Early Childhood Antibiotic Treatment for Otitis Media and Other Respiratory Tract Infections Is Associated With Risk of Type 1 Diabetes: A Nationwide Register-Based Study With Sibling Analysis

Author:

Wernroth Mona-Lisa12,Fall Katja34,Svennblad Bodil5,Ludvigsson Jonas F.46,Sjölander Arvid4,Almqvist Catarina47,Fall Tove1ORCID

Affiliation:

1. Molecular Epidemiology, Department of Medical Sciences, and Science for Life Laboratory, Uppsala University, Uppsala, Sweden

2. Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden

3. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden

4. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

5. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

6. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden

7. Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden

Abstract

OBJECTIVE The effect of early-life antibiotic treatment on the risk of type 1 diabetes is debated. This study assessed this question, applying a register-based design in children up to age 10 years including a large sibling-control analysis. RESEARCH DESIGN AND METHODS All singleton children (n = 797,318) born in Sweden between 1 July 2005 and 30 September 2013 were included and monitored to 31 December 2014. Cox proportional hazards models, adjusted for parental and perinatal characteristics, were applied, and stratified models were used to account for unmeasured confounders shared by siblings. RESULTS Type 1 diabetes developed in 1,297 children during the follow-up (median 4.0 years [range 0–8.3]). Prescribed antibiotics in the 1st year of life (23.8%) were associated with an increased risk of type 1 diabetes (adjusted hazard ratio [HR] 1.19 [95% CI 1.05–1.36]), with larger effect estimates among children delivered by cesarean section (P for interaction = 0.016). The association was driven by exposure to antibiotics primarily used for acute otitis media and respiratory tract infections. Further, we found an association of antibiotic prescriptions in pregnancy (22.5%) with type 1 diabetes (adjusted HR 1.15 [95% CI 1.00–1.32]). In general, sibling analysis supported these results, albeit often with statistically nonsignificant associations. CONCLUSIONS Dispensed prescription of antibiotics, mainly for acute otitis media and respiratory tract infections, in the 1st year of life is associated with an increased risk of type 1 diabetes before age 10 years, most prominently in children delivered by cesarean section.

Funder

Vetenskapsrådet

Publisher

American Diabetes Association

Subject

Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine

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