title: Effect of early neonatal vitamin A supplementation on mortality during infancy in Ghana (Neovita): a randomised, double-blind, placebo-controlled trial.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  The results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation grant to the WHO.
authors.affiliation: School of Paediatrics and Health, University of Western Australia, Perth, WA, Australia. Electronic address: karen.edmond@uwa.edu.au.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Edmond
authors.affiliation: Kintampo Health Research Centre, Kintampo, Ghana; London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Newton
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Shannon
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Maureen
authors.initials: M
authors.lastname: O'Leary
authors.affiliation: School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hurt
authors.affiliation: Kintampo Health Research Centre, Kintampo, Ghana.
authors.forename: Gyan
authors.initials: G
authors.lastname: Thomas
authors.affiliation: Kintampo Health Research Centre, Kintampo, Ghana.
authors.forename: Seeba
authors.initials: S
authors.lastname: Amenga-Etego
authors.affiliation: Kintampo Health Research Centre, Kintampo, Ghana.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Tawiah-Agyemang
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Lu
authors.initials: L
authors.lastname: Gram
authors.affiliation: School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Chris N
authors.initials: CN
authors.lastname: Hurt
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Bahl
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK; Kintampo Health Research Centre, Kintampo, Ghana.
authors.forename: Seth
authors.initials: S
authors.lastname: Owusu-Agyei
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Betty R
authors.initials: BR
authors.lastname: Kirkwood
mesh_terms: D000284:Administration, Oral; D019587:Dietary Supplements; D004224:Diterpenes; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D000084562:Retinyl Esters; D016896:Treatment Outcome; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014802:Vitamin A Deficiency / Q000188:drug therapy* / Q000401:mortality; D014810:Vitamin E; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D004224:Diterpenes; D004338:Drug Combinations; D000084562:Retinyl Esters; D014815:Vitamins; D014801:Vitamin A; D014810:Vitamin E; C014794:retinol palmitate