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Review Article

Nutrition (Micronutrients) in Child Growth and Development: A


Systematic Review on Current Evidence, Recommendations and
Opportunities for Further Research
Mohammad Yawar Yakoob, MD, MS, DS,* Clifford W. Lo, MD, PhD†

ABSTRACT: Objective: An important aspect of malnutrition is deficiency of different micronutrients during


pregnancy or early childhood. We systematically reviewed the role of nutrition in child growth (weight or
height gain) and development. Methods: A comprehensive literature search was done on PubMed/Cochrane
Library browsing through 38,795 abstracts until December 31, 2016 to select systematic reviews/meta-
analyses and individual randomized controlled trials (RCTs) of micronutrient supplementation. Results:
Micronutrients studied included iron, iodine, folate, zinc, calcium, magnesium, selenium, vitamin D, vitamin
A, vitamin B complex, and multiple micronutrients. We summarize evidence with details and results of RCTs,
highlight strengths/weaknesses, and critically interpret findings. Effects of breastfeeding-promotion, food-
supplementation (complementary and school feeding), conditional-cash-transfers, and integrated nutrition/
psychosocial interventions are discussed. Conclusion: Based on this evidence we make policy and pro-
grammatic recommendations for supplementation to mothers and children at high-risk of deficiency.
(J Dev Behav Pediatr 0:1–15, 2017) Index terms: micronutrient supplementation, pregnancy, child growth and development.

T he future of human societies depends on children


being able to achieve their optimal growth and de-
first 2 years of life. This requires a diet that provides suf-
ficient nutrients for normal, healthy growth.3 Maternal
velopment. The Lancet Series on Child Development undernutrition can lead to low birth weight (LBW), pre-
identified 4 risk factors in resource-poor countries where term births, and small-for-gestational age babies.4 Preterm
the need for intervention is urgent in terms of improving and LBW infants are at increased risk of major impair-
child development, 3 of which were nutrition-related: ments, as well as below-average cognitive abilities and
stunting, iodine deficiency, and iron deficiency anemia. greater behavioral problems at school age, even in the
These, along with other undernutrition factors, are com- absence of obvious neurological deficits.5 Therefore,
mon during pregnancy and early childhood in resource- interventions can be targeted at the periconceptional
poor countries. It is important to address nutrition-related phase and during pregnancy.
risks to support optimal development in early childhood The development of the brain occurs at an earlier
with implications throughout life.1,2 stage than the rest of the body. This can be illustrated by
Inadequate maternal and early child nutrition may limit the fact that a newborn’s brain is about 10% of the body
the development of important aspects of the brain’s ar- weight, whereas in the adult, it is only 2%. By the age of
chitecture. The brain is vulnerable to nutritional influen- 1 year, the child will be about 15% of the final body
ces from the preconception period as well as the earliest weight but the brain will be already about 70% of that of
stages of pregnancy from the time the neural plate is a young adult. By 2 years of age, the brain will be about
formed leading to a neural tube, a process that is complete 77% of its final weight, whereas the body is about 20% of
from 21 to 28 days after conception.3 The brain also the adult level.6 After birth, the key window of oppor-
grows very rapidly in the last trimester of pregnancy and tunity for interventions is during the first 24 months of
life, since the brain development is in an important
From the *Department of Epidemiology, Harvard T. H. Chan School of Public phase during this period. This is the period of peak in-
Health, Boston, MA; †Department of Nutrition, Children’s Hospital Boston,
Boston, MA. cidence of growth faltering, micronutrient deficiencies,
Received June 2016; accepted June 2017. and infectious illnesses in resource-poor countries.7 After
Disclosure: The authors declare no conflict of interest. this period, the effects of malnutrition on stunting may
Supplemental digital content is available for this article. Direct URL citations be irreversible, and some of the functional deficits may
appear in the printed text and are provided in the HTML and PDF versions of this become permanent.8 Exclusive breastfeeding is recom-
article on the journal’s Web site (www.jdbp.org). mended for the first 6 months of life, after which com-
Address for reprints: Mohammad Yawar Yakoob, MD, MS, DS, Department of plementary foods should be introduced. Therefore,
Nutrition, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue,
Boston, MA 02115; e-mail: myyakoob@mail.harvard.edu. interventions like breastfeeding-promotion and comple-
mentary feeding strategies (provision of complementary
Copyright Ó 2017 Wolters Kluwer Health, Inc. All rights reserved.
foods with or without nutrition education is discussed

