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Custer randomized trials are often used to study large-scale public health interventions. In large trials, even small improvements in statistical efficiency can have profound impacts on the required sample size and cost. Pair matched randomization is one strategy with potential to increase trial efficiency, but to our knowledge there have been no empirical evaluations of pair-matching in large-scale, epidemiologic field trials. Location integrates many socio-demographic and environmental characteristics into a single feature. Here, we show that geographic pair-matching leads to substantial gains in statistical efficiency for 14 child health outcomes that span growth, development, and infectious disease through a re-analysis of two large-scale trials of nutritional and environmental interventions in Bangladesh and Kenya. We estimate relative efficiencies ≥ 1.1 for all outcomes assessed and relative efficiencies regularly exceed 2.0, meaning an unmatched trial would have needed to enroll at least twice as many clusters to achieve the same level of precision as the geographically pair-matched design. We also show that geographically pair-matched designs enable estimation of fine-scale, spatially varying effect heterogeneity under minimal assumptions. Our results demonstrate broad, substantial benefits of geographic pair-matching in large-scale, cluster randomized trials.

Choline is an essential micronutrient that may influence growth and development; however, few studies have examined postnatal choline status and children's growth and development in low- and middle-income countries. The aim of this observational analysis was to examine associations of plasma choline with growth and development among Malawian children aged 6-15 months enrolled in an egg intervention trial. Plasma choline and related metabolites (betaine, dimethylglycine and trimethylamine N-oxide) were measured at baseline and 6-month follow-up, along with anthropometric (length, weight, head circumference) and developmental assessments (the Malawi Developmental Assessment Tool [MDAT], the Infant Orienting with Attention task [IOWA], a visual paired comparison [VPC] task and an elicited imitation [EI] task). In cross-sectional covariate-adjusted models, each 1 SD higher plasma choline was associated with lower length-for-age z-score (-0.09 SD [95% confidence interval, CI -0.17 to -0.01]), slower IOWA response time (8.84 ms [1.66-16.03]) and faster processing speed on the VPC task (-203.5 ms [-366.2 to -40.7]). In predictive models, baseline plasma choline was negatively associated with MDAT fine motor z-score at 6-month follow-up (-0.13 SD [-0.22 to -0.04]). There were no other significant associations of plasma choline with child measures. Similarly, associations of choline metabolites with growth and development were null except higher trimethylamine N-oxide was associated with slower information processing on the VPC task and higher memory scores on the EI task. In this cohort of children with low dietary choline intake, we conclude that there were no strong or consistent associations between plasma choline and growth and development.

Background Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNS) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting. Objective We aimed to identify the effect of SQ-LNS on prevalence of severe wasting (weight-for-length z-score < -3) and severe stunting (length-for-age z-score < -3). Methods We conducted a two-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNS provided to children 6 to 24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS vs. control and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. Results SQ-LNS provision led to a relative reduction of 31% in severe wasting (Prevalence Ratio, PR 0.69 (0.55, 0.86), n=34,373) and 17% in severe stunting (PR 0.83 (95% CI: 0.78, 0.90), n=36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded: PR 0.74 (0.57, 0.96), n=26,327 for severe wasting and PR 0.88 (0.81, 0.95), n=28,742 for severe stunting. Study-level characteristics generally did not significantly modify the effects of SQ-LNS, but results suggested greater effects of SQ-LNS in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation. Conclusions Including SQ-LNS in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. Registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592. This is a pre-copyedited, author-produced PDF of an article accepted for publication in The American Journal of Clinical Nutrition following peer review. The version of record [Preventive small-quantity lipid-based nutrient supplements reduce severe wasting and severe stunting among young children: an individual participant data meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition (2022)] is available online at: https://doi.org/10.1093/ajcn/nqac232. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing help@openaccessbutton.org.

BackgroundYoung children with diets lacking diversity with low consumption of animal source foods are at risk of iron deficiency anemia (IDA).ObjectivesOur objectives were to determine the impact of supplementing diets with 1 egg/d on 1) plasma ferritin, soluble transferrin receptor (sTfR), body iron index (BII), and hemoglobin concentrations and 2) the prevalence of iron deficiency (ID), anemia, and IDA.MethodsMalawian 6-9-mo-old infants in the Mazira trial (clinicaltrials.gov; NCT03385252) were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329). In this secondary analysis, hemoglobin, plasma ferritin, sTfR, C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) were measured at enrollment and 6-mo follow-up. Iron biomarkers were corrected for inflammation. Ferritin, sTfR, BII, and hemoglobin were compared between groups using linear regression. Prevalence ratios (PRs) for anemia (hemoglobin 8.3 mg/L, or BII

BACKGROUND: Vitamin A deficiency (VAD) is common in populations with limited dietary diversity and access to vitamin A-rich foods. OBJECTIVES: This analysis aimed to determine the impact of supplementing children’s diets with 1 egg/d on the concentration of plasma retinol and RBP and the prevalence of VAD. METHODS: Children age 6–9 mo living in the Mangochi district of Malawi were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329) in the Mazira trial (clinicaltrials.gov; NCT03385252). This secondary analysis measured plasma retinol by HPLC and RBP, CRP, and α-1-acid glycoprotein (AGP) by ELISA techniques at enrollment and 6 mo follow-up. Retinol and RBP were adjusted for inflammation, and mean concentrations were compared between groups using linear regression models. In addition, prevalence ratios of VAD (retinol 5 mg/L or AGP >1 g/L: 62%) and inflammation-adjusted VAD (7%) at enrollment did not differ between groups. At follow-up, the egg intervention group did not differ from the control in inflammation-adjusted retinol [geometric mean (95% CI); egg: 1.10 μmol/L (1.07, 1.13); control: 1.08 (1.05, 1.12)], RBP [egg: 0.99 μmol/L (0.96, 1.02); control: 0.97 (0.94, 1.00)], or prevalence of VAD [egg: 6%; control: 3%; prevalence ratio: 1.87 (0.83, 4.24)]. CONCLUSIONS: Provision of 1 egg/d did not impact VAD, plasma retinol, or RBP among young children in rural Malawi, where the prevalence of VAD was low. Curr Dev Nutr 2023;x:xx. This trial was registered at [clinicaltrials.gov] as [NCT03385252].

