Promoting Early Development WithTyler Vaivada, MSc, Interventionsa​ Michelle F. Gaffey, MSc,a​ Zulfiqar A. Bhutta, in PhD a,Healthb​ and

CONTEXT: : A Systematic Reviewabstract

Although effective health and nutrition interventions for reducing child mortality and morbidity exist, direct evidence of effects on cognitive, motor, and psychosocial OBJECTIVE: development is lacking. To review existing evidence for health and nutrition interventions affecting direct DATA SOURCES: measures of (and pathways to) early . Reviews and recent overviews of interventions across the continuum of care and STUDY SELECTION: component studies. We selected systematic reviews detailing the effectiveness of health or nutrition interventions that have plausible links to child development and/or contain direct DATA EXTRACTION: measures of cognitive, motor, and psychosocial development. RESULTS: A team of reviewers independently extracted data and assessed their quality. Sixty systematic reviews contained the outcomes of interest. Various interventions reduced morbidity and improved child growth, but few had direct measures of child development. Of particular benefit were food and micronutrient supplementation for to reduce the risk of small for and , strategies to reduce anemia in infancy, and early neonatal care (appropriate resuscitation, delayed cord clamping, and Kangaroo Care). Neuroprotective interventions for imminent showed the largest effect sizes (antenatal corticosteroids for developmental delay: risk ratio 0.49, 95% confidence interval 0.24 to 1.00; magnesium LIMITATIONS: sulfate for gross motor dysfunction: risk ratio 0.61, 95% confidence interval 0.44 to 0.85). Given the focus on high-quality studies captured in leading systematic reviews, CONCLUSIONS: only effects reported within studies included in systematic reviews were captured. These findings should guide the prioritization and scale-up of interventions within critical periods of early infancy and childhood, and encourage research into their implementation at scale.

aCentre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada; and bCenter of Excellence in Women and Child Health, The Aga Khan University, Karachi, Pakistan

Mr Vaivada designed the study protocol, coordinated data extraction, and drafted the initial manuscript; Ms Gaffey designed the study protocol and data analysis plan and critically reviewed and revised the manuscript; Dr Bhutta conceptualized and designed the study, obtained funding, oversaw the data abstraction and analysis, and critically reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. DOI: https://​doi.​org/​10.​1542/​peds.​2016-​4308

To cite: Vaivada T, Gaffey MF, Bhutta ZA. Promoting Early Child Development With Interventions in Health and Nutrition: A Systematic Review. . 2017;140(2):e20164308

Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 140, number 2, August 2017:e20164308 REVIEW ARTICLE Despite recent improvement, in children <5 years old, high rates of mortality and morbidity, poverty, and chronic undernutrition are pervasive in many low- and middle- income countries (LMIC). For children who survive infancy, many remain at a high risk for stunted growth and impaired development. In 2014, ~23.8% of children (159 million) <5 years old were stunted1 Lancet’ and at a high risk2 of impaired child development. The s 20163 Early Child Development Series estimated that based on stunting and extreme poverty, 43% of children (249.4 million) <5 years old in

LMIC were at 4risk for suboptimal development,​ which effectively FIGURE 1 forfeits a quarter of the annual adult Conceptual framework of the risk factors in early life for suboptimal child growth and development. income because of lost cognitive The dotted box highlights the focus of this overview on interventions that address biological risk 5 factors. potential and reduced productivity. Recent predictive modeling that used the Human Development Index, nutrition status, and Early Child evidence for an intergenerational number of children surviving infancy, Development Index data (from the impact of early11 stunting on child the importance 7of enhancing the Multiple Indicator Cluster Survey development and a potential survival agenda to reduce morbidity and Demographic Health Survey) second window of opportunity for and support child development is suggests that 36.8% of children supporting development12 in the evident. (80.8 million) ages 3 to 4 years in adolescent period. LMIC do not reach fundamental ‍Table 1 summarizes the theoretical cognitive or socioemotional6 A variety of interventions that rationale for the beneficial development milestones. Moving support maternal, newborn, and child neurodevelopmental impacts of a forward, achieving the Sustainable health and nutrition (MNCH&N) have variety of interventions at various Development Goals of zero been identified as both effective and time points. Particularly impactful (Goal 2), good health and well-being feasible for scale-up. The rationale targets ameliorate maternal “ ” at all ages (Goal 3), and quality for focusing on interventions that and infection during and equitable education (Goal 4) target the First 1000 Days of preconception and pregnancy, will require maximizing every life (from conception to 2 years of which contribute to intrauterine opportunity to institute appropriate age) is that the mitigation of risk growth restriction (IUGR), children interventions at scale. factors during this critical period being born small for gestational

has substantial13 benefits over the age (SGA), or preterm births, and To assist in selecting and prioritizing life course. There is evidence to neonatal infections. In addition to key interventions, we developed suggest, however, that this period the developmental risks associated10 a conceptual framework of risk may be somewhat arbitrary because with maternal iodine deficienc14 y factors and– opportunities for highly effective interventions also and folic acid deficiency,​ recent interventions7 9 across the life course exist for the preconception period, evidence demonstrating the link (Fig 1). ‍‍ For this overview, we late childhood, and adolescence between Zika virus infection were focused on the biological that could benefit developmental during pregnancy and subsequent15 risk factors for suboptimal outcomes. Nevertheless, supporting microcephaly in some development, which broadly include development in utero and early life highlights the potential infectious 16 undernutrition, infectious10 disease, is important and is when much of risks to neurodevelopment in utero. and toxin exposure,​ many of the fetal morbidity, stillbirths, and Postnatally, reducing environmental which affect both child7 survival <5 years of age3 child mortality is enteropathy is key because it may and development. There is also concentrated. With an increasing mediate the relationship between Downloaded from www.aappublications.org/news by guest on September 29, 2021 2 Vaivada et al TABLE 1 Theoretical Rationale for the Neurodevelopmental Impact of MNCH&N Interventions Through a Reduction in Risk Factors poor personal and food hygiene Intervention Targets Potential Mechanisms for Impact and environmental factors that Improving maternal Reduce inflammation and protect a developing fetus by preventing and contribute to developmental deficits physical, mental treating infection.9,‍16,​ ‍23​ through chronic intestinal17 mucosal, health, and nutritional Protect a fetus from maternal hormonal imbalances and deleterious 24 systemic inflammation,​18 and status epigenetic changes by reducing chronic stress and preventing and nutrient malabsorption. Both acute treating depression.25 malnutrition and stunted growth in Prevent IUGR and support optimal gestational growth and development by ensuring adequate food and micronutrient intake, particularly iodine and childhood are associated with poorer19 iron.10 cognitive and motor development. Improving birth Protect against neurologic damage by reducing the risk of preterm birth and Despite these obvious links, most outcomes and complications associated with prematurity.26 studies or programs of MNCH&N reducing incidence Ensure skilled birth attendance and hygienic delivery practices to prevent 23 interventions typically only of newborn neurologic harm from sepsis. complications, Reduce complications and neurologic damage from birth asphyxia and measure proximal measures, such neonatal infection associated hypoxia23 by preventing obstructed labor, being large for as anthropometry, birth outcomes, gestational age, or postmature births and providing emergency cesarean or clinically apparent health deliveries and effective resuscitation when required. outcomes. The associations between Special care for preterm Enhance lung adaptation and neuroprotection for vulnerable fetuses before 27 these intermediate outcomes and and SGA infants imminent preterm birth with antenatal corticosteroids and magnesium sulfate.28 brain development are not only Provide appropriate thermal care and support prevention of neonatal biologically plausible20 but have been infection, especially in preterm neonates who are vulnerable.29,‍30​ demonstrated,21 ​ and they22 include Delay cord clamping to maximize umbilical transfusion and improve iron IUGR,​ preterm birth,​ and neonatal stores.31 23 9 insults among others. Promoting optimal Promote optimal and complementary feeding practices to and child nutrition, protect against malnutrition, infection, enteropathy,18​ and linear growth 10 32 By building on recent– overviews care, and growth stunting and optimize gut microbiome development. Ensure adequate psychosocial stimulation10 is provided during the period of of evidence-based36 40 MNCH&N interventions,​ ‍ we synthesized rapid brain development. Prevent and treat acute malnutrition and micronutrient deficiencies to the outcome data on indirect risks prevent cognitive deficits.10 and direct measures of early child Infectious disease Provide routine childhood vaccinations and malaria prophylaxis,10​ which can development. We also mapped the prevention and prevent and mitigate direct neurologic damage from infectious agents. outcome data to identify gaps in the management in Support access to safe water, improve infrastructure, and promote evidence where additional research infancy and childhood hygienic practices to protect against environmental enteropathy and its sequelae.18 is needed. Reducing exposure Minimize indoor air pollution to prevent placental pathology33 and Methods to toxins and neurodevelopmental deficits.34 environmental Reduce lead and arsenic exposure10 at home and in the workplace to protect Identifying the Universe of contaminants against cognitive deficits. Interventions to Assess Support smoking cessation during pregnancy to prevent neurobehavioral deficits in children,​35 and address maternal drug and alcohol exposure.

We identified (from recently Review Selection and Eligibility published overviews) a universe Screening of evidence-based interventions relevant literature was also done that have been identified in the to identify existing or forthcoming literature as supporting MNCH&N systematic reviews or meta-analyses and could plausibly affect early child– From the listing of interventions for which data were available. development. The source overviews36 38 in each overview, citations for Nonsystematic reviews, drug included relevant Lancet series ‍ ‍ the corresponding systematic comparisons, reviews with no child- and summaries of essential39,40​ reviews and meta-analyses were related outcome data, and those intervention packages. We extracted from the reference lists. superseded by newer publications restricted ourselves to interventions We conducted relevant keyword were excluded. Also excluded were that target the biological risk factors searches in Medline, PubMed, and reviews that focused on life-saving for impaired child development and the Cochrane Database of Systematic interventions to prevent maternal thus did not examine interventions Reviews for more recent reviews of or perinatal mortality. If a cited related to education, poverty pertinent interventions that were Cochrane review had been updated, alleviation, the built environment, published in the past 2 years that the most recent published version or other sectors that affect the social may not have been captured in (up to April 1, 2016) was selected for determinants of health. the overviews. Hand searching of data extraction. Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 140, number 2, August 2017 3 intervention is summarized in Supplemental Figure 6. ‍Figure 3 displays a mapping of the outcomes reported in systematic reviews of the effectiveness of 35 selected interventions or intervention categories with promising effects on developmentally relevant outcomes. These are also depicted within a conceptual framework in Fig 4. Most commonly reported were birth outcomes for interventions delivered during preconception and pregnancy, growth outcomes and disease morbidity for interventions delivered during infancy and childhood, and mortality throughout FIGURE 2 these critical windows. Out of 60 ≥ Overview flow diagram. reviews of interventions in which 1 statistically significant effect Data Extraction and Quality on an outcome of interest had Assessment been reported, only 16 reviews Infant Development score or Ages covering 13 discrete interventions and Stages Questionnaire score) reported summary estimates for were included in our final list of Two reviewers used a standardized outcomes that were direct measures ’ interventions with impact estimates. form to independently extract of child development. Pooled This encompassed direct effects on each review s characteristics, data on direct measures of child child development as well as effects meta-analyzed the outcome data development reported in meta- on intermediate outcomes that are (including pooled effect sizes, analyses often consisted of a small linked to development through a confidence intervals, study counts, number of studies with relatively pathway related to malnutrition and heterogeneity), and performed few participants when compared and infectious disease morbidity. A Measurement Tool to Assess with other outcome types. Effect Nonsignificant effect estimates Systematic Reviews (AMSTAR) estimates for outcomes that directly 41 for outcomes of interest for each quality assessments. Any measure child development and included intervention are also ’ disagreements in the subjective study characteristics of individual displayed. quality ratings were resolved by studies found within the reviews consensus or a third reviewer. Results meta-analyses are reported in Additionally, we reviewed the Supplemental Table 8. Data for those focus, reported outcomes and individual studies with the direct characteristics of each study included measurements of child development In total, 120 systematic reviews within each review, retrieved included in reviews but not were selected for full data extraction, the full text when relevant, and presented within their meta-analyses 60 of which were included in the extracted any summary outcome data are found in Supplemental Table 9. outcome mapping exercise (see Fig Preconception and Antenatal Care related to direct measures of child 2). All but 1 of these received an development. Targeted Outcome Mapping AMSTAR rating of medium or high quality. Review characteristics, Early preventive interventions ≥ pooled effect estimates, and quality that seek to minimize rates of Interventions that included 1 ratings are reported in Supplemental SGA, prematurity, and newborn statistically significant effect on Table 7. Select interventions that had complications include supporting an anthropometric, nutritional, statistically significant effects on the access to family planning and severe morbidity or disability outcomes of interest are highlighted antenatal care services and an optimal outcome or a direct measure of below. The corresponding source environment for fetal growth (Table development (eg, Bayley Scales of overview for each highlighted 2). Family planning for promoting Downloaded from www.aappublications.org/news by guest on September 29, 2021 4 Vaivada et al FIGURE 3 Mapping of the outcomes reported in reviews of the impact of interventions across the continuum of care. Bold text shows pooled outcome(s) reported with significant beneficial effect(s). Regular text shows pooled outcome(s) reported with nonsignificant effect(s). Italic text shows pooled outcome(s) reported with significant detrimental effect(s). a Pooled outcomes reported in 2 or more separate meta-analyses with both significant beneficial and nonsignificant and/or detrimental effects (eg, different subgroups).b Effects from observational data, rather than a family planning intervention.

