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

Objective To assess the impact on mortality related to pregnancy of supplem enting women of reproductive age each. week with a recommended dietary allo wance of vitamin A, either preformed or as beta 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 recei ve weekly a single oral supplement of placebo, vitamin A (7000 mu g retinol equivalents) or beta carotene (42 mg, or 7000 mu g retinol equivalents) fo r over 3 1/3 years. Main outcome measures All cause mortality in women during pregnancy up to 1 2 weeks post partum (pregnancy related mortality) and mortality during preg nancy to 6 weeks postpartum, excluding deaths apparently related to injury (maternal mortality). Results, Mortality related to pregnancy in the placebo, vitamin A, and beta carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yiel ding 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 6 carotene. Combined, vita min A or beta 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 1 00 000 live births, or by 40% (P < 0.02). Differences in cause of death cou ld not be reliably distinguished between supplemented and placebo groups. Conclusion Supplementation of women with either vitamin A or beta carotene at recommended dietary amounts during childbearing years can lower mortalit y related to pregnancy in rural, undernourished populations of south Asia.