ARTICLEPEDIATRICS Volume 138 , number 2 , August 2016 :e 20154698

Linear Growth and Child Development in Burkina Faso, Ghana, and MalawiElizabeth L. Prado, PhD, a Souheila Abbeddou, PhD, a Seth Adu-Afarwuah, PhD, b Mary Arimond, MS, a Per Ashorn, MD, PhD, c, d Ulla Ashorn, PhD, c Kenneth H. Brown, MD, a, e Sonja Y. Hess, PhD, a Anna Lartey, PhD, b Kenneth Maleta, MD, PhD, f Eugenia Ocansey, MPhil, a, b Jean-Bosco Ouédraogo, MD, PhD, g John Phuka, MD, PhD, f Jérôme W. Somé, MD, a Steve A. Vosti, PhD, h Elizabeth Yakes Jimenez, PhD, i, j Kathryn G. Dewey, PhDa

abstractOBJECTIVES: We aimed to produce quantitative estimates of the associations between 4

domains of child development and linear growth during 3 periods: before birth, early

infancy, and later infancy. We also aimed to determine whether several factors attenuated

these associations.

METHODS: In 3700 children in Burkina Faso, Ghana, and Malawi, growth was measured

several times from birth to age 18 months. At 18 months, language, motor, socioemotional,

and executive function development were assessed. In Burkina Faso (n = 1111), personal-

social development was assessed rather than the latter 2 domains.

RESULTS: Linear growth was significantly associated with language, motor, and personal-

social development but not socioemotional development or executive function. For

language, the pooled adjusted estimate of the association with length-for-age z score (LAZ)

at 6 months was 0.13 ± 0.02 SD, and with ΔLAZ from 6 to 18 months it was 0.11 ± 0.03 SD.

For motor, these estimates were 0.16 ± 0.02 SD and 0.22 ± 0.03 SD, respectively. In 1412

children measured at birth, estimates of the association with LAZ at birth were similar

(0.07–0.16 SD for language and 0.09–0.18 SD for motor development). These associations

were weaker or absent in certain subsets of children with high levels of developmental

stimulation or mothers who received nutritional supplementation.

CONCLUSIONS: Growth faltering during any period from before birth to 18 months is

associated with poor development of language and motor skills. Interventions to provide

developmental stimulation or maternal supplementation may protect children who are

faltering in growth from poor language and motor development.

Departments of aNutrition, and hAgricultural and Resource Economics, University of California Davis, Davis,

California; bDepartment of Nutrition and Food Science, University of Ghana, Legon, Ghana; cCenter for Child

Health Research, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland; dDepartment of Paediatrics, Tampere University Hospital, Tampere, Finland; eBill & Melinda Gates Foundation,

Seattle, Washington; fSchool of Public Health and Family Medicine, University of Malawi College of Medicine,

Blantyre, Malawi; gInstitut de Recherche en Sciences de la Santé/DRO, Bobo-Dioulasso, Burkina Faso; and

Departments of iIndividual, Family, and Community Education and jFamily and Community Medicine, University

of New Mexico, Albuquerque, New Mexico

The fi ndings and conclusions contained within are those of the authors and do not necessarily

refl ect positions or policies of the Bill & Melinda Gates Foundation.

Dr Prado designed data collection instruments, conceptualized the analyses of linear growth and

development, conducted data analysis, and drafted the manuscript; Drs Abbeddou, Phuka, Somé,

and Yakes Jimenez and Mss Arimond and Ocansey designed the data collection instruments,

coordinated and supervised data collection, and critically reviewed the manuscript; Drs Adu-

Afarwuah, Ashorn, Ashorn, Brown, Hess, Lartey, Maleta, Ouédraogo, Vosti, and Dewey designed

To cite: Prado EL, Abbeddou S, Adu-Afarwuah S, et al.

Linear Growth and Child Development in Burkina Faso,

Ghana, and Malawi. Pediatrics. 2016;138(2):e20154698

WHAT’S KNOWN ON THIS SUBJECT: One meta-

analysis has examined associations between linear

growth and development in low- and middle-income

countries, reporting cross-sectional estimates

pooling 3 to 4 studies in children aged <2 years

for language and motor development but not

socioemotional development or executive function.

WHAT THIS STUDY ADDS: Linear growth was

signifi cantly associated with the development of

motor and language skills but not socioemotional

or executive function, with similar estimates across

4 different studies comprising 3700 children and

across 3 periods of infancy from birth to 18 months.

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In many populations in low- and

middle-income countries (LMICs),

faltering in linear growth begins

before birth and continues until

at least 2 years of age. 1, 2 Brain

development occurs rapidly during

this same period, from conception to

age 2 years, laying the foundation for

the development of cognitive, motor,

and socioemotional skills throughout

childhood and adulthood. The

extent to which children globally are

faltering in the development of these

abilities during the first 2 years of life

is less clear. Although stunted linear

growth has been used as a proxy for

children’s broader developmental

status, the nature of the association

between growth and development is

not fully understood. 3

Several qualitative reviews of studies

reporting associations between

growth and development in LMICs

concluded that growth stunting

is associated with concurrent and

longer term deficits in cognition,

behavior, motor skills, and school

performance. 3 – 5 The only systematic

review and meta-analysis of

associations between linear growth

and development reported a cross-

sectional unadjusted pooled estimate

of 0.28 SD difference in cognitive

score and 0.24 SD difference in motor

score with each 1 SD difference

in length-for-age z score (LAZ) in

children aged <2 years. 6 However,

due to methodologic inconsistencies

across studies or lack of data, this

estimate was derived from only

3 studies in the cognitive domain

and 4 studies in the motor domain;

pooled estimates in other domains,

such as socioemotional development

and executive function, could not

be generated. Similarly, pooled

estimates for studies examining the

associations with change in LAZ

over time could not be generated

due to the small number of studies

and differences across studies in the

timing of height measurements.

We address these gaps by using data

from the International Lipid-Based

Nutrient Supplements (iLiNS)

Project. The iLiNS Project comprised

4 randomized trials that enrolled

>7000 pregnant women or infants

in Burkina Faso, Ghana, and Malawi.

All trials included groups of mothers

and/or children who received

various doses and formulations of

lipid-based nutrient supplements

(LNS) and control groups who did

not receive LNS. Linear growth was

measured at multiple time points

during infancy, and developmental

assessments were conducted at 18

months of age. The main outcomes

of the trials have been reported

elsewhere. 7 – 10 In brief, results

differed across trials, with positive

effects on 18-month linear growth

in Burkina Faso9 and Ghana 7 but not

in the 2 trials in Malawi. 8, 10 Effects

on 18-month child development also

differed across trials, with positive

effects in Burkina Faso 11 but not in

Ghana12 or Malawi (E.L.P., S.A.A., A.L.,

et al, unpublished observations). 13

The focus of the present study was

on the associations between linear

growth and development in the 4

cohorts, regardless of intervention

group (ie, controlling for intervention

group as a covariate). We also

investigated intervention group as a

potential effect modifier (as detailed

in the fourth objective).

