Articles www.thelancet.com Published online December 11, 2014 http://dx.doi.org/10.1016/S0140-6736(14)60880-1 1 Effect of early neonatal vitamin A supplementation on mortality during infancy in Ghana (Neovita): a randomised, double-blind, placebo-controlled trial Karen M Edmond, Sam Newton, Caitlin Shannon, Maureen O’Leary, Lisa Hurt, Gyan Thomas, Seeba Amenga-Etego, Charlotte Tawiah-Agyemang, Lu Gram, Chris N Hurt, Rajiv Bahl, Seth Owusu-Agyei, Betty R Kirkwood Summary 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. Copyright ©2014. World Health Organization. Published by Elsevier Ltd. All rights reserved. Introduction When vitamin A supplements are given to children they substantially reduce mortality at 6–59 months but they have no effect on mortality in children aged 1–5 months. 1–5 Whether newborn (age 1–3 days) vitamin A supplementation can reduce neonatal (age 1–28 days) and infant mortality has been of substantial interest. However, results of randomised trials have been inconclusive. 6–13 A WHO technical consultation in December, 2008, stated that the evidence base to make a public health recommendation about neonatal vitamin A supplementation was insufficient. 14,15 Three additional randomised placebo-controlled trials were recommended (two in Africa and one in Asia). The consultation recommended that the trials should be done in areas with high infant mortality and low HIV prevalence. The consultation also recommended that the trials exclude populations with adequate vitamin A status and exclude areas with high levels of vitamin A fortification. 14,15 WHO secured funding to coordinate randomised trials in three sites. Ghana, India, and Tanzania were selected. The primary objective of all three trials was to see if a single vitamin A oral dose of 50 000 IU given to newborn infants on the day of birth or in the next 2 days could reduce post-supplementation mortality by at least 15% in the first 6 months of life. Secondary objectives were to: assess effects on post-supplementation mortality to 28 days and 12 months of age; assess effects on risk of hospital admission to 6 months of age; document any potential adverse effects in the 3 days after supplementation; and to Published Online December 11, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)60880-1 See Online/Comment http://dx.doi.org/10.1016/ S0140-6736(14)62342-4 School of Paediatrics and Health, University of Western Australia, Perth, WA, Australia (Prof K M Edmond PhD); Kintampo Health Research Centre, Kintampo, Ghana (S Newton PhD); London School of Hygiene and Tropical Medicine, London, UK (S Newton PhD, C Shannon MSc, M O’Leary MSc, L Gram MSc, S Owusu Agyei PhD, Prof B R Kirkwood FMedSci); Kintampo Health Research Centre, Kintampo, Ghana (G Thomas MPH, S Amenga-Etego MSc, C Tawiah-Agyemang MSc, S Owusu-Agyei PhD); School of Medicine, Cardiff University, Cardiff, UK (L Hurt PhD, C N Hurt MSc); and World Health Organization, Geneva, Switzerland (R Bahl PhD) Correspondence to: Prof Karen M Edmond, School of Paediatrics and Health, University of Western Australia, Roberts Rd, Perth 6008, WA, Australia karen.edmond@uwa.edu.au See Online for appendix