Autism spectrum disorder in a rural community in Bangladesh: A mid-childhood assessment.

Population-based studies employing standardized diagnostics are needed to determine the burden of autism spectrum disorder (ASD) in low-resource settings. A community-based study was conducted among 8-11 year old children in rural, northwestern Bangladesh to establish the prevalence of ASD. A standardized screening and diagnosis protocol was adapted and deployed comprising the social communication questionnaire (SCQ), and the autism diagnostic observation schedule 2, (ADOS-2), and the autism diagnostic interview, revised (ADI-R), respectively. A year-long research training was conducted for a clinical psychologist to be certified to administer ADOS-2 and ADI-R. Over 8000 children were visited at home and administered the SCQ leading to some, based on their score, being further evaluated using the ADOS-2 and ADI-R by the clinical psychologist. Based on ADOS-2 applying the diagnoses of autism or autism spectrum, the prevalence was 40 (95% CI: 27, 54) per 10,000. Autistic disorder using ADI-R was found at 12 (95% CI: 5, 20) per 10,000. Boys were at a higher risk than girls with the rates among boys being 46 (95% CI: 25, 67) using ADOS-2 and 19 (95% CI:6, 33) using ADI-R. Among girls the rates were 34 (95% CI:16, 52) and 5 (95% CI:0, 12) per 10,000, respectively. Challenges to undertaking ASD research in a rural South Asian context are discussed. There was a low-to-moderate prevalence of ASD in a rural, child population in Bangladesh. Future research is needed to estimate rates of ASD and its causes and socioeconomic consequences in rural and urban settings of South Asia. LAY SUMMARY: In a study of over 8000, 8-11 year old children in a rural area of Bangladesh, two to four out of 1000 had ASD. Boys more than girls had ASD. Conducting ASD assessment in this setting was difficult, but more such research is needed to understand what causes ASD and its consequences for the individual, families and the society in rural and urban areas of low-income countries.

mCARE, a digital health intervention package on pregnancy surveillance and care-seeking reminders from 2018 to 2027 in Bangladesh: a model-based cost-effectiveness analysis.

OBJECTIVE: We estimated the cost-effectiveness of a digital health intervention package (mCARE) for community health workers, on pregnancy surveillance and care-seeking reminders compared with the existing paper-based status quo, from 2018 to 2027, in Bangladesh. INTERVENTIONS: The mCARE programme involved digitally enhanced pregnancy surveillance, individually targeted text messages and in-person home-visit to pregnant women for care-seeking reminders for antenatal care, child delivery and postnatal care. STUDY DESIGN: We developed a model to project population and service coverage increases with annual geographical expansion (from 1 million to 10 million population over 10 years) of the mCARE programme and the status quo. MAJOR OUTCOMES: For this modelling study, we used Lives Saved Tool to estimate the number of deaths and disability-adjusted life years (DALYs) that would be averted by 2027, if the coverage of health interventions was increased in mCARE programme and the status quo, respectively. Economic costs were captured from a societal perspective using an ingredients approach and expressed in 2018 US dollars. Probabilistic sensitivity analysis was undertaken to account for parameter uncertainties. RESULTS: We estimated the mCARE programme to avert 3076 deaths by 2027 at an incremental cost of $43 million relative to the status quo, which is translated to $462 per DALY averted. The societal costs were estimated to be $115 million for mCARE programme (48% of which are programme costs, 35% user costs and 17% provider costs). With the continued implementation and geographical scaling-up, the mCARE programme improved its cost-effectiveness from $1152 to $462 per DALY averted from 5 to 10 years. CONCLUSION: Mobile phone-based pregnancy surveillance systems with individually scheduled text messages and home-visit reminder strategies can be highly cost-effective in Bangladesh. The cost-effectiveness may improve as it promotes facility-based child delivery and achieves greater programme cost efficiency with programme scale and sustainability.

Novel Method for Estimating Nutrient Intakes Using a Semistructured 24-Hour Diet Recall for Infants and Young Children in Rural Bangladesh.

