title: Efficacy of early neonatal vitamin A supplementation in reducing mortality during infancy in Ghana, India and Tanzania: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo.
  
  
  METHODS
  The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrollment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation.
  
  
  CONCLUSIONS
  The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.
authors.affiliation: Department of Maternal Newborn Child and Adolescent Health, World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland. bahlr@who.int
authors.forename: Rajiv
authors.initials: R
authors.lastname: Bahl
authors.forename: Nita
authors.initials: N
authors.lastname: Bhandari
authors.forename: Brinda
authors.initials: B
authors.lastname: Dube
authors.forename: Karen
authors.initials: K
authors.lastname: Edmond
authors.forename: Wafaie
authors.initials: W
authors.lastname: Fawzi
authors.forename: Olivier
authors.initials: O
authors.lastname: Fontaine
authors.forename: Jasmine
authors.initials: J
authors.lastname: Kaur
authors.forename: Betty R
authors.initials: BR
authors.lastname: Kirkwood
authors.forename: Jose
authors.initials: J
authors.lastname: Martines
authors.forename: Honorati
authors.initials: H
authors.lastname: Masanja
authors.forename: Sarmila
authors.initials: S
authors.lastname: Mazumder
authors.forename: Salum
authors.initials: S
authors.lastname: Msham
authors.forename: Sam
authors.initials: S
authors.lastname: Newton
authors.forename: Maureen
authors.initials: M
authors.lastname: Oleary
authors.forename: Julia
authors.initials: J
authors.lastname: Ruben
authors.forename: Caitlin
authors.initials: C
authors.lastname: Shannon
authors.forename: Emily
authors.initials: E
authors.lastname: Smith
authors.forename: Sunita
authors.initials: S
authors.lastname: Taneja
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000367:Age Factors; D002662:Child Health Services; D019587:Dietary Supplements; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D012107:Research Design; D013636:Tanzania / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D014801:Vitamin A / Q000008:administration & dosage*
chemical_list: D014801:Vitamin A