– longer birth intervals42 can improve women, improve infant growth and growth and development.44 46 Malaria birth outcomes,​ and preconception birth outcomes, and27 prevent motor prophylaxis; ‍ ‍ antibiotic treatment47 diabetes care can reduce deficits in infancy. of asymptomatic bacteriuria,48 ​ perinatal mortality43 and congenital a confirmed infection,49 ​ or preterm malformations. Antiplatelet agents Infection and inflammation during membrane rupture ; and50 smoking can prevent preeclampsia in at-risk pregnancy negatively influence fetal cessation interventions can all Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 140, number 2, August 2017 5 improve pregnancy and birth outcomes. Magnesium sulfate given to mothers who are at ’ risk for preterm birth reduce infants risk of cerebral palsy28 and gross motor dysfunction.51 In appropriate populations,​ antenatal corticosteroids for women who are at risk for preterm birth prevent intracranial hemorrhage and 52 developmental delay in childhood as well as neonatal mortality in53 both Nutritionhigh- and Duringlow-income Preconception settings. and Pregnancy to Optimize Fetal Growth and Development

FIGURE 4 Adequate macronutrient intake is Conceptual framework of key interventions in early life that support optimal child growth and essential for optimal fetal growth development. and development, and balanced protein-energy supplementation ∼ during pregnancy improves fetal 58 cognition. Iron supplementation newborns, 3% to 6% require basic growth and birth outcomes, 59 during pregnancy improves birth resuscitation at birth, and providing with greater effects observed in 54 outcomes and infant iron status in training in neonatal resuscitation malnourished women. Provision 62,63​ areas with high malarial burden, with impacts neonatal mortality. ‍ of nutrient supplements to food- potential developmental benefits Skilled birth attendance in insecure or wasted expectant seen in areas with a high burden of community settings reduces perinatal mothers supports optimal growth iron deficiency (See Supplemental and early neonatal mortality and and development both in the Table 9). A Cochrane review reveals risks of morbidity associated with womb and after birth (Table 64 that multiple micronutrient (MMN) intrapartum complications. 3). The significant effects of the 60 supplementation during pregnancy aforementioned interventions on Social support for women during can reduce the prevalence of SGA, key birth outcomes are summarized has been shown to low , and preterm in Fig 5. Adequate micronutrient improve Apgar scores in neonates, births, with potential cognitive and intake is essential for satisfying which underscores the importance motor development benefits (see the physiologic requirements of addressing63 maternal anxiety and Supplemental Table 9) and gains of a developing fetus. Ideally, 61 stress. Appropriate aftercare and in head circumference in the interventions to address maternal strategies to protect the brains of offspring of undernourished mothers. undernutrition and micronutrient newborns after birth asphyxia can Notwithstanding these potential deficiencies should start in the 61 further mitigate neurodevelopmental 55 benefits, a recent review of MMN preconception period. Folic deficits and disabilities. Therapeutic 56 supplementation in pregnancy did acid supplementation and hypothermia for newborns with 57 not find any developmental benefits fortification during preconception hypoxic ischemic encephalopathy in the limited set of studies that had effectively prevents neural tube reduces the risk of developmental measured such outcomes. defects. During pregnancy, folic acid Care During Labor, Birth, and delay and cerebral palsy, although 43 the Neonatal Period to Prevent also improves birth weight,​ evidence65 is currently lacking from Complications and Morbidity and iodine supplementation in LMIC. Delayed cord clamping in deficient populations prevents preterm neonates reduce the23, risks66​ for intraventricular hemorrhage ‍ and cretinism and infant mortality and58 66 improves cognitive development. The provision of appropriate and anemia,​ but the reported effects67 Observational studies reveal that skilled care during labor, birth, and on neurodevelopment are mixed. the use of iodized salt in at-risk the immediate newborn period In addition to its survival benefits, populations is a cost-effective should be afforded to all infants, with Kangaroo Mother Care (KMC) in way to improve iodine status and additional protective interventions preterm infants has been shown to confers substantial benefits to for at-risk neonates (Table 4). Of improve mother-infant attachment, Downloaded from www.aappublications.org/news by guest on September 29, 2021 6 Vaivada et al TABLE 2 Review of Key Impacts of Health Interventions Delivered During Preconception and Pregnancy Key Interventions Summary Effects With Implications for Developmental Outcomes (Direct Developmental Effects) Preconception diabetes care, 1 SR, HIC and Improved fetal development: reduced risk of congenital malformations (RR 0.30, 95% CI 0.22 to 0.41; N = 4760 in 20 LMIC studies) Antiplatelet agents in pregnancy for Improved birth outcomes: reduced risk of preterm birth (RR 0.92, 95% CI 0.88 to 0.97; N = 31 151 in 29 studies), SGA preeclampsia prevention, 1 SR, HIC and birth (RR 0.90, 95% CI 0.83 to 0.98; N = 23 638 in 36 studies) LMIC Fewer motor deficits in infancy: reduced risk of poor gross or fine motor function at 18 mo (RR 0.49, 95% CI 0.26 to 0.91; N = 788 in 1 study) Nonsignificant effects: poor gross motor function at 18 mo (RR 0.82, 95% CI 0.57 to 1.17;N = 4365 in 1 study), poor language expression at 18 mo (RR 0.94, 95% CI 0.74 to1.19; N = 4365 in 1 study) IPTp and insecticide-treated bed nets for Improved birth weight: IPTp with sulfadoxine-pyrimethamine reduced risk of low birth weight (RR 0.81, 95% CI 0.67 malaria prevention, 3 SRs, LMIC to 0.99; N = 3043 in 7 studies) and IPTp combined with bed net usage reduced risk of low birth weight (RR 0.65, 95% CI 0.55 to 0.77; N = 3360 in 5 studies) Antibiotics for premature rupture of Longer gestation: reduced the chance of birth within 7 d of treatment (RR 0.79, 95% CI 0.71 to 0.89; N = 5965 in 7 membranes, 2 SR, HIC and LMIC studies) Fewer brain injuries: reduced risk of major cerebral abnormalities on ultrasound (RR 0.81, 95% CI 0.68 to 0.98; N = 6289 in 11 studies) Protection from infection: reduced risk of neonatal infections including pneumonia (RR 0.67, 95% CI 0.52 to 0.85; N = 1680 in 12 studies) Lower genital tract infection screening and Improved birth outcomes: reduced risk of preterm birth (RR 0.55, 95% CI 0.41 to 0.75; N = 4155 in 1 study) and treatment, 1 SR, HIC preterm and low birth weight (RR 0.48, 95% CI 0.34 to 0.66; N = 4155 in 1 study) Antibiotics for asymptomatic bacteriuria, 1 Improved birth outcomes: reduced risk of preterm birth (RR 0.27, 95% CI 0.11 to 0.62; N = 242 in 2 studies) and low SR, HIC birth weight (RR 0.64, 95% CI 0.45 to 0.93; N = 1437 in 6 studies) Detection and treatment of syphilis, 1 SR, Improved birth outcomes: reduced risk of preterm birth (RR 0.36, 95% CI 0.27 to 0.47; N = 1959 in 7 studies) HIC and LMIC Protection from syphilis infection at birth: reduced risk of congenital syphilis (RR 0.03, 95% CI 0.02 to 0.07; N = 3460 in 3 studies) Smoking cessation interventions, 1 SR, HIC Improved birth outcomes: reduced risk of low birth weight (RR 0.82, 95% CI 0.71 to 0.94; N = 8562 in 14 studies) and and LMIC preterm birth (RR 0.82, 95% CI 0.70 to 0.96; N = 7852 in 14 studies) Magnesium sulfate for neuroprotection in Protection from motor disability and dysfunction: reduced risk of cerebral palsy (RR 0.68, 95% CI 0.54 to 0.87; N = imminent preterm births, 1 SR, HIC and 6145 in 5 studies) and gross motor dysfunction (RR 0.61, 95% CI 0.44 to 0.85; N = 5980 in 4 studies) LMIC Nonsignificant effects: developmental delay or intellectual impairment (RR 0.99, 95% CI 0.91 to 1.09;N = 5980 in 4 studies) Antenatal corticosteroids, 2 SRs, HIC and Fewer neonatal complications: reduced risk of cerebroventricular hemorrhage (RR 0.54, 95% CI 0.43 to 0.69; N = LMIC 2872 in 12 studies), respiratory distress syndrome (RR 0.66, 95% CI 0.59 to 0.73; N = 4038 in 21 studies), sepsis within 48 h (RR 0.56, 95% CI 0.38 to 0.85; N = 1319 in 4 studies), and necrotizing enterocolitis (RR 0.46, 95% CI 0.29 to 0.74; N = 1675 in 8 studies) Improved child development: reduced risk of developmental delay in childhood (RR 0.49, 95% CI 0.24 to 1.00; N = 518 in 2 studies) Nonsignificant effects: neurodevelopmental delay in childhood (RR 0.64, 95% CI 0.14 to 2.98;N = 988 in 1 study), intellectual impairment in childhood (RR 0.86, 95% CI 0.44 to 1.69; N = 778 in 3 studies), and behavioral and/or learning difficulties in childhood (RR 0.86, 95% CI 0.35 to 2.09;N = 90 in 1 study) CI, confidence interval; HIC, high-income country; IPTp, intermittent preventive therapy in pregnancy; RR, risk ratio; SR, systematic review.

