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Background: The World Health Organization (WHO) recommends balanced energy and protein (BEP) supplementation be provided to all pregnant women living in undernourished populations, usually defined as having a prevalence > 20% of underweight women, to reduce the risk of stillbirths and small-for-gestational-age neonates. Few geographies meet this threshold, however, and a large proportion of undernourished women and those with inadequate gestational weight gain could miss benefiting from BEP. This study compares the effectiveness of individual targeting approaches for supplementation with micronutrient-fortified BEP vs. multiple micronutrient supplements (MMS) alone as control in pregnancy in improving birth outcomes. Methods: The TARGET-BEP study is a four-arm, cluster-randomized controlled trial conducted in rural northwestern Bangladesh. Eligible participants are married women aged 15–35 years old identified early in pregnancy using a community-wide, monthly, urine-test-based pregnancy detection system. Beginning at 12–14 weeks of gestation, women in the study area comprising 240 predefined sectors are randomly assigned to one of four intervention arms, with sector serving as the unit of randomization. The interventions involving daily supplementation through end of pregnancy are as follows: (1) MMS (control); (2) BEP; (3) targeted BEP for those with pre-pregnancy body mass index (BMI) < 18.5 kg/m2 and MMS for others; (4) targeted BEP for those with pre-pregnancy BMI < 18.5 kg/m2, MMS for others, and women with inadequate gestational weight gain switched from MMS to BEP until the end of pregnancy. Primary outcomes include birth weight, low birth weight (< 2500 g), and small for gestational age, defined using the 10th percentile of the INTERGROWTH-21st reference, for live-born infants measured within 72 h of birth. Project-hired local female staff visit pregnant women monthly to deliver the assigned supplements, monitor adherence biweekly, and assess weight regularly during pregnancy. Trained data collectors conduct pregnancy outcome assessment and measure newborn anthropometry in the facility or home depending on the place of birth. Discussion: This study will assess the effectiveness of targeted balanced energy and protein supplementation to improve birth outcomes among pregnant women in rural Bangladesh and similar settings. Trial registration: ClinicalTrials.gov NCT05576207. Registered on October 5th, 2022. [ABSTRACT FROM AUTHOR]

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

This study aimed to describe the timing and patterns of pubertal maturation of girls living in rural Bangladesh. Starting in September 2015, a total of 15,320 girls from a birth cohort, aged 9 to 15 years at initial encounter, were visited twice at about a one year interval, typically in their birth month. Participants were asked to self-report extent of pubertal maturation, including breast development, pubic hair growth and age at menarche, if applicable. Pubertal stage (abbreviated as B2 and B3-4 for breast development and PH2 and PH3-4 for pubic hair growth) was assigned. Data from both visits were pooled, yielding a total of 29,377 age-related observations per pubertal characteristic. Probit regression models were used to estimate distributions of age at which each stage of pubertal development was attained. Before age 8, <3% of the study population initiated pubertal maturation as indicated by onset of breast development (B2). The median (95% confidence interval) age of B2 and B3-4 was 11.02 (11.00–11.04) and 12.82 (12.80–12.83) years, respectively; and 12.93 (12.91–12.94) and 14.29 (14.27–14.31) years for the onset (PH2) and advanced stage (PH3-4) of pubic hair growth, respectively. Median age at menarche was 13.17 (13.15–13.19) years, with 2.15 years of timespan from B2 to menarche. Girls in rural Bangladesh progressed through puberty following a well-documented sequence of sexual maturation stages. The age at which each pubertal milestone took place was somewhat later, but the tempo from breast development to menarche was comparable to that observed elsewhere. Our findings present a current norm of pubertal maturation in a typical, rural adolescent population in South Asia, which could help inform future studies and interventions to preserve or improve early adolescent health and development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Mothers were assessed early in pregnancy for anthropometric status, dietary diversity and socio-economic status. Infants were assessed for weight, length, and arm, chest and head circumferences and breast and complementary feeding status at birth and 6 months of age. Extent of HFI shared a negative, dose–response association with all measures of infant size at 6 months and odds of wasting and stunting; 57–89 % of variances in the unadjusted models were explained by prenatal factors (maternal nutritional status and dietary diversity), and birth size adjusted for gestational age. Postnatal infant breast and complementary feeding and morbidity exposures explained the remaining fraction of the significant association between HFI and differences in infant arm and chest circumferences and odds of underweight. Contextual (i.e. socio-economic) factors finally brought remaining non-significant fractions of the food insecurity-related mid-infancy growth deficit to practically zero. Improving food security prior to pregnancy and during gestation would likely improve infant growth the most in rural Bangladesh. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. EED was defined with faecal myeloperoxidase, α-1 antitrypsin and neopterin and serum endotoxin core antibody and glucagon-like peptide-2, consolidated into gut inflammation (GI) and permeability (GP) scores, and urinary lactulose:mannitol α-1 acid glycoprotein (AGP) characterised SI. Biomarker associations with anthropometry (15-, 18- and 24-month length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z scores) were examined in pairwise correlations and adjusted mixed-effects regressions. Stunting, wasting and underweight prevalence at 18 months were 45, 15 and 37 %, respectively, with elevated EED and SI markers common. EED and SI were not associated with 15–24-month length trajectory. Elevated (worse) GI and GP scores predicted reduced 18–24-month WLZ change (β −0·01 (se 0·00) z score/month for both). Elevated GP was also associated with reduced 15–18-month WLZ change (β −0·03 (se 0·01) z score/month) and greater 15-month WLZ (β 0·16 (se 0·05)). Higher AGP was associated with reduced prior and increased subsequent WLZ change (β −0·04 (se 0·01) and β 0·02 (se 0·00) z score/month for 15–18 and 18–24 months). The hypothesised link from EED to stunting was not observed in this sample of Bangladeshi 18-month-olds, but the effects of EED on constrained weight gain may have consequences for later linear growth or for other health and development outcomes. [ABSTRACT FROM PUBLISHER]

