normal 

recorded during first 24 months of age. Compared to the remaining controls, the index group had 

significantly more family problems and neonatal abnormalities such as poor suckling, jaundice, 

and suspected sepsis, p < .01 and p < .05, respectively. Behavioral evaluation was conducted at a 

follow-up visit conducted at age 3-6 years, using a behavioral problems questionnaire and the 

McCarthy Scale of Children's abilities. Children with FTT had more behavioral problems 

reported and scored lower on intelligence tests (Evidence Table 5).

Drotar and Sturm (1992) evaluated preschool American children with FTT in a comparison 

trial of three different interventions involving varying degrees of psychosocial support. The 

scores of the three FTT groups (N= 48) were pooled and compared to healthy controls (N-47). 

Children were enrolled at age 3 and assessed at age 5. Comparisons were based on use of the 

California Child Q-set to assess their personality development, the Lock Box to measure 

organization in problem-solving, and the Child Behavior Checklist (CBCL) to assess problem 

behaviors. Results showed poor psychosocial development in the five-year-olds who had a 

history of FTT as infants. Scores in ego resiliency and behavioral organization were lower for the 

FTT group compared to controls; 376.06 versus 397.37, p < .05, and .95 versus 8.45, p < .01, 

respectively. The incidence of behavioral problems on the CBCL was also significantly higher 

for the index group compared to the controls, 58.5 versus 53.2, p < .05. There was no difference 

in ego control.

A cohort of inner city British white children who were born in 1980 were identified from 

medical records. Puckering, Pickles, Skuse, et al. (1995) reported on those diagnosed with FTT 

based on height and weight below 10th percentile compared with control children who were 

matched on the basis of sex, birth weight, and ethnic origin. Children with a history of FTT were 

found to have clinically and statistically significant behavioral deficits using the Behaviour 

Screening Questionnaire, 8.7 versus 6.9 for controls. These observed deficits did not appear to 

result from parenting practices or other environmental influences.
34

The study by Kerr, Black, and Krishnakumar (2000) is a follow-up of children 6 years of age 

from an earlier study (Mackner, Starr, Jr., and Black, 1997) consisting of two initial samples, 

FTT and adequately nourished children. History of maltreatment was based on at least one report 

to the Child Protective Services and was not part of the initial recruitment criteria. There was no 

effort to discern maltreatment in children not reported. Though it was reported that “most 

children had recovered” from FTT, there were no specific data provided. Three percent of the 

FTT sample persisted with weight for height below the 5th percentile. The one hundred ninety 

three, mainly poor, mostly African American inner-city children were divided into four risk 

factor groups; FTT (n=64), FTT with history of maltreatment (n=28), history of maltreatment 

alone (n=21), and neither risk factor (n=80). Behavior problems were documented by teacher 

reports of adaptive functioning at school and the Teacher Report Form; children’s behavior at 

home was measured by the Child Behavior Checklist. Analyses of covariance showed main 

effects for risk status for all behavioral outcomes, p < 0.01. Analyses revealed statistical 

significance between the FTT and maltreatment versus the neither risk factor groups for adaptive 

functioning and school behavior, p < 0.05 (Evidence Table 5).

Corbett, Drewett, and Wright (1996) identified from records from a clinic serving a 

predominant low income, white population of Newcastle, 52 cases and 52 controls. The five-year 

follow-up for 48 FTT children and 46 controls found a trend towards behavior problems as 

measured by Child Behavior Checklist, p < 0.296 (Evidence Table 5).

The Kelleher, Casey, Bradley, et al. (1993) study, which followed a large cohort of low birth 

weight infants, assessed 180 who developed FTT. Though there were no significant differences 

between the 180 FTT cases and 591 nonFTT as measured by the Bates Temperamental Scale at 

12 months, there was a trend for more behavior problems as measured by the Child Behavior 

Checklist at 24 months.

Table 6. Studies with association of behavioral correlates to Failure to Thrive compared to healthy 

comparison groups in developed and developing countries

Author,

Year,

UI Sample N

Age (mo) at 

assessment

Follow-up 

duration 

(mo) Applicability

Internal 

validity Correlates / outcomes Association

Pollitt,

1976

76109110

FTT 19

Ctrl 19

> 33a

> 34 7-11 wk ÇÇ £

Eating disorder;

Autoerotic & self-harm

Mitchell,

1980

80166667

FTT 30

Ctrl 282 36-60 12-36 ÇÇÇ = Behavior problems

Galler,

1983b

83136863

Gp 129

Ctrl 129 60-132 48-120 ÇÇ £ Classroom behavior

Positive affect during 

feeding Polan,

1991

92098539

FTT 28

Ctrl 14

16.7b

18.9 NAc ÇÇ £ Negative affect during 

feeding

Drotar, 

1992

92372721

FTT 48

Ctrl 47 36 > 24a ÇÇÇ £

Personality 

development 

Behavioral 

organization 

Behavioral problems 
35

Author,

Year,

UI Sample N

Age (mo) at 

assessment

Follow-up 

duration 

(mo) Applicability

Internal 

validity Correlates / outcomes Association

Hutcheson, 

1993

94015754

FTT 34

Ctrl 34

15.0b

14.9 NAc ÇÇÇ £ Child temperament

Kelleher, 

1993

93234174

FTT 180

Ctrl 591 12 & 24 12 & 24 ÇÇ £ Behavioral disorder

Skuse,

1994 

94253258

FTT 47

Ctrl 47

14.6b

14.2 ND ÇÇÇ = Behavior Assessment

Puckering,

1995

95378341

FTT 23

Ctrl 23 48 > 12a ÇÇÇ = Behavior score

Corbett,

1996

97113595

FTT 48

Ctrl 46 72-84 > 36a ÇÇÇ =

Behavioral disorder

 Teacher’s report

 Parent’s report

Wilensky, 

1996

97022837

FTT 50

Ctrl 50 20b NAc ÇÇ = Feeding problems

Chatoor,

1998

99026462

Gp1 33d

Gp2 34

Ctrl 34

12-37 NAc ÇÇ °

Attachment 

classification

Attachment security

scale rating

Wright,

2000

20161504

FTT 97

Ctrl 28

15.1

g

 (7-28)

(16-18) NAc ÇÇ £

Behavior & 

temperament

Kerr,

2000

20277217

FTT 92h

Ctrl 101

~73.8

~73.3 48 ÇÇÇ £

Adaptive functioning at 

school

School behavior

Home behavior

Steward,

2001

21291243

FTT 14

Ctrl 14

9.2

8.6 NAc ÇÇÇ £

Communication

Mood effect

Ctrl, control; FTT, failure-to-thrive; Gp, group; Mo, month(s); NA, not applicable; ND, no data; UI, Medline® unique identifier; 

Wk, week(s).

a

 See Chapter 2 – Methods.

b Mean age.

c

 Cross-sectional study.

d

 Gp1 Infantile anorexia, Gp2 “Picky eaters”, Ctrl “Healthy eaters”.

e

 2 FTT and 9 Ctrl with definite medical condition affecting growth; 1 FTT and 2 Ctrl with possible medical condition affecting 

growth.

f

 Five were age 9 y, ND whether cases or controls.

g

 Median age.

h

 4 Study arms collapsed to 2: FTT group includes 64 diagnosed FTT and 28 diagnosed FTT & Maltreatment; Ctrl group includes 

80 with neither diagnosis and 21 diagnosed with Maltreatment.

FTT associated with increased behavioral disorders or variables compared to controls, (statistically significant, p < .05).

FTT associated with decreased behavioral variables compared to controls, (statistically significant, p < .05).

FTT associated with behavioral disorders compared to controls.

 FTT not associated with behavioral disorders compared to controls.
36

Developmental Disorders Associated with Failure to Thrive

FTT is consistently associated with evidence of neurodevelopmental disabilities. Insufficient 

intake of both macro and micronutrients exerts diverse functional and structural effects on the 

nervous system, with effects particularly likely to persist if they occur during the vulnerable 

periods of rapid neuraldevelopment. Since FTT most often occurs in early life, during the period 

of most rapid postnatal brain development, developmental concomitants and lasting sequelae are 

to be expected. Subtle neurological deficits may interfere with the normal progression of feeding 

skills even in the absence of clinically evident palsies. They contribute to FTT by interfering 

with the child's ability to take in adequate nutrients. FTT also appears to heighten developmental 

vulnerability to other adverse environmental factors (Barrett & Frank, 1987). 

For the purposes of this review we reported whatever indicators were chosen by particular 

investigators as indicative of developmental deviations. These heterogeneous indicators range in 

specificity and in severity. They include, for example, sucking/swallowing difficulties, delays in 

age of tolerating solid foods, pica, motor delays, and global developmental delays. We attempted 

to summarize comparisons made by diverse investigators between children failing to thrive and 

children growing normally. It is important to note that in spite of the highly variable 

developmental outcomes assessed, the presence of impairment in children who are not growing 

normally is found consistently across studies and circumstances.

The following discussion is divided by source of subject population (developed versus 

developing country) and within each category by 3 domains 1) oral motor and other neurological 

findings; 2) developmental/cognitive functioning concurrent with the identification of FTT; and 

3) developmental/cognitive function in later childhood among survivors of early FTT.

Developed Countries

Oral Motor and other Neurological Findings

Prospective, epidemiological, and observational studies consistently note increased rates of 

feeding difficulties in children with FTT, with some investigators also noting clinically poorly 

specified "neurological" findings other than in feeding skills. Since these studies are often based 

on parental report, it is hard to distinguish true subtle neurological (either oral motor or sensory) 

deficits in feeding from parental perception and from learned behaviors. However, slow feeding 

and delayed acquisition of age-appropriate feeding skills are a consistent finding in every study 

where they have been assessed.

Prospectively, in the newborn period, Kelleher, Casey, Bradley, et al. (1993) noted increased 

rates of abnormal or suspect neurological exams among infants who later failed to thrive, 

compared to those who did not. Mitchell, Gorrell, and Greenberg (1980) found "suckling 

difficulties" were more likely to be noted in the newborn records of children who later failed to 

thrive. Hack, Merkatz, Gordon, et al. (1982) found increased rates of "neurological" 

abnormalities at 8 months among infants who failed to thrive compared to those who grew well. 

In a large epidemiological study, Wright and Birks (2000) in Newcastle, England utilized a 

screening program that identified 120 cases of FTT during the two-year enrollment period. 

Twenty-eight of the forty controls identified from three general practices that agreed to 

participate were compared to the 97 FTT cases who had completed data. FTT cases were 

reported to start solid foods later than controls, 3.89 months versus 3.04 months, p = .003, 
37

respectively, as well as starting finger foods later, 7.15 months versus 6.14 months, p = .005. 

Also reported were more feeding problems during infancy for the FTT cases, 28 percent versus 

two percent for the controls, p = .022. FTT parents were more likely to describe their children as 

variable, uninterested, or poor eaters, 11 instances reported for FTT versus none by the control 

parents, p = .003. In a detailed observational study in the United States, (Pollitt and Eichler, 

1976) 19 FTT children and age/sex-matched controls were evaluated over several weeks in open 

trial. FTT children were found to differ from controls in feeding behaviors as well as in other 

domains of development.

Developmental/Cognitive Impairments Concurrent with Identification of FTT

From developed countries there are relatively few controlled papers that document the 

developmental status of children with FTT at the time the condition is diagnosed either clinically 

or epidemiologically. The focus has been on follow-up studies, which are therefore described 

below. The issue is complicated further because developmental delay historically was considered 

by some authors (Coleman and Provence, 1957) as one of the criteria of FTT in addition to 

growth failure. It is only in recent decades that children have been labeled as FTT on the basis of 

weight alone. Moreover, except as noted, most of the studies of FTT children at the time of 

identification do not use masked testers (and indeed it is difficult to mask testers to the 

differences in size between acutely underweight FTT children and normally growing comparison 

children of the same age). Therefore an experimenter effect cannot be ruled out in the studies 

summarized below. Most, although not all, of the samples in these studies also contribute to long 

term outcome studies.

There are three US studies, two based on hospitalized samples (Haynes, Cutler, Gray, et al.,

1984; Singer and Fagan, III, 1984) and the other on a sample not hospitalized but drawn from an 

outpatient inner city clinic (Mackner, Starr, Jr., and Black, 1997). In the Singer and Fagan, III 

(1984) study, 8 month old infants with FTT showed on average a large deficit (30-40 points) on 

the Bayley Mental Development Index compared to controls, and among some FTT children, a 

difference also in visual recognition memory. As a baseline for an intervention study, Haynes, 

Cutler, Gray, et al. (1984) compared 50 FTT children with 25 "thriving" children on the Bayley 

Scales of Infant Development and found that 62 percent of the FTT sample were either delayed 

or retarded (22 percent with an MDI less than 70) compared to only 19 percent of controls who 

were delayed, with none retarded.

Mackner, Starr, Jr., and Black (1997) performed a cross sectional study controlled for 

maternal IQ and child age on a large sample of 177 inner city toddlers, 3-30 months old who 

were predominantly African American. Ninety-seven children had FTT defined as weight for age 

less than 5th percent before age 2. Of these, 27 were also characterized as "neglected," defined as 

the lowest tercile on a Home Observation for Measurement of the Environment (HOME) score 

obtained by a masked examiner. It is not clear if the psychometrician who performed the Bayley 

tests was masked to FTT status. Children with both FTT and low HOME scores attained Bayley 

Mental Development Index scores one standard deviation lower than children with neither. 

Children with FTT with HOME scores above the lowest tercile scored on average 3 points lower 

than children with neither on Bayley MDI.

Skuse, Pickles, Wolke, et al. (1994) reports on a population survey of low SES infants in 

south London born in the year 1986. Forty-seven infants with FTT and matched forty-seven 

controls were identified. They were assessed at approximately 15 months of age, using the 
38

Bayley MDI and PDI scores. Infants with FTT had scores which were significantly lower than 

controls on both the MDI (98.2 vs.108.5) and the PDI (96.7 vs. 103.6). In addition, there was a 

negative correlation between the FTT children’s oral motor skills and their MDI scores (r= -0.38, 

p = .008). Modeling predicted a correlation between the standardized weight falling during the 

first 6 months to a 10-point loss in mental and psychomotor development during the second 

postnatal year. The prediction included weight loss commencing after the first 4 months would 

have a 3 point loss in development whereas a weight loss after 8 months which would have no 

effect on development.

Kelleher, Casey, Bradley, et al. (1993) followed a large cohort of babies who had been born 

with low birth weight of 2500 grams or less and with gestational age up to 37 weeks. Of the 

4,551 infants born at the eight Infant Health and Development Program sites, 842 met the 

inclusion criteria for this study and of those, 180 developed FTT. At 12 and 24 months, Bayley 

Mental and Psychomotor Development Indexes were lower for children with FTT than children 

without FTT (p < 0.005) (Evidence Table 7). At 36 months, the Stanford-Binet IQ scores were 

lower for children with FTT, 84.7 vs. 89.9 for non-FTT, p < 0.007.

Corbett, Drewett, and Wright (1996) reviewed records from the “most economically deprived 

wards in Newcastle” to identify children with FTT. Diagnosis of FTT required at least 6 recorded 

weights during their first 18 months. The controls were also from the same clinic serving a 

predominant low income, white population of Newcastle. The children were assessed at school 

entry using the CBCL and the Wechsler Pre-School and Primary Scale of Intelligence - Revised. 

The severity of FTT was significantly associated with full-scale IQ, though no overall group 

differences were noted between children with a history of FTT and normal controls.

Drewett, Corbett, and Wright (1999) enrolled 136 children with a thrive index < 5 percent, 

and 136 controls, matched for age and residential area. Follow-up occurred at ages 5.5 to 7.5 

years. Assessment was conducted by interviews and testing using the WISC-III and WORD 

tests. Lower IQ scores were noted in children with a history of FTT compared to controls (mean 

IQ, FTT 87.6 vs. 90.6).

A cohort of inner city British white children who were born in 1980 were identified from 

medical records. Puckering, Pickles, Skuse, et al. (1995) reported on those diagnosed with FTT 

based on height and weight below 10 percentile compared with control children who were 

matched on the basis of sex, birth weight, and ethnic origin. Using the McCarthy Scales of 

Children’s Abilities, children with a history of FTT were found to have clinically and statistically 

significant cognitive deficits (FTT 77.1 vs. Control 97.7).

Kerr, Black, and Krishnakumar (2000) followed children 6 years of age from an earlier study 

(Mackner, Starr, Jr., and Black, 1997). Children with FTT and adequately nourished children 

were compared. Developmental assessment included cognitive performance measured by 

Wechsler Preschool and Primary Scale of Intelligence-Revised Edition, and showed that children 

with FTT consistently had lower cognitive test scores than nutritionally adequate children (FTT 

81.98/FTT with maltreatment 77.98 vs. Controls 83.95).

In summary, at the time of identification, FTT is associated with depressed developmental 

test scores, with most profound depression seen in clinically identified hospitalized children. 

However, even in samples identified epidemiologically rather than by clinicians, FTT is 

associated on average with roughly two-thirds of a standard deviation decrease in developmental 

test scores, so that many more FTT children will score in the SSI qualifying range of 

developmental delay than children in a reference population.
39

Developmental/Cognitive Functions in Childhood Among Survivors of FTT in 

Early Childhood 

Duration of follow-up of children with FTT varies widely between studies, as does the 

setting in which FTT was initially identified (hospital, outpatient clinic, or epidemiological 

survey). There is often ambiguity in these studies as to whether the deficits identified are 

attributable to FTT in early life or to concurrent undernutrition and environmental stressors at the 

time the outcome is measured. Nevertheless, there is a consistent trend for children with a history 

of FTT to score lower than their social class peers on developmental/cognitive test scores. In 

contrast to the studies of developmental status of children with FTT at the time of diagnosis, 

many of the follow-up studies (Corbett, Drewett, and Wright, 1996; Drewett, Corbett, and 

Wright, 1999; Mitchell, Gorrell, and Greenberg, 1980; Puckering, Pickles, Skuse, et al., 1995; 

Wilensky, Ginsberg, Altman, et al., 1996) specify that psychometric examiners were masked to 

the children's early growth history.

The Haynes, Cutler, Gray, et al. (1984) and Singer and Fagan, III (1984) studies which 

followed small cohorts of hospitalized children for six months after diagnosis and up to age 3 

years respectively found persistent and profound decrements in scores on the Bayley Scales of 

Infant Development compared to the scores of controls. In contrast, Drotar and Sturm (1992) 

reported in passing that previously hospitalized FTT and not hospitalized comparison children 

retained until age 4 for a behavioral outcome study did not differ at age 3 in their Stanford-Binet 

Scores, which were roughly one standard deviation below the mean in both groups (86 vs. 88).

Among samples selected from outpatient clinics the trend is similar across diverse settings 

Mitchell, Gorrell, and Greenberg (1980) in rural North Carolina measured McCarthy Scores 

between 3 and 6 years among 12/30 children who had failed to thrive in earlier life and 16/282 

comparison cases. On average the children with FTT scored 5 points lower than the comparisons 

(87.5 vs. 92.5) but the difference was not significant in the sample overall, although girls with a 

history of FTT scored significantly lower than those without.

Kerr, Black, and Krishnakumar (2000) conducted a follow-up of children at 6 years of age 

from an earlier study (Mackner, Starr, Jr., and Black, 1997) of one hundred ninety-three, mainly 

poor, predominantly African American inner-city children divided into four risk factor groups; 

FTT (n=64), FTT with history of "maltreatment" (n=28), history of "maltreatment" alone (n=21), 

and neither risk factors (n=80). History of "maltreatment" was based on at least one report to the 

Child Protective Services (primarily for neglect, but some also for suspected physical or sexual 

abuse) and was not part of the initial recruitment criteria. There was no effort to discern 

maltreatment in children not reported. Developmental assessment measured by an abbreviated 

version of the Wechsler Preschool and Primary Scale of Intelligence-Revised Edition revealed 

statistically significance differences (78 vs. 84) between the FTT and maltreatment versus the 

neither risk factor group, with a non-significant trend toward depressed scores among children 

with FTT but without "maltreatment" (82 vs. 84). There are two urban Israeli studies, one from 

Jerusalem (Wilensky, Ginsberg, Altman, et al., 1996) and one from Tel Aviv (Reif, Beler, Villa, 

et al., 1995). Wilensky, Ginsberg, Altman, et al. (1996) found statistically significant differences 

in average Bayley Mental Development Scores (99.7 vs. 107) and a higher incidence of MDI 

below 80 (11.5 vs. 4.6%) in 50 children with a history of FTT compared to 50 matched controls. 

Reif, Beler, Villa, et al. (1995) in a five year follow-up study found almost identical statistically 

significant rates of developmental delay (not precisely defined) (11.5% vs. 0%) and "learning 

difficulties" (18% vs. 3%) among 61 children with a history of FTT compared to 65 controls.
40

The epidemiological studies fall into two main categories -- American studies which follow 

prospectively low birthweight cohorts and English studies which evaluate term birth cohorts in 

defined urban neighborhoods. Hack, Merkatz, Gordon, et al. (1982), examined very low birth 

weight infants’ mental, in relation to catch-up growth, at 8 months. One hundred and ninety two 

infants less than 1,500 grams were divided into two groups, thirty-eight SGA and one hundred 

fifty-four AGA. At eight months, eight tertiary subgroups were created and measurements were 

taken again along with the Bayley performance assessment. The developmental scores at eight 

months for all five normal weight subgroups were above 100, significantly different from those 

of the subnormal weight groups; SGA (n=19) at 99, AGA (n=30) at 93, and AGA at eight 

months only (n=13) at 89, p < .005.

The more recent Kelleher, Casey, Bradley, et al. (1993) study incorporates the Infant Health 

and Development Program which follows a large cohort of low birth weight of 2500 grams or 

less and with gestation age up to 37 weeks. One hundred eighty of 842 children in the cohort 

developed FTT. Bayley Mental and Psychomotor Development Indexes were lower for children 

with FTT than children without FTT for assessments at 12 and 24 months, p < 0.005. At 36 

months, the Stanford-Binet IQ scores were lower for children with FTT, 84.7 vs. 89.9 for nonFTT, p < 0.007.

In contrast, the English epidemiologic studies are restricted to infants born at term. 

Puckering, Pickles, Skuse, et al. (1995) identified from medical records, a cohort of inner city 

British white children born in 1980. The twenty-three diagnosed with FTT compared to 

demographically matched controls were found to have strikingly lower developmental quotients 

on average (77 vs. 97) with deficits of similar magnitude in all the sub-scales of the McCarthy 

Scales of Children's Abilities. When FTT is defined by slower weight gain, but not by attained 

weight percentile at any given age, two studies (Corbett, Drewett, and Wright, 1996; Drewett, 

Corbett, and Wright, 1999) from the same Newcastle research group, but with independent 

cohorts, at age 6-7 years found on average a three point decrement in WPPSI full scale IQ (84 vs. 

87) in one (Corbett, Drewett, and Wright, 1996) and on the Wechsler Intelligence Scale for 

Children (WISC)-III at 7-9 years (88 vs. 91), but the differences were not statistically significant.

In summary, there is a consistent association between FTT in early life and depressed 

developmental test scores in the pre and primary school years. While the studies are 

methodologically disparate and therefore difficult to compare, the direction of the effect is 

consistent across multiple study designs with samples of diverse ethnicities and gestational age. 

The magnitude of these effects is quite variable, ranging from 3 to 20 point deficits on 

standardized cognitive test scores compared to controls. From the perspective of the SSA, the 

research literature from developed countries suggests that FTT is associated with persistent 

deficits in cognitive development both at presentation and in follow-up, even if the child's 

growth has improved. The precise degree of developmental delay that would constitute 

“disability” from the perspective of the SSA cannot be determined. Most investigators describe 

developmental scores that are ≥ 1 standard deviation lower than the standard mean score for the 

test.
41

Table 7. Studies with association of cognitive & neurological development to Failure to Thrive 

compared to healthy comparison groups in developed countries 

Author,

Year,

UI Sample N

Age (mo) at 

assessment

Follow-up 

duration (mo) Applicability

Internal 

validity Instrument Association

Mitchell,

1980

80166667

FTT 30

Ctrl 282 36-60 12-36 ÇÇÇ = McCarthy-GCI

Hack,

1982

82227864

Gp1 38 a

Gp2 154 8

i ~ 5-7g ÇÇ = Bayley

Neurological exam

Singer,

1984

85057547

FTT 11

Ctrl 11 20.6h ~ 12g ÇÇÇ £

Bayley MDI-Kent 

Scoring Adaptation

Haynes,

1984

84233543

FTT 50 b

Ctrl 25 ND 6 ÇÇÇ £ Bayley MDI & PDI

Drotar,

1992

92372721

FTT 48

Ctrl 47 36 > 24 ÇÇÇ £ Stanford-Binet

Kelleher, 

1993

93234174

FTT 180

Ctrl 591 12 & 24 12 & 24 ÇÇ £ Bayley MDI & PDI

Skuse,

1994

94253258

FTT 47

Ctrl 47

14.6h

14.2 NAj ÇÇÇ = Bayley MDI & PDI

Reif,

1995

95362505

FTT 61

Ctrl 65

74.4h

81.6 61.5 ÇÇÇ £

Developmental 

delay / academic 

performance

Puckering,

1995

95378341

FTT 23

Ctrl 23 48 > 12 ÇÇÇ = McCarthy-GCI

Corbett,

1996

97113595

FTT 48

Ctrl 46 72-84 > 36g ÇÇÇ = Bayley MDI

Wilensky, 

1996

97022837

FTT 50

Ctrl 50 20h NAj ÇÇ = Bayley MDI

Mackner,

1997

97381196

FTT 97c

Ctrl 80

~14

~17.7 NAj ÇÇÇ £ Bayley MDI

Drewett,

1999

99284054

FTT 107d

Ctrl 117

97.4h

97.2 > 60g ÇÇ £ WISC-III

Kerr,e

2000

20277217

FTT 92f

Ctrl 101

~73.8

~73.3 > 46 ÇÇÇ £ WPPSI-R

Ctrl, control; FTT, failure-to-thrive; GCI, general cognitive index; Gp, group; IQ, intelligence quotient; MDI, mental 

development index; Mo, month; NA, not applicable; ND, no data; UI, Medline® unique identifier; WISC, Wechsler Intelligence 

Scale for Children; WPPSI-R, Wechsler Pre-school and Primary Scale of Intelligence.

a

 Gp1 (n=38) = small for gestational age, Gp2 (n=154) = appropriate for gestational age.

b

 25 FTT had Lay Health Visitor intervention. 

c

 4 Study arms collapsed to 2: FTT group includes 70 diagnosed FTT and 27 diagnosed FTT & Neglect; Ctrl group includes 57 

with neither diagnosis and 23 diagnosed with Neglect.
42

d

 2 FTT and 9 Ctrl with definite medical condition affecting growth; 1 FTT and 2 Ctrl with p ossible medical condition affecting 

growth.

e

 Sample overlaps with Mackner, 1997.

f

 4 Study arms collapsed to 2: FTT group includes 64 diagnosed FTT and 28 diagnosed FTT & Maltreatment; Ctrl group includes 

80 with neither diagnosis and 21 diagnosed with Maltreatment.

g

 See Chapter 2 – Methods.

h

 Mean age.

i

 Corrected age.

j

 Cross-sectional study.

FTT associated with decreased cognitive, motor, or neurological measures compared to controls, (statistically significant, p 

< .05).

 FTT associated with decreased cognitive, motor, or neurological measures compared to controls.

