An Egg Intervention Improves Ponderal But Not Linear Growth Among Infants 6-12 mo of Age in Rural Bangladesh.

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 (ß: 0.05, 95% confidence interval [CI]: -0.01, 0.10) or stunting prevalence (ß: 0.98, 95% CI: 0.89, 1.13) at 12 mo. Mean weight (ß: 0.07 kg, 95% CI: 0.02, 0.11) and WAZ (ß: 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.

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. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

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 Pregnancy, Arsenic, and Immune Response (PAIR) Study in rural northern Bangladesh.

BACKGROUND: Arsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the foetus, and maternal and infant acute morbidity. OBJECTIVES: The Pregnancy, Arsenic, and Immune Response (PAIR) Study was designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal and newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy. POPULATION: The PAIR Study recruited pregnant women across a large rural study area in Gaibandha District, northern Bangladesh, 2018-2019. DESIGN: Prospective, longitudinal pregnancy and birth cohort. METHODS: We conducted home visits to enrol pregnant women in the late first or early second trimester (11-17 weeks of gestational age). Women received a quadrivalent seasonal inactivated influenza vaccine at enrolment. Follow-up included up to 13 visits between enrolment and 3 months postpartum. Arsenic was measured in drinking water and maternal urine. Micronutrient deficiencies were assessed using plasma biomarkers. Vaccine-specific antibody titres were measured in maternal and infant serum. Weekly telephone surveillance ascertained acute morbidity symptoms in women and infants. PRELIMINARY RESULTS: We enrolled 784 pregnant women between October 2018 and March 2019. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visits to 3 months postpartum. Arsenic was detected (≥0.02 µg/L) in 99.7% of water specimens collected from participants at enrolment. The medians (interquartile ranges) of water and urinary arsenic at enrolment were 5.1 (0.5, 25.1) µg/L and 33.1 (19.6, 56.5) µg/L, respectively. Water and urinary arsenic were strongly correlated (Spearman's ⍴ = 0.72) among women with water arsenic ≥ median but weakly correlated (⍴ = 0.17) among women with water arsenic < median. CONCLUSIONS: The PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants. REGISTRATION: NCT03930017.

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. POPULATION: Live birth neonates. METHODS: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. RESULTS: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. CONCLUSIONS: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

Anthropometric measures and arsenic methylation among pregnant women in rural northern Bangladesh.

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/m2, 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) cm2, and 29.9 (25.6, 34.2) cm2, 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.

Household animal ownership is associated with infant animal source food consumption in Bangladesh.

Context-specific research is needed on the relationship between household animal production and nutrition outcomes to inform programmes intervening in small-scale animal production. We examined associations between household animal/fishpond ownership and animal source food (ASF) consumption among 6- to 12-month-old infants enroled in the control arm of a cluster-randomised controlled trial in rural Bangladesh. We measured ASF consumption using a 7-day food frequency questionnaire at 6, 9 and 12 months and assessed household animal/fishpond ownership at 12 months. We developed negative binomial regression models with random intercepts for infant and cluster, controlling for infant age and sex, maternal age, socioeconomic status and season. Models were stratified by a dichotomised maternal decision-making score. Compared with infants in households without each animal type, those with 4-10 and ≥11 poultry consumed eggs 1.3 (95% confidence interval [CI]: 1.1, 1.6) and 1.6 (95% CI: 1.3, 2.0) times more, respectively; 2-3 and ≥4 dairy-producing animals consumed dairy 1.9 (95% CI: 1.3, 2.7) and 2.0 (95% CI: 1.3, 3.1) times more, respectively; and ≥12 meat-producing animals consumed meat 1.4 (95% CI: 1.0, 1.8) times more. It was unclear whether there was an association between fishpond ownership and fish consumption. Our results did not suggest that maternal decision-making power was a modifier in the relationship between animal/fishpond ownership and ASF consumption. In this South Asian context, strategies intervening in household animal production may increase infant consumption of eggs, dairy and meat, but not necessarily fish. Research is needed on the role of market access and other dimensions of women's empowerment.

Acceptability of a balanced energy protein (BEP) supplement for pregnant women in Bangladesh.