The first objective of this study

was to explore the extent to which

children in each cohort had faltered

in growth and development by age

18 months. The second objective

was to examine the association of

each developmental domain with

attained length and linear growth

increments during different periods

of infancy. The third objective was

to examine the extent to which these

associations were confounded by

other factors such as socioeconomic

status, maternal education, and

the developmental stimulation

the child received. Association

does not indicate causality; thus,

evidence for such confounding

would suggest that linear growth

may not be a determinant of child

development but rather a proxy for

an environment that constrains both

linear growth and development.

The fourth objective was to examine

3 potential modifiers of these

associations. In populations with

few environmental constraints on

growth, the height that children

attain is likely to be constrained

only by genetic potential. 14 In such

populations, an association between

linear growth and development is not

observed. 15 This lack of association is

also likely to be observed in certain

populations within LMIC contexts.

For example, growth faltering in

later infancy might not be associated

with poor development if growth

was sufficient during an earlier time

period. It is also possible that growth

faltering is not associated with

poor development among children

with high levels of developmental

stimulation from the environment.

For example, in 6- to 8-year-old

children in Vietnam, concurrent

growth stunting was associated with

cognitive scores among children who

had not participated in a preschool

educational program at age 3 to

4 years but not among those who

had participated in the program. 16

Thus, we examined the following:

(1) the interaction between early

growth status and later growth; (2)

the interaction with the amount of

developmental stimulation from the

environment; and (3) the interaction

with trial group.

METHODS

iLiNS Project Trial Designs

The methods of the iLiNS Project

interventions are summarized in

Table 1 and have been described

in detail elsewhere. 7 –10 Additional

details are presented in the

Supplemental Information.

Participants

All children for whom complete data

were available are included in the

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PEDIATRICS Volume 138 , number 2 , August 2016

present study, including LAZ scores,

18-month development scores, and

complete covariate information.

Complete information was available

for a total of 3700 children: 1111

in iLiNS-ZINC, 1107 in iLiNS-DOSE,

568 in iLiNS-DYAD-M, and 914 in

iLiNS-DYAD-G. In the iLiNS-ZINC

trial, only a random subsample of

4 of the 5 trial groups was targeted

for developmental assessment. 11

Baseline characteristics of the

samples included in the analysis

compared with those excluded are

presented in Supplemental Tables 7,

8, 9, and 10.

Measurement of Linear Growth

In all trials, child length was

measured to the nearest 1 mm

at multiple time points by teams

of 2 trained and standardized

anthropometrists using length

boards. Length measurements from

the following time points were used

in the analyses reported here: for

the iLiNS-ZINC trial, age 9 and 18

months; for the iLiNS-DOSE trial,

age 6 and 18 months; and for the 2

iLiNS-DYAD trials, within 6 weeks of

birth and age 6 and 18 months. LAZ

was calculated by using the World

Health Organization (WHO) growth

standards. 17

Developmental Assessment in Burkina Faso

In the iLiNS-ZINC trial in Burkina

Faso, motor, language, and personal-

social development at age 18

months was assessed by using the

Developmental Milestones Checklist–

II (DMC-II). 18 This tool evaluates

the child's motor, language, and

personal-social development through

both interviewing the caregiver and

observing the child. Motor items

measured fine and gross motor skills;

language items measured receptive

and expressive language skills;

and personal-social items included

skills such as joining others in play,

dressing, feeding, and toilet training.

The score for each subscale was the

sum of the item scores.

Developmental Assessment in Malawi and Ghana

In the iLiNS-DOSE and iLiNS-DYAD

trials in Malawi and Ghana, the

following assessments were used.

Motor development was assessed

by using the Kilifi Developmental

Inventory (KDI), which is a tool

developed in Kenya based on several

standard tests. 19 The child’s score

was the total number of fine and

gross motor skills he or she was

observed to perform. Language

development was assessed by using

a 100-word vocabulary checklist

based on the MacArthur-Bates

Communicative Development

Inventory (CDI). 20 We developed

the checklist in the local languages

at each site through interviews with

caregivers and pilot testing. The

child’s score was the total number of

words the child said, from the 100-

word list, as reported by the mother.

Socioemotional development was

assessed by using the Profile of Social

and Emotional Development, a test

developed in Kenya based in part

on the Brief Infant-Toddler Social

and Emotional Assessment. The 19

items probe emotional regulation

(eg, throwing tantrums, showing

jealousy), behavioral regulation

(eg, sitting still, paying attention),

aggression (eg, hitting others), and

social competence (eg, sharing

toys). The items were summed for a

total score, such that a higher score

indicated fewer socioemotional

problems.

Executive function was assessed

by using a version of the A-not-B

task, which is a widely used test

of working memory and executive

function in very young children that

has been previously used successfully

in Kenya and Uganda. 21 – 23 In each of

3

TABLE 1 Summary of the iLiNS Project Interventions

Variable iLiNS-ZINC iLiNS-DOSE iLiNS-DYAD-M iLiNS-DYAD-G

Study site Rural Burkina Faso Partly rural, partly semi-urban Malawi Semi-urban Ghana

Intervention period 9–18 mo 6–18 mo <20 wk gestation to 18 mo postpartum

Intervention group 20 g LNS/d containing

varying amounts of zinc,

and weekly diarrhea and

malaria surveillance and

treatment

10 g, 20 g, or 40 g of LNS/d

and weekly diarrhea and

malaria surveillance and

referral

20 g LNS/d for mother until 6 mo postpartum and for child age

6–18 mo

Biweekly morbidity surveillance and referral for the mother and

weekly morbidity surveillance and referral for the child

Control group No contact between

enrollment and 18 mo

Weekly diarrhea and malaria

surveillance and referral

(1) MMN group: daily multiple micronutrient tablet (18 vitamins

and minerals) until 6 mo postpartum

(2) IFA group: daily iron/folic acid tablet until delivery and placebo

until 6 mo postpartum

Biweekly morbidity surveillance and referral for the mother and

weekly morbidity surveillance and referral for the child

No. enrolled Intervention: 2435 Intervention: 1612 Intervention: 288 Intervention: 440

Control: 785 Control: 320 MMN group: 291 MMN group: 439

IFA group: 290 IFA group: 441

No. included in analysis Intervention: 739 Intervention: 921 Intervention: 182 Intervention: 308

Control: 372 Control: 186 MMN group: 187 MMN group: 310

IFA group: 199 IFA group: 296

IFA, iron and folic acid.