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later in this article) that are effective at reducing mal- 2016, and involved screening a further approximate
nutrition during this vulnerable period should be a high 2795 abstracts. The approximate search terms used
priority. Early childhood stunting caused by malnutrition were, for example, (iron) AND (growth OR de-
is associated with adverse developmental outcomes, es- velopment) AND (infan* OR child OR children); (“vita-
pecially, deficits in cognition and school achievement min a”) AND (growth OR development) AND (infan* OR
from early childhood to late adolescence.9–11 child OR children) AND suppl*; (breastfeeding) AND
Malnutrition, especially, micronutrient deficiencies, (growth OR development) AND (infan* OR child OR
can also occur in resource-rich countries. Subtle dif- children) AND (promotion OR support); (food OR
ferences in diet composition can lead to micronutrient feeding) AND (growth OR development) AND (infan*
deficiencies. Micronutrient deficiencies may also in- OR child OR children) AND (complementary OR pre-
teract with the gut microbiome and alter the immune school OR preschool OR school); and (“conditional cash
response of the intestine. For example, iron deficiency transfer*”) AND (growth OR development) AND (infan*
can deplete lactobacilli that convert lactose and other OR child OR children).
sugars to lactic acid and may result in diarrhea, or zinc Studies that reported outcomes on growth (weight
deficiency can decrease richness and species diversity, and height gain) and/or development were selected and
decrease Gram-negative facultative anaerobes and lac- were from both resource-rich and resource-poor coun-
tobacilli, and affect the immune system.12,13 tries. The priority was to obtain systematic reviews and
It is also now widely recognized that nutritional the most recent randomized controlled trials on the
well-being is not only related to dietary adequacy and topic. In the absence of such evidence, observational
quality, but also to the process of feeding and parenting studies were also selected. We have made separate
psychosocial determinants. These include areas like cog- sections of supplementation during pregnancy and
nitive stimulation, caregiver sensitivity and responsiveness during childhood and within each section described the
to the child, and caregiver affect (emotional warmth or outcomes of growth first and then development. We
rejection of the child). It is known that responsive feeding excluded studies of food fortification and where
might have a role in ameliorating child undernutrition micronutrients were part of the diet and not given as
because positive caregiver verbalizations during feeding supplements.
can increase child acceptance of food.14 Similarly, par-
enting styles and feeding practices can influence a child’s RESULTS
body mass index (BMI), for example, indulgent or pro- Role of Micronutrients
tective parenting was associated with higher BMI and The main micronutrients considered in this review in-
authoritative parenting with a healthy BMI.15 Besides, clude iron, iodine, folic acid, zinc, vitamin A and vitamin
studies by Galler et al. and Lozoff et al. have shown that D. Deficiency may occur for more than 1 nutrient;
compromised nutritional status during the first year of therefore, the role of multiple micronutrients (MMNs) is
life is associated with neurocognitive impairments per- also covered in this article (Supplemental Digital Content
sisting into adulthood despite complete catch-up physical 1, http://links.lww.com/JDBP/A143). Other miscellaneous
growth at adolescence.16–18 micronutrients are also discussed in brief like calcium,
This review, therefore, includes the efficacy and ef- magnesium, selenium and vitamin B complex.
fectiveness of nutrition-only–related interventions along
with integrated nutrition-psychosocial interventions af- Iron Supplementation
fecting child growth (weight or height gain) and de- Globally, anemia affects 47.4% of preschool children
velopment. We conclude with considerations for policy and 25.4% of school age children,3 most of which is due
and program planners for large-scale implementation. to iron deficiency. Iron deficiency anemia is, therefore,
one of the most prevalent yet neglected nutritional
METHODOLOGY deficiencies in the world. The influence of iron de-
We did a comprehensive literature search on PubMed ficiency in children has been reviewed in several studies
(MEDLINE) and the Cochrane Clinical Trials using the leading to very similar conclusions. It has been seen that
following search strategy: it leads to poorer developmental outcomes in infancy
(“Micronutrients” [Mesh] OR nutrition OR micro- and childhood, especially, motor, cognitive, social-
nutrient* OR “multiple micronutrient*” OR zinc OR emotional and neurophysiologic development in the
iodine OR calcium OR magnesium OR “vitamin D” OR short term and in the long term.19–24 The effects of early
“vitamin A” OR iron OR “folic acid” OR “vitamin B” OR iron deficiency include decreased myelination, changes
breastfeeding OR food OR “cash transfer*”) AND in dopamine metabolism in the striatum, and alterations
(growth OR development) AND (infan* OR child OR in the energy metabolism of the hippocampus, an area of
children). the brain important for memory.25 New findings also
The last date of search was January 31, 2010. A total of point to the need for more attention to the de-
36,000 abstracts were screened and evaluated. The velopmental effects of prenatal iron deficiency. The most
search for recent systematic reviews and meta-analyses common etiology of reduced iron supply to the fetus is
was updated in December 2016 up to December 31, maternal iron deficiency, and fetal and neonatal iron

2 Nutrition in Child Growth and Development Journal of Developmental & Behavioral Pediatrics

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deficiency adversely affects developing brain-behavior these reviews and the findings for iron-replete children
systems.23 have been conflicting. Gahagan et al.39 retrospectively
Iron Supplementation in Pregnancy examined short- and long-term growth in iron-sufficient
A recent systematic review by Chmielewska et al.26 (IS) infants from a randomized trial of iron supplemen-
that studied prenatal iron supplementation during preg- tation among breastfed, low- to middle-income Chilean
nancy showed no effect of iron supplementation on the infants. Growth trajectories between iron supplemented
mental development or the behavioral status of their and usual nutrition groups did not differ during or after
children. Individual studies found from our literature supplementation indicating no adverse effect of iron in IS
search reported similar findings. In a randomized study infants. Similarly, in Bangladesh, iron was found to have
by Frith et al.27 from Bangladesh, mothers from 14 weeks no impact on the rate of length or weight gain for infants
of gestation to 12 weeks postpartum were assigned into aged 6 to 12 months or when stratified by baseline he-
3 groups: 30 mg Fe 1 400 mg folic acid, 60 mg Fe 1 400 moglobin concentration.40 However, Lind et al. from
mg folic acid, and MMNs. Compared with 30 mg Fe, 60 secondary analysis of 6-month old Indonesian infants
mg Fe decreased the quality of maternal-infant feeding participating in a randomized trial showed that weight-
interaction by approximately 10%. This could be because for-age Z score (WAZ) from 6 to 12 months and mean
of a higher dose of iron inhibiting zinc absorption lead- WAZ at 12 months were significantly lower in the iron-
ing to decreased plasma zinc concentrations, gastroin- replete iron-supplemented group compared with iron-
testinal side effects, and increased maternal morbidity replete non–iron-supplemented infants.41 In another re-
because of reduced immunity or higher bacterial viru- cent randomized trial42 on breastfed infants enrolled at 1
lence. MMNs compared with 30 mg of iron did not im- month and supplemented from 4 months, medicinal iron
prove interaction but reduced early postpartum distress. was associated with a small but significant reduction in
This may be related to the effect of micronutrients on length gain and a trend toward reduced weight gain at
significant neurotransmitters. A randomized controlled the end of supplementation at 9 months. However,
trial from Australia28 by Zhou et al. on prenatal 20 mg/ provision of medicinal iron or iron-fortified cereal did
d iron supplementation from 20 weeks of gestation to improve the iron status in this study.
delivery compared with placebo group found no differ- We identified a few reviews on the relationship be-
ence in the mean composite IQ score or any of its sub- tween iron and developmental outcomes. The results
scales or in the proportion of children with IQ 1 or 2 SD were mixed. Reviews32,34,38,43,44 of oral, preventive ,and
below the mean at 4 years of age after multiple con- therapeutic iron supplementation in children showed
founder adjustments such as sex, birth order, gestational reductions or improvement in cognitive and motor de-
age, maternal age, maternal education, paternal educa- velopment deficits, and improvement in memory and
tion, home environment, and breastfeeding. Another learning in iron-deficient or anemic children, particu-
Chinese study by Li et al. on prenatal iron and folic acid larly, with longer-duration, lower-dose regimens. The
supplementation (60 mg iron and 400 mg/d folic acid) review by Low et al. reported improvement in global
compared with folic acid alone showed no effect on the cognitive scores, IQ, attention, and concentration.43
Bayley mental development index and Bayley psycho- Similarly, a recent review by Lam and Lawlis45 was based
motor development index (PDI) of children at 3, 6, and on 2 trials, of which 1 reported improvement in in-
12 months of age.29,30 telligence and attention after iron supplementation,46
Iron Supplementation in Infancy/Children whereas the other reported higher increase in IQ score
Petry et al.,30 Ramakrishnan et al.,31,32 US Preventive in weekly versus daily supplementation but no differ-
Services Task Force,31 Baumgartner et al.,32 Pasricha ence between weekly and placebo.47 Another review,
et al.,33,34 Vucic et al.35 and Sachdev et al.36 did meta- based on 5 RCTs, suggested a possible moderate im-
analyses/systematic reviews of randomized controlled provement in PDI score that was most evident at 12
intervention trials of the impact of iron supplementation months of age with no effect on mental development or
on child growth and showed that iron had no significant behavior of children.26 Another systematic review by
effect on child growth. There was no significant effect of Sachdev et al.48 comprising 15 randomized studies on
iron therapy on any of the anthropometric variables 2827 children showed that after supplementation the
studied: weight-for-age, weight-for-height, height-for-age, combined mental development score standardized mean
mid-upper arm circumference, skinfold thickness, and difference (SMD) (random model) was 0.30 (95% CI,
head circumference.30,36 Overall, effect sizes were 0.09 0.15–0.46; p , .001). Baseline anemia and iron de-
[95% confidence interval (CI), 20.07 to 0.24] for height ficiency anemia were responsible for heterogeneity. For
and 0.13 (95% CI, 20.05 to 0.30) for weight.37 Iron IQ scores (4 trials on children $ 8 years of age), the
therapy, however, did significantly improve hemoglobin combined SMD was 0.41 (95% CI, 0.20–0.62, p , .001).
levels in these reviews.30,37 Also, another 2006 review38 There was no effect of iron on motor development
showed that with iron supplementation, weight gains score. In contrast, other recent reviews concluded that
were adversely affected in iron-replete children and the iron supplementation in children under 2 years of age
effects on height were inconclusive. Many studies, in- did not have an effect on Bayley MDI (MD 1.65, 95% CI
cluding randomized trials, have been published after 20.63 to 3.94; 6 studies, n 5 1093) and PDI (1.05, 21.36

