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Research ArticleArticle

Repeated Exposure to Antibiotics in Infancy: A Predisposing Factor for Juvenile Idiopathic Arthritis or a Sign of This Group’s Greater Susceptibility to Infections?

Miika Arvonen, Lauri J. Virta, Tytti Pokka, Liisa Kröger and Paula Vähäsalo
The Journal of Rheumatology October 2014, jrheum.140348; DOI: https://doi.org/10.3899/jrheum.140348
Miika Arvonen
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. Supported by grants from the Finnish Pediatric Research Foundation, the Finnish Society for Rheumatology, and the Kuopio University Hospital Research Foundation. 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. Address correspondence to Dr. M. Arvonen, Department of Pediatrics, Kuopio University Hospital, P.O. Box 100, FIN 70029, Kuopio, Finland. E-mail: miika.arvonen@kuh.fi. Accepted for publication August 20, 2014.
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Lauri J. Virta
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. Supported by grants from the Finnish Pediatric Research Foundation, the Finnish Society for Rheumatology, and the Kuopio University Hospital Research Foundation. 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. Address correspondence to Dr. M. Arvonen, Department of Pediatrics, Kuopio University Hospital, P.O. Box 100, FIN 70029, Kuopio, Finland. E-mail: miika.arvonen@kuh.fi. Accepted for publication August 20, 2014.
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Tytti Pokka
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. Supported by grants from the Finnish Pediatric Research Foundation, the Finnish Society for Rheumatology, and the Kuopio University Hospital Research Foundation. 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. Address correspondence to Dr. M. Arvonen, Department of Pediatrics, Kuopio University Hospital, P.O. Box 100, FIN 70029, Kuopio, Finland. E-mail: miika.arvonen@kuh.fi. Accepted for publication August 20, 2014.
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Liisa Kröger
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. Supported by grants from the Finnish Pediatric Research Foundation, the Finnish Society for Rheumatology, and the Kuopio University Hospital Research Foundation. 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. Address correspondence to Dr. M. Arvonen, Department of Pediatrics, Kuopio University Hospital, P.O. Box 100, FIN 70029, Kuopio, Finland. E-mail: miika.arvonen@kuh.fi. Accepted for publication August 20, 2014.
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Paula Vähäsalo
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. Supported by grants from the Finnish Pediatric Research Foundation, the Finnish Society for Rheumatology, and the Kuopio University Hospital Research Foundation. 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. Address correspondence to Dr. M. Arvonen, Department of Pediatrics, Kuopio University Hospital, P.O. Box 100, FIN 70029, Kuopio, Finland. E-mail: miika.arvonen@kuh.fi. Accepted for publication August 20, 2014.
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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).

Conclusion 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.

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Repeated Exposure to Antibiotics in Infancy: A Predisposing Factor for Juvenile Idiopathic Arthritis or a Sign of This Group’s Greater Susceptibility to Infections?
Miika Arvonen, Lauri J. Virta, Tytti Pokka, Liisa Kröger, Paula Vähäsalo
The Journal of Rheumatology Oct 2014, jrheum.140348; DOI: 10.3899/jrheum.140348

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Repeated Exposure to Antibiotics in Infancy: A Predisposing Factor for Juvenile Idiopathic Arthritis or a Sign of This Group’s Greater Susceptibility to Infections?
Miika Arvonen, Lauri J. Virta, Tytti Pokka, Liisa Kröger, Paula Vähäsalo
The Journal of Rheumatology Oct 2014, jrheum.140348; DOI: 10.3899/jrheum.140348
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