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10 trials, a small piece of cracker was

hidden under 1 of 2 identical cups

on a wooden board. The board was

removed from sight for 5 seconds,

during which the child was distracted

with a song. The board was then

returned, and the child was invited to

find the cracker. Every time the child

achieved 2 correct consecutive trials,

the cracker was then hidden at the

alternate location. The score was the

total number of correct trials.

Nurturing and Developmental Stimulation in the Home Environment

The child’s stimulation from the

home environment was evaluated

by using the Family Care Indicators

(FCI) interview. 24, 25 The mother

was interviewed with regard to the

child’s play materials and activities

with caregivers in the past 3 days

(Supplemental Information). The

overall FCI score was calculated as

the sum of the 18 item scores.

Tester Training and Reliability

The first author trained the

developmental assessment teams

in each trial. All data collectors

were required to pass knowledge-

and practice-based evaluations

before administering the tests and

interviews. Inter-scorer agreement

and test–retest reliability were

evaluated for each team and have

been reported elsewhere (E.L.P.,

S.A.A., A.L., et al, unpublished

observations). 12, 13, 18, 20 Further

details are given in Supplemental

Table 11.

Description of Covariates

At baseline, data collectors recorded

maternal and household information.

Maternal education and household

assets were coded as above or

below the median for that cohort.

We used a cutoff of >2 to indicate

a relatively higher level of food

insecurity. A detailed description

of these variables is given in the

Supplemental Information.

Statistical Analysis

For the DMC-II scores, z scores

in the iLiNS-ZINC sample were

calculated by standardizing to a

mean of zero and an SD of 1. For

the Kilifi Developmental Inventory,

CDI, Profile of Socio-Emotional

Development, and A-not-B task,

z scores were calculated on the

full sample of children from the 3

cohorts. To reduce skewness to <1,

the Kilifi Developmental Inventory

motor score and the DMC-II motor

and personal-social scores were log-

transformed and the CDI vocabulary

score was square root transformed

before calculating the z scores. For all

other scores, skewness was <1.

The first objective was assessed

in the following ways. To evaluate

faltering in linear growth, mean

LAZ was calculated according to

WHO standards, 17 which indicate

the extent to which each cohort had

faltered, on average, compared with

the WHO sample, in units of SD. For

the developmental assessments,

no such norms exist. We therefore

calculated the mean developmental

scores in a subsample of children

across the cohorts with fewer

environmental constraints on

development. This low-risk sample

comprised all children without any of

the following risk factors: asset index

below the cohort median, maternal or

paternal education below the cohort

median, FCI score below the cohort

median, stunted (LAZ less than –2) at

6/9 or 18 months, and anemic (blood

hemoglobin concentration <110 g/L)

at 6/9 or 18 months. We selected risk

factors for poor child development

that have been identified in previous

studies 26 and were available in all

of our data sets. The distribution

of scores in the low-risk sample

provides an estimate of the potential

scores that children could reach with

fewer health and environmental

constraints on development. We

also compared scores in the highest

and lowest wealth quartile, based

on the asset index (Supplemental

Information), using generalized

linear models controlling for child

age and sex. This method allowed

us to evaluate the extent to which

economically disadvantaged children

had faltered compared with their

more advantaged peers.

For the second objective, 2 steps

were used. First, in each cohort, we

examined growth status in early

infancy (LAZ at 6/9 months) and

growth in late infancy (ΔLAZ from

6/9 to 18 months). We calculated

ΔLAZ by subtracting LAZ at 6/9

months from LAZ at 18 months.

Second, in each iLiNS-DYAD cohort,

we examined LAZ at birth, ΔLAZ from

birth to 6 months, and ΔLAZ from 6

to 18 months.

For the third objective, 2 linear

regression models were fit in each

step. In model 1, the LAZ and ΔLAZ

scores, child age and sex, data

collector, and trial group were

included ( Table 1 presents the trial

groups). In model 2, all additional

covariates were added: baseline

maternal age and education, asset

index below median, household food

insecurity access (HFIA) >2, HIV

status, and FCI score.

For the pooled analysis of the iLiNS-

DOSE and iLiNS-DYAD cohorts,

trial cohort group was coded as an

8-category variable indicating both

trial cohort and intervention group (2

groups in the iLiNS-DOSE cohort and

3 groups in each of the DYAD trial

cohorts) ( Table 1). We calculated

both a fixed effects model, which

assumes no heterogeneity between

trial cohorts, and a random effects

model, with random effects of trial

cohort on intercept, slope of LAZ at 6

months, and slope of ΔLAZ from 6 to

18 months. The latter model allows

the associations between linear

growth and development to vary

between trial cohorts. 27

For the fourth objective, we

examined the data from the iLiNS-

ZINC cohort and the pooled data

from the iLiNS-DOSE and iLiNS-DYAD

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PEDIATRICS Volume 138 , number 2 , August 2016

cohorts. To evaluate whether the

association with later growth was

modified by early growth status,

the interaction between LAZ at 6/9

months and ΔLAZ from 6/9 to 18

months was added to each model.

To evaluate whether the association

was modified by stimulation from

the environment, we added to each

model the interaction between the

following factors: (1) FCI score and

6/9-month LAZ; and (2) FCI score

and ΔLAZ from 6/9 to 18 months.

To evaluate whether the association

was modified according to trial

group, each cohort was examined

separately, and we added to the

model the interaction between: (1)

trial group and 6- month LAZ for the

DYAD cohorts; and (2) trial group

and ΔLAZ from 6/9 to 18 months

for all 4 cohorts. If any interaction

was significant at the P < .1 level, the

association within each tertile of the

effect modifier or within each trial

group was examined. All statistical

analyses were conducted by using

SAS version 9.4 (SAS Institute, Cary,

NC), except the I2 statistic, which was

calculated by using Stata version 14.1

(StataCorp, College Station, TX).

RESULTS

Table 2 displays the mean LAZ and

developmental scores in each cohort.

At birth, LAZ of the cohort in iLiNS-

DYAD-M was on average 1 SD below

the mean of the WHO norm sample.