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to 3.46; 6 studies, n 5 1086).30,33,49 A review by Guo experimental or observational studies were found. A
et al. reported no difference in global cognitive perfor- nonrandomized intervention study75 compared psycho-
mance in primary school children after iron supple- logical development of infants aged 3 to 18 months for
mentation50 and similarly, US Preventive Services Task 300 mg/d of KI (n 5 133) during the first trimester of
Force review found mostly nonsignificant results for pregnancy versus no iodine supplements (n 5 61). This
developmental test scores after 3 to 12 months of follow- study found that children of iodine-supplemented
up.31 A Cochrane review51,52 on iron therapy in children mothers had a more favorable psychometric assess-
less than 3 years of age with iron deficiency anemia in- ment than those of the unexposed group. They had
cluded 5 trials and studied measures of psychomotor higher scores on the PDI (p 5 .02) and the Behavior
development within 30 days of commencement of Rating Scale. However, this study was not controlled for
therapy. The combined difference in pretreatment to different confounding factors but is the best evidence
posttreatment change in Bayley PDI between iron and available. Another recent intervention study76 of preg-
placebo groups and in Bayley MDI was also non- nant women with mild hypothyroxinemia reported
significant, but the days elapsed since the start of treat- delayed neurodevelopmental outcomes among children
ment were few. of nonsupplemented mothers. The mean developmental
quotient of children of mothers with thyroxine levels
Iodine Supplementation above the 20th percentile at the beginning of gestation
Iodine is a clear example of a nutrient that, if deficient (4–6 weeks) was 101.8 6 9.7 versus 87.5 6 8.9 in non-
during a critical period of brain development, has long- supplemented mothers. The timing of the start of in-
term adverse consequences.3 Iodine deficiency is the tervention was potentially important; supplementation
single most important cause of preventable brain damage starting at 12 to 14 weeks of gestation was associated
and mental retardation. It is required for the production with worse scores than supplementation starting at 4 to
of thyroid hormones that are essential for brain de- 6 weeks. In a small pilot study in France (n 5 44) of
velopment, and the fetus, newborn, and young child are prenatal 150 mg/d of iodine supplementation from , 10
particularly vulnerable to iodine deficiency. Severe io- weeks of gestation to 3 months postpartum, scores in
dine deficiency during gestation results in fetal brain Bayley Scales of Infant Development were not different
damage that is irreversible by mid-gestation, commonly in exposed at 24 months compared with unexposed
leading to cretinism and impaired cognitive function in group.77 However, 2 other studies78,79 from Spain
children.53 Mild-to-moderate maternal hypothyroxinemia reported that women with self-reported iodine intake of
may also result in suboptimal neurodevelopment.54 Even 150 mg/d compared with ,100 mg/d had infants with
mild-to-moderate deficiency in children has been asso- lower PDI (PDI , 85, OR 5 1.8, 1.0–3.3). The compar-
ciated with lower IQs and more disruptive behavior.55–57 ison range of iodine intake was narrower in these studies
Iodine Supplementation During Pregnancy with potential for misclassification in reporting intakes.
Multiple systematic reviews and meta-analyses have Meta-analysis comprising some of these non-RCTs plus
studied maternal iodine supplementation.54,58–64 The additional ones found that iodine supplementation be-
findings from the trials have also been mixed. In 1 trial fore or early in pregnancy compared with control had an
from Peru, there was no difference between iodine and average effect size of 0.51 (8 non-RCTs) for mental de-
placebo groups in gross development of newborns, but velopment score that was smaller (d 5 0.17) for late
in subgroup observational analysis, iodine-supplemented pregnancy supplementation (4 non-RCTs).63
mothers had infants with higher IQ scores (85.6 6 13.9 Iodine Supplementation in Children
compared with 74.4 6 14.8, p 5 .002) and lower psy- Childhood iodine supplementation has been covered
chological age retardation (15.5 6 11.6% compared with in multiple systematic reviews and meta-analyses.58–
26.6 6 14.1%, p , .01).65–67 In the trial from Papua New 60,63,80
The Cochrane review80 on iodine supplementa-
Guinea, incidence proportion of cretinism in iodine- tion in children under 18 years of age in iodine de-
supplemented villages was 2% versus 6% in placebo ficiency areas included a total of 26 studies. Different
group (RR 5 0.27, 0.12–0.60, p 5 .002) up to a follow-up forms of iodine supplementation were used in these
period of 15 years after intervention.68–71 RCTs on studies, including iodized salt, iodized oil (oral form),
pregnant women with mild thyroid dysfunction found intramuscular oil, iodized water, etc. Body weight was
no effect on children’s IQ status or cognitive functioning given as an outcome in 4 studies81–84: weight increased
through 3 or 5 years with levothyroxine treatment versus by 5.2% (after 4 months) to 27.5% (after 22 months) in
none started before 18 weeks of gestation.72,73 Similarly, the intervention groups (oral-iodized oil) and 3.4% to
another recent randomized intervention study74 com- 13.2% (both after 10 months) in the control groups. In 3
prising 3 groups (iodized salt in cooking and at the table, of these 4 trials, increases were slightly greater in the
200 mg of potassium iodide (KI)/d, 300 mg/d of KI) intervention group than in the control, but were non-
evaluated maternal iodine supplementation in 131 preg- significant. Increase in height was also given in 4 stud-
nant women during the first trimester and found no ef- ies.81–83,85 It was 2.7% (after 10 months) to 7% (after 22
fect on children’s neurological development nor effect months) in the intervention (oral-iodized oil) group and
modification by treatment groups. Five other quasi- 2.3% (after 10 months) to 7.9% (after 22 months) in the

