title: Repeated exposure to antibiotics in infancy: a predisposing factor for juvenile idiopathic arthritis or a sign of this group's greater susceptibility to infections?
abstract: OBJECTIVE
  Previous exposure to antibiotics has been associated with the pathogenesis of several autoimmune diseases. Our objective was to explore whether childhood exposure to antibiotics would be associated with the risk of developing juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  The material was collected from national registers containing all children born in 2000-2010 in Finland and diagnosed with JIA by the end of December 2012 (n = 1298) and appropriate controls (n = 5179) matched for age, sex, and place of birth. All purchases of antibiotics were collected from birth until the index date (i.e., the date of special reimbursement for JIA medications). A conditional logistic regression was performed to evaluate the association between the exposure to antibiotics and the risk of JIA.
  
  
  RESULTS
  The risk of JIA increased with the number of antibiotic purchases from birth to the index date: for ≥ 1 purchases versus none, OR 1.6, 95% CI 1.3-1.9 with an upward trend in OR (p < 0.001). Antibiotic groups lincosamides and cephalosporins showed the strongest association with JIA (OR 6.6, 95% CI 3.7-11.7, and OR 1.6, 95% CI 1.4-1.8, respectively). Overall exposure to antibiotics before 2 years of age was associated with an increased risk of JIA (OR 1.4, 95% CI 1.2-1.6), with the trend test of OR (p < 0.001).
  
  
  CONCLUSIONS
  Previous early and repeated exposure to antibiotics may predispose individuals to develop JIA. Alternatively, the apparent association may reflect shared susceptibility to infections and JIA.
authors.affiliation: From the Department of Pediatrics, Kuopio University Hospital, Kuopio, and University of Eastern Finland, Kuopio; Research Department, Social Insurance Institution, Turku; Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland.M. Arvonen, MD, PhD, Department of Pediatrics, Kuopio University Hospital, University of Eastern Finland, and Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, University of Oulu; L.J. Virta, MD, PhD, Research Department, Social Insurance Institution; T. Pokka, MSc, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu; L. Kröger, MD, PhD, Department of Pediatrics, Kuopio University Hospital, and University of Eastern Finland; P. Vähäsalo, MD, PhD, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu. miika.arvonen@kuh.fi.
authors.forename: Miika
authors.initials: M
authors.lastname: Arvonen
authors.affiliation: From the Department of Pediatrics, Kuopio University Hospital, Kuopio, and University of Eastern Finland, Kuopio; Research Department, Social Insurance Institution, Turku; Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland.M. Arvonen, MD, PhD, Department of Pediatrics, Kuopio University Hospital, University of Eastern Finland, and Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, University of Oulu; L.J. Virta, MD, PhD, Research Department, Social Insurance Institution; T. Pokka, MSc, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu; L. Kröger, MD, PhD, Department of Pediatrics, Kuopio University Hospital, and University of Eastern Finland; P. Vähäsalo, MD, PhD, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu.
authors.forename: Lauri J
authors.initials: LJ
authors.lastname: Virta
authors.affiliation: From the Department of Pediatrics, Kuopio University Hospital, Kuopio, and University of Eastern Finland, Kuopio; Research Department, Social Insurance Institution, Turku; Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland.M. Arvonen, MD, PhD, Department of Pediatrics, Kuopio University Hospital, University of Eastern Finland, and Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, University of Oulu; L.J. Virta, MD, PhD, Research Department, Social Insurance Institution; T. Pokka, MSc, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu; L. Kröger, MD, PhD, Department of Pediatrics, Kuopio University Hospital, and University of Eastern Finland; P. Vähäsalo, MD, PhD, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu.
authors.forename: Tytti
authors.initials: T
authors.lastname: Pokka
authors.affiliation: From the Department of Pediatrics, Kuopio University Hospital, Kuopio, and University of Eastern Finland, Kuopio; Research Department, Social Insurance Institution, Turku; Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland.M. Arvonen, MD, PhD, Department of Pediatrics, Kuopio University Hospital, University of Eastern Finland, and Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, University of Oulu; L.J. Virta, MD, PhD, Research Department, Social Insurance Institution; T. Pokka, MSc, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu; L. Kröger, MD, PhD, Department of Pediatrics, Kuopio University Hospital, and University of Eastern Finland; P. Vähäsalo, MD, PhD, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu.
authors.forename: Liisa
authors.initials: L
authors.lastname: Kröger
authors.affiliation: From the Department of Pediatrics, Kuopio University Hospital, Kuopio, and University of Eastern Finland, Kuopio; Research Department, Social Insurance Institution, Turku; Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland.M. Arvonen, MD, PhD, Department of Pediatrics, Kuopio University Hospital, University of Eastern Finland, and Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, University of Oulu; L.J. Virta, MD, PhD, Research Department, Social Insurance Institution; T. Pokka, MSc, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu; L. Kröger, MD, PhD, Department of Pediatrics, Kuopio University Hospital, and University of Eastern Finland; P. Vähäsalo, MD, PhD, Medical Research Center Oulu, Department of Pediatrics, Oulu University Hospital, and University of Oulu.
authors.forename: Paula
authors.initials: P
authors.lastname: Vähäsalo
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000209:etiology*; D001424:Bacterial Infections / Q000188:drug therapy*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D005387:Finland; D006801:Humans; D007223:Infant; D008297:Male; D012042:Registries; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents
keywords: ANTIBACTERIAL AGENTS; CHILD EPIDEMIOLOGY; ENVIRONMENTAL EXPOSURE; JUVENILE IDIOPATHIC ARTHRITIS; MATCHED CASE-CONTROL STUDIES