75 rates of exclusive68 breastfeeding, Supplemental Table 9). Massage microbiome. Optimal breastfeeding therapy in preterm infants has been and growth rates and prevent69 is linked to significant reductions found to promote weight gain when pneumonia, sepsis,70 jaundice,​ and 74 in infectious– disease mortality, coconut or sunflower oil is used. hypothermia. Skin-to-skin contact, Nutrition During Infancy and , and76 78 lower respiratory which is a core component of KMC, Childhood for Optimal Growth and infections. ‍ Breastfeeding can can improve measures of infant71 Development impact cognitive development during cardiorespiratory stability. Topical infancy, and whereas there is debate79,80​ emollient therapy for preterm about the magnitude of effect,​ ‍ 81 infants, which is a neonatal skincare meta-analysis of observational data A variety of effective nutritional strategy for hypothermia and and a single randomized controlled interventions exist that are delivered 82 infection prevention,72 can improve during infancy and childhood, when trial suggest improved intelligence. infant growth and prevent hospital- rapid growth and development Various effective breastfeeding acquired infections73 and neonatal 72 occur (Table 5). Breast milk education or support interventions mortality. Cleminson and McGuire regulates infant immunity, metabolic exist that increase the coverage of83 conducted a small study and showed processes, and brain development, early and exclusive breastfeeding improved psychomotor development which are mediated through the with a consistently84 larger effect size in low-risk preterm neonates (see establishment of the intestinal in LMIC settings. A recent Lancet Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 140, number 2, August 2017 7 TABLE 3 Review of Key Impacts of Nutrition Interventions Delivered During Preconception and Pregnancy Key Interventions Summary Effects With Implications for Developmental Outcomes (Direct Developmental Effects) Folic acid fortification and Prevention of neural tube defects: reduced risk of neural tube defects with supplementation (RR 0.31, 95% CI 0.17 to supplementation for women of 0.58; N = 6708 in 5 studies) and fortification (RR 0.59, 95% CI 0.52 to 0.68; 11 studies) childbearing age, 3 SRs, HIC and LMIC Iodine supplementation, 1 SR, HIC and Protection from severe developmental deficits: reduced risk of cretinism (RR 0.27, 95% CI 0.12 to 0.60;N = 9500 in 5 LMIC studies) Improved cognitive development: 10% to 20% increase in cognitive development scores (N = 1200 in 4 studies) Iron and iron-folate supplementation, 1 Improved birth outcomes: reduced risk of early-preterm (<34 wk) birth (RR 0.51, 95% CI 0.29 to 0.91; N = 3743 in 5 SR, HIC and LMIC studies) and reduced risk of low birth weight (RR 0.83, 95% CI 0.73 to 0.94; N = 4645 in 5 studies) in areas with high malarial burden only Improved infant iron stores: increased infant (<6 mo) serum ferritin concentration (MD 11.00 µg/L, 95% CI 4.37 to 17.63; N = 197 in 1 study) MMN supplementation, 2 SRs, HIC and Improved birth outcomes: reduced risk of SGA birth (RR 0.91, 95% CI 0.84 to 0.97; N = 67 036 in 14 studies), low birth LMIC weight (RR 0.88, 95% CI 0.85 to 0.90; N = 70 044 in 15 studies), and preterm birth in (BMI <20) mothers (RR 0.85, 95% CI 0.80 to 0.90; 4 studies) Improved growth during gestation: increased head circumference (SMD 0.08, 95% CI 0.00 to 0.15; N = 2692 in 4 studies) Nonsignificant effects: mental development scores at 6 mo (MD− 0.02, 95% CI −6.78 to 6.74; N = 770 in 1 study) and 12 mo (MD 1.21, 95% CI −5.06 to 7.48; N = 744 in 1 study) and psychomotor development scores at 6 mo (MD −0.16, 95% CI −3.91 to 3.59; N = 770 in 1 study) and 12 mo (MD 0.34, 95% CI −2.73 to 3.41; N = 744 in 1 study) Balanced protein-energy Improved birth outcomes: reduced risk of low birth weight (RR 0.68, 95% CI 0.51 to 0.92; N = 522 in 5 studies) and SGA supplementation, 1 SR, HIC and LMIC birth (RR 0.66, 95% CI 0.49 to 0.89; N = 5250 in 9 studies) Augmented linear growth during gestation: increased birth length (MD 0.16 cm, 95% CI 0.02 to 0.31; N = 3698 in 7 studies) Nonsignificant effects: mental development scores at 1 y (MD− 0.74, 95% CI −1.95 to 0.47; N = 411 in 1 study) CI, confidence interval; HIC, high-income country; MD, mean difference; RR, risk ratio; SMD, standard mean difference; SR, systematic review.

85 series outlined a variety of sectors in which breastfeeding promotion is effective at improving early86 and exclusive breastfeeding rates.