4 Nutrition in Child Growth and Development Journal of Developmental & Behavioral Pediatrics

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control group. Moreover, 3 prospective double-blind Zinc Supplementation
supplementation intervention versus placebo stud- Zinc is involved in the activity of over 200 enzymes, in
ies86,87 were conducted on 7- to 10-year-old severely particular, those associated with synthesis of DNA and
iodine-deficient Moroccan children (n 5 71; 10-month RNA. An estimated 17.3% of the world population has
study of iodized salt), moderately deficient 10- to 12- inadequate zinc intakes.91 Although zinc plays essential
year-old Albanian children (n 5 310; 6-month study; developmental roles both before and after birth, its role
400 mg iodine as oral iodized oil), and mildly deficient 5- in the brain is poorly understood. In animal studies, it has
to 14-year-old South African children (n 5 188; 6-month been shown that zinc deficiency during gestation and
study; 2 doses of 200 mg iodine as oral-iodized oil). At lactation results in irreversible cognitive impairment.3
follow-up, supplementation did not have a significant Zinc deficiency in infants may also compromise behav-
effect on somatic growth among South African children iors necessary for cognitive functioning including activ-
but increased WAZ and height-for-age Z scores (HAZ) in ity and attention.92
Moroccan and Albanian children.
Shrestha83 showed significant improvement in hand Zinc Supplementation During Pregnancy
grip between intervention and control groups (32 vs The Cochrane review on zinc supplementation during
23.3% after 10 months). The difference in sitting/stand- pregnancy by Ota et al.93 has reported birth outcomes and
ing ability was also significant. The same study reported growth outcomes. Based on a meta-analysis of 14 RCTs
significant differences in ball-throwing abilities with no involving 5643 women, zinc supplementation during
differences in pegboard and balancing tests after 4 pregnancy was found to have no significant difference in
months. Huda 200184 evaluated 12 different cognitive low birth weight (LBW) (RR 5 0.93; 95% CI, 0.78–1.12),
and motor function tests without any significant differ- head circumference (7 RCTs), or mid-upper arm circum-
ences between the 2 groups. IQ was measured in 1 study ference (3 RCTs). Infant WAZ score was similar at 6
by Bautista et al.81 There were no significant differences months in the 2 groups based on 2 RCTs,94,95 but by 13
in increase in IQ, improvement in school grades, or in months, no-zinc group showed significantly higher scores
perceptual-motor development between intervention based on 1 RCT.94 Weight-for-height was also not different
and control groups. Improvement in cognitive perfor- between the 2 groups at 6 months. In a recent trial of
mance was also nonsignificant between the 2 groups as antenatal micronutrient supplementation,96 the mean
measured by Untoro et al.88 However, children who height of school age children in rural Nepal of mothers in
were more iodine-deficient exhibited greater increase in the iron 1 folic acid 1 zinc group was 113.93 (65.79)
cognitive performance than those who were more io- cm, compared with 113.33 (65.32) cm in iron 1 folic
dine replete. acid group (nonsignificant). The mean weight was also
A randomized, double-blind placebo-controlled trial89 of 18.12 (62.36) kg in the intervention versus 18.05 (62.32)
iodine supplementation was conducted in Dunedin, New kg in the iron 1 folic acid group. Another maternal sup-
Zealand, among 184 children aged 10 to 13 years who plementation study in Peru showed no effect on linear
were mildly iodine-deficient. Children were randomly growth, but it was associated with greater weight gain
assigned a daily tablet of 150 mg iodine or placebo for 28 through age 1 year of infancy (p , .001).97
weeks. Iodine supplementation significantly improved A meta-analysis by Warthon-Medina et al.98 showed no
scores for 2 of the 4 cognitive subsets (picture concepts effects of maternal zinc supplementation on the child’s
[p 5 .023] and matrix reasoning [p 5 .040]) but not for cognitive domains of intelligence, executive function, and
letter-number sequencing (p 5 .480) or symbol search motor skills. In the Cochrane review on maternal zinc
(p 5 .608). The overall cognitive score of the iodine- supplementation,99 2 trials100,101 measured child de-
supplemented group was 0.19 SDs higher than that of velopment outcomes. Hamadani et al.100 found that among
the placebo group (p 5 .011). After 28 weeks of supple- 168 Bangladeshi infants studied at 13 months, the zinc
mentation, iodine status improved in intervention group, group had significantly worse mental development, PDI
whereas the placebo group remained iodine-deficient. scores, emotional tone, and cooperation compared with
Another randomized double-blind trial of iodine supple- no-zinc group, with infant approach, activity, and vocali-
mentation in iodine-deficient 10- to 12-year-old children in zation showing no differences. The other RCT101 that fol-
Albania90 showed that compared with placebo, iodine lowed 355 infants of African-American mothers at 5 years
treatment significantly improved performance on 4 of 7 of age found no significant differences for differential
tests: rapid target marking, symbol search, rapid object abilities, visual or auditory sequential memory scores, Knox
naming, and Raven’s Colored Progressive Matrices cube, gross motor scale, and grooved pegboard scores.
(p , .0001). Meta-analysis based on these 2 studies58 Another review by Hess and King102 reports data from
showed a significant improvement in global cognitive a study in Peru103 where some improvements in infant
scores (adjusted SMD 5 0.27, 0.10–0.44, p 5 .002) and in neurobehavioral development (novelty preference) was
perceptual reasoning (0.55, 0.05–1.04, p 5 .03) with sig- observed in zinc-supplemented group at 6 months of age.
nificant between-study heterogeneity for the latter out- Zinc Supplementation in Children
come (I2 5 90%, p 5 .001). There was no benefit for the The impact of zinc supplementation in prepubertal
domains of processing speed index and working memory. and under-5 children on growth has been the subject of