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%. A genetic link suggests that interventions that halve the risk of malaria episodes could reduce the prevalence of iron deficiency in African children by nearly 50%.

ObjectiveRecent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modeling framework to estimate the cost and cost-effectiveness of SQ-LNS and apply the framework in the context of rural Uganda.DesignWe adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anemia, and developmental disability.SettingRural Uganda.ParticipantsNot applicable.ResultsProviding SQ-LNS daily to all children in rural Uganda (>1 million) for 12 months (from 6-18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars), or ∼$58.7 million annually. Annually, SQ-LNS could avert an average of >242,000 disability adjusted life years (DALYs) as a result of preventing 3,689 deaths, >160,000 cases of moderate or severe anemia, and ∼6,000 cases of developmental disability. The estimated cost per DALY averted is $242, which is considered “very cost effective” relative to the Uganda per capita GDP of $822.ConclusionsIn this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a program including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility.

In the 5 years since our article ‘Cracking the egg potential during pregnancy and lactation’ was published, the recognition that eggs likely provide critical nutrients during pregnancy and lactation for newborn and child health and neurodevelopment, and also that they can contribute to reducing poverty and supporting sustainable food systems has continued to grow. Eggs are rich in choline and docosahexaenoic acid (DHA), two nutrients hypothesized to have favorable effects on birth outcomes as well as on child growth, morbidity, inflammation, and neurodevelopment. They contain high levels of several other nutrients and vitamins, including lutein and other carotenoids, and vitamins E, D, and B12, and folate; they are also rich in selenium and iodine. In as much as pregnant and lactating women have higher protein and other nutrient requirements compared with nonpregnant women, eggs are an ideal food to consume during this time. Nonetheless, because they are expensive relative to other sources of energy, consumption is low among women.

It should not be surprising that a simple egg, which provides a chicken embryo nutritive support from conception to the time it hatches, might also be an important food to support fetal growth and development during pregnancy. Eggs have great potential to improve nutrition among vulnerable populations living in resource-poor settings. They provide a nearly complete source of protein and are also an important source of essential fatty acids, choline, vitamins A and B12, selenium, and other critical nutrients. At the same time, compared to other animal-source foods, they cost less and are available and valued as a food in virtually all parts of the world.

Background We evaluated the impact of low-cost water, sanitation, and handwashing (WSH) and child nutrition interventions on enteropathogen carriage in the WASH Benefits cluster-randomized controlled trial in rural Bangladesh. Methods We analyzed 1411 routine fecal samples from children 14 ± 2 months old in the WSH (n = 369), nutrition counseling plus lipid-based nutrient supplement (n = 353), nutrition plus WSH (n = 360), and control (n = 329) arms for 34 enteropathogens using quantitative polymerase chain reaction. Outcomes included the number of co-occurring pathogens; cumulative quantity of 4 stunting-associated pathogens; and prevalence and quantity of individual pathogens. Masked analysis was by intention-to-treat. Results Three hundred twenty-six (99.1%) control children had 1 or more enteropathogens detected (mean, 3.8 ± 1.8). Children receiving WSH interventions had lower prevalence and quantity of individual viruses than controls (prevalence difference for norovirus: –11% [95% confidence interval {CI}, –5% to –17%]; sapovirus: –9% [95% CI, –3% to –15%]; and adenovirus 40/41: –9% [95% CI, –2% to –15%]). There was no difference in bacteria, parasites, or cumulative quantity of stunting-associated pathogens between controls and any intervention arm. Conclusions WSH interventions were associated with fewer enteric viruses in children aged 14 months. Different strategies are needed to reduce enteric bacteria and parasites at this critical young age.

Background Undernutrition is associated with an elevated risk of mortality among children in low- and middle-income countries. Small-quantity lipid-based nutrient supplements (LNS) have been evaluated as a method to prevent undernutrition and improve infant development, but the effects on mortality are unknown. Objective Our objective was to evaluate the effect of LNS on all-cause mortality among children 6-24 mo old. Methods We conducted a systematic review and meta-analysis of randomized controlled trials of LNS designed to prevent undernutrition, with or without other interventions. Literature was searched in May 2019 and trials were included if they enrolled children between 6 and 24 mo old and the period of supplementation lasted ≥6 mo. We extracted data from participant flow diagrams and contacted study investigators to request data. We conducted a meta-analysis to produce summary RR estimates. Results We identified 18 trials conducted in 11 countries that enrolled 41,280 children and reported 586 deaths. The risk of mortality was lower in the LNS arms than in the non-LNS comparison arms (RR: 0.73; 95% CI: 0.59, 0.89; 13 trials). Estimates were similar when trials with maternal LNS intervention arms were added or when alternative formulations of LNS were excluded. The results appeared stronger in trials in which LNS were compared with passive control arms. Excluding these contrasts and only comparing multicomponent arms with LNS groups and comparison groups that contained all the same components without LNS attenuated the effect estimate (RR: 0.82; 95% CI: 0.61, 1.10). Conclusions LNS provided for the prevention of undernutrition may reduce the risk of mortality, but more trials with appropriate comparison groups allowing isolation of the effect of LNS alone are needed.This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019128718.