BACKGROUND: Nutrient-level intakes from home-prepared complementary foods are rarely estimated among infants and young children in low-income settings. The major constraints are related to lack of standard recipes and ingredients and portion sizes. OBJECTIVES: This article describes the feasibility, applicability, and validity of a post hoc qualitative methodology to estimate nutrient intakes in children using 24-h dietary recall. METHODS: Semistructured, interviewer-administered caregiver 24-h diet recalls were conducted to assess food intake among children participating in a randomized trial of complementary food supplementation at ages 6, 9, 12, 15, 18, and 24 mo in rural Bangladesh. At the end of the diet data collection, focus group discussions with mothers (n = 6) and cooking activities (n = 5) were conducted to obtain standard recipes (and ingredients) and portion sizes for reported foods given at different ages. Nutrient intakes were calculated for children in the control group (n = 1438), and convergent validity of the data was tested by examining the association of energy and protein intakes with child age and socioeconomic status (SES). RESULTS: Focus group discussions generated standardized recipes for 21 commonly consumed mixed dishes being fed to children. These recipes were cooked, and portion sizes of standardized measures used in 24-h recalls were quantified in grams. For discrete foods, we quantified women's perceptions of "small," "medium," and "large" in grams. Across all ages, food groups consumed consisted mostly of staples, with the most common being rice, potatoes, and biscuits. Using portion size data and recipe ingredients, the 24-h dietary data, and Bangladeshi food composition tables, we successfully estimated nutrient intakes in children. Convergent validity analysis showed that energy and protein intakes were strongly associated with age and SES (both P < 0.001). CONCLUSIONS: We demonstrated the use of a validated, qualitative methodology for estimating nutrient intakes in young children from complementary foods in undernourished contexts. This trial was registered at clinicaltrials.gov as NCT01562379.

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.

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.

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

Little is known of the usual food intakes of rural adolescents in South Asia. This study describes dietary patterns, based on >91,000 7-day food frequencies among 30,702 girls and boys, aged 9-15 years in rural northwest Bangladesh. Three intake assessments per child, taken across a calendar year, were averaged to represent individual annual intake patterns for 22 food groups. Latent class analysis was used to assign individuals to dietary patterns based on class membership probabilities. The following five dietary patterns (class membership probabilities) were identified: (1) "least diverse" (0.20); (2) "traditional" (0.28); (3) "low vegetable/low fish" (0.23), (4) "moderately high meat" (0.20); and (5) "most diverse" (0.09). The least diverse pattern had the lowest median consumption of most foods and traditional had a relatively higher intake of most vegetables and fish. The most diverse pattern consumed both healthy and processed foods much more often than other patterns. The two most diverse patterns (4 and 5) were associated with higher socioeconomic status, body mass index, height-for-age Z-score, and male gender, and the least diverse pattern showed inverse associations with these characteristics. The most diverse pattern may represent an early wave of the nutrition transition in rural Bangladesh.

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.

Costs and cost-effectiveness analyses of mCARE strategies for promoting care seeking of maternal and newborn health services in rural Bangladesh.

OBJECTIVE: We examined the incremental cost-effectiveness between two mHealth programs, implemented from 2011 to 2015 in rural Bangladesh: (1) Comprehensive mCARE package as an intervention group and (2) Basic mCARE package as a control group. METHODS: Both programs included a core package of census enumeration and pregnancy surveillance provided by an established cadre of digitally enabled community health workers (CHWs). In the comprehensive mCARE package, short message service (SMS) and home visit reminders were additionally sent to pregnant women (n = 610) and CHWs (n = 70) to promote the pregnant women's care-seeking of essential maternal and newborn care services. Economic costs were assessed from a program perspective inclusive of development, start-up, and implementation phases. Effects were calculated as disability adjusted life years (DALYs) and the number of newborn deaths averted. For comparative purposes, we normalized our evaluation to estimate total costs and total newborn deaths averted per 1 million people in a community for both groups. Uncertainty was assessed using probabilistic sensitivity analyses with Monte Carlo simulation. RESULTS: The addition of SMS and home visit reminders based on a mobile phone-facilitated pregnancy surveillance system was highly cost effective at a cost per DALY averted of $31 (95% uncertainty range: $19-81). The comprehensive mCARE program had at least 88% probability of being highly cost-effective as compared to the basic mCARE program based on the threshold of Bangladesh's GDP per capita. CONCLUSION: mHealth strategies such as SMS and home visit reminders on a well-established pregnancy surveillance system may improve service utilization and program cost-effectiveness in low-resource 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.

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.

Complementary Food Supplements Increase Dietary Nutrient Adequacy and Do Not Replace Home Food Consumption in Children 6-18 Months Old in a Randomized Controlled Trial in Rural Bangladesh.