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many reviews30,104–111 and multiple other studies. In anemia at baseline modified the effect of zinc on HAZ and
a 2009 review on preventive zinc supplementation by WAZ scores. Anemic infants supplemented for 6 months
Brown et al.,105 it was shown that there was a signifi- had significantly higher HAZ (0.17) and WAZ (0.14)
cantly greater change in height among prepubertal chil- scores, with no effect on growth in infants not anemic at
dren who received zinc supplements, with an overall baseline. Among Bangladeshi infants, Fischer Walker et al.
effect size of 0.170 (95% CI, 0.075–0.264), p 5 .001 showed that there was no effect of zinc on the rate of
based on 37 controlled trials (47 data sets). There was no length or weight gain for infants aged 6 to 12 months or
correlation between mean initial HAZ and effect size in even when stratified by baseline hemoglobin (Hb)
this analysis, unlike the results of a previous review106 concentration.40
where a positive response to zinc was only seen among The combined effects of zinc supplementation in
studies that enrolled children with initial mean children on the final MDI and PDI using the Bayley
HAZ , 21.5 z. The reason could be exclusion of studies scores have been reported in the reviews by Brown
of hospitalized, severely malnourished children from the et al.,105 Nissensohn et al.115 and Gogia et al.116 Most
2009 review. Similarly, zinc had a significant positive studies in the Brown et al. review did not present intra-
overall impact on change in weight from 35 trials (45 individual changes in developmental scores during the
data sets): mean effect size of 0.119 (95% CI, 0.048– course of the intervention that allowed only final values
0.190), p 5 .002. The effect on change in weight-for- to be compared. There was no impact of preventive zinc
height Z score (WHZ), although small, was also margin- on final MDI (effect size 5 0.021, 95% CI: 20.133 to
ally significant.105 Meanwhile, the review by 0.175, p 5 .76) or on final PDI (effect size: 0.025, 95% CI:
Ramakrishnan et al.104 showed that overall weighted 20.149 to 0.198, p 5 .75). We also identified a few other
mean effect for change in height was small and not sig- studies besides those included in this review. Heinig
nificant with zinc supplementation (0.07; 95% CI, 20.03 et al.117 in a double-blind, randomized, placebo-
to 0.17). Similar was the result for weight gain (0.09; 95% controlled trial showed that gross motor development
CI, 20.11 to 0.25). The difference between Brown et al. was not significantly different in zinc-supplemented
and Ramakrishnan et al. analyses is the inclusion/exclu- infants aged 4 to 10 months compared with placebo
sion criteria used. Ramakrishnan et al. included only group based on mean Alberta Infant Motor Scale (AIMS)
studies with children younger than 5 years compared scores. However, in another meta-analysis by Warthon-
with prepubertal children in a review by Brown et al. Medina et al.,98 zinc supplementation during childhood
Brown et al. excluded studies of zinc fortification and had positive impacts on executive function and motor
those studies where SD for change in length was not skills and no effect on intelligence but was limited by
given in the paper, whereas Ramakrishnan et al. included a few data sets.
them. Several studies have been published after these
reviews. Another meta-analysis by Petry et al. showed Folic Acid Supplementation
that zinc supplementation had no effect on childhood Folic acid is involved in nucleotide synthesis, DNA
wasting, stunting, and underweight in children.30 A re- integrity, and transcription that explains its importance
cent randomized, double-blind trial112 in New Delhi, In- for brain development.118 It has an established role
dia, published after these reviews on 2482 children aged periconceptionally in decreasing the incidence of neural
6 to 30 months showed that after 4 months of supple- tube defects. Although the data are very limited, there
mentation, there were no differences between in- are suggestions that an adequate supply of folate is also
tervention (zinc) and placebo groups with respect to important for growth and development at later stages
weight and length gains, and with respect to length-for- because Gross et al.119 found that infants born to moth-
age Z scores, WAZ, and weight-for-length Z scores. An- ers with severe folate deficiency during pregnancy
other community-based randomized study of zinc in showed abnormal or delayed development. Other stud-
preschool children in Iran with retarded linear growth ies, however, have not found associations between folate
showed significantly increased weight gain in children status in the second half of pregnancy and neuro-
compared with placebo, but no effect on mid-upper arm psychological development of children at age 5. This
circumference increment. A highly significant impact may be because of their classification of low-folate status
was seen in boys’ height increment at the end of the based on biochemical measures rather than megaloblas-
follow-up period.113 This trial, however, had a small total tic anemia.120
sample size of 85. Data from another 4 randomized, Folate Use in Pregnancy
double-blind trials in 4 different countries114 show that In a meta-analysis review, folic acid supplementation
zinc supplementation in infants aged 4 to 6 months had during pregnancy had no impact on pregnancy out-
no effect on increments in height or weight during the 6- comes such as preterm birth; however, improvements
month supplementation period, nor on mean HAZ, WAZ, were seen in mean birth weight (mean difference
or WHZ scores. However, in logistic regression analysis, [MD] 5 135.75 g, 95% CI, 47.85–223.68).121 Multiple
infants receiving zinc were less likely to be stunted than reviews have studied maternal folate supplementation or
infants not getting zinc (OR 5 0.80; 95% CI, 0.64–1.0, p 5 intake and effects on cognition and neuro-
.049). Another interesting finding in this analysis was that development.26,122–124 A systematic review on folic acid