Given the link between87 childhood anemia and cognition,​ there is interest in addressing childhood deficiency in iron and other 88 micronutrients. A Cochrane review of intermittent iron supplementation in children 0 to 12 years old found improvements in motor development but a decrease in IQ. In another 89 review, Sachdev, Gera, and Nestel examined iron supplementation in children 0 to 15 years old and found improvements in mental development scores. MMN supplementation can improve motor development in infants

6 to 12 months old and academic 90 performance in school-aged children.

Reductions in iron deficiency 91 FIGURE 5 anemia have also been observed in Range of effects of interventions during pregnancy on birth outcomes. BEP, balanced protein-energy; CI, confidence interval; IFA, iron-folic acid; IPTp, intermittent preventive therapy for malaria during addition to better motor milestone pregnancy; ITN, insecticide treated nets; LGTI, lower genital tract infection. attainment (see Supplemental Table 9). Vitamin A supplementation in children effectively reduces vitamin A92 deficiency and associated morbidities,​ Complementary feeding education for decreases stunting93 in food-insecure including reductions in all-cause92 and in food-secure populations populations. Food provision in diarrhea-associated mortality. improves infant growth and also food-insecure populations can Downloaded from www.aappublications.org/news by guest on September 29, 2021 8 Vaivada et al TABLE 4 Review of Key Impacts of Interventions Delivered in the Neonatal Period Key Interventions Summary Effects With Implications for Developmental Outcomes (Direct Developmental Effects) Delayed cord clamping, 4 SRs, HIC, Fewer complications of prematurity: reduced risk of intraventricular hemorrhage in preterm (RR 0.59, 95% CI 0.41 to 0.85; and LMIC N = 539 in 10 studies) and early-preterm neonates (RR 0.62, 95% CI 0.43 to 0.91; N = 390 in 9 studies) and reduced risk of necrotizing enterocolitis (RR 0.62, 95% CI 0.43 to 0.90; N = 241 in 5 studies) Improved iron status: in premature infants, increased hematocrit at 24 h (MD 3.28, 95% CI 1.34 to 5.22; N = 199 in 3 studies); in extremely low birth weight infants, increased hemoglobin on NICU admission (MD 3.42 g/dL, 95% CI 3.11 to 3.74; N = 137 in 10 studies); and in term infants, reduced iron deficiency at –3 6 mo (early versus delayed RR 2.65, 95% CI 1.04 to 6.73; N = 1152 in 5 studies) Reduced risk of infection: decreased odds of late-onset sepsis in extremely low birth weight infants (OR 0.39, 95% CI 0.18 to 0.81; 10 studies) Mixed effects on development at 4 mo in term infants: improved problem-solving ASQ score (MD 1.80, 95% CI 0.22 to 3.38; N = 365 in 1 study) and reduced personal-social ASQ score (MD −2.30, 95% CI −4.09 to −0.51; N = 365 in 1 study) Nonsignificant effects: total ASQ score at 4 mo (MD− 1.40, 95% CI −7.31 to 4.51; N = 365 in 1 study) and BSID mental development score <70 at 24 mo (OR 0.52, 95% CI 0.14 to 1.98; 2 studies) Therapeutic hypothermia for hypoxic Reduced cognitive developmental and motor disability: reduced risk of major developmental disability (RR 0.77, 95% CI ischemic encephalopathy, 1 SR, 0.63 to 0.94; N = 1344 in 8 studies), cerebral palsy (RR 0.66, 95% CI 0.54 to 0.82; N = 881 in 7 studies), neuromotor delay HIC, and LMIC (RR 0.75, 95% CI 0.59 to 0.94; N = 657 in 6 studies), and developmental delay (RR 0.74, 95% CI 0.58 to 0.94; N = 667 in 6 studies) Nonsignificant effects: neuromotor development score (MD 0.77, 95% CI− 4.39 to 5.94; N = 271 in 3 studies) and mental development score (MD 2.47, 95% CI −2.77 to 7.71; N = 271 in 3 studies) KMC, skin-to-skin contact, and other Improved feeding practices: more exclusive breastfeeding at 1–3 mo (RR 1.20, 95% CI 1.01 to 1.43; N = 600 in 5 studies) and thermal care methods in preterm 3–6 mo (RR 1.97, 95% CI 1.37 to 2.83; N = 149 in 3 studies) infants, 4 SR, HIC, and LMIC Reduced risk of infection: reduced risk of sepsis (RR 0.56, 95% CI 0.40 to 0.78; N = 1343 in 7 studies) Improved mother-infant attachment score (MD 6.24, 95% CI 5.57 to 6.91; N = 100 in 1 study) Nonsignificant effects: psychomotor development at 12 mo (MD 1.05, 95% CI− 0.75 to 2.85; N = 579 in 1 study) Topical emollient therapy, 2 SR, HIC, Reduced infection risk in preterm infants: reduced risk of hospital-acquired infection in LMIC (RR 0.50, 95% CI 0.36 to 0.71; and LMIC N = 697 in 3 studies) Increased early growth: increased rate of length gain (MD 1.22 mm per wk, 95% CI 1.01 to 1.44; N = 320 in 5 studies), head circumference (MD 0.45 mm per wk, 95% CI 0.19 to 0.70; N = 320 in 5 studies), weight gain (MD 2.55 g/kg/d, 95% CI 1.76 to 3.34; N = 379 in 6 studies), and weight gain at 28 d in LMIC (SMD 1.57, 95% CI 0.79 to 2.36; N = 192 in 2 studies) ASQ, Ages and Stages Questionnaire; BSID, Bayley Scales of Infant Development; CI, confidence interval; HIC, high-income country; MD, mean difference; OR, odds ratio; RR, risk ratio; SMD, standard mean difference; SR, systematic review.