Background: In utero or early-life exposure to aflatoxin, which contaminates staple crops in disadvantaged settings, may compromise pregnancy and infant outcomes, but investigations into the extent, persistence, and determinants of aflatoxin exposure at these life stages have lacked longitudinal data collection and broad geographic representation. Objectives: Aflatoxin exposure and selected determinants thereof were characterized in mother–child dyads with serial plasma/serum samples in prenatal, perinatal, and early life in Malawi and Bangladesh. Methods: Circulating aflatoxin B1 (AFB1)–lysine albumin adducts were measured in dyads from Bangladesh (n = 573; maternal first and third trimester, 3 mo postpartum, cord blood, infant 24 mo) and Malawi (n = 255; maternal second and third trimester, 6 mo postpartum, infant 6 and 18 mo) with isotope dilution mass spectrometry. We examined AFB1-lysine adduct magnitude, persistence, seasonality, and associations with infant feeding, and estimated daily AFB1 intake. Results: Maternal AFB1-lysine was higher in Malawi (98% detectable; median: 0.469, IQR: 0.225–1.027 pg/μL) than in Bangladesh (59%; 0.030, nondetectable [nd]–0.077 pg/μL). Although estimated dietary exposure in Malawi was temporally stable (648 ng AFB1/day), estimated intake in Bangladesh was reduced by 94% between rainy and winter seasons (98 to 6 ng/day). AFB1-lysine was low in cord blood from Bangladesh (15% detectable; 0.045, 0.031–0.088 pg/μL among detectable) and in Malawian infants at 6 mo of age (0.072, nd–0.236 pg/μL), but reached maternal concentrations by 18 or 24 mo (Bangladesh: 0.034, nd–0.063 pg/μL; Malawi: 0.370, 0.195–0.964 pg/μL). In Malawian infants, exclusive breastfeeding at 3 mo was associated with 58% lower AFB1-lysine concentrations at 6 mo compared with other feeding modes (P = 0.010). Conclusions: Among pregnant women, aflatoxin exposure was persistently high in Malawi, while lower and seasonal in Bangladesh. Infants were partially protected from exposure in utero and with exclusive breastfeeding, but exposures reached adult levels by 18–24 mo of age. The Bangladesh and Malawi trials are registered at clinicaltrials.gov as NCT00860470 and NCT01239693. Curr Dev Nutr 2022;6:nzab153. publishedVersion

ImportanceA regulated stress response is essential for healthy trajectories, but the integrated effects of early childhood environmental and nutritional interventions on stress physiology are unknown.ObjectiveTo assess the effects of a combined nutritional, water, sanitation, and handwashing intervention on physiological stress response, oxidative stress, and DNA methylation.Design, Setting, and ParticipantsIn a trial in rural Bangladesh, we randomized geographical clusters of pregnant women and their in-utero children into either the combined nutritional, water, sanitation, and handwashing intervention or the control group. Physiological stress response, oxidative stress, and methylation levels of 757 children were measured at ages one and two years. Analysis was intention-to-treat.InterventionsThe intervention group received combined nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap (N+WSH). The control group did not receive interventions.Main Outcomes and MeasuresWe measured four isomers of urinary F2-isoprostanes [iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI] at year one. At year two, we measured pre- and post-stressor concentrations of salivary alpha-amylase and cortisol, overall methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including methylation levels at the nerve growth factor-inducible protein A (NGFI-A) binding site, mean arterial pressure, and resting heart rate.ResultsChildren in the N+WSH group had lower levels of F2-isoprostanes compared to controls (difference -0.16 to -0.19 log ng/mg of creatinine, PPP=0.023) in the N+WSH group. Children in the N+WSH group exhibited decreased logit-transformed methylation of the NGFI-A transcription factor binding site (−0.04; 95% CI, -0.08 to 0; P=0.037).Conclusions and RelevanceA nutritional, water, sanitation, and handwashing intervention reduced oxidative stress, enhanced hypothalamic-pituitary-adrenocortical axis activity, and reduced methylation levels in a transcription factor binding site of the glucocorticoid receptor gene. A targeted environmental and nutritional intervention affected the set point, reactivity, and regulation of the physiological stress system in early childhood, which may have implications for long-term health and developmental trajectories.Trial RegistrationClinicalTrials.govNCT01590095Key PointsQuestionDo intensive nutritional and environmental interventions alter physiological stress response, oxidative stress levels, and epigenetic programming during the first two years of life?FindingsIn this cluster randomized clinical trial of 757 children, a combined nutritional, drinking water, sanitation, and handwashing intervention significantly reduced oxidative stress, enhanced the cortisol response, and reduced methylation levels in a transcription factor binding site of the glucocorticoid receptor gene.MeaningThe integrated nutritional, drinking water, sanitation, and handwashing intervention enhanced adaptive responses of the physiological stress system in early childhood, which may have implications for long-term health and developmental trajectories.

