title: Interaction between neonatal vitamin A supplementation and timing of measles vaccination: a retrospective analysis of three randomized trials from Guinea-Bissau.
abstract: BACKGROUND
  In Guinea-Bissau we conducted three trials of neonatal vitamin A supplementation (NVAS) from 2002 to 2008. None of the trials found a beneficial effect on mortality. From 2003 to 2007, an early measles vaccine (MV) trial was ongoing, randomizing children 1:2 to early MV at 4.5 months or no early MV, in addition to the usual MV at 9 months. We have previously found interactions between vitamin A and vaccines.
  
  
  OBJECTIVE
  We investigated whether there were interactions between NVAS and early MV.
  
  
  METHODS
  We compared the mortality of NVAS and placebo recipients: first, from 4.5 to 8 months for children randomized to early MV or no early MV; and second, from 9 to 17 months in children who had received two MV or one MV. Mortality rates (MR) were compared in Cox models producing mortality rate ratios (MRR).
  
  
  RESULTS
  A total of 5141 children were randomized to NVAS (N=3015) or placebo (N=2126) and were later randomized to early MV (N=1700) or no early MV (N=3441). Between 4.5 and 8 months, NVAS compared with placebo was associated with higher mortality in early MV recipients (MR=30 versus MR=0, p=0.01), but not in children who did not receive early MV (p for interaction between NVAS and early MV=0.03). From 9 to 17 months NVAS was not associated with mortality. Overall, from 4.5 to 17 months NVAS was associated with increased mortality in early MV recipients (Mortality rate ratio=5.39 (95% confidence interval: 1.62, 17.99)).
  
  
  CONCLUSIONS
  These observations indicate that NVAS may interact with vaccines given several months later. This may have implications for the planning of future child intervention programs.
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Artillerivej 5, 2300 Copenhagen S, Denmark; OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, Denmark. Electronic address: cb@ssi.dk.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Benn
authors.affiliation: Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau.
authors.forename: Cesario L
authors.initials: CL
authors.lastname: Martins
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Artillerivej 5, 2300 Copenhagen S, Denmark.
authors.forename: Ane B
authors.initials: AB
authors.lastname: Fisker
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Artillerivej 5, 2300 Copenhagen S, Denmark.
authors.forename: Birgitte R
authors.initials: BR
authors.lastname: Diness
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Artillerivej 5, 2300 Copenhagen S, Denmark.
authors.forename: May-Lill
authors.initials: ML
authors.lastname: Garly
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: Amabelia
authors.initials: A
authors.lastname: Rodrigues
authors.affiliation: The London School of Hygiene and Tropical Medicine, Keppel Street, London, UK.
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Artillerivej 5, 2300 Copenhagen S, Denmark; Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
mesh_terms: D019587:Dietary Supplements; D005260:Female; D006169:Guinea-Bissau; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007223:Infant; D008297:Male; D008457:Measles / Q000517:prevention & control; D008458:Measles Vaccine / Q000008:administration & dosage*; D009026:Mortality; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D014611:Vaccination; D014801:Vitamin A / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D008458:Measles Vaccine; D014801:Vitamin A
keywords: Children; Low-income countries; Measles vaccine; Mortality; Vitamin A