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, still-birth, 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.