title: Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovita): a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality. The efficacy of neonatal supplementation with vitamin A to reduce mortality in the first 6 months of life is plausible but not established. We aimed to assess the efficacy of neonatal oral supplementation with vitamin A to reduce mortality between supplementation and 6 months of age.
  
  
  METHODS
  We undertook an individually randomised, double-blind, placebo-controlled trial in Haryana, India. We identified pregnant women through a surveillance programme undertaken every 3 months of all female residents in two districts of Haryana, India, aged 15-49 years, and screened every identified livebirth. Eligible participants were neonates whose parents consented to participate, were likely to stay in the study area until at least 6 months of age, and were able to feed orally at the time of enrolment. Participants were randomly assigned to receive oral capsules containing vitamin A (retinol palmitate 50,000 IU plus vitamin E 9·5-12·6 IU) or placebo (vitamin E 9·5-12·6 IU) within 72 h of birth. Randomisation was in blocks of 20 according to a randomisation list prepared by a statistician not otherwise involved with the trial. Investigators, participants' families, and the data analysis team were masked to treatment allocation. The primary outcome was mortality between supplementation and 6 months of age. Analysis included all participants assigned to study groups. This trial is registered with ClinicalTrials.gov, number NCT01138449, and the Indian Council of Medical Research Clinical Trial Registry, number CTRI/2010/091/000220.
  
  
  RESULTS
  Between June 24, 2010, and July 1, 2012 we screened 47,777 neonates and randomly assigned 44,984 to receive vitamin A (22,493) or placebo (22,491). Between supplementation and 6 months of age, 656 infants died in the vitamin A group compared with 726 in the placebo group (29·2 per 1000 vs 32·3 per 1000; difference -3·1 per 1000, 95% CI -6·3 to 0·1; risk ratio 0·90, 95% CI 0·81 to 1·00). We noted no significant interactions between the intervention effect and sex on mortality at 6 months (p=0·409). Supplementation with 50,000 IU vitamin A within the first 72 h of life was generally safe and well tolerated, with the exception of a small excess risk of transient bulging fontanelle (205 cases in the vitamin A group confirmed by physician vs 80 cases in the placebo group, risk ratio 2·56 [95% CI 1·98-3·32]).
  
  
  CONCLUSIONS
  The findings of this study, done in a population in which vitamin A deficiency is a moderate public health problem, are consistent with a modest reduction in mortality between supplementation and 6 months of age. These findings must be viewed together with similar trials in other populations to enable determination of appropriate public health policy.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation to WHO.
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Sarmila
authors.initials: S
authors.lastname: Mazumder
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Sunita
authors.initials: S
authors.lastname: Taneja
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Bhatia
authors.affiliation: Department of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland.
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Brinda
authors.initials: B
authors.lastname: Dube
authors.affiliation: Centre for Promotion of Nutrition Research and Training, Indian Council of Medical Research, New Delhi, India.
authors.forename: G S
authors.initials: GS
authors.lastname: Toteja
authors.affiliation: Department of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Bahl
authors.affiliation: Department of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fontaine
authors.affiliation: Centre for Intervention Science in Maternal and Child Health (CISMAC), Centre for International Health, University of Bergen, Bergen, Norway.
authors.forename: Jose
authors.initials: J
authors.lastname: Martines
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India. Electronic address: CHRD@sas.org.in.
authors.forename: Nita
authors.initials: N
authors.lastname: Bhandari
mesh_terms: D000284:Administration, Oral; D002214:Capsules; D019587:Dietary Supplements; D004224:Diterpenes; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; 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 / 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