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Background: The nutrition transition underway in South Asia is likely mediated by changes to the food environment. Yet, few studies have been conducted in rural areas of South Asia to describe how the food environment has changed., Objective: This analysis assessed changes in household availability of and proximity to markets, grocery shops, and tea shops over a 16-year time period in Gaibandha, Bangladesh., Methods: We analyzed household demographic and geospatial data collected at 3 time points from 2004 to 2020 in a contiguous rural area (435 km 2 ). We defined availability as number of food vendors within 400- and 1600-m radius of households and proximity as distance to nearest vendor. We used linear and Poisson models to estimate associations between household socioeconomic status (SES) and food vendor availability and proximity. We used multi-level models to conduct similar analyses for community-level urbanicity., Results: From 2004 to 2020, the numbers of markets, grocery shops and tea shops increased by 21%, 66% and 270%, respectively. Food vendor proximity did not change by household SES, but less urban households witnessed larger increases in proximity to markets (p for interaction<0.001) and tea shops (p for interaction<0.001) over time. Grocery shop and tea shop availability was initially higher and increased more over time for households in higher urbanicity areas (p for interaction<0.001)., Conclusion: Over a 16-year period, this rural area of Bangladesh became more urbanized, increasing the availability of and proximity to markets, grocery shops, and tea shops. Further research is needed to see how these changes impact rural residents' intake and nutritional status., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Animal source foods are rich in multiple nutrients. Regular egg consumption may improve infant growth in low- and middle-income countries., Objectives: To assess the impact of daily egg consumption on linear growth among 6-12-mo olds in rural Bangladesh., Methods: We conducted a 2 × 4 factorial cluster-randomized controlled trial allocating clusters (n = 566) to treatment for enteric pathogens or placebo and a daily egg, protein supplement, isocaloric supplement, or control. All arms received nutrition education. Here, we compare the effect of the egg intervention versus control on linear growth, a prespecified aim of the trial. Infants were enrolled at 3 mo. We measured length and weight at 6 and 12 mo and visited households weekly to distribute eggs and monitor compliance. We used linear regression models to compare 12-mo mean length, weight, and z-scores for length-for-age (LAZ), weight-for-length, and weight-for-age (WAZ), and log-binomial or robust Poisson regression to compare prevalence of stunting, wasting, and underweight between arms. We used generalized estimating equations to account for clustering and adjusted models for baseline measures of outcomes., Results: We enrolled 3051 infants (n = 283 clusters) across arms, with complete 6 and 12 mo anthropometry data from 1228 infants (n = 142 clusters) in the egg arm and 1109 infants (n = 141 clusters) in the control. At baseline, 18.5%, 6.0%, and 16.4% were stunted, wasted, and underweight, respectively. The intervention did not have a statistically significant effect on mean LAZ (β: 0.05, 95% confidence interval [CI]: -0.01, 0.10) or stunting prevalence (β: 0.98, 95% CI: 0.89, 1.13) at 12 mo. Mean weight (β: 0.07 kg, 95% CI: 0.02, 0.11) and WAZ (β: 0.06, 95% CI: 0.02, 0.11) were significantly higher in the egg compared with control arms., Conclusions: Provision of a daily egg for 6 mo to infants in rural Bangladesh improved ponderal but not linear growth., Trial Registration Number: NCT03683667, https://clinicaltrials.gov/ct2/show/NCT03683667., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Introduction: Arsenic methylation converts inorganic arsenic (iAs) to monomethyl (MMA) and dimethyl (DMA) arsenic compounds. Body mass index (BMI) has been positively associated with arsenic methylation efficiency (higher DMA%) in adults, but evidence in pregnancy is inconsistent. We estimated associations between anthropometric measures and arsenic methylation among pregnant women in rural northern Bangladesh., Methods: We enrolled pregnant women (n = 784) (median [IQR] gestational week: 14 [13, 15]) in Gaibandha District, Bangladesh from 2018 to 2019. Anthropometric measures were BMI, subscapular and triceps skinfold thicknesses, and mid-upper arm circumference (MUAC), fat area (MUAFA), and muscle area (MUAMA). Arsenic methylation measures were urinary iAs, MMA, and DMA divided by their sum and multiplied by 100 (iAs%, MMA%, and DMA%), primary methylation index (MMA/iAs; PMI), and secondary methylation index (DMA/MMA; SMI). In complete cases (n = 765 [97.6%]), we fitted linear, beta, and Dirichlet regression models to estimate cross-sectional differences in iAs%, MMA%, DMA%, PMI, and SMI per IQR-unit difference in each anthropometric measure, adjusting for drinking water arsenic, age, gestational age, education, living standards index, and plasma folate, vitamin B12, and homocysteine., Results: Median (IQR) BMI, subscapular skinfold thickness, triceps skinfold thickness, MUAC, MUAFA, and MUAMA were 21.5 (19.4, 23.8) kg/m 2 , 17.9 (13.2, 24.2) mm, 14.2 (10.2, 18.7) mm, 25.9 (23.8, 28.0) cm, 15.3 (10.5, 20.3) cm 2 , and 29.9 (25.6, 34.2) cm 2 , respectively. Median (IQR) iAs%, MMA%, DMA%, PMI, and SMI were 12.0 (9.3, 15.2)%, 6.6 (5.3, 8.3)%, 81.0 (77.1, 84.6)%, 0.6 (0.4, 0.7), and 12.2 (9.3, 15.7), respectively. In both unadjusted and adjusted linear models, all anthropometric measures were negatively associated with iAs%, MMA%, and PMI and positively associated with DMA% and SMI. For example, fully adjusted mean differences (95% CI) in DMA% per IQR-unit difference in BMI, subscapular skinfolds thickness, triceps skinfold thickness, MUAC, MUAFA, and MUAMA were 1.72 (1.16, 2.28), 1.58 (0.95, 2.21), 1.74 (1.11, 2.37), 1.45 (0.85, 2.06), 1.70 (1.08, 2.31), and 0.70 (0.13, 1.27) pp, respectively., Conclusions: Anthropometric measures were positively associated with arsenic methylation efficiency among pregnant women in the early second trimester., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Eggs are nutrient-rich. Strengthening evidence of the impact of egg consumption on dietary quality can inform complementary feeding guidance., Objectives: We aimed to assess the effect of an egg intervention on dietary intakes among infants aged 6-12 mo in rural Bangladesh., Methods: We conducted a cluster-randomized controlled trial allocating clusters (n = 566) to enteric pathogen control or placebo treatment, with daily provision of a protein-rich meal, isocaloric meal, egg, or control. Nutrition education was provided to all arms. Our focus here is on the egg and control arms. Infants were enrolled at 3 mo. From 6 mo, we visited households weekly to distribute eggs and measure compliance. A semistructured feeding questionnaire assessed 24-h intake at 6, 9, and 12 mo. Assessments were repeated in ∼10% of subjects 2-29 d later. Using NCI SAS macros, we estimated usual intake distributions for energy, protein, fat, and 18 micronutrients and the proportion meeting intake recommendations. We compared the outcomes between the arms using clustered bootstrapping., Results: Data were available from 757 infants (137 clusters) and 943 infants (141 clusters) in the egg and control arms, respectively. In the egg arm compared with the control arm, the mean usual intakes were higher for energy (610 compared with 602 kcal/d, 9 mo; 669 compared with 658 kcal/d, 12 mo), crude protein (2.2 compared with 1.7 g/(kg·d), 9 mo; 2.4 compared with 1.9 g/(kg·d), 12 mo), available protein (2.0 compared with 1.6 g/(kg·d), 9 mo; 2.1 compared with 1.8 g/(kg·d), 12 mo), and for 13 and 14 micronutrients at 9 and 12 mo, respectively. The proportion meeting intake recommendations for most micronutrients was higher in the egg arm but remained <50% for 15 and 13 micronutrients at 9 and 12 mo, respectively., Conclusions: Daily egg consumption improved dietary intakes among Bangladeshi infants, but was insufficient to meet multiple micronutrient intake recommendations, demonstrating the need to be coupled with other strategies., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Low birth weight predicts risk of infant death. However, several birth measurements may be equally predictive, for which cutoffs and associated risks are less explored., Objectives: We assessed and optimized population cutoffs of birth length, weight, and midupper arm circumference (MUAC), head circumference (HC), and chest circumference (CC) for predicting neonatal (≤28 d) and infant (≤365 d) mortality in northwest Bangladesh., Methods: Among 28,026 singletons born in an antenatal micronutrient supplement trial, 21,174 received anthropometry ≤72 h after birth, among whom 583 died in infancy. Optimization for predicting mortality for each measurement was guided by the Youden Index (sensitivity + specificity - 1). Relative risk ratios (RRRs) and positive predictive values (PPVs) were calculated across cutoff ranges for individual and any pair of measurements., Results: Optimal cutoffs, harmonized to 100-g or 0.5-cm readings, for neonatal and infant mortality were 44.5 cm for length, 2200 g for weight, 9.0 cm for MUAC, 31.0 cm for HC, and 28.5 cm for CC, below which all predicted mortality. However, a CC <28.5 cm, alone and combined with HC <31.0 cm, yielded the highest RRR [9.68 (95% CI: 7.84, 11.94) and 15.74 (95% CI: 12.54, 19.75), respectively] and PPV (11.3% and 10.7%) for neonatal mortality and highest RRR [6.02 (95% CI: 5.15, 7.02) and 9.19 (95% CI: 7.72, 10.95)] and PPV (16.3% and 14.5%) for infant mortality. Pairs of measurements revealed a higher RRR for neonatal and infant mortality than individual measurements of any one pair, although the ranges of PPV remained comparable., Conclusions: In Bangladesh, multiple birth measurements alone or in combination, particularly chest circumference, predict neonatal and infant mortality., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Growth failure in sub-Saharan Africa leads to a high prevalence of child stunting starting in infancy, and is attributed to dietary inadequacy, poor hygiene, and morbidity., Objectives: To evaluate the impact of a program in Malawi providing a lipid-based nutrient supplement to infants from 6-23 months of age, accompanied by a social and behavior change communication intervention to optimize caregiver feeding and handwashing practices., Methods: This impact evaluation was a quasi-experimental, longitudinal study with 1 program and 1 comparison district. Infants were enrolled at 6-7 months of age. Anthropometry, child morbidity, and caregiver feeding and handwashing practices were assessed at enrollment and at 6, 12, and 18 month follow-ups (ages 6, 12, 18, and 24 months, respectively). Changes in the length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and midupper arm circumference (MUAC) were compared using mixed-effects models. Program impacts on child stunting (LAZ < -2), wasting (WLZ < -2), morbidity, and feeding and handwashing practices were estimated using difference-in-differences., Results: We enrolled 367 infants across the program (n = 176) and comparison (n = 191) districts. The combined prevalences of stunting and wasting at enrollment were 42.1% and 1.4%, respectively, and did not differ by district. At enrollment, the prevalence of severe stunting (LAZ < -3) was higher in the program (15.5%) versus comparison (7.6%) district (P = 0.02), with corresponding lower LAZ scores (-1.9 vs. -1.7, respectively; P = 0.12). Growth velocities favored program children, such that LAZ, WLZ, and MUAC measurements increased by +0.12/y (P = 0.06), +0.12/y (P = 0.04), and +0.24 cm/y (P < 0.001), respectively, leading to comparable LAZ distributions across districts by 24 months of age. Program exposure was associated with 19.8 percentage point (pp) and 13.8 pp reductions in the prevalences of malaria (P = 0.001) and fever (P = 0.02), respectively, at the 18-month follow-up. Improvements of 20 pp (P < 0.01) in minimum dietary diversity and minimum acceptable diet were seen in the program versus comparison district at 18 months of follow-up., Conclusions: The program improved child growth patterns, with benefits to health and diet apparent after 18 months of exposure. This trial was registered at clinicaltrials.gov as NCT02985359., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The prevalence of stunting in central rural Malawi is ∼50%, which prompted a multipronged nutrition program in 1 district from 2014 to 2016. The program distributed a daily, fortified, small-quantity lipid-based nutritional supplement, providing 110 kcal and 2.6 g of protein to children aged 6-23 mo, and behavior change messages around optimal infant and young child feeding (IYCF) and water, sanitation, and hygiene., Objectives: Our objective was to perform an impact evaluation of the program using a neighboring district as comparison., Methods: Using a quasi-experimental study design, with cross-sectional baseline (January-March, 2014; n = 2404) and endline (January-March, 2017; n = 2453) surveys, we evaluated the program's impact using a neighboring district as comparison. Impact on stunting was estimated using propensity score weighted difference-in-differences regression analyses to account for baseline differences between districts., Results: No differences in mean length-for-age z-score or prevalence of stunting were found at endline. However, mean weight, weight-for-length z-score, and mid-upper arm circumference were higher at endline by 150 g, 0.22, and 0.19 cm, respectively, in the program compared with the comparison district (all P < 0.05). Weekly reports of high fever and malaria were also lower by 6.4 and 4.7 percentage points, respectively, in the program compared with the comparison district (both P < 0.05). There was no impact on anemia. Children's dietary diversity score improved by 0.17, and caregivers' infant and young child feeding and hand-washing practices improved by 8-11% in the program compared with the comparison district (all P < 0.05)., Conclusions: An impact evaluation of a comprehensive nutrition program in rural Malawi demonstrated benefit for child ponderal growth and health, improved maternal IYCF and hand-washing practices, but a reduction in stunting prevalence was not observed., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Daily antenatal multiple micronutrient (MM) compared with iron folic acid (IFA) supplementation from early pregnancy improved birth outcomes and maternal micronutrient status in rural Bangladesh, but effects on newborn status are unknown., Objective: We examined cord blood micronutrient biomarkers in relation to antenatal MM and IFA supplementation and maternal gestational micronutrient status in rural Bangladeshi newborns., Design: In a double-blinded, cluster-randomized trial of antenatal IFA or MM (with the same IFA content), we analyzed cord blood plasma from 333 singleton births, and corresponding maternal plasma at 32.5 ± 2.6 wk of gestation, for ferritin (iron stores), folate, cobalamin (vitamin B-12), retinol (vitamin A), 25-hydroxyvitamin D [25(OH)D, vitamin D status], α-tocopherol (vitamin E), zinc, thyroglobulin, and free thyroxine (iodine status). Intervention effects and associations were determined using linear regression, exploring maternal status as a mediator of intervention effects on cord biomarkers., Results: The MM intervention increased cord ferritin (mean: +12.4%; 95% CI: 1.3, 24.6%), 25(OH)D (mean: +14.7%; 95% CI: 4.8, 25.6%), and zinc (mean: +5.8%; 95% CI: 1.0, 10.8%). Cord folate (mean: +26.8%; 95% CI: 19.6, 34.5%), cobalamin (mean: +31.3%; 95% CI: 24.6, 38.3%), 25(OH)D (mean: +26.7%; 95% CI: 23.2, 30.3%), α-tocopherol (mean: +8.7%; 95% CI: 3.6, 13.7%), zinc (mean: +2.3%; 95% CI: 0.5, 4.2%), thyroglobulin (mean: +20.1%; 95% CI: 9.0, 32.2%) and thyroxine (mean: +1.5%; 95% CI: 0.0, 3.0%) increased per 1-SD increment in maternal status (all P < 0.05); ferritin and retinol changed by +2.0%; 95% CI: -8.9, 14.3%; P = 0.72; and +3.5%; 95% CI: -0.4, 7.3%; P = 0.07, respectively. Ferritin, folate, cobalamin, zinc, and thyroglobulin averaged 1.57-6.75 times higher and retinol, α-tocopherol, and 25(OH)D 0.30-0.84 times lower in cord than maternal plasma, suggesting preferential maternal-fetal transfer of iron, folate, cobalamin, and zinc; limited transfer of fat-soluble vitamins; and high fetal iodine demand., Conclusions: Antenatal MM supplementation increased newborn ferritin, 25(OH)D, and zinc, while maternal and newborn folate, vitamins B-12, D, and E, zinc, and iodine biomarkers were positively related. Despite limited effects of MM, better maternal micronutrient status was associated with improved micronutrient status of Bangladeshi newborns. This trial was registered at clinicaltrials.gov as NCT00860470., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Complementary food supplementation enhances linear growth and may affect body composition in children., Objective: We aimed to determine the effect of complementary food supplements provided from the age of 6 to 18 mo on fat-free mass (FFM) and fat mass (FM) gain among children in rural Bangladesh., Methods: In an unblinded, cluster-randomized, controlled trial we tested the effects of 4 complementary food supplements for 1 y [chickpea, rice lentil, Plumpy'doz, and wheat-soy-blend++ (WSB++)] compared with no supplements on linear growth. Body composition was estimated using weight-length-based, age- and sex-specific equations at 6, 9, 12, 15, and 18 mo and postintervention aged 24 mo. Generalized estimating equations (GEEs) were applied to estimate the effect of each complementary food on mean FFM and FM from 9 to 18 and 24 mo compared with the control, adjusting for baseline measures. Sex interactions were also explored., Results: In total, 3592 (65.9% of enrolled) children completed all anthropometric assessments. Estimated FFM and FM (mean ± SD) were 5.3 ± 0.6 kg and 1.4 ± 0.4 kg, respectively, at the age of 6 mo. Mean ± SE FFM and FM from 9 to 18 mo were 75.4 ± 14.0 g and 32.9 ± 7.1 g, and 61.0 ± 16.6 g and 30.0 ± 8.4 g, higher with Plumpy'doz and chickpea foods, respectively, than the control (P < 0.001). Estimated FFM was 41.5 ± 16.6 g higher in rice-lentil-fed versus control (P < 0.05) children. WSB++ had no impact on FFM or FM. A group-sex interaction (P < 0.1) was apparent with Plumpy'doz and rice-lentil foods, with girls involved in the intervention having higher estimated FFM and FM than control girls compared with no significant effect in boys. At 24 mo, FFM and FM remained higher only in girls eating Plumpy'doz compared with the controls (P < 0.01)., Conclusions: In this randomized trial, supplementation effected small shifts in apparent body composition in rural Bangladeshi children. Where seen, FFM increments were twice that of FM, in proportion to these compartments, and more pronounced in girls. FFM increased in line with reported improvements in length. This trial was registered at clinicaltrials.gov as NCT01562379., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Animal-source foods (ASFs) are a food group of interest for interventions aimed at reducing stunting and other inadequate growth measures in early childhood. The aim of this systematic review was to examine the relation between ASF consumption and stunting in children aged 6-60 mo in low- and middle-income countries (LMICs). The secondary aim was to examine the relation between ASF consumption and other indicators of growth and development (length/height, weight, head circumference, and anemia). A search of the peer-reviewed and grey literature published from January 1980 to June 2017 was conducted. Databases searched included CINAHL, Embase, Global Index Medicus, PubMed, and Web of Science. There were 14,783 records and 116 full text articles dual screened; 21 studies were included in the review and were dual evaluated for risk of bias (RoB). The relation between ASF and stunting (length- or height-for-age z-score←2) was examined in randomized-controlled trials [(RCTs), n = 3] and cross-sectional studies (n = 4) only; ASF reduced stunting in 1 RCT and was associated with reduced stunting in 1 cross-sectional study. We did not identify any longitudinal cohorts that examined this relation. The relation between ASF and secondary indicators length/height, weight, head circumference, and anemia were largely nonsignificant across study designs. The intervention/exposure, comparator, outcome measures, methods, and analyses were highly heterogeneous. Although we did not find a consistent relation between ASF consumption and our primary and secondary outcomes, this may have been a function of inconsistencies in study design. Foods in the whole diet, particularly combination dishes, are inherently difficult to assess. To quantitatively assess the relation between ASF and stunting and other indicators of growth and iron status in early childhood, future research should provide consistency in the definition and quantification of the exposure and outcomes allowing for interstudy quantitative comparisons., (Copyright © American Society for Nutrition 2019.)