Developing Countries

Oral, Motor, and Other Neurologic Findings

In contrast to the data from developed countries which look at neurological findings 

preceding or concurrent with FTT, studies from the developing world focus on neurological 

outcomes months to years after the initial diagnosis. Bartel, Griesel, Burnett, et al. (1978) studied 

the long-term effects of kwashiorkor in 6-12 year old black African children, five to ten years 

after their hospitalization during infancy. The thirty-one in the index group were compared to 

siblings and yardmates in the area of psychomotor development. The Lincoln-Oseretsky motor 

development scale, Smedley hand dynamometer, Reitan Indiana and Halstead 

neuropsychological test batteries measured motor development, grip strength, and fingertapping/fine motor speed, but showed no group effects. Two of the ninety-three items involving 

tapping with feet and fingers were lower for the index group and yardmates compared to the 

sibling group by Scheffé’s multiple comparison, p < 0.10 (Evidence Table 10). In contrast, 

Galler, Ramsey, and Solimano (1985) reported that children who had been hospitalized for 

malnutrition in the first year of life showed more neurologic soft signs at ages 5-11 years and 

impaired scores on the Purdue Pegboard Test between 8 and 15 years, although the latter effect 

seems to be mediated by IQ. Evans, Hansen, Moodie, et al. (1980) found no impact of early 

nutritional growth failure on Bender-Gestalt scores between 8 and 9 using sibling controls of 

children with kwashiokhor.

Bartel, Griesel, Freiman, et al. (1979) in the cohort described above also examined the effect 

of kwashiorkor on the electroencephalogram using the same study design and comparison 

groups, but also adding a large control of ninety white children of a higher SES. EEG frequency 

results were significant for group effect for both hemispheres. There was group effect for the 

incidence of alpha and delta bands in the right and alpha, delta, and omega in the left 

hemisphere, p < 0.01. The kwashiorkor consistently scored higher in the delta and lower in the 

alpha bands compared to the other groups (Evidence Table 10).

Developmental/Cognitive Functions Concurrent with Identification of FTT

A hospitalized Jamaican cohort (Grantham-McGregor, Stewart, and Schofield, 1980; 

Grantham-McGregor, Stewart, and Desai, 1978) and an epidemiologic out patient cohort from 

India (Agarwal, Awasthy, Upadhyay, et al., 1992) provide some information about the 
43

developmental function of children from developing countries concurrent with acute 

malnutrition. Grantham-McGregor, Stewart, and Desai (1978, 1980) compared two cohorts of 

children with third degree malnutrition (one of which later received developmental intervention) 

with a hospitalized control group at the time of admission and found that the two malnourished 

groups scored nearly 20 points lower than controls on the Griffith’s Mean Development Quotient 

(61,64, vs. 86), with similar differences in each of the sub-scales of the Griffith’s Test. Agarwal, 

Awasthy, Upadhyay, et al. (1992) looked at Gesell Developmental quotient scores concurrent 

with the severity of malnutrition at 18,24, and 30 months. At every age there was an inverse 

relationship between the mean scores on the Gesell and degree of malnutrition. At 3 years of age, 

the Binet Kulshrestha Intelligence Scale, an Indian adaptation of the Stanford-Binet test, was 

administered to assess IQ. For overall cognitive development, or IQ, there was a main effect by 

group; normal group 95.5, Grade I 91.9, Grade II/III 86.8, F = 13.27, p < 001. This result was 

parallel for measures of motor development, language, and reasoning, p < 001, and concept 

formation at the level of p < .01. None of the normally nourished children, 23 % of the Grade I 

malnourished children, and 51% of the Grade II-III children attained scores at age 36 months 

below 85 (more than 1 std. below the mean).

Developmental/Cognitive Functions in Childhood Among Survivors of FTT in 

Childhood and Early Adolescence

Two investigators, Evans, Hansen, Moodie, et al. (1980) and Drewett, Wolke, Asefa, et al. 

(2001) reported on South African and Ethiopian cohorts respectively. To account for possible 

genetic influences on outcome, Evans, Hansen, Moodie, et al. (1980) performed a longitudinal 

study in South Africa looking at the long-term effects of early infant food supplements on the 

development of a group of newborns from fourteen families with older children with a history of 

undernutrition. The siblings constituted one control group. Fourteen children with kwashiorkor, 

who at one time were hospitalized, and their closest in age siblings, formed two more 

comparison groups. Height and weight data was taken at 4 years of age, 2 years after 

supplementation for the intervention group. The children who had food supplements during 

infancy were statistically greater in weight than the other groups at age 4 years, indicating less 

malnutrition. At 7 years post intervention, height and weight data was collected again, at which 

time, all children were tested with the New South African Individual Intelligence scale. At 

testing time the advantage in height and weight by the intervention group were gone. Results of 

the intelligence scale for full scale score showed an overall significance for the intervention 

group 82.0 over the other 3 groups; 71.9, 70.0, 72.0, p < 0.05. For verbal, the trend was higher 

for the intervention group, with significant difference over their siblings, 81.3 vs. 70.6, p < 0.05. 

Their performance score for the intervention group was also higher, 86.3 vs. 71.3 for the 

kwashiorkor, p < 0.01, and 74.4 for the kwashiorkor’s siblings, p < 0.05. In a group of normal 

birthweight Ethiopian children, Drewett, Wolke, Asefa, et al. (2001) compared children with 

nutritional growth faltering to weight below the third percentile before 4 months of age to those 

whose growth faltered between 10 and 12 months of age and those who maintained weights 

above the third percentile throughout the first year. When evaluated by masked assessors at 24 

months of age on an Ethiopian adaptation of the Bayley Scales of Infant Development, both 

groups of growth falterers scored below the controls, and those who faltered early scored below 

those who faltered late. Mean PDI scores were 6.6 for the early falterers, 8.5 for the late, and 

10.2 for controls. Similarly for the MDI mean scores were 22.6 for the early falterers, 26.6 for 
44

the late and 28.9 for controls. All differences were significant at p < .001. However, in this 

cohort malnutrition was untreated and enduring, and the effects were not attributable to early 

growth faltering after weight at time of testing was controlled statistically.

There are multiple reports from two prospectively followed West Indian cohorts -- one from 

Jamaica (Grantham-McGregor, Schofield, and Harris, 1983; Grantham-McGregor, Schofield, 

and Powell, 1987; Grantham-McGregor, Stewart, and Schofield, 1980; Grantham-McGregor, 

Powell, Stewart, et al., 1982; Grantham-McGregor, Stewart, and Desai, 1978) and the other from 

Barbados (Galler, Ramsey, Solimano, et al., 1983a; Galler, Ramsey, Solimano, et al., 1983b). 

Grantham-McGregor, Schofield, and Harris (1983), Grantham-McGregor, Schofield, and Powell 

(1987), Grantham-McGregor, Stewart, and Schofield (1980), Grantham-McGregor, Powell, 

Stewart, et al. (1982), and Grantham-McGregor, Stewart, and Desai (1978) studied the short- and 

long-term effects of a psychosocial intervention on the mental development of Jamaican children 

hospitalized with severe malnutrition. The study consisted of three arms: the intervention FTT 

group, a nonintervention FTT group, and a comparison group hospitalized for reasons unrelated 

to malnutrition. The later two groups received standard care. Intervention consisted of structured 

daily play during hospitalization. After discharge the sessions were weekly over 2 years and once 

every 2 weeks for the third year. Using the Griffith’s Mental Development Scales, the 

Development Quotient (DQ) scores were determined for the three groups at various intervals. 

When scores at admission were compared with those 6 months later, there were increases for all 

groups; the intervention group’s DQs increased from 86 to 96 compared to 98 to 105 for the 

control group, p < 0.1 at both intervals. The nonintervention group was statistically behind 

compared to both intervention and control groups. At 60 months after discharge, the relative 

positions remained unchanged, with the nonintervention group’s DQ score less than the 

intervention group’s DQ score, which was lower than the control group's, 78 vs. 86 vs. 93, 

respectively, p < 0.01. All groups improved over time with respect to anthropomorphic 

measures. Samples sizes were small for the intervention, nonintervention, and control groups, 18, 

16, and 20, respectively.

Galler, Ramsey, Solimano, et al. (1983a, 1983b) examined the intellectual and behavioral 

development of 5 to 11 year old Barbadian children hospitalized in their first year of life with 

Grades II and III malnutrition. The Wechsler Intelligence Scale for Children was administered to 

119 index children who had a mean IQ score 12 points lower than the 127 controls, with 50 

percent of the index group scoring below 90 compared to 14 percent for the later group. One 

percent of the comparison and nine percent of the index groups had scores below 70. The sex, 

age, or socioeconomic status of the child had no significant effect on the Full IQ scores.

 In summary, while cohorts in the developing world tend to contain a higher proportion of 

more severely malnourished children than those in the developed world, there is considerable 

overlap between the distribution of anthropometric measurements in the two settings. 

Malnutrition with edema (kwashiokhor) is rare in developed countries, but appears to have 

similar sequelae to malnutrition without edema which is widely prevalent in both settings.

The evidence from developing countries is mixed with regard to persistent non-cognitive 

neurological findings after early undernutrition. However, in the developing world children 

malnourished in the first three years of life, who in developed countries would be diagnosed as 

"FTT," consistently show concurrent and persistent developmental/cognitive delay compared to 

their ethnic and SES peers, with an apparent dose response such that children with the most 

severe degree and the earliest onset of malnutrition show the greatest magnitude of effect. While 

controlled follow-up data from the developed world do not extend beyond age 9 years, data from 
45

the developing world provide evidence of the persistence of effect into later elementary school 

and early adolescent age groups.

Table 8. Studies with association cognitive & neurological development and malnourished cases 

compared to well-nourished controls in developing countries 

Author,

Year,

UI Sample N

Age (y) at 

assessment

Follow-up 

duration (y)

Applicabil

ity

Internal 

validity Correlates Association

Bartel,

1978,

1979

78180773

79162492

Gp2 30

Ctrl 150a

6-12 4-12 Ç °

LOMDS

Smedley hand 

dynamometer

Reitan Indiana & 

Halstead 

neuropsychological test 

batteries

New S. African 

Individual Intelligence 

scale

h

Evans,

1980

81008912

Gp1 14

Gp2 14

Ctrl 26b

8.9(0.5)

13(1.9)

10.7, 12

6-7 Ç =

Bender-Gestalt 

test/Koppitz scoring

Galler, 

1983a,

83136873

Gpc 108

Ctrl 107 5-11 4-10 ÇÇ £

WISC

Perdue Pegboard Tasks

Griffith’s Mental 

Development Scale

GranthamMcGregor, 

1987, 1978, 

1980, 1982,

1983

87117313

79086701

81051042

82236679

83246270

Gpd 34

Ctrl 20 5 5 ÇÇ =

Stanford-Binet Test

Agarwal,

1992

92372206

Gp1e

245

Gp2e

324

Ctrl 64

3 3 ÇÇ £

Binet Kulshrestha 

Intelligence Scale

i

Drewett,

2001

21174599

Gp1f 25

Gp2f 66

Ctrl 100

2 = 1g ÇÇ £ Bayley PDI & MDI j

Ctrl, control; Gp1, undernourished, Gp2, Kwashiorkor; LOMDS, Lincoln-Oseretsky motor development scale; MDI, mental 

development index; PDI, psychomotor development index; UI, MEDLINE® unique identifier; WISC, Wechsler Intelligence 

Scale for Children; Y, year.

a

 3 control arms collapsed into 1: controls consist of 30 siblings, 30 yardmates of index cases, 90 High SES Whites.

b

 2 control arms collapsed into 1: controls consist of 13 siblings with hx of undernourishment, 13 siblings of kwashiorkor cases 

with no hx of kwashiorkor but underweight.

c

 PEM Grade II – III.

d

 2 groups with severe PEM collapsed into 1: 18 had intervention, 16 had standard care.

e

 Gp1 = Grade I, Gp2 = Grade II-III based on NCHS.

f

 Gp1 = early growth faltering, Gp2 = late growth faltering.

g

 See Chapter 2 – Methods.

h

 Undernourished vs. Kwashiorkor & Control groups (Gp1 vs. Gp2 & Ctrl).

i

 Grade I & Grade II/III vs. Control groups; Grade I vs. Grade II/III (Gp1 & Gp2 vs. Ctrl; Gp1 vs. Gp2).
46

j

 Early growth faltering & late growth faltering vs. Control groups; early growth faltering vs. late growth faltering (Gp1 & Gp2 

vs. Ctrl; Gp1 vs. Gp2).

Index cases associated with decreased cognitive, motor, or neurological measures compared to controls, (statistically 

significant, p < .05).

Index cases associated with decreased cognitive, motor, or neurological measures compared to controls.

 Index cases not associated with difference in cognitive, motor, or neurological measures compared to 

 controls.

Evidence that Failure to Thrive (FTT) is Associated with 

Other Clinical, Psychosocial and Family Factors

Fourteen studies assessed diverse risks associated with FTT. These studies were from 

developed countries (9 from the US, 4 from the UK and 1 from Israel) and were highly 

comparable to the FTT population in the US. Some of the associated factors are assumed to 

precede the development of the clinical syndrome of FTT while others are likely to have 

followed. We make no attempt to discern direction of causality but describe the associations that 

have been found to be correlated with the development of FTT.

Among studies from the United States, Pollitt and Eichler (1976) reported that children with 

FTT demonstrated lower maternal education level (p< .05) and per capita income (p<.01) than 

their matched controls (N=19). Mitchell, Gorrell, and Greenberg (1980) examined a cohort of 

children from a rural US health center, of whom 30 (9.6 percent) met criteria for FTT (weight for 

age <80 percent of the Harvard 50 percentile). Compared to their well-nourished controls (282 

cases; 90.4 percent of cohort), FTT cases demonstrated a higher incidence of neonatal problems 

(jaundice, possible sepsis, and poor feeding, 15% vs. 30%, p<.05). There were no differences in 

the incidence of prematurity, LBW, or maternal pregnancy complications. Family problems, 

assessed by Coddington scale, were more common for the FTT group (FTT 36.7% vs. Controls 

11%, p< .01). The fact that the diagnosis of FTT generated increased inquiry into home 

situations presents a potential bias. No SES differences were noted, although the clinic 

population was 70 percent black and of low SES overall (49-53 percent Medicaid). Evidence of 

concurrent disability was not sought or described.

Hack, Merkatz, Gordon, et al. (1982) reported on the development of FTT in a population of 

VLBW infants, both SGA infants who failed to catch up and AGA infants who subsequently fell 

off in growth. FTT was defined as weight for age more than 2 SD below the mean. Assessment 

of FTT was at term and again at 8 months corrected age. The diagnosis of FTT at 8 month 

corrected age correlated with neonatal risk score, an index of severity of the neonatal course, as 

well as the duration of initial hospitalization (r= 0.28, 0.30, 0.32, p< .005). The incidence of 

rehospitalization after the neonatal period was also significantly greater in children who failed to 

thrive (p< .001, Evidence Table 9).

Sherrod, O'Connor, Vietze, et al. (1984) reported on 31 cases of FTT within a study 

examining abused, neglected, and FTT children with a comparison group. FTT was defined as 

weight for age less than 2/3 of Harvard 50 percentile weight for age. FTT cases revealed more 

“anatomical abnormalities” (chi-square=5.44, p< .025) and more family dysfunction (chi square 

5.32, p< .025) accounting for or identified at clinic visits over the first three years of life 

compared to controls (N=24) (Evidence Table 9).

Casey, Bradley, and Wortham (1984) compared 23 FTT cases (<3 percentile weight for age 

or > 3 SD fall off over time) to 23 appropriate weight controls, all of whom had been referred to 
47

a Growth and Development Clinic. Despite close matching for SES, the FTT cases scored lower 

on the HOME inventory for both total score (p< .04) as well as subsets for maternal responsivity 

(7.7 vs. 8.9, p< .03), maternal acceptance (5.1 vs. 6.2, p< .01), and organization of home 

environment (4.7 vs. 5.3, p< .02).

Hutcheson, Black, and Starr, Jr. (1993) presented findings of an observational study 

examining maternal-infant interactions during feedings in 31 FTT cases (weight <5 percent 

NCHS) and 39 well nourished controls. No differences were found between FTT and controls for 

parenting stress, “informal supports”, negative “life events” or negative affect. Age-related 

differences were found--i.e., maternal affect was rated less positive towards FTT toddlers than 

FTT infants (p< .05). They noted that as all study subjects were drawn from similar low SES, 

this may account for the lack of distinction between children with FTT and controls; i.e., poverty 

may prove a stronger marker for negative maternal interactions than FTT (Evidence Table 9).

Kelleher, Casey, Bradley, et al. (1993) reported on 180 FTT cases, all of whom were 

preterm/LBW. In comparison to 591 well-nourished preterm/LBW controls, the FTT group 

manifested a significantly higher incidence of SGA (p< .05) and more suspect or abnormal 

neurological exams (4.6 vs. 8.9, respectively, p< .005). These children also scored lower on the 

Rand General Health Rating (p< .05), but not the Stein Total Health Scores. FTT also scored 

lower on the HOME inventory (32.6 vs. 33.9, p< .03).

Drotar, Pallotta, and Eckerle (1994) studying 31 FTT infants (weight < 5th percentile), found 

them to have lower composite Family Relationship Index (FRI) scores than 39 controls (p< .01), 

both at intake (1-9 mos of age) as well as at follow-up at 4 years of age, despite the fact that total 

scores did show improvement over time (Evidence Table 9).

Four studies were from the United Kingdom (Evidence Table 9). Skuse, Gill, Reilly, et al. 

(1995) found a four-fold increase in the risk of abuse or neglect among 47 FTT cases (weight for 

age <3rd percentile) compared to 47 non-FTT controls (RR 4.43; p< .01).

Puckering, Pickles, Skuse, et al. (1995) described fewer positive maternal interactions and a 

higher incidence of negative interactions among FTT cases (weight <10 percent for age; N=23) 

compared to controls (N=23; p=. 01). In a matched paired comparison (136 FTT; 136 Control), 

Drewett, Corbett, and Wright (1999) reported that for those infants noted as failing to thrive 

during the first 18 months of life (at least 2 weights <5 percent), subsequent follow-up at 

approximately 8 years of age revealed a significantly greater likelihood for hospital admission, or 

visit to hospital outpatient clinic compared to controls (p=.033).

Wright and Birks (2000) using a definition of FTT related to fall off in weight gain rather 

than absolute weight percentiles, found a higher incidence of abuse, neglect, or involvement with 

social services, although it did not prove statistically significant. FTT infants were found to 

experience a later onset for solid food feedings (p< .03).

Wilensky, Ginsberg, Altman, et al. (1996) reported that Israeli children with FTT (weight <3 

percent for age) were twice as likely to be admitted to hospital in the first year compared to 

controls (N=50 each group; p< .05). They were also noted to have less stimulating home 

environments (0.84 vs. 0.92, p< .05).

Studies from developing countries again presented much more severe cases of protein energy 

malnutrition (PEM), and are therefore less directly comparable to the US FTT population. These 

studies noted a variety of outcomes associated with FTT. Ghosh, Vaid, Mohan, et al. (1979), in a 

study from India, compared two groups of children with FTT; mild-moderate PEM (weight 71-

80 percent of Harvard 50th percentile for age; N=28) and severe PEM (weight for age <60 

percent of Harvard 50 percentile; N=39) to well nourished controls (N=60). Lower nerve 
48

conduction was observed in severe PEM cases compared to controls (p< .001); no difference was 

found between controls and the mild-moderate PEM group. Further significant difference was 

found between those cases whose PEM had its onset before 12 months compared to those with 

onset after 12 months (p<.001) (Evidence Table 10).

Bartel, Griesel, Burnett, et al. (1978) published two studies from South Africa; the first study 

examined psychomotor development among 31 patients identified by hospitalization for 

kwashiorkor during the first 27 months of life. These cases were studied 5-10 years after 

identification and treatment to consider the potential long-term effects of early severe PEM. 

Comparison was made to two control groups; well nourished siblings (N=31) and age matched 

“yardmates”(N=31). There were no significant differences noted between groups for a variety of 

psychomotor tasks. Subsequently, these same three groups, with an additional control group of 

age-matched, well-nourished white children (N=90) were studied by EEG monitoring. Findings 

included significantly lower mean frequency for both hemispheres in kwashiorkor cases 

compared to white and sibling controls (p<.05). No difference was found among groups for mean 

EEG amplitude. There was a higher incidence of delta and theta waves, as well as a lower 

incidence of alpha waves for kwashiorkor cases than for either sibling or white controls (p<.05). 

The differences between groups, however, fell within range normal variation and thus the 

biologic significance of these findings is not clear (Evidence Table 10).

Kothari, Patel, Shetalwad, et al. (1992) studied cardiac mass and function by doppler 

ultrasound in 25 cases of FTT in India, all of whom had severe marasmus or marasmic 

kwashiorkor. Left ventricular mass was less in FTT cases than controls (N=26; p<.05), but the 

LV mass/body weight ratio was higher (p<.001); this represents a poor prognostic factor. 

Ejection fraction was not different between the groups, but cardiac index was higher (p<.05) in 

FTT cases. The severity of these cases of malnutrition is underscored by the fact that 2 of the 25 

FTT cases died within 3 weeks of study.

Benefice (1992) found that Senegalese children with moderate chronic FTT (N=64) scored 

lower in physical activity (p<.05); lower work capacity and pulmonary function (FVC) than 

controls (N=34; p<.001).

In summary, there is persuasive evidence that failure to thrive is associated with a range of 

organic and psychosocial difficulties that may in themselves secondarily predict or cause 

significant disability. Categories of associations include socioeconomic factors (lower income, 

lower maternal education, less enriched family environment/interactions); neonatal morbidity; 

acute illnesses and hospitalizations; neurological/anatomical abnormalities; family dysfunction; 

and abuse/neglect.
49

Chapter 4. Conclusions

Overview

This research has produced an evidence base that the SSA can use to help update its 

disability guidelines and to revise its disability policy. The review was designed to address the 

following question: Among children defined by investigators as failing to thrive (FTT) or grow 

adequately, what evidence exists that they have a concurrent disability (or will have one within 

six months)?

We reviewed 275 articles and used 52 articles encompassing 43 studies to produce this 

evidence report. It should be stressed that the single most common reason for exclusion was the 

lack of a non-FTT comparison group, as we thought that no valid associations could be drawn 

from descriptive reports or interventional studies that lacked an appropriate control. The quality 

of the studies we were able to use was variable. While the study question regarding FTT is clear, 

most of the studies were not designed to specifically address issues relating to disability as 

defined by the U.S. Congress and interpreted by SSA. Despite this, the evidence extracted from 

the articles we reviewed clearly suggests a relationship between FTT and concurrent disability, 

disability within 6 months, and disability beyond 6 months. We described this evidence with 

respect to specific disabilities in Chapter 3, and in this section we review the implications of 

those findings as well as some limitations of the studies.

There are a number of potential confounders that need to be considered. The studies from 

developed countries looked at FTT mainly in lower social-economic status (SES) groups. 

Several potential risk factors for developing FTT are prevalent among lower SES populations, 

such as lower family income and maternal level of education, higher incidence of abuse or 

neglect, family dysfunction and negative maternal interaction. Such factors may exert 

independent and potentially stronger negative influences on childhood health, well-being and 

development than those of growth failure, thereby masking the specific deleterious impact of the 

failure to thrive. Alternatively, the diagnosis of FTT may inherently create bias by increasing 

clinicians' suspicion and subsequent investigation for potential covariates such as disturbances in 

family dynamics, or maternal interaction, abuse and neglect.

Studies from developing countries were generally examining the effects of severe 

malnutrition, often marasmus or kwashiorkor. The extrapolation of their results to the FTT 

population in the US must be approached with some caution. Lastly, even within developed 

countries, where the population of FTT children was generally well matched to those in the US, 

the available studies still demonstrated significant variation, both in specific FTT inclusion 

criteria, and exclusion criteria (e.g., LBW/SGA).

Persistent Disorders of Growth

There is substantial evidence that long term growth in all parameters (weight, height, and 

head circumference) of children with FTT compares unfavorably with thriving children and that 

this disparity persists even with appropriate attempts at intervention. This pattern of a persistent 

growth deficit is seen in both developed and developing countries and across a wide spectrum of 

severity of FTT.
50

The effect on head growth is especially concerning, since increasing head circumference 

reflects brain growth, and therefore any impairment in head growth impacts neurodevelopmental 

outcomes. There is also evidence that the longer the growth failure continues, the less likely it 

becomes that treatment will be effective in reversing the negative long-term outcomes. These 

findings highlight the importance of early identification and intensive nutritional intervention for 

children with FTT syndrome to improve efficacy of the therapy and to minimize long-term 

damage.

Associations of FTT With Immunologic/infectious Outcomes

The evidence that children with FTT have significantly greater susceptibility to infection is 

strong, and includes both markers of immunologic dysfunction at the cellular level and clinical 

correlates seen consistently across a variety of conditions. The laboratory indices of cellular 

immunologic dysfunction were apparent in children with moderate severity and, at least in such 

moderate cases, may be amenable to nutritional intervention. As expected, the more seve re 

complications were most prevalent among the most severely malnourished children. The 

evidence is supportive of identifying children with growth failure as being at risk for multiple 

acute and chronic infections, especially as this may be an area where intervention may 

effectively reverse the associated risk.

Behavior Difficulties Associated With Failure to Thrive

The evidence identified by the search showed that children with FTT exhibited a variety of 

behavioral disorders, both concurrently at diagnosis as well as at follow-up. All except one of the 

relevant studies were conducted in developed countries, on a population of children with 

moderate degrees of FTT, representing a strong match to the case mix of FTT children in the US.

Studies involving concurrent behavioral abnormalities in FTT cases examined children up to 

3 years of age. The behavioral problems exhibited by the children diagnosed with FTT included 

various eating disorders, such as delayed introduction of solid foods, spitting, disinterest, and 

food aversions. Other behavioral disorders that were noted involve increased negative and 

decreased positive affective expressiveness, and lower scores on measures of communication and 

mood. These behavioral difficulties do not in themselves constitute disabilities using the SSA 

definition, but may contribute to functional deficits noted in neurologic and cognitive/social 

development.

Studies examining behavior problems in children diagnosed with FTT at follow-up focused 

on social situations such as classroom behavior. School-related behavioral problems such as 

attention deficit disorder (ADD) were found in one study to be more common among FTT 

children than controls. In addition, one investigator found interference with problem-solving 

skills more often in FTT children than in well-nourished controls.

Developmental Disorders Associated With Failure to Thrive

The evidence identified by the search showed that children with FTT exhibited consistently 

poorer scores in a variety of tests of cognitive, neurological, and psychomotor development. 

Indeed, the deleterious effect of growth failure and malnutrition on neurodevelopment is among 
51

the strongest and most important associations found. This trend toward poor neurodevelopmental 

performance was consistent for all fourteen of the studies conducted in developed countries, and 

five of the six studies conducted in the developing countries.

Despite exclusion of children with overt neurodevelopmental abnormalities from the case 

definition of FTT, at the time of identification, FTT is still strongly associated with poorer 

developmental test scores. Again, not unexpectedly, the most severe developmental delays are 

found among the most severely malnourished, often hospitalized children. However, even in 

larger epidemiological studies, the effect of FTT on neurodevelopmental outcome is apparent. 

Such studies indicate that the diagnosis of FTT is associated with an average decrease in 

developmental test scores of roughly two-thirds of a standard deviation. This means that children 

with failure to thrive are also more likely to meet criteria for the SSA qualifying range of 

developmental delay than are children in the general population. Adding to the concern of such 

cases is the fact that these lower neurodevelopmental testing scores persisted regardless of 

intervention.

Evidence that Failure to Thrive is Associated With Other 

Clinical, Psychosocial and Family Factors

There is persuasive evidence that FTT is associated with a range of organic and psychosocial 

difficulties. Some of these associations may be potential causal factors for the growth failure, 

such as low socioeconomic status and maternal education level, family dysfunction and the 

presence of neonatal morbidities. Others, such as the frequency of hospitalization, general health 

status, and specific neurologic abnormalities are more likely the result of the malnutrition. 

Furthermore, several of these factors may also independently predict or place a child at risk for 

significant disability. The possible interrelation of such factors complicates the delineation of the 

true nature of their association with FTT; nonetheless, they provide further insight into the 

complexities of the risks inherent in the diagnosis of growth failure.

Overall, the results are generally consistent across a broad spectrum of growth failure 

severity, and the majority of the studies are readily and creditably generalizable to the population 

of children with FTT as defined by SSA. Additionally, the study results further highlight the

severity and potential long-term impact of these associations in their consistent finding that these 

psychosocial and family difficulties are not readily amenable to current interventions.

The implications of FTT on long-term morbidity and disability can vary depending upon the 

severity of FTT, its cause, and most importantly the chronological age at which FTT occurred. 

Thus, in spite of an appropriate review of literature, we may still be not be able to assess the full 

magnitude of FTT on developing children because of the wide age range of subjects in the 

reported studies. One thing we can certainly conclude is that a major FTT event in a child's life 

occurring particularly at a critical phase of the growth curve (which varies among body systems; 

brain, skeleton etc.) has a high likelihood of causing major disability. The age of the child and 

the magnitude of FTT thus may have differing effects on different body systems. This is an 

important area in which to target intervention programs as well as further probe molecular and 

genetic bases for such impairments.
53

Chapter 5. Future Research

The studies comprising this report, though insufficient in number and variable in their 

methodologic quality and their potential biases, were of sufficient validity to provide significant 

information regarding the association of FTT with disability. The variety and long-term nature of 

the disabilities associated with FTT have major impact on the child, the family, and society.

Notwithstanding this, it may well be that the most significant finding of this review was the 

paucity of information available on the subject. Much remains to be learned regarding the extent 

and specifics of these associations and disabilities. Even more remains to be determined as to the 

optimal management of these patients.

Similarly, whatever limitations may have been found in these studies, they have also served 

to better define relevant outcomes for further study. With this in mind, we offer the following 

recommendations for future research addressing specific problematic issues and limitations 

identified from review of existing research.

• One of the central problems in interpreting these studies was the heterogeneity of 

definitions of FTT. This variability in case definition makes it unclear how well the 

population at risk is being identified at present. Future research should apply a uniform 

definition of FTT. This would serve to facilitate comparison and perhaps even allow a 

meta-analysis of studies. It would also define more clearly the true prevalence of FTT.

• Within the definition of FTT, provisions should be made for categorization based upon 1) 

severity and 2) longevity or duration of growth failure. The data currently available 

indicate that both of these factors are strong predictors not only for the risk of associated 

disabilities but for potential response to therapy as well. Refining the classification of the 

FTT population in this way would facilitate identification of the relative risk of disability 

for an individual FTT child. It would also help in the evaluation of intervention studies.

• Although it is clear that the degree of disability increases with increasing severity of 

growth failure, this is an imprecise correlation especially in regards to children with mild 

to moderate FTT. Since the majority of FTT that is seen in the US tends not to be the 

most severe forms of marasmus and kwashiorkor, future research should specifically 

target those children with mild to moderate growth failure.

• Similarly, more research needs to be conducted in the US, or in developed countries with 

comparable social-economic structures and health care systems.

• Special emphasis should be given to outcomes focusing on neurodevelopmental and 

cognitive disorders. The data presented in this report indicate that this is likely one of the 

areas of strongest impact of FTT and certainly one with the greatest relevance for long 

term disability. Specifically, very few studies have focused on the issue of FTT and brain 

growth during the immediate post-neonatal period and early infancy. This is one of the 

most critical periods for dendritic arborization, axonal myelination, and the development 

of cognitive functions. More studies are needed in this area.
54

• Further study is also needed on the association of FTT with general health outcomes 

because of their potential impact on the healthcare system. Beyond the risk to the 

individual child, the data linking FTT to increased risk of infections and poorer general 

health may have important implications at a broader level. Such data may help us 

understand the true "cost" of FTT and prove useful in evaluating intervention strategies.

• In order to better define the true nature and extent of the disabilities associated with FTT, 

more studies are needed that prospectively follow children for a sufficient duration to 

capture the more complex disabilities that may result from FTT.

• A consistent finding among these studies reviewed was the ineffectiveness of existing 

intervention programs. Although strictly beyond the focus of this report, much work still 

needs to be done on developing effective treatment programs for children with FTT. 

Unfortunately, the optimal intervention will yet require better definition of the complex 

physical, medical, cognitive, and psychosocial problems associated with failure to thrive.
55

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Alvear J, Artaza C, Vial M et al. Physical growth and 

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Evidence Table 1. Studies associating anthropometrics to Failure to Thrive cases compared to healthy control roup in developed countries

Part I

61

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Mitchell,

1980

80166667

Country: US

Setting: Outpatient clinic

FTT Ctrl

Age(y) 2-5 2-5

Wt/age ND ND

Ht/length ND ND

Enrolled : cohort of 312(323)*

Evaluated 30 282

% Male 36.7 51.8

% Black 70 70

* See Potential biases column

Maternal educ: ND

Income: ND

Health insur: 

FTT-53% Medicaid

Ctrl-49% Medicaid

See Definition of FTT

Controls - wt = 80% of nl, 

matched for age, sex, 

mother’s age/ marital 

status & family problems

Organic cause of FTT, 

single anomalous 

low wt recorded, 

clinic registration by 

age 6 mo, < 3 visits

Wt for age < 80% of 

nl up to age 24 

mo 

Ambidirectional 

longitudinal

1 fwup at age 3 – 6 y

Haynes,

1984

84233543

Country: US

Setting: Inpatient & Outpatient

Age: ND

Wt/age: ND

Ht/length: ND

FTT1* FTT2† Ctrl

Enrolled/Eval 25 25 25

% Race

 Sp-Am? 44 44 44

 Sp-Am? 40 52 52

 White? 36 44 36

 White? 36 24 28

 Black? 20 12 20

 Black? 24 24 20

% Male: ND

* std care & lay health visitor 

intervention, † std care only

Maternal

 Educ Income*

Gp1 10 379(0-750)

Gp2 11 372(0-950)

Ctrl 10 362(0-1100)

Health insur: ND

* @ mo

Consecutive admissions 

for NOFTT

Controls - thriving nonhospitalized patients 

matched for age, sex, 

birth wt, & mother’s age, 

ethnicity, number of 

living children

ND < 5 percentile or 

significant decline 

from birth wt 

percentiles

Prospective 

longitudinal

1 assessment 6 mo 

after intake
Evidence Table 1. Studies associating anthropometrics to Failure to Thrive cases compared to healthy control roup in developed countries

Part I

62

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Kelleher, 

1993

93234174

Country: US

Setting: Primary care clinic

FTT Ctrl

GA(wk)* 33.0 33.1

Wt(g)* 1679 1845

Enrolled: 842*

Evaluated 180 591

% Male 52.2 47.9

Race: % Black 50 53.8

* At birth

FTT Ctrl

Maternal

 educ(%) <HS 40.6 38.1

HS 30.0 29.3

Some col 14.4 20.8

≥col grad 15.0 11.8

Income <10K 38.6 34.5

10-20K 19.9 23.9

 >20K 38.1 37.4

Health insur: ND

Gestation age ≤ 37 wks, 

birth wt ≤ 2500 g, FTT

Controls matched for –

birth wt +/- 250 g, 

maternal education, 

maternal race, & infant 

sex

Live outside catchment 

area, discharged 

outside recruitment 

period, discharge or 

died within 48 hr, 

hospitalized > 60 d, 

oxygen support > 90 

d, twin, triplet or 

quadruplet of 

ineligible child, 

maternal 

drug/alcohol abuse, 

insufficient Eng skills, 

psychiatric hosp

< 5th percentile for 

gestation corrected 

age based on 

NCHS, growth 

status on “wt curve 

below that recorded 

at last regular 

assessment visit.”

Prospective 

longitudinal

Fwup at ages 12, 24, 

36 mo

Reif,

1995

95362505

Country: Israel

Setting: Outpatient

FTT Ctrl

Mean age(y) 6.2 6.8

Wt/age* 18.05 36.15

Ht/length* 21 33.55

Enrolled 86 65

Evaluated 61 65

% Male 52.5 54

Race:

 Sephardic 38 36

 Ashkenazi 23 29

FTT Ctrl

Maternal 12.27 12.14

 educ* (0.29) (0.24)

Income: ND

Health insur: Socialized 

medicine

* Mean (SD)

FTT, < 2 y, term infants > 

2500g birth wt

Controls matched for age, 

sex, social class, & ethnic 

affiliation; admitted or 

evaluated in ER for 

intercurrent & nonsign 

disease

Organic cause of FTT, 

malnutrition, serious 

perinatal morbidity

Ht & wt < 5% in ≥ 2 

measurements 

within 6 mo on 

Hamill PVV, Drizd 

TA growth chart,

Ambidirectional 

longitudinal

Re-evaluation at mean 

5.12 yr
Evidence Table 1. Studies associating anthropometrics to Failure to Thrive cases compared to healthy control roup in developed countries

Part I

63

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Corbett,

1996

97113595

Country: UK

Setting: Clinic

Age: 6-7 yr

FTT Ctrl

Wt/age ND ND

Ht/length ND ND

Enrolled 52 52

Evaluated 48 46

% Male: ND

Race: 100% White

Maternal educ: ND

Income: “...most 

economically deprived 

wards in Newcastle”

Health insur: National 

healthcare

Full term singleton with 

records of 6 or more 

weights over first 18 

months age

Consecutive controls 

matched for age & sex

Non-Caucasian, “poor 

growth resulting 

from major organic 

disease”

Weight deviated 

downward from 

maximal centile 

achieved at 4-8 

wks, across ≥ 2 

centile lines, & 

stayed at level ≥ 2 

measurements ( 

1 mo (Tanner 

& Whitehouse)

Ambidirectional 

longitudinal

5 year follow-up 

of cases

Black,

1999

9916209

0

Country: US

Setting: Outpatient

FTT Ctrl

Age: ND ND

Wt/age <5% >5%

Ht/length <5% >5%

Enrolled/Eval 127 98

Male: ND

Race: 92% African 

American

FTT Ctrl 

Maternal 10.76

11.4

educ* (1.62) (1.44)

Income: AFDC 76%

Health insur: ND

* Mean (SD)

< 25 mo, full-term, 

AGA, no 

congenital or 

handicapping 

conditions

ND < 5% for wt for 

age or wt vs. 

ht by NCHS 

growth charts

Prospective 

longitudinal

FTT: three 6 mo 

followed by 

annual visits 

from ages 3-6

Control: annual 

visits ages 3-6
Evidence Table 1. Studies associating anthropometrics to Failure to Thrive cases compared to healthy control roup in developed countries

Part I

64

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Drewett,

1999

9928405

4

Country: UK

Setting: Clinic / home visits

FTT Ctrl

Age(y) 8.12(0.62)

8.10(0.57)

Wt(kg)* 23.8

27.9

BMI* 14.9 16.3

Enrolled 136 136

Eval† 107/111 117/122

% Male‡ 40 38

% White‡ 91 91

* Median, † Psychological 

/ anthropometric 

evaluation, ‡ FTT = 107, 

Ctrl = 117

FTT Ctrl

Maternal 72 66

 educ*

Income: NA

Health insur: National 

healthcare

* % left school at 16 y

At least 1 wt at 

age 0-2 mo & 2 

subsequent wts, 

thrive index < 5th 

centile = 2 

occasions between 

3 & 18 mo

Controls with at least 1 wt 

at age 0–2 mo & 2 

subsequent wts, no thrive 

index < 10th centile, age 

± 1 mo, similar/same 

residential area or GP 

practice

ND Lowest 5% for 

change of SD 

score; avg taken of 

SD scores for all 

wt bet 0-2 mo, 

expected wt from 

3-18 mo calculated 

for “thrive index”

Ambidirectional 

longitudinal

Five years from 

enrollment of age 1 

y
Evidence Table 1. Studies associating anthropometrics to Failure to Thrive cases compared to healthy control group in developed countries

Part II

65

Author,

Year

Correlates Associations found Potential biases Comments

Mitchell,

1980

80166667

Weight - % of normal

Height - % of normal

HC - % of normal

Expect wt and HC of the FTT group was 

significantly lower than the controls (p < .05 

each), wt remained ~15% below control group 

through age 5, ht ~5% below till age 4. 

Expected ht was not significant. FTT girls 

recovered more slowly.

Physical exams & growth status by PI 

not blinded

Government & privately 

funded

Haynes,

1984

84233543

Weight All FTT had some wt gain during hospitalization, at 

reeval-some minor wt gain, 8 FTT gain > 20 

percentile pts or within 5 percentile of birth wt 

percentile. There were no differences for both 

FTT groups compared to the controls after 6 

mo for wt gain except in some minor cases.

“...because of scheduling, few 

admissions were not evaluated”, 2 

refused participation; 10 Gp1 & 3 

Gp2 premature – overall similar 

from FTT vs. Ctrl; at 6 mo fwup: for 

FTT1 & FTT2 each-3 cases 

refused reevaluation & from1 

dissolution of pair, 1Gp1 died SIDS, 

1 Gp2 mother gave up child

Block assignment to Gp1 & 

Gp2 for hospital 

convenience & case load 

requirements; 

government funded

Kelleher, 1993

93234174

Anthropometric outcomes FTT length, weight, & head circumference below 

5

th percentile at 12, 24, 36 mo, below Control 

averages, p < 0.0001.

Of 985 enrolled, 71 LTF 21% of sample developed 

FTT by 36 wks; ND on 

funding source

Reif,

1995

95362505

Final weight

Final height

Ideal weight 

Long-term weight of FTT

Long-term height of FTT

Mother’s education

Persons @ room

There were significant differences between FTT 

and Control groups for height (p < .01) and 

weight (p < .001), as well as compared to ideal 

ht/wt (p < .001). Mother’s education was a 

significant covariate for FTT long-term wt (p < 

.05). Number of person’s per room was a 

significant covariate for FTT long-term wt (p < 

.05) & long-term ht (p < .0005)

25 cases not re-evaluated because not 

located or refused participation; 

inpatient enrollment of FTT-48 & 

Ctrl-42; outpatient enrollment of 

FTT-13 & Ctrl-23(ER)

ND on funding source
Evidence Table 1. Studies associating anthropometrics to Failure to Thrive cases compared to healthy control group in developed countries

Part II

66

Author,

Year

Correlates Associations found Potential biases Comments

Corbett,

1996

97113595

Mean height SDS

Mean weight SDS

Height and weight centiles were significantly lower 

(p = .020 & p < .001) in the FTT group at time 

of entering school

3 from each group refused consent at 

follow-up, LTF or moved - 2 cases, 

3 controls, 1 case not originally 

studied participated for follow-up 

study, 4 of those cases were the 

slowest growing 5% - also removed 

from home, all controls stayed with 

parents. Edward’s diagnostic criteria 

for growth measure considered 

limited.

ND on funding source.

Black,

1999

99162090

Height

Weight

Gender

Despite catch-up, wt & ht growth were significantly 

slower than controls for all fwup intervals; sex & 

education did not predict outcome; perception of 

poor child health correlates with poor growth; 

no gender differences for ht or wt, but girls 

grew faster than males.

---

Government funded

Drewett,

1999

99284054

Height

Weight

Head circumference

FTT children were smaller in ht (t = 6.3, p < .01), 

wt (χ2 = 27.9, p < .001), and head 

circumference (t = 3.86, p < .01), as well as 

have fathers who were also shorter than the 

controls.

Of 136 cases, 1 died, 9 LTF, 15 

declined psychological testing, 4 

moved; of 136 controls, 2 were 

preterm, 5 LTF, 12 declined 

psychological testing, 14 moved & 

were replaced. 2 FTT cases & 1 

control with medical condition 

affecting growth, & 9 FTT cases & 2 

controls with possible medical 

conditions

Testers blinded to child’s 

status; privately funded
Evidence Table 2. Studies associating anthropometrics with malnourished patients compared to well-nourished control subjects in 

developing countries 

Part I

67

Author,

Year Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study design

Branko,

1979

79228898

Country: Ethiopia

Setting: Outpatient

Gp1* Gp2† Ctrl

Age(y) 5.5-14 5.5-12.8 5-14

Wt/age ND ND ND

Ht/age ND ND ND

Enrolled/eval 44 43 559

% Male 61 48 52

Race: 100% Black

* Marasmus, † Kwashiorkor

Maternal educ: ND

Income: ND

Health insur: Free 

medical care

Formerly hospitalized & for 

successful treatment of 

marasmus or kwashiorkor

ND Marasmus: 

nutritional 

etiology, wt < 

60% of Boston 

50th percentile 

for age/sex, 

absence of 

edema

Kwashiorkor: 

nutritional 

edema, growth 

retardation, 

muscular 

atrophy, 

“psychomotor 

alterations”, hair 

or pigment chg, 

or “moon face”

Ambidirectional

Last assessment 

avg 71⁄2 (2.5) y 

after D/C

Evans,

1980

81008912

Country: South Africa

Setting: outpatient clinic

Wt/age See Correlates column

Ht/length See Correlates column

Gp1 Ctrl1 Gp2 Ctrl2

Mean 8.9 10.7 13 12

 age(SD) (0.5) (1.0) (1.9) (2.1)

Enrolled 14 14 14 14

Evaluated 14 13 14 13

% Male 64 54 100 77

Race: “Cape coloured”

ND Gp1 – newborns of families 

with hx of undernutrition

Ctrl1 – siblings with hx of 

undernourishment, record of 

`< 3rd percentile for ht & wt

Gp2 – at least 1 hospitalization 

for kwashiorkor

Ctrl2 – siblings closet in age 

Gp2 w/no hx of kwashiorkor 

but underweight

ND ND Prospective 

longitudinal

Fwup 6 1⁄2 y after 

intervention
Evidence Table 2. Studies associating anthropometrics with malnourished patients compared to well-nourished control subjects in 

developing countries 

Part I

68

Author,

Year Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study design

Galler, 

1985a

85241832

Country: Barbados

Setting: Outpatient

Age(y): 9-15

Gp Ctrl

Wt/age ND ND

Ht/length ND ND

Enrolled 141 129

Evaluated 108 107

% Male 57 60

Race: 100% Black

Maternal educ: ND, 

universal education, 

95% population literate

Income: lower for cases 

compared to control 

group

Health insur: ND

Discharged 5 – 11 yr olds 

w/dx at age 1 yr with PEM 

Grade II-III, BW > 5 lbs

Controls without PEM, matched 

for age, gender, handedness, 

& same school / 

neighborhood

Pre- or peri-natal 

complications, 

edema, 

seizures, head 

trauma, loss of 

consciousness, 

high fever

1985a/1985b: hx 

head seizures

Gomez Scale

PEM: Grade II61-75% or 

Grade III- ≤

60% standard 

wt for age on 

Harvard 

Standard Scale

Ambidirectional 

longitudinal

Fwup 6 – 12 y 

after D/C

Alvear,

1986

86185605

Country: Chile

Setting: Outpatient

Gp Ctrl

Age(mo) 16(8-20) ND

Wt/age* ND ND

Ht/length* ND ND

Enrolled/Eval 40 38

% Male 45 47

Race: ND*

* See Inclusion criteria

ND Hx of hospitalization for PEM at 

yrs 1-2, Chilean population & 

white Amerindian origin from 

Santiago Chile, SES grade 5 

or 6 (modified Graffar scale)

Controls matched for 

age/sex/SES, attend same 

nursery sch as cases, no hx 

of mal-nourishment, normal wt 

& ht (WHO)

Hormonal 

imbalance, 

debilitating 

disease not due 

to nutritional 

deficiency

PEM at yrs 1-2; < 

60% wt for age, 

< 85% wt for 

length

Prospective 

longitudinal

4 y after D/C
Evidence Table 2. Studies associating anthropometrics with malnourished patients compared to well-nourished control subjects in 

developing countries 

Part I

69

Author,

Year Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study design

GranthamMcGregor, 

1987,

1982

82236679

87117313

Country: Jamaica

Setting-Recruitment: hospital

Follow-up: hospital & home

Gp1* Gp2† Ctrl†

Age: 12.8 13.4 12.2

(2.9) (4.5) (4.4)

Ht/age‡ 89.0 88.4 101.3

(4.5) (4.4) (3.5)

HC/age‡ 91.3 91.2 99.0

(3.7 (3.3) (3.8)

Wt/ht‡ 74.9 72.4 89.0

(9.2) (10.2) (10.1)

Enrolled 21 18 21

Evaluated 18 16 20

% Male: 67 38 60

Race: ND, assumed Black

Mean (SD) for evaluated cases;

* Intervention, † Standard care, ‡ % of 

expected value

Maternal educ: HS not 

completed

Income: housing ‘below 

certain defined 

standards’

Health insur: ND

Maternal

PPVT

Gp1 62.3(14.7)

Gp2 59.7(15)

Ctrll 67.4(9.3)

Gp, age 6 – 24 mo, attempt for 

SES of mothers who had not 

completed secondary 

education, substandard 

housing, residence in city of 

Kingston

Control - included above 

criteria but adequately 

nourished, hospitalized with 

diseases other than 

malnutrition

Physical 

handicap, 

disease that 

might affect 

mental 

development 

(other than 

malnutrition)

Severe PEM 

based on 

Wellcome 

classification

Prospective 

longitudinal

6 fwups from 6 to 

72 m after D/C l

Bénéfice,

1992

92296639

Country: Senegal

Setting: Outpatient

Age: ND

Enrolled: 100

Evaluated: Gp 64, Ctrl 34

% Male: 46

Race: ND

ND Age 9 – 14 y from 2 villages 

with per capita caloric intake of 

2200 & 2400

Recent serious 

illness, clinical 

signs of 

malnutrition or 

anemia

Wt/age < -1 SD 

median 

WHO/NCHS

Prospective

cross-sectional
Evidence Table 2. Studies associating anthropometrics with malnourished patients compared to well-nourished control subjects in 

developing countries 

Part I

70

Author,

Year Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study design

Walker,

1996

97154651

Country: Jamaica

Setting: Outpatient

Mean age*: 18.7(4.1) mo

Enrolled: Stunted 129

Nonstunted 32

Gp1† Gp2‡ Gp3§ Ctrl1||

Ctrl2¶

Eval 31 29 30 32 32

Wt(kg)** Ht(cm)** % 

Male††

Gp1 8.61(0.97) 73.3(3.5) 61

Gp2 8.43(0.90) 72.9(3.9) 55

Gp3 8.37(0.99) 72.9(3.6) 57

Ctrl1 8.65(1.03) 72.8(4.3) 59

Ctrl2 11.46(1.06) 82.3(4.6) 56

Race: ND

Mean(SD), * N = 129, † Supplement, ‡ 

Psychosocial, § Both intervention, || No 

intervention, ¶ Nonstunted, ** Enrollment, †† 

Evaluation

ND Stunted children 9 – 24 mo, 

weight for age < -2 SD, 

housing & maternal education 

below standard level, 

singleton, BW > 1,8 kg

Nonstunted children matched 

for age, sex, & neighborhood

Physical or 

mental 

handicap

See Inclusion 

criteria

Prospective 

longitudinal

Assessments @ 2 

& 4 y after 

intervention
Evidence Table 2. Studies associating anthropometrics with malnourished patients compared to well-nourished control subjects in 

developing countries

Part II

71

Author,

Year Correlate & measures Associations found Potential biases Comments

Branko,

1979

79228898

Gp1 Gp2 Ctrl*

Ht (cm) 93-154 90.0-143 99.1(3.6)-144.7(3.3)

Wt (Kg) 11.4-35.0 11.0-29.5 14.6(1.2)-34.3(5.4)

HC (cm) 47.0-53.0 48.0-53 49.0(0.8)-53.4(1.1)

* mean range by sex & age ranges of 6 mo from age 5 to 14 y

Maramus gp was on avg 3 cm smaller than 

Ctrl (p < .011), weighed 2.1 kg less, (p < 

.011), and their HC was 0.85 cm less (p < 

.007);

The Kwashiorkor gp was smaller than Ctrl on 

avg 0.84 cm (p < .607), weighed 0.6 kg less 

(p < .082), & their HC was 0.3 cm smaller (p 

< .368);

Comparing Marasmus vs. Kwashiorkor gps, 

the Kwashiorkor gp was heavier (p < .05), 

taller (p < .02), & had larger HC (p < .05).

--- ND on funding 

source

Evans,

1980

81008912

Gp1 Ctrl1 Gp2 Ctrl2

~Wt1* 86 77 75 72

~Ht1y* 90 84 82.5 82

~Wt2† 79 78 77 76

~Ht2† 90 89.5 90 90

* 2 y after supplements, † 6.7 y after supplements

2 years after supplementation had ceased, 

height & weight were significantly higher for 

Gp1 (p < 0.01) vs. 3 other groups; by 6.5 + 

y post-intervention, there were no 

differences.

1 child died in each of the 

controls, sex unkn

Gp1 received 

supplements until 

mean 28 mo, 

examiner blinded 

to subject’s group 

status, testing 6-7 

y after cessation 

of supplements; 

US government 

& South African 

Medical 

Research 

Council
Evidence Table 2. Studies associating anthropometrics with malnourished patients compared to well-nourished control subjects in 

developing countries

Part II

72

Author,

Year Correlate & measures Associations found Potential biases Comments

Galler, 1985a

85241832

Gp? Ctrl? Gp? Ctrl?

Ht* 148.92 150.4 145.25 149.63

(12.5) (12.18) (11.4) (11.02)

Wt† 37.02 39.37 35.42 41.9

(10.74) (10.35) (7.63) (35.42)

*cm, † kg

At ages 9-15, there was persistent poor height 

& weight gain for the index group with 

emphasis on the girls’ weight (F = 28.88, p < 

.001). Early PEM was a predictor of sexual 

maturation for females (F = 5.69, p < .001).

1983-Withdraws/nonparticipation – 4 refused 

consent, 7 LTF, 1 cerebral 

palsy; Severe PEM

Relevant WISC 

subtests utilized & 

some items 

altered for cultural 

setting; findings of 

dominant hand 

performance of 

fine motor skill 

tasks deficient in 

formerly 

malnourished 

children 

correlates or covaries with IQ & 

other soft 

neurologic signs; 

private & hospital 

funded

Alvear,

1986

86185605

Gp? Gp? Ctrl? Ctrl?

Birth wt 3018.2 2654.6 3453.5 3328.4

(490.3) (579.0) (522.3) (563.4)

Birth length 48.4 46.8 51.1 49.5

(2.2) (2.6) (2.3) (2.2)

Bone age* 60.3 76.7 69.2 86.7

(8.6) (14.2) (9.7) (27.2)

Arm fat area 73.5 64.5 91.0 95.7

(15.3) (16.5) (24.7) (28.5)

* Gp n=25 (?=12, ?=13), Ctrl n=20 (?s=9, ?=11)

At birth, the cases were smaller in wt (boys p < 

0.01, girls p < 0.001) and length (boys p < 

0.01, girls p < 0.001) compared to controls. 

At the end of follow-up, there was no 

difference in bone age between cases and 

control groups by group or by sex, but there 

was a significant difference for female cases 

who were smaller than male cases for bone 

age (p < .01). Arm fat areas were greater 

for controls vs. cases (girls p < .001, boys p 

< .05).

--- No data on whether 

children were 

failing to thrive at 

4-6 years when 

anthropological 

data were 

collected; 

university funded
Evidence Table 2. Studies associating anthropometrics with malnourished patients compared to well-nourished control subjects in 

developing countries

Part II

73

Author,

Year Correlate & measures Associations found Potential biases Comments

GranthamMcGregor, 

1987,

1982

82236679

87117313

Gp1 Gp2 Ctrl

Wt for ht * 91.7(7.5) 95.1(8.4) 92.5(6.8)

Ht for age* 94.9(2.5) 93.9(4.5) 100.6(3.8)

Assessment at 72 mo, * Mean percentages

Assessments 6, 12, 18, 24 months; weight for 

height measures were not statistically 

significant, but the two case groups were 

significantly shorter for all time points than the 

control group (p < 0). At 24, 36, 48, 60, & 

72 month; height for age was significantly 

lower for the two groups vs. controls.

