Vitamin A Maternal Mortality and Infection

Maternal vitamin A deficiency affects 5.6% of pregnant women worldwide [63]. Maternal night blindness, resulting from vitamin A deficiency, annually affects 5-15% women during pregnancy in the developing world [64]. A randomized trial of vitamin A and beta-carotene supplementation to women 15-45 years of age in rural Nepal showed a 40 and 50% reduction, respectively, in all cause pregnancy-related mortality relative to a placebo, although cause-specific mortality using verbal autopsy data provided no information for type of maternal causes of death that were affected [65]. However, pregnant women who experienced night blindness in the placebo group and representing a subgroup at high risk experienced a significantly increased risk of pregnancy-related (42 days) and 2-year postpartum mortality compared to non -night-blind women or night-blind women who received either vitamin A or beta-carotene [66]. Moreover, causes of death among night-blind women were more likely (RR = 5, 95% CI: 2.2-10.6) to be infection. It is well known that vitamin A deficiency can reduce immunocompetence and resistance to severe infection, and that vitamin A maintains the integrity of epithelial and endothelial cells and preserves natural killer cell activity. While the relationship between vitamin A deficiency and childhood morbidity and mortality is well established, only two previous studies provide the link between vitamin A deficiency and puerperal infection [67]. For example, in England, a trial conducted in the 1930s showed that maternal vitamin A supplementation in later pregnancy through the first week postpartum reduced the occurrence of puerperal sepsis [68], a finding replicated more recently among Indonesian women

[69]. There was a 78% reduction in puerperal infection assessed by the occurrence of fever in the first 10 days postpartum following supplementation.

Other biologically plausible mechanisms for the vitamin A effect are described by Faisel et al. [33]. The trial in Nepal reported a reduction in the length of labor (by 1.5 h among primiparas and 50 min in multiparas) associated with vitamin A supplementation

[70]. The hematopoietic activity of vitamin A is well known and vitamin A may act by reducing anemia, one of the known causes of maternal deaths. Using data from Nepal, it is estimated that about 20% of all cause maternal mortality could be attributable to vitamin A deficiency [63]. Two trials in Bangladesh and Ghana are currently underway to test the efficacy of vitamin A in reducing maternal mortality. Results of these trials are awaited before any policy or program decisions are made for supplementing women with vitamin A.

The role of zinc in reproductive health is well established in animal models and in small observational studies in humans [71, 72]. Yet zinc supplementation trials have not provided evidence for an impact on pregnancy and maternal health outcomes [71, 72]. A two- to ninefold increased odds of premature rupture of membrane, preterm birth, protracted first- and second-stage labor, and inefficient uterine contractions were associated with zinc deficient diets or low plasma zinc concentrations [72]. However, supplementation trials have failed to show efficacy, perhaps due to inadequate sample size, or because the studies were conducted in populations that were not likely to be zinc deficient. In a recent review of eight randomized trials of antenatal zinc supplementation conducted in developing countries, there was no clear evidence of a benefit of maternal zinc supplementation on maternal outcomes, although pregnancy or delivery complications were not assessed in some of these studies [73]. In a study in Central Java, daily zinc supplementation failed to reduce postpartum infection [69], whereas in a study conducted in West Java, zinc supplementation was associated with significantly higher delivery complications relative to the controls (n = 12 vs. 3) [73]. Thus, it is not clear if zinc supplementation in pregnancy can result in a decrease in pregnancy-related infection or other adverse outcomes or perhaps even increase delivery complications.

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