On average, this cohort faltered an

additional 0.2 SD between birth and

6 months and 0.3 SD between 6 and

18 months. Mean LAZ of the cohort

in iLiNS-DYAD-G was 0.6 SD below

the mean of the WHO norm sample at

birth, and they faltered an additional

0.1 SD from birth to 6 months and 0.1

SD from 6 to 18 months. The iLiNS-

ZINC cohort was 1.2 SD below the

mean of WHO norms at age 9 months

and faltered an additional 0.4 SD

from 9 to 18 months. The iLiNS-DOSE

cohort was on average 1.4 SD below

the mean of WHO norms at age 6

months and faltered an additional 0.5

SD from 6 to 18 months.

The distributions of motor, language,

socioemotional, and executive

function scores were similar in the 3

cohorts in Ghana and Malawi ( Table 2).

The low-risk sample included

5 children in the iLiNS-ZINC cohort,

56 children in the iLiNS-DOSE

cohort, 17 children in the iLiNS-

DYAD-M cohort, and 80 children

in the iLiNS-DYAD-G cohort. For

the motor, socioemotional, and

executive function scores, the mean

and SD of the low-risk sample were

within the same range as the means

and SDs of each cohort. For language

development, the mean vocabulary

score of the low-risk sample was

40 words, whereas the mean

vocabulary scores of the full cohorts

in Ghana and Malawi were 25 to 28

words.

Figure 1 displays the differences in

z scores between the highest and

lowest wealth quartile in each cohort.

In all 4 cohorts, children in the lowest

wealth quartile had significantly

lower LAZ scores than children in

the highest wealth quartile, with

differences ranging from 0.2 to 0.3

SD. Significant differences between

the lowest and highest wealth

quartiles were found for motor

development in the iLiNS-ZINC (0.3

SD) and iLiNS-DOSE (0.4 SD) cohorts,

and for language development

in the iLiNS-DOSE (0.4 SD) and

iLiNS-DYAD-G (0.2 SD) cohorts.

No significant differences between

wealth quartiles were found for

personal-social, socioemotional, or

executive function.

Table 3 presents the estimates of

the association of early growth

status (LAZ at 6/9 months) and

growth in later infancy (ΔLAZ

from 6/9 to 18 months) with each

developmental score. In all cohorts,

both measures of linear growth

were significantly associated with

language and motor development,

and neither measure was associated

with socioemotional development.

Both measures of linear growth

were significantly associated with

personal-social development, which

was only measured in the iLiNS-

ZINC cohort. Executive function was

not associated with early growth

status in any cohort and was

associated with growth from 6 to

18 months only in the iLiNS-DOSE

cohort.

For language, motor, and personal-

social development, the coefficients

for early growth status were similar

in magnitude to the coefficients for

later infant growth. The coefficients

for model 1 were similar to the

coefficients for model 2, indicating

that the household and family factors

included in model 2 did not greatly

confound the associations between

linear growth and development.

The associations of both measures

of growth with language and motor

development were somewhat

smaller in Ghana, compared with

Malawi and Burkina Faso. I2 statistics

indicated substantial heterogeneity

between trials for the motor and

language coefficients; however,

when combining only 3 trials,

heterogeneity between trials cannot

be estimated with precision, and

the confidence intervals were very

large. The coefficients were not

significantly different between trials

except for the association between

6-month LAZ and language score

(for the interaction with trial,

P = .04; all other P values >.1). The

adjusted estimates pooling the data

from Ghana and Malawi indicate

that a 1 SD difference in 6-month

LAZ was associated with a 0.13 SD

difference in language scores and a

0.16 SD difference in motor scores.

Each 1 SD difference in ΔLAZ from

6 to 18 months was associated with

a difference of 0.11 SD in language

scores and 0.22 SD in motor scores.

In the random effects models, which

accounted for heterogeneity, the

estimates were similar and the

P values were larger; the confidence

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intervals took into account the

variance both within and between

trials, and the variance between only

3 trials cannot be estimated with

precision. 27

The analysis of the 3 measures of

growth (LAZ at birth, ΔLAZ from

birth to 6 months, and ΔLAZ from

6 to 18 months) in the iLiNS-DYAD

cohorts revealed a similar pattern

( Table 4). Significant associations

were found for language and

motor development but not for

socioemotional development or

executive function. The coefficients

for the 3 measures of growth

were similar to each other, except

growth from birth to 6 months in

Ghana, which was not significantly

related to any developmental

score. However, the coefficients

were not significantly different

between Ghana and Malawi (for

the interactions with trial, all

P values >.1). The cross-sectional

estimates of the associations

between 18-month LAZ and each

developmental score are reported

in Supplemental Table 12.

We examined the potential

effect modifiers only for the 3

developmental scores for which

significant associations with

growth were found: language,

motor, and personal-social scores.

No significant interactions were

found between LAZ at 6/9 months

and ΔLAZ from 6/9 to 18 months

(P values >.1). Three interactions

were found with the FCI score: in

the pooled data, the interaction

with LAZ at 6 months for motor

development (P = .07) and in the

iLiNS-ZINC cohort, the interaction

with LAZ at 9 months for motor

development (P = .09) and with

ΔLAZ from 9 to 18 months for

language development (P = .04).

Table 5 displays these associations

between growth and development

stratified according to FCI tertile.

As expected, stronger associations

were found in the lowest tertile of

6

TABL

E 2

Mea

n G

row

th a

nd

Dev

elop

men

t S

core

s in

Eac

h C

ohor

t

Vari

able

iLiN

S-Z

INC

(Bu

rkin

a Fa

so)ab

iLiN

S-D

OS

E (M

alaw

i)iL

iNS

-DYA

D-M

(M

alaw

i)iL

iNS

-DYA

D-G

(G

han

a)Lo

w R

isk

Sam

ple

c

NM

ean

or

Med

ian

± S

DN

Mea

n o

r M

edia

n ±

SD

NM

ean

or

Med

ian

± S

DN

Mea

n o

r M

edia

n ±

SD

NM

ean

or

Med

ian

± S

D

Lin

ear

grow

th

M

ean

LAZ

at

bir

th—

——

—52

7−1

.04

± 1

.14

886

−0.6

1 ±

0.9

893

−0.3

5 ±

0.9

4

M

ean

ΔLA

Z b

irth

to

6 m

o—

——

—52

7−0

.20

± 0

.99

886

−0.0

8 ±

0.8

193

−0.0

7 ±

0.9

1

LA

Z at

6 o

r 9d

mo:

mea

n11

11−1

.19

± 1

.09

1107

−1.3

9 ±

1.0

156

8−1

.26

± 1

.15

914

−0.7

0 ±

1.0

015

8−0

.48

± 0

.76

M

ean

ΔLA

Z 6

or 9

d t

o 18

mo

1111

−0.3

6 ±

0.6

111

07−0

.46

± 0

.75

568

−0.2

8 ±

0.7

291

4−0

.13

± 0

.61

158

−0.1

9 ±

0.6

3

M

ean

LAZ

at

18 m

o11

11−1

.55

± 1

.09

1107

−1.8

5 ±

1.0

656

8−1

.54

± 1

.14

914

−0.8

3 ±

1.0

115

8−0

.68

± 0

.75

18-m

o d

evel

opm

ent

M

edia

n la

ngu

age

scor

ee—

—11

0626

± 2

356

825

± 2

391

328

± 1

915

340

± 2

1

M

edia

n m

otor

sco

ref

——

1073

39 ±

456

339

± 5

837

40 ±

314

440

± 3

M

ean

soc

ioem

otio

nal

sco

reg

——

1106

22 ±

556

722

± 6

913

21 ±

415

321

± 5

M

ean

exe

cuti

ve f

un

ctio

n s

core

h—

—80

95.