Controls had better housing 

than other 2 groups 

regardless of attempts to 

match; 2 died & 1 WD from 

intervention group, 1 from 

nonintervention moved & 1 

was adopted by middle-class 

family, 1 from control WD; 

edema: Gp1 10 of 21, Gp2 4 

of 18, Ctrl 0 of 21

Tester blinded to 

subjects’ group, 

controls 

hospitalized 

mainly for 

gastroenteritis & 

respiratory 

infections; 

government & 

private funding

Bénéfice,

1992

92296639

Gp Ctrl

% body fat 15.0(0.28) 16.9(0.39)

Arm muscle area 18.7(0.33) 21.8(0.47)

Adjusted mean (SD)

Children with malnutrition had less body fat (t = 

3.5, p < .001) & arm muscle (t = 6.0, p < 

.001) compared to nourished controls.

Child’s age determined by 

recall, no records available; 

no explanation on missing 

case from each group not in 

analyses

ND on funding 

source

Walker,

1996

97154651

Gp1 Gp2 Gp3 Ctrl1 Ctrl2

Ht(c) 119.8 119.5 118.8 118.9 130.9

(5.0) (5.4) (4.1) (4.7) (4.9)

Wt(k) 21.2 20.9 19.9 20.4 26.2

(3.5) (3.1) (1.9) (2.2) (2.3)

HC(c) 51.2 50.9 51.0 50.8 52.4

(1.3) (1.4) (1.3) (1.5) (1.4)

Signf for three measures of Ctrl2 vs. combined 

stunted groups, p < .001, covariates - sex & 

age (mean 7.7 @ gp)

No difference between the different groups of 

stunted children in height, weight, and head 

circumference, but difference between the 

combined stunted groups with non-stunted 

children.

127 of 129 children completed 

studies; 4 yr after completion 

of intervention, of stunted gps 

- 3 relocated & 2 LTF

Observers blinded 

to child’s group, 

evaluation 4 y 

after 2 y 

intervention; 

privately funded
Evidence Table 3. Studies associating immunologic response or infectious diseases with Failure to Thrive patients compared to healthy 

control subjects in developed countries

Part I

74

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT Study design

Carvalho,

1984

85145406

Country: Brazil

Setting: Outpatient clinic 

Age: ND

FTT Ctrl

Enrolled/Eval 20 40

% Male: ND

Race: ND

ND Moderate & chronic 

primary PCM, > 6 mo < 

5 y, body wt 25.1 & 

40% of “standard 

values”, subcutaneous 

tissue, absence of 

edema, arm 

circumference < 13.5 

cm, ht “within normal 

limits”, low SES

Controls - same criteria 

but “normal” body 

weight, “goodeconomic level and 

enjoyed good nutritional 

intake”

Infection, 

transfusions, 

general anesthetics, 

corticosteroids or 

immunotherapy < 6 

mo prior, drug tx

ND Prospective

cross-sectional

Sherrod,

1984

85026403

Country: US

Setting-Recruitment: Prenatal clinic

Follow-up: Pediatric clinic

NOFTT Ctrl

Birth wt(g) 3031 3054

Enrolled/

 Eval* 31 24

Race-White 10 14

Black 21 10

% Male: ND

* 4 arm study – Data for FTT & Ctrl only; 

abused or neglected cases excluded

NOFTT Ctrl

Maternal

 educ 10.3 11.2

Income* 13 13

Health

 Insur† ND ND

* # employed, † p < .05, ‡ p < 

.01

NOFTT, abused, or 

neglected

Controls – no hx of abuse, 

FTT, or neglect

ND Wt gain fallen below 

2/3 of Harvard 

50th percentile on 

growth curve

Retrospective 

longitudinal

3 annual 

assessments
Evidence Table 3. Studies associating immunologic response or infectious diseases with Failure to Thrive patients compared to healthy 

control subjects in developed countries

Part II

75

Author,

Year, UI Correlates Measures Method / Instruments utilized

Phagocytosis

Eagle solution

Nl human serum

Patient serum

FTT Ctrl % variation

18.7(7.3) 27.6(9.2) -32.3 p < .01

54.2(24.6) 78.5(7.8) -30.9 p < .001

56.7(22.4) 75.9(10.9) -25.3 p < .01

Light microscope phagocytosis assay (% 

zymosan particles ingested)

Chemotaxis

Eagle solution

LPS & nl human serum

LPS & patient serum

25.4(10.0) 34.2(8.0) -26.0 p < .01

42.6(17.7) 64.4(15.3) -33.8 p < .001

44.3(19.0) 68.5(18.4) -35.3 p < .001

Boydan chamber (avg distance cells 

migrate)

Carvalho,

1984

85145406

Total complement (u/ml)

C3 (mg/dl)

C4 (mg/dl)

235.2(55.1) 244.6(61.6) -3.8 NS

89.3(21.3) 80.5(19.3) +10.9 NS

38.5(11.2) 37.3(13.3) +3.4 NS

Percent cell lysis

Sherrod,

1985

85026403

Infections NOFTT Ctrl

1y 1.13 .46

2y .35 .29

3y .03 .00

Chart review
Evidence Table 3. Studies associating immunologic response or infectious diseases with Failure to Thrive patients compared to healthy 

control subjects in developed countries

Part III

76

Author,

Year

Associations found Potential biases Comments

Carvalho,

1984

85145406

The values for phagocytosis response and chemotactic function were 

significantly lower for the malnourished children in 3 tests: 

Zymosan incubated in Eagle, incubated with pooled normal 

human serum & incubated with serum from patient. The values 

were not significant for total complement, C3 and C4 components.

Cases and controls from different hospitals 

serving different SES groups; no data on 

age matching

Phagocytosis tests on 20 children, 

chemotaxis on other 20, total 

complement on 20 chosen at random; 

privately funded

Sherrod,

1985

85026403

NOFTT had more infections than controls during the 1st year (χ2 = 

5.38, p < .025) and across all 3 years (χ2 = 5.79, p < .025). 

NOFTT illness were significantly increased during first 6 mo of life. 

Attending physicians alerted to give special 

treatment to children suffering from 

maltreatment, analysis showed no increase 

in outcome variability; study design to 

identify relationship of illness to abuse, not 

FTT to illness

Data collectors blind to child group 

assignment; government & privately 

funded
Evidence Table 4. Studies associating immunologic response or infectious diseases with malnourished patients compared to wellnourished control subjects in developing countries

Part I

77

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study

design

Ferguson,

1974

75022280

Country: Ghana

Setting: Cases – inpatient

Controls – ND

Gp Ctrl

Mean age(mo) 28.9 38.8

(12-48) (24-55)

Wt/age ND ND

Ht/length ND ND

Enrolled/Eval 10 10

% Male ND ND

Race ND ND

ND Severe protein-calorie 

malnutrition

Controls – “normal”, 

matched for age 

ND Severe protein-calorie 

malnutrition

Prospective crosssectional

Neumann,

1975

75106463

Country: Ghana

Setting: hospital/in & outpatient clinic

Age: 6 mo – 6 y

Wt/age: ND

Ht/length: ND

GpI* Gp2† Ctrl

Enrolled/Eval 34 42 41

% Male 62 50 44

Race: Africans (assumed black)

* Severely malnourished: kwashiorkor(23) 

& marasmus(11), † Moderately 

malnourished

ND See Definition of FTT

Controls matched for 

age, = 81% Harvard 

Std, nl serum albumin, 

no signs of malnutrition 

ND Gp1: 51-60% of 50th

percentile Harvard Std 

for American children & 

albumin < 2.5 g/100ml, 

Gp2: 71-80% of 

Harvard Std & albumin 

> 2.5 g/100ml

Prospective crosssectional
Evidence Table 4. Studies associating immunologic response or infectious diseases with malnourished patients compared to wellnourished control subjects in developing countries

Part I

78

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study

design

Tuck,

1979

79254720

Country: Australia & Indonesia

Setting: Hospital

Age(mo): ND

Wt/age: ND

Ht/length: ND

Enrolled/Eval:

 Gp1 marasmic 21

 Gp2 underweight 23

 Gp3 normal 25

% Male: ND

Race: ND

ND ND Immunological 

deficiencies in 

normal children 

attending hospital in 

one site

NA

(Patients classified 

according to Wellcome 

Working Party: 

underweight - 60-80% 

SWFA, marasmic - < 

60% SWFA)

Prospective crosssectional

Friedland,

1992

93159117

Country: South Africa

Setting: Inpatient

Gp Ctrl

Age(mo) 11 12

Enroled/Eval 1582 7282

% Male ND ND

Race: ND (assumed all black)

ND Children 

w/kwashiorkor, 

marasmus, marasmic 

kwashiorkor admitted, 

ages 2 – 84 mo

Controls - “wellnourished & children 

w/nutritional growth 

retardation admitted 

during same time 

period”, same age 

range

ND Wellcome criteria with 

growth charts from 

NCHS

Prospective

cross-sectional
Evidence Table 4. Studies associating immunologic response or infectious diseases with malnourished patients compared to wellnourished control subjects in developing countries

Part I

79

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study

design

Ballard,

1995

95239862

Country: Kenya

Setting: Rural village/

community outreach

Mean age*: 19.2 m (17.7-25.1)

Wt/age: ND

Ht/length: ND

Enrolled: 114

Evaluated† Gp1 Gp2 Ctrl

27 51 31

49% Male (enrollment)

Race: 100% Black Africans

* At enrollment, † Gp1 Mod-severe 

malnutrition, Gp2 Mild malnutrition

Maternal reading level 

– average 3.5 yrs of 

schooling

14-25 mo, free from 

lower respiratory 

infections for = 4 wks

Controls – “normal”

ND Gp1 - ht/age < 90% of 

median

Gp2 - ht/age 90% to 

<95% of median

Prospective 

longitudinal cohort

Followed for max of 

12 mos

Pandey,

1996

97246349

Country: India

Setting: Outpatient

Age(mo): Range 0-59, Mode 24-35

Enrolled: 200 households

Evaluated:

Gr1 GrII GrIII GrIV Nl

37 56 18 4 85

% Male: ND

Race: ND

ND Random selection of < 5 

y

ND Graded nutritional status 

as GrI though GrIV 

clinically & by wt/age

Prospective 

longitudinal

Assessments @ 2 wks 

for 1 y
Evidence Table 4. Studies associating immunologic response or infectious diseases with malnourished patients compared to wellnourished control subjects in developing countries

Part II

80

Author,

Year

Correlates / Outcomes

 and measures Associations found Potential biases Comments

Ferguson,

1974

75022280

Immunologic - Rosette forming cells (percent of total lymphocytes) Gp - 16.6% (2.7 SE), Ctrl –

59.7% (1.4 SE)

Marked decrease in rosette forming cells (measure of cellular 

immunity) in severe malnutrition; RFC re-measured in 5/10 

cases 7-17 d after feeding high protein, high calorie diet –

values returned to nl (%RFC = 63.2% ± 2.4). Other 

measures of impaired immune function – in vitro response of 

lymphocytes to PHA stimulation showed trend to be 

diminished in cases, but NS (no data)

7 diagnosed 

kwashiorkor & 3 with 

marasmus

US government 

funded
Evidence Table 4. Studies associating immunologic response or infectious diseases with malnourished patients compared to wellnourished control subjects in developing countries

Part II

81

Author,

Year

Correlates / Outcomes

 and measures Associations found Potential biases Comments

Neumann,

1975

75106463

Clinical infections / parasites

Antibody responses

Gp1 Gp2 Ctrl

Tonsil size* (%) (%) (%)

Score† 0 36 5 0

1+ 52 50 34

2+ 12 40 56

3+ 0 5 10

Delayed hypersensitivity response

Lymphocyte response† 19 0 0

PHA‡ 44 29 5

Monilia‡ 59 38 20

SK-SD‡ 76 57 23

KLH‡ 5 0 0

Total serum proteins(SE) 5.1(.4)/ 7.5(.1) 7.9(.1)

6.3(.4)§

CBC & differential

Hemoglobin 60 17.5 12.5

Iron 44.8 29.7 20

%Transferrin saturation 41.3 55.3 50

Complement - C3 60.4(4.1) 86(3.9) 86.9(2.4)

* 0 = trace or absent, 1 = visible, 2 = enlarged beyond arch, 3 = 

extended past arch to uvula midline; † Percent reduced 

response; ‡ Percent nonresponders, § kwashiorkor/marasmus

There was a marked increased in infections for severely 

malnourished group (Gp1), slight increase for the moderate 

malnourished group (Gp2) compared to Ctrl. The incidence 

of intestinal parasites were similar across the 3 gps, except for 

10x increase in strongyloides stercoralis for Gp1, and 1 

malarial case @ gp. Tonsil sz was decreased signf in Gp1 vs. 

Gp2 & Ctrl. 

Antibody responses were similar across all 3 gps. Lymphocyte 

response was signf lower in Gp1 vs. Gp2 or Ctrl. Cutaneous 

delayed hypersensitivity to PHA, monilia, SK-SD was signf 

lower in Gp1 & Gp2 vs. Ctrl. Response to KLH was slightly 

lower in the cases.

Vitamin deficiencies in all groups, most prevalent in Gp1. 

Complement C3 decreased signf in Gp1 vs. Gp2 & Ctrl; NS 

results for C4. Other nutritional deficiencies included 

decreased iron & transferrin in Gp1.

Gp1 hospitalized cases, 

16 of 34 had received 

nutritional tx before 

studies, Gp2 included 

25 newly admitted & 

17 living in orphanage 

or attendance at rehab 

clinic & were treated. 

Controls attended 

private nursery school 

or resided in 

orphanage & had 

some vitamin/mineral 

deficiencies

Government 

funded
Evidence Table 4. Studies associating immunologic response or infectious diseases with malnourished patients compared to wellnourished control subjects in developing countries

Part II

82

Author,

Year

Correlates / Outcomes

 and measures Associations found Potential biases Comments

Tuck,

1979

79254720

Candida killing capacity

Marasmic Underweight Normal

13.7% 17.6% 44.5%

(3.4)* (4.4)* (8.8)* * SEM

Candida-killing ability, as determined by Kolmogorov-Smirnov 

test, was reduced in each of two underweight populations 

compared with the well-nourished population (p < .001), NS 

between the underweight & marasmic gps

Normal adults included 

in the control group, 

number of adults not 

known, site(s) of 

adults unknown, one 

of the 3 sites had no 

malnourished 

children who may 

have also been 

outpatients

NS between the 

two 

malnourished 

groups on 

ability to resist 

candida; ND 

on funding 

source

Friedland,

1992

93159117

Gp Ctrl

Bacteraemia (%) (%)

Community acquired 7.7 4.9

Nosocomial 2.2 1.1

Overall 9.9 6.0

Mortality

Overall 13.3 4.1

With bacteremia 31 13

Index group are statistically significantly at higher risk than 

control group for community -acquired bacteremia (p < 

0.001, RR for FTT 1.6, CI 1.3 – 1.9), nosocomial 

bacteremia (p < 0.001, RR for FTT 2.0, CI 1.4 – 3.0), and 

mortality, including mortality related to bacteremia (p < 0.001, 

RR for FTT 3.2, CI 2.7 – 3.8).

Index group 

considered severe 

malnutrition. Control 

group consisting of 

“nutritional growth 

retardation” which 

most likely represents 

what is recognized as 

FTT. Both factors 

invalidates the 

“controls’

Risk of death of 

malnourished

children 2.5 

more likely to 

die than 

bacteremic 

nonmalnourished; 

ND on funding 

source; 

Government, 

private, & 

hospital funded

Ballard,

1995

95239862

Acute lower respiratory infection Children classified as having moderate to severe 

stunting/malnutrition were at higher risk for ALRI (RR = 4.5, 

ht/age < 90% median) compared to nonstunted/malnourished children (ht/age = 95% of median) 

(classification by NCHS criteria)

8 LTF within 1 month of 

enrollment or had 

ALRI 4-8 wk period 

prior to observation; 

inconsistent data for # 

pts at evaluation; 

potential recall bias

US government 

& privately 

funded
Evidence Table 4. Studies associating immunologic response or infectious diseases with malnourished patients compared to wellnourished control subjects in developing countries

Part II

83

Author,

Year

Correlates / Outcomes

 and measures Associations found Potential biases Comments

Pandey,

1996

97246349

 No. of # ARI episodes

children per child / yr

Vit A deficient 28 7.4

Not deficient 172 5.6

Age(mo) 0-11 12-23 24-35 36-47 48-59

# ARI 6.2 5.8 5.7 5.9 5.8

Sample n 27 31 62 34 46

ARIs / year

GrI GrII GrIII GrIV Nl

5.6 6.9 7.4 7.7 4.8

The 28 children with evidence of vitamin A deficiency had 

significantly higher # ARI than children without vit A 

deficiency (χ2 = 8.64, p < .01). There was association of 

increased malnutrition with more frequent # ARIs (χ2 = 

36.17, p < .05). There was no age or sex difference.

Vit A deficiency 

diagnosed by “ocular 

signs using a brightly 

illuminated torch”

Follow-up 

intervals @ 2 

wk for 1 yr; ND 

on funding 

source
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I 

83

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT Study design

Pollitt,

1976

76109110

Country: US

Setting: Outpatient

FTT Ctrl

Mean age*: Male 33(14) 34(13)

Female 39(14) 39(15)

Mean ht†: Male 93(2) 101(1)

Female 90(2) 102(3)

Enrolled/Eval 19 19

% Male 47 47

Race: ND

* Months, † centimeters

FTT Ctrl

Maternal 11 12

 educ (2) (1)

Income -

 Gross 6943 9541

 annual (3444) (4768)

 Per capita 1557 2648

(725) (1517)

Health 

 insur ND ND

Outpatient clinic, 12-60 

mo, ht & wt < 3%, bw = 

2500 gm, GA = 36 wks, 

nl birth, nonorganic, 

singleton, maternal ht = 

154.5 cm & Englishspeaking ability

Controls matched for age 

(± 3 mo), sex, race, ht 

& wt = 25%

Birth complications, 

physical disability, 

genetic or organic 

retardation, brain 

damage, organic 

growth retardation

Boston Growth 

Standards – ht & 

wt = 3rd percentile

Prospective

 cross-sectional

Weekly interviews 

for 7-11 sessions

Mitchell,

1980

80166667

Country: US

Setting: Outpatient clinic

FTT Ctrl

Age(y) 2-5 2-5

Wt/age ND ND

Ht/length ND ND

Enrolled : cohort of 312(323)*

Evaluated 30 282

% Male 36.7 51.8

% Black 70 70

* See Potential biases column

Maternal education: ND

Income: ND

Health insur: 

FTT-53% Medicaid

Ctrl-49% Medicaid

See definition of FTT

Controls: wt = 80% of nl, 

matched for age, sex, 

mother’s age/ marital 

status & family problems

Organic cause of 

FTT, single 

anomalous low wt 

recorded, clinic 

registration by age 

6 mo, < 3 visits

Wt for age < 80% of 

nl up to age 24 mo 

Ambidirectional 

longitudinal

1 fwup at age 3 –

6 y
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I 

84

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT Study design

Polan,

1991

92098539

Country: US

Setting: Outpatient clinic

FTT Ctrl

Mean age* 16.7(6.9) 18.9(7.3)

Wt/age ND ND

Ht/age ND ND

Enrolled/Eval 28 14

% Male 50 43

Race: ND ND

* Months

Maternal education: ND

Income($1,000):

FTT Ctrl

Mean 39.4 40.1

(51.4) (49.6)

Median 27.5 28.5

Health 

 insur ND ND

FTT, age 6 – 36 mo 

Controls from same site, 

wt & ht = 10th percentile 

on NCHS growth charts

Life threatening or 

terminal illnesses

= 35 wks gestation 

& normal birth wt, 

wt fell < 5th

percentile, or 

decrease in wt 

gain in 6 mo = 2 

major percentiles 

based on NCHS

Prospective

cross-sectional

Drotar, 

1992

92372721

Country: US

Setting: Outpatient fwup

FTT Ctrl

Mean age* 4.92(2.81) 5.05(2.85)

Wt/age ND ND

Ht/length ND ND

Enrolled 68 68

Evaluated 48 47

% Male 71 57

Race: Black 29(60%) 35(74%)

White 29(40%) 12(26%)

*At intake

FTT Ctrl

Maternal 10.94 11.51

 educ (1.74) (1.57)

Income 5446 7792

(5561) (10309)

Health 

 insur ND ND

Mean (SD)

Hospitalized for NOFT 

with nutritional 

intervention, age 1 – 9 

months

Controls matched for age 

at intake, sex, race, 

birth order, gestational 

age, maternal educ & 

age, family income & 

size

Physical abuse, 

residence > 1 hr 

from hospital, bw < 

1500 gm

Wt < 5th percentile 

based on NCHS, 

absence of 

disease, wt gain in 

hospital, poor wt 

velocity

Prospective 

longitudinal

1 fwup at age 42-

48 months
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I 

85

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT Study design

Hutcheson, 

1993

94015754

Country: US

Setting: Primary care clinic

FTT Ctrl

Mean age* 15.1(5.2) 14.9(5.1)

Wt/age 2.83 63.17

Ht/age 23 63

Enrolled/Eval 34 34

% Male 62 62

Race: Black 32 32

* Months

FTT Ctrl

Maternal

 educ* 38 70

Income† 64 70

Health 

 insur ND ND

* % HS graduate

† % receiving AFDC

NOFTT, age 8 – 24 mo

Controls matched for 

age, sex, race

Congenital disorder, 

chronic disease, < 

37 wk gestation, 

SGA

Wt for age ≤ 5th

percentile, or wt for 

ht ≤ 10th

percentile, based 

on NCHS

Prospective crosssectional

Kelleher, 

1993

93234174

Country: US

Setting: Primary care clinic

FTT Ctrl

GA(wk)* 33.0 33.1

Wt(g)* 1679 1845

Enrolled: 842*

Evaluated 180 591

% Male 52.2 47.9

Race: % Black 50 53.8

* At birth

FTT Ctrl

Maternal

 educ* <HS 40.6 38.1

HS 30.0 29.3

 Some col 14.4 20.8

 ≥col grad 15.0 11.8

Income -

 <10K 38.6 34.5

 10-20K 19.9 23.9

 >20K 38.1 37.4

Health insur ND ND

* % HS graduate

Gestation age ≤ 37 wks, 

birth wt ≤ 2500 g, FTT

Controls matched for –

birth wt +/- 250 g, 

maternal education, 

maternal race, & infant 

sex

Live outside 

catchment area, 

D/C outside 

recruitment period, 

D/C or died within 

48 hr, hospitalized > 

60 d, oxygen 

support > 90 d, twin, 

triplet or quadruplet 

of ineligible child, 

maternal 

drug/alcohol abuse, 

insufficient English 

skills, psychiatric 

hosp

< 5th percentile for 

gestation corrected 

age based on 

NCHS, growth 

status on “wt curve 

below that 

recorded at last 

regular 

assessment visit.”

Prospective 

longitudinal

Fwup at ages 12, 

24, 36 mo
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I 

86

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT Study design

Skuse,

1994 

94253258

Country: UK

Setting: Outpatient

FTT Ctrl

Age(mo)* 14.6(1.4) 14.2(1.4)

Wt/age† -2.07(.44) .10(.96)

Ht/length† -1.27(.94) .18(.73)

Enrolled 49 50

Evaluated 47 47

% Male 49 49

% Non-white 43 34

* Mean (SD), † z score, p < .001

Maternal educ: ND

Income: income/welfare 

support FTT-16, Control-11

Health insur: National 

healthcare

District-centered until 12 

mo of age, singleton 

deliveries of 38-41 

wks gestation

Controls matched for 

sex, age, ethnic origin, 

bw within 300 g, 

ordinal position, SES

≤ 3rd centile, no wt 

data 

Wt for age ≥ -1.88 

by 12 mo of age & 

sustained 3 mo 

(based on NCHS)

Prospective 

longitudinal

Assessments at 

age 15 mo & 4y

Puckering,

1995

95378341

Country: UK

Setting: Outpatient

FTT Ctrl

Age(mo) 48.9(1.8) 48.2(0.8)

Wt/age(SDS)* -2.01(0.6) -0.32(1.1)

Ht/length(SDS)* -2.24(0.5) -0.6(0.9)

Enrolled/Eval 23 23

% Male 48 48

Race: 100% White

* based on NCHS, p < .001

FTT Ctrl

Maternal 15.6 15.6

 educ* (1.4) (1.4)

Income† 11 7

48% 30%

Health insur: Socialized 

medicine

* Age leaving full-time 

education

† Income support/welfare

From inner city 

population sample -

Caucasian born in 

1980 with longitudinal 

growth data from birth 

to 4 years

Controls matched for 

sex, gestational age ≥

38 wks, & ethnic origin

Prematurity, 

congenital defects/ 

diseases affecting 

growth, no 

perinatal insults

Ht & wt < 10% 

based on standard 

British growth 

charts (Tanner & 

Whitehouse)

Ambidirectional 

cross-sectional
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I 

87

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT Study design

Corbett,

1996

97113595

Country: UK

Setting: Clinic

Age at follow-up: 6-7 yr

FTT Ctrl

Wt/age ND ND

Ht/length ND ND

Enrolled 52 52

Evaluated 48 46

% Male: ND

Race: 100% White

Maternal educ: ND

Income: “...most 

economically deprived 

wards in Newcastle”

Health insur: National 

healthcare

Full term singleton with 

records of 6 or more 

weights over first 18 

months age

Consecutive controls 

matched for age & sex

Non-Caucasian, 

“poor growth 

resulting from 

major organic 

disease”

Weight deviated 

downward from 

maximal centile 

achieved at 4-8 

wks, across ≥ 2 

centile lines, & 

remained at level 

≥ 2 measurements 

≥ 1 mo – chart 

based on Tanner 

& Whitehouse

Ambidirectional 

longitudinal

5 year follow-up of 

cases

Wilensky, 

1996

97022837

Country: Israel

Setting: Community pediatric clinic

FTT Ctrl

Mean age(mo)* 15/20 15/20

Wt/age ND ND

Ht/length ND ND

Enrolled† 55 1352

Evaluated 50 50

% Male ND ND

Race: ND;

 Maternal country of birth –

 68% Israel, 25% Europe/America, 

 5% N Africa, 2% Asia

* At entry / assessment

FTT Ctrl

Maternal 13.8 13.4

 educ* (1.62) (1.44)

Income: AFDC 76%

Health insur: ND

* Mean (SD), based on record 

review of potential subjects

FTT infants by review of 

records who have 

reached 15 months 

born in 1991

Controls from same 

maternal & child health 

clinic matched for birth 

month, maternal educ, 

maternal age, parity, 

and infants’ birth wt

Birth wt < 2500 gm, < 

37 weeks, wt/ht 

ratio > 10 %, 

organic cause of 

FTT

Wt < 3% by NCHS 

for = 3 months 

prior to age 15 

months

Ambidirectional 

cross-sectional
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I 

88

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT Study design

Chatoor,

1998

99026462

Country: US

Setting: Outpatient

Gp1* Gp2† Ctrl

Age(mo) 21.4 23.7 22.5

 range (12-37) (13-37) (13-36)

Wt/age ND ND ND

Ht/length ND ND ND

Enrolled 34 34 34

Evaluated 33 34 34

% Male 39 58 44

Race

White 58 58 59

Af-Am 27 27 29

Latino 3 6 6

Asian 15 12 6

* Infantile anorexia, † Picky eaters

Maternal educ: ND

Income: 