6 Nutrition in Child Growth and Development Journal of Developmental & Behavioral Pediatrics

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supplementation/intake122 during pregnancy on neuro- significantly greater in the infants of supplemented
developmental and autism outcomes found 22 studies (2 mothers compared with nonsupplemented group (MD:
RCTs, 18 cohorts, and 2 case-control studies) of which 0.41; 95% CI, 0.18–0.64).
15 showed a beneficial effect, 6 showed no association,
whereas 1 showed a harmful effect. A large retrospective Breastfeeding Promotion Activities
study125 based on 1988 National Maternal Infant Health Human breast milk contains 3 to 5% fat, 0.8 to 0.9%
Survey and the 1991 follow-up supplement in the United protein, 6.9 to 7.2% carbohydrates, and 0.2% mineral
States studied the effect of prenatal folic acid use on early constituents that include sodium, potassium, calcium,
child development. Folate use was associated with sig- magnesium, phosphorus, and chloride.133 Proteins in
nificant reduced odds for moderate risk on gross motor breast milk also include immunoglobulin A, lysozyme,
scale (OR 5 0.5), but was also associated with marginally and albumin related to child’s immune function. There
significant increased odds for moderate risk on the are numerous observational studies linking breast milk
personal-social scale (OR 5 1.8). A population-based to higher scores on cognitive tests and in motor and
cohort study—The Generation R Study—prospectively mental development, especially, in LBW or preterm
assessed maternal folic acid supplement use during the infants134–136 because of breast milk being rich in long-
first trimester by questionnaire.126 Child outcomes were chain polyunsaturated fatty acids (LCPUFAs). Studies
assessed at 18 months of age in 4214 toddlers. Results have supported the hypothesis that breast milk promotes
showed that children of mothers who did not use folic brain development, particularly white matter growth.137
acid supplements in the first trimester had a higher risk Exclusive breastfeeding for the first 6 months is of prime
of total behavioral problems (OR 5 1.44; 95% CI, 1.12– importance as it reduces the incidence of infections,138
1.86). Folic acid supplement use also significantly pro- but evidence on its effect on child’s growth is conflict-
tected from both internalizing and externalizing prob- ing. Some studies report better growth with formula
lems, even when adjusted for maternal characteristics.126 milk, whereas others report that breast milk is sufficient
Folate Use in Infancy/Childhood for adequate growth during the first 6 months of life.139
A study by Olney et al.127 showed that combined iron Some studies have also reported higher weight gains
and folic acid supplementation with or without zinc with exclusive breastfeeding in early days of life that
from 5 to 7 months of age in children was associated then transforms in favor of formula milk by 6 to 7 months
with earlier initiation of walking by approximately 1 of life.138,140 Breast milk also contains adiponectin,
month than in children without iron/folate (p 5 .020). a protein that is associated with lower obesity,141 along
Supplementation with MMNs and long-chain poly- with other hormones and growth factors, namely ghre-
unsaturated fatty acids is discussed in the online Sup- lin, resistin, and obestatin that are involved in food intake
plemental Material. regulation and energy balance.142 It may also, therefore,
have a role in reducing obesity. The World Health Or-
Supplementation with Other Individual ganization currently recommends exclusive breastfeed-
Micronutrients i.e. Vitamin A and Vitamin D ing up to 6 months of age after which complementary
A meta-analysis by Ramakrishnan et al.104 on vitamin A foods should be introduced and breastfeeding then
supplementation on child growth in children under 5 continued up to 2 years of age.143
years of age was based on 17 studies with 19 data sets. Multiple reviews on the effect of breastfeeding pro-
The overall weighted mean effect size for change in motion activities on child growth exist.144,145 Based on
height was small and not significant (0.08; 95% CI, 20.18 16 to 17 data sets between 2006 and 2014, breastfeeding
to 0.34). The weighted mean effect size for weight gain promotion had no impact on weight or height z-scores
was 20.03; 95% CI, 20.23 to 0.18. Semba et al.128 but had a modest, significant reduction in body mass
reported the effect of expanded national vitamin A pro- index (BMI) or WHZ scores in studies from resource-
gram among preschool children in India. The prevalence poor countries. However, Kramer et al.146 from their
of stunting, severe stunting, underweight, and severe large PROBIT trial included in this meta-analysis reported
underweight was higher among children who did not no significant effects of breastfeeding promotion in-
receive vitamin A compared with those who received it tervention on height, BMI, waist or hip circumference,
(p , .0001). triceps, or subscapular skinfold thickness. The authors
Vitamin D is another vitamin that is thought to play an present the latest evidence of the effect of prolonged and
important role in brain development and functioning and exclusive breastfeeding on child’s cognitive ability at 6.5
its deficiency may affect growth and development po- years of age.147 The intervention was based on the Baby-
tential of infants and children. Meta-analyses of vitamin D Friendly Hospital Initiative, which was developed by the
supplementation during pregnancy report significantly WHO and UNICEF, whereas the control maternity hos-
greater birth weight and birth length in neonates by pitals and polyclinics continued the practices and poli-
107.6 and 0.3 cm, respectively,129 and reduction in risk cies in effect at the time of randomization. A total of
of LBW.130 A Cochrane review on vitamin D supple- 17,046 healthy breastfeeding infants were enrolled, of
mentation in pregnancy131 reported infant weight at 12 whom 13,889 (81.5%) were followed-up at age 6.5 years.
months of age based on 1 study.132 The weight was The experimental group had higher means on all of the