97 prevent stunting, being underweight,93 mortality,98 particularly from measles,99 ​ diarrhea, reduce ,104 and and respiratory infections. diarrhea,​ and pneumonia. increase height105 and weight. Gogia Supplementary feeding for healthy and Sachdev conducted a review but socioeconomically disadvantaged Interventions that improve the of the effect of zinc supplementation children <5 years old in LMIC uptake of clean water, sanitation on mental and motor development improves hemoglobin, growth, 94 infrastructure, and optimal hygiene in children and concluded that and psychomotor development,​ practices can prevent diarrhea and there was insufficient evidence of but reported94 effects on cognition other water-borne diseases and 36 developmental benefits in young were mixed. Chronic protein reduce environmental enteropathy,​ children. and caloric deficits during acute although there are few direct malnutrition lead to stunting and measures of developmental benefits. Intermittent preventive treatment and contribute to suboptimal Promotion of optimal hand-washing among children who live in malaria- neurodevelopment, and treatment and water quality-improvement endemic areas can prevent106 severe with specially formulated therapeutic95,96​ strategies can improve weight 100for age malaria and 107anemia and improve foods can facilitate recovery. ‍ and height for age among girls and hemoglobin in anemic children. Infection Prevention and Control 101 reduce diarrheal morbidity,​ A Cochrane review of deworming During Childhood with some evidence of gains in infected children showed improved development quotients at 5 to 7 years growth, but presumptive treatment (See Supplemental Table 9). within population settings (such Strategies for preventing and as mass deworming programs) has mitigating childhood infection are Zinc as a diarrhea102 treatment can not been shown to have significant108 essential to optimizing child health improve growth and103 reduce growth or developmental benefits,​ and development (Table 6). Routine persistent diarrhea. Zinc which is a finding that is echoed by childhood vaccines are effective supplementation among healthy a recent network meta-analysis109 on in reducing both morbidity and children can mitigate the severity of mass deworming. Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 140, number 2, August 2017 9 TABLE 5 Review of Key Impacts for Nutrition Interventions Delivered During Infancy and Childhood Key Interventions Summary Effects With Implications for Developmental Outcomes (Direct Developmental Effects) Breastfeeding promotion, 2 SRs, HIC, Improved breastfeeding practices from a variety of promotion interventions: more early initiation of breastfeeding in and LMIC the first hour (OR 1.25, 95% CI 1.19 to 1.32; 49 studies), improved exclusive breastfeeding at day 1 (RR 1.43, 95% CI 1.09 to 1.87; N = 10 409 in 15 studies), in the first 6 mo (OR 1.44, 95% CI 1.38 to 1.51; 130 studies), and at –1 5 mo in LMIC (RR 2.88, 95% CI 2.11 to 3.93; 29 studies) Iron supplementation, 2 SRs, HIC, and Improved iron status with intermittent supplementation: reduced risk of anemia (RR 0.51, 95% CI 0.37 to 0.72; N = 1824 LMIC in 10 studies) and iron deficiency (RR 0.24, 95% CI 0.06 to 0.91; N = 431 in 3 studies) Mixed effects on development: improved motor quality (Behavior Rating Scale score MD 15.60, 95% CI 7.66 to 23.54; N = 172 in 1 study), improved psychomotor development (BSID II score MD 6.90, 95% CI 1.35 to 12.45; N = 172 in 1 study), reduced IQ (MD −3.00, 95% CI −5.96 to −0.04; N = 252 in 1 study), improved IQ (SMD 0.41, 95% CI 0.20 to 0.62; 9 studies), and improved mental development (combined score SMD 0.30, 95% CI, 0.15 to 0.46; 14 studies) Nonsignificant effects: motor development score (SMD 0.09, 95% CI− 0.08 to 0.26; N = 1246 in 10 studies) MMN supplementation, 3 SRs, HIC, and Improved iron status: reduced risk of anemia (RR 0.66, 95% CI 0.57–0.77; N = 2524 in 11 studies), iron deficiency LMIC anemia (RR 0.43, 95% CI 0.35 to 0.52; N = 1390 in 7 studies), and improved hemoglobin (SMD 0.98, 95% CI 0.55 to 1.40; N = 8354 in 14 studies) Increased diarrhea: small significant increase in diarrheal risk (RR 1.04, 95% CI 1.01 to 1.06;N = 3371 in 4 studies) Small cognitive and motor benefits: improved academic performance at ages –5 16 (SMD 0.30, 95% CI 0.01 to 0.58; 4 studies) and motor development milestone score (MD 1.1, 95% CI 0.3 to 1.9; N = 361 in 1 study) Improved linear growth, weight gain, and hemoglobin was reported in 1 review with a low AMSTAR rating Nonsignificant effects: fluid intelligence (SMD 0.14, 95% CI− 0.02 to 0.29; 12 studies) and crystallized intelligence (SMD −0.03, 95% CI −0.21 to 0.14; 11 studies) Vitamin A supplementation, 1 SR, HIC, Improved vitamin A status: reduced risk of (RR 0.71, 95% CI 0.65 to 0.78;N = 2262 in 4 studies), and LMIC night blindness (RR 0.32, 95% CI 0.21 to 0.50; N = 22 972 in 2 studies), and xerophthalmia (RR 0.31, 95% CI 0.22 to 0.45; N = 57 866 in 2 studies) Reduced infectious disease morbidity: reduced incidence of diarrhea (RR 0.85, 95% CI 0.82 to 0.87; N = 37 710 in 13 studies), measles (RR 0.50, 95% CI 0.37 to 0.67; N = 19 566 in 6 studies), and malaria (RR 0.73, 95% CI 0.60 to 0.88; N = 480 in 1 study) Complementary feeding education and Improved growth and nutrition status: reduced risk of stunting (RR 0.71, 95% CI 0.56 to 0.91; N = 1940 in 5 studies), provision, 1 SR, LMIC and in food-secure populations improved height gain (SMD 0.35, 95% CI 0.08 to 0.62; 4 studies) and weight gain (SMD 0.40, 95% CI 0.02 to 0.78; 4 studies) Improved growth and nutrition status: reduced risk of stunting (RR 0.33, 95% CI 0.11 to 1.00; N = 1652 in 7 studies) and being underweight (RR 0.35, 95% CI 0.16 to 0.77; N = 319 in 12 studies) in food-insecure populations Reduced risk of respiratory infections (RR 0.67, 95% CI 0.49 to 0.91; N = 823 in 3 studies) Supplementary feeding, 1 SR, HIC, and Improved iron status in LMIC: increased hemoglobin (SMD 0.49, 95% CI 0.07 to 0.91; N = 300 in 5 studies) LMIC Improved growth and nutrition status in LMIC: increased weight-for-age z score (MD 0.15, 95% CI 0.05 to 0.24; N = 1565 in 8 studies) and height-for-age z score (MD 0.15, 95% CI 0.06 to 0.24; N = 4544 in 9 studies) Mixed effects on development in LMIC: increased psychomotor development score (SMD 0.41, 95% CI 0.10 to 0.72; N = 178 in 2 studies), reduced cognitive development score (SMD −0.40, 95% CI −0.79 to 0); N = 113 in 1 study), and increased cognitive development test battery score (SMD 0.58, 95% CI 0.17 to 0.98; N = 99 in 1 study) Therapeutic foods for moderate and Improved growth rate with therapeutic foods: increased rate of height gain (MD 0.14 mm per d, 95% CI 0.05 to 0.22; 3 severe acute malnutrition, 2 SR, LMIC studies), rate of weight gain (MD 1.27 g/kg per d, 95% CI 0.16 to 2.38; 3 studies) in severe acute malnutrition, and rate of mid-upper arm circumference gain in moderate acute malnutrition (MD 0.04 mm per d, 95% CI 0.02 to 0.06; N = 4568 in 4 studies) BSID II, Bayley Scales of Infant Development, Second Edition; CI, confidence interval; HIC, high-income country; MD, mean difference; OR, odds ratio; RR, risk ratio; SMD, standard mean difference; SR, systematic review.