Gp1 Gp2 Ctrl

SES* II II II

† I 41 35 32

II 29 32 44

III 9 26 9

IV 9 3 12

V 12 3 3

Health insur: ND

* Mean Hollingshead Four 

Factor Index rating of SES

† % toddlers in each 

Hollingshead category

Infantile anorexia, 

toddlers who are picky 

eaters

Controls & picky eaters 

matched for age, sex, 

SES ethnicity

Organic cause for 

feeding problems, 

food refusal after 

traumatic 

event/posttraumatic feeding 

disorder, 

gestational age < 

36 wks, psychiatric 

illness, mother with 

medical or mental 

illness that 

compromised 

ability to care for 

child or was 

nonEnglish 

speaking

Infantile anorexia: 

onset 6-36 mo, 

food refusal ≥

1mo, acute and/or 

chronic 

malnutrition, 

parental concern & 

anxiety, conflictual 

feeding interactions

Picky eating: food 

selectivity ≥ 1mo, 

no malnutrition, 

variable parental 

concern

Prospective crosssectional

Wright,

2000

20161504

Country: UK

Setting: Outpatient

FTT Ctrl

Age(mo) 15.1* ND

(7-28) (16-18)

Wt/age -2.00(.93) ND

Ht/length -1.06(.96) ND

Enrolled 120 40

Evaluated 97 28

% Male 54 61

% Nonwhite 9 0

* Median

Maternal educ: ND

Income: ND

FTT* Ctrl l* 

Unemployed

 parent 39 13

Nonhome-

 owner 54.7 53.6

No car 48.3 50

Health insur: National 

healthcare

* Percent

Baseline wt at 6-8 wk & 

2

nd wt at 9-18 mo

Controls from 3 

“generally 

representative” of 

Newcastle

2

nd twin sibling Weight decline of 

1.26 SD from age 

6-8 wks to 2nd

weighing at 9-18 

months

Prospective crosssectional
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I 

89

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT Study design

Kerr,

2000

20277217

Country: US

Setting: Inner-city hospital clinic

Age Mean Ht/

(mo) wt/age length

Gp1* 73.3±1.9 ND ND

Gp2† 74.2±3.2 ND ND

Ctrl1‡ 73.0±1.2 ND ND

Ctrl2§ 73.5±1.9 ND ND

Evaluated % Male % Race||

Gp1 64 56 88

Gp2 28 48 87

Ctrl1 21 53 94

Ctrl2 80 51 97

Mean, * FTT, † FTT & maltreatment, ‡ 

Maltreatment, § Neither, || % African Am

Maternal

educ Income*

Gp1 11.2(1.9) 56

Gp2 10.4(1.7) 81

Ctrl1 11.2(1.4) 65

Ctrl2 11.4(1.9) 62

Health insur: ND

Mean, * percent AFDC

FTT, < 24 mo, wt/age < 

5

th %, gestational age = 

37 wks & appropriate 

birth wt

Ctrl from same site, bet 

ages 3 – 30 mo, wt/age 

> 10th %, gestational 

age = 37 wks & 

appropriate birth wt

Subgroups Gp2 & Ctrl1: 

including hx of 

maltreatment defined as 

at least one report with 

Child Protective 

Services (CPS) by age 

6, including neglect, 

physical abuse, & 

sexual abuse

History of perinatal 

complications, 

congenital 

disorders, chronic 

illness

Wt/age < 5th % by 

NCHS growth 

charts

Ambidirectional 

longitudinal

Assessment at age 

6 y

Steward,

2001

21291243

Country: US

Setting: Outpatient primary care clinic

FTT Ctrl

Age (mo) 9.2 8.6

Wt/age(kg)* 7.14 8.54

Ht/length ND ND

Enrolled 17 16

Evaluated 14 14

% Male 36 36

Race: white 9 9

black 5 5

Mean * p < 0.05

FTT Ctrl

Maternal

 educ* 12.2 12.5

Income: ND

Health insur: ND

* NS for educ & age

Diagnosed FTT, 2-12 

months, birthweight ≥

2500g

Controls matched for 

age, sex, & race –

“growing appropriately”

Absence of disease 

process, pre- or 

post-natal 

complications

Weight for age fallen 

below 5 

percentiles or 

fallen across 2 

major percentiles

Prospective crosssectional
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

90

Author,

Year Correlates & correlate measures Method / Instrument

Associations found

Pollitt,

1976

76109110

FTT Ctrl

Feeding difficulty 10 2

Meal pattern-often 

skipped/skimpy 16 6

Caloric intake 1400(300) 1700(500)

Response to food -

correlation to wt % ND ND

Eating disorder –

FTT 4 exhibiting eating & drinking nonfood items, 

polydipsia, gorging, & hiding food

Ctrl none reported

Autoerotic 2 0

Self harm 2 0

Sum children with

abnormal behavior 10 1

Reported or observed feeding, 

history of other behaviors, 

direct measures

FTT were reported to have significantly more feeding behavior 

problems than controls in difficulty in feeding (χ2 = 5.97, p < .02); 

eating patterns (χ2 = 8.74, p < .03); supported by caloric intake 

measures (t = 2.06, p = .03). FTT had a trend for exhibiting 

autoerotic & self-harm behavior problems; analyzed for sum any of 

these atypical behaviors, the FTT exhibited significant higher 

incidence (χ2 = 8.19, p < .01)

Mitchell,

1980

80166667

Behavior problems FTT Ctrl

3.3% 2.8%

Behavior problems 

questionnaire

NS but FTT group had higher incidence of behavioral problems.

Polan,

1991

92098539

FTT status on positive & negative affect in feeding in 4 

channels of emotion – facial display pattern, vocalization, 

gesture, body posture & movement

Kiddie Affect Inventory and 

Assessment of 11 affects 

scored independently

FTT had significantly decreased positive affect during feeding & 

nonfeeding (t=-2.92, p=.04; t=-3.151, p = .003, respectively) Also 

FTT had significantly increased negative affect during feeding 

(t=2.567, p=.01).

Drotar,

1992

92372721

FTT Ctrl

Personality development

• ego control 376.67(32.28) 413.42(30.73)

• ego resiliency 376.06(41.21) 397.37(41.45)

Behavioral organization .95(1.92) 8.45(12.08)

Behavioral problems 58.5(10.7) 53.2(12.7)

California Child Q-set

Lock box – Rectangular 

container w/10 locked 

compartments

Child Behavior Checklist

FTT children have poor problem-solving, behavior problems, & 

“deficiencies in personality development” versus controls. The ego 

development score was lower, ego resiliency score was significantly 

lower (p<.05). FTT behavior organization & problem scores were 

significant lower (p<.001, p<.05, respectively)
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

91

Author,

Year Correlates & correlate measures Method / Instrument

Associations found

Hutcheson, 

1993

94015754

Child temperament FTT1* FTT2† Ctrl1* Ctrl 2†

0.48 0.49 0.06 -0.19

* Infants: 8 – 13.4 mo

† Toddlers: 13.5 – 24 mo

Infant Characteristics 

Questionnaire

The FTT cases rated as more difficult with significant finding on effect of 

infant age on maternal report of infant level of difficulty (F=4.21, p = 

0.04). Though no age or group differences found on perceived life 

stresses, parenting stresses, informal support, and negative 

affectivity, the FTT infants had fewer life events than FTT toddlers, 

whereas the reverse was true for the comparison group. The 

maternal effect was less positive toward FTT toddlers than FTT 

infants. Controlling for maternal education, wt for age, & ht for age -

significant group by age interaction for maternal factors (F=4.98, p = 

0.02) due to maternal affective tone (F=9.33, p = 0.005)

Behavioral disorder FTT Ctrl

Age(m) 12 73.0 73.6 Bates Temperament scale

Kelleher, 

1993

93234174 24 9.4 8.9 CBCL

Sample of LBW or premature infants followed had lower HOME scores 

at 12 months, NS. There was a trend towards more behavioral 

problems for the FTT as reported by parents. 

Skuse,

1994 

94253258

Behavior Assessment at 15 mo TRIB No difference between groups for expression of positive affect in 

relation to task directed behavior or task persistence

Puckering,

1995

95378341

Behavior score FTT Ctrl

8.7(4.4) 6.9(3.5)

Behavior Screening 

Questionnaire (BSQ)

There was no difference in BSQ scores for the two groups (p=.2). 

MANOVA performed on calculated mean GCI & BSQ scores vs. 

unconditional & conditional interactions grouped by high or low 

(above & below overall mean value for interaction) – results indicate 

that parenting style does not account for GCI or BSQ differences 

between FTT & Ctrl.

Corbett,

1996

97113595

Behavioral disorder FTT Ctrl

Parental reporting 33 34

Teacher reporting 23 14

Median

CBCL There was a trend towards more behavioral problems for the FTT as 

reported by teachers (NS, p = .296)
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

92

Author,

Year Correlates & correlate measures Method / Instrument

Associations found

Wilensky, 

1996

97022837

Feeding problems FTT Ctrl

• showing hunger 53.4% 46.2%

• turns head from food 59.7% 20.7%

• shows pleasure at meals 76.7% 94.3%

• nervous at meals 23.2% 5.6%

• eats variety 48.8% 69.8%

• spits out food 65.1% 33.9%

Maternal questionnaire FTT children had significantly more feeding problems than the controls 

(p < .05)

Chatoor,

1998

99026462

Gp1 Gp2 Ctrl

Attachment classification

Secure 20 30 28

Avoidant 4 3 3

Resistant 7 1 3

Disorganized 2 0 0

Attachment security

scale rating 4.9(2.1) 6.1(1.3) 6.0(1.5)

 Percent ideal weight

Ainsworth & Cassidy & Marvin 

attachment classification

Strange Situation Security 

Scale / 9 point Likert 

There was significant relationship between diagnostic group and 

frequency of insecure attachments (χ2 = 8.0, p < .05). Infant 

anorexia group exhibited more frequent insecure relationships 

compared to picky eater or healthy eater groups (χ2 = 6.7, p < .01; 

χ2 = 3.9, p < .05). There was main effect for group for Attachment 

security scale (F = 5.8, p < .01) with the infantile anorexia group as 

least secure. The closer to ideal weight was correlated to increased 

security (r = 0.31, p < .01).

Behavior & temperament

FTT Ctrl

Sociable 47 26

Average 17 2

Shy 12 0

Wright,

2000

20161504

Demanding 18 13

Average 48 15

Undemanding 11 0

Parental reporting / Likert scale FTT had higher maternal reporting of infants as undemanding & shy in 

temperament (p = .005 & p = .002, respectively). Higher maternal 

reporting of infancy feeding problems, variable eating pattern.

Gp1 Gp2 Ctrl1 Ctrl2

Adaptive functioning 15.85 13.88 16.92 17.85

at school (7.2) (6.9) (6.9) (9.7)

Teacher Report Form (↑

numbers = better score)

Kerr,

2000

20277217

School behavior 31.45 53.53 29.18 28.87

(27.1) (35.7) (25.0) (29.1)

Teacher Report Form (↓

numbers = better score)

There is main effect from risk status (FTT, FTT & maltreatment, 

maltreatment alone) as being associated with worse scores in 

cognitive & adaptive performance (F = 3.527, p < .01), school & 

home behavior (F = 2.986, p < .01; F = 2.453, p < .05, 

respectively). There was a trend for worse scores in all areas for 

FTT vs. no risks factors or maltreatment alone.
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

93

Author,

Year Correlates & correlate measures Method / Instrument

Associations found

Home behavior 28.11 34.85 29.00 26.67

(22.8) (21.2) (20.5) (18.4)

Child Behavior Checklist (↓

numbers = better score)

Steward,

2001

21291243

FTT Ctrl

Communication 3.19 4.07

Mood effect 3.65 4.26

PCERA subscale FTT group scored significantly lower on the communication subscale 

(p < 0.02); during interactions with the mother had less visual 

contact, more gaze aversion & vocalized less than controls, had 

difficult to read cues. They also scored lower than controls on the 

mood scale, were more irritable & apathetic (p < 0.05).
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part III

94

Author,

Year Potential biases Comments

Pollitt,

1976

76109110

4 cases with FTT hx within ht 3rd & 10th percentiles included in study Government & privately funded

Mitchell,

1980

80166667

Physical exams & growth status by PI not blinded Government & privately funded

Polan,

1991

92098539

37% of mothers of normal growth children refused study or failed to appear for 1st

appointment, no FTT mothers refused study; randomly selected subset of 107 

who completed video lab observation session; acute and chronic conditions in 

sample, 6 organic FTT based on Woolston score

FTT subgroup analyses no difference in sex, mother’s marital status, family 

income, but organic FTT significantly younger at 10.8 mo vs. 18.3 for NOFTT, 

p = 0.016. NS for degree of acute or chronic malnutrition and positive or 

negative affect in feeding & nonfeeding activities; government & privately 

funded

Drotar, 

1992

92372721

--- No difference for attrition group vs group evaluated, index gp hospitalized avg 14 

d for dx & nutritional intervention; government funded

Hutcheson, 

1993

94015754

76% of index group met both criteria for NOFTT (wt for age, & ht for age), 24% 

met one criterion; unknown n for age by group comparisons

Government & privately funded

Kelleher, 

1993

93234174

Of 985 enrolled, 71 LTF, 12%(20) OFTT, 16%(28) were both OFTT & NOFTT 21% of babies develop FTT by 36 wks; ND on funding source

Skuse,

1994 

94253258

2 cases & 3 controls didn’t complete assessments & were excluded from analyses, 

1 case had microcephaly, hypotonia, & an action tremor or ataxia of unknown 

origin

Researchers blinded to patient’s status in measures except anthropometry; 

privately funded
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part III

95

Author,

Year Potential biases Comments

Puckering,

1995

95378341

--- Other than clinic anthropometric measures, home visits by assessors blinded to 

child’s group status; The FTT children were significantly smaller than the 

controls; government funded

Corbett,

1996

97113595

3 from each group refused consent at follow-up, LTF or moved - 2 cases, 3 

controls, 1 case not originally studied participated for follow-up study, 4 of 

those cases were the slowest growing 5% - also removed from home, all 

controls stayed with parents. Edward’s diagnostic criteria for growth measure 

considered limited.

Additional aubgroup analyses for FTT cases showed significant association 

between full-scale IQ and cases with lowest Thrive Index values, p = 0.03; 

ND on funding source

Wilensky, 

1996

97022837

Feeding behaviors and HOME environment are causal factors given time 

dissociation as FTT was established at 15 months, where as, maternal 

interview/home assessment at 25 months

2/5th of infants diagnosed as FTT no longer fit the criteria at 20-month follow-up, 

yet had positive association on Bayley MDI. Reported associations for FTT 

without specific data: paternal age (p<.01), maternal education, & behavioral 

observations of lower sociability (p<.05) & fear of examiner (p<.05); ND on 

funding source

Chatoor,

1998

99026462

1 infant anorexia withdrew because mother became ill Testers blinded to child’s status; poor discussion of SES markers, no quantification 

of malnutrition, no demonstration of equivalency of control groups; government 

funded

Wright,

2000

20161504

Of 120 cases, 23 recovered above screening threshold & had no subsequent 

data, 21 families received social work input of which, 4 cases registered at risk 

of abuse or neglect, 17 cases had “relevant organic conditions”...but only 4 

said to be main explanation for their FTT”, age difference between groups

Government & privately funded

Kerr,

2000

20277217

Hx of maltreatment not part of original recruitment criteria; unknown number of 

original sample, also in Mackner 1997 sample (n=177) is reported to be a 

subsample; maltreatment group may not include all because of definition of a 

CPS report filed

At 6 year, most FTT children had recovered & 3% had weight for height < 5th

percentile; government funded

Steward,

2001

21291243

Withdraws include: mother changed mind, not available for home visit, opposition 

of mother’s significant other (numbers of each not given)

Majority of single mothers, difference in birthwt – FTT, 2822 g vs. controls, 3344 g 

(p < 0.013); government & privately funded
Evidence Table 5. Studies associating behavioral problems with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part III

96
Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT Study design

Galler,

1983b

83136863

Country: Barbados

Setting-Outpatient

Age(y): 5-11

Gp Ctrl

Wt/age ND ND

Ht/length ND ND

Enrolled 141 129

Evaluated 129 129

% Male 60 ND

Race: 100% Black

Maternal educ: ND, 

universal education, 95% 

 population literate

Income: lower for cases 

compared to controls

Health insur: ND

Discharged 5 – 11 y 

olds w/dx at age 1 y 

with PEM Grade II-III, 

BW > 5 lbs

Controls without PEM, 

matched for age, 

gender, handedness, & 

same school / 

neighborhood

Pre- or peri-natal 

complications, 

edema, seizures, 

head trauma, loss of 

consciousness, high 

fever

Gomez Scale PEM: 

Grade II- 61-75% 

or Grade III- ≤

60% standard wt 

for age on 

Harvard Standard 

Scale

Ambidirectional 

longitudinal

Fwup 4 – 10 y 

after D/C

Evidence Table 6. Studies associating behavioral problems with malnourished patients compared to healthy control subjects in 

developing country

Part II

Author,

Year Correlates & correlate measures Method / Instrument Associations found Potential biases Comments

Galler,

1983b

83136863

Classroom behavior –

Gp status by

Factor 1-attention deficit

Factor 2-social interaction

Factor 3-physical appearance

Study specific teacher 

questionnaire

From ages 5-11, The index group’s behavioral 

development was lower than the comparison 

group. Early PEM is associated with increased 

problems in attention, deficit, social interaction, & 

physical appearance.

Signf for –

Factor 1 Factor 2 Factor 3

Gp status F = 37.2 F = 8.3 F = 14.3

p ≤ .001 p ≤ .05 p ≤ .001

Gp vs. Ctrl t = 5.5 t =4.1 t = 3.1

p ≤ .01 p ≤ .01 p ≤ .01

Withdraws/nonparticipation – 4 

refused consent, 7 

LTF, 1 cerebral 

palsy; severe PEM

Private & hospital 

funded
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part I

97

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Mitchell,

1980

80166667

Country: US

Setting: Outpatient clinic

FTT Ctrl

Age(y) 2-5 2-5

Wt/age ND ND

Ht/length ND ND

Enrolled : cohort of 312(323)*

Evaluated 30 282

% Male 36.7 51.8

% Black 70 70

* See Potential biases column

Maternal educ: ND

Income: ND

Health insur: 

FTT-53% Medicaid

Ctrl-49% Medicaid

See Definition of FTT

Controls: wt = 80% of nl, 

matched for age, sex, 

mother’s age/ marital 

status & family problems

Organic cause of 

FTT, single 

anomalous low wt 

recorded, clinic 

registration by 

age 6 mo, < 3 

visits

Wt for age < 80% of 

nl up to age 24 

mo 

Ambidirectional 

longitudinal

1 fwup at age 3 –

6 y

Hack,

1982

82227864

Country: US

Setting-Recruitment: Hospital

Follow-up: hospital/clinic

Gp1* Gp2†

Mean age‡ 32(2.8) 29(1.9)

Wt/age(g) 1141(285) 1197(206)

Length(cm) 37.9(3.8) 38(2.7)

Enrolled|| ND ND

Evaluated 38 154

% Male 47 47

% Black 52 63

* SGA, † AGA, ‡ wks gestation, || n = 204

Gp1 Gp2

Maternal

 educ <HS 12 32

Income* 28 99

Health insur ND ND

* Hollingshead Social Class 4 & 5

VLBW, < 1500g, divided 

into two groups: SGA < 

2 SD or AGA

ND Wt < 2 SD below 

mean for age @ 

term and/or @ 8 

mo of age

Prospective 

longitudinal

Assessments at 

age 40 wk & 8 

m
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part I

98

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Singer,

1984

85057547

Country: US

Setting-Recruitment: hospital

 Follow-up: ND

NOFTT OFTT Ctrl

GA(wk)* 39(1.8) 37(3.5) 38(1.8)

 range 36-40 28-40 36-40

PA(wk)† 30(7.0) 30(7.5) 30(10.1)

 range 20-44 21-44 20-44

Birth wt 2847 2378 3027

Enrolled 13 13 13

Eval‡ 11 11 11

Age: 20.6 mo

% Male: ND

Race: ND

Mean (SD), * gestational age, † postnatal 

age, ‡ 20 mo follow -up 

NOFTT OFTT

Ctrl

Maternal 12.5 11.4 12.5

 educ* (1.4) (1.4) (12.5)

Income: ND

Health insur: ND

* At evaluation

NOFTT-unknown organic 

cause of condition, 

absence of wt gain 

during or shortly after 

hospitalization

NFTT-documented 

organic cause of 

condition

Controls -“not FTT”

ND ND Prospective 

longitudinal

Assessments at 

age 8 mo, 20 

mo, 3 y

Haynes,

1984

84233543

Country: US

Setting: In & Out-patient

Age: ND

Wt/age: ND

Ht/length: ND

FTT1* FTT2† Ctrl

Enrolled/Eval 25 25 25

% Sp-Am? 44 44 44

 Sp-Am? 40 52 52

 White? 36 44 36

 White? 36 24 28

 Black? 20 12 20

 Black? 24 24 20

% Male: ND

* std care & lay health visitor intervention, 

† std care only

FTT1 FTT2 Ctrl

Maternal

 educ 10 11 10

Income* 379 372 362

(0-750) (0-950) (0-

1100)

Health insur: ND

* @ mo

Consecutive admissions 

for NOFTT

Controls - thriving nonhospitalized patients 

matched for age, sex, 

birth wt, & mother’s age, 

ethnicity, number of 

living children

ND < 5 percentile or 

significant decline 

from birth wt 

percentiles

Prospective 

longitudinal

1 assessment 6 

mo after intake
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part I

99

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Drotar,

1992

92372721

Country: US

Setting: Inpatient with outpatient 

 follow-up

FTT Ctrl

Mean age* 4.92(2.81) 5.05(2.85)

Wt/age ND ND

Ht/length ND ND

Enrolled 68 68

Evaluated 48 47

% Male 71 57

Race: Black 29(60%) 35(74%)

White 29(40%) 12(26%)

* Age in months, at intake 

FTT Ctrl

Maternal 10.94 11.51

 educ (1.74) (1.57)

Income 5446 7792

(5561) (10309)

Health

 insur ND ND

Mean (SD)

Hospitalized for NOFT 

with nutritional 

intervention, age 1 – 9 

months

Controls matched for age 

at intake, sex, race, 

birth order, gestational 

age, maternal educ & 

age, family income & 

size

Physical abuse, 

residence > 1 hr 

from hospital, bw < 

1500 gm

Wt < 5th percentile 

based on NCHS, 

absence of 

disease, wt gain in 

hospital, poor wt 

velocity

Prospective 

longitudinal

1 fwup at age 42-

48 mo

Kelleher, 

1993

93234174

Country: US

Setting: Primary care clinic

FTT Ctrl

GA(wk)* 33.0 33.1

Wt(g)* 1679 1845

Enrolled: 842*

Evaluated 180 591

% Male 52.2 47.9

Race: % Black 50 53.8

* At birth

FTT Ctrl

Maternal educ* -

 <HS 40.6 38.1

 HS 30.0 29.3

 Some col 14.4 20.8

 ≥col grad 15.0 11.8

Income –

 <10K 38.6 34.5

 10-20K 19.9 23.9

 >20K 38.1 37.4

Health insur ND ND

* % HS graduate

Gestation age ≤ 37 wks, 

birth wt ≤ 2500 g, FTT

Controls matched for –

birth wt +/- 250 g, 

maternal education, 

maternal race, & infant 

sex

Live outside 

catchment area, 

D/C outside 

recruitment period, 

D/C or died within 

48 hr, hospitalized 

> 60 d, oxygen 

support > 90 d, 

twin, triplet or 

quadruplet of 

ineligible child, 

maternal drug/ 

alcohol abuse, 

insufficient Eng 

skills, psychiatric 

hospitalization

< 5th percentile for 

gestation corrected 

age based on 

NCHS, growth 

status on “wt curve 

below that 

recorded at last 

regular 

assessment visit.”