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Copyright Ó 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Wechsler Abbreviated Scales of Intelligence measures, icant impact in South Africa160 or India.161 School feeding
with cluster-adjusted mean difference of 17.5 (10.8 to programs and conditional cash transfers are discussed in
114.3) for verbal IQ that was statistically significant. the online Supplemental Material.
Other means for performance IQ and full scale IQ were
higher in the intervention group as well, but non- Integrated Nutrition and Psychosocial
significant. Teachers’ academic ratings were significantly Interventions
higher in the experimental group for both reading and Malnutrition can have a major influence on a child’s
writing. The same authors in another article148 report no behavioral development; for example, iron-deficient
significant treatment effects on either the mother or the children are irritable and tired, and protein deficiency
teacher, Strengths and Difficulties Questionnaire ratings can lead to lethargy and unhappiness among children
of total difficulties, emotional symptoms, conduct prob- that can reduce their interaction with parents or sib-
lems, hyperactivity, peer problems, or prosocial behav- lings.162,163 Research has shown that in combined nu-
ior or on the supplemental behavioral questions. trition and psychosocial interventions, the psychosocial
support provided by increased stimulation can have
Complementary/Preschool Feeding greater effects on psychological functioning than on
To sustain optimal growth and development of physical growth, whereas nutrition supplementation
infants and children is important for their future and would improve both growth and development. The
also for development of societies in which they live.149 combination of stimulation and supplement inter-
Common factors causing malnutrition in infancy in- ventions appears to have a greater effect on cognitive
clude inappropriate feeding practices such as lack of development than either one alone.164 Similar results
exclusive breastfeeding and premature introduction of have been shown by large-scale programs including
weaning foods. Later on during childhood, inadequate Integrated Child Development Services (ICDS) Project
diets in quantity and quality are important causes.150 in India165 and Head Start in the United States166 and
Studies have linked household food insecurity with risk Chile.167 Other programs include PANDAI (Child De-
of stunting and underweight in preschool children,151 velopment and Mother’s Care) Project in Indonesia,
and also with negative effects on development and PRONOEI in Peru, Hogares Comunitarios de Bienestar
learning potential.152,153 Similarly, household food se- (Homes of Well-Being) in Columbia, Programa de Ali-
curity has been associated with greater growth among mentacao de Pre-escolar (PROAPE) in Brazil and In-
children.154 Complementary/supplementary feeding tegrated Programme for Child and Family Development
interventions are usually targeted to children aged 6 to (IFBECD), and Family Development Programme (FCP)
24 months because this is the period of peak incidence in Thailand. The aim of ICDS in India165 was to improve
of growth faltering, micronutrient deficiencies, and in- nutritional and health status of children under age 6.
fectious illnesses.7 The preschool years (i.e., 1–5 years This program combined supplementary feeding for
of age) is also a time of rapid and dramatic postnatal children with health and nutrition education. The pro-
brain development (i.e., neural plasticity), and of fun- gram had an impact on physical growth of children as
damental acquisition of cognitive development (i.e., evidenced by lower levels of undernutrition in ICDS
working memory, attention, and inhibitory control). A areas. Children who attended the program regularly also
food-based, comprehensive approach may be more ef- scored higher on cognitive tests than nonparticipants.
fective and sustainable than programs targeting in- The Head Start program in the United States166 was
dividual nutrient deficiencies. started to provide comprehensive child development
A systematic review by Imdad et al. showed significant services for low-income children and their families. It
positive effects/gains of complementary feeding with or enrolled children aged 3 to 5 years. Snacks and pre-
without nutrition counseling and nutrition counseling school education were provided, along with health
alone on weight (WMD 5 0.34 SD, 0.11–0.56; 0.30 SD, care services. No impact was seen on height-for-age,
0.05–0.54) and height (0.26 SD, 0.08–0.43; 0.21 SD, 0.01– but positive effects were noted on the Peabody
0.41).155 Similar positive findings have been shown for Picture Vocabulary Test (PPVT). Effects persisted into
food supplementation in socioeconomically disadvan- and translated into improved school attainment for
taged children aged 3 months to 5 years in another re- white and Hispanic children but not African-American
view156 and in other reviews in children under 2 years of children.
age157,158 in resource-poor countries. However, in a re-
view published earlier, Dewey and Adu-Afarwuah7 on Nutrition Plus Responsive Care/Responsive Feeding
complementary feeding interventions found that pro- Aboud et al.168 using a cluster randomized field trial in
vision of complementary foods (often fortified) had Bangladesh evaluated a 6-session educational program of
a positive, but nonsignificant, impact on weight and linear responsive complementary feeding that emphasized
growth. In this review, 4 efficacy trials provided data on child self-feeding and maternal responsiveness. A total of
behavioral development. The provision of a fat-based 108 mothers and their 8- to 20-month-old children
fortified food product or micronutrients alone improved attended the sessions, whereas 95 mothers and children
gross motor development in Ghana,159 but had no signif- served as controls and received sessions on foods to feed

