title: Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood: long-term follow-up of a randomized controlled trial.
abstract: BACKGROUND
  Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood.
  
  
  METHODS
  In Guinea-Bissau, low-birthweight infants were randomized to early (intervention) or delayed (usual policy) BCG. A subgroup was also randomly assigned vitamin A supplementation or placebo in a two-by-two factorial design. Participants were followed up at age 3-9 years. The main outcome was atopy defined as skin prick test reaction ≥3 mm. Secondary outcomes were symptoms of eczema, asthma and food allergy.
  
  
  RESULTS
  Two hundred eighty-one children had valid skin prick tests performed, and 14% (39/281) were atopic. There was no significant difference in atopy between the early and delayed BCG groups (OR, 0.71; 95% CI, 0.34-1.47). Atopy was significantly reduced in children who had responded to BCG with a scar (OR, 0.42; 0.19-0.94). Vitamin A supplementation was associated with increased atopy (OR, 2.88; 1.26-6.58), especially in those who received simultaneous BCG (5.99; 1.99-18.1, P = 0.09 for interaction between vitamin A supplementation and BCG). Early vs delayed BCG was not associated with symptoms of atopic disease, but vitamin A supplementation increased odds of wheeze within the past 12 months (OR, 2.45; 1.20-4.96).
  
  
  CONCLUSIONS
  There were no statistically significant effects of early vs delayed BCG on atopy or symptoms of atopic disease. Having a BCG scar was associated with reduced atopy, whereas neonatal vitamin A supplementation was associated with increased atopy.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT 01420705.
authors.affiliation: Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau, Australia; Murdoch Childrens Research Institute, Parkville, VIC, Australia; Deakin University School of Medicine, Geelong, VIC, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Kiraly
authors.forename: C S
authors.initials: CS
authors.lastname: Benn
authors.forename: S
authors.initials: S
authors.lastname: Biering-Sørensen
authors.forename: A
authors.initials: A
authors.lastname: Rodrigues
authors.forename: K J
authors.initials: KJ
authors.lastname: Jensen
authors.forename: H
authors.initials: H
authors.lastname: Ravn
authors.forename: K J
authors.initials: KJ
authors.lastname: Allen
authors.forename: P
authors.initials: P
authors.lastname: Aaby
mesh_terms: D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D019587:Dietary Supplements; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology / Q000209:etiology*; D007231:Infant, Newborn; D008297:Male; D008458:Measles Vaccine / Q000008:administration & dosage / Q000276:immunology; D015995:Prevalence; D012307:Risk Factors; D014801:Vitamin A / Q000008:administration & dosage*
chemical_list: D001500:BCG Vaccine; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D008458:Measles Vaccine; D014801:Vitamin A
keywords: BCG; allergy; asthma; atopy; vitamin A supplementation