Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial

Abstract

Summary Background Supplementation of vitamin A in children aged 6–59 months improves child survival and is implemented as global policy. Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results. We aimed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days (6 months). Methods We did an individually randomised, double-blind, placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania. Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam. In Kilombero, Ulanga, and Kilosa districts, women were seen at home as part of the health and demographic surveillance system. Newborn infants were eligible for randomisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months. We randomly assigned infants to receive one dose of 50 000 IU of vitamin A or placebo in the first 3 days after birth. Infants were randomly assigned in blocks of 20, and investigators, participants’ families, and data analysis teams were masked to treatment assignment. We assessed infants on day 1 and day 3 after dosing, as well as at 1, 3, 6, and 12 months after birth. The primary endpoint was mortality at 6 months, assessed by field interviews. The primary analysis included only children who were not lost to follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12610000636055. Findings Between Aug 26, 2010, and March 3, 2013, 31 999 newborn babies were randomly assigned to receive vitamin A (n=15 995) or placebo (n=16 004; 15 428 and 15 464 included in analysis of mortality at 6 months, respectively). We did not find any evidence for a beneficial effect of vitamin A supplementation on mortality in infants at 6 months (26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group; risk ratio 1·10, 95% CI 0·95–1·26; p=0·193). There was no evidence of a differential effect for vitamin A supplementation on mortality by sex; risk ratio for mortality at 6 months for boys was 1·08 (0·90–1·29) and for girls was 1·12 (0·91–1·39). There was also no evidence of adverse effects of supplementation within 3 days of dosing. Interpretation Neonatal vitamin A supplementation did not result in any immediate adverse events, but had no beneficial effect on survival in infants in Tanzania. These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation.

Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt

“…In many developing countries, including Tanzania, maternal and newborn death and morbidity are major issues, often propagated by malnourishment (3,4). Efforts to reduce infant mortality by supplementation with vitamin A have failed (5). Fermented foods, including dairy products, have long been part of tradition in many parts of the African continent.…”

Nutrition and maternal, neonatal, and child health

“…In India the newborn vitamin A supplementation showed a 6-month survival benefit (RR ¼ 0.90, 95% CI: 0.81À1.00), 61 whereas neither study in Africa showed an impact. 62,63 In the meta-analysis that was undertaken, a clear 6-month survival benefit in Asia was observed (RR ¼ 0.87, 95% CI: 0.78À0.96), whereas the pooled effect size in Africa was 1.10 (95% CI: 1.00À1.21). 64 The major difference between the two geographic regions that has been consistent is the level of maternal vitamin A deficiency in the population in which the studies were done.…”

Transgenic Pro-Vitamin A Biofortified Crops for Improving Vitamin A Deficiency and Their Challenges

“…In Ghana, the Relative Risk Ratio (RRR) between the VAS and control group was 1.12 with 95% CI 0.95-1.33 and p-value 0.18 [31]. In Tanzania, RRR was 1.10 with 95% CI 0.95-1.26 and p-value 0.19 [16]. In India, RRR was 0.90 with 95% CI 0.81-1.0 and p-value 0.06 [32].…”

“…Neonatal VAS (within the first 28 days after birth) was proposed to improve infant survival by increased VA body storage. Presently, WHO does not recommend neonatal VAS due to conflicting evidence on neonatal mortality [30], which prompted large-scale trials for more conclusive evidence and better decision-making [16]. With WHO funding, three large-scale randomized trials were conducted in Ghana, Tanzania and India to assess whether an oral dose of 50,000 IU VA to newborn infants reduced post-VAS mortality by at least 15% in the first six months of life [31].…”