Discussion

We mitigated this by specifically remarkable paucity of the direct scanning for and including measures of child development This overview has several limitations developmental impacts that were not outcomes reported in both reviews inherent to the search strategy that reported in the main reviews. We do and studies of interventions, which was used, and as such, it cannot recognize that incomplete reporting would plausibly have developmental comprehensively represent the of study characteristics at the review impacts. In many instances, this full extent of the potential impact level may have excluded potentially could be related to study designs, of MNCH&N interventions on relevant study-level data. primary objectives, and the child development. Studies that duration of follow-up. For example, contributed to the pooled estimates Despite the large volume of the studies of asphyxia prevention and reported here were selected on the literature reviewed, and although management typically only assessed basis of the included systematic effects on anthropometry, morbidity, outcomes in the short-term, such reviews, which may not have and survival were consistently as neonatal mortality, hypoxia, and focused on developmental impacts. reported, our analysis shows a encephalopathy. In other cases, the Downloaded from www.aappublications.org/news by guest on September 29, 2021 10 Vaivada et al TABLE 6 Review of Key Impacts for Infectious Disease Prevention and Treatment Delivered During Infancy and Childhood Key Interventions Summary Effects With implications for Developmental Outcomes (Direct Developmental Effects) Rotavirus, H. influenzae B, Reduced diarrheal morbidity: rotavirus vaccine reduced risk of severe rotavirus infection (RR 0.39, 95% CI 0.25 to 0.62; pneumococcal vaccines, and N = 1081 in 1 study) and severe gastrointestinal infection (RR 0.68, 95% CI 0.57 to 0.81; N = 2901 in 6 studies) routine , 2 SRs, Reduced pneumonia morbidity: HiB and pneumococcal vaccine reduced risk of clinically severe HiB pneumonia (RR 0.94, 95% LMIC CI 0.89 to 0.99; N = 5304 in 3 studies) and radiologically confirmed pneumococcal pneumonia (RR 0.74, 95% CI 0.63 to 0.88; N = 1619 in 3 studies) Improved water, sanitation, and Improved growth in girls: increased weight-for-age z score (MD 0.11, 95% CI 0.01 to 0.21; N = 2283 in 7 studies) and height-for- hygiene, 2 SRs, LMIC age z score (MD 0.15, 95% CI 0.04 to 0.26; N = 2283 in 5 studies) in girls only Water quality improvement: reduced diarrheal morbidity in children <5 y (RR 0.60, 95% CI 0.44 to 0.81; N = 5682 in 29 studies) Hand-washing with soap: reduced diarrheal morbidity (RR 0.53, 95% CI 0.37 to 0.76; N = 1896 in 7 studies) Excreta disposal: reduced diarrheal morbidity (RR 95% CI 0.37 to 0.92; 4 studies) Zinc supplementation and Improved growth: increased height gain (SMD 0.19, 95% CI 0.08 to 0.30; 34 studies), height (SMD 0.09, 95% CI 0.06 to 0.13; diarrhea treatment, 5 SRs, HIC, N = 13 669 in 50 studies) and weight gain (SMD 0.10, 95% CI 0.07 to 0.14; N = 12 305 in 44 studies) and LMIC Improved zinc status but lowered iron status: reduced zinc deficiency (RR 0.49, 95% CI 0.45 to 0.53; 15 studies) and reduced serum ferritin (SMD −0.07, 95% CI −0.13 to 0.00; 18 studies) Mixed effects on respiratory infection prevalence, more vomiting: increased lower respiratory tract infection prevalence (RR 1.20, 95% CI 1.10 to 1.30; 3 studies), decreased pneumonia morbidity (RR 0.81, 95% CI 0.73 to 0.90; 6 studies), and more vomiting episodes (RR 1.68, 95% CI 1.61 to 1.75; N = 4095 in 5 studies) Reduced infectious disease morbidity: lower incidence of diarrhea (RR 0.87, 95% CI 0.81 to 0.94; 14 studies), persistent diarrhea (RR 0.73, 95% CI 0.62 to 0.85; 8 studies), and severe diarrhea (RR 0.89, 95% CI 0.84 to 0.95; 6 studies) Less diarrhea, more vomiting: reduced duration of persistent diarrhea (MD −15.84 h, 95% CI −25.43 to −6.24; N = 529 in 5 studies) and increased risk of vomiting (RR 1.59, 95% CI 1.27 to 1.99; N = 5189 in 10 studies) Nonsignificant effects: mental development score (MD− 0.5, 95% CI −2.06 to 1.06; N = 2134 in 8 studies) and psychomotor development score (MD 1.54, 95% CI −2.26 to 5.34; N = 2134 in 8 studies) Intermittent preventive therapy Improved hemoglobin status: during intervention, reduced risk of severe anemia (RR 0.24, 95% CI 0.06 to 0.94; N = 3282 and bed nets, 2 SR, LMIC in 2 studies) and moderately severe anemia (RR 0.71, 95% CI 0.52 to 0.98; N = 8805 in 5 studies), and higher change in hemoglobin at 12 wk follow-up (MD 0.32 g/dL, 95% CI 0.19 to 0.45; N = 1672 in 4 studies) Reduced malaria morbidity: reduced risk of severe malaria (RR 0.27, 95% CI 0.10 to 0.76; N = 5964 in 2 studies) and clinical malaria (RR 0.26, 95% CI 0.17 to 0.38; N = 9321 in 6 studies) Deworming drugs, 1 SR, LMIC Improved anthropometric measures: treatment of infected children increased weight (MD 0.75 kg, 95% CI 0.24 to 1.26; N = 627 in 5 studies), height (MD 0.25 cm, 95% CI 0.01 to 0.49; N = 647 in 5 studies), and mid-upper arm circumference (MD 0.49 cm, 95% CI 0.39 to 0.58; N = 396 in 4 studies) CI, confidence interval; HiB, Haemophilus influenzae B; HIC, high-income country; MD, mean difference; RR, risk ratio; SMD, standard mean difference; SR, systematic review.

