Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study

Abstract

BackgroundStudies 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 MethodsA 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.ResultsRedemption 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.ConclusionsRedemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section.

The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids

“…For instance, delivery mode by cesarean section might predispose children to obesity [14]. Moreover, children who were treated with antibiotics early in life (which possibly affected their microbial composition) had increased risk of becoming overweight and suffering autoimmune diseases later on [15,16].…”

Current understanding of the role of gut dysbiosis in type 1 diabetes

“…A Danish study including 858 201 singletons born between 1997 and 2010 revealed that use of broad-spectrum antibiotics during the first 2 years of life was associated with an increased risk of T1D during later years of life. 82 It is also of note that this rate of antibiotic-associated risk for T1D was modified by mode of delivery, being higher in children delivered by Csection than in their vaginally delivered counterparts. 82 2.7 | Breast milk feeding, gut microbiome, and T1D…”

“…Surprisingly, this trend was not seen with previous exposure to either antiviral or antifungal drugs, suggesting that the increased risk of T1D was primarily a consequence of disrupted communities of gut bacteria. A Danish study including 858 201 singletons born between 1997 and 2010 revealed that use of broad‐spectrum antibiotics during the first 2 years of life was associated with an increased risk of T1D during later years of life . It is also of note that this rate of antibiotic‐associated risk for T1D was modified by mode of delivery, being higher in children delivered by C‐section than in their vaginally delivered counterparts …”

Antibiotics, gut microbiota, environment in early life and type 1 diabetes

“…Amarri and colleagues have previously found that gut bacteria and gut permeability as well as other immune markers were significantly altered in breast-fed infants (89). Other early influences have been demonstrated in a Danish study where the authors found that antibiotics used in early-life increased the incidence of type 1 diabetes in young children: however, this was also related to the mode of birth delivery, which has major effects on determining the composition of gut microbiota at the time of birth (91). …”