7 ±

2.3

477

6.3

± 2

.580

36.

6 ±

2.2

129

6.3

± 2

.3

a D

evel

opm

enta

l sco

res

in B

urk

ina

Faso

wer

e n

ot c

omp

arab

le t

o th

e ot

her

tri

als.

In t

he

1111

ch

ildre

n a

nal

yzed

her

e, t

he

med

ian

± S

D D

MC

-II la

ngu

age

scor

e w

as 2

0 ±

3, t

he

mot

or s

core

was

53

± 6

, an

d t

he

per

son

al-s

ocia

l sco

re w

as 4

8 ±

4.

b L

AZ w

as n

ot m

easu

red

at

bir

th in

iLiN

S-Z

INC

an

d iL

iNS

-DO

SE.

c Th

e lo

w r

isk

sam

ple

com

pri

sed

all

child

ren

wit

h n

one

of t

he

follo

win

g ri

sk f

acto

rs: a

sset

ind

ex b

elow

th

e m

edia

n, m

ater

nal

or

pat

ern

al e

du

cati

on b

elow

th

e m

edia

n, f

amily

car

e in

dic

ator

s sc

ore

bel

ow t

he

med

ian

, stu

nte

d (

LAZ

less

th

an –

2) a

t 6/

9

or 1

8 m

onth

s, a

nd

an

emic

(h

emog

lob

in le

vel <

110

g/L)

at

6/9

or 1

8 m

onth

s. T

his

sam

ple

incl

ud

ed 5

ch

ildre

n in

th

e ZI

NC

coh

ort,

56

child

ren

in t

he

DO

SE

coh

ort,

17

child

ren

in t

he

DYA

D-M

coh

ort,

an

d 8

0 ch

ildre

n in

th

e D

YAD

-G c

ohor

t.d In

Bu

rkin

a Fa

so, L

AZ w

as m

easu

red

at

9 m

onth

s; in

all

oth

er t

rial

s, L

AZ w

as m

easu

red

at

6 m

onth

s.e

Exp

ress

ive

voca

bu

lary

fro

m a

100

-wor

d v

ocab

ula

ry c

hec

klis

t.f N

um

ber

of

gros

s an

d fi

ne

mot

or s

kills

th

e ch

ild p

erfo

rmed

fro

m 6

9 it

ems.

g To

tal o

f 19

item

s sc

ored

0, 1

, or

2 in

dic

atin

g th

e fr

equ

ency

of

cert

ain

beh

avio

rs s

how

ing

beh

avio

ral a

nd

em

otio

nal

reg

ula

tion

.h T

otal

cor

rect

fro

m a

10-

item

A-n

ot-B

tas

k as

sess

ing

wor

kin

g m

emor

y an

d in

hib

itio

n.

by guest on August 14, 2020www.aappublications.org/newsDownloaded from

PEDIATRICS Volume 138 , number 2 , August 2016

FCI score, compared with the mid

and high tertiles.

Two significant interactions were

found with trial group: for language

development, the interaction with

6-month LAZ in the iLiNS-DYAD-M

(P = .02) and iLiNS-DYAD-G (P =

.08) cohorts. Table 6 displays these

associations according to trial group.

In both iLiNS-DYAD cohorts, the

association between 6-month LAZ

and language development was

significant in the iron and folic acid

group but not in the LNS group. In

Ghana, there was also no association

in the multiple micronutrients

(MMN) group.

DISCUSSION

We examined associations between

linear growth from birth to 18

months and 4 domains of child

development in 3700 children in 4

cohorts in Burkina Faso, Ghana, and

Malawi. With regard to the extent to

which children in these cohorts had

faltered in growth by age 18 months,

this factor ranged from 0.8 SD below

the mean of the WHO standard in

Ghana to 1.8 SD below the mean in

the iLiNS-DOSE cohort in Malawi. In

contrast, the difference in attained

length between the highest and

lowest wealth quartile within each

cohort was only 0.2 to 0.3 SD. This

finding suggests that even the most

economically advantaged children

within these samples were faltering

in linear growth compared with

global standards.

Conclusions are more difficult

to draw regarding the extent to

which children in these cohorts had

faltered in development because

no global standards exist. The

socioeconomic disparities in motor

development in the iLiNS-DOSE and

iLiNS-ZINC cohorts and in language

development in the iLiNS-DOSE

and iLiNS-DYAD-G cohorts were

similar to the disparities in linear

growth (0.2 to 0.4 SD). This finding

suggests that for these cohorts

and developmental domains,

economically disadvantaged children

were faltering to a similar extent as

in linear growth. The socioeconomic

disparities for all other cohorts

and domains were smaller and

nonsignificant, which suggests

that for these cohorts and domains,

even the most disadvantaged

children were not greatly falling

behind their more advantaged

peers. However, if the most

advantaged children were not

achieving their potential in linear

growth, it is possible that they

also were not achieving their

potential in development. Even

the subsample with the fewest

environmental constraints on

development, which included only

158 of 3700 children, had faltered

in linear growth 0.7 SD below the

WHO mean by age 18 months. This

low-risk sample scored on average

within the same range in motor,

socioemotional, and executive

function as the 4 cohorts. Their

median vocabulary score was 40

words, compared with a median

of 25 to 28 words in each cohort.

A difference of 12 to 15 words is

equivalent to ∼0.5 to 0.8 SD. These

findings suggest that with fewer

constraints on development, a

higher level of vocabulary could

have been achieved.