Background: Antenatal multiple micronutrient (MM) supplementation improves birth outcomes relative to iron-folic acid (IFA) in developing countries, but limited data exist on its impact on pregnancy micronutrient status., Objective: We assessed the efficacy of a daily MM (15 nutrients) compared with IFA supplement, each providing approximately 1 RDA of nutrients and given beginning at pregnancy ascertainment, on late pregnancy micronutrient status of women in rural Bangladesh. Secondarily, we explored other contributors to pregnancy micronutrient status., Methods: Within a double-masked trial (JiVitA-3) among 44,500 pregnant women, micronutrient status indicators were assessed in n = 1526 women, allocated by cluster to receive daily MM (n = 749) or IFA (n = 777), at 10 wk (baseline: before supplementation) and 32 wk (during supplementation) gestation. Efficacy of MM supplementation on micronutrient status indicators at 32 wk was assessed, controlling for baseline status and other covariates (e.g., inflammation and season), in regression models., Results: Baseline status was comparable by intervention. Prevalence of deficiency among all participants was as follows: anemia, 20.6%; iron by ferritin, 4.0%; iron by transferrin receptor, 4.7%; folate, 2.5%; vitamin B-12, 35.4%; vitamin A, 6.7%; vitamin E, 57.7%; vitamin D, 64.0%; zinc, 13.4%; and iodine, 2.6%. At 32 wk gestation, vitamin B-12, A, and D and zinc status indicators were 3.7-13.7% higher, and ferritin, γ-tocopherol, and thyroglobulin indicators were 8.7-16.6% lower, for the MM group compared with the IFA group, with a 15-38% lower prevalence of deficiencies of vitamins B-12, A, and D and zinc (all P < 0.05). However, indicators typically suggested worsening status during pregnancy, even with supplementation, and baseline status or other covariates were more strongly associated with late pregnancy indicators than was MM supplementation., Conclusions: Rural Bangladeshi women commonly entered pregnancy deficient in micronutrients other than iron and folic acid. Supplementation with MM improved micronutrient status, although deficiencies persisted. Preconception supplementation or higher nutrient doses may be warranted to support nutritional demands of pregnancy in undernourished populations. This trial was registered at clinicaltrials.gov as NCT00860470., (Copyright © American Society for Nutrition 2019.)

