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Abstract Background Does preschool height predict adult stature in undernourished settings? The extent to which preschool length or height forecasts young adult stature is unclear in chronically undernourished populations. Methods In 2006-8, we assessed height in a cohort of 2074 young adults, aged 16–23 years, in rural Nepal who, as preschoolers (≤ 4 year), were measured at baseline and again 16 months later during a vitamin A supplementation trial in 1989-91. We assessed by linear regression the ability of preschool length (L, measured -1) increased from 38–40% mid-infancy to ∼ 69–74% by 6 years of age. By 3–6 years of age heights of stunted children (L/HAZ

Abstract Background The World Health Organization (WHO) recommends balanced energy and protein (BEP) supplementation be provided to all pregnant women living in undernourished populations, usually defined as having a prevalence > 20% of underweight women, to reduce the risk of stillbirths and small-for-gestational-age neonates. Few geographies meet this threshold, however, and a large proportion of undernourished women and those with inadequate gestational weight gain could miss benefiting from BEP. This study compares the effectiveness of individual targeting approaches for supplementation with micronutrient-fortified BEP vs. multiple micronutrient supplements (MMS) alone as control in pregnancy in improving birth outcomes. Methods The TARGET-BEP study is a four-arm, cluster-randomized controlled trial conducted in rural northwestern Bangladesh. Eligible participants are married women aged 15–35 years old identified early in pregnancy using a community-wide, monthly, urine-test-based pregnancy detection system. Beginning at 12–14 weeks of gestation, women in the study area comprising 240 predefined sectors are randomly assigned to one of four intervention arms, with sector serving as the unit of randomization. The interventions involving daily supplementation through end of pregnancy are as follows: (1) MMS (control); (2) BEP; (3) targeted BEP for those with pre-pregnancy body mass index (BMI)

BackgroundIn 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.ObjectivesAflatoxin 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.MethodsCirculating 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.ResultsMaternal 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).ConclusionsAmong 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.

Abstract Introduction Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. Methods We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. Results Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. Conclusions Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.

Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = -0.43∼0.70), triglycerides (r = -0.39∼0.53), and HDL-C (r = -0.49∼0.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 4∼40%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 3∼20%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease.

Background: Malnutrition affects body growth, size, and composition of children. Yet, few functional biomarkers are known to be associated with childhood morphology.Objective: This cross-sectional study examined associations of anthropometric indicators of height, musculature, and fat mass with plasma proteins by using proteomics in a population cohort of school-aged Nepalese children.Methods: Height, weight, midupper arm circumference (MUAC), triceps and subscapular skinfolds, upper arm muscle area (AMA), and arm fat area (AFA) were assessed in 500 children 6-8 y of age. Height-for-age z scores (HAZs), weight-for-age z scores (WAZs), and body mass index-for-age z scores (BAZs) were derived from the WHO growth reference. Relative protein abundance was quantified by using tandem mass spectrometry. Protein-anthropometry associations were evaluated by linear mixed-effects models and identified as having a false discovery rate (q)

Subclinical micronutrient deficiencies remain a hidden aspect of malnutrition for which comprehensive data are lacking in school-aged children. We assessed the micronutrient status of Nepalese children, aged 6 to 8 y, born to mothers who participated in a community-based antenatal micronutrient supplementation trial from 1999 to 2001. Of 3305 participants, plasma indicators were assessed in a random sample of 1000 children. Results revealed deficiencies of vitamins A (retinol 2 μg/L, 20%), B-12 (cobalamin 8.3 mg/L, 40.1%; TfR:ferritin >500 μg/μg, 14.3%], iodine (thyroglobulin >40 μg/L, 11.4%), and selenium (plasma selenium 1 g/L, C-reactive protein >5 mg/L, or both) was present in 31.6% of children, affecting the prevalence of deficiency as assessed by retinol, β-carotene, PLP, ferritin, TfR, selenium, copper, or having any or multiple deficiencies. For any nutrient, population deficiency prevalence estimates were altered by ≤5.4% by the presence of inflammation, suggesting that the majority of deficiencies exist regardless of inflammation. Multiple micronutrient deficiencies coexist in school-aged children in rural Nepal, meriting more comprehensive strategies for their assessment and prevention.

Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = −0.43∼0.70), triglycerides (r = −0.39∼0.53), and HDL-C (r = −0.49∼0.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 4∼40#x0025;, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 3∼20#x0025;. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease.

This study aimed to describe the timing and patterns of pubertal maturation of girls living in rural Bangladesh. Starting in September 2015, a total of 15,320 girls from a birth cohort, aged 9 to 15 years at initial encounter, were visited twice at about a one year interval, typically in their birth month. Participants were asked to self-report extent of pubertal maturation, including breast development, pubic hair growth and age at menarche, if applicable. Pubertal stage (abbreviated as B2 and B3-4 for breast development and PH2 and PH3-4 for pubic hair growth) was assigned. Data from both visits were pooled, yielding a total of 29,377 age-related observations per pubertal characteristic. Probit regression models were used to estimate distributions of age at which each stage of pubertal development was attained. Before age 8,

Background: Micronutrient deficiencies are common among women in low-income and middle-income countries. Data from randomised trials suggest that maternal multiple micronutrient supplementation decreases the risk of low birthweight and potentially improves other infant health outcomes. However, heterogeneity across studies suggests influence from effect modifiers. We aimed to identify individual-level modifiers of the effect of multiple micronutrient supplements on stillbirth, birth outcomes, and infant mortality in low-income and middle-income countries. Methods: This two-stage meta-analysis of individual patient included data from 17 randomised controlled trials done in 14 low-income and middle-income countries, which compared multiple micronutrient supplements containing iron-folic acid versus iron-folic acid alone in 112 953 pregnant women. We generated study-specific estimates and pooled subgroup estimates using fixed-effects models and assessed heterogeneity between subgroups with the χ2 test for heterogeneity. We did sensitivity analyses using random-effects models, stratifying by iron-folic acid dose, and exploring individual study effect. Findings: Multiple micronutrient supplements containing iron-folic acid provided significantly greater reductions in neonatal mortality for female neonates compared with male neonates than did iron-folic acid supplementation alone (RR 0·85, 95% CI 0·75–0·96 vs 1·06, 0·95–1·17; p value for interaction 0·007). Multiple micronutrient supplements resulted in greater reductions in low birthweight (RR 0·81, 95% CI 0·74–0·89; p value for interaction 0·049), small-for-gestational-age births (0·92, 0·87–0·97; p=0·03), and 6-month mortality (0·71, 0·60–0·86; p=0·04) in anaemic pregnant women (haemoglobin