While studies have speculated that immune function may play a role in how water, sanitation, hygiene, and nutritional (N+WSH) interventions may individually impact child growth and development, the combined effects of these interventions on immune system development are unknown. Here, we report on a trial in rural Bangladesh, where we cluster-randomized pregnant women into control and N+WSH arms. Among the birth cohort, we quantified plasma IL-1β, IL-6, TNF-α, IL-2, IL-12p70, IFN-γ, IL-4, IL-5, IL-13, IL-17A, IL-21, IL-10, and GM-CSF at ages 14 and 28 months. Cytokine ratios were included as prespecified outcomes to examine the net inflammatory environment. We assessed 704 children. After one year, TNF-α/IL-10, IL-12/IL-10, and IL-17A/IL-10 ratios were lower in the intervention group compared to the control group (mean difference: -0.12 to -0.19, p

Author(s): Dewey, Kathryn G; Wessells, K Ryan; Arnold, Charles D; Prado, Elizabeth L; Abbeddou, Souheila; Adu-Afarwuah, Seth; Ali, Hasmot; Arnold, Benjamin F; Ashorn, Per; Ashorn, Ulla; Ashraf, Sania; Becquey, Elodie; Bendabenda, Jaden; Brown, Kenneth H; Christian, Parul; Colford, John M; Dulience, Sherlie JL; Fernald, Lia CH; Galasso, Emanuela; Hallamaa, Lotta; Hess, Sonja Y; Humphrey, Jean H; Huybregts, Lieven; Iannotti, Lora L; Jannat, Kaniz; Lartey, Anna; Port, Agnes Le; Leroy, Jef L; Luby, Stephen P; Maleta, Kenneth; Matias, Susana L; Mbuya, Mduduzi NN; Mridha, Malay K; Nkhoma, Minyanga; Null, Clair; Paul, Rina R; Okronipa, Harriet; Ouedraogo, Jean-Bosco; Pickering, Amy J; Prendergast, Andrew J; Ruel, Marie; Shaikh, Saijuddin; Weber, Ann M; Wolff, Patricia; Zongrone, Amanda; Stewart, Christine P | Abstract: ABSTRACTBackgroundMeta-analyses have demonstrated that small-quantity lipid-based nutrient supplements (SQ-LNS) reduce stunting and wasting prevalence among infants and young children. Identification of subgroups who benefit most from SQ-LNS may facilitate program design.ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child growth outcomes.MethodsWe conducted a two-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n=37,066). We generated study-specific and subgroup estimates of SQ-LNS vs. control and pooled the estimates using fixed-effects models, with random-effects models as sensitivity analyses. We used random effects meta-regression to examine study-level effect modifiers. Heterogeneity was assessed using I2 and Tau2 statistics. Sensitivity analyses were conducted to examine whether results differed depending on inclusion criteria for arms within trials and types of comparisons.ResultsSQ-LNS provision decreased stunting (length-for-age z-score l −2) by 12% (relative reduction), wasting (weight-for-length (WLZ) z-score l −2) by 14%, low mid-upper arm circumference (MUAC l 125 mm or MUACZ l −2) by 18%, acute malnutrition (WLZ l −2 or MUAC l 125 mm) by 14%, underweight (weight-for-age z-score l −2) by 13%, and small head size (head-circumference z-score l −2) by 9%. Effects of SQ-LNS on growth outcomes generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact or average reported compliance with SQ-LNS. Effects of SQ-LNS on stunting, wasting, low MUAC and small head size were greater among girls than among boys; effects on stunting, underweight and low MUAC were greater among later-born (vs. first-born) children; and effects on wasting and acute malnutrition were greater among children in households with improved (vs. unimproved) sanitation. Results were similar across sensitivity analyses.ConclusionsThe positive impact of SQ-LNS on growth is apparent across a wide variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNS in the mix of interventions to prevent both stunting and wasting. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

In utero or early-life exposure to aflatoxin, which contaminates staple crops in disadvantaged settings, may compromise pregnancy and infant outcomes, but investigations into the extent, persistence, and determinants of aflatoxin exposure at these life stages have lacked longitudinal data collection and broad geographic representation.Aflatoxin exposure and selected determinants thereof were characterized in mother-child dyads with serial plasma/serum samples in prenatal, perinatal, and early life in Malawi and Bangladesh.Circulating aflatoxin BMaternal AFBAmong pregnant women, aflatoxin exposure was persistently high in Malawi, while lower and seasonal in Bangladesh. Infants were partially protected from exposure in utero and with exclusive breastfeeding, but exposures reached adult levels by 18-24 mo of age. The Bangladesh and Malawi trials are registered at clinicaltrials.gov as NCT00860470 and NCT01239693.

Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12-14% lower prevalence of stunting, wasting, and underweight; were 16-19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663.

Background:Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth.Methods:We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders.Results:In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes.Conclusions:Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address ‘emergency states’ with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories.Funding:Funded by the Bill and Melinda Gates Foundation.Clinical trial number:NCT01590095

Choline and DHA are nutrients that, when provided during the first 1000 days from conception to age 2 years, may have beneficial effects on child neurodevelopment as well as related health factors, including birth outcomes and child growth, morbidity, and inflammation. Because these nutrients are found mainly in animal-source foods, they may be lacking in the diets of pregnant and lactating women and young children in low- and middle-income countries, potentially putting children at risk for suboptimal development and health. Prior reviews of these nutrients have mainly focused on studies from high-income countries. Here, a narrative review is presented of studies describing the pre- and postnatal roles of choline, docosahexaenoic acid, and a combination of the 2 nutrients on child neurodevelopment, birth outcomes, growth, morbidity, and inflammation in low- and middle-income countries. More studies are needed to understand the specific, long-term effects of perinatal choline and docosahexaenoic acid intake in various contexts.