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., (Copyright © 2019 Lee et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: Impairments in visual function have been well characterized in vitamin A deficiency. However, eye function may also be sensitive to other nutrient deficiencies., Objective: We examined associations between visual function-characterized by pupillary threshold or pupillary responsiveness-and nutritional status in Zambian children., Methods: We used digital pupillometry to measure visual responses to calibrated light stimuli (-2.9 to 0.1 log cd/m2) among dark-adapted children aged 4-8 y (n = 542). We defined pupillary threshold as the first light stimulus at which pupil diameter decreased by ≥10% and considered a pupillary threshold ≥-0.9 log cd/m2 as impaired. Pupillary responsiveness was defined by absolute percentage of change in pupil diameter from pre- to poststimulus. We tested associations between these measures and serum concentrations of retinol, β-carotene, ferritin, soluble transferrin receptor, and hemoglobin (Hb <11.0 or 11.5 g/dL were used to define anemia, depending on age), as well as anthropometric indexes, with the use multilevel mixed-effects models., Results: Pupillary threshold was correlated only with serum retinol (r = 0.12, P < 0.05). The strongest correlates of pupillary responsiveness were Hb (r = -0.16, P < 0.01), height-for-age z score (r = 0.14, P < 0.05), weight-for-age z score (r = 0.14, P < 0.05), and soluble transferrin receptor (r = 0.12, P < 0.05). In multivariate models, anemia was positively associated with pupillary responsiveness (β = 2.99; 95% CI: 1.26, 4.72)., Conclusions: In this marginally nourished population, we found positive correlations between vitamin A status, iron status, or anthropometric indexes and visual function. Hb was negatively associated with visual function, with greater pupillary responsiveness among anemic children. We posit that this may signal altered parasympathetic activity, possibly driven by infection. Future studies should consider a broader range of indicators to better characterize the relation between nutrition and visual function. This trial was registered at clinicaltrials.gov as NCT01695148.

Carotenoids are naturally occurring pigments that function as vitamin A precursors, antioxidants, anti-inflammatory agents or biomarkers of recent vegetable and fruit intake, and are thus important for population health and nutritional assessment. An assay approach that measures proteins could be more technologically feasible than chromatography, thus enabling more frequent carotenoid status assessment. We explored associations between proteomic biomarkers and concentrations of 6 common dietary carotenoids (α-carotene, β-carotene, lutein/zeaxanthin, β-cryptoxanthin, and lycopene) in plasma from 500 6-8 year old Nepalese children. Samples were depleted of 6 high-abundance proteins. Plasma proteins were quantified using tandem mass spectrometry and expressed as relative abundance. Linear mixed effects models were used to determine the carotenoid:protein associations, accepting a false discovery rate of q < 0.10. We quantified 982 plasma proteins in >10% of all child samples. Among these, relative abundance of 4 were associated with β-carotene, 11 with lutein/zeaxanthin and 51 with β-cryptoxanthin. Carotenoid-associated proteins are notably involved in lipid and vitamin A transport, antioxidant function and anti-inflammatory processes. No protein biomarkers met criteria for association with α-carotene or lycopene. Plasma proteomics may offer an approach to assess functional biomarkers of carotenoid status, intake and biological function for public health application. Original maternal micronutrient trial from which data were derived as a follow-up activity was registered at ClinicalTrials.gov: NCT00115271., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prevalence of young adult hearing loss is high in low-resource societies; the reasons for this are likely complex but could involve early childhood undernutrition., Objective: We evaluated preschool childhood stunting, wasting, and underweight as risk factors for hearing loss in young adulthood in Sarlahi District, southern Nepal., Design: Ear health was assessed in 2006-2008 in a cohort of 2193 subjects aged 16-23 y, who as children <60 mo of age participated in a 16-mo placebo-controlled, randomized vitamin A supplementation trial from 1989 to 1991. At each of five 4-mo assessments, field staff measured children's weight, height, and mid-upper arm circumference (MUAC) and recorded validated parental history of ear discharge in the previous 7 d. Children were classified as stunted [<-2 z score height-for-age (HAZ)], underweight [<-2 z score weight-for-age (WAZ)], or wasted [<-2 z score MUAC-for-age (MUACAZ) or body mass index-for-age (BMIAZ)]. At follow-up, hearing was tested by audiometry and tympanometry, with hearing loss defined as pure-tone average >30dB in the worse ear (0.5, 1, 2, 4 kHz) and middle-ear dysfunction as abnormal tympanometric peak height (<0.3 or >1.4 mmho) or width (<50 or >110 daPa)., Results: Hearing loss, present in 5.9% (95% CI: 5.01%, 7.00%) of subjects, was associated with early childhood stunting (OR: 1.64; 95% CI: 1.10, 1.45), underweight (OR: 1.70; 95% CI: 1.18, 2.44) and wasting by BMIAZ (OR: 1.88; 95% CI: 1.19, 2.97) and MUACAZ (OR: 2.14; 95% CI: 1.47, 3.12). Abnormal tympanometry, affecting 16.6% (95% CI: 15.06%, 18.18%), was associated with underweight (OR: 1.46; 95% CI: 1.16, 1.84) and wasting by BMIAZ (OR: 1.80; 95% CI: 1.32, 2.46) and MUACAZ (OR: 1.42; 95% CI: 1.10, 1.84), but not stunting (OR: 1.18; 95% CI: 0.93, 1.49) in early childhood. Highest ORs were observed for subjects with both hearing loss and abnormal tympanometry, ranging from 1.87 to 2.24 (all lower 95% CI >1.00)., Conclusions: Early childhood undernutrition is a modifiable risk factor for early adulthood hearing loss.

