An Egg Intervention Improves Dietary Intakes but Does Not Fill Intake Gaps for Multiple Micronutrients among Infants in Rural Bangladesh.

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.

The Baltimore Urban Food Distribution (BUD) App: Study Protocol to Assess the Feasibility of a Food Systems Intervention.

Low-income urban communities in the United States commonly lack ready access to healthy foods. This is due in part to a food distribution system that favors the provision of high-fat, high-sugar, high-sodium processed foods to small retail food stores, and impedes their healthier alternatives, such as fresh produce. The Baltimore Urban food Distribution (BUD) study is a multilevel, multicomponent systems intervention that aims to improve healthy food access in low-income neighborhoods of Baltimore, Maryland. The primary intervention is the BUD application (app), which uses the power of collective purchasing and delivery to affordably move foods from local producers and wholesalers to the city's many corner stores. We will implement the BUD app in a sample of 38 corner stores, randomized to intervention and comparison. Extensive evaluation will be conducted at each level of the intervention to assess overall feasibility and effectiveness via mixed methods, including app usage data, and process and impact measures on suppliers, corner stores, and consumers. BUD represents one of the first attempts to implement an intervention that engages multiple levels of a local food system. We anticipate that the app will provide a financially viable alternative for Baltimore corner stores to increase their stocking and sales of healthier foods, subsequently increasing healthy food access and improving diet-related health outcomes for under-resourced consumers. The design of the intervention and the evaluation plan of the BUD project are documented here, including future steps for scale-up. Trial registration #: NCT05010018.

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 32.5 ± 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.

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 ß-carotene supplementation trial. Thinness was defined as a left mid-upper arm circumference (MUAC) ≤21.5 versus >21.5 cm. At each visit, staff obtained a monthly history of menstruation. Report of amenorrhea prompted a human chorionic gonadotropin urine test to confirm pregnancy. We derived hazard ratios (with 95% confidence intervals [CI]) for pregnancy and Kaplan-Meier curves for TTP. Ages of women at marriage and pregnancy detection (mean ± standard deviation) were 15.3 ± 1.9 and 17.0 ± 1.9 years, respectively. A total of 82.7% of thinner and 87.3% of better nourished women became pregnant. The unadjusted and multivariable relative hazard of ever becoming pregnant was 0.84 (95% CI [0.78, 0.89]) and 0.86 (95% CI [0.81, 0.92]), respectively, and TTP was 12 weeks longer (median [95% CI]: 63 [58-68] vs. 51 [49-54]) in women whose MUAC was ≤21.5 versus >21.5 cm. In rural Bangladesh, thin adolescent newlywed girls have a lower probability of becoming pregnant and experience a longer time to pregnancy.

Antenatal care in rural Bangladesh: current state of costs, content and recommendations for effective service delivery.

BACKGROUND: Measurement of antenatal care (ANC) service coverage is often limited to the number of contacts or type of providers, reflecting a gap in the assessment of quality as well as cost estimations and health impact. The study aims to determine service subcomponents and provider and patient costs of ANC services and compares them between community (i.e. satellite clinics) and facility care (i.e. primary and secondary health centers) settings in rural Bangladesh. METHODS: Service contents and cost data were collected by one researcher and four interviewers in various community and facility health care settings in Gaibandha district between September and December 2016. We conducted structured interviews with organization managers, observational studies of ANC service provision (n = 70) for service contents and provider costs (service and drug costs) and exit interviews with pregnant women (n = 70) for patient costs (direct and indirect costs) in health clinics at community and facility levels. Fisher's exact tests were used to determine any different patient characteristics between community and facility settings. ANC service contents were assessed by 63 subitems categorized into 11 groups and compared within and across community and facility settings. Provider and patient costs were collected in Bangladesh taka and analyzed as 2016 US Dollars (0.013 exchange rate). RESULTS: We found generally similar provider and patient characteristics between the community and facility settings except in clients' gestational age. High compliance (> 50%) of service subcomponents were observed in blood pressure monitoring, weight measurement, iron and folate supplementation given, and tetanus vaccine, while lower compliance of service subcomponents (< 50%) were observed in some physical examinations such as edema and ultrasonogram and routine tests such as blood test and urine test. Average unit costs of ANC service provision were about double at the facility level ($2.75) compared with community-based care ($1.62). ANC patient costs at facilities ($2.66) were about three times higher than in the community ($0.78). CONCLUSION: The study reveals a delay in pregnant women's initial ANC care seeking, gaps in compliance of ANC subcomponents and difference of provider and patient costs between facility and community settings.

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. 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.

Identifying maternal and infant factors associated with newborn size in rural Bangladesh by partial least squares (PLS) regression analysis.

