title: BCG vaccination at birth and early childhood hospitalisation: a randomised clinical multicentre trial.
abstract: BACKGROUND
  The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting.
  
  
  METHODS
  Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses.
  
  
  RESULTS
  4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics.
  
  
  CONCLUSIONS
  BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population.
  
  
  BACKGROUND
  NCT01694108, results.
authors.affiliation: The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Copenhagen Ø, Denmark.
authors.forename: Lone Graff
authors.initials: LG
authors.lastname: Stensballe
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen S, Denmark.
authors.forename: Signe
authors.initials: S
authors.lastname: Sørup
authors.affiliation: Bandim Health Project, Statens Serum Institut, Copenhagen S, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Copenhagen S, Denmark.|OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, Denmark.
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
authors.affiliation: The Neonatal Department, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Copenhagen Ø, Denmark.
authors.forename: Gorm
authors.initials: G
authors.lastname: Greisen
authors.affiliation: Department of Paediatrics, 460, Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark.
authors.forename: Dorthe Lisbeth
authors.initials: DL
authors.lastname: Jeppesen
authors.affiliation: Department of Paediatrics, 460, Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark.
authors.forename: Nina Marie
authors.initials: NM
authors.lastname: Birk
authors.affiliation: Research Unit Womens' and Childrens' Health, The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Copenhagen Ø, Denmark.|Denmark Copenhagen University Hospital, Copenhagen Ø, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjærgaard
authors.affiliation: Department of Paediatrics, 460, Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark.
authors.forename: Thomas Nørrelykke
authors.initials: TN
authors.lastname: Nissen
authors.affiliation: Department of Paediatrics, Kolding Hospital, Kolding, Denmark.|Institute of Regional Health Research, University of Southern Denmark, Denmark.
authors.forename: Gitte Thybo
authors.initials: GT
authors.lastname: Pihl
authors.affiliation: Department of Paediatrics, Kolding Hospital, Kolding, Denmark.|Institute of Regional Health Research, University of Southern Denmark, Denmark.
authors.forename: Lisbeth Marianne
authors.initials: LM
authors.lastname: Thøstesen
authors.affiliation: Department of Paediatrics, Kolding Hospital, Kolding, Denmark.|Institute of Regional Health Research, University of Southern Denmark, Denmark.
authors.forename: Poul-Erik
authors.initials: PE
authors.lastname: Kofoed
authors.affiliation: Department of Paediatrics, 460, Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Pryds
authors.affiliation: OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, Denmark.|Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen S, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ravn
mesh_terms: D001500:BCG Vaccine; D002675:Child, Preschool; D003718:Denmark; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018743:Perinatal Care; D012307:Risk Factors; D012959:Socioeconomic Factors; D014376:Tuberculosis / Q000517:prevention & control*
chemical_list: D001500:BCG Vaccine
keywords: Bacillus Calmette-Guérin (BCG; hospitalisation; infant; non-specific effect; vaccine