dearth of developmental measures are included, hence our effort at processes is needed. Some is potentially related to the difficulty collating the evidence from individual interventions may confer additional in assessing such outcomes in studies that were reported outside developmental benefits alongside addition to mortality and morbidity. meta-analyses.Research Gaps those that are mediated through The available evidence suggests improved nutrition and reduced that benefits to development can infectious disease burden, and be derived from maternal and child There is currently no global set they cannot be captured solely nutrient supplementation and of standard indicators for the 110 through typical anthropometric or protective interventions for at-risk measurement of child development,​ clinical measures. A key example infants both before and after birth. and few direct measures of child is KMC for preterm infants, which In fairness, most interventions are development have actually been can reduce mortality, infection, implemented for direct benefits on validated in the LMIC with the and hypothermia in addition to 31 child survival, and this is sufficient highest burdens of undernutrition111 improving breastfeeding practices rationale to provide them. However, and developmental delay. (and so addressing multiple risk there is insufficient information on Longitudinal data collection in a factors simultaneously). The recently113 whether a reduction in mortality in broader set of countries is needed updated Cochrane review on KMC a population with a given health and to quantify the social and economic shows a 50% reduced risk of severe nutrition intervention also reduces benefits of MNCH&N interventions, Ninfection or sepsis (risk ratio 0.50, the incidence of severe morbidities, including those deriving from 112 95% confidence interval 0.36 to 0.69; subsequent developmental deficits, averted developmental delays. = 1463 in 8 studies). Whereas KMC or the converse. Even in those Mainstreaming the collection and could affect development through reviews that do have meta-analyses reporting of child development mitigating infection and improving of effects on cognitive or motor outcomes for interventions that have nutrition, improved68 mother-infant development, relatively few studies a plausible link to developmental attachment suggests additional Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 140, number 2, August 2017 11 benefits could be mediated through immediate neonatal period present macronutrient and micronutrient stimulation and early socioemotional a variety of risks to both mother supplementation programs in development. and and child, particularly for infants children showed small but significant emollient therapy are other neonatal who are born preterm or SGA and effects on mental development interventions with stimulation those without access to skilled whereas stimulation interventions components that require additional birth attendance. Recent evidence 121have shown greater effect sizes,​ research to determine their from rural Nepal (a setting with ‍ which suggests that delivering Implicationseffectiveness, for particularly Policy and in Research LMIC. extremely low coverage of skilled nutrition interventions alone may be birth attendance) demonstrated a insufficient. These data collectively significant association between SGA reinforce the potential integration and low birth weight and poorer of early child health and nutrition The benefits of maternal health and 118 neurocognitive outcomes. In interventions with strategies such as nutrition interventions in pregnancy a high-income setting, moderate stimulation and responsive feeding to for both mother and infant are well preterm birth combined with SGA optimizePanel: Recommended development Coreoutcomes. established. The consequences has been associated with general Package of MNCH&N Interventions of IUGR for child growth and and Actions to Support Child cognitive deficits in adolescents development are myriad and include Development 18 years later, although the study neurodevelopmental deficits, poorer 119,120​ subgroup size was small. ‍ school performance, and behavioral 114 Links between preventable issues in childhood. At least one- intrauterine and neonatal disease 1. During preconception and fifth of all stunting at 6 months is and neurodevelopmental outcomes pregnancy: determined by fetal malnutrition and 37 have also been demonstrated, with a. improve nutritional status with SGA. Prevention and early detection preterm birth and neonatal sepsis micronutrients as a supplement of IUGR to institute interventions ≥ being associated with substantially to a diverse and calorically may mitigate detrimental effects 21 increased risk of 1 neurocognitive adequate diet on the developing fetus. Limited 23 or motor deficit. available evidence suggests that b. reduce the risk of infection interventions addressing maternal with screening, treatment, and There exists ample evidence undernutrition and micronutrient prophylaxis supporting the benefits of deficiencies should start early and 55 breastfeeding, yet global coverage of c. support maternal mental preferably before conception. this intervention remains low with health and well-being by Whereas supporting maternal mental little change over time. Implementing addressing domestic violence health is essential, antidepressant use breastfeeding promotion and and preventing and treating during pregnancy may increase the 115,116​ support strategies also necessitates depression risk of poorer birth outcomes. ‍ investments in strategies to secure Perinatal psychosocial support and 2. During labor, child birth, and the appropriate maternity leave, counseling provided to mothers immediate neonatal period: supportive work environments, can be successfully delivered a. ensure access to a safe, hygienic 117 and protection of this precious in low-resource settings. birth and essential newborn care public health intervention from Additional research is also needed inappropriate marketing of breast b. mitigate the effects of preterm to understand the effects of violence milk substitutes. Further highlighting birth and complications with and stress on maternal mental health the critical role of nutrition in early neuroprotective interventions and subsequent effects on child developmental processes are recent and KMC development (particularly in conflict findings from the Pelotas birth zones) so that targeted interventions c. promote early and exclusive cohort in Brazil, where 30 years can be developed. breastfeeding later, breastfeeding was found to 3. During infancy and early The findings of this overview further be associated with intelligence120 strengthen recommendations and educational attainment. A childhood: for the scale-up of both nutrition large-cluster randomized trial of a. promote and support optimal and infection prevention and breastfeeding promotion using the breastfeeding and responsive treatment interventions delivered Baby-Friendly Hospital Initiative complementary feeding during the prenatal and immediate model in Belarus found that this practices coupled with adequate neonatal period to support intervention significantly82 increased psychosocial stimulation (eg, both child survival36 and optimal verbal IQ at 6.5 years. Recent meta- the Care for Child Development development. Childbirth and the analyses of the effect of a variety of package) Downloaded from www.aappublications.org/news by guest on September 29, 2021 12 Vaivada et al b. provide micronutrients for is associated with greater benefits populations with both prevention children at risk for deficiency than traditional iron-folic acid therapy and treatment (eg, undernourished c. reduce infectious disease predicate a concerted move to scale mothers, preterm infants, anemic morbidity through screening, these up for global use. Similarly, infants, and rural and underserved treatment, and prophylaxis supporting food-insecure and actively populations) is necessary to have malnourished women with proper maximum impact. Additional research d. support access to safe water and supplements or food baskets is not attempting to quantify developmental sanitation facilities, and promote only a humanitarian imperative; the impacts would strengthen current hygienic behaviors for mothers benefits to maternal health and infant recommendations and provide and children outcomes are considerable. The period governments with additional economic 4. Future research on early from birth to 2 years is a particularly incentives to invest in MNCH&N. interventions should prioritize crucial time to intervene and set Acknowledgments follow-up in early childhood and children on optimal developmental measure developmental progress trajectories and affords the ability whenever possible to integrate the implementation of We thank Sabrina Azwim, Renee 5. Encourage intersectoral complementary actions that support Sharma, and Matthew Buccioni for cooperation throughout the nutrition and stimulation. Interactions their assistance in data extraction continuum of care, and support with the health sector offer unique and the quality appraisal of the opportunities for promoting early child included reviews. the concurrent delivery of both ’ ’ Abbreviations life-saving and brain-saving development, and this is leveraged in interventions (such as packages the United Nations Children s Fund s122 of care) in each of these critical Care for Child Development Package. AMSTAR: A Measurement Tool Recommendationswindows for Integrated Such strategies for integrating early to Assess Systematic Implementation and Research child health, nutrition, and stimulation interventions through community Reviews IUGR: intrauterine growth health workers123, have124​ been successful in restriction Of the existing interventions, those rural Pakistan. ‍ KMC: Kangaroo Mother Care that are recommended for scaling-up Overall, the evidence supports existing LMIC: low- and middle-income are cost-effective packages of recommendations for a scale-up of ’ countries care to enhance adolescent and interventions across the continuum of ’ MMN: multiple micronutrient young women s nutrition and care to reduce mortality and morbidity MNCH&N: maternal, newborn, health status complemented with and for potential benefits to children s and child health and continued preventive and protective cognitive, motor, and socioemotional nutrition interventions during pregnancy. The development. Maintaining an equity SGA: small for gestational age findings that MMN supplementation focus and targeting specific at-risk Accepted for publication May 4, 2017 Address correspondence to Zulfiqar A. Bhutta, PhD, Centre for Global Child Health, The Hospital for Sick Children, 686 Bay Street, 11th Floor, Suite 11.9805, Toronto, ON M5G 0A4, Canada. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2017 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: All stages of this study were supported by unrestricted grants from Grand Challenges Canada, the World Health Organization, and core funding from the SickKids Centre for Global Child Health. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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