Although female infants may have an early life biological advantage over males, gendered treatment can alter health outcomes. Ecuador has an unusually high ratio of male to female infant mortality, but gender norms have been reported to favor boys. This analysis of baseline data from the Lulun Project, a randomized controlled trial conducted in rural Andean communities of Ecuador, investigates the roles of sex and gender in undernutrition among infants 6 to 9 months of age. Twenty-four-hour recall frequencies were used to assess dietary intake. Food outcome models were analyzed as prevalence ratios calculated using a binomial distribution with a log link or robust Poisson regression. Linear regression was used to analyze the continuous growth outcome length-for-age z score. Socioeconomic and health history variables were comparable between male and female infants. Boys were more often fed liquids other than breastmilk within their first 3 days of life (17.1% vs. 5.2%, P = 0.026). Compared with girls, boys were less likely to be fed eggs by 33% (95% CI 0.46, 0.96), cheese, yogurt, or other milk products by 40% (95% CI 0.39, 0.92), yellow fruit by 44% (95% CI 0.33, 0.97), water by 37% (95% CI 0.45, 0.88), thin porridge by 29% (95% CI 0.56, 0.92), and tea without milk by 67% (95% CI 0.11, 0.99). Prevalence of boys with an adequate dietary diversity score (≥ 4) was reduced by 27% relative to girls (95% CI 0.54, 0.99). Males fared worse in length-for-age z scores (− 2.16 vs. − 1.56, P = 0.000), weight-for-age z scores (− 0.86 vs. − 0.33, P = 0.002), prevalence of stunting (50.6% vs. 23.4%, P = 0.000), and plasma concentrations of dimethylglycine (1.25 vs. 1.65 µg/mL, P = 0.021). After adjusting for demographic, caregiver perceptions of appetite, and biological factors, length-for-age z score for a male child was 0.62 units lower than for a female (95% CI − 0.98, − 0.26). Male infants were shown to receive lower quality complementary foods and have worse anthropometric measures than female infants.Trial registration clinicaltrials.gov, NCT02446873. Registered February 28, 2015, https://clinicaltrials.gov/ct2/show/NCT02446873.

Eggs are a rich source of multiple nutrients that support child growth and development. Provision of eggs as a complementary food may improve dietary adequacy among young children at risk for undernutrition. Our objective was to test the impact of an egg intervention on the adequacy of total nutrient intakes and micronutrient density among 6‐ to 15‐month‐old Malawian children. Children 6 to 9 months old, living in Mangochi District, Malawi, were randomly assigned to the intervention group (n = 331) receiving an egg per day or a control group (n = 329) consuming their usual diet. Dietary intakes of macronutrients, vitamins and minerals were assessed using 24‐h recalls at baseline, 3‐month midline and 6‐month endline, with repeat recalls in a subsample. Usual nutrient intake and micronutrient density distributions were modelled to estimate group means and prevalence of inadequacy. Group differences at midline and endline were tested using unequal variance t tests with bootstrapped standard errors. The egg intervention resulted in higher intakes of fat and protein and lower intakes of carbohydrates. The egg group had lower prevalence of inadequacy for selenium, vitamin A, riboflavin, vitamin B5, vitamin B12 and choline. Micronutrient density inadequacy was lower in the egg group for vitamin A and choline at midline and endline, riboflavin at midline and vitamin B5 at endline. Inadequacy of nutrient intakes or density remained highly prevalent in both groups for multiple micronutrients. Though the egg intervention increased intakes of protein and several micronutrients, total intakes and micronutrient density of multiple micronutrients remained far below recommendations.

OBJECTIVES: The purpose of the study was to assess the safety of using eggs as a nutritional intervention for stunting in infants living in a rural indigenous community in Ecuador and to further understand the prevalence of egg allergy in this population. METHODS: The Lulun Project was a randomized controlled trial conducted in a rural indigenous population in Ecuador. Infants age 6–9 months were recruited and randomly assigned to the intervention (1 egg/day; n = 80) or control (no intervention, n = 83) group. At baseline and end line, enumerators collected anthropometric, dietary intake, morbidity, and sociodemographic data along with blood samples. Symptoms of allergies were assessed, including rash, congestion, coughing or wheezing, and diarrhea. Children in the intervention group were monitored by the study team for allergy symptoms during consumption of the first study egg. All children were monitored for illness and allergy symptoms throughout the study. We used ELISA assays to determine serum anti-ovomucoid and ovalbumin IgE levels, a validated approach to identify “risk of” egg allergy. RESULTS: 131 of the children had a sufficient serum sample to be analyzed for IgE levels. Ovomucoid levels were

OBJECTIVES: Choline has been positively associated with child growth and development, but few studies have been in areas of high stunting and low choline intake. This secondary analysis examines the association of plasma choline with growth/development in Malawian children enrolled in a randomized trial of 1 egg/day versus nonintervention control. METHODS: Venous blood, anthropometric, and developmental measures were collected at enrollment (at age 6–9 mos) and at endline 6 mos later. Plasma choline, betaine, dimethylglycine, and trimethylamine N-oxide were measured using untargeted metabolomics among 400 children. Length, weight, and head circumference were converted to z-scores using WHO Growth Standards. Developmental measures included fine and gross motor, personal social, and language skills (measured and normed using the Malawi Developmental Assessment Tool), memory (elicited imitation [endline only] and visual paired comparison tasks), and attention (Infant Orienting with Attention [IOWA] task). Generalized linear models, adjusted for covariates including group assignment, were used to examine the association of plasma choline with growth/developmental outcomes. RESULTS: In cross-sectional models including both time points (baseline, endline) and adjusting for repeated measures, a 1 SD-unit increase in plasma choline was negatively associated with length-for-age z-score (–0.11 SD [95% CI: –0.20, –0.02]) and positively associated with IOWA reaction time (8.8 ms [1.7, 16.0]), meaning slower shifts in attention with higher plasma choline. In predictive models, higher baseline plasma choline predicted lower endline fine motor z-scores (–0.13 SD [–0.22, –0.04]). There were no associations of plasma choline with weight-for-age, head-circumference-for-age, weight-for-length, or the other developmental outcomes. Analysis of other biomarkers revealed few significant associations with growth/development. CONCLUSIONS: Plasma choline was not strongly associated with growth or development in this sample of Malawian children. The few significant associations suggested poorer growth/development with higher plasma choline. Further research in various contexts is needed. FUNDING SOURCES: Bill and Melinda Gates Foundation; Egg Nutrition Center.