Background: Dietary diversity scores and dichotomous indicators derived from them are widely used to assess dietary quality, and specific scoring methods have been recommended for women and 6- to 23-mo-old children. However, there is no specific score recommended for older children and the effect of seasonal dietary changes on score performance is not well documented., Objective: We assessed performance of 2 recommended dietary diversity scores as indicators of dietary quality over 3 seasons., Methods: We conducted 7 repeat 24-h dietary recalls among 4- to 8-y-old rural Zambian children (n = 200) over 6 mo. Dietary diversity was assessed using a 7-food group score for assessing infant and young child feeding (DDS-IYCF) and a 10-food group score for use among women of reproductive age (DDS-W). Micronutrient intake adequacy was described by mean probability of adequacy (MPA) over 11 micronutrients. Longitudinal models were fit to test the association between each score and MPA overall and by season. Receiver operating characteristic (ROC) curves were used to describe indicator performance of each score., Results: Mean ± SE scores were 4.11 ± 0.03 for DDS-IYCF and 4.39 ± 0.03 for DDS-W. Both scores varied by season, but DDS-W better reflected seasonal dietary changes. Across seasons, MPA increased 1-6 percentage points/unit increase in DDS-IYCF or 1-10 percentage points for DDS-W (P < 0.05). Score performance as a predictor of MPA > 0.75 was moderate, with area under the ROC curve values by season ranging from 0.63 to 0.77 for DDS-IYCF and from 0.66 to 0.72 for DDS-W., Conclusions: DDS-W performed better than DDS-IYCF in characterizing seasonal variability and micronutrient adequacy among rural Zambian children., (© 2018 American Society for Nutrition. All rights reserved.)

Background: Higher iron stores, defined by serum ferritin (SF) concentration, may increase malaria risk. Objective: We evaluated the association between SF assessed during low malaria season and the risk of malaria during high malaria season, controlling for inflammation. Methods: Data for this prospective study were collected from children aged 4-8 y ( n = 745) participating in a biofortified maize efficacy trial in rural Zambia. All malaria cases were treated at baseline (September 2012). We used baseline SF and malaria status indicated by positive microscopy at endline (March 2013) to define exposure and outcome, respectively. Iron status was defined as deficient (corrected or uncorrected SF <12 or <15 μg/L, depending on age <5 or ≥5 y, respectively), moderate (<75 μg/L, excluding deficient), or high (≥75 μg/L). We used a modified Poisson regression to model the risk of malaria in the high transmission seasons (endline) as a function of iron status assessed in the low malaria seasons (baseline). Results: We observed an age-dependent, positive dose-response association between ferritin in the low malaria season and malaria incidence during the high malaria season in younger children. In children aged <6 y (but not older children), we observed a relative increase in malaria risk in the moderate iron status [incidence rate ratio (IRR) with SF: 1.56; 95% CI: 0.64, 3.86; IRR with inflammation-corrected SF: 1.92; 95% CI: 0.75, 4.93] and high iron status (IRR with SF: 2.66; 95% CI: 1.10, 6.43; or IRR with corrected SF: 2.93; 95% CI: 1.17, 7.33) categories compared with the deficient iron status category. The relative increase in malaria risk for children with high iron status was statistically significant only among those with a concurrently normal serum soluble transferrin receptor concentration (<8.3 mg/L; IRR: 1.97; 95% CI: 1.20, 7.37). Conclusions: Iron adequacy in 4- to 8-y-old children in rural Zambia was associated with increased malaria risk. Our findings underscore the need to integrate iron interventions with malaria control programs. This trial was registered at clinicaltrials.gov as NCT01695148., Competing Interests: Author disclosures: MAB, KJS, CLC, JC, NK, MA, WS, WJM, KPW, and ACP, no conflicts of interest. The views expressed do not necessarily reflect those of HarvestPlus., (© 2017 American Society for Nutrition.)

Background: The impact of early vitamin A supplementation on neurodevelopmental function has not been adequately studied. In rural Bangladesh we examined cognitive and motor function and scholastic achievement in a cohort of children who were exposed to vitamin A in utero or at birth. Objective: The aim of this study was to examine independent and combined effects of antenatal and newborn supplementation with vitamin A on the cognitive function of children at 8 y of age. Design: A cohort of rural Bangladeshi children from 2 previous double-blind, placebo-controlled cluster-randomized trials were revisited at age 8 y between February 2013 and June 2014. Data on sociodemographic, social, and physical conditions; schooling; child care behavior; anthropometric measures; and cognitive function were collected with the use of various psychometric assessment tools. Results: Among 11,950 children from the parent trial who were last known to be alive, a subset of 1803 children balanced by treatment group in a selected contiguous study area were re-enrolled and 1613 (89%) provided consent for assessments. Of these, 1577 (87%) children had a complete cognitive evaluation. All groups were highly comparable on baseline variables collected in the previous trials and factors measured at re-enrollment. Overall, there was no impact of either maternal or newborn supplementation with vitamin A on intelligence, memory, and motor function. Compared with placebo, children who received both interventions had significantly better performance in reading, spelling, and math computation, with increased mean (95% CI) scores of 8.0 (2.2, 13.8), 6.8 (1.9, 11.7), and 4.8 (0.6, 9.0), respectively. Conclusions: General intelligence or memory and motor functions were not affected by antenatal or newborn supplementation with vitamin A. Scholastic performance and aspects of executive function improved when both interventions were provided. These trials were registered at clinicaltrials.gov as NCT00198822 and NCT00128557., (© 2017 American Society for Nutrition.)

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 ) <5%. Results: Among 982 proteins, 1, 10, 14, and 17 proteins were associated with BAZ, HAZ, MUAC, and AMA, respectively ( q < 0.05). Insulin-like growth factor (IGF)-I, 2 IGF-binding proteins, and carnosinase-1 were associated with both HAZ and AMA. Proteins involved in nutrient transport, activation of innate immunity, and bone mineralization were associated with HAZ. Several extracellular matrix proteins were positively associated with AMA alone. The proteomes of MUAC and AMA substantially overlapped, whereas no proteins were associated with AFA or triceps and subscapular skinfolds. Myosin light-chain kinase, possibly reflecting leakage from muscle, was inversely associated with BAZ. The proteome of WAZ was the largest ( n = 33) and most comprehensive, including proteins involved in neural development and oxidative stress response, among others. Conclusions: Plasma proteomics confirmed known biomarkers of childhood growth and revealed novel proteins associated with lean mass in chronically undernourished children. Identified proteins may serve as candidates for assessing growth and nutritional status of children in similar undernourished settings. The antenatal micronutrient supplementation trial yielding the study cohort of children was registered at clinicaltrials.gov as NCT00115271.

