title: High-dose vitamin A with vaccination after 6 months of age: a randomized trial.
abstract: BACKGROUND
  The World Health Organization recommends vitamin A supplementation (VAS) at routine vaccination contacts after 6 months of age based on the assumption that it reduces mortality by 24%. The policy has never been evaluated in randomized controlled trials for its effect on overall mortality. We conducted a randomized double-blind trial to evaluate the effect of VAS with vaccines.
  
  
  METHODS
  We randomized children aged 6 to 23 months 1:1 to VAS (100000 IU if aged 6-11 months, 200000 IU if aged 12-23 months) or placebo at vaccination contacts in Guinea-Bissau. Mortality rates were compared in Cox proportional-hazards models overall, and by gender and vaccine.
  
  
  RESULTS
  Between August 2007 and November 2010, 7587 children were enrolled. Within 6 months of follow-up 80 nonaccident deaths occurred (VAS: 38; placebo: 42). The mortality rate ratio (MRR) comparing VAS versus placebo recipients was 0.91 (95% confidence interval 0.59-1.41) and differed significantly between boys (MRR 1.92 [0.98-3.75]) and girls (MRR 0.45 [0.24-0.87]) (P = .003 for interaction between VAS and gender). At enrollment, 42% (3161/7587) received live measles vaccine, 29% (2154/7587) received inactivated diphtheria-tetanus-pertussis-containing vaccines, and 21% (1610/7587) received both live and inactivated vaccines. The effect of VAS did not differ by vaccine group.
  
  
  CONCLUSIONS
  This is the first randomized controlled trial to assess the effect of the policy on overall mortality. VAS had no overall effect, but the effect differed significantly by gender. More trials to ensure an optimal evidence-based vitamin A policy are warranted.
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; Department of Biostatistics, Institute of Public Health, University of Aarhus, Aarhus, Denmark; and a.fisker@bandim.org.
authors.forename: Ane B
authors.initials: AB
authors.lastname: Fisker
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau;
authors.forename: Carlito
authors.initials: C
authors.lastname: Bale
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau;
authors.forename: Amabelia
authors.initials: A
authors.lastname: Rodrigues
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau;
authors.forename: Ibraima
authors.initials: I
authors.lastname: Balde
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau;
authors.forename: Manuel
authors.initials: M
authors.lastname: Fernandes
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark;
authors.forename: Mathias J
authors.initials: MJ
authors.lastname: Jørgensen
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark;
authors.forename: Niels
authors.initials: N
authors.lastname: Danneskiold-Samsøe
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau;
authors.forename: Linda
authors.initials: L
authors.lastname: Hornshøj
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau;
authors.forename: Julie
authors.initials: J
authors.lastname: Rasmussen
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau;
authors.forename: Emil D
authors.initials: ED
authors.lastname: Christensen
authors.affiliation: Department of Biostatistics, Institute of Public Health, University of Aarhus, Aarhus, Denmark; and.
authors.forename: Bo M
authors.initials: BM
authors.lastname: Bibby
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark;
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Benn
mesh_terms: D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006169:Guinea-Bissau / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D008458:Measles Vaccine / Q000008:administration & dosage*; D009026:Mortality / Q000639:trends; D014611:Vaccination / Q000379:methods* / Q000401:mortality*; D014801:Vitamin A / Q000008:administration & dosage*
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D008458:Measles Vaccine; D014801:Vitamin A
keywords: child mortality; randomized controlled trial; vaccinations; vitamin A supplementation