8 Nutrition in Child Growth and Development Journal of Developmental & Behavioral Pediatrics

Copyright Ó 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
without any intervention of responsive complementary 6 to 24 months. The undernourished intervened children
feeding. At follow-up, the percent of self-fed mouthfuls (intervention for 12 months) showed significantly greater
and the number of responsive verbalizations were sig- improvements in their MDI (4.6 6 2.0; p , .01), response
nificantly higher in the intervention group compared to examiner (p 5 .001), and cooperation (p 5 .005)
with controls. Mouthfuls of food eaten by children and compared with undernourished controls. Change in PDI
weight were equivalent in the 2 groups. (3.5 6 2.2; p 5 .06), emotional tone (p 5 .03), maternal
knowledge about rearing (p , .001), and vocalization
Nutrition Plus Stimulation (p 5 .04) also approached significance between the 2
Gardner et al. assessed the effects of zinc supple- groups. Two other efficacy studies on this topic found
mentation and psychosocial stimulation given together from the WHO document164 include 1 from Bogota,
or separately on the psychomotor development of un- Colombia, and the other from Cali, Colombia. In the
dernourished Jamaican children.169 Zinc was given as 10 Bogota study on undernourished children, there was
mg elemental zinc daily for 6 months, whereas the psy- no added benefit of the combined supplementation-
chosocial stimulation program focused on improving stimulation interventions on psychological development,
maternal-child interactions. There were 4 groups in this but it had a greater effect on physical growth than sup-
study: zinc and stimulation, zinc alone, stimulation alone, plementation alone.175 The study from Cali showed that
and a control group. Developmental quotient and all combined supplementation and stimulation had the
subscale scores declined in all the 4 groups after 6 greatest effects on psychological development, whereas
months of the study period probably because the chil- supplementation alone (before initiating the preschool)
dren were from poor, disadvantaged backgrounds where had no effect on psychological development.176
other micronutrient deficiencies may coexist. In multi-
level model, children who received both zinc and stim-
ulation had the highest developmental quotients after DISCUSSION/CONCLUSIONS
the intervention. There was no main effect of zinc sup- This review has great implications for the promotion
plementation alone, although stimulation alone also had of child growth and development, especially in
a significant effect on development quotient. There was resource-poor countries. There are some clear messages
also a significant interaction between zinc and stimula- emanating from this review. It highlights the role of
tion on the hand and eye subscale that indicated that micronutrients and other nutrition interventions like
children having both treatments had the highest scores. breastfeeding and complementary feeding. Iron folate is
Zinc alone, however, also benefited the hand and eye routinely used during pregnancy in resource-poor
subscale. Stimulation alone had significant main effects countries and its role in preventing and treating ane-
on hearing and speech and performance. Neither in- mia is well established, preventing numerous compli-
tervention benefited locomotor development. cations in the mother and newborn. Folate during
Another recent study by the same group170–173 ran- pregnancy is also well known for preventing neural
domly assigned 129 stunted children aged 9 to 24 months tube defects and should be given periconceptionally as
to 4 groups: control, nutrition supplemented (milk-based well. Almost no studies have assessed the impact of iron
formula), stimulated, or both treatments in poor Kingston and/or folate during pregnancy on short- and long-term
(Jamaica) neighborhoods. A fifth group of nonstunted development of children, possibly because of its proven
children matched for baseline characteristics was also beneficial role in anemia and further randomized con-
studied. After 2 years, supplementation and stimulation trolled trials (RCTs) being unethical. There is a debate
had independent benefits on the children’s development currently on replacing iron folate with multiple micro-
and the effects were additive. The group receiving both nutrients (MMNs) during pregnancy in resource-poor
treatments caught up to the nonstunted children. Four countries. A major concern is increase in birth weight
years after the end of the 2-year intervention, a battery of in the setting of limited cesarean facilities that may lead
cognitive function, school achievement, and fine motor to increased mortality later in pregnancy i.e., during
tests were performed. The perceptual-motor factor labor. Besides this, other procedures such as symphy-
showed a significant benefit from stimulation, and sup- siotomies during delivery can be debilitating and sub-
plementation benefitted only those children whose sequent impaired maternal health can affect child
mothers had higher verbal IQs. However, each in- development balancing out the benefits of a well-
tervention group had higher scores than the stunted nourished child. More evidence for MMNs supplemen-
control subjects on more tests than would be expected by tation is needed in remote or rural areas of resource-
chance (supplemented and both groups on 14 of 15 tests, poor countries before a recommendation for universal
p 5 .002; stimulated group in 13 of 15 tests, p 5 .01). use can be made. Iodine should be given to all mothers
There was no longer an additive effect of combined in iodine-deficient areas, mostly through the fortifica-
treatments at this 4-year follow-up. The third study we tion of salt. Routine use of zinc during pregnancy is not
found174 looked at the addition of psychosocial stimula- recommended because of null results on newborn or
tion to the nutrition interventions (food packets) for other growth or developmental outcomes. There are no
malnutrition in undernourished Bangladeshi children aged separate data evaluating zinc supplementation in zinc-

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Copyright Ó 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
deficient mothers. Studies are needed, particularly in nutrition supplementation would improve both growth
resource-poor countries. and development. Studies have shown that combination
Iron should be supplemented to all iron-deficient of stimulation and supplement interventions appears to
children, and mass supplementation is not recom- have a greater effect on cognitive development than ei-
mended because it does not appear to have utility for ther one alone.164 Similar results have been shown by
improving growth or developmental outcomes in iron- large-scale programs in different countries including In-
replete children. However, iodine should be provided to tegrated Child Development Services (ICDS) Project in
all children in iodine-deficient areas. Data on the impact India165 and Head Start in the United States.166 Therefore,
of preventive zinc on growth are conflicting. Before nutrition and psychosocial interventions should be com-
large-scale recommendation for routine preventive sup- bined to achieve optimal benefits in large-scale programs.
plementation is made, its impact on other outcomes The need of the hour is to translate these recom-
such as mortality and morbidity, specifically because of mendations into large-scale, community-based public
infections, needs to be studied. More RCTs are needed to health programs and increase their coverage, especially
assess the impact of zinc on growth, especially height, for the most impoverished pregnant women and chil-
among children who are anemic or are stunted. The role dren in resource-poor countries. Other research oppor-
of vitamin A supplementation in children in preventing tunities also exist. More evidence is needed for MMNs
all-cause and infection-specific mortality have been well supplements compared with iron folate, particularly in
demonstrated in recent reviews.177 It should be part of regions that do not have appropriate health care delivery
large-scale programs for children at risk despite con- facilities. Zinc and vitamin D supplementation in preg-
flicting results on growth. It is hypothesized that by re- nancy may be important for women deficient in these
ducing incidence of infections like diarrhea and measles, nutrients but current evidence does not show any con-
it should have a positive effect on growth and de- vincing benefits for child growth and development. Al-
velopment as well. There is only 1 study evaluating the though we recommend vitamin A supplementation for
use of folic acid for child development outcomes and children at risk in resource-poor countries, its effects on
there is no substantial evidence to recommend it rou- growth are conflicting. Furthermore, there are no studies
tinely with iron in iron-deficient children. of vitamin A supplementation evaluating developmental
All children should be exclusively breastfed up to the outcomes. Observational studies could be done to ob-
first 6 months of life based on its protective effect on serve effects on these outcomes because according to
infections and also optimal growth, despite some studies new evidence,177 further RCTs of vitamin A supple-
on growth being conflicting. It is important that weaning mentation would be unethical in children. Zinc supple-
foods be started in the right quantity and quality to have mentation in children also has a potential role to play,
positive impacts on child growth and development, with particularly in preventing stunting, but more evidence is
breast milk continued up to 2 years of age. More data are needed before it can be recommended routinely. Its role,
needed on the impact of complementary feeding inter- however, in preventing infections like diarrhea and
ventions on early child development. Provision of com- pneumonia in children is strong.178
plementary foods also had a positive impact on growth. In conclusion, micronutrient supplementation plays
With maternal education for complementary feeding, also a significant role in child growth and development either
there was an additional increase in weight and height. during pregnancy or early childhood. In making policy
Studies from Africa and South Asia generally showed recommendations or guidelines, it is important to rec-
positive results for growth, whereas those in other regions ognize that micronutrients also provide benefits beyond
were more variable. This could be explained by higher those of growth and development. This can potentially
food insecurity rates in Africa and South Asia. Other include reduction in incidence of infections and mortal-
interventions such as managing poverty and improving ity such as for zinc and vitamin A supplementation in
sanitation and health care need to be coupled with com- children. This review has highlighted current evidence
plementary feeding interventions to have a more sub- and further areas of research opportunities related to
stantial impact on child growth and development. The micronutrient deficiencies, and supplementation efforts
key challenge would, however, be to introduce high- to overcome these deficiencies.
quality programs that incorporate these interventions that
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