Prenatal micronutrient deficiencies are associated with negative maternal and birth outcomes. Multiple micronutrient supplementation (MMS) during pregnancy is a cost‐effective intervention to reduce these adverse outcomes. However, important knowledge gaps remain in the implementation of MMS interventions. The Child Health and Nutrition Research Initiative (CHNRI) methodology was applied to inform the direction of research and investments needed to support the implementation of MMS interventions for pregnant women in low‐ and middle‐income countries (LMIC). Following CHNRI methodology guidelines, a group of international experts in nutrition and maternal health provided and ranked the research questions that most urgently need to be resolved for prenatal MMS interventions to be successfully implemented. Seventy‐three research questions were received, analyzed, and reorganized, resulting in 35 consolidated research questions. These were scored against four criteria, yielding a priority ranking where the top 10 research options focused on strategies to increase antenatal care attendance and MMS adherence, methods needed to identify populations more likely to benefit from MMS interventions and some discovery issues (e.g., potential benefit of extending MMS through lactation). This exercise prioritized 35 discrete research questions that merit serious consideration for the potential of MMS during pregnancy to be optimized in LMIC., The specific aim of this research prioritization exercise was to inform the direction of research and investments needed to support the implementation of multiple micronutrient supplementation (MMS) interventions for pregnant women in low‐ and middle‐income countries (LMIC) using the Child Health and Nutrition Research Initiative methodology. This exercise prioritized 35 discrete research questions that merit serious consideration for the potential of MMS during pregnancy to be optimized in LMIC.

BackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) reduce child stunting and provide many of the fatty acids and micronutrients that are necessary for rapid brain development that occurs during infancy and early childhood. Positive effects of SQ-LNS on developmental outcomes have been found in some trials, but not others.ObjectivesOur objectives were to generate pooled estimates of the effect of SQ-LNS, compared to control groups that received no intervention or an intervention without any nutritional supplement, on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.MethodsWe conducted a two-stage meta-analysis of individual participant data from 14 intervention versus control group comparisons in 13 randomized trials of SQ-LNS provided to infants and young children age 6 to 24 months in 9 low- or middle-income countries (total n=30,024). We generated study-specific estimates of SQ-LNS vs. control groups (including main effects and subgroup estimates for individual-level effect modifiers) and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.ResultsIn 11-13 intervention versus control group comparisons (n=23,588-24,561), SQ-LNS increased mean language (mean difference: 0.07 standard deviations; 95% CI: 0.04, 0.10), social-emotional (0.08; 0.05, 0.11), and motor scores (0.08; 0.05, 0.11) and reduced the prevalence of children in the lowest decile of these scores by 17% (prevalence ratio: 0.83, 95% CI 0.76, 0.91), 19% (0.81; 0.74, 0.90), and 16% (0.84; 0.77, 0.92), respectively. SQ-LNS also increased the prevalence of children walking without support at 12 months by 9% (1.09; 1.05, 1.14). Effects of SQ-LNS on language, social-emotional, and motor outcomes were larger among study populations with a higher burden (≥ 35%) of child stunting at 18 months (mean difference 0.11-0.13 SD; 8-9 comparisons) than in populations with lower stunting burden (estimates near zero). At the individual level, greater effects of SQ-LNS were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socio-economic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11).ConclusionsSQ-LNS provided daily to children in the range of 6-24 months of age can be expected to result in modest, but potentially important, developmental gains, particularly in populations with high child stunting burden. Certain groups of children who experience higher risk environments, such as those from poor households or with poor baseline nutritional status, have greater potential to benefit from SQ-LNS in developmental outcomes. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Small-quantity lipid-based nutrient supplements (SQ-LNS) were designed to provide multiple micronutrients within a food base that also provides energy, protein and essential fatty acids, and were targeted towards the prevention of malnutrition in low- and middle-income countries. Previous meta-analyses have demonstrated beneficial effects of SQ-LNS on child growth, anemia and mortality. To further examine efficacy and effectiveness of SQ-LNS, and explore study-level and individual-level modifiers of the effects, we conducted an individual participant data (IPD) meta-analysis of 14 randomized controlled trials of SQ-LNS provided to infants and young children 6 to 24 mo of age (n > 37,000). We examined growth, development, anemia and micronutrient status outcomes. Children who received SQ-LNS had a 12-14% lower prevalence of stunting, wasting and underweight, were 16-19% less likely to score in the lowest decile for language, social-emotional, and motor development, and had a 16% lower prevalence of anemia and 64% lower prevalence of iron-deficiency anemia, compared to control group children. For most outcomes, beneficial effects of SQ-LNS were evident regardless of study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact or average reported compliance with SQ-LNS. For certain outcomes, targeting based on population-level socioeconomic status or undernutrition may be worthwhile, as the benefits of SQ-LNS for iron status, anemia and child development were larger in sub-groups with a greater potential to benefit. A greater impact of SQ-LNS might be possible by co-packaging it with interventions that reduce constraints on response, such as prevention and control of pre-and postnatal infections, improving maternal nutrition, improving health care access, and promotion of early child development. Policy-makers and program planners should consider including SQ-LNS in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency and developmental impairments. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971 and CRD42020156663.