Prospective 

longitudinal

Fwup at ages 12, 

24, 36 mo
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part I

100

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Skuse,

1994

94253258

Country: UK

Setting: Outpatient

FTT Ctrl

Age(mo)* 14.6(1.4) 14.2(1.4)

Wt/age† -2.07(.44) .10(.96)

Ht/length† -1.27(.94) .18(.73)

Enrolled 49 50

Evaluated 47 47

% Male 49 49

% Non-white 43 34

* Mean (SD), † z score, p < .001

Maternal educ: ND

Income:

 Income/welfare supportFTT 16, Ctrl 11

Health insur: National 

healthcare

District-centered until 12 

mo of age, singleton 

deliveries of 38-41 wks 

gestation

Controls matched for sex, 

age, ethnic origin, bw 

within 300 g, ordinal 

position, SES

≤ 3rd centile, no wt 

data 

Wt for age ≥ -1.88 

by 12 mo of age 

& sustained 3 mo 

(based on 

NCHS)

Prospective 

longitudinal

Assessments at 

age 15 mo & 4 

y

Reif,

1995

95362505

Country: Israel

Setting: Outpatient fwup

FTT Ctrl

Mean age(y)* 6.2 6.8

Wt/age* 18.05 36.15

Ht/length* 21 33.55

Enrolled 86 65

Evaluated 61 65

% Male 52.5 54

Race:

 Sephardic 38 36

 Ashkenazi 23 29

* At re-evaluation

FTT Ctrl

Maternal 12.27 12.14

 educ* (0.29) (0.24)

Income ND ND

Health insur: Socialized 

medicine 

* Mean (SD)

FTT, < 2 yrs, term infants 

> 2500g birth wt

Controls matched for age, 

sex, social class, & 

ethnic affiliation; admitted 

or evaluated in ER for 

intercurrent & nonsign 

disease

Organic cause of 

FTT, malnutrition, 

serious perinatal 

morbidity

Ht & wt < 5% in ≥ 2 

measurements 

within 6 mo on 

Hamill PVV, 

Drizd TA growth 

chart,

Ambidirectional 

longitudinal

Re-evaluation at 

mean 5.12 y
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part I

101

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Puckering,

1995

95378341

Country: UK

Setting: Outpatient

FTT Ctrl

Age(mo) 48.9(1.8) 48.2(0.8)

Wt/age(SDS)* -2.01(0.6) -0.32(1.1)

Ht/length(SDS)* -2.24(0.5) -0.6(0.9)

Enrolled/Eval 23 23

% Male 48 48

Race: 100% White

* based on NCHS, p < .001

FTT Ctrl

Maternal 15.6 15.6

 educ* (1.4) (1.4)

Income† 11 7

48% 30%

Health insur: Socialized 

medicine

* Age leaving full-time education

† Income support/welfare

From inner city population 

sample - Caucasian born 

in 1980 with growth data 

from birth to 4 years

Controls matched for sex, 

gestational age ≥ 38 

wks, ethnic origin

Prematurity, 

congenital defects/ 

diseases affecting 

growth, no 

perinatal insults

Ht & wt < 10% 

based on standard 

British growth 

charts (Tanner & 

Whitehouse)

Ambidirectional 

cross-sectional

Corbett,

1996

97113595

Country: UK

Setting: Clinic

Age at follow-up: 6-7 y

FTT Ctrl

Wt/age ND ND

Ht/length ND ND

Enrolled 52 52

Evaluated 48 46

% Male: ND

Race: 100% White

Maternal educ: ND

Income: “...most economically 

deprived wards in 

Newcastle”

Health insur: National 

healthcare

Full term singleton with 

records of 6 or more 

weights over first 18 

months age

Consecutive controls 

matched for age & sex

Non-Caucasian, 

“poor growth 

resulting from 

major organic 

disease”

Weight deviated 

downward from 

maximal centile 

achieved at 4-8 

wks, across ≥ 2 

centile lines, & 

remained at level 

≥ 2 measurements 

≥ 1 mo – chart 

based on Tanner 

& Whitehouse

Ambidirectional 

longitudinal

5 year follow-up 

of cases
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part I

102

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Wilensky, 

1996

97022837

Country: Israel

Setting: Community pediatric clinic

FTT Ctrl

Mean age(m)* 20 20

Wt/age ND ND

Ht/length ND ND

Enrolled† 55 1352

Evaluated 50 50

% Male ND ND

Race: ND; Maternal country of birth: 

 68% Israel, 25% Europe/America, 

 5% N Africa, 2% Asia

* At assessment

FTT Ctrl

Maternal 13.8 13.4

 educ* (1.62) (1.44)

Income: AFDC 76%

Health insur: ND

* Mean (SD), based on record 

review of potential subjects

FTT infants by review of 

records who have 

reached 15 months 

born in 1991

Controls from same health 

clinic matched for birth 

month, maternal educ, 

maternal age, parity,

and infants’ birth wt

Birth wt < 2500 gm, 

< 37 weeks, wt/ht 

ratio > 10 %, 

organic cause of 

FTT

Wt < 3% by NCHS 

for = 3 months 

prior to age 15 

months

Ambidirectional 

cross-sectional

Mackner,a

1997

97381196

Country: US

Setting: Inner-city hospital prenatal 

clinic

Age* Mean Ht/ Enrolled

(mo) wt/age lngth /Eval

Gp1† 14±5.3 <5% ND 27

Gp2‡ 14±5.6 <5% ND 70

Ctrl1§ 16±5.9 >10% ND 23

Ctrl2|| 18±6.9 >10% ND 57

% Male: 58

Race: 94.4 % African American

5.6 % White

* p < 0.001, † FTT & neglect, ‡ FTT only, 

§ Neglect only, || Neither

 Maternal* Health

 educ Income† insur‡

Gp1 10.58 70 89

Gp2 11.09 68 78

Ctrl1 11.04 74 82

Ctrl2 11.72 81 89

* p < 0.05, † percent AFDC,

‡ percent Medicaid

Original criteria: FTT, , 24 

mo, wt/age < 5th %, 

gestational age = 37 

wks & appropriate birth 

wt

Controls from same site, 

bet ages 3 – 30 mo, 

wt/age > 10th %, 

gestational age = 37 

wks & appropriate birth 

wt

Neglect defined = 33rd % 

& normal > 50th % by 

HOME scale

History of perinatal 

complications, 

congenital 

disorders, 

chronic illness

Wt/age < 5th % by 

NCHS growth 

charts

Ambidirectional 

cross-sectional
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part I

103

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study design

Drewett,

1999

99284054

Country: UK

Setting: Clinic / home visits

FTT Ctrl

Age(y) 8.12(0.62) 8.10(0.57)

Wt(kg)* 23.8 27.9

BMI* 14.9 16.3

Enrolled 136 136

Evaluated† 107/111 117/122

% Male‡ 40 38

%White‡ 91 91

* Median, † Psychological / anthropometric 

evaluation, ‡ FTT = 107, Ctrl = 117

FTT Ctrl

Maternal 72 66

 educ*

Income: NA

Health insur: National 

healthcare

* % left school at 16 y

At least 1 wt at age 0-2 

mo & 2 subsequent wts, 

thrive index < 5th centile 

= 2 occasions between 3 

& 18 mo

Controls with at least 1 wt 

at age 0–2 mo & 2 

subsequent wts, no 

thrive index < 10th

centile, age ± 1 mo, 

similar/same residential 

area or GP practice

ND Lowest 5% for 

change of SD 

score; avg taken 

of SD scores for 

all wt bet 0-2 mo, 

expected wt from 

3-18 mo 

calculated for 

“thrive index”

Ambidirectional 

longitudinal

Five years from 

enrollment of 1 

y old cases

Kerr,a

2000

20277217

Country: US

Setting: Inner-city hospital clinic

Age Mean Ht/

(mo) wt/age lngth

Gp1* 73.3±1.9 ND ND

Gp2† 74.2±3.2 ND ND

Ctrl1‡ 73.0±1.2 ND ND

Ctrl2§ 73.5±1.9 ND ND

Evaluated % Male % Race||

Gp1 64 56 88

Gp2 28 48 87

Ctrl1 21 53 94

Ctrl2 80 51 97

Mean, * FTT, † FTT & maltreatment, ‡ 

Maltreatment, § Neither, || % African Am

Maternal

educ Income*

Gp1 11.2(1.9) 56

Gp2 10.4(1.7) 81

Ctrl1 11.2(1.4) 65

Ctrl2 11.4(1.9) 62

Health insur: ND

Mean, * percent AFDC

History of FTT & Controls

see Mackner 1997

Subgroups - Gp2 & Ctrl1: 

hx of maltreatment defined 

as at least one report with 

Child Protective Services 

(CPS) by age 6, including 

neglect, physical abuse, & 

sexual abuse

History of perinatal 

complications, 

congenital 

disorders, 

chronic illness

Wt/age < 5th % by 

NCHS growth 

charts

Ambidirectional 

longitudinal

Assessment at 

age 6 y
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part II

104

Author,

Year

Development

measures

Instruments utilized

 & criteria Associations found

Mitchell,

1980

80166667

General cognitive index

FTT Ctrl

87.5 92.5

McCarthy scale Though there was a trend for lower GCI scores for FTT group, there was 

no statistical difference between the two groups.

Gp1Sub* Gp2Sub1† Gp2Sub2‡ Ctrl§

99(18) 89(22) 93(17) 108

Hack, Bayley

1982

82227864 Neurosensory impairment

6(32%) 6(46%) 8(27%) 13(10%)

* SGA-subnormal wt at 40 wk & 8 m (n=19), † AGA-subnormal wt at 

8 m (n=13), ‡ AGA-subnormal wt at 40 wk & 8 m (n=30), § 4 

subgroups - appropriate for age (n=130)

Neurological examine

At 8 months, infants from both groups had similar developmental quotients if 

catch-up growth is achieved. Subnormal wts at 8 months experienced by 

subset of both groups is associated with lower DQ scores (p < .005) and 

higher rate of neurological impairment.

Cognitive & sensorimotor development

8 m 20 m Placed outside Home

assessment assessment home* placement*

NOFTT 77.6(20.5) 80.5 70.2 67.4

OFTT 67.7(13.8) 75.4 90 83.3

Ctrl 120.2(10.7) ND ND ND

* 20 mo assessment, sample size unknown

Bayley MDI/Kent Scoring 

Adaptation

Singer,

1984

85057547

Visual recognition memory (8 m assessment)

NOFTT OFTT Ctrl

68%(9.1) 52.6(8.5) 62.5(9.2)

Recognition memory tasks 

- fixation of familiar vs. 

novel

At initial 8 month assessment, there was main effect of group (F = 23.98, p < 

.001). Both FTT groups showed a significant delay in sensorimotor skills 

compared to control group (F=46.45, p < .001). At 20 months, it was also 

reported that there was a main effect of group (F = 21.3, p < .001). Home 

placement or placement outside the home affected the MDI scores with 

mean MDI home scores higher regardless of group status (87.5 vs. 

68.8).

At 8 month assessment, the OFTT showed a significant delay in visual 

perceptual-cognitive abilities compared to NOFTT vs. controls where 

there were no significant differences (F = 19.88, p < .001).

Haynes,

1984

84233543

Cognitive & motor development

FTT*(%) Ctrl(%)

Intake† ≥ 90 19(38) 21(81)

< 70-89 31(62) 5(19)

Fwup‡ ≥ 90 15(40.5) 17(81)

< 70-89 22(59.5) 4(19)

* intervention & non-intervention combined, † FTT=50 Ctrl=25, ‡ 

FTT=37 Ctrl=21

Bayley Scale of Infant 

Development

There were no differences for the FTT groups after 6 mo for development 

except for a few cases. Approximately 60% FT were developmentally 

delayed or retarded vs. 5 Ctrls as delayed. Intervention, or home vs. 

foster care had no effect.
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part II

105

Author,

Year

Development

measures

Instruments utilized

 & criteria Associations found

Drotar,

1992

92372721

Intelligence quotient

FTT Ctrl

86.3(15.34) 88.74(14.32)

Stanford Binet Intelligence 

Scale

---

Kelleher, 

1993

93234174

FTT Ctrl

Mental 103.7 / 92.6 109.5 / 98.1

Psychomotor 90.9 / 90.1 98.2 / 95.8

age 12 m / age 24 m

Bayley MDI & PDI LBW & premature infants were followed & subjects who developed FTT 

scored significantly lower in cognitive & motor development at 12 and 24 

months (p < 0.005).

Skuse,

1994

94253258

FTT Ctrl

Mental 98.2(19.0) 108.5(14.4)

Psychomotor 96.7(17.3) 103.6(14.4)

Bayley MDI & PDI At 15 months of age, FTT had lower cognitive & motor development scores 

than controls (F = 8.07, p = .007). Model predicted lowering wt up to 6 

months of age to lower MDI & PDI scores at 15 months. Increased oral 

motor score was negative correlated with FTT MDI score (r = -.38, p = 

.008).

Reif,

1995

95362505

FTT Ctrl

Developmental delay 7(11.5%) 0

Learning difficulties 11(18%) 2(3.1%)

Reporting/survey FTT had reported developmental delays and none were for Controls (p < 

.005). Academic performance was lower for the FTT compared to Controls 

(p < .01).

Puckering,

1995

95378341

General cognitive index

FTT Ctrl

77.1(17.6) 97.7(15.2)

McCarthy scale The FTT children had significantly lower DQ scores (t = -3.93, p = .001) & 

had few positive & more negative mother – child interactions than the 

controls. MANOVA performed on calculated mean GCI & BSQ scores vs. 

unconditional & conditional interactions grouped by high or low (above & 

below overall mean value for interaction) – results indicate that parenting 

style does not account for GCI or BSQ differences between FTT & Ctrl.

Corbett,

1996

97113595

Intelligence quotient

FTT Ctrl

83.6(11.5) 87.0(11.9)

WPPSI-R omitting optional 

animal pegs & 

sentences subtests

Though not statistically significant, there was a trend for lower IQ score for 

FTT group with correlation to the severity of FTT (p = .160).
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part II

106

Author,

Year

Development

measures

Instruments utilized

 & criteria Associations found

Wilensky, 

1996

97022837

FTT Ctrl

Mental 99.7 107.2

Bayley MDI At 20 months, the FTT group mental development lagged behind the control 

group (p < .05). In addition, an assessment showed the home 

environment to be less stimulating. 2/5th of infants diagnosed as FTT no 

longer fit the criteria at 20 mo fwup, yet had positive association on 

Bayley MDI.

Mackner,a

1997

97381196

Gp1 Gp2 Ctrl1 Ctrl2

Mental* 85.45 97.38 97.72 100.81

(13.62) (13.79) (12.25 ) (16.4)

* Adjusted score

Bayley MDI Main effect for grouping (F = 4.899, p < .01). The Neglect & FTT group 

scored significantly lower than FTT only or Neglect only group, both of 

which scored lower than the group with neither risk factors in cognitive 

development, (p < .01). Maternal IQ & child age as covariates –significant 

relationship with Bayley MDI, F = 4.90, p < .01

FTT Ctrl

Mean IQ* 87.6(17.4) 90.6(17.1) WISC-III

Drewett,

1999

99284054 Mean Reading† 93.5(162) 94.5(15.6)

* FTT n = 105, Ctrl n = 117

† FTT n = 105, Ctrl n = 116

WORD test

The IQs & reading scores from the FTT to the controls were not significantly 

different, but there was a significant relationship between the child’s IQ & 

their mother’s IQ (β = 0.76 ± 0.06, t = 12.09, p < .0001). Also a significant 

relationship between the child’s reading score & their mother’s IQ (β = 

0.56 ±0.07, t = 8.21 p < .0001). There was a relationship between 

reading scores & FTT cases (n=9) with possible organic causes (β = -

11.91 ±4.49, t = 2.65, p < .01).

Kerr,a

2000

20277217

Gp1 Gp2 Ctrl1 Ctrl2

81.98 77.98 83.58 83.95

(12.8) (13.8) (12.4) (12.5)

WPPSI-R: scores 

standardized score with 

mean of 100 ± 15

In all four outcome measures were consistent for main effect from risk status 

(FTT, FTT & maltreatment, maltreatment alone) as being associated with 

worse scores in cognitive & adaptive performance, school & home 

behavior (F = 2.930, p < .01). In addition, there was a significant difference 

between the FTT & maltreatment group vs. the group with no risk factors for 

cognitive & adaptive development, and school performance (p < .05).
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part III

107

Author,

Year Potential biases Comments

Mitchell,

1980

80166667

Physical exams & growth status by PI not blinded Government & privately funded

Hack,

1982

82227864

8 LTF, 4 incomplete data SGA mothers incr % pregnancy HTN (p < .05) & multiple births (p < .05) than 

AGA, also incr antepartum risk score (p < .005) & greater gestational age (p < 

.005); privately funded

Singer,

1984

85057547

Recognition memory tasks differed based on age; etiology for OFTT includes 

primary neurological disease, methadone addiction, cerebral palsy, congenital 

heart disease, pulmonary stenosis, cyanotic heart disease, polycystic renal 

disease, necrotizing enterocolitis, & Aarskoog syndrome

Government funded

Haynes,

1984

84233543

“...because of scheduling, few admissions were not evaluated”, 2 refused 

participation; 10 Gp1 & 3 Gp2 premature – overall similar from FTT vs. Ctrl; at 

6 mo fwup: for FTT1 & FTT2 each-3 cases refused reevaluation & from1 

dissolution of pair, 1Gp1 died SIDS, 1 Gp2 mother gave up child

Block assignment to Gp1 & Gp2 for hospital convenience & case load 

requirements; government funded

Drotar,

1992

92372721

--- No difference for attrition group vs. group evaluated, index gp hospitalized avg 

14 d for dx & nutritional intervention; government funded

Kelleher, 1993

93234174

Of 985 enrolled, 71 LTF, 12%(20) OFTT, 16%(28) were both OFTT & NOFTT 21% of babies develop FTT by 36 wks; ND on funding source

Skuse,

1994

94253258

2 cases & 3 controls didn’t complete assessments & were excluded from analyses, 

1 case had microcephaly, hypotonia, & an action tremor or ataxia of unknown 

origin

Researchers blinded to patient’s status in measures except anthropometry; 

government & privately funded

Reif,

1995

95362505

25 cases not re-evaluated because not located or refused participation; inpatient 

enrollment of FTT-48 & Ctrl-42; outpatient enrollment of FTT-13 & Ctrl-23(ER)

ND on funding source
Evidence Table 7. Studies associating cognitive & neurological development with Failure to Thrive patients compared to healthy control 

subjects in developed countries

Part III

108

Author,

Year Potential biases Comments

Puckering,

1995

95378341

--- Other than clinic anthropometric measures, home visits by assessors blinded to 

child’s group status; The FTT children were significantly smaller than the 

controls; government funded

Corbett,

1996

97113595

3 from each group refused consent at follow-up, LTF or moved - 2 cases, 3 

controls, 1 case not originally studied participated for follow-up study, 4 of 

those cases were the slowest growing 5% - also removed from home, all 

controls stayed with parents. Edward’s diagnostic criteria for growth measure 

considered limited.

Additional aubgroup analyses for FTT cases showed significant association 

between full-scale IQ and cases with lowest Thrive Index values, p = 0.03; 

ND on funding source.

Wilensky, 1996

97022837

Feeding behaviors and HOME environment are causal factors given time 

dissociation as FTT was established at 15 months, where as, maternal 

interview/home assessment at 25 months.

Reported associations for FTT without specific data: paternal age (p<.01), 

maternal education, & behavioral observations of lower sociability (p<.05) & 

fear of examiner (p<.05); ND on funding source

Mackner,a

1997

97381196

By group sex data not given, unknown whether Bayley tester was blinded to 

subject’s group assignment

Government funded

Drewett,

1999

99284054

Of 136 cases, 1 died, 9 LTF, 15 declined psychological testing, 4 moved; of 136 

controls, 2 were preterm, 5 LTF, 12 declined psychological testing, 14 moved 

& were replaced. 2 FTT cases & 1 control with medical condition affecting 

growth, & 9 FTT cases & 2 controls with possible medical conditions

Testers blinded to child’s status; privately funded

Kerr,a

2000

20277217

Hx of maltreatment not part of original recruitment criteria; unknown number of 

original sample, also in Mackner 1997 sample (n=177) is reported to be a 

subsample; maltreatment group may not include all because of definition of a 

CPS report filed

At 6 year, most FTT children had recovered & 3% had weight for height < 5th

percentile; government funded

a

 Overlapping sample for Mackner 1997 & Kerr 2000.
Evidence Table 8. Studies associating cognitive & neurological development with malnourished patients compared to well-nourished 

control subjects in developing countries 

Part I

109

Author,

Year Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study

design

Bartel,

1978,

1979

78180773

79162492

Country: South Africa

Setting: Outpatient

Age: ND

Wt/age: ND

Ht/length: ND

Enrolled* Eval* Race

Gp 31/30 31/30 Black

Ctrll1 31/30 31/30 Black

Ctrll2 31/30 31/30 Black

Ctrll3† NA/90 NA/90 White

% Male: ND

* Bartel 1978 / Bartel 1979

† reported in Bartel 1979

ND Bk 6 – 12 yr olds 

hospitalized during first 27 

months of life for 

kwashiorkor, 5 – 10 yrs 

prior to commencement of 

study 

Controls close in age, no 

hx of PCM:

 Ctrl1-Siblings close in age

Ctrl2-Yardmates of cases

Ctrl3-High SES Whites

Neurological 

involvement, brain 

damage, fits, birth 

trauma, hospital 

coma, 

hypoglycemia

Wellcome criteria for 

kwashiorkor: <3rd

percentile, 

edematous, and 

dermatitis and/or 

nutritional hair 

changes

Ambidirectional 

longitudinal

Assessment at 4 –

12 y after 

hospitalization

Evans,

1980

81008912

Country: South Africa

Setting: Outpatient clinic

Wt/age: See Cognitive development 

measures column

Ht/length: See Cognitive development 

measures column

Gp1 Ctrl1 Gp2 Ctrl2

Mean 8.9 10.7 13 12

 age(SD) (0.5) (1.0) (1.9) (2.1)

Enrolled 14 14 14 14

Evaluated 14 13 14 13

% Male 64 54 100 77

Race: “Cape coloured”

ND Gp1 – newborns of families 

with hx of undernutrition

Ctrl1 – siblings with hx of 

undernourishment, 

record of `< 3rd percentile 

for ht & wt

Gp2 – at least 1 

hospitalization for 

kwashiorkor

Ctrl2 – siblings closet in age 

Gp2 w/no hx of 

kwashiorkor but 

underweight

ND ND Prospective 

longitudinal

Fwup 6 1⁄2 y after 

intervention
Evidence Table 8. Studies associating cognitive & neurological development with malnourished patients compared to well-nourished 

control subjects in developing countries 

Part I

110

Author,

Year Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study

design

Galler, 

1983a,

1985b

83136873

85241833

Country: Barbados

Setting: Outpatient

Age(y): 5-11 (1983)

9-15 (1985)

Gp Ctrl

Wt/age ND ND

Ht/length ND ND

Enrolled 141 129

Eval 1983a 129 129

1985b 109 107

% Male 1983a 60 ND

1985b 58 60

Race: 100% Black

Maternal educ: Universal 

education, 95% 

population literate

Income: lower for cases 

compared to Ctrl

Health insur: ND

5 – 11 yr olds with hx at 

age 1 yr of hospitalization 

for PEM Grade II-III, BW 

> 5 lbs

Controls without PEM, 

matched for age, gender, 

handedness, & same 

school / neighborhood

Pre- or peri-natal 

complications, 

edema, seizures, 

head trauma, loss of 

consciousness, high 

fever

Gomez Scale PEM: 

Grade II- 61-75% 

or Grade III- ≤

60% standard wt 

for age on 

Harvard Standard 

Scale

Ambidirectional 

longitudinal

Fwup 4 – 10 y 

after D/C

GranthamMcGregor, 

1987, 1978, 

1980, 1982,

1983

87117313

79086701

81051042

82236679

83246270

Country: Jamaica

Setting-Recruitment: hospital

Follow-up: hospital & home

Gp1* Gp2† Ctrl†

Age(m) 12.8 13.4 12.2

(2.9) (4.5) (4.4)

Ht/age‡ 89.0 88.4 101.3

(4.5) (4.4) (3.5)

HC/age‡ 91.3 91.2 99.0

(3.7 (3.3) (3.8)

Wt/ht‡ 74.9 72.4 89.0

(9.2) (10.2) (10.1)

Enrolled 21 18 21

Evaluated 18 16 20

% Male 67 38 60

Race: ND, assumed Black

Mean (SD) for evaluated cases;

* Intervention, † Standard care, ‡ % of 

expected value

Maternal educ: HS not 

completed

Income: housing ‘below 

certain defined 

standards’

Health insur: ND

Maternal

PPVT

Gp1 62.3(14.7)

Gp2 59.7(15)

Ctrl 67.4(9.3)

PEM, age 6 – 24 mo, 

attempt for SES of 

mothers who had not 

completed secondary 

education, substandard 

housing, residence in city 

of Kingston

Controls, included above 

criteria but adequately 

nourished, hospitalized 

with diseases other than 

malnutrition

Physical handicap, 

disease that might 

affect mental 

development 

(other than 

malnutrition)

Severe PEM based 

on Wellcome 

classification

Prospective 

longitudinal

6 fwups from 6 to 

72 m after D/C
Evidence Table 8. Studies associating cognitive & neurological development with malnourished patients compared to well-nourished 

control subjects in developing countries 

Part I

111

Author,

Year Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study

design

Agarwal,

1992

92372206

Country: India

Setting: Outpatient

Age: NA

Wt/age: ND

Ht/age: ND

Enrolled: 650

GpI* Gp2† Ctrl

Evaluated: 245 324 64

% Male: ND

Race: ND (assumed Indians)

* Grade I, † Grade II/III

Maternal educ: < 4% > 

grade school, 31.9% 

overall women’s literacy

Income: 40% household 

per capita < Rs.60 p.m.

Health insur: ND

Newborns between 

11/1981 – 31983; see 

Definition of malnutrition

Controls > 80% of 50th % 

wt for age,

ND Malnutrition based on 

NCHS 50th centile 

wt for age as 

reference pt: wt ≥

80% of 50

th% = 

normal, Grade I < 

80-70%, Grade II < 

70-60%, Grade III 

< 60%

Prospective

longitudinal

Assessments at 

age 18, 24, 30, 

36 m

Drewett,

2001

21174599

Country: Ethiopia

Setting: Outpatient

Gp1* Gp2† Ctrl

Age‡ ND ND ND

Wt§ ? 8.3(1.6) 8.9(1.0) 10.4(1.0)

? 8.5(1.1) 9.4(1.0) 10.6(1.1)

Lngth§? 72.6 75.2 79.6

(5.0) (4.4) (3.2)

? 74.9 76.2 80.4

(2.5) (3.6) (3.9)

Enrolled 27 70 100

Evaluated 27 70 100

% Male 33 70 55

Race: ND

* Early growth faltering, † Late growth 

faltering, ‡ criteria < 16 d, § age 2 y, (SD), wt 

in kg, length in cm

Maternal In- Health

educ* come† insur

Gp1 37 37 ND

Gp2 51 41 ND

Ctrl 41 35 ND

* % > 3 y, † % > 2 key 

possessions

All subjects: < 2 y on Nov 

1, 1994, recorded initial (< 

16 d) wt ≥ 2500 g, 

recorded 7th visit (alive at 

1 yr)

Gp1: wt < 3rd centile at visits 

2 or 3(2 & 4 mo)

Gp2: wt < 3rd centile at visits 

6 or 7(10 & 12 mo), & 

not visits 2 or 3

Control: wt ≥ 3rd centile at 

visit 2, 3, 6, & 7

ND Centiles based on 

NCHS

Ambidirectional 

longitudinal

Assessment at age 

2 y (22-24 m)

See Comments 

section
Evidence table 8. Studies associating cognitive & neurological development with malnourished patients compared to well-nourished 

control subjects in developing countries

Part II

112

Author,

Year

Development

measures Instrument

Associations found

Psychomotor development

Gp Ctrl1 Ctrl2

 Motor development 80.73 91.16 82.55

LOMDS

 Grip strength* 14.80 16.59 15.15

(5.24) (6.22) (5.41)

Smedley hand dynamometer

Bartel,

1978, 1979

78180773

79162492

 Finger-tapping / 34.47 37.25 35.21

 fine motor speed* (6.35) (8.22) (5.17)

Mean(SD), * Dominant hand scores

Reitan Indiana & Halstead 

neuropsychological test batteries

There were no significant difference (F=1.50) between the children 

with history of kwashiorkor, siblings, & yardmates on motor skills 

except for intergroup comparisons for 2 of 93 items tested of 

LOMDS. The groups did not differ significantly on grip strength 

(F=1.45) or finger tapping tests (F=1.43).

Evans,

1980

81008912

Gp1 Ctrl1 Gp2 Ctrl2

Full scale 82.0 71.9 70.0 72.0

(13.0) (12.5) (13.5) (14.6)

Verbal 81.3 70.6 74.3 75.0

(13.0) (13.3) (16.1) (17.3)

Performance 86.3 80.5 71.3 74.4

(10.4) (11.2) (8.8) (9.2)

mean(SD)

New S. African Individual 

Intelligence scale

Bender-Gestalt test/Koppitz 

scoring

6-7 years after early infant supplements, the Gp1 full scale intelligence 

score was significantly higher than Ctrl1 (older siblings), p < .05; or

Gp2 (kwashiorkor), p < .01; or Ctrl2 (siblings of kwashiorkor), p < 

.05. There were higher trends for verbal & performance scores with 

Gp1 verbal score higher than Ctrl1, p < 05; and Gp 1 higher than 

Gp2, p < .05; or Ctrl2, p < .01. Bender-Gestalt test reported NS 

findings.

Gp? Ctrl? Gp ? Ctrl?

Full scale IQ 91.3 100.1 90.5 107.7

(14.3) (13.0) (16.7) (12.1)

Galler, 1983a, WISC

1985b

83136873

85241833 Motor coordination deficiency –

8-10 yr 11-13 yr 14-15 yr

 Dominant hand performance

Gp 11.24(2.22) 13.1(2.38) 12.81(2.07)

Ctrl 12.41(0.94) 13.53(1.72) 12.73(2.02)

 Assembly tests

Gp 23.94(4.08) 29.40(4.51) 30.27(5.66)

Ctrl 23.00(4.21) 26.77(6.00) 29.81(7.21)

Purdue pegboard tasks, NeumanKeuls

1983 - From ages 5-11, the index group scored significantly lower 

than the controls by sex, p < .05; the mean score for the index group 

was 12 points lower than the controls. There was no effect on Full IQ 

by sex, age, or SES.

1985 - At ages 9-14The index group had statistically significant deficits 

in fine motor coordination of the dominant hand compared to controls 

(F = 2.85 , p < .05) with significant effect by age (F = 6.3, p < .001).
Evidence table 8. Studies associating cognitive & neurological development with malnourished patients compared to well-nourished 

control subjects in developing countries

Part II

113

Author,

Year

Development

measures Instrument

Associations found

Gp1 Gp2 Ctrl

DQ at D/C 86(12.7) 77(12.0) 98(14.8)

DQ at 6 m 96(11.3) 82(12.1) 105(11.2)

DQ at 60 m 86.1(8.2) 78.1(9.7) 93.2(11.2)

Griffith’s Mental Development 

Scales for Babies and Young 

Children including subscales –

hand & eye coord, hearing & 

speech, performance, practical 

reasoning, & locomotor

PPVT at 36 m 26.9(10.6) 18.3(7.5) 26.2(12.2) Peabody Picture Vocabulary Test

GranthamMcGregor, 

1987, 1978, 

1980, 1982, 

1983

87117313

79086701

81051042

82236679

83246270

IQ at 60 m 71.5(8.7) 63.3(7.8) 75.2(10.5) Stanford-Binet Test

Development assessment taken at D/C, 6, 12, 18, 24 months, and 

annual thereafter showed consistently the nonintervention group 

(Gp2) was significantly behind the control group with intervention 

group (Gp1) scoring higher than the nonintervention group, but still 

behind the control group. At 6 months, the Gp1 was significantly 

behind the Gp2, (F = 4.43, p < 0001), but NS vs. Ctrl (F = 1.85). 