7

FIGURE 1Socioeconomic disparities in growth and development at age 18 months in each cohort. ***P < .001, **P < .01, *P < .05.

by guest on August 14, 2020www.aappublications.org/newsDownloaded from

PRADO et al 8

TABL

E 3

Asso

ciat

ion

s B

etw

een

Lin

ear

Gro

wth

an

d D

evel

opm

ent

in E

ach

Coh

ort

Vari

able

NM

odel

1a

Mod

el 2

b

R2

LAZ

at 6

or

9c M

onth

s:

Esti

mat

e ±

SE

ΔLAZ

Fro

m 6

or

9c to

18

Mon

ths:

Est

imat

e ±

SE

R2

LAZ

at 6

or

9c M

onth

s:

Esti

mat

e ±

SE

ΔLAZ

Fro

m 6

or

9c to

18

Mon

ths:

Est

imat

e ±

SE

18-m

o la

ngu

age

z sc

ore

iL

iNS

-ZIN

C (

Bu

rkin

a Fa

so)

1111

0.14

0.19

± 0

.03*

**0.

25 ±

0.0

5***

0.21

0.16

± 0

.03*

**0.

19 ±

0.0

5***

iL

iNS

-DO

SE

(Mal

awi)

1106

0.06

0.19

± 0

.03*

**0.

12 ±

0.0

4**

0.13

0.18

± 0

.03*

**0.

10 ±

0.0

4*

iL

iNS

-DYA

D-M

(M

alaw

i)56

80.

080.

17 ±

0.0

4***

0.22

± 0

.07*

**0.

160.

15 ±

0.0

4***

0.18

± 0

.06*

*

iL

iNS

-DYA

D-G

(G

han

a)91

30.

040.

07 ±

0.0

3*0.

11 ±

0.0

5*0.

170.

05 ±

0.0

3*0.

08 ±

0.0

5†

D

OS

E an

d D

YAD

poo

led

: fi x

ed e

ffec

ts m

odel

2587

0.06

0.14

± 0

.02*

**0.

14 ±

0.0

3***

0.14

0.13

± 0

.02*

**0.

11 ±

0.0

3***

D

OS

E an

d D

YAD

poo

led

: ran

dom

eff

ects

mod

eld

2587

—0.

14 ±

0.0

3†0.

14 ±

0.0

3*—

0.12

± 0

.03†

0.11

± 0

.03†

I2

(95%

CI)

——

77%

(26

–93

)0%

(0–

90)

—80

% (

37–

94)

0% (

0–90

)

18-m

o m

otor

z s

core

iL

iNS

-ZIN

C (

Bu

rkin

a Fa

so)

1111

0.22

0.34

± 0

.03*

**0.

47 ±

0.0

5***

0.33

0.30

± 0

.02*

**0.

39 ±

0.0

4***

iL

iNS

-DO

SE

(Mal

awi)

1073

0.16

0.21

± 0

.03*

**0.

31 ±

0.0

4***

0.18

0.21

± 0

.03*

**0.

30 ±

0.0

4***

iL

iNS

-DYA

D-M

(M

alaw

i)56

30.

170.

20 ±

0.0

4***

0.23

± 0

.06*

**0.

200.

18 ±

0.0

4***

0.21

± 0

.06*

**

iL

iNS

-DYA

D-G

(G

han

a)83

60.

070.

09 ±

0.0

3**

0.11

± 0

.05*

0.09

0.08

± 0

.03*

0.09

± 0

.05†

D

OS

E an

d D

YAD

poo

led

: fi x

ed e

ffec

ts m

odel

2472

0.14

0.17

± 0

.02*

**0.

24 ±

0.0

3***

0.16

0.16

± 0

.02*

**0.

22 ±

0.0

3***

D

OS

E an

d D

YAD

poo

led

: ran

dom

eff

ects

mod

eld

2472

—0.

17 ±

0.0

3*0.

22 ±

0.0

5†—

0.15

± 0

.03*

0.20

± 0

.06†

I2

(95%

CI)

——

78%

(30

–93

)80

% (

35–

94)

—80

% (

37–

94)

81%

(42

–94

)

18-m

onth

per

son

al-s

ocia

l z s

core

iL

iNS

-ZIN

C (

Bu

rkin

a Fa

so)

1111

0.14

0.18

± 0

.03*

**0.

27 ±

0.0

5***

0.20

0.16

± 0

.03*

**0.

21 ±

0.0

5***

18-m

o so

cioe

mot

ion

al z

sco

re

iL

iNS

-DO

SE

(Mal

awi)

1106

0.15

0.01

± 0

.03

0.01

± 0

.04

0.17

0.02

± 0

.03

0.01

± 0

.04

iL

iNS

-DYA

D-M

(M

alaw

i)56

70.

250.

00 ±

0.0

40.

01 ±

0.0

60.

260.

00 ±

0.0

40.

02 ±

0.0

6

iL

iNS

-DYA

D-G

(G

han

a)91

20.

07−0

.01

± 0

.03

0.00

± 0

.05

0.07

−0.0

2 ±

0.0

30.

00 ±

0.0

5

D

OS

E an

d D

YAD

poo

led

: fi x

ed e

ffec

ts m

odel

2585

0.14

−0.0

1 ±

0.0

20.

01 ±

0.0

30.

150.

00 ±

0.0

20.

02 ±

0.0

3

D

OS

E an

d D

YAD

poo

led

: ran

dom

eff

ects

mod

eld

2585

—−0

.01

± 0

.02

0.01

± 0

.03

—0.

00 ±

0.0

20.

02 ±

0.0

3

I2

(95%

CI)

——

0% (

0–90

)0%

(0–

90)

—0%

(0–

90)

0% (

0–90

)

18-m

o ex

ecu

tive

fu

nct

ion

z s

core

iL

iNS

-DO

SE

(Mal

awi)

809

0.03

0.03

± 0

.04

0.14

± 0

.05*

*0.

030.

04 ±

0.0

40.

14 ±

0.0

5**

iL

iNS

-DYA

D-M

(M

alaw

i)47

70.

06−0

.01

± 0

.05

0.04

± 0

.07

0.09

−0.0

1 ±

0.0

50.

03 ±

0.0

7

iL

iNS

-DYA

D-G

(G

han

a)80

20.

010.

02 ±

0.0

40.

01 ±

0.0

60.

030.

02 ±

0.0

40.

02 ±

0.0

6

D

OS

E an

d D

YAD

poo

led

: fi x

ed e

ffec

ts m

odel

2088

0.05

0.02

± 0

.02

0.07

± 0

.03*

0.06

0.02

± 0

.02

0.07

± 0

.03*

D

OS

E an

d D

YAD

poo

led

: ran

dom

eff

ects

mod

eld

——

0.02

± 0

.02

0.07

± 0

.04

—0.