Birth weight, length and circumferences of the head, chest and arm are key measures of newborn size and health in developing countries. We assessed maternal socio-demographic factors associated with multiple measures of newborn size in a large rural population in Bangladesh using partial least squares (PLS) regression method. PLS regression, combining features from principal component analysis and multiple linear regression, is a multivariate technique with an ability to handle multicollinearity while simultaneously handling multiple dependent variables. We analyzed maternal and infant data from singletons (n = 14,506) born during a double-masked, cluster-randomized, placebo-controlled maternal vitamin A or ß-carotene supplementation trial in rural northwest Bangladesh. PLS regression results identified numerous maternal factors (parity, age, early pregnancy MUAC, living standard index, years of education, number of antenatal care visits, preterm delivery and infant sex) significantly (p<0.001) associated with newborn size. Among them, preterm delivery had the largest negative influence on newborn size (Standardized ß = -0.29 - -0.19; p<0.001). Scatter plots of the scores of first two PLS components also revealed an interaction between newborn sex and preterm delivery on birth size. PLS regression was found to be more parsimonious than both ordinary least squares regression and principal component regression. It also provided more stable estimates than the ordinary least squares regression and provided the effect measure of the covariates with greater accuracy as it accounts for the correlation among the covariates and outcomes. Therefore, PLS regression is recommended when either there are multiple outcome measurements in the same study, or the covariates are correlated, or both situations exist in a dataset.

Provitamin A Carotenoid-Biofortified Maize Consumption Increases Pupillary Responsiveness among Zambian Children in a Randomized Controlled Trial.

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 ß-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/m2) 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/m2), 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.

Maternal Dietary Diversity Decreases with Household Food Insecurity in Rural Bangladesh: A Longitudinal Analysis.

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.

Effects of prenatal multiple micronutrient supplementation on growth and cognition through 2 y of age in rural Bangladesh: the JiVitA-3 Trial.

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.

Arsenic exposure and hepatitis E virus infection during pregnancy.

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.

First-trimester plasma tocopherols are associated with risk of miscarriage in rural Bangladesh.

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 ß-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.

Preferred delivery method and acceptability of Wheat-Soy Blend (WSB++) as a daily complementary food supplement in northwest Bangladesh.

Fortified blended foods (FBFs) are widely used to prevent undernutrition in early childhood in food-insecure settings. We field tested enhanced Wheat Soy Blend (WSB++)-a FBF fortified with micronutrients, milk powder, sugar, and oil-in preparation for a complementary food supplement (CFS) trial in rural northwestern Bangladesh. Formative work was conducted to determine the optimal delivery method (cooked vs. not) for this CFS, to examine mothers' child feeding practices with and acceptance of the WSB++, and to identify potential barriers to adherence. Our results suggest WSB++ is an acceptable CFS in rural Bangladesh and the requirement for mothers to cook WSB++ at home is unlikely to be a barrier to its daily use as a CFS in this population.

Effect of maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial.

IMPORTANCE: Maternal micronutrient deficiencies may adversely affect fetal and infant health, yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia. OBJECTIVE: To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized, double-masked trial in Bangladesh, with pregnancy surveillance starting December 4, 2007, and recruitment on January 11, 2008. Six-month infant follow-up ended August 30, 2012. Surveillance included 127,282 women; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants. Median gestation at enrollment was 9 weeks (interquartile range, 7-12). INTERVENTIONS: Women were provided supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause infant mortality through 6 months (180 days). Prespecified secondary outcomes in this analysis included stillbirth, preterm birth (<37 weeks), and low birth weight (<2500 g). To maintain overall significance of α = .05, a Bonferroni-corrected α = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes (.05/5). RESULTS: Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group, there were 14,374 and 14,142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1000 live births) in the multiple micronutrient group (relative risk [RR], 0.95; 95% CI, 0.86-1.06). Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1000 births; RR, 0.89; 95% CI, 0.81-0.99; P = .02) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births; RR, 0.85; 95% CI, 0.80-0.91; P < .001) and low birth weight (40.2 vs 45.7 per 100 live births; RR, 0.88; 95% CI, 0.85-0.91; P < .001). CONCLUSIONS AND RELEVANCE: In Bangladesh, antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00860470.

Risk factors for reported obstetric complications and near misses in rural northwest Bangladesh: analysis from a prospective cohort study.

