title: Risk of inflammatory bowel disease following Bacille Calmette-Guérin and smallpox vaccination: a population-based Danish case-cohort study.
abstract: BACKGROUND
  Childhood immunology has been suggested to play a role in development of inflammatory bowel disease (IBD) based on the studies of childhood vaccinations, infections, and treatment with antibiotics. Bacille Calmette-Guérin (BCG) and smallpox vaccinations were gradually phased-out in Denmark for children born between 1965 and 1976, hence allowing the study of subsequent risk of Crohn's disease and ulcerative colitis in a unique prospective design.
  
  
  METHODS
  The Copenhagen School Health Records Register contains detailed documentation of vaccination. Among the background cohort of individuals born between 1965 and 1976 (N = 47,622), cases with Crohn's disease (n = 218) and ulcerative colitis (n = 256) were identified through linkage to the Danish National Patient Registry. The vaccination status of the cases was compared with that of a subcohort (n = 5741) of the background cohort and analyzed in a case-cohort design.
  
  
  RESULTS
  No difference in risk of IBD was observed between individuals vaccinated and unvaccinated with BCG (hazard ratio = 0.95; 95% confidence interval, 0.75-1.19) or smallpox vaccine (hazard ratio = 1.01; 95% confidence interval, 0.77-1.32). This was also the case for Crohn's disease and ulcerative colitis separately. However, BCG given before 4 months of age may decrease the risk of IBD (hazard ratio = 0.43; 95% confidence interval, 0.20-0.93).
  
  
  CONCLUSIONS
  This prospective long-term case-cohort study shows that BCG and smallpox vaccination do not cause IBD later in life. These findings are important for the etiological understanding of IBD and of clinical importance because BCG is still one of the most commonly used childhood vaccinations, smallpox vaccine has been reintroduced in the U.S. military, and both vaccines may be used as vectors in new vaccines.
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Marie
authors.initials: M
authors.lastname: Villumsen
authors.forename: Tine
authors.initials: T
authors.lastname: Jess
authors.forename: Signe
authors.initials: S
authors.lastname: Sørup
authors.forename: Henrik
authors.initials: H
authors.lastname: Ravn
authors.forename: Erik
authors.initials: E
authors.lastname: Sturegård
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.forename: Adam
authors.initials: A
authors.lastname: Roth
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000209:etiology*; D003424:Crohn Disease / Q000453:epidemiology / Q000209:etiology*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009161:Mycobacterium / Q000502:physiology; D011212:Poxviridae / Q000502:physiology; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012899:Smallpox / Q000150:complications* / Q000188:drug therapy; D012900:Smallpox Vaccine / Q000009:adverse effects*; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D012900:Smallpox Vaccine