Background: Impaired dark adaptation is an early functional indicator of vitamin A deficiency that may be prevented by regular dietary intake of foods containing provitamin A carotenoids., Objective: We tested the impact of provitamin A carotenoid-biofortified maize consumption (∼15 μg β-carotene/g) on dark adaptation in Zambian children., Methods: We used a cluster-randomized trial of children aged 4-8 y (n = 1024) in Mkushi District, Zambia, and compared the regular consumption (2 meals/d, 6 d/wk for 6 mo) of biofortified orange maize (OM) to white maize (WM). The primary outcome was the serum retinol response. In a random sample (n = 542), we used a digital pupillometer to test pre- and postintervention responses to graded light stimuli (-2.9 to 0.1 log cd/m 2 ) in a dark-adapted state., Results: At baseline, 11.7% of the children had serum retinol <0.7 μmol/L, 14.4% had impaired dark adaptation (pupillary threshold ≥ -1.11 log cd/m 2 ), and 2.3% had night blindness. The mean ± SD pupillary responsiveness to light stimuli was poorer at baseline in the OM group (16.1% ± 6.6%) than the WM group (18.1% ± 6.4%) (P = 0.02) but did not differ at follow-up (OM: 17.6% ± 6.5%; WM: 18.3% ± 6.5%). Among children with serum retinol <1.05 μmol/L at baseline, there was greater improvement in pupillary responsiveness in the OM group (2.2%; 95% CI: 0.1%, 4.3%) than the WM group (0.2%; 95% CI: -1.1%, 1.5%; P = 0.01), but there were no differences in children with adequate baseline status. We found no effect of treatment on pupillary threshold or night blindness., Conclusions: The regular consumption of provitamin A carotenoid-biofortified maize increased pupillary responsiveness among children with marginal or deficient vitamin A status, providing evidence of a functional benefit to consuming this biofortified crop. This trial was registered at clinicaltrials.gov as NCT01695148., (© 2016 American Society for Nutrition.)

Background: Complementary food supplements (CFSs) can enhance growth where stunting is common, but substitution for the usual diet may reduce observed benefits., Objective: We aimed to characterize dietary diversity from home foods in a CFS efficacy trial and determine whether supplementation reduced breastfeeding frequency or displaced home foods., Design: In a cluster-randomized controlled trial in rural Bangladesh, children (n = 5499) received, for 1 y starting at age 6 mo, periodic child feeding counseling for mothers (control) or counseling plus 1 of 4 CFSs fed as a daily snack. Breastfeeding status and past 24-h diet were assessed at enrollment and every 3 mo thereafter until 18 mo of age. A 7-food group dietary diversity score (DDS) was calculated from home foods only, and a DDS ≥4 constituted minimum dietary diversity (MDD)., Results: Most children (97%) were breastfed through 18 mo of age, and 24-h breastfeeding frequency did not differ by supplementation group. Child dietary diversity was low; only 51% of children met the MDD by 18 mo. Rice, potatoes, and biscuits (cookies) were the most frequently consumed foods, whereas the legumes, dairy, eggs, and vitamin A-rich fruit and vegetable food groups were each consumed by <50% of children. The odds of meeting the MDD through the consumption of home foods were equal or greater in the supplemented groups compared with the control group at all ages. High socioeconomic status and any maternal education were associated with increased odds of MDD at age 18 mo, whereas child sex and household food security were not associated with MDD., Conclusions: In a setting where daily complementary food supplementation improved linear growth, there was no evidence that supplementation displaced breastfeeding or home foods, and the supplementation may have improved dietary diversity. Pathways by which supplementation with fortified foods may enhance dietary diversity, such as an improved appetite and increased body size, need elucidation. This trial was registered at clinicaltrials.gov as NCT01562379.

Background: Household food insecurity (HFI) can lead to a poor diet and malnutrition. Yet, little is known about the extent to which maternal diet covaries with food insecurity during pregnancy and lactation., Objective: Longitudinal associations between HFI and maternal dietary diversity from early pregnancy to 3 mo postpartum were examined in rural Bangladesh., Methods: We repeatedly assessed dietary intake by using a 7-d food-frequency questionnaire in the first and third trimesters of pregnancy and at 3 mo postpartum among 14,600 women enrolled into an antenatal micronutrient supplementation trial. Maternal dietary diversity score (DDS) was constructed as the sum of 10 food groups reportedly consumed at each assessment. Households were classified at 6 mo postpartum as being food secure or having mild, moderate, or severe HFI on the basis of a 9-item standard scale. Generalized estimating equations were used to estimate the longitudinal relation between HFI status and DDS and the likelihood of individual food-group consumption, adjusting for confounders at the maternal and household levels., Results: The DDS decreased with progressively worse HFI, an association best explained by a derived household wealth index. Compared with women from food-secure households, women of mild, moderate, and severe HFI were less likely, in a dose-response fashion, to have consumed dairy products [adjusted ORs (95% CIs): 0.73 (0.69, 0.78), 0.62 (0.58, 0.66), and 0.52 (0.48, 0.55), respectively], eggs [0.81 (0.76, 0.85), 0.73 (0.68, 0.77), and 0.61 (0.57, 0.65)], meat [0.83 (0.79, 0.88), 0.73 (0.69, 0.78), and 0.60 (0.56, 0.64)], fish [0.87 (0.80, 0.94), 0.76 (0.70, 0.83), and 0.59 (0.54, 0.65)], legumes and nuts [0.88 (0.83, 0.93), 0.81 (0.76, 0.87), and 0.79 (0.74, 0.85)], and yellow and orange fruit and vegetables [0.85 (0.80, 0.91), 0.78 (0.73, 0.84), and 0.72 (0.67, 0.78)]. Neither intakes of dark-green leafy vegetables nor of vegetable oil were associated with HFI status., Conclusion: Antenatal and postnatal maternal dietary diversity, especially intakes of animal-source foods, fruit, and vegetables, declined with worsening food insecurity in rural Bangladesh., (© 2016 American Society for Nutrition.)

Background: Childhood undernutrition may have prenatal origins, and the impact of prenatal interventions on postnatal growth is not well known., Objective: We assessed the effects of prenatal multiple micronutrient (MM) supplementation on child growth and cognitive development., Design: In a cluster-randomized controlled trial in rural Bangladesh, prenatal MM supplementation compared with iron-folic acid (IFA) supplementation was examined for its impact on growth assessed longitudinally from birth up to 24 mo of age (n = 8529) and, in a subsample (n = 734), on cognitive function at 24 mo of age by use of the Bayley scales of infant and toddler development-third edition test., Results: Prevalence of stunting at birth [length for age z score (LAZ): <-2] was 31.9% in the MM and 35.7% in the IFA groups (P < 0.001); however, LAZ increased during the first 3-4 mo in both groups. With the use of a linear random-effects model, prenatal MM-exposed children sustained a higher mean predicted LAZ of ∼0.10 at 1 and 3 mo and 0.06 at 6 mo of age compared with children in the IFA group. Supplementation reduced the prevalence of stunting at 1 (RR: 0.95; 95% CI: 0.92, 0.98) and 3 (RR: 0.91; 95% CI: 0.88, 0.94) mo of age. Differences between groups were absent by 6, 12, and 24 mo of age, when nearly 50% of children had stunted growth. Ponderal and linear growth velocities were somewhat slower from 3 to 12 mo of age in the MM group than in the IFA group, but not from 12 to 24 mo of age. There was no difference between groups on composite scores of cognition, language, and motor performance at 24 mo of age., Conclusions: In this Bangladeshi trial, maternal pre- and postnatal MM supplementation resulted in improvements in LAZ and reduction in stunting through 3 mo of age, but not thereafter and had no impact on cognitive and motor function at 2 y. This trial was registered at clinicaltrials.gov as NCT000860470., (© 2016 American Society for Nutrition.)

Background: Provitamin A carotenoid-biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating biofortified maize may increase vitamin A in breast milk-a critical source of vitamin A for breastfeeding infants., Objective: We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women., Methods: Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 μg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 μg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and β-carotene concentrations, and plasma inflammatory protein concentrations., Results: Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 μmol/L (95% CI: 0.86, 1.05 μmol/L); 56% of samples had milk retinol <1.05 μmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk β-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM [1.15 μmol/L (0.96, 1.39 μmol/L)] and VA [1.17 μmol/L (0.99, 1.38 μmol/L)] groups than in the WM group [0.91 μmol/L (0.72, 1.14 μmol/L); P = 0.13], and the proportion of women with milk retinol <1.05 μmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16)., Conclusions: Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713., (© 2016 American Society for Nutrition.)

