Double blind, cluster randomised trial of low dose supplementation with vitamin A or β carotene on mortality related to pregnancy in Nepal

OBJECTIVE: To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as β carotene. DESIGN: Double blind, cluster randomised, placebo controlled field trial. SETTING: Rural southeast central plains of Nepal (Sarlahi district). SUBJECTS: 44 646 married women, of whom 20 119 became pregnant 22 189 times. INTERVENTION: 270 wards randomised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo, vitamin A (7000 μg retinol equivalents) or β carotene (42 mg, or 7000 μg retinol equivalents) for over 3½ years. MAIN OUTCOME MEASURES: All cause mortality in women during pregnancy up to 12 weeks post partum (pregnancy related mortality) and mortality during pregnancy to 6 weeks postpartum, excluding deaths apparently related to injury (maternal mortality). RESULTS: Mortality related to pregnancy in the placebo, vitamin A, and β carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yielding relative risks (95% confidence intervals) of 0.60 (0.37 to 0.97) and 0.51 (0.30 to 0.86). This represented reductions of 40% (P<0.04) and 49% (P<0.01) among those who received vitamin A and β carotene. Combined, vitamin A or β carotene lowered mortality by 44% (0.56 (0.37 to 0.84), P<0.005) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births, or by 40% (P<0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups. CONCLUSION: Supplementation of women with either vitamin A or β carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia.