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JAMA | 2011

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

Keith P. West; Parul Christian; Alain B. Labrique; Mahbubur Rashid; Abu Ahmed Shamim; Rolf Klemm; Allan B. Massie; Sucheta Mehra; Kerry Schulze; Hasmot Ali; Barkat Ullah; Lee S.-F. Wu; Joanne Katz; Hashina Banu; Halida H. Akhter; Alfred Sommer

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.


JAMA | 2014

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

Keith P. West; Abu Ahmed Shamim; Sucheta Mehra; Alain B. Labrique; Hasmot Ali; Saijuddin Shaikh; Rolf Klemm; Lee S.-F. Wu; Maithilee Mitra; Rezwanul Haque; Abu A. M. Hanif; Allan B. Massie; Rebecca Day Merrill; Kerry Schulze; Parul Christian

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.


Food and Chemical Toxicology | 2014

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

John D. Groopman; Patricia A. Egner; Kerry Schulze; Lee S.-F. Wu; Rebecca D. Merrill; Sucheta Mehra; Abu Ahmed Shamim; Hasmot Ali; Saijuddin Shaikh; Alison D. Gernand; Subarna K. Khatry; Steven C. LeClerq; Keith P. West; Parul Christian

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.


International Journal of Epidemiology | 2015

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

Parul Christian; Saijuddin Shaikh; Abu Ahmed Shamim; Sucheta Mehra; Lee Wu; Maithilee Mitra; Hasmot Ali; Rebecca D. Merrill; Nuzhat Choudhury; Monira Parveen; Rachel Fuli; Iqbal Hossain; M. Munirul Islam; Rolf Klemm; Kerry Schulze; Alain B. Labrique; Saskia de Pee; Tahmeed Ahmed; Keith P. West

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.


Journal of Nutrition | 2011

Iron Status of Women Is Associated with the Iron Concentration of Potable Groundwater in Rural Bangladesh

Rebecca D. Merrill; Abu Ahmed Shamim; Hasmot Ali; Nusrat Jahan; Alain B. Labrique; Kerry Schulze; Parul Christian; Keith P. West

Women of reproductive age are at a high risk of iron deficiency, often as a result of diets low in bioavailable iron. In some settings, the iron content of domestic groundwater sources is high, yet its contribution to iron intake and status has not been examined. In a rural Bangladeshi population of women deficient in dietary iron, we evaluated the association between groundwater iron intake and iron status. In 2008, participants (n = 209 with complete data) were visited to collect data on 7-d food frequency, 7-d morbidity history, 24-h drinking water intake, and rice preparation, and to measure the groundwater iron concentration. Blood was collected to assess iron and infection status. Plasma ferritin (μg/L) and body iron (mg/kg) concentrations were [median (IQR)] 67 (46, 99) and 10.4 ± 2.6, respectively, and the prevalence of iron deficiency (ferritin < 12 μg/L) was 0%. Daily iron intake from water [42 mg (18, 71)] was positively correlated with plasma ferritin (r = 0.36) and total body iron (r = 0.35) (P < 0.001 for both). In adjusted linear regression analyses, plasma ferritin increased by 6.1% (95% CI: 3.8, 8.4%) and body iron by 0.3 mg/kg (0.2, 0.4) for every 10-mg increase in iron intake from water (P < 0.001). In this rural area of northern Bangladesh, women of reproductive age had no iron deficiency likely attributable to iron consumed from drinking groundwater, which contributed substantially to dietary intake. These findings suggest that iron intake from water should be included in dietary assessments in such settings.


Journal of Nutrition | 2013

Early Neonatal Feeding Is Common and Associated with Subsequent Breastfeeding Behavior in Rural Bangladesh

Maria E. Sundaram; Alain B. Labrique; Sucheta Mehra; Hasmot Ali; Abu Ahmed Shamim; Rolf Klemm; Keith P. West; Parul Christian

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.


The American Journal of Clinical Nutrition | 2015

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

Abu Ahmed Shamim; Kerry Schulze; Rebecca D. Merrill; Alamgir Kabir; Parul Christian; Saijuddin Shaikh; Lee Wu; Hasmot Ali; Alain B. Labrique; Sucheta Mehra; Rolf Klemm; Mahbubur Rashid; Pongtorn Sungpuag; Emorn Udomkesmalee; Keith P. West

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.


