Sucheta Mehra

Effects of Vitamin A or Beta Carotene Supplementation on Pregnancy-Related Mortality and Infant Mortality in Rural Bangladesh: A Cluster Randomized Trial

CONTEXT Maternal vitamin A deficiency is a public health concern in the developing world. Its prevention may improve maternal and infant survival. OBJECTIVE To assess efficacy of maternal vitamin A or beta carotene supplementation in reducing pregnancy-related and infant mortality. DESIGN, SETTING, AND PARTICIPANTS Cluster randomized, double-masked, placebo-controlled trial among pregnant women 13 to 45 years of age and their live-born infants to 12 weeks (84 days) postpartum in rural northern Bangladesh between 2001 and 2007. Interventions Five hundred ninety-six community clusters (study sectors) were randomized for pregnant women to receive weekly, from the first trimester through 12 weeks postpartum, 7000 μg of retinol equivalents as retinyl palmitate, 42 mg of all-trans beta carotene, or placebo. Married women (n = 125,257) underwent 5-week surveillance for pregnancy, ascertained by a history of amenorrhea and confirmed by urine test. Blood samples were obtained from participants in 32 sectors (5%) for biochemical studies. MAIN OUTCOME MEASURES All-cause mortality of women related to pregnancy, stillbirth, and infant mortality to 12 weeks (84 days) following pregnancy outcome. RESULTS Groups were comparable across risk factors. For the mortality outcomes, neither of the supplement group outcomes was significantly different from the placebo group outcomes. The numbers of deaths and all-cause, pregnancy-related mortality rates (per 100,000 pregnancies) were 41 and 206 (95% confidence interval [CI], 140-273) in the placebo group, 47 and 237 (95% CI, 166-309) in the vitamin A group, and 50 and 250 (95% CI, 177-323) in the beta carotene group. Relative risks for mortality in the vitamin A and beta carotene groups were 1.15 (95% CI, 0.75-1.76) and 1.21 (95% CI, 0.81-1.81), respectively. In the placebo, vitamin A, and beta carotene groups the rates of stillbirth and infant mortality were 47.9 (95% CI, 44.3-51.5), 45.6 (95% CI, 42.1-49.2), and 51.8 (95% CI, 48.0-55.6) per 1000 births and 68.1 (95% CI, 63.7-72.5), 65.0 (95% CI, 60.7-69.4), and 69.8 (95% CI, 65.4-72.3) per 1000 live births, respectively. Vitamin A compared with either placebo or beta carotene supplementation increased plasma retinol concentrations by end of study (1.46 [95% CI, 1.42-1.50] μmol/L vs 1.13 [95% CI, 1.09-1.17] μmol/L and 1.18 [95% CI, 1.14-1.22] μmol/L, respectively; P < .001) and reduced, but did not eliminate, gestational night blindness (7.1% for vitamin A vs 9.2% for placebo and 8.9% for beta carotene [P < .001 for both]). CONCLUSION Use of weekly vitamin A or beta carotene in pregnant women in Bangladesh, compared with placebo, did not reduce all-cause maternal, fetal, or infant mortality. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00198822.

Vitamin A Intake and Status in Populations Facing Economic Stress

Dietary quality and diversity reflect adequacy of vitamin A. Both can deteriorate in response to economic crises. Although the nutritional consequences of the 2008 world food price crisis remain unclear, past studies of diet, status, and socioeconomic standing under usual (deprived) and unusually disruptive times suggest dietary quality and vitamin A status decline in mothers and young children. This is presumably the result of shifting diets to include less preformed vitamin A-rich animal source foods and, to a lesser extent, vegetables and fruits. Cross-sectional assessments of diet, deficiency, and socioeconomic status in a number of countries and surveillance data collected during the Indonesian economic crisis of 1997-8 indicate that the prevalence of vitamin A deficiency, night blindness, and other related disorders (e.g., anemia) may have increased during the 2008 crisis, and that it might not have necessarily recovered once food prices waned later in 2008. Lost employment may be a factor in slow nutritional recovery, despite some easing of food prices. Vitamin A deficiency should still be preventable amid economic instabilities through breast feeding promotion, vitamin A supplementation, fortification of foods targeted to the poor, and homestead food production that can bolster income and diversify the diet.

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.

Aflatoxin exposure during the first 1000 days of life in rural South Asia assessed by aflatoxin B1-lysine albumin biomarkers

Aflatoxin B1 is a potent carcinogen, occurring from mold growth that contaminates staple grains in hot, humid environments. In this investigation, aflatoxin B1-lysine albumin biomarkers were measured by mass spectrometry in rural South Asian women, during the first and third trimester of pregnancy, and their children at birth and at two years of age. These subjects participated in randomized community trials of antenatal micronutrient supplementation in Sarlahi District, southern Nepal and Gaibandha District in northwestern Bangladesh. Findings from the Nepal samples demonstrated exposure to aflatoxin, with 94% detectable samples ranging from 0.45 to 2939.30 pg aflatoxin B1-lysine/mg albumin during pregnancy. In the Bangladesh samples the range was 1.56 to 63.22 pg aflatoxin B1-lysine/mg albumin in the first trimester, 3.37 to 72.8 pg aflatoxin B1-lysine/mg albumin in the third trimester, 4.62 to 76.69 pg aflatoxin B1-lysine/mg albumin at birth and 3.88 to 81.44 pg aflatoxin B1-lysine/mg albumin at age two years. Aflatoxin B1-lysine adducts in cord blood samples demonstrated that the fetus had the capacity to convert aflatoxin into toxicologically active compounds and the detection in the same 2-year-old children illustrates exposure over the first 1000 days of life.