BACKGROUND: In rural Bangladesh, more than 75% of all births occur at home in the absence of skilled birth attendants. Population-based data are lacking on the burden and risk factors for obstetric complications in settings with low rates of institutional delivery. We sought to describe the prevalence of reported complications and to analyze risk factors for obstetric complications and near misses, using data from a representative, rural setting of Bangladesh. METHODS: This study utilized existing data on 42,214 pregnant women enrolled in a micronutrient supplementation cohort trial between 2007 and 2011 in rural northwest Bangladesh. Based on self-report of complications, women were categorized as having obstetric complications, near misses, or non-complicated pregnancies using definitions modified from the World Health Organization. Multivariable multinomial regression was used to analyze the association of biological, socioeconomic, and psychosocial variables with obstetric complications or near misses. RESULTS: Of enrolled women, 25% (n = 10,380) were classified as having at least one obstetric complication, 2% (n = 1,004) with reported near misses, and 73% (n = 30,830) with non-complicated pregnancies. Twelve percent (n = 5,232) reported hemorrhage and 8% (n = 3,259) reported sepsis. Of the 27,241 women with live births or stillbirths, 11% (n = 2,950) reported obstructed labor and 1% (n = 328) reported eclampsia. Biological risk factors including women's age less than 18 years (Relative Risk Ratio [RRR] 1.26 95%CI:1.14-1.39) and greater than 35 years (RRR 1.23 95%CI:1.09-1.38), history of stillbirth or miscarriage (RRR 1.15 95%CI:1.07-1.22), and nulliparity (RRR 1.16 95%CI:1.02-1.29) significantly increased the risk of obstetric complications. Neither partner wanting the pregnancy increased the risk of obstetric complications (RRR 1.33 95%CI:1.20-1.46). Mid-upper arm circumference <21.5 cm increased the risk of hemorrhage and sepsis. CONCLUSIONS: These analyses indicate a high burden of obstetric morbidity. Maternal age, nulliparity, a history of miscarriage or stillbirth, and lack of pregnancy wantedness were associated with increased risk of obstetric complications. Policies to address early marriage, unmet need for contraception, and maternal undernutrition may help mitigate this morbidity burden in rural Bangladesh.

Canonical correlation analysis of infant's size at birth and maternal factors: a study in rural northwest Bangladesh.

This analysis was conducted to explore the association between 5 birth size measurements (weight, length and head, chest and mid-upper arm [MUAC] circumferences) as dependent variables and 10 maternal factors as independent variables using canonical correlation analysis (CCA). CCA considers simultaneously sets of dependent and independent variables and, thus, generates a substantially reduced type 1 error. Data were from women delivering a singleton live birth (n = 14,506) while participating in a double-masked, cluster-randomized, placebo-controlled maternal vitamin A or ß-carotene supplementation trial in rural Bangladesh. The first canonical correlation was 0.42 (P<0.001), demonstrating a moderate positive correlation mainly between the 5 birth size measurements and 5 maternal factors (preterm delivery, early pregnancy MUAC, infant sex, age and parity). A significant interaction between infant sex and preterm delivery on birth size was also revealed from the score plot. Thirteen percent of birth size variability was explained by the composite score of the maternal factors (Redundancy, RY/X = 0.131). Given an ability to accommodate numerous relationships and reduce complexities of multiple comparisons, CCA identified the 5 maternal variables able to predict birth size in this rural Bangladesh setting. CCA may offer an efficient, practical and inclusive approach to assessing the association between two sets of variables, addressing the innate complexity of interactions.

Screening utility, local perceptions, and care-seeking for reported jaundeesh among respondents lacking signs of icterus in rural Bangladesh.

In rural Bangladesh, acute viral hepatitis presents a significant burden on the public-health system. As part of the formative work for a large epidemiologic study of hepatitis E in rural Bangladesh, we sought to identify local terms that could be used for population-based screening of acute viral hepatitis. Exploration of the local term jaundeesh for screening utility identified a high burden of reported jaundeesh among individuals without symptoms of icterus. Recognizing that local perceptions of illness may differ from biomedical definitions of disease, we also sought to characterize the perceived aetiology, care-seeking patterns, diagnostic symptoms, and treatments for reported jaundeesh in the absence of icteric symptoms to inform future population-based studies on reported morbidities. We conducted a cross-sectional survey among 1,441 randomly-selected subjects to identify the prevalence of reported jaundeesh and to test the validity of this local term to detect signs of icterus. To characterize the perceived aetiology and care-seeking patterns for jaundeesh among the majority of respondents, we conducted in-depth interviews with 100 respondents who self-reported jaundeesh but lacked clinical signs of icterus. To describe diagnostic symptoms and treatments, in-depth interviews were also performed with 25 kabirajs or traditional faith healers commonly visited for jaundeesh. Of the 1,441 randomly-selected participants, one-fourth (n=361) reported jaundeesh, with only a third (n=122) reporting yellow eyes or skin, representative of icterus; Jaundeesh had a positive predictive value of 34% for detection of yellow eyes or skin. Anicteric patients with reported jaundeesh perceived their illnesses to result from humoral imbalances, most commonly treated by amulets, ritual handwashing, and bathing with herbal medicines. Jaundeesh patients primarily sought folk and spiritual remedies from informal care providers, with only 19% visiting allopathic care providers. Although the local term jaundeesh appeared to have limited epidemiologic utility to screen for acute symptomatic viral hepatitis, this term described a syndrome perceived to occur frequently in this population. Future population-based studies conducting surveillance for acute hepatitis should use caution in the use and interpretation of self-reported jaundeesh. Further study of jaundeesh may provide insight into the appropriate public-health response to this syndrome.

Early neonatal feeding is common and associated with subsequent breastfeeding behavior in rural Bangladesh.

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 ß-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.

Development of bioelectrical impedance analysis-based equations for estimation of body composition in postpartum rural Bangladeshi women.

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 ß-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.

Maternal weight and body composition during pregnancy are associated with placental and birth weight in rural Bangladesh.

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.