Gp2 was significantly behind the Ctrl (F = 5.83, p < .0001). PPVT at 

36 months, showed effect by group, p < .005. At 60 months after D/C, 

(2 yr post intervention) both Gp1 & Gp2 were statistically behind the 

control group, p < 0.01. At 60 months, the results of Stanford-Binet 

Test showed that the “relative positions of groups maintained”.

Agarwal,

1992

92372206

Gp1 Gp2 Ctrl

Cognitive 91.9(8.6) 86.8(7.7) 95.5(7.9)

Motor coordination 1.13(.22) 0.97(.27) 1.16(.19)

Language 0.85(.14) 0.78(.11) 0.90(.14)

Concept formation 1.32(.43) 1.07(.54) 1.38(.37)

Reasoning 1.15(.79) 0.75(.79) 1.43(.89)

Binet Kulshrestha Intelligence 

Scale

Developmental Quotient calculated 

for Binet Kulshrestha intelligence 

subsets

Caldwell Inventory

At 36 month assessment, there were differences in scores between the 

normal, Grade I, and Grade II/III for cognitive (F = 13.27, p < .001) & 

language (F = 9.308, p < .001) development, motor coordination (F 

= 10.52, p < .001), concept formation (F = 6.235, p < .01), and 

reasoning (F = 7.774, p < .001). The mean scores decreased with 

increasing degrees of malnutrition. Home environment was most 

important variable in predicting IQ, accounting for 26.22% of total 

variance in IQ, p < .001
Evidence table 8. Studies associating cognitive & neurological development with malnourished patients compared to well-nourished 

control subjects in developing countries

Part II

114

Author,

Year

Development

measures Instrument

Associations found

Drewett,

2001

21174599

Gp1 Gp2 Ctrl

Psychomotor 6.6*(4.2) 8.5*(4.3) 10.2(3.7)

Mental 22.6(6.2) 26.6(6.1) 28.9(5.8)

Initial wt (g) 2819(323) 3141(351) 3368(430)

* Gp1 n= 25, Gp2 n=66

Bayley PDI & MDI – nonstandard 

scoring based on number of 

items passed

Group status was correlated to psychomotor development (F = 9.3, p 

< .001; Gp1&Gp2 vs. Ctrl, t = 3.8, p < .001; Gp1 vs .Gp2, t = 2.0, p < 

.05) with early growth faltering group scoring lower than the late 

growth faltering group who in turn scored lower than the controls. 

Similar pattern for mental development scores (Group effect, F = 12.7, 

p < .001; Gp1 vs. Gp2, t = 4.0, p < .01; Gp1 vs. Gp2, t = 3.0, p < 

.01). Child’s wt at 2 years was related to both scores (PDI: r = .53, 

MDI: r = .49, p < .001), & maternal education related to mental 

development (MDI: t = 2.1, p < .05). No relationship between 

households with greater than 2 key possessions and psychomotor 

&mental scores. The difference in initial weights of the 3 groups were 

statistically significant (F = 21.4, p < .01).
Evidence table 8. Studies associating cognitive & neurological development with malnourished patients compared to well-nourished 

control subjects in developing countries

Part III

115

uthor,

Year

Potential biases Comments

Bartel, 1978, 1979

78180773

79162492

No data on difference of number of children between two reports Single tester blinded to child’s group assignment for Bartel 1978; partially funded by 

African Medical Research Council

Evans, 1980

81008912

1 child died in each of the controls, sex unkn Gp1 received supplements until mean 28 months, one examiner blinded to subject’s group 

status, testing 6-7 years after cessation of supplements; US government & South African 

Medical Research Council

Galler, 1983a, 1985b

83136873

85241833

Withdraws/non-participation – 4 refused consent, 7 LTF, 1 

cerebral palsy; Severe PEM

Relevant WISC subtests utilized & some items altered for cultural setting; findings of 

dominant hand performance of fine motor skill tasks deficient in formerly malnourished 

children correlates or co-varies with IQ & other soft neurologic signs; private & hospital 

funded

Grantham-McGregor, 

1987,

1978, 1980, 1982, 

1983

87117313

79086701

81051042

82236679

83246270

Controls had better housing than other 2 groups in spite of attempts 

to match; 2 died & 1 WD from intervention group, 1 from 

nonintervention moved & 1 was adopted by middle-class family, 

1 from control WD; 10 of 21 Gp1 had edema, 4 of 18 in Gp2, & 

none in the control group

Tester blinded to subjects’ group, controls hospitalized mainly for gastroenteritis & 

respiratory infections; government & private funding

Agarwal, 1992

92372206

ND on 17 of 650 in cohort; 5.5% of population were normal for 

growth at 24 months corresponding to 5.9% for 1989-90.

Funded by Indian Council of Medical Research

Drewett,

2001

21174599

Initial weight a proxy for birth weight as most births at home; 27 of 

40 early wt faltering group recruited & tested; significant higher 

proportion of males in Gp2 vs. Gp1, χ2 = 5.56, p < .05; 6 cases 

(Gp1-2 & Gp2-4) with lower limb disabilities could not participate 

in psychomotor test

Sample subset of Jimma Birth Cohort study; Gp2 & Controls selected at random from 

sampling frame; systematic method for selection of broad comparisons for Control 

group; testers blinded to child’s status; Private & hospital funded
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I

116

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study

design

Pollitt,

1976

76109110

Country: US

Setting: Outpatient

FTT Ctrl

Mean age(SD)*

 Male 33(14) 34(13)

 Female 39(14) 39(15)

Mean ht†

 Male 93(2) 101(1)

 Female 90(2) 102(3)

Enrolled/Eval 19 19

% Male 47 47

Race: ND

* months, † centimeters

FTT Ctrl

Maternal 11 12

 educ (2) (1)

Income

 Gross 6943 9541

 annual (3444) (4768)

 Per capita 1557 2648

(725) (1517)

Health Insur: ND

Outpatient clinic, 12-60 mo, 

ht & wt < 3%, bw = 2500 

gm, GA = 36 wks, nl birth, 

nonorganic, singleton, 

maternal ht = 154.5 cm & 

English-speaking ability

Controls matched for age (± 

3 mo), sex, race, ht & wt 

= 25%

Birth complications, 

physical 

disability, genetic 

or organic 

retardation, brain 

damage, organic 

growth 

retardation

Boston Growth 

Standards – ht & wt 

= 3rd percentile

Prospective

 cross-sectional

Weekly interviews 

for 7-11 sessions

Mitchell,

1980

80166667

Country: US

Setting: Outpatient clinic

FTT Ctrl

Age(y) 2-5 2-5

Wt/age ND ND

Ht/length ND ND

Enrolled : cohort of 312

Evaluated 30 282

% Male 36.7 51.8

% Black 70 70

Maternal educ: ND

Income: ND

Health insur: 

FTT-53% Medicaid

Ctrl-49% Medicaid

See Definition of FTT

Controls: wt = 80% of nl, 

matched for age, sex, 

mother’s age / marital 

status & family problems

Organic cause of 

FTT, single 

anomalous low wt 

recorded, clinic 

registration by age 

6 mo, < 3 visits

Wt for age < 80% 

of nl up to age 24 

mo 

Ambidirectional 

longitudinal

1 fwup at age 3 – 6 

y
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I

117

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study

design

Hack,

1982

82227864

Country: US

Setting-Recruitment: Hospital

Follow-up: hospital/clinic

Gp1* Gp2†

Mean age‡ 32(2.8) 29(1.9)

Wt/age(g) 1141(285) 1197(206)

Length(cm) 37.9(3.8) 38(2.7)

Enrolled|| ND ND

Evaluated 38 154

% Male 47 47

% Black 52 63

* SGA, † AGA, ‡ wks gestation, || n = 204

Gp1 Gp2

Maternal

 educ <HS 12 32

Income* 28 99

Health

 Insur ND ND

* Hollingshead Social Class 4 & 

5

VLBW, < 1500g, divided into 

two groups: SGA < 2 SD 

or AGA

ND Wt < 2 SD below 

mean for age @ 

term and/or @ 8 

mo of age

Prospective 

longitudinal

Assessments at age 

40 wk & 8 mo

Haynes,

1984

84233543

Country: US

Setting: In & Out-patient

Age: ND

Wt/age: ND

Ht/length: ND

FTT1* FTT2† Ctrl

Enrolled/Eval 25 25 25

% Race

 Sp-Am? 44 44 44

 Sp-Am? 40 52 52

 White? 36 44 36

 White? 36 24 28

 Black? 20 12 20

 Black? 24 24 20

% Male: ND

* std care & lay health visitor intervention, 

† std care only

Maternal

 educ Income*

Gp1 10 379(0-750)

Gp2 11 372(0-950)

Ctrl 10 362(0-1100)

Health insur: ND

* @ mo

Consecutive admissions for 

NOFTT

Controls - thriving nonhospitalized patients 

matched for age, sex, 

birth wt, & mother’s age, 

ethnicity, number of living 

children

ND < 5 percentile or 

significant decline 

from birth wt 

percentiles

Prospective 

longitudinal

1 assessment 6 mo 

after intake
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I

118

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study

design

Sherrod,

1984

85026403

Country: US

Setting-Recruitment: Prenatal clinic

Follow-up: Pediatric clinic

NOFTT Ctrl

Birthwt(g) 3031 3054

Enrolled/

 Eval* 31 24

Race-White 10 ND

Black 21 ND

% Male: ND

* 4 arm study – Data for FTT & Ctrl only; 

abused or neglected cases excluded

NOFTT Ctrl

Maternal

 educ 10.3 11.2

Income* 13 13

Health

 Insur† ND ND

* # employed, † p < .05, ‡ p < 

.01

NOFTT, abused, or 

neglected

Controls – no hx of abuse, 

FTT, or neglect

ND Wt gain fallen below 

2/3 of Harvard 

50th percentile 

on growth curve

Retrospective 

longitudinal

3 annual 

assessments

Casey,

1985

84206364

Country: US

Setting: Outpatient clinic or home

FTT Ctrl

Age(mo)* 16.4 16.9

Wt/age* 72.5% 94.5%

Ht/length* 93.9% 98.5%

Enrolled/Eval 23 23

% Male 57 57

Race:

 % White 26 26

* At diagnosis

FTT Ctrl

Maternal

 educ 11.3 10.9

Income 5,451 6,188

Health insur: ND

All pts referred for FTT 

evaluation, > 12 wks age, 

FTT as defined or wt % 

decreased > 2 SD over 

time, residence ≤ 30 miles 

of clinic

Control with normal growth, 

matched for age, race, 

sex, maternal education, 

household income, marital 

status, & crowdedness

Organic illness Weight < 3rd

percentile for 

corrected age

Prospective crosssectional

3 wk assessment

from time of 

diagnosis
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I

119

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study

design

Hutcheson, 

1993

94015754

Country: US

Setting: Primary care clinic

FTT Ctrl

Age(mo) 15.1(5.2) 14.9(5.1)

Wt/age 2.83 63.17

Ht/age 23 63

Enrolled/Eval 34 34

% Male 62 62

Race: Black 32 32

FTT Ctrl

Maternal

 educ* 38 70

Income† 64 70

Health ND ND

 insur

* % HS graduate

† % receiving AFDC

Age 8 – 24 mo, NOFTT

Controls matched for age, 

sex, race

Congenital 

disorder, chronic 

disease, < 37 wk 

gestation, SGA

Wt for age ≤ 5th

percentile, or wt 

for ht ≤ 10th

percentile, based 

on NCHS

Prospective crosssectional

Kelleher, 

1993

93234174

Country: US

Setting: Primary care clinic

FTT Ctrl

GA(wk)* 33.0 33.1

Wt(g)* 1679 1845

Enrolled: 842*

Evaluated 180 591

% Male 52.2 47.9

Race: % Black 50 53.8

* At birth

FTT Ctrl

Maternal

 educ* <HS 40.6 38.1

HS 30.0 29.3

Some col 14.4 20.8

 ≥col grad 15.0 11.8

Income <10K 38.6 34.5

10-20K 19.9 23.9

>20K 38.1 37.4

Health insur ND ND

* % HS graduate

Gestation age ≤ 37 wks, 

birth wt ≤ 2500 g, FTT

Controls matched for – birth 

wt +/- 250 g, maternal 

education, maternal race, & 

infant sex

Live outside 

catchment area, 

D/C outside 

recruitment period, 

D/C or died within 

48 hr, hospitalized 

> 60 d, oxygen 

support > 90 d, 

twin, triplet or 

quadruplet of 

ineligible child, 

maternal drug/ 

alcohol abuse, 

insufficient Eng 

skills, psychiatric 

hosp

< 5th percentile for 

gestation 

corrected age 

based on NCHS, 

growth status on 

“wt curve below 

that recorded at 

last regular 

assessment visit.”

Prospective 

longitudinal

Fwup at ages 12, 

24, 36 mo
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I

120

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study

design

Drotar,

1994

94308313

Country: US

Setting: Inpatient with outpatient followup

FTT Ctrl

Age(mo)* 4.7(2.8) 5.0(2.7)

Wt/age: ND ND

Ht/length: ND ND

Enrolled 48 52

Evaluated 31 39

Male 23(74%) 25(64%)

Race: Black 17(55%) 28(72%)

White 14(45%) 11(28%)

*Mean (SD), at enrollment

FTT Ctrl

Maternal 10.9 11.3

 educ (2.0) (1.4)

Income 6414 7495

(6669) (10721)

Health insur: ND

Mean (SD)

Hospitalized for NOFTT, 

ages 1-9 m

Controls matched for age at 

intake, sex, race, birth 

order, gestational age, 

maternal educ & age, family 

income & size

Physical abuse, 

residence > 1 hr 

from hospital, bw 

< 1500 gm

Wt =5th percentile 

based on NCHS, 

absence of 

disease, wt gain 

with inpatient tx, 

poor wt velocity

Prospective 

longitudinal

1 follow-up at 3 yrs

Skuse,

1994, 1995

94253258

96091265

Country: UK

Setting: Outpatient

FTT Ctrl

Mean age(SD)*14.6(1.4) 14.2(1.4)

Wt/age† -2.07(.44) .10(.96)

Ht/length† -1.27(.94) .18(.73)

Enrolled 49 50

Evaluated 47 47

% Male 49 49

% Non-white 43 34

* Age in months † z score, p < .001

Maternal education: ND

Income: income/welfare 

support FTT-16, Ctrl-11

Health insur: National 

healthcare

District-centered until 12 mo 

of age, singleton 

deliveries of 38-41 wks 

gestation

Control matched for sex, 

age, ethnic origin, bw 

within 300 g, ordinal 

position, SES

≤ 3rd centile, no wt 

data 

Wt for age ≥ -1.88 

by 12 mo of age & 

sustained 3 mo 

(based on NCHS)

Prospective 

longitudinal

Assessments at age 

15 mo & 4y
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I

121

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study

design

Puckering,

1995

95378341

Country: UK

Setting: Outpatient

FTT Ctrl

Age(mo) 48.9(1.8) 48.2(0.8)

Wt/age* -2.01(0.6) -0.32(1.1)

Ht/length* -2.24(0.5) -0.6(0.9)

Enrolled/Eval 23 23

% Male 48 48

Race: 100% White

* SDS, based on NCHS, p < .001

FTT Ctrl

Maternal 15.6 15.6

 educ* (1.4) (1.4)

Income† 11 7

48% 30%

Health insur:

 Socialized medicine

* Age leaving full-time education

† Income support/welfare

From inner city population 

sample - Caucasian born 

in 1980 with longitudinal 

growth data from birth to 4 

years

Controls matched for sex, 

gestational age ≥ 38 wks, 

& ethnic origin

Prematurity, 

congenital defects/ 

diseases affecting 

growth, no 

perinatal insults

Ht & wt < 10% 

based on Tanner 

& Whitehouse 

growth charts 

Ambidirectional 

cross-sectional

Wilensky, 

1996

97022837

Country: Israel

Setting: Community pediatric clinic

FTT Ctrl

Mean age(mo)* 15/20 15/20

Wt/age ND ND

Ht/length ND ND

Enrolled† 55 1352

Evaluated 50 50

% Male ND ND

Race: ND;

 Maternal country of birth –

 68% Israel, 25% Europe/America, 

 5% N Africa, 2% Asia

* At entry / assessment

FTT Ctrl

Maternal 13.8 13.4

 educ* (1.62) (1.44)

Income: AFDC 76%

Health insur: ND

* Mean (SD), based on record 

review of potential subjects

FTT infants by review of 

records who have 

reached 15 months born 

in 1991

Controls from same maternal 

& child health clinic 

matched for birth month, 

maternal educ, maternal 

age, parity, and infants’ 

birth wt

Birth wt < 2500 gm, 

< 37 weeks, wt/ht 

ratio > 10 %, 

organic cause of 

FTT

Wt < 3% by NCHS 

for = 3 months 

prior to age 15 

months

Ambidirectional 

cross-sectional
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part I

122

Author,

Year, UI Demographics

Maternal / household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of FTT

Study

design

Drewett,

1999

99284054

Country: UK

Setting: Clinic / home visits

FTT Ctrl

Age(y) 8.12(0.62) 8.10(0.57)

Wt(kg)* 23.8 27.9

BMI* 14.9 16.3

Enrolled 136 136

Evaluated† 107/111 117/122

% Male‡ 40 38

%White‡ 91 91

* Median, † Psychological / anthropometric 

evaluation, ‡ FTT = 107, Ctrl = 117

FTT Ctrl

Maternal 72 66

 educ*

Income: NA

Health insur: National 

healthcare

* % left school at 16 y

At least 1 wt at age 0-2 mo 

& 2 subsequent wts, thrive 

index < 5th centile = 2 

occasions between 3-18 

mo

Controls - at least 1 wt at 

age 0–2 mo & 2 

subsequent wts, no thrive 

index < 10th centile, age ± 

1 mo, similar/same 

residential area or GP 

practice

ND Lowest 5% for 

change of SD 

score; avg taken 

of SD scores for 

all wt bet 0-2 mo, 

expected wt from 

3-18 mo 

calculated for 

“thrive index”

Ambidirectional 

longitudinal

Five years from 

enrollment of 1 y 

old cases

Wright,

2000

20161504

Country: UK

Setting: Outpatient

FTT Ctrl

Median age* 15.1 ND

 range (7-28 m) (16-18 m)

Wt/age -2.00(.93) ND

Ht/length -1.06(.96) ND

Enrolled 120 40

Evaluated 97 28

% Male 54 61

% Nonwhite 9 0

Maternal educ: ND

Income: ND

FTT* Ctrl* 

Unemployed

 parent 39 13

Nonhome-

 owner 54.7 53.6

No car 48.3 50

Health insur: National 

healthcare

* Percent

Baseline wt at 6-8 wk & 2nd

wt at 9-18 mo

Controls from 3 “generally 

representative” of 

Newcastle

2

nd twin sibling Weight decline of 

1.26 SD from 

age 6-8 wks to 

2

nd weighing at 

9-18 months

Prospective crosssectional
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

123

Author,

Year

Correlates / outcomes

 & measures

Associations found Potential biases Comments

Pollitt,

1976

76109110

FTT* Ctrl *

Maternal educ 11(2) y 12(1) y

Income

 Gross annual 6943(3444) 9541(4768)

 Per capita 1557(725) 2648(1517)

* Mean (SD)

The FTT mothers had less education (t = 

1.88, p = 0.05) and the FTT household per 

capita income levels were also lower than 

the controls’ (t = 2.77, p = .01).

4 cases with FTT hx within 

ht 3rd & 10th percentiles 

included in study

Government & privately 

funded

Mitchell,

1980

80166667

FTT(%) Ctrl(%)

Neonatal abnormalities 30 15

Prematurity (<37 wk) 16.7 9.2

Family problems 36.7 11

Physical abuse 3.3 2.1

Acute or chronic illness ND ND

The FTT had significantly more neonatal 

problems (p < .05) such as jaundice, poor 

suckling, & possible sepsis, and family 

problems (p < .01) compared to controls. 

NS but FTT group had higher incidence of 

prematurity and physical abuse. There 

were no differences in occurrences of 

illness, or “problems noted on physical 

examination”.

Physical exams & growth 

status by PI not blinded; 

significantly fewer cases 

had completed 

immunizations, p < .01

Government & privately 

funded

Hack,

1982

82227864

Neonatal risk score

Extended hospital stay

Chronic disease

Subnormal wts at 8 months experienced by 

subset of both groups is associated with 

lower neonatal period (r = 0.28, p < .001), 

extended hospital stay (r = 0.30, p < .001) 

and increased illness severity (r = 0.32, p < 

.005).

8 LTF, 4 incomplete data SGA mothers incr % 

pregnancy HTN (p < 

.05) & multiple births (p 

< .05) than AGA, also 

incr antepartum risk 

score (p < .005) & 

greater gestational age 

(p < .005); privately 

funded
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

124

Author,

Year

Correlates / outcomes

 & measures

Associations found Potential biases Comments

Haynes,

1984

84233543

Catch-up growth

ADL

FTT(%)* Ctrl(%)

Prematurity 13(26) 5(20)

LBW 11(22) 5(20)

Re-hospitalization 13(26) 0

* intervention & non-intervention combined

All FTT had some wt gain during 

hospitalization, at reeval-some minor wt 

gain, 8 FTT gain > 20 percentile pts or 

within 5 percentile of birth wt percentile

At reeval, only minor improvement in mother’s 

response to child’s needs, majority of 

mothers hostile or incoordination

Though NS as a risk factor, FTT had higher 

trend for prematurity and LBW

26% of FTT were re-hospitalized, 0% for Ctrl

“...because of scheduling, 

few admissions were not 

evaluated”, 2 refused 

participation; 10 Gp1 & 3 

Gp2 premature – overall 

similar from FTT vs. Ctrl; 

at 6 mo fwup: for FTT1 & 

FTT2 each-3 cases 

refused reevaluation & 

from1 dissolution of pair, 

1Gp1 died SIDS, 1 Gp2 

mother gave up child

Block assignment to 

Gp1 & Gp2 for 

hospital convenience 

& case load 

requirements; 

government funded

Sherrod,

1985

85026403

Anatomical defects –

FTT Ctrl

1y .13 .08

2y .06 .04

3y .13 .00

Family dysfunction

 (ND due to low frequencies)

Compared to controls, NOFTT group 

revealed more anatomical abnormalities 

such as hernias and heart disease during 

the 1st year (χ2 = 4.23, p < .05) and during 

all 3 years (χ2 = 5.44, p < .025); and more 

family dysfunction during the 1st year or 

during all 3 years (χ2 = 9.29, p < .01; χ2 = 

5.32, p < .025) accounting for clinic visits or 

identified at clinic visits.

Attending physicians alerted 

to give special treatment to 

children suffering from 

maltreatment, analysis 

showed no increase in 

outcome variability; study 

design to identify 

relationship of illness to

abuse, not NOFTT to 

illness

Data collectors blind to 

child group 

assignment; 

government & 

privately funded
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

125

Author,

Year

Correlates / outcomes

 & measures

Associations found Potential biases Comments

Casey,

1985

84206364

HOME environment

FTT Ctrl

Total score 29.2(7.7) 33.0(6.1)

Maternal responsivity 7.7(2.3) 8.9(1.9)

Maternal acceptance 5.1(1.6) 6.2(1.1)

Organization of environment 4.7(1.2) 5.3(0.7)

There is an association between the lower 

HOME total (p < .04)& subset scores in 

maternal responsiveness (p < .03), maternal 

acceptance (p < .01), home organization p < 

.02), and FTT group. Coddington Life 

Events showed no difference between 

groups.

--- All FTT pts referred to 

Growth & 

Development Clinic at 

hospital, all SES 

represented-majority 

low SES, assessor 

blinded to subject’s 

group; government & 

privately funded

FTT1* FTT2† Ctrl1* Ctrl2†

Maternal psychological functioning -

Negativity affectivity 0.38 0.20 0.28 -0.11

Family stress/support -

• Parenting stress 0.53 0.57 0.70 0.67

• Informal support 1.12 1.19 1.26 1.46

• Life events 11.29 7.32 9.31 10.13

Hutcheson, 

1993

94015754

Mother-child interaction –

Maternal affective tone

4.26 3.51 3.96 4.05

Ζ scores given

* Infants: 8 – 13.4 m

† Toddlers: 13.5 – 24 m

Though there were no age or group 

differences found on perceived life stresses, 

parenting stresses, informal support, and 

negative affectivity, the FTT infants had 

fewer life events than FTT toddlers, whereas 

the reverse was true for the comparison 

group. Controlling for maternal education, wt 

for age, & ht for age - significant group by 

age interaction for maternal factors (F=4.98, 

p = 0.02) due to maternal affective tone 

(F=9.33, p = 0.005). The maternal affect was 

less positive toward FTT toddlers than FTT 

infants.

76% of index group met 

both criteria for NOFTT 

(wt for age, & ht for age), 

24% met one criterion; 

unknown n for age by 

group comparisons

Government & privately 

funded
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

126

Author,

Year

Correlates / outcomes

 & measures

Associations found Potential biases Comments

Kelleher, 

1993

93234174

FTT(%) Ctrl(%)

Prematurity 100 100

LBW 100 100

Bronchopulmonary dysplasia 13.9 9.6

Congenital heart disease 7.2 .3

Neurological – cerebral palsy 8.9 4.6

Environmental variables* 32.6 33.9

General health ratings ND ND

Gastrointestinal disorders ND ND

* HOME Inventory - total score

Sample of LBW or premature infants were 

followed. Infants who developed FTT were 

more likely to have congenital heart disease, 

bronchopulmonary dysplasia, and cerebral 

palsy. General health status was lower for 

FTT as measured by Stein Total health 

Score (p < .003) and by the Rand General 

Health Ratings (p < .0001). For GI 

disorders, NS for vomiting & diarrhea. There 

were significant differences in environmental 

variables between the two gps (p < 0.03).

Of 985 enrolled, 71 LTF, 

12%(20) OFTT, 16%(28) 

were both OFTT & 

NOFTT

21% of babies develop 

FTT by 36 wks; ND 

on funding source

Drotar,

1994

94308313

Family Relationship Index

FTT Ctrl

Intake 47.9 (0.8) 53.7 (5.6)

Follow-up 51.2 (8.2) 56.0 (9.4)

Patients with NOFTT had poor family 

relationships at time of diagnosis which 

persisted for 3.6 years despite various 

interventions compared to the control group 

(F = 8.11, p < .01). There was an effect of 

time in the scores for both groups (F = 

5.13, p < .05).

--- Government & privately 

funded

Skuse,

1994, 1995

94253258

96091265

15 month assessment –

FTT Ctrl

Mother’s IQ 83.4(17.1) 86.4(16.2)

Maternal/child interaction ND ND

Oral-motor function ND ND

Anemia 25.5% 23.9%

Abuse/neglect -

6 FTT & 90 nonFTT from sampling frame 2609

At 15 month assessment, NS but the cases 

had a trend for anemia & lower maternal IQ. 

At 4 year fwup, FTT at high risk for child 

abuse or neglect (RR = 4.43).