Effect of fortified complementary food supplementation on child growth in rural Bangladesh: a cluster-randomized trial

Background: Growth faltering in the first 2 years of life is high in South Asia where prevalence of stunting is estimated at 40–50%. Although nutrition counselling has shown modest benefits, few intervention trials of food supplementation exist showing improvements in growth and prevention of stunting. Methods: A cluster-randomized controlled trial was conducted in rural Bangladesh to test the effect of two local, ready-to-use foods (chickpea and rice-lentil based) and a fortified blended food (wheat-soy-blend++, WSB++) compared with Plumpy’doz, all with nutrition counselling vs nutrition counselling alone (control) on outcomes of linear growth (length and length-for-age z-score, LAZ), stunting (LAZ < −2), weight-for-length z-score (WLZ) and wasting (WLZ < −2) in children 6–18 months of age. Children (n = 5536) were enrolled at 6 months of age and, in the food groups, provided with one of the allocated supplements daily for a year. Results: Growth deceleration occurred from 6 to 18 months of age but deceleration in LAZ was lower (by 0.02–0.04/month) in the Plumpy’doz (P = 0.02), rice-lentil (< 0.01), and chickpea (< 0.01) groups relative to control, whereas WLZ decline was lower only in Plumpy’doz and chickpea groups. WSB++ did not impact on these outcomes. The prevalence of stunting was 44% at 18 months in the control group, but lower by 5–6% (P ≤ 0.01) in those receiving Plumpy’doz and chickpea. Mean length and LAZ at 18 months were higher by 0.27–0.30 cm and 0.07–0.10 (all P < 0.05), respectively, in all four food groups relative to the control. Conclusions: In rural Bangladesh, small amounts of daily fortified complementary foods, provided for a year in addition to nutrition counselling, modestly increased linear growth and reduced stunting at 18 months of age.

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 β-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.

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 β-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.

Analyzing the Mobile “Digital Divide”: Changing Determinants of Household Phone Ownership Over Time in Rural Bangladesh

Background We had a unique opportunity to examine demographic determinants of household mobile phone ownership in rural Bangladesh using socioeconomic data collected as part of a multiyear longitudinal cohort study of married women of reproductive age. Objectives This paper explores how the demographics of household mobile phone owners have changed over time in a representative population of rural Bangladesh. Methods We present data collected between 2008 and 2011 on household mobile phone ownership and related characteristics including age, literacy, education, employment, electricity access, and household wealth among 35,306 individuals. Respondents were enrolled when found to be newly pregnant and contributed socioeconomic information once over the course of the time period serving as a “sample” of families within the population at that time. Univariate and multiple logistic regressions analyses were performed to identify the socioeconomic determinants of household phone ownership. Results Across 3 fiscal years, we found that reported household ownership of at least 1 working mobile phone grew from 29.85% in the first fiscal year to 56.07% in the third fiscal year. Illiteracy, unavailability of electricity, and low quartiles of wealth were identified as overall demographic constraints to mobile phone ownership. However, over time, these barriers became less evident and equity gaps among demographic status began to dissipate as access to mobile technology became more democratized. We saw a high growth rate in ownership among households in lower economic standing (illiterate, without electricity, low and lowest wealth index), likely a result of competitive pricing and innovative service packages that improve access to mobile phones as the mobile phone market matures. In contrast, as market saturation is rapidly attained in the most privileged demographics (literate, secondary schooling, electricity, high wealth index), members of the lower wealth quartiles seem to be following suit, with more of an exponential growth. Conclusions Upward trends in household mobile phone ownership in vulnerable populations over time underline the potential to leverage this increasingly ubiquitous infrastructure to extend health and finance services across social and economic strata.

Accounts of severe acute obstetric complications in Rural Bangladesh

BackgroundAs maternal deaths have decreased worldwide, increasing attention has been placed on the study of severe obstetric complications, such as hemorrhage, eclampsia, and obstructed labor, to identify where improvements can be made in maternal health. Though access to medical care is considered to be life-saving during obstetric emergencies, data on the factors associated with health care decision-making during obstetric emergencies are lacking. We aim to describe the health care decision-making process during severe acute obstetric complications among women and their families in rural Bangladesh.MethodsUsing the pregnancy surveillance infrastructure from a large community trial in northwest rural Bangladesh, we nested a qualitative study to document barriers to timely receipt of medical care for severe obstetric complications. We conducted 40 semi-structured, in-depth interviews with women reporting severe acute obstetric complications and purposively selected for conditions representing the top five most common obstetric complications. The interviews were transcribed and coded to highlight common themes and to develop an overall conceptual model.ResultsWomen attributed their life-threatening experiences to societal and socioeconomic factors that led to delays in seeking timely medical care by decision makers, usually husbands or other male relatives. Despite the dominance of male relatives and husbands in the decision-making process, women who underwent induced abortions made their own decisions about their health care and relied on female relatives for advice. The study shows that non-certified providers such as village doctors and untrained birth attendants were the first-line providers for women in all categories of severe complications. Coordination of transportation and finances was often arranged through mobile phones, and referrals were likely to be provided by village doctors.ConclusionsStrategies to increase timely and appropriate care seeking for severe obstetric complications may consider targeting of non-certified providers for strengthening of referral linkages between patients and certified facility-based providers. Future research may characterize the treatments and appropriateness of emergency care provided by ubiquitous village doctors and other non-certified treatment providers in rural South Asian settings. In addition, future studies may explore the use of mobile phones in decreasing delays to certified medical care during obstetric emergencies.

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 &agr;-1 acid glycoprotein >100 mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and &agr;-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.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.