Effect of early neonatal vitamin A supplementation on mortality during infancy in Ghana (Neovita): a randomised, double-blind, placebo-controlled trial

Lancet. 2015 Apr 4;385(9975):1315-23. doi: 10.1016/S0140-6736(14)60880-1. Epub 2014 Dec 11.


Background: Results of randomised controlled trials of newborn (age 1-3 days) vitamin A supplementation have been inconclusive. The WHO is coordinating three large randomised trials in Ghana, India, and Tanzania (Neovita trials). We present the findings of the Neovita trial in Ghana.

Methods: This study was a population-based, individually randomised, double-blind, placebo-controlled trial in the Brong Ahafo region of Ghana. The trial participants were infants aged at least 2 h, identified at home or facilities on the day of birth or in the next 2 days, able to feed orally, and likely to stay in the study area for at least 6 months. They were randomly assigned (ratio 1:1) to receive either one oral dose of vitamin A (50,000 IU) or placebo immediately after recruitment. The research team and parents of the infants were masked to treatment assignment. Follow-up home visits were undertaken every 4 weeks, when data were recorded for deaths, facility use, and care seeking. The primary outcome was post-supplementation mortality to 6 months of age. Analysis was by intention to treat. Potential adverse events were recorded at 1 and 3 days after supplementation. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)CTRN12610000582055.

Findings: We assessed 26,414 livebirths for eligibility between Aug 16, 2010, and Nov 7, 2011. We recruited 22,955 newborn infants, with 11,474 randomly assigned to receive vitamin A and 11,481 to receive placebo. Loss to follow-up was low with vital status at 6 months of age reported for 22,698 (98·9%) infants. We recorded 278 post-supplementation deaths to 6 months of age in the vitamin A group (mortality risk 24·5 in 1000 supplemented infants) and 248 deaths in the placebo group (mortality risk 21·8 per 1000 supplemented infants), relative risk (RR) 1·12 (95% CI 0·95-1·33; p=0·183) and risk difference (RD) 2·66 (95% CI -1·25 to 6·57; p=0·18). Adverse events within 3 days of supplementation did not differ by trial group. 122 infants died in the first 3 days after supplementation; 70 (0·6%) in the vitamin A and 52 (0·5%) in the placebo group (risk ratio [RR] 1·35, 95% CI 0·94-1·93, p=0·102). 53 infants were reported to have a bulging fontanelle; 32 (0·3%) in the vitamin A group and 21 (0·2%) in the placebo group (RR 1·53, 0·88-2·62, p=0·130).

Interpretation: The results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana.

Funding: Bill & Melinda Gates Foundation grant to the WHO.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Dietary Supplements
  • Diterpenes
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Ghana / epidemiology
  • Humans
  • Infant
  • Infant Mortality
  • Infant, Newborn
  • Kaplan-Meier Estimate
  • Male
  • Retinyl Esters
  • Treatment Outcome
  • Vitamin A / administration & dosage
  • Vitamin A / analogs & derivatives*
  • Vitamin A Deficiency / drug therapy*
  • Vitamin A Deficiency / mortality
  • Vitamin E
  • Vitamins / administration & dosage*


  • Diterpenes
  • Drug Combinations
  • Retinyl Esters
  • Vitamins
  • Vitamin A
  • Vitamin E
  • retinol palmitate

Associated data

  • ANZCTR/ACTRN12610000582055