1994: 2 cases & 3 controls 

didn’t complete 

assessments & were 

excluded from analyses, 1 

case had microcephaly, 

hypotonia, & an action 

tremor or ataxia of 

unknown origin

Researchers blinded to 

patient’s status in 

measures except 

anthropometry, 1994 

noted 1554 potential 

subjects in population 

sample vs. 2609 in 

1995; privately funded
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

127

Author,

Year

Correlates / outcomes

 & measures

Associations found Potential biases Comments

Puckering,

1995

95378341

Maternal interactions

FTT Ctrl

Positive –

Unconditional -1.37 1.37

Conditional -0.16 0.16

Negative –

Unconditional 1.16 -1.16

Conditional 0.04 -0.12

FTT signf less positive mother-child 

interactions compared to Ctrls dyads 

(combined unconditional measures, t = -

2.69, p = .01); 

FTT signf less positive interactions (combined 

conditional measures), t = -0.88, p = 0.4

NS but trend for more negative mother-child 

interactions (combined unconditional 

measures, t = 1.22, p = 0.2)

NS (combined conditional measures), t = 

0.12, p = 0.8

--- Other than clinic 

anthropometric 

measures, home visits 

by assessors blinded 

to child’s group status; 

The FTT children 

were significantly 

smaller than the 

controls; government 

funded

Wilensky, 

1996

97022837

FTT Ctrl

Birthweight* 3074 3230

Hypotonia* 7.27% 2.27%

Hospitalization 33.9% 16.9%

HOME environment

• Active stimulation .84 (.17) .92 (.11)

• Family encouraging development .55 (.31) .71 (.24)

• Verbal & emotional reactivity .85 (.20) .93 (.14)

* Record review of 55 FTT & 1352 Ctrl

The FTT group was found to have lower 

birth weight (p < .05), and were more likely 

to be hypotonic than the control population (p 

< .05). They were twice as likely to be 

admitted in the hospital during their first year 

(χ2 = 5.10, p < .05). In addition, an 

assessment showed the home environment 

to be less stimulating (p < .05).

Feeding behaviors and 

HOME environment are 

causal factors given time 

dissociation as FTT was 

established at 15 months, 

where as, maternal 

interview/home 

assessment at 25 months.

2/5th of infants 

diagnosed as FTT no 

longer fit the criteria at 

20-month follow-up, 

yet had positive 

association on Bayley 

MDI. Reported 

associations for FTT 

without specific data: 

paternal age (p<.01), 

maternal education, & 

behavioral 

observations of lower 

sociability (p<.05) & 

fear of examiner 

(p<.05); ND on 

funding source
Evidence Table 9. Studies associating other correlates / outcomes with Failure to Thrive patients compared to healthy control subjects in 

developed countries

Part II

128

Author,

Year

Correlates / outcomes

 & measures

Associations found Potential biases Comments

Drewett,

1999

99284054

FTT Ctrl

Hx hospital admission

/ hospital outpatient clinic 66(62%) 56(48%)

Father’s height 174.2(7.8) 177.0(7.2)

Medical condition affecting growth –

 “definitely” / “possibly” 2/9 1⁄2

Feeding problems 49(46%) 28(24%)

FTT children were significantly more likely to 

visit the hospital or outpatient clinic than the 

controls (χ2 = 4.54, p = .033). Paternal ht of 

FTT were significantly shorter than controls 

(t = 2.69, p < .01). 9% of cases vs. 3% of 

controls had relevant medical conditions that 

may have affected growth. FTT children had 

significantly more feeding problems than the 

controls (χ2 = 12.1, p < .01)

Of 136 cases, 1 died, 9 

LTF, 15 declined 

psychological testing, 4 

moved; of 136 controls, 2 

were preterm, 5 LTF, 12 

declined psychological 

testing, 14 moved & were 

replaced. 2 FTT cases & 

1 control with medical 

condition affecting growth, 

& 9 FTT cases & 2 

controls with possible 

medical conditions

Testers blinded to 

child’s status; privately 

funded

Wright,

2000

20161504

FTT Ctrl

Social work input 21/97 0/28

Abuse/neglect risk 4/97 0/28

Started solids* 3.89 3.04

Started finger foods* 7.15 6.14

* age (mo) 

(Belongs in Developmental table)

22% of cases received social work input of 

which 4% were registered as at risk for 

abuse or neglect vs. none for the controls. 3 

or 4 FTT registered placed in foster care. 

FTT significantly later start in eating solids (p 

= .003) & finger foods (p = .005) compared 

to control group.

Of 120 cases, 23 

recovered above 

screening threshold & had 

no subsequent data, 21 

families received social 

work input of which, 4 

cases registered at risk of 

abuse or neglect, 17 

cases had “relevant 

organic conditions”...but 

only 4 said to be main 

explanation for their FTT”, 

age difference between 

groups

Government & privately 

funded
Evidence Table 10. Studies associating other correlates / outcomes with malnourished patients compared to well-nourished control 

subjects in developing countries 

Part I

129

Author,

Year Demographics

Maternal / 

household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study

design

Ghosh,

1979

80028795

Country: India

Setting: Inpatient

Gp1* Gp2† Ctrl

Age(mo) 6-36 6-48 6-48

Wt/age ND ND ND

Ht/age ND ND ND

Enrolled/Eval 28 39 60

% Male 64 54 67

Race: ND (assumed Indians)

* Mild-moderately malnourished, † Severe 

malnutrition

ND 6 – 48 months, children with 

PEM, see Definition of 

FTT

Control matched for age, > 

80% of 50% weight for 

age

ND Based on 50th

percentile by Harvard 

scale: Grade 1-mild 

71-80%, Grade 2-

malnutrition 61-70%, 

Grades 3 & 4 severe 

≤ 60%

Prospective 

cross-sectional

Bartel,

1978,

1979

78180773

79162492

Country: South Africa

Setting: Outpatient

Age: ND

Wt/age: ND

Ht/length: ND

Enrolled* Eval* Race

Gp 31/30 31/30 Black

Ctrll1 31/30 31/30 Black

Ctrll2 31/30 31/30 Black

Ctrll3† 90 90 White

% Male: ND

* Bartel 1978 / Bartel 1979, † reported in Bartel 1979

ND Bk 6 – 12 yr olds 

hospitalized during first 27 

months of life for 

kwashiorkor, 5 – 10 yrs 

prior to commencement of 

study 

Controls close in age, no 

hx of PCM:

 Ctrl1-Siblings close in age

Ctrl2-Yardmates of FTT

Ctrl3-High SES Whites

Neurological 

involvement, 

brain damage, 

fits, birth trauma, 

hospital coma, 

hypoglycemia

Wellcome criteria for 

kwashiorkor:

<3rd percentile, 

edematous, and 

dermatitis and/or 

nutritional hair 

changes

Ambidirectional 

longitudinal

Assessment at 4 

– 12 y after 

hospitalization
Evidence Table 10. Studies associating other correlates / outcomes with malnourished patients compared to well-nourished control 

subjects in developing countries 

Part I

130

Author,

Year Demographics

Maternal / 

household 

demographics

Inclusion

 criteria

Exclusion

 criteria

Definition

of malnutrition

Study

design

Kothari,

1992

92225733

Country: India (Developing)

Setting: Inpatient

FTT Ctrl

Mean age(y) 2.65±0.88 ND

Enrolled 25 26

Evaluated 25* 26

% Male 52 50

Race: ND (assumed Indians)

* Marasmus – 15, marasmic kwashiorkor - 10

ND Ages 1-5 yr with severe 

PEM

Controls matched for age & 

sex with normal 

nutritional status

Controls without 

anemia, 

infection, or 

cardiac disease

Grade IV malnutrition < 

50th percent of body 

wt based on 50th

percentile by Harvard 

scale

Prospective 

cross-sectional

Bénéfice,

1992

92296639

Country: Senegal

Setting: Outpatient

Age: ND

Enrolled: 100

Evaluated: FTT 64, Control 34

% Male: 46

Race: ND

ND Age 9 – 14 y from 2 

villages with per capita 

caloric intake of 2200 & 

2400

Recent serious 

illness, clinical 

signs of 

malnutrition or 

anemia

Wt/age < -1 SD median 

WHO/NCHS

Prospective

cross-sectional
Evidence Table 10. Studies associating other correlates / outcomes with malnourished patients compared to well-nourished control 

subjects in developing countries

Part II

131

Author,

Year Correlates / outcome & measures Associations found Potential biases Comments

Ghosh,

1979

80028795

Nerve conduction –

 ulnar, median, peroneal nerves

Highly significant results with lower nerve conduction 

velocities in all age groups in the severe 

malnutrition group compared to controls (p < .001). 

No difference between mild/moderate group and 

controls. Specific n not given, however significant 

delay in nerve conduction in each nerve in infants 

with onset PEM < 12 mo vs. cases onset > 12 mo, 

p < .001

--- ND on funding source

Bartel,

1978,

1979

78180773

79162492

Cardiovascular –

 Avg EEG freq

• freq-R 8.17 8.63 8.44 8.70

• freq-L 8.19 8.67 8.54 8.75

Incidence of EEG activity of specified freq bands

• theta-R 15.59 9.49 11.76 9.12

• alpha-R 43.96 55.54 51.78 56.41

Mean(SD), * Dominant hand scores

EEG frequency results were significant for group 

effect for both hemisphere (p < 0.01). Also there 

was group effect for the incidence of a & d bands in 

the right & a, d, & ? in the left hemisphere (p < 

0.01). The kwashiorkor consistently scored higher 

in the d and lower in the a bands vs. the other 

groups (p < 0.05).

No data on difference of 

number of children 

between two reports

Single tester blinded to 

child’s group assignment 

for Bartel 1978; partially 

funded by African 

Medical Research 

Council

Kothari,

1992

92225733

Cases Ctrl

Left ventricular mass 25.75(8.09) 32.44(11.64)

Left ventricular 4.44(1.45) 2.42(0.87)

mass / body wt

Cardiac index* 5.95(1.95) 4.97(1.41)

Ejection fraction 62.4(10.7) 67.0(7.8)

Anemia – Mean hemoglobin – 7.16±1.78 g/dl

* l/min/m2

Left ventricular mass was less in the cases vs 

controls (p < 0.05, CI 2.08-11.30), but left 

ventricular mass/body wt was higher in the cases 

(p < 0.001, CI 1.28-2.76) which is associated with 

poorer prognosis. Cardiac index increased in the 

cases vs. controls (p < 0.05, 0.04-1.92) Relative 

cardiac sparing in most cases, although there was 

atrophy. No difference between groups in EJ, but 

there were EF < 50% in 5 cases, 2 of 5 died within 

3 wks.

--- ND on funding source
Evidence Table 10. Studies associating other correlates / outcomes with malnourished patients compared to well-nourished control 

subjects in developing countries

Part II

132

Author,

Year Correlates / outcome & measures Associations found Potential biases Comments

Bénéfice,

1992

92296639

FTT Ctrl

Power work capacity 60.9(2.8) 75.1(4.4)

FVC, < 132 months 1.33(0.04) 1.61(0.04)

FVC, > 132 months 1.73(0.03) 2.23(0.09)

33 m dash (sec) 7.22(0.10) 6.60(0.15)

Jumping (m) 1.34(0.02) 1.43(0.03)

Throwing (m) 13.4(0.4) 15.7(0.6)

Hand grip (kPa) 47.5(2.0) 54.6(2.9)

HR (%) > 125 8.85(1.45) 7.85(2.06)

Adjusted mean (SD)

Children with malnutrition scored lower in areas of 

physical activity (p < .05), had less work capacity (t 

= 3.2, p < .001), had lower pulmonary function (p < 

.001), arm muscle compared to nourished controls. 

There was no difference in HR (t =0.37) or level of 

physical activity.

Child’s age determined 

by recall, no records 

available; no 

explanation on missing 

case from each group 

not in analyses

ND on funding source
135

Appendix A. Literature Search Strategies

Search #1

1. follow-up studies/

2. follow-up.tw.

3. exp Case-Control Studies/

4. case-control.tw.

5. exp Longitudinal Studies/

6. longitudinal.tw.

7. exp Cohort Studies/

8. cohort.tw.

9. (random$ or rct).tw.

10. exp Randomized Controlled Trials/

11. exp random allocation/

12. exp Double-Blind Method/

13. exp Single-Blind Method/

14. randomized controlled trial.pt.

15. clinical trial.pt.

16. (clin$ adj trial$).tw.

17. ((singl$ or doubl$ or trebl$ or tripl$) adj (blind$ or mask$)).tw.

18. exp PLACEBOS/

19. placebo$.tw.

20. exp Research Design/

21. Comparative Study/

22. exp Evaluation Studies/

23. exp Prospective Studies/

24. 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 or 22 or 23

25. disab$.af.

26. limitation$.af.

27. handicap$.af.

28. impair$.af.

29. 25 or 26 or 27 or 28

30. exp growth disorders/ or failure to thrive/

31. exp Nutrition Disorders/

32. failure to thrive.af.

33. 30 or 31

34. 24 and 29 and 33

35. limit 34 to human

36. limit 35 to english language

37. limit 36 to (newborn infant or infant <1 to 23 months> or preschool child <2 to 5 years> or 

child <6 to 12 years> or adolescence <13 to 18 years>)

38. 36 not 37

39. limit 38 to (adult <19 to 44 years> or middle age <45 to 64 years> or "aged <65 and over>" 
136

or "aged, <80 and over>")

40. 36 not 39

41. 24 and 32

42. limit 41 to (newborn infant or infant <1 to 23 months> or preschool child <2 to 5 years> or 

child <6 to 12 years> or adolescence <13 to 18 years>)

43. 41 not 42

44. limit 43 to (adult <19 to 44 years> or middle age <45 to 64 years> or "aged <65 and over>" 

or "aged, <80 and over>")

45. 41 not 44

46. limit 45 to human

47. limit 46 to english language

48. 40 not 47

49. 47 or 48

50. exp Body Weight/

51. 24 and 29 and 50

52. limit 51 to human

53. limit 52 to (newborn infant or infant <1 to 23 months> or preschool child <2 to 5 years> or 

child <6 to 12 years> or adolescence <13 to 18 years>)

54. 52 not 53

55. limit 54 to (adult <19 to 44 years> or middle age <45 to 64 years> or "aged <65 and over>" 

or "aged, <80 and over>")

56. 52 not 55

57. limit 56 to english language

58. 49 or 57

Search #2

1. exp Failure to thrive/

2. exp Infant nutrition disorders/

3. exp Nutrition disorders/

4. exp failure to thrive/ or exp growth/

5. exp Growth/

6. exp Growth disorders/

7. exp Nutrition disorders/

8. exp Protein-energy malnutrition/

9. exp Child nutrition disorders/

10. exp Child nutrition/

11. exp Infant nutrition disorders/

12. exp Body weight/

13. exp Growth/

14. exp Protein-energy malnutrition/

15. exp Growth disorders/

16. exp Body height/

17. exp Dwarfism, pituitary/

18. exp Dwarfism, pituitary/
137

19. exp Psychosocial deprivation/

20. exp Dwarfism/

21. exp Stress, psychological/

22. exp Stress, psychological/

23. exp Psychophysiologic disorders/

24. exp Hyperphagia/

25. exp Child behavior/

26. exp Child abuse/

27. FAILURE TO THRIVE.mp.

28. childhood malnutriton.mp. [mp=title, abstract, registry number word, mesh subject heading]

29. failure to thrive.mp. [mp=title, abstract, registry number word, mesh subject heading]

30. protein energy malnutrition.mp. [mp=title, abstract, registry number word, mesh subject 

heading]

31. growht failure.mp. [mp=title, abstract, registry number word, mesh subject heading]

32. growth failure.mp. [mp=title, abstract, registry number word, mesh subject heading]

33. failure to grow.mp. [mp=title, abstract, registry number word, mesh subject heading]

34. pshchosocial dwarfism.mp. [mp=title, abstract, registry number word, mesh subject heading]

35. psychosocial dwarfism.mp. [mp=title, abstract, registry number word, mesh subject heading]

36. hyperphagic short stature.mp. [mp=title, abstract, registry number word, mesh subject 

heading]

37. childhood neglect.mp. [mp=title, abstract, registry number word, mesh subject heading]

38. childhood neglect.mp. [mp=title, abstract, registry number word, mesh subject heading]

Search #3

 1 thriv$.af. 

 2 follow-up studies/

 3 follow-up.tw.

 4 exp Case-Control Studies/

 5 case-control.tw.

 6 exp Longitudinal Studies/

 7 longitudinal.tw.

 8 exp Cohort Studies/

 9 cohort.tw.

 10 (random$ or rct).tw.

 11 exp Randomized Controlled Trials/

 12 exp random allocation/

 13 exp Double-Blind Method/

 14 exp Single-Blind Method/

 15 randomized controlled trial.pt.

 16 clinical trial.pt.

 17 (clin$ adj trial$).tw.

 18 ((singl$ or doubl$ or trebl$ or tripl$) adj (blind$ or mask$)).tw.

 19 exp PLACEBOS/

 20 placebo$.tw.
138

 21 exp Research Design/

 22 Comparative Study/

 23 exp Evaluation Studies/

 24 exp Prospective Studies/

 25 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 or 22 or 23 or 24

 26 1 and 25

 27 limit 26 to human

 28 limit 27 to english language
Appendix B. Data Abstraction Form

139

FAILURE TO THRIVE Association with Disability

Instructions: Check or fill-in where appropriate. Only one answer except where indicated by an *

Reviewer: Review date: / / First author: Year: UI: 

Is there a Non-FTT comparison group? Yes No IF NOT, DO NOT DATA EXTRACT!

Other reason(s) for rejection (no data reported, wrong population, etc):

STUDY CHARACTERISTICS

*Name of Country(s): Developed Developing ND

Number of Sites: ND

*Study setting during recruitment : *Study setting at follow-up: 

 

Duration of Study: ND to Other 

Funding source: Government Pharmaceutical Private Hospital ND

METHODS

Study Design: (CHOOSE ONE): Longitudinal Cross-sectional

(CHOOSE ONE): Prospective Retrospective Unclear

(CHOOSE ONE-(PI’S INTENTION)): RCT Cross-over Case-Control Other ______________________________ 

Definition (or categories) of Failure to Thrive (as defined by authors): ND

STUDY POPULATION

Inclusion criteria for FTT: 

 Inclusion criteria for Control: 

 Exclusion criteria for FTT: 

 

Exclusion criteria for Control: 

 

Total number of subjects enrolled - FTT Control ND

If longitudinal study - # follow-up visits: Follow-up intervals: 

Number of subjects evaluated (Final sample size) - FTT Control ND

Number of subjects who died prior to evaluation - FTT Control ND

Other reasons for withdrawals/non-participation (by group):

Applicability to question of interest:

How representative was FTT study population to the US FTT population? Excellent Good Fair Poor
Appendix B. Data Abstraction Form

140
Appendix B. Data Abstraction Form (continued)

141

DEMOGRAPHICS OF INITIAL POPULATION (if no data – write ND in the box)

Brief 

 Description

 of groups ?

Circle mean or 

median ?

Group 1 (eg. FTT 

tx)

Group 2 (eg. FTT 

placebo)

Group 3 Group 4 Non FTT

(eg. Control)

Sample size 

evaluated

Mean/median 

age at entry 

(range)

Mean/median 

weight for age

Mean/median 

ht/ length

Race- Incl #

 eg. 5 bk

 10 wh

 7 asian

 2 Nat 

Amer

# Males

Maternal educ 

level (range)

Income level 

(range)

Health insur 

type

Additional SES:
Appendix B. Data Abstraction Form (continued)

142

*VARIABLES (predictors or outcome) WITH DISABILITY EXAMINED – Fill in 1st column (Variables) with codes listed below

1 – PERINATAL 2 – DEMOGRAPHIC 3 – ANTHROPOMETRIC 4 - ORGANIC ILLNESS 5 – DEVELOPMENTAL MARKERS

a. tobacco a. education a. weight a. congenital h. Immunologic a. Cognitive development

b. alcohol b. income b. weight for age b. pulmonary i. Infectious b. Behavioral disorder

c. cocaine c. health coverage c. height d. cardiovascular j. endocrine c. ADHD 

 (incl precocious puberty)

d. infection d. maternal IQ d. height for age e. gastrointestinal k. other d. Learning disability

e. prematurity e. quality of e. head circumference f. renal e. Speech/lang/communication 

 HOME Envirmnt disorder

f. LBW f. age f. wt for ht g. neurological f. Activities of daily living

g. other g. gender g. other (incl oral-motor dysf) g. School performance

i. other h. other
Appendix B. Data Abstraction Form (continued)

142

Variables

(outcome or 

predictors)

Time 

to f/u

N

(total # 

eval by 

Gp)

Measurement tool

(eg. Child Behavior 

Checklist)

Statistical

 methods

Tool 

appropriate?

Criteria / cut-point

(text description 

and/or cut-point value 

for test ⊕ or test T)

Outcome 

values/measures (by 

Gp)

Results (incl p-value)

eg. 2g 

(maternal 

edu)

NA FTT-19

Cntl-19

Questionnaire One-tail t test Y NA FTT – 11 yr (SD = 2)

Control – 12 yr (SD = 1)

There was a difference 

between the two 

groups in maternal 

educ. (p< 0.05)
Appendix B. Data Abstraction Form (continued)

143

Other findings/Results/Conclusions of interest: 

BIAS/LIMITATIONS

Eligibility criteria: Explicit & appropriate No Sample size: Sufficient Small

Funding source: Not of concern Of concern No data Dropout rate/reasons: Not of concern Of concern No data

Predictors & outcomes: Relevant Not relevant Follow-up duration: Adequate Inadequate Cross-sectional

Methodology: Adequate Inadequate Unsure Statistical analysis: Adequate Inadequate Unsure

Control group: Appropriate Inappropriate No control group Sample representative of inclusion criteria: Yes No

Post hoc analyses: All Some None Unsure

Other: 

Internal Validity (Quality of Methods)

A Prospective (Not Retrospective). Complete reporting of methods and results (incl. inclusion/exclusion criteria, “Table 1 data,”) proper reference 

(“gold”) standard, correct analyses performed (No data inconsistency and discrepancy).

B Prospective or Retrospective. Not all criteria of A. Some deficiencies, however, unlikely to cause major bias

C Prospective or Retrospective. Significant design or reporting errors, large amount of missing information or bias. No reference standard provided or 

use of inappropriate reference standard.

If B or C: Deficiency:

Study Summary – (A brief paragraph for the Results section of the report including the basic methodology, population, outcomes, stats & results and biases)
145

Appendix C. Acknowledgments

The Evidence-based Practice Center staff acknowledges the collaboration of the clinical experts 

who served on the EPC Technical Expert Panel. The EPC also acknowledges the contributions 

by those who acted as peer reviewers for the evidence report.

New England Medical Center EPC Project Staff

Joseph Lau, MD; EPC/Project Director

Ethan Balk, MD, MPH, Assistant Project Director and Project Leader, Short Stature

Cynthia Cole, MD, MPH, Coordinating Team Leader

Deirdre DeVine, M Litt, Project Manager

Priscilla Chew, MPH, Project Leader, Failure to Thrive

Kimberly Miller, BA, Research Assistant

Chenchen Wang, MD, MSc, Project Leader, Low Birth Weight

Technical Expert Panel

Evidence Review Teams, Tufts New England Medical Center

Very Low Birth Weight 

Dr. Cynthia Cole, Project Coordinator and Team Leader

Drs. Geoffrey Binney, John Fiascone, James Hagadorn, and Chiwan Kim

Patricia Casey, NNP

Short Stature

Dr. Patricia Wheeler, Team Leader

Drs. Barbara Shephard and Karen Bresnahan

Failure To Thrive

Dr. Ellen Perrin, Team Leader

Drs. Stephan Glicken, Nicholas Guerina, Kevin Petit, Robert Sege, MaryAnn Volpe, 

and Deborah Frank 

James Perrin, MD, Pediatric Consultant to the EPC 

Social Security Administration 

Science Partner: Dr. Paul Burgan, MD, PhD; Regina Connell, MS 

Agency for Healthcare Research and Quality (AHRQ)

Marian James, PhD, Task Order Officer 
146

American Academy of Pediatrics 

Marilee Allen, MD (Very Low Birth Weight)

Professor

Neonatology, Department of Pediatrics

Johns Hopkins University 

Baltimore, Maryland

Joseph Hersh, MD (Short Stature)

Louisville, Kentucky

Michael Farrell, MD (Failure to Thrive)

Chief of Staff

Childrens’ Hospital Medical Center

Cincinnati, Ohio

Carla Herrerias, BS, MPH

Senior Health Policy Analyst

Department of Practice and Research

American Academy of Pediatrics

Elk Grove Village, Illinois

Disability Law Center, Inc.

Linda Landry, Esq.

Peer Reviewers

American Academy of Pediatrics

Very Low Birth Weight

Deborah Campbell, MD

Hartsdale, New York 

Warren N. Rosenfeld, MD

Department of Pediatrics

Winthrop University Hospital

Mineola, New York

Short Stature

Susan Rose, MD

Department of Endocrinology

Childrens’ Hospital Medical Center of Cincinnati

Cincinnati, Ohio

Failure to Thrive

William Cochran, MD
147

Department of Pediatric GI/Nutrition

Geisinger Health System

Danville, Pennsylvania

American Association of Clinical Endocrinologists

A. Jay Cohen, MD

The Endocrine Clinic, PC

Memphis, Tennessee

Lawson Wilkins Pediatric Endocrine Society

David M. Brown, MD

Professor of Pediatrics

University of Minnesota

Minneapolis, Minnesota

National Institute of Child Health and Human Development

Gilman Grave, MD

Chief, Endocrinology, Nutrition and Growth Branch 

Center for Research for Mothers and Children 

Bethesda, Maryland

Catherine Y. Spong, MD (for VLBW and Failure to Thrive)

Chief, Pregnancy and Perinatology Branch

Center for Research for Mothers and Children

Bethesda, Maryland

Tonse Raju, MD (for VLBW and Failure to Thrive)

Pregnancy and Perinatology Branch

Center for Research for Mothers and Children

Bethesda, Maryland

Society for Developmental and Behavioral Pediatrics

Denis Drotar, MD

Professor and Chief

Division of Behavioral Pediatrics and Psychology

Rainbow Babies and Childrens’ Hospital

Cleveland, Ohio

Daniel Kessler, MD

Phoenix, Arizona
149

Appendix D: Acronyms/Abbreviations

ADHD Attention deficit hyperactivity disorders

ADL Activities of daily living

AFDC Aid to Families with Dependent Children

AGA appropriate for gestational age

ALRI acute lower respiratory infections

ANCOVA analyses of covariance

ARI acute respiratory infections

BGS Boston Growth Standard

BMI body mass index

CBCL Child Behavior Checklist

Ctrl control

D day(s)

D/C discharge

FU follow-up

FVC forced vital capacity

GCI general cognitive index

GA gestational age

Gp group

HC head circumference

HOME Home Observation for Measurement of the Environment

HR heart rate

HS high school

Ht height

Hx history

Incr increase(d)

LBW low birth weight

LOMDS Lincoln-Oseretsky motor development scale

MANCOVA multivariate of analyses of covariance

Mo month(s)

MDI mental development index

ND no data

Nl normal

NOFTT non-organic failure to thrive

NS not significant

NCHS National Center for Health Statistics

Nonsignf nonsignificant

OFTT organic failure to thrive

PCERA Parent-Child Early Relational Assessment scale

PCM protein-calorie malnutrition

PDI psychomotor development index

PEM protein-energy malnutrition

PHA phytohemagglutinin

PPVT Peabody Picture Vocabulary Test
150

RFC rosette forming cells

RR relative risk

SD standard deviation

SDS standard deviation score

SES social-economic status

SGA small for gestational age

Signf significant

SK-SD streptokinase-streptodornase

Std standard

SOMA Schedule for Oral Motor Assessment

SWFA standard weight for age

THE tetrahydrocortisol

THF tetrahydrocortisone

TRIB Tester’s Rating of Infant Behaviour

UI Medline unique indentifer

WAIS Wechsler Adult Intelligence Scale

WD withdrawn

WPPSI / 

 WPPSI-R Wechsler Pre-school and Primary Scale of Intelligence

WISC Wechsler Intelligence Scale for Children

WORD test Wechsler Objective Reading Dimensions manual

Wt weight