Balanced energy protein (BEP) supplementation in pregnancy is recommended in the context of undernutrition for the reduction of small-for-gestational age neonates and stillbirths. To inform an effectiveness trial, we evaluated the acceptability of a packaged, ready-to-eat fortified BEP product among women of reproductive age and their health care providers (HCPs) in rural Bangladesh and explored the feasibility of adhering to daily supplementation. We implemented a formative study using focus groups discussions with women (n = 29) and HCPs (n = 17) to introduce the product and investigate components of acceptability. A "trials of improved practice" activity was conducted in subset of women (n = 16) to evaluate adherence to BEP over a 2-week period, followed by focus group discussions to identify challenges with adherence and strategies employed. Contributors to BEP acceptability included the product's sensory attributes, such as taste, smell and texture; the attractive packaging and informative labelling; and the perceived benefits of use. Participants also identified household and community level factors influencing the adoption of BEP, such as trust in the provider, cultural beliefs on supplement use in pregnancy, and family member tasting and approval. Over the 2-week period, women consumed over 80% of the supplements provided to them and identified strategies for adherence, including visual aids and reminders from family members or providers. HCPs recommended targeted communication messages for mothers-in-law to foster a supportive home environment. Findings informed changes to the BEP product to improve acceptability and shaped the content of communication messages to optimise adherence in a forthcoming effectiveness trial.

Assessing implementation outcomes for launching balanced energy protein supplementation: A formative study in rural Bangladesh.

Balanced energy protein (BEP) supplementation is an efficacious intervention in pregnancy for improving birthweight and is recommended by World Health Organization (WHO) in countries with high maternal undernutrition. Few countries have implemented BEP programmes due in part to high cost, lack of data on acceptability and feasibility, and complexity of delivery. We sought to address implementation gaps in BEP interventions through a formative study designed to understand implementation outcomes. We conducted 52 in-depth interviews and 8 focus-group discussions with married women of reproductive age, family members, health care providers and pharmacists in three unions of the Gaibandha district in rural Bangladesh. Interviews were translated and transcribed in English and analysed using an analytic framework for implementation science in nutrition. BEP was viewed as an acceptable and appropriate intervention to combat undernutrition in this setting. There was a lack of clarity on who should or could be responsible for providing/distributing BEP in a way convenient to mothers. Many participants preferred door-to-door delivery and thought this approach could address social and gender inequities, but providers mentioned already being overworked and worried about adding new tasks. Participants were concerned about the affordability of BEP and opportunity costs associated with travel to proposed distribution sites such as ANC or pharmacies. Women in these communities do not always have the agency to travel without supervision or make purchasing decisions. BEP supplementation is a complex intervention; future trials seek to assess ways to overcome these implementation challenges and inform a long-term systems-owned BEP intervention.

Digitalization of routine health information systems: Bangladesh, Indonesia, Pakistan.

Objective: To describe a systematic process of transforming paper registers into a digital system optimized to enhance service provision and fulfil reporting requirements. Methods: We designed a formative study around primary health workers providing reproductive, maternal, newborn and child health services in three countries in Bangladesh, Indonesia and Pakistan. The study ran from November 2014 to June 2018. We developed a prototype digital application after conducting a needs assessment of health workers' responsibilities, workflows, routine data requirements and service delivery needs. Methods included desk reviews, focus group discussions, in-depth interviews; data mapping of paper registers; observations of health workers; co-design workshops with health workers; and usability testing. Finally, we conducted an observational feasibility assessment to monitor uptake of the application. Findings: Researchers reviewed a total of 17 paper registers across the sites, which we transformed into seven modules within a digital application running on mobile devices. Modules corresponded to the services provided, including household enumeration, antenatal care, family planning, immunization, nutrition and child health. A total of 65 health workers used the modules during the feasibility assessment, and average weekly form submissions ranged from 8 to 234, depending on the health worker and their responsibilities. We also observed variability in the use of modules, requiring consistent monitoring support for health workers. Conclusion: Lessons learnt from this study shaped key global initiatives and resulted in a software global good. The deployment of digital systems requires well-designed applications, change management and strengthening human resources to realize and sustain health system gains.

Supplementation with Fortified Lipid-Based and Blended Complementary Foods has Variable Impact on Body Composition Among Rural Bangladeshi Children: A Cluster-Randomized Controlled Trial.

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.

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. 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.

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 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.

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.

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. 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 (ß -0·01 (se 0·00) z score/month for both). Elevated GP was also associated with reduced 15-18-month WLZ change (ß -0·03 (se 0·01) z score/month) and greater 15-month WLZ (ß 0·16 (se 0·05)). Higher AGP was associated with reduced prior and increased subsequent WLZ change (ß -0·04 (se 0·01) and ß 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.

Unintended pregnancy is a risk factor for depressive symptoms among socio-economically disadvantaged women in rural Bangladesh.