02 ±

0.0

20.

07 ±

0.0

4

I2

(95%

CI)

——

0% (

0–90

)36

% (

0–79

)—

0% (

0–90

)32

% (

0–93

)

CI,

con

fi d

ence

inte

rval

. ***

P <

.001

, **P

< .0

1, *

P <

.05,

† P <

.1.

a Ad

just

ed f

or c

hild

age

, sex

, dat

a co

llect

or, a

nd

tri

al c

ohor

t gr

oup

.b A

dju

sted

for

ch

ild a

ge, s

ex, d

ata

colle

ctor

, an

d t

rial

coh

ort

grou

p, p

lus

bas

elin

e m

ater

nal

age

an

d e

du

cati

on, a

sset

ind

ex b

elow

med

ian

, HFI

A sc

ore

>2,

HIV

sta

tus,

an

d F

CI s

core

.c

In B

urk

ina

Faso

, LAZ

was

mea

sure

d a

t 9

mon

ths;

in a

ll ot

her

tri

als,

LAZ

was

mea

sure

d a

t 6

mon

ths.

d A

dju

sted

for

ran

dom

eff

ects

of

tria

l coh

ort

on in

terc

ept,

slo

pe

of L

AZ a

t 6

mon

ths,

an

d s

lop

e of

ΔLA

Z fr

om 6

to

18 m

onth

s.

by guest on August 14, 2020www.aappublications.org/newsDownloaded from

PEDIATRICS Volume 138 , number 2 , August 2016

Linear growth was associated with

language, motor, and personal-social

development but not socioemotional

development or executive function,

with the exception that the

association between ΔLAZ from

6 to 18 months and executive

function was significant in the

iLiNS-DOSE cohort in Malawi. This

finding suggests that from birth to

18 months, children’s growth in

height is generally related to the

development of language, motor,

and personal-social skills (feeding,

dressing, and toilet training) but not

executive function or socioemotional

skills (paying attention, regulating

anger and aggression). This lack

of association is consistent with

1 study that found no association

between child height and scores

on the A-not-B task in 15-month-

old children in Uganda 23 and 1

study that found no association

with attention in 6- to 9-month-old

infants. 28 Few studies examining

linear growth in children aged <2

years have assessed socioemotional

or executive function, partly

because these factors are difficult to

assess at this age. Children aged <2

years have only begun to develop

these skills, and few assessments

exist, particularly for executive

function, whereas even fewer have

been evaluated for psychometric

properties, such as predictive

validity. 29 A few studies in older

children have reported associations

between socioemotional skills and

height-for-age, but even in older

children, few studies of linear

growth have examined these

domains. 6

For language development, the

pooled adjusted estimate of the

association with LAZ at 6 months

was 0.13 SD; with ΔLAZ from 6 to

18 months, it was 0.11 SD (model

2). For motor development, these

estimates were 0.16 SD and 0.22

SD, respectively. The sums of these

estimates in each domain were the

same as the cross-sectional pooled

9

TABL

E 4

Asso

ciat

ion

s B

etw

een

Lin

ear

Gro

wth

an

d D

evel

opm

ent

From

Bir

th t

o 18

Mon

ths

in t

he

iLiN

S-D

YAD

Coh

orts

Vari

able

NM

odel

1a

Mod

el 2

b

R2

LAZ

at B

irth

:

Esti

mat

e ±

SE

ΔLAZ

Fro

m B

irth

to

6

Mon

ths:

Est

imat

e ±

SE

ΔLAZ

Fro

m 6

to

18

Mon

ths:

Est

imat

e

± S

E

R2

LAZ

at B

irth

:

Esti

mat

e ±

SE

ΔLAZ

Fro

m B

irth

to

6

Mon

ths:

Est

imat

e ±

SE

ΔLAZ

Fro

m 6

to

18

Mon

ths:

Est

imat

e ±

SE

Lan

guag

e z

scor

e

iL

iNS

-DYA

D-M

527

0.08

0.19

± 0

.05*

**0.

18 ±

0.0

6**

0.25

± 0

.07*

**0.

180.

16 ±

0.0

5**

0.15

± 0

.05*

*0.

20 ±

0.0

7**

iL

iNS

-DYA

D-G

885

0.05

0.11

± 0

.03*

*0.

02 ±

0.0

40.

11 ±

0.0

5*0.

170.

07 ±

0.0

3*0.

03 ±

0.0

40.

08 ±

0.0

5†

Mot

or z

sco

re

iL

iNS

-DYA

D-M

524

0.17

0.20

± 0

.04*

**0.

22 ±

0.0

5***

0.26

± 0

.07*

**0.

200.

18 ±

0.0

5***

0.21

± 0

.05*

**0.

23 ±

0.0

7***

iL

iNS

-DYA

D-G

812

0.07

0.11

± 0

.04*

*0.

07 ±

0.0

4†0.

13 ±

0.0

6*0.

090.

09 ±

0.0

4*0.

07 ±

0.0

4†0.

10 ±

0.0

6†

Soc

ioem

otio

nal

z s

core

iL

iNS

-DYA

D-M

526

0.25

0.00

± 0

.04

0.00

± 0

.05

0.00

± 0

.06

0.26

0.01

± 0

.04

−0.0

1 ±

0.0

50.

01 ±

0.0

7

iL

iNS

-DYA

D-G

884

0.07

−0.0

1 ±

0.0

3−0

.01

± 0

.04

0.01

± 0

.05

0.08

−0.0

1 ±

0.0

3−0

.01

± 0

.04

0.00

± 0

.05

Exec

uti

ve f

un

ctio

n z

sco

re

iL

iNS

-DYA

D-M

445

0.05

0.01

± 0

.05

−0.0

5 ±

0.0

6−0

.01

± 0

.08

0.09

−0.0

1 ±

0.0

5−0

.06

± 0

.06

−0.0

2 ±

0.0

8

iL

iNS

-DYA

D-G

779

0.02

0.05

± 0

.04

−0.0

2 ±

0.0

50.

01 ±

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PRADO et al

adjusted estimates reported by

Sudfeld et al 6 for children aged <2

years, which were 0.24 SD in the

cognitive domain and 0.38 SD in the

motor domain. When we examined

growth status separately at birth

and from birth to 6 months, both

growth measures showed significant

associations with language and

motor development in Malawi;

in Ghana, only the associations

for LAZ at birth were significant.

Together, these findings show

that growth faltering during any

period before birth, from birth to 6

months, and from 6 to 18 months is

similarly associated with the motor

and language skills children have

attained by 18 months, suggesting

that no period is more important

than another but rather that this

entire period is important for

intervention.

