title: High-dose vitamin A supplementation administered with vaccinations after 6 months of age: sex-differential adverse reactions and morbidity.
abstract: BACKGROUND
  WHO recommends vitamin A supplementation (VAS) at vaccination contacts after six months of age. The effect of this recommendation on mortality has not been evaluated.
  
  
  METHODS
  We tested the effect of VAS at vaccination contacts on mortality in a randomised trial in Guinea-Bissau. In a subgroup within this trial we studied adverse reactions to VAS and whether VAS modified known adverse reactions to live and inactivated vaccines and general morbidity during the first month after supplementation overall and by sex. Children aged 6-17 months were randomised to VAS or placebo at the day of vaccination (day 0). We interviewed the caretaker, assessed the fontanel and measured temperature and local reaction at the injection site at home visits on day 1, 2, 3, 7, 14, 21, and 31. We defined systemic adverse reactions to inactivated and live vaccines as fever on day 1 and 2 and on 4-14 respectively. Clinical symptoms associated with increased intracranial pressure (ICP) on day 1 were considered possible adverse reactions to VAS.
  
  
  RESULTS
  In 1673 children VAS had no overall effect on clinical symptoms associated with increased ICP (Relative Risk(RR)=1.07 (95%CI: 0.85-1.35)). However, VAS was associated with such clinical symptoms in boys RR=1.38 (1.00-1.91)) but not in girls (p=0.03 for interaction between VAS and sex). VAS had no effect on fever after inactivated vaccines. VAS had no overall effect on fever after live vaccines (RR=0.86 (0.53-1.39)), but tended to reduce the prevalence of fever in boys (RR=0.58 (0.30-1.14)), but not in girls (RR=1.37 (0.66-2.84)) (p=0.09 for interaction between VAS and sex). VAS was associated with increased local reactions to measles vaccine in both sexes (RR=3.65 (1.20-11.12)).
  
  
  CONCLUSIONS
  Adverse reactions were rare, mild and transient and may not in their own right cause concern. However, VAS caused sex-differential adverse reactions and may have sex-differential effects on adverse reactions to vaccines.
authors.affiliation: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. a.fisker@bandim.org
authors.forename: Ane Bærent
authors.initials: AB
authors.lastname: Fisker
authors.forename: Carlito
authors.initials: C
authors.lastname: Bale
authors.forename: Mathias Jul
authors.initials: MJ
authors.lastname: Jørgensen
authors.forename: Ibriama
authors.initials: I
authors.lastname: Balde
authors.forename: Linda
authors.initials: L
authors.lastname: Hornshøj
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
mesh_terms: D019587:Dietary Supplements; D004347:Drug Interactions; D005260:Female; D006169:Guinea-Bissau; D006801:Humans; D007223:Infant; D008297:Male; D009017:Morbidity; D012737:Sex Factors; D014612:Vaccines / Q000008:administration & dosage*; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D015164:Vaccines, Inactivated / Q000008:administration & dosage; D014801:Vitamin A / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014612:Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D014801:Vitamin A