Micronutrient dose response (MiNDR) study among women of reproductive age and pregnant women in rural Bangladesh: study protocol for double-blind, randomised, controlled trials.

Introduction: Optimising the micronutrient status of women before and during reproduction confers benefits to them and their offspring. Antenatal multiple micronutrient supplements (MMS), given as a daily tablet with nutrients at ~1 recommended dietary allowance (RDA) or adequate intake (AI) reduces adverse birth outcomes. However, at this dosage, MMS may not fully address micronutrient deficiencies in settings with chronically inadequate diets and infection.

Complementary Food Supplements Fill Energy and Protein Gaps among Children with Dietary Inadequacy in a Complementary Feeding Trial in Rural Bangladesh.

Background: Few studies have evaluated the dietary impact of complementary food supplements (CFSs) designed to deliver macro- and micronutrients to children at risk for undernutrition. In a randomized controlled trial in rural Bangladesh, we previously reported that CFSs increased children's micronutrient adequacy.

Objectives: To longitudinally characterize energy and macronutrient intakes and inadequacies and evaluate the extent to which CFSs fill intake gaps.

Early childhood height is a determinant of young adult stature in rural Nepal.

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 < 24 mo) or height (Ht, 24-59 mo), at each year of age to predict 16-23 year old height, adjusted for month of young adult age, interval duration (in months), caste, preschool weight-for-height z-score and, in young women, time since menarche, marriage status and pregnancy history.

Targeting strategies for balanced energy and protein (BEP) supplementation in pregnancy: study protocol for the TARGET-BEP cluster-randomized controlled trial in rural Bangladesh.

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.

Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

Objective: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017.

Design: Descriptive multi-country secondary data analysis.

Setting: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America.

Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 203 live births in low- and middle-income settings from 2000 to 2017.

Objective: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs).

Design: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000.

Setting: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America.

Longitudinal Assessment of Prenatal, Perinatal, and Early-Life Aflatoxin B Exposure in 828 Mother-Child Dyads from Bangladesh and Malawi.

Background: In utero or early-life exposure to aflatoxin, which contaminates staple crops in disadvantaged settings, may compromise pregnancy and infant outcomes, but investigations into the extent, persistence, and determinants of aflatoxin exposure at these life stages have lacked longitudinal data collection and broad geographic representation.

Objectives: Aflatoxin exposure and selected determinants thereof were characterized in mother-child dyads with serial plasma/serum samples in prenatal, perinatal, and early life in Malawi and Bangladesh.

Methods: Circulating aflatoxin B (AFB)-lysine albumin adducts were measured in dyads from Bangladesh (= 573; maternal first and third trimester, 3 mo postpartum, cord blood, infant 24 mo) and Malawi (= 255; maternal second and third trimester, 6 mo postpartum, infant 6 and 18 mo) with isotope dilution mass spectrometry.

Birth anthropometry predicts neonatal and infant mortality in rural Bangladesh: a focus on circumferential measurements.

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.

Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers.

Background: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development.

Objectives: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.

Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024).

Characterization of pubertal development of girls in rural Bangladesh.

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.

Newborn micronutrient status biomarkers in a cluster-randomized trial of antenatal multiple micronutrient compared with iron folic acid supplementation in rural Bangladesh.

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.

Thinness and fecundability: Time to pregnancy after adolescent marriage in rural Bangladesh.

Undernutrition may affect fecundability, but few studies have quantified this relationship. In rural Bangladesh, where newlywed couples face strong pressures to become pregnant, we assessed fecundability, estimated by time to pregnancy (TTP), and its association with preconceptional thinness among nulligravid, newlywed female adolescents. During 2001-2002, 5,516 newlywed women aged 12-19 years participated in a home-based, 5-weekly surveillance system for 5-6 years to enrol pregnant women into an antenatal vitamin A or β-carotene supplementation trial.

Maternal nutritional status mediates the linkage between household food insecurity and mid-infancy size in rural Bangladesh.

Household food insecurity (HFI) is a major concern in South Asia. The pathways by which HFI may reduce child growth remain inadequately understood. In a cohort study of 12 693 maternal-infant dyads in rural Bangladesh, we examined association and likely explanatory pathways linking HFI, assessed using a validated nine-item perception-based index, to infant size at 6 months.

Inflammation throughout pregnancy and fetal growth restriction in rural Nepal.

Maternal systemic inflammation during pregnancy may restrict embryo-fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal-newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.

Dietary patterns of >30,000 adolescents 9-15 years of age in rural Bangladesh.

Little is known of the usual food intakes of rural adolescents in South Asia. This study describes dietary patterns, based on >91,000 7-day food frequencies among 30,702 girls and boys, aged 9-15 years in rural northwest Bangladesh. Three intake assessments per child, taken across a calendar year, were averaged to represent individual annual intake patterns for 22 food groups.

Antenatal Multiple Micronutrient Supplementation Compared to Iron-Folic Acid Affects Micronutrient Status but Does Not Eliminate Deficiencies in a Randomized Controlled Trial Among Pregnant Women of Rural Bangladesh.

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.

Plasma proteome correlates of lipid and lipoprotein: biomarkers of metabolic diversity and inflammation in children of rural Nepal.

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.

Household food insecurity is associated with low dietary diversity among pregnant and lactating women in rural Malawi.

Objective: To examine the association between household food insecurity and dietary diversity in the past 24h (dietary diversity score (DDS, range: 0-9); minimum dietary diversity (MDD, consumption of three or more food groups); consumption of nine separate food groups) among pregnant and lactating women in rural Malawi.

Design: Cross-sectional study.

Setting: Two rural districts in Central Malawi.

Novel Plasma Proteins in Nepalese School-aged Children are Associated with a Small Head Size at Birth.

Fetal growth restriction increases the risk of poor childhood growth and development and chronic disease in adulthood. Yet, little is known about biological pathways that mediate the long-lasting effects of suboptimal intrauterine growth. We explored the plasma proteome in a cohort of 500 Nepalese children 6-8 years of age to identify plasma proteins associated with multiple anthropometric size indicators at birth.

Plasma proteins associated with circulating carotenoids in Nepalese school-aged children.

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.

Environmental enteric dysfunction and systemic inflammation predict reduced weight but not length gain in rural Bangladeshi children.

Environmental enteric dysfunction (EED) and systemic inflammation (SI) are common in developing countries and may cause stunting. In Bangladesh, >40 % of preschool children are stunted, but EED and SI contributions are unknown. We aimed to determine the impact of EED and SI (assessed with multiple indicators) on growth in children (n 539) enrolled in a community-based randomised food supplementation trial in rural Bangladesh.

Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries.

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.

Effect of maternal antenatal and newborn supplementation with vitamin A on cognitive development of school-aged children in rural Bangladesh: a follow-up of a placebo-controlled, randomized trial.

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. 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.