Equations for predicting body composition from bioelectrical impedance analysis (BIA) parameters are age-, sex- and population-specific. Currently there are no equations applicable to women of reproductive age in rural South Asia. Hence, we developed equations for estimating total body water (TBW), fat-free mass (FFM) and fat mass in rural Bangladeshi women using BIA, with 2H2O dilution as the criterion method. Women of reproductive age, participating in a community-based placebo-controlled trial of vitamin A or β-carotene supplementation, were enrolled at 19·7 (sd 9·3) weeks postpartum in a study to measure body composition by 2H2O dilution and impedance at 50 kHz using multi-frequency BIA (n 147), and resistance at 50 kHz using single-frequency BIA (n 82). TBW (kg) by 2H2O dilution was used to derive prediction equations for body composition from BIA measures. The prediction equation was applied to resistance measures obtained at 13 weeks postpartum in a larger population of postpartum women (n 1020). TBW, FFM and fat were 22·6 (sd 2·7), 30·9 (sd 3·7) and 10·2 (sd 3·8) kg by 2H2O dilution. Height2/impedance or height2/resistance and weight provided the best estimate of TBW, with adjusted R2 0·78 and 0·76, and with paired absolute differences in TBW of 0·02 (sd 1·33) and 0·00 (sd 1·28) kg, respectively, between BIA and 2H2O. In the larger sample, values for TBW, FFM and fat were 23·8, 32·5 and 10·3 kg, respectively. BIA can be an important tool for assessing body composition in women of reproductive age in rural South Asia where poor maternal nutrition is common. [ABSTRACT FROM PUBLISHER]

The article discusses a cluster randomized trial that evaluated the efficacy of vitamin A or beta carotene supplementation in reducing mortality related to pregnancy as well as infant mortality in rural northern Bangladesh from 2001 and 2007. The trial involved pregnant women who were randomly assigned to receive retinyl palmitate, all-trans beta carotene or placebo. Those who received vitamin A and beta carotene showed no significant difference from those who took placebo in terms of mortality outcomes. The rates of stillbirth and infant mortality in the placebo, vitamin A and beta carotene groups were 47.9 and 45.6, 51.8 and 68.1 and 65.0 and 69.8, respectively. Vitamin A supplementation was found to have reduced gestational night blindness.