Author(s): Wessells, K Ryan; Arnold, Charles D; Stewart, Christine P; Prado, Elizabeth L; Abbeddou, Souheila; Adu-Afarwuah, Seth; Arnold, Benjamin F; Ashorn, Per; Ashorn, Ulla; Becquey, Elodie; Brown, Kenneth H; Byrd, Kendra A; Campbell, Rebecca K; Christian, Parul; Fernald, Lia CH; Fan, Yue-Mei; Galasso, Emanuela; Hess, Sonja Y; Huybregts, Lieven; Jorgensen, Josh M; Kiprotich, Marion; Kortekangas, Emma; Lartey, Anna; Le Port, Agnes; Leroy, Jef L; Lin, Audrie; Maleta, Kenneth; Matias, Susana L; Mbuya, Mduduzi NN; Mridha, Malay K; Mutasa, Kuda; Naser, Abu Mohd; Paul, Rina R; Okronipa, Harriet; Ouedraogo, Jean-Bosco; Pickering, Amy J; Rahman, Mahbubur; Schulze, Kerry; Smith, Laura E; Weber, Ann M; Zongrone, Amanda; Dewey, Kathryn G | Abstract: ABSTRACTBackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to reduce the prevalence of anemia and iron deficiency among infants and young children, but effects on other micronutrients are less well known. Identifying subgroups who may experience greater benefits from SQ-LNS, or who are more likely to respond to the intervention, may facilitate the development of public health policies and programs.ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child hematological and micronutrient status outcomes.MethodsWe conducted a two-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n = 15,946). Outcomes were hemoglobin (Hb), inflammation-adjusted plasma ferritin, soluble transferrin receptor, zinc, retinol and retinol binding protein (RBP), and erythrocyte zinc protoporphyrin, and respective dichotomous outcomes indicative of anemia and micronutrient deficiency. We generated study-specific estimates of SQ-LNS vs. control, including main effects and subgroup estimates for individual-level effect modifiers, and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.ResultsProvision of SQ-LNS decreased the prevalence of anemia (Hb l 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin l 12 µg/L) by 56% and iron deficiency anemia (IDA; Hb l 110 g/L and plasma ferritin l 12 µg/L) by 64%. We observed positive effects of SQ-LNS on hematological and iron status outcomes within all subgroups of the study-level and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNS on anemia and iron status were greater in trials that provided SQ-LNS for g 12 months and provided 9 mg/d vs. l 9 mg iron/d, and among later-born (vs. first-born) children. There was no effect of SQ-LNS on plasma zinc or retinol, but there was a 7% increase in plasma RBP and a 56% reduction in vitamin A deficiency (RBP l 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics.ConclusionsSQ-LNS provided to infants and young children 6-24 months of age can substantially reduce the prevalence of anemia, iron deficiency, and IDA across a range of individual, population and study design characteristics. Policy-makers and program planners should consider SQ-LNS within intervention packages to prevent anemia and iron deficiency. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Author(s): Prado, Elizabeth L; Maleta, Kenneth; Caswell, Bess L; George, Matthews; Oakes, Lisa M; DeBolt, Michaela C; Bragg, Megan G; Arnold, Charles D; Iannotti, Lora L; Lutter, Chessa K; Stewart, Christine P | Abstract: BACKGROUND:Eggs are a rich source of nutrients important for brain development, including choline, riboflavin, vitamins B-6 and B-12, folate, zinc, protein, and DHA. OBJECTIVE:Our objective was to evaluate the effect of the consumption of 1 egg per day over a 6-mo period on child development. METHODS:In the Mazira Project randomized controlled trial, 660 children aged 6-9 mo were randomly allocated into an intervention or control group. Eggs were provided to intervention households during twice-weekly home visits for 6 mo. Control households were visited at the same frequency. At enrollment, blinded assessors administered the Malawi Developmental Assessment Tool (MDAT), and 2 eye-tracking tasks using a Tobii-Pro X2-60 eye tracker: a visual paired comparison memory task and an Infant Orienting with Attention task. At endline, 6-mo later, blinded assessors administered the MDAT and eye-tracking tasks plus an additional elicited imitation memory task. RESULTS:At endline, intervention and control groups did not significantly differ in any developmental score, with the exception that a smaller percentage of children were delayed in fine motor development in the intervention group (10.6%) compared with the control group (16.5%; prevalence ratio: 0.59, 95% CI: 0.38-0.91). Among 10 prespecified effect modifiers for the 8 primary developmental outcomes, we found 7 significant interactions demonstrating a consistent pattern that children who were less vulnerable, for example, those with higher household wealth and maternal education, showed positive effects of the intervention. Given multiple hypothesis testing, some findings may have been due to chance. CONCLUSION:The provision of 1 egg per day had no overall effect on child development in this population of children, however, some benefits may be seen among children in less vulnerable circumstances. This trial was registered at clinicaltrials.gov as NCT03385252.

Poor nutrition and hand hygiene are risk factors for acute respiratory infections (ARIs). Safe drinking water and sanitation can reduce exposure to pathogens and encourage healthy immune responses, reducing the risk of ARIs. Within a trial assessing impacts of water, sanitation, and handwashing (WASH), and nutritional interventions, we evaluated effects on ARIs. The WASH Benefits cluster-randomized trial enrolled pregnant women from Kenyan villages and evaluated health outcomes in children born to enrolled mothers 1 and 2 years after intervention delivery. Geographically adjacent clusters were block-randomized into a passive control (no promotional visits), a double-sized active control (monthly visits to measure mid–upper arm circumference), and six intervention groups: chlorinated drinking water (W), improved sanitation (S), handwashing with soap (H), combined WSH, improved nutrition (N) through counseling and lipid-based nutrient supplementation (LNS), and combined WSHN. The main outcome was the prevalence of ARI symptoms (cough, panting, wheezing, or difficulty breathing) in children younger than 3 years. Masking participants was not possible. Analyses were intention-to-treat. Between November 2012 and May 2014, 702 clusters were enrolled, including 6,960 (year 1) and 7,088 (year 2) children with ARI data. The cluster-level intra-cluster correlation coefficient for ARIs was 0.026 across both years. Water, sanitation, and handwashing interventions with behavior change messaging did not reduce ARIs. Nutrition counseling and LNS modestly reduced ARI symptoms compared with controls in year 1 [prevalence ratio (PR): 0.87, 95% confidence interval (CI): 0.77–0.99], but no effect in the combined WSHN group weakens this finding.