Improving child cognition in impoverished countries is a public health priority. Yet, biological pathways and associated biomarkers of impaired cognition remain poorly understood and largely unknown, respectively. This study aimed to explore and quantify associations between functional plasma protein biomarkers and childhood intellectual test performance. We applied proteomics to quantify proteins in plasma samples of 249 rural Nepalese children, 6-8years of age who, 1year later at 7-9years of age, were administered the Universal Nonverbal Intelligence Test (UNIT). Among 751 plasma proteins quantified, 22 were associated with UNIT scores, passing a false discovery rate threshold of 5.0% (q<0.05). UNIT scores were higher by 2.3-9.2 points for every 50% increase in relative abundance of two insulin-like growth factor binding proteins (IGFBPs), six subclasses of apolipoprotein (Apo) and transthyretin, and lower by 4.0-15.3 points for each 50% increase in relative abundance of 13 proteins predominantly involved in inflammation. Among them, IGFBP-acid labile subunit, orosomucoid 1 (ORM1), Apo C-I, and pyruvate kinase isoenzymes M1/M2 jointly explained 37% of the variance in UNIT scores. After additional adjustment for height-for-age Z-score and household socio-economic status as indicators of long-term nutritional and social stress, associations with 6 proteins involved in inflammation, including ORM1, α-1-antichymotrypsin, reticulocalbin 1, and 3 components of the complement cascade, remained significant (q<0.05). Using untargeted proteomics, stable, constitutive facets of subclinical inflammation were associated with lower developmental test performance in this rural South Asian child population. Plasma proteomics may offer opportunities to identify functional, antecedent biomarkers of child cognitive development., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to improve vitamin A status in maize-consuming populations., Objective: We evaluated the efficacy of regular provitamin A carotenoid-biofortified "orange" maizemeal (∼15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children., Design: This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ∼400-km(2) area were identified and grouped by proximity into clusters of ∼15-25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and α1-acid glycoprotein., Results: Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms., Conclusion: In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol. This trial was registered at clinicaltrials.gov as NCT01695148., (© 2016 American Society for Nutrition.)

Purpose: We examined stillbirth and neonatal death as predictors of depressive symptoms in women experiencing these events during the first 6 months postpartum., Methods: We performed secondary analyses using data from 41,348 married women aged 13-44 years, originally collected for the JiVitA-1 study (2001-2007) in northwest Bangladesh. Adjusted relative risk ratios were estimated to determine the associations between stillbirth and early infant death and women's risk of reported depressive symptoms (trichotomized 0, 1-2, 3-5) up to 6 months after the death. Adjusted risk ratios, comparing 0-2 versus 3-5 depressive symptoms, were used in stratified analyses., Results: Women having fetal/infant deaths had elevated risk of experiencing 1-2 postpartum depressive symptoms (adj RRRs between 1.2 and 1.7) and of experiencing 3-5 postpartum depressive symptoms (adj RRRs between 1.9 and 3.3), relative to women without a fetal/infant death. Notably, those whose infants died in the early postneonatal period had over a three-fold risk of 3-5 depressive symptoms (adj relative risk ratio [RRR] = 3.3; 95% confidence interval [CI], 2.6-4.3) compared to a two-fold risk for women experiencing a stillbirth (adj RRR = 1.9; 95% CI, 1.7-2.1). After early postneonatal deaths, women with higher levels of education were more likely to suffer 3-5 depressive symptoms (adj relative risk [RR] = 10.6; 95% CI, 5.2-21.7, ≥10 years of education) compared to women with lower levels of education (adj RR = 2.0; 95% CI, 1.6-2.4, no education; adj RR = 2.2; 95% CI, 1.6-2.9, 1-9 years of education)., Conclusions: Women's mental health needs should be prioritized in low-resource settings, where these outcomes are relatively common and few mental health services are available., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The term vitamin E describes a family of 8 vitamers, 1 of which is α-tocopherol, that is essential for human health. Vitamin E status remains largely unknown in low-income countries because of the complexity and cost of measurement. Quantitative proteomics may offer an approach for identifying plasma proteins for assessing vitamin E status in these populations., Objective: To improve options for vitamin E status assessment, we sought to detect and quantify a set of plasma proteins associated with α- and γ-tocopherol concentrations in a cohort of 500 rural Nepalese children aged 6-8 y and, based on nutrient-protein associations, to predict the prevalence of vitamin E deficiency (α-tocopherol <12 μmol/L)., Methods: Study children were born to mothers enrolled in an earlier antenatal micronutrient trial in Sarlahi District, Nepal. Plasma α- and γ-tocopherol concentrations were measured by high-performance liquid chromatography. Plasma aliquots were depleted of 6 high-abundance proteins, digested with trypsin, labeled with isobaric mass tags, and assessed for relative protein abundance by tandem mass spectrometry. Linear mixed-effects models were used to evaluate the association between α-tocopherol status and relative protein abundance and to predict deficiency., Results: We quantified 982 plasma proteins in >10% of all child samples, of which 119 correlated with α-tocopherol (false discovery rate, q < 0.10). Proteins were primarily involved in lipid transport, coagulation, repair, innate host defenses, neural function, and homeostasis. Six proteins [apolipoprotein (apo)C-III; apoB; pyruvate kinase, muscle; forkhead box 04; unc5 homolog C; and regulator of G-protein signaling 8] explained 71% of the variability in plasma α-tocopherol, predicting an in-sample population prevalence of vitamin E deficiency of 51.4% (95% CI: 46.4%, 56.3%) compared with a measured prevalence of 54.8%. Plasma γ-tocopherol was associated with 12 proteins (q < 0.10), 2 of which (apoC-III and Misato 1) explained 20% of its variability., Conclusions: In this undernourished population of children in South Asia, quantitative proteomics identified a large plasma α-tocopherome from which 6 proteins predicted the prevalence of vitamin E deficiency. The findings illustrate that protein biomarkers, once absolutely quantified, can potentially predict micronutrient deficiencies in populations. The maternal micronutrient supplementation trial from which data were derived as a follow-up activity was registered with clinicaltrials.gov as NCT00115271., (© 2015 American Society for Nutrition.)

Nearly all countries in the world today are burdened with malnutrition, manifesting as undernutrition, micronutrient deficiencies, and/or overweight and obesity. Despite some progress, efforts to alleviate malnutrition are hampered by a shortage in number, skills, and geographic coverage, of a workforce for nutrition. Here, we report the findings of the Castel Gandolfo workshop, a convening of experts from diverse fields in March 2014 to consider how to develop the capacity of a global cadre of nutrition professionals for the post-2015 development era. Workshop participants identified several requirements for developing a workforce for nutrition, including an ability to work as part of a multisectoral team; communication, advocacy, and leadership skills to engage decision makers; and a set of technical skills to address future challenges for nutrition. Other opportunities were highlighted that could immediately contribute to capacity development, including the creation of a consortium to link global North and South universities, online training modules for middle managers, and practical, hands-on experiences for frontline nutrition workers. Institutional and organizational support is needed to enable workshop recommendations on education and training to be effectively implemented and sustained. The findings from the Castel Gandolfo workshop can contribute to the delivery of successful nutrition-relevant actions in the face of mounting external pressures and informing and attaining the forthcoming Sustainable Development Goals., (© 2015 American Society for Nutrition.)

Background: Arsenic has immunomodulatory properties and may have the potential to alter susceptibility to infection in humans., Objectives: We aimed to assess the relation of arsenic exposure during pregnancy with immune function and hepatitis E virus (HEV) infection, defined as seroconversion during pregnancy and postpartum., Methods: We assessed IgG seroconversion to HEV between 1st and 3rd trimester (TM) and 3 months postpartum (PP) among 1100 pregnancies in a multiple micronutrient supplementation trial in rural Bangladesh. Forty women seroconverted to HEV and were matched with 40 non-seroconverting women (controls) by age, parity and intervention. We assessed urinary inorganic arsenic plus methylated species (∑As) (µg/L) at 1st and 3rd TM and plasma cytokines (pg/mL) at 1st and 3rd TM and 3 months PP., Results: HEV seroconverters' urinary ∑As was elevated throughout pregnancy. Non-seroconverters' urinary ∑As was similar to HEV seroconverters at 1st TM but declined at 3rd TM. The adjusted odds ratio (95% confidence interval) of HEV seroconversion was 2.17 (1.07, 4.39) per interquartile range (IQR) increase in average-pregnancy urinary ∑As. Increased urinary ∑As was associated with increased concentrations of IL-2 during the 1st and 3rd TM and 3 months PP among HEV seroconverters but not non-seroconverters., Conclusions: The relation of urinary arsenic during pregnancy with incident HEV seroconversion and with IL-2 levels among HEV-seroconverting pregnant women suggests arsenic exposure during pregnancy may enhance susceptibility to HEV infection., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Tocopherols were discovered for their role in animal reproduction, but little is known about the contribution of deficiencies of vitamin E to human pregnancy loss., Objective: We sought to determine whether higher first-trimester concentrations of α-tocopherol and γ-tocopherol were associated with reduced odds of miscarriage (pregnancy losses <24 wk of gestation) in women in rural Bangladesh., Design: A case-cohort study in 1605 pregnant Bangladeshi women [median (IQR) gestational age: 10 wk (8-13 wk)] who participated in a placebo-controlled vitamin A- or β-carotene-supplementation trial was done to assess ORs of miscarriage in women with low α-tocopherol (<12.0 μmol/L) and γ-tocopherol (<0.81 μmol/L; upper tertile cutoff of the γ-tocopherol distribution in women who did not miscarry)., Results: In all women, plasma α- and γ-tocopherol concentrations were low [median (IQR): 10.04 μmol/L (8.07-12.35 μmol/L) and 0.66 μmol/L (0.50-0.95 μmol/L), respectively]. In a logistic regression analysis that was adjusted for cholesterol and the other tocopherol, low α-tocopherol was associated with an OR of 1.83 (95% CI: 1.04, 3.20), whereas a low γ-tocopherol concentration was associated with an OR of 0.62 (95% CI: 0.41, 0.93) for miscarriage. Subgroup analyses revealed that opposing ORs were evident only in women with BMI (in kg/m(2)) ≥18.5 and serum ferritin concentration ≤150 μg/L, although low BMI and elevated ferritin conferred stronger risk of miscarriage., Conclusions: In pregnant women in rural Bangladesh, low plasma α-tocopherol was associated with increased risk of miscarriage, and low γ-tocopherol was associated with decreased risk of miscarriage. Maternal vitamin E status in the first trimester may influence risk of early pregnancy loss. The JiVitA-1 study, from which data for this report were derived, was registered at clinicaltrials.gov as NCT00198822., (© 2015 American Society for Nutrition.)

