title: Antibiotic exposure and IBD development among children: a population-based cohort study.
abstract: OBJECTIVE
  To determine whether childhood antianaerobic antibiotic exposure is associated with the development of inflammatory bowel disease (IBD).
  
  
  METHODS
  This retrospective cohort study employed data from 464 UK ambulatory practices participating in The Health Improvement Network. All children with ≥ 2 years of follow-up from 1994 to 2009 were followed between practice enrollment and IBD development, practice deregistration, 19 years of age, or death; those with previous IBD were excluded. All antibiotic prescriptions were captured. Antianaerobic antibiotic agents were defined as penicillin, amoxicillin, ampicillin, penicillin/β-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin.
  
  
  RESULTS
  A total of 1072426 subjects contributed 6.6 million person-years of follow-up; 748 developed IBD. IBD incidence rates among antianaerobic antibiotic unexposed and exposed subjects were 0.83 and 1.52/10000 person-years, respectively, for an 84% relative risk increase. Exposure throughout childhood was associated with developing IBD, but this relationship decreased with increasing age at exposure. Exposure before 1 year of age had an adjusted hazard ratio of 5.51 (95% confidence interval [CI]: 1.66-18.28) but decreased to 2.62 (95% CI: 1.61-4.25) and 1.57 (95% CI: 1.35-1.84) by 5 and 15 years, respectively. Each antibiotic course increased the IBD hazard by 6% (4%-8%). A dose-response effect existed, with receipt of >2 antibiotic courses more highly associated with IBD development than receipt of 1 to 2 courses, with adjusted hazard ratios of 4.77 (95% CI: 2.13-10.68) versus 3.33 (95% CI: 1.69-6.58).
  
  
  CONCLUSIONS
  Childhood antianaerobic antibiotic exposure is associated with IBD development.
authors.affiliation: Division of Infectious Diseases, Seattle Children's Hospital, University of Washington, Seattle, Washington 98105, USA. matthew.kronman@seattlechildrens.org
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Kronman
authors.forename: Theoklis E
authors.initials: TE
authors.lastname: Zaoutis
authors.forename: Kevin
authors.initials: K
authors.lastname: Haynes
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.forename: Susan E
authors.initials: SE
authors.lastname: Coffin
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001421:Bacteria, Anaerobic; D015780:Carbapenems / Q000009:adverse effects; D002440:Cefoxitin / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002981:Clindamycin / Q000009:adverse effects; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced* / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008795:Metronidazole / Q000009:adverse effects; D010406:Penicillins / Q000009:adverse effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D013752:Tetracycline / Q000009:adverse effects; D006113:United Kingdom / Q000453:epidemiology; D014640:Vancomycin / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D010406:Penicillins; D008795:Metronidazole; D002981:Clindamycin; D002440:Cefoxitin; D014640:Vancomycin; D013752:Tetracycline