OBJECTIVES: Adequate protein quantity and quality are necessary for child health, growth and development, but may be lacking in complementary feeding diets with limited variety and few animal source foods. We assessed the impact of an egg feeding intervention on protein quality and quantity among rural Malawian children aged 9 to 15 months. METHODS: We enrolled 660 children into a 6-month trial to test the effect of eggs on child growth. Children were randomly assigned to the egg group (n = 331), who received one egg per day, or the control group (n = 329). Dietary intake data were collected at 3-month midline (9–12 months old) and 6-month endline visits (12–15 months old) by 24-hour recall interview with the primary caregiver. Repeat recalls were collected in a subsample at each timepoint. Crude protein intakes were calculated using local recipe and food composition tables. Breast milk intake was estimated as the difference between the estimated energy requirement and energy intake from complementary diet. Protein intakes were adjusted using the Digestible Indispensible Amino Acid Score (DIAAS), which weighs crude amino acid intakes against amino acid requirements. Treatment group differences in DIAAS were tested with ANCOVA. Group differences in adjusted total protein intakes from complementary diet and breastfeeding were tested using the National Cancer Institute method for estimating usual mean intakes with bootstrap standard errors. Adequacy was assessed using World Health Organization protein requirements. RESULTS: The egg intervention improved protein quality of the complementary feeding diet (DIAAS of 79 egg v 61 control at midline, 86 v 72 at endline, P 0.05). CONCLUSIONS: The egg intervention increased quantity and quality of protein intakes among young Malawian children, though protein inadequacy was uncommon. FUNDING SOURCES: The Bill and Melinda Gates Foundation.

BackgroundIron deficiency anemia affects hundreds of millions of women and children worldwide and is associated with impaired infant outcomes. Small-quantity lipid-based nutrient supplement (LNS) have been found to reduce the prevalence of anemia and iron deficiency in some trials.ObjectivesWe evaluated the effectiveness of daily LNS supplementation on child anemia and micronutrient status in Madagascar within the context of an existing, scaled-up nutrition program.MethodsWe cluster-randomized 125 communities to (T0) a routine program with monthly growth monitoring and nutrition education; (T1) T0+home visits for intensive nutrition counselling; (T2) T1+LNS for children aged 6-18mo; (T3) T2+LNS for pregnant/lactating women; or (T4) T1+parenting messages. Pregnant women and infants aged

The Lulun Project, a randomized controlled trial conducted in 2015, found that one egg per day for 6 months during early complementary feeding reduced stunting by 47% and increased linear growth by 0.63 length‐for‐age Z (LAZ). This follow‐up cohort study (Lulun Project II) aimed to test whether the growth effect remained in the egg intervention group compared with the control group after approximately 2 years. Mothers or caregivers from the Lulun Project were recontacted and recruited for this study. Enumerators collected data on socio‐economic and demographic factors, 24‐hr frequency of dietary intakes, morbidities, and anthropometric measures of height, weight, and head circumference using World Health Organization protocols. Statistical analyses followed the same analytical plan as Lulun Project, applying generalized linear models and regression modelling to test group differences in height‐for‐age z (HAZ) from LAZ at Lulun Project endline, and structural equation modelling for mediation. One hundred thirty‐five mother–child dyads were included in Lulun II, with 11% losses to follow‐up from endline Lulun Project. Growth faltering across all children was evident with HAZ −2.07 ± 0.91 and a stunting prevelance of 50%. Regression modelling showed no difference between egg and control groups for the HAZ outcome and other anthropometric outcomes, and significant declines in HAZ from endline Lulun Project in the egg intervention are compared with control groups. Current dietary egg intake, however, was associated with reduced growth faltering in HAZ from Lulun Project endline to Lulun Project II, independent of group assignment and through mediation, explaining 8.8% of the total effect. Findings suggest the need for a longer intervention period and ongoing nutrition support to young children during early childhood.

Childhood obesity has been associated with consumption of energy‐dense foods such as caloric beverages and fast foods. Many low‐ and middle‐income countries like Bangladesh are now experiencing a rising problem of noncommunicable diseases along with the long‐standing problem of stunting and undernutrition. WASH Benefits Bangladesh was a large community‐based cluster randomized controlled trial conducted in rural Bangladesh. Study clusters were randomized into seven arms: single nutrition (N); water (W); sanitation (S); hygiene (H); combined water, sanitation, and hygiene (WSH); WSH and nutrition (N + WSH); and a double sized control (C). Nutrition intervention messages included four promotional components: maternal nutrition, breastfeeding, complementary feeding, and lipid‐based nutrient supplements. The World Health Organization infant food frequency questionnaire (24‐hr recall and 7‐day recall) was administered at Year 1 and Year 2 of intervention. The likelihood of any snack food consumption was significantly lower (odds ratio 0.37: 95% confidence interval [0.28, 0.49]) in the nutrition intervention arms compared to the control arm in Year 2 follow‐up. In addition, in the water intervention arm, fewer children (about 50% less) consumed soft drinks, but not the other sugar‐sweetened beverages, compared with control in Year 2. There were no other differences between groups. Simple messages about balanced diet and feeding family foods were effective in lowering commercially produced snack food consumption of the young children in low‐income rural communities of Bangladesh. Provision of safe water apparently encouraged mothers to reduce offering unhealthy beverages to the young children.