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 <0.70 μmol/L, 8.5%), D (25-hydroxyvitamin D <50 nmol/L, 17.2%), E (α-tocopherol <9.3 μmol/L, 17.9%), K (decarboxy prothombin >2 μg/L, 20%), B-12 (cobalamin <150 pmol/L, 18.1%), B-6 [pyridoxal-5'-phosphate (PLP) <20 nmol/L, 43.1%], and β-carotene (41.5% <0.09 μmol/L), with little folate deficiency (6.2% <13.6 nmol/L). Deficiencies of iron [ferritin <15 μg/L, 10.7%; transferrin receptor (TfR) >8.3 mg/L, 40.1%; TfR:ferritin >500 μg/μg, 14.3%], iodine (thyroglobulin >40 μg/L, 11.4%), and selenium (plasma selenium <0.89 μmol/L, 59.0%) were observed, whereas copper deficiency was nearly absent (plasma copper <11.8 μmol/L, 0.7%). Hemoglobin was not assessed. Among all children, 91.7% experienced at least 1 micronutrient deficiency, and 64.7% experienced multiple deficiencies. Inflammation (α-1 acid glycoprotein >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., (© 2014 American Society for Nutrition.)

Micronutrient deficiencies are common in undernourished societies yet remain inadequately assessed due to the complexity and costs of existing assays. A plasma proteomics-based approach holds promise in quantifying multiple nutrient:protein associations that reflect biological function and nutritional status. To validate this concept, in plasma samples of a cohort of 500 6- to 8-y-old Nepalese children, we estimated cross-sectional correlations between vitamins A (retinol), D (25-hydroxyvitamin D), and E (α-tocopherol), copper, and selenium, measured by conventional assays, and relative abundance of their major plasma-bound proteins, measured by quantitative proteomics using 8-plex iTRAQ mass tags. The prevalence of low-to-deficient status was 8.8% (<0.70 μmol/L) for retinol, 19.2% (<50 nmol/L) for 25-hydroxyvitamin D, 17.6% (<9.3 μmol/L) for α-tocopherol, 0% (<10 μmol/L) for copper, and 13.6% (<0.6 μmol/L) for selenium. We identified 4705 proteins, 982 in >50 children. Employing a linear mixed effects model, we observed the following correlations: retinol:retinol-binding protein 4 (r = 0.88), 25-hydroxyvitamin D:vitamin D-binding protein (r = 0.58), α-tocopherol:apolipoprotein C-III (r = 0.64), copper:ceruloplasmin (r = 0.65), and selenium:selenoprotein P isoform 1 (r = 0.79) (all P < 0.0001), passing a false discovery rate threshold of 1% (based on P value-derived q values). Individual proteins explained 34-77% (R(2)) of variation in their respective nutrient concentration. Adding second proteins to models raised R(2) to 48-79%, demonstrating a potential to explain additional variation in nutrient concentration by this strategy. Plasma proteomics can identify and quantify protein biomarkers of micronutrient status in undernourished children. The maternal micronutrient supplementation trial, from which data were derived as a follow-up activity, was registered at clinicaltrials.gov as NCT00115271.

Exclusive breastfeeding of newborns, a practice recommended by WHO, is hindered in many countries by practices such as prelacteal feeding (feeding other foods before breast milk is fed to infants). This paper describes maternal and infant characteristics and trends over time associated with early neonatal feeding (ENF) in Bangladesh. The analysis used data from 24,992 participants in a randomized controlled trial supplementing vitamin A and β-carotene to women in northwestern rural Bangladesh. A majority of newborns (89.2%) were fed substances other than breast milk in the first 3 d of life. Early neonatal feeding practices were found to be significantly associated with lower maternal education, higher gravidity, lower socioeconomic status, and younger maternal age. A perceived inability to suckle normally after birth was closely related to the risk of an infant being fed a food other than breast milk in the first 3 d of life [OR = 0.09 (95% CI: 0.08, 0.11)]. Only 18.8% of newborns fed an early neonatal food were exclusively breastfed between 3 d and 3 mo postpartum compared with 70.6% of those not fed an early neonatal food during this period (P < 0.05). Early neonatal feeding practices should be addressed when scaling-up exclusive breastfeeding in South Asia. Maternal education, antenatal care, and support during labor and delivery may help reduce ENF and promote exclusive breastfeeding.

Background: Micronutrient deficiencies may be related to poor fetal growth and short gestation. Few studies have investigated the contribution of maternal vitamin A deficiency to these outcomes., Objective: In rural northwestern Bangladesh, we examined the effects of weekly antenatal vitamin A and β-carotene supplementation on birth weight, length, circumferential body measures, and length of gestation., Design: With the use of a cluster-randomized, placebo-controlled trial design, pregnant women were enrolled in the first trimester and began receiving their allocated supplements (vitamin A, β-carotene, or placebo) weekly until 3 mo postpartum. Birth anthropometric measures were made at home., Results: Of 13,709 newborns whose birth weight was measured within 72 h of birth, mean (±SD) weight was 2.44 ± 0.42 kg, the prevalence of low birth weight (LBW) was 54.4%, and that of small-for-gestational age (SGA) was 70.5%. Birth weight, length, and chest, head, and arm circumferences did not differ between supplementation and placebo groups nor did rates of LBW and SGA. Mean gestational age at birth was 38.3 ± 2.9 wk, and 25.6% of births occurred before 37 wk. Neither gestational age nor preterm birth rate differed with vitamin A or β-carotene supplementation., Conclusions: In this rural South Asian population with a high burden of LBW and preterm birth but modest levels of maternal vitamin A deficiency, antenatal vitamin A or β-carotene supplementation did not benefit these birth outcomes. Other nutritional and nonnutritional interventions should be examined to reduce risks of these adverse outcomes in rural South Asia. This trial was registered at clinicaltrials.gov as NCT00198822.

Placental growth is a strong predictor of fetal growth, but little is known about maternal predictors of placental growth in malnourished populations. Our objective was to investigate in a prospective study the associations of maternal weight and body composition [total body water (TBW) estimated by bioelectrical impedance and fat and fat-free mass derived from upper arm fat and muscle areas (UAFA, UAMA)] and changes in these with placental and birth weights. Within a cluster-randomized trial of maternal micronutrient supplementation, a subsample of 350 women was measured 3 times across gestation. Longitudinal analysis was used to examine independent associations of ∼10-wk measurements and ∼10-20 wk and ∼20-32 wk changes with birth outcomes. Weight, TBW, and UAMA, but not UAFA, at ∼10 wk were each positively and independently associated with placental weight and birth weight (P < 0.05). Of the maternal ∼10-20 wk changes in measurements, only TBW change and placental weight, and maternal weight and birth weight were positively associated (P < 0.05). Gains in weight, TBW, and UAMA from 20 to 32 wk were positively and UAFA gain was negatively associated with placental weight (P ≤ 0.01). Gains in weight and UAMA from 20 to 32 wk were positively associated with birth weight (P ≤ 0.01). Overall, higher maternal weight and measures of fat-free mass at ∼10 wk gestation and gains from 20 to 32 wk are independently associated with higher placental and birth weight.