Background: Inadequate complementary feeding is common in low- and middle-income countries, contributing to growth deficits. Complementary food supplements (CFSs) aim to fill dietary gaps, but few CFS studies have measured nutrient intake. In a community-based, randomized CFS trial in Bangladesh, we previously reported poor dietary diversity in 6-18-mo-old participants. Objective: We investigated, in a secondary analysis in the same trial, micronutrient intake adequacy in supplemented compared with control-arm children. Methods: At age 6 mo, children were assigned to 1 y of child-feeding counseling for mothers (control) or counseling plus 1 of 4 CFS formulations. Mothers were administered quantitative past 24-h diet questionnaires for their children at ages 6, 9, 12, 15, and 18 mo. Nutrient intakes were estimated with local recipes and food composition tables assuming average age-specific breastmilk intake. Adequacy was evaluated relative to estimated average requirements or adequate intakes. Multivariate analysis of variance and generalized estimating equation (GEE) regression models estimated the effect of each CFS on nutrient adequacy. GEE models tested dietary predictors of nutrient adequacy in the control arm. Results: A total of 25,964 dietary modules across 5 interviews were completed. Nutrient adequacy from home foods combined with assumed breastmilk intake was low. Only 5 of 16 micronutrients were adequately consumed by >60% of children at 18 mo of age. Daily CFSs did not affect energy-adjusted micronutrient intake from home foods at any follow-up age (P > 0.05). CFSs increased the mean adequacy ratio for all micronutrients (P < 0.001 at all ages), to ≥1 for 14 of 16 micronutrients at 18 mo. Dietary diversity predicted adequate iron, zinc and calcium intake at 15 mo in unsupplemented controls. Conclusions: Home foods did not meet the estimated micronutrient needs of 9-18-mo-old children in rural Bangladesh. Daily supplementation with fortified complementary foods filled many micronutrient intake gaps and did not displace home foods. Previously, CFSs were shown to also improve linear growth and reduce stunting in this cohort. Findings support the need for CFSs in similar settings to promote nutritional well being and growth. This trial was registered at clinicaltrials.gov as NCT01562379.

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.

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.

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.

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

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

Early newborn ritual foods correlate with delayed breastfeeding initiation in rural Bangladesh.

BACKGROUND: Early and exclusive breastfeeding may improve neonatal survival in low resource settings, but suboptimal breastfeeding still exists in areas with high infant mortality. Prelacteal feeding, the practice of giving a non-breastmilk food as a neonate's first food, has been associated with suboptimal breastfeeding practices. We examined the association of feeding a non-breastmilk food in the first three days of life (early neonatal food, or ENF) with time from birth to initiation of breastfeeding among 25,286 Bangladeshi mother-neonate pairs, in a secondary analysis of a randomized controlled trial in northwestern rural Bangladesh conducted from 2001-2007. METHODS: Trained interviewers assessed the demographic characteristics during pregnancy. At three months postpartum, the interviewers visited participants again and retrospectively assessed demographic and breastfeeding characteristics surrounding the birth. We assessed the relationship between ENF and time to initiation of breastfeeding in hours in both unadjusted and adjusted linear regression analyses. We also calculated reverse cumulative distribution curves for time to initiation of breastfeeding and analyses were stratified by an infant's ability to breastfeed normally at birth. RESULTS: The mean ± SD time from birth to initiation of breastfeeding was 30.6 ± 27.9 hours. Only 2,535 (10.0%) of women reported initiating breastfeeding in the first hour after birth and 10,207 (40.4%) reported initiating breastfeeding in the first 12 hours after birth. In adjusted linear regression analyses, feeding ENF was associated with a significant increase in time, in hours, to breastfeeding initiation both among children not able to breastfeed at birth (37.4; 95% CI 33.3, 41.5) and among children able to breastfeed at birth (13.3; 95% CI 12.7, 14.0). CONCLUSIONS: Feeding ENF was strongly associated with delayed initiation of breastfeeding, even after adjusting for other related factors and stratifying on the neonate's ability to suckle normally after birth. More research is needed to understand the impact of these findings on optimal breastfeeding in this setting. It is possible that ENF feeding and the ability to breastfeed immediately after birth are interrelated in their respective associations to suboptimal breastfeeding initiation. This study in a large population representative of other populations in rural South Asia, demonstrates significantly longer times to breastfeeding initiation than previously appreciated, with a possible important role of ENF feeding. TRIAL REGISTRATION: The randomized controlled trial on which this analysis is based, "Impact of Maternal Vitamin A or Beta-Carotene Supplementation on Maternal and Infant Mortality in Bangladesh", was registered with ClinicalTrials.gov as trial number ID GHS-A-00-03-00019-00 and identifier NCT00198822. The identifier was first received September 12, 2005 (retrospectively registered). The first participant was enrolled in August 2001.

Effect of complementary food supplementation on breastfeeding and home diet in rural Bangladeshi children.

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

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.