Abstract: We reviewed 106 reports of 35 trials, published between 1931 and 2015. We included 19 trials including over 310,000 women, excluded 15 trials and one is ongoing. Overall, seven trials were judged to be of low risk of bias, three were high risk of bias and for nine it was unclear. 1) Vitamin A alone versus placebo or no treatment Overall, when trial results are pooled, vitamin A supplementation does not affect the risk of maternal mortality (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.65 to 1.20; four trials Ghana, Nepal, Bangladesh, UK, high quality evidence), perinatal mortality (RR 1.01, 95% CI 0.95 to 1.07; one study, high quality evidence), neonatal mortality, stillbirth, neonatal anaemia, preterm birth (RR 0.98, 95% CI 0.94 to 1.01, five studies, high quality evidence), or the risk of having a low birthweight baby. Vitamin A supplementation reduces the risk of maternal night blindness (RR 0.79, 95% CI 0.64 to 0.98; two trials). There is evidence that vitamin A supplements may reduce maternal clinical infection (RR 0.45, 95% CI 0.20 to 0.99, five trials; South Africa, Nepal, Indonesia, Tanzania, UK, low quality evidence) and maternal anaemia (RR 0.64, 95% CI 0.43 to 0.94; three studies, moderate quality evidence). 2) Vitamin A alone versus micronutrient supplements without vitamin A Vitamin A alone compared to micronutrient supplements without vitamin A does not decrease maternal clinical infection (RR 0.99, 95% CI 0.83 to 1.18, two trials, 591 women). No other primary or secondary outcomes were reported 3) Vitamin A with other micronutrients versus micronutrient supplements without vitamin A Vitamin A supplementation (with other micronutrients) does not decrease perinatal mortality (RR 0.51, 95% CI 0.10 to 2.69; one study, low quality evidence), maternal anaemia (RR 0.86, 95% CI 0.68 to 1.09; three studies, low quality evidence), maternal clinical infection (RR 0.95, 95% CI 0.80 to 1.13; I² = 45%, two studies, low quality evidence) or preterm birth (RR 0.39, 95% CI 0.08 to 1.93; one study, low quality evidence). In HIV-positive women vitamin A supplementation given with other micronutrients was associated with fewer low birthweight babies (< 2.5 kg) in the supplemented group in one study (RR 0.67, 95% CI 0.47 to 0.96; one study, 594 women). The pooled results of three large trials in Nepal, Ghana and Bangladesh (with over 153,500 women) do not currently suggest a role for antenatal vitamin A supplementation to reduce maternal or perinatal mortality. However, the populations studied were probably different with regard to baseline vitamin A status and there were problems with follow-up of women. There is good evidence that antenatal vitamin A supplementation reduces maternal night blindness, maternal anaemia for women who live in areas where vitamin A deficiency is common or who are HIV-positive. In addition the available evidence suggests a reduction in maternal infection, but these data are not of a high quality.

Plain-language summary: This review included 19 studies involving over 310,000 women. Seven trials were conducted in Africa, six in Indonesia, two in Bangladesh, and one each in Nepal, China, India, UK and USA. Most of the trials were conducted in populations considered to be vitamin A deficient (except USA and UK). The overall risk of bias was low to unclear in most of the trials, and the body of evidence was moderate to high quality. The findings indicate that routine supplementation with vitamin A (either alone or in combination with other supplements) during pregnancy did not reduce mother or newborn baby deaths. There is good evidence that antenatal vitamin A supplementation does reduce maternal anaemia in women who live in areas where vitamin A deficiency is common or who are HIV-positive. The trials published so far did not report any side effects or adverse events. The available evidence suggests a reduction in maternal infection but these data are not of a high quality and further trials would be needed to confirm or refute this. Taking vitamin A supplements during pregnancy does not help to prevent maternal deaths (related to pregnancy) or perinatal or newborn baby deaths. Taking vitamin A supplements during pregnancy does not help to prevent other problems that can occur such as stillbirth, preterm birth, low birthweight of babies or newborn babies with anaemia. However, the risk of maternal anaemia, maternal infection and maternal night blindness is reduced.