Broad Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study
Background Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut microbiota. We aimed to evaluate the association of broad spectrum antibiotic treatment during the first two years of life with subsequent onset of childhood type 1 diabetes and the potential effect modification by mode of delivery. Materials and Methods A Danish nationwide cohort study including all singletons born during 1997 2010. End of follow up by December 2012. Four national registers provided information on antibiotic redemptions, outcome and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow spectrum or broad spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 858,201 singletons contributed 5,906,069 person years, during which 1,503 children developed type 1 diabetes. Results Redemption of broad spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years of life (HR 1.13; 95% CI 1.02 to 1.25) however, the rate was modified by mode of delivery. Broad spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39) but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation. Conclusions Redemption of broad spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section.
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