BACKGROUND: Little is known about the relation between unwanted pregnancy and intention discordance and maternal mental health in low-income countries. The study aim was to evaluate maternal and paternal pregnancy intentions (and intention discordance) in relation to perinatal depressive symptoms among rural Bangladeshi women. METHODS: Data come from a population-based, community trial of married rural Bangladeshi women aged 13-44. We examined pregnancy intentions among couples and pregnancy-intention discordance, as reported by women at enrollment soon after pregnancy ascertainment, in relation to depressive symptoms in the third trimester of pregnancy (N = 14,629) and six months postpartum (N = 31,422). We calculated crude and adjusted risk ratios for prenatal and postnatal depressive symptoms by pregnancy intentions. RESULTS: In multivariable analyses, women with unwanted pregnancies were at higher risk of prenatal (Adj. RR = 1.60, 95% CI: 1.37-1.87) and postnatal depressive symptoms (Adj. RR = 1.32, 95% CI: 1.21-1.44) than women with wanted pregnancies. Women who perceived their husbands did not want the pregnancy also were at higher risk for prenatal (Adj. RR = 1.42, 95% CI: 1.22-1.65) and postnatal depressive symptoms (Adj. RR = 1.30, 95% CI: 1.19-1.41). Both parents not wanting the pregnancy was associated with prenatal and postnatal depressive symptoms (Adj. RR = 1.34, 95% CI: 1.19-1.52; Adj. RR = 1.13, 95% CI: 1.06-1.21, respectively), compared to when both parents wanted it. Adjusting for socio-demographic and pregnancy intention variables simultaneously, maternal intentions and pregnancy discordance were significantly related to prenatal depressive symptoms, and perception of paternal pregnancy unwantedness and couple pregnancy discordance, with postnatal depressive symptoms. CONCLUSIONS: Maternal, paternal and discordant couple pregnancy intentions, as perceived by rural Bangladeshi women, are important risk factors for perinatal maternal depressive symptoms.

Biomarkers of Environmental Enteric Dysfunction Among Children in Rural Bangladesh.

OBJECTIVES: Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. METHODS: In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool, and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation. EED scores for each participant were developed using principal component analysis and partial least squares regression. Associations between scores and L:M and with child sociodemographic and health characteristics were evaluated using regression analysis. RESULTS: EED prevalence (L:M > 0.07) was 39.0%; 60% had elevated acute phase proteins (C-reactive protein >5 mg/L or α-1 acid glycoprotein >100 mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and α-1 antitrypsin (r = 0.33, P < 0.01), and biomarker values did not differ by supplementation history. A 1-factor partial least squares model with L:M as the dependent variable explained only 8.6% of L:M variability. In adjusted models, L:M was associated with child sex and socioeconomic status index, whereas systemic inflammation was predicted mainly by recent illness, not EED. CONCLUSIONS: Impaired intestinal health is widespread in this setting of prevalent stunting, but a panel of serum and stool biomarkers demonstrated poor agreement with L:M. Etiologies of intestinal and systemic inflammation are likely numerous and complex in resource-poor settings, underscoring the need for a better case definition with corresponding diagnostic methods to further the study of EED.

Risk of Depressive Symptoms Associated with Morbidity in Postpartum Women in Rural Bangladesh.

Objectives Depression following pregnancy is common, but its extent and association with maternal morbidity in the first 6 months postpartum have not been well described in low resource settings such as rural Bangladesh. Methods We used data from a population-based, community trial of approximately 39,000 married rural Bangladeshi women aged 13-44 between 2001 and 2007 to examine the relation between women's reported morbidity symptoms from childbirth to 3 months postpartum, and subsequent depressive symptoms assessed at 6 months postpartum. We calculated crude and adjusted risk ratios for depressive symptoms following women's reports of reproductive, urinary, neurologic, nutrition and other illness measures constructed based on symptomatic reporting. Results In models adjusted for sociodemographic factors and co-morbidities, all postpartum illnesses were associated with an increased relative risk [RR, with 95% confidence intervals (CI) excluding 1] of depressive symptoms by 6 months postpartum. These morbidities included uterine prolapse (RR 1.20, 95% CI 1.04-1.39), urinary tract infection (RR 1.24, 95% CI 1.11-1.38), stress related incontinence (SRI) (RR 1.49, 95% 1.33-1.67), simultaneous SRI and continuously dripping urine (RR 1.60-2.96), headache [RR 1.20 (95% CI 1.12-1.28)], convulsions (RR 1.67, 95%CI 1.36-2.06), night blindness (RR 1.33, 95% CI 1.19-1.49), anemia (RR 1.38, 95% CI 1.31-1.46), pneumonia (RR 1.24, 95% CI 1.12-1.37), gastroenteritis (RR 1.24, 95% CI 1.17-1.31) and hepatobiliary disease (RR 2.10, 96% CI 1.69-2.60). Conclusions for Practice Illnesses during the first three postpartum months were risk factors for depressive symptoms, with the strongest associations noted for convulsions and hepatobiliary disease. Symptoms of depression may be of particular concern among women suffering from physical illnesses. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT0019882.

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.