Plasma volume expansion has been associated with fetal growth. Our objective was to examine the associations between maternal nutritional status in early pregnancy and extracellular water (ECW), total body water (TBW), and percentage plasma volume change across pregnancy. In a subsample of 377 pregnant women participating in a cluster-randomized trial of micronutrient supplementation, hemoglobin, hematocrit, and multi-frequency bioelectrical impedance were measured at ~10, 20, and 32 wk of gestation. In early pregnancy, women were short (mean ± SD, 148.9 ± 5.3 cm) and thin (19.5 ± 2.5 kg/m(2)). In mixed-effects multiple regression models, a 1-unit higher BMI at ~10 wk was associated with higher ECW and TBW (0.27 and 0.66 kg per kg/m(2), respectively; P < 0.01) at ~10, ~20, and ~32 wk. Height was also positively associated with ECW and TBW at each time point. Early pregnancy BMI was negatively associated with gains in ECW and TBW (-0.06 and -0.14 kg per kg/m(2), respectively; P < 0.01) from 10 to 20 wk, but not with 20- to 32-wk gains after accounting for weight gain. BMI was positively associated with percentage changes in plasma volume from 20 to 32 wk (0.57% per kg/m(2); P < 0.05). Height was not associated with changes in body water or plasma volume. Women with low BMI and height in early pregnancy have lower ECW and TBW in early, mid, and late pregnancy and lower late pregnancy plasma volume expansion, potentially increasing risk of fetal growth restriction.

Characterization of normal changes in the serum proteome during pregnancy may enhance understanding of maternal physiology and lead to the development of new gestational biomarkers. In 23 Nepalese pregnant women who delivered at term, two-dimensional difference in-gel electrophoresis (DIGE) was used to assess changes in relative protein abundance between paired serum samples collected in the first and third trimesters. One-hundred and forty-five of over 700 protein spots in DIGE gels (pI 4.2-6.8) exhibited nominally significant (p < 0.05) differences in abundance across trimesters. Additional filtering using a Bonferroni correction reduced the number of significant (p < 0.00019) spots to 61. Mass spectrometric analysis detected 38 proteins associated with gestational age, cytoskeletal remodeling, blood pressure regulation, lipid and nutrient transport, and inflammation. One new protein, pregnancy-specific β-glycoprotein 4 was detected. A follow-up isotope tagging for relative and absolute quantitation (iTRAQ) experiment of six mothers from the DIGE study revealed 111 proteins, of which 11 exhibited significant (p < 0.05) differences between trimesters. Four of these proteins: gelsolin, complement C1r subcomponent, α-1-acid glycoprotein, and α-1B-glycoprotein also changed in the DIGE analysis. Although not previously associated with normal pregnancy, gelsolin decreased in abundance by the third trimester (p < 0.01) in DIGE, iTRAQ and Western analyses. Changes in abundance of proteins in serum that are associated with syncytiotrophoblasts (gelsolin, pregnancy-specific β-1 glycoprotein 1 and β-2-glycoprotein I) probably reflect dynamics of a placental proteome shed into maternal circulation during pregnancy. Measurement of changes in the maternal serum proteome, when linked with birth outcomes, may yield biomarkers for tracking reproductive health in resource poor settings in future studies., (Published by Elsevier Ltd.)

Background: Bacterial vaginosis (BV) in pregnancy is linked to preterm birth, but its risk factors are not well understood. Micronutrient deficiencies may be associated with an increased risk of this condition., Objective: We assessed the effect of weekly vitamin A or β-carotene supplementation during pregnancy until 3 mo postpartum on BV risk in rural northeastern Bangladesh., Design: In this cluster-randomized, placebo-controlled trial, 33 clusters (n = 33) were randomly assigned to 3 groups. Women (n = 1812) were examined for BV by using self-administered swabs and the Nugent scoring method in early pregnancy, at 32 wk of gestation, and at 3 mo postpartum., Results: The prevalence of BV in early pregnancy, before supplementation, was 7.6% (95% CI: 6.3%, 9.1%) overall. Neither the prevalence nor the incidence of BV in the third trimester differed by supplement group. However, the prevalence (OR: 0.71; 95% CI: 0.52, 0.98) and incidence (RR: 0.58; 95% CI: 0.41, 0.81) of BV at 3 mo postpartum was lower among women in the vitamin A group (9.1% and 6.7%, respectively) than in the placebo group (12.4% and 11.8%, respectively), but not in the β-carotene group. Both vitamin A and β-carotene reduced the prevalence and incidence of BV at both time points (ie, third trimester and 3 mo postpartum) by 30-40% compared with placebo (all P < 0.05)., Conclusions: Weekly vitamin A supplementation reduced the risk of maternal BV in this rural Bangladeshi population. Enhancement of vitamin A status before and during pregnancy may reduce the risk of BV in areas with vitamin A deficiency. This trial is registered at clinicaltrials.gov as NCT00198822.

Nasopharyngeal (NP) carriage of S. pneumoniae (Spn) is a risk factor for pneumococcal disease and its transmission. We assessed the impact of vitamin A (VA) supplementation shortly after birth in reducing Spn colonization in early infancy in rural Bangladesh. We recruited 500 infants participating in a cluster-randomized trial that reported a 15% reduction in mortality following receipt of an oral dose of VA (52.25 μmol) compared to placebo. NP specimens were collected at the age of 3 mo to study the effect of VA on the prevalence of culture-confirmed Spn. Analyses were conducted by intention to treat. Spn carriage prevalence did not differ between VA and placebo recipients [OR = 0.83 (95% CI: 0.55-1.27); P = 0.390]. Spn carriage at the age of 3 mo was not lowered by VA given at birth. Results are similar to those from an Indian study in which impact on Spn carriage was assessed at the age of 4 mo [OR = 0.73 (95% CI: 0.48-1.10); P = 0.128]. The point estimate of the pooled effect size for the 2 studies is OR = 0.78 [(95% CI: 0.58-1.04); P = 0.095], which may imply a modest impact on carriage. If so, then the evidence thus far would suggest that Spn carriage reduction is unlikely to be a primary ancillary benefit of newborn VA supplementation.

Questions have been raised about potentially negative effects of antenatal folic acid use in populations with a high prevalence of vitamin B-12 deficiency. Our objective was to examine the association between maternal folate and vitamin B-12 status in pregnancy on offspring insulin resistance and examine whether the effects of maternal micronutrient supplementation varied by baseline maternal folate and/or vitamin B-12 status. Pregnant women were cluster randomized to receive daily supplements containing vitamin A alone or with folic acid, folic acid+iron, folic acid+iron+zinc, or a multiple micronutrient. In a subsample (n = 1132), micronutrient status biomarkers were analyzed at baseline and late pregnancy. Children born to the women who participated in the trial were visited at 6-8 y of age. Fasting plasma glucose and insulin were used to estimate insulin resistance using the homeostasis model assessment (HOMA-IR). Children whose mothers were deficient in vitamin B-12 (<148 pmol/L, 27%) during early pregnancy had a 26.7% increase in HOMA-IR (P = 0.02), but there was no association with maternal folate status. Among children born to women who were vitamin B-12 deficient at baseline, the percent difference in HOMA-IR compared to the control group was 15.1% (95% CI: -35.9, 106.4), 4.9% (-41.6, 88.5), 3.3% (-38.4, 73.5), and 18.1% (-29.0, 96.7) in the folic acid, folic acid-iron, folic acid-iron-zinc, and multiple micronutrient supplementation groups, respectively, none of which were significant. Maternal vitamin B-12 deficiency is associated with an elevated risk of insulin resistance, but supplementation with folic acid or other micronutrients led to no significant change in insulin resistance in school-aged offspring.

Women of reproductive age are at a high risk of iron deficiency, often as a result of diets low in bioavailable iron. In some settings, the iron content of domestic groundwater sources is high, yet its contribution to iron intake and status has not been examined. In a rural Bangladeshi population of women deficient in dietary iron, we evaluated the association between groundwater iron intake and iron status. In 2008, participants (n = 209 with complete data) were visited to collect data on 7-d food frequency, 7-d morbidity history, 24-h drinking water intake, and rice preparation, and to measure the groundwater iron concentration. Blood was collected to assess iron and infection status. Plasma ferritin (μg/L) and body iron (mg/kg) concentrations were [median (IQR)] 67 (46, 99) and 10.4 ± 2.6, respectively, and the prevalence of iron deficiency (ferritin < 12 μg/L) was 0%. Daily iron intake from water [42 mg (18, 71)] was positively correlated with plasma ferritin (r = 0.36) and total body iron (r = 0.35) (P < 0.001 for both). In adjusted linear regression analyses, plasma ferritin increased by 6.1% (95% CI: 3.8, 8.4%) and body iron by 0.3 mg/kg (0.2, 0.4) for every 10-mg increase in iron intake from water (P < 0.001). In this rural area of northern Bangladesh, women of reproductive age had no iron deficiency likely attributable to iron consumed from drinking groundwater, which contributed substantially to dietary intake. These findings suggest that iron intake from water should be included in dietary assessments in such settings.