title: Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation to WHO.
authors.affiliation: Ifakara Health Institute, Dar es Salaam, Tanzania. Electronic address: hmasanja@ihi.or.tz.
authors.forename: Honorati
authors.initials: H
authors.lastname: Masanja
authors.affiliation: Harvard School of Public Health, Department of Global Health and Population, Boston, MA, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Smith
authors.affiliation: African Academy for Public Health, Dar es Salaam, Tanzania.
authors.forename: Alfa
authors.initials: A
authors.lastname: Muhihi
authors.affiliation: Harvard School of Public Health, Department of Global Health and Population, Boston, MA, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Briegleb
authors.affiliation: African Academy for Public Health, Dar es Salaam, Tanzania.
authors.forename: Salum
authors.initials: S
authors.lastname: Mshamu
authors.affiliation: Harvard School of Public Health, Department of Global Health and Population, Boston, MA, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Ruben
authors.affiliation: Harvard School of Public Health, Department of Global Health and Population, Boston, MA, USA; African Academy for Public Health, Dar es Salaam, Tanzania.
authors.forename: Ramadhani Abdallah
authors.initials: RA
authors.lastname: Noor
authors.affiliation: Harvard School of Public Health, Department of Global Health and Population, Boston, MA, USA.
authors.forename: Polyna
authors.initials: P
authors.lastname: Khudyakov
authors.affiliation: Department of Maternal, Newborn, Child and Adolescent Health, WHO, Geneva, Switzerland.
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Maternal, Newborn, Child and Adolescent Health, WHO, Geneva, Switzerland.
authors.forename: Jose
authors.initials: J
authors.lastname: Martines
authors.affiliation: Department of Maternal, Newborn, Child and Adolescent Health, WHO, Geneva, Switzerland.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Bahl
authors.affiliation: Harvard School of Public Health, Department of Global Health and Population, Boston, MA, USA.
authors.forename: Wafaie W
authors.initials: WW
authors.lastname: Fawzi
mesh_terms: D000284:Administration, Oral; D002214:Capsules; D019587:Dietary Supplements; D004224:Diterpenes; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D000084562:Retinyl Esters; D013636:Tanzania / Q000453:epidemiology; D016896:Treatment Outcome; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014802:Vitamin A Deficiency / Q000188:drug therapy* / Q000401:mortality; D014810:Vitamin E / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D002214:Capsules; D004224:Diterpenes; D004338:Drug Combinations; D000084562:Retinyl Esters; D014815:Vitamins; D014801:Vitamin A; D014810:Vitamin E; C014794:retinol palmitate