Associations between all measures

of growth and development

were similar with and without

adjusting for maternal age and

education, household asset index

and food insecurity, HIV status, and

developmental stimulation in the

home. Thus, we found no evidence

that linear growth is a proxy for

these aspects of the environment

but rather the associations between

growth and development remained

consistent when controlling

for these factors. However, it is

possible that other unmeasured

factors confound the association.

Convincing evidence for causality

would be an intervention that

positively affects both growth

and development, in which the

effect on development is mediated

by the effect on growth. We are

unaware of such a study. In the

iLiNS-ZINC trial, the intervention

positively affected both linear

growth 9 and development 11;

however, the effect on development

was not mediated by the effect

on growth. 30 The finding that the

intervention had independent

effects on growth and development

suggests that these effects

occurred through different

mechanisms and does not support

a causal link between growth and

development.

Although the associations of linear

growth with language and motor

development were remarkably

consistent across sites, they

were weaker or absent in certain

subsamples of children, specifically

children with a high level of

developmental stimulation from

the environment and children

whose mothers received LNS or

MMNs during pregnancy. The lack

of association between growth

and aspects of development in

these subsamples is consistent

with samples of children with

few environmental constraints on

growth. 14 This scenario suggests

that both developmental stimulation

and maternal supplementation

can protect children from the

commonly observed association

between growth faltering and

poorer language and motor skills.

The interaction with maternal

supplementation was only evident

for the associations with growth

in early infancy (age 6 months).

We found no evidence that

child supplementation with LNS

attenuated the association

between linear growth and

development from 6 to 18 months.

We also found no evidence that

sufficient growth during an

earlier time period (before

6/9 months) protected children

from an association between

growth faltering and poor

development in later infancy. This

outcome further supports the

conclusion that healthy growth

during each period before

6 months and from 6 to

18 months is similarly associated

with motor and language

development.

CONCLUSIONS

Linear growth faltering from birth

to 18 months is associated with

deficits in the development of

10

TABLE 5 Associations Between Linear Growth and Development According to FCI Score

Variable Lowest Tertile

FCI Score

Middle Tertile

FCI Score

Highest Tertile

FCI Score

iLiNS-ZINC

Association between 9-mo LAZ and 18-mo

motor z score

0.35 (0.04)*** 0.31 (0.04)*** 0.25 (0.04)***

Association between ΔLAZ from 9 to 18 mo

and 18-mo language z score

0.32 (0.07)*** 0.09 (0.09) 0.11 (0.09)

iLiNS-DOSE and iLiNS-DYAD pooled

Association between 6-mo LAZ and 18-mo

motor z score

0.20 (0.03)*** 0.14 (0.03)*** 0.14 (0.03)***

Data are presented as estimate (SE). Adjusted for child age, sex, data collector, and trial cohort group, plus baseline

maternal age and education, asset index below median, HFIA score > 2, HIV status, and FCI score. ***P < .001.

TABLE 6 Associations Between Linear Growth and Development According to Trial Group

Variable IFA Group MMN Group LNS Group

iLiNS-DYAD-M

Association between 6-mo LAZ and 18-mo

language z score

0.25 (0.06)*** 0.15 (0.06)* 0.00 (0.07)

iLiNS-DYAD-G

Association between 6-mo LAZ and 18-mo

language z score

0.14 (0.05)*** 0.03 (0.05) 0.00 (0.05)

Data are presented as estimate (SE). Adjusted for child age, sex, data collector, and trial group, plus baseline maternal

age and education, asset index below median, HFIA score >2, HIV status, and FCI score. IFA, iron and folic acid. ***P < .001,

*P < .05.

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PEDIATRICS Volume 138 , number 2 , August 2016

language, motor, and personal-

social skills but not socioemotional

or executive function skills, at least

as measured in this study. Linear

growth during different periods

(before birth, in early infancy, and in

later infancy) is similarly associated

with the development of these

skills, indicating that children who

falter in growth during any of these

periods have poorer motor and

language skills at age 18 months.

Developmental stimulation from

the environment and maternal

supplementation with LNS or MMNs

may protect children who are faltering

in growth from poor development of

language and motor skills.

ACKNOWLEDGMENTS

We thank the families and

communities who participated in the

iLiNS trials and the iLiNS teams who

executed the studies. Rosemonde

Guissou, Zinewendé Ouédraogo,

Harriet Okronipa, Martin Ndelemani,

Thokozani Phiri, Nozgechi Phiri, Chiza

Kumwenda, Jaden Bendabenda, and

Andrew Matchado contributed to the

coordination of the studies. Boateng

Bannerman, Joy Thakwalakwa, Lotta

Alho, and Basho Poelman contributed

to data cleaning and database

management. Charles Arnold and

Rebecca Young provided statistical

support. Mamane Zeilani served on

the iLiNS project Steering Committee.

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11

ABBREVIATIONS

CDI:  communicative

development inventory

DMC-II:  Developmental

Milestones Checklist–II

FCI:  family care indicators

HFIA:  household food insecurity

access

iLiNS:  International Lipid-Based

Nutrient Supplements

LAZ:  length-for-age z score

LMICs:  low- and middle-income

countries

LNS:  lipid-based nutrient

supplements

MMN:  multiple micronutrients

WHO:  World Health Organization

and supervised the iLiNS trials, designed the data collection instruments, served on the iLiNS Project steering committee, and critically reviewed the manuscript;

and all authors approved the fi nal manuscript as submitted.

This trial has been registered at www. clinicaltrials. gov (identifi ers NCT00944281, NCT00945698, NCT01239693, and NCT00970866).

DOI: 10.1542/peds.2015-4698

Accepted for publication May 24, 2016

Address correspondence to Elizabeth L. Prado, PhD, Program in International and Community Nutrition, University of California at Davis, 3253 Meyer Hall, One

Shields Ave, Davis, CA 95616. E-mail: elprado@ucdavis.edu

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2016 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: Dr Brown worked as a consultant and later as an employee for the Bill & Melinda Gates Foundation. The other authors have indicated

they have no fi nancial relationships relevant to this article to disclose.

FUNDING: Based on research funded in part by a grant to the University of California Davis from the Bill & Melinda Gates Foundation, with additional funding

from the Offi ce of Health, Infectious Diseases, and Nutrition, Bureau for Global Health, US Agency for International Development under terms of Cooperative

Agreement No. AID-OAA-A-12-00005, through the Food and Nutrition Technical Assistance III Project, managed by FHI 360. The sponsors of the study had no role in

the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study

and had fi nal responsibility for the decision to submit for publication.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose.

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