Public Health Nutrition | 2013

Plasma zinc, vitamin B 12 and α-tocopherol are positively and plasma γ-tocopherol is negatively associated with Hb concentration in early pregnancy in north-west Bangladesh

Abu Ahmed Shamim; Alamgir Kabir; Rebecca D. Merrill; Hasmot Ali; Mahbubur Rashid; Kerry Schulze; Alain B. Labrique; Keith P. West; Parul Christian

OBJECTIVE The objective of the current analysis was to explore the association of multiple micronutrients with Hb concentration among pregnant women in a South Asian setting, a topic that has not been adequately explored. DESIGN Sociodemographic, anthropometric and micronutrient status (plasma ferritin, transferrin receptor, retinol, a- and g-tocopherol, folate, vitamin B12, Zn) and Hb concentration were assessed at early pregnancy. SETTING The biochemical sub-study was nested within a double-blind, placebo-controlled, community-based vitamin A and b-carotene supplementation trial in rural north-western Bangladesh (JiVitA). All assessments were conducted before trial supplementation was initiated. SUBJECTS A systematic sample of 285 women was selected from those enrolled in the biochemical sub-study. RESULTS Seventeen per cent of women were mildly anaemic; moderate and severe anaemia was uncommon (2.1 %). a-Tocopherol, vitamin B12 and Zn deficiencies were common (43.5%, 19.7% and 14.7%, respectively); however, vitamin A, folate and Fe deficiencies were comparatively rare (7.4%, 2.8% and ,1%,respectively). Plasma Zn, vitamin B12 and a-tocopherol were positively associated and plasma g-tocopherol was negatively associated with Hb (P < 0.05) after adjustment for gestational age, inflammation status, season and nutritional status measured by mid-upper arm circumference. CONCLUSIONS Among pregnant women in rural Bangladesh with minimal Fe deficiency, plasma Zn, vitamin B12, and a- and g-tocopherol concentrations were associated with Hb concentration. Appreciating the influence on Hb of micronutrients in addition to those with known associations with anaemia, such as Fe, folate, and vitamin A, is important when addressing anaemia in similar settings.


Jmir mhealth and uhealth | 2015

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

Michael Clifton Tran; Alain B. Labrique; Sucheta Mehra; Hasmot Ali; Saijuddin Shaikh; Maithilee Mitra; Parul Christian; Keith P. West

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.


The American Journal of Clinical Nutrition | 2011

Maternal vitamin A and β-carotene supplementation and risk of bacterial vaginosis: a randomized controlled trial in rural Bangladesh

Parul Christian; Alain B. Labrique; Hasmot Ali; Mark Jason Richman; Lee Wu; Mahbubur Rashid; Keith P. West

BACKGROUND Bacterial vaginosis (BV) in pregnancy is linked to preterm birth, but its risk factors are not well understood. Micronutrient deficiencies may be associated with an increased risk of this condition. OBJECTIVE We assessed the effect of weekly vitamin A or β-carotene supplementation during pregnancy until 3 mo postpartum on BV risk in rural northeastern Bangladesh. DESIGN In this cluster-randomized, placebo-controlled trial, 33 clusters (n = 33) were randomly assigned to 3 groups. Women (n = 1812) were examined for BV by using self-administered swabs and the Nugent scoring method in early pregnancy, at 32 wk of gestation, and at 3 mo postpartum. RESULTS The prevalence of BV in early pregnancy, before supplementation, was 7.6% (95% CI: 6.3%, 9.1%) overall. Neither the prevalence nor the incidence of BV in the third trimester differed by supplement group. However, the prevalence (OR: 0.71; 95% CI: 0.52, 0.98) and incidence (RR: 0.58; 95% CI: 0.41, 0.81) of BV at 3 mo postpartum was lower among women in the vitamin A group (9.1% and 6.7%, respectively) than in the placebo group (12.4% and 11.8%, respectively), but not in the β-carotene group. Both vitamin A and β-carotene reduced the prevalence and incidence of BV at both time points (ie, third trimester and 3 mo postpartum) by 30-40% compared with placebo (all P < 0.05). CONCLUSIONS Weekly vitamin A supplementation reduced the risk of maternal BV in this rural Bangladeshi population. Enhancement of vitamin A status before and during pregnancy may reduce the risk of BV in areas with vitamin A deficiency. This trial is registered at clinicaltrials.gov as NCT00198822.

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Keith P. West

Johns Hopkins University

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Sucheta Mehra

Johns Hopkins University

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Kerry Schulze

Johns Hopkins University

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Rolf Klemm

Johns Hopkins University

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Lee Wu

Johns Hopkins University

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