Antibiotics, acetaminophen and infections during prenatal and early life in relation to type 1 diabetes

Abstract

Background: Infections in early life have been linked to type 1 diabetes (T1D) risk, but no previous study has comprehensively analysed exposure to antibiotics, acetaminophen and infections during pregnancy and early childhood in relation to offspring risk of T1D.

Methods: Participants in the Norwegian Mother and Child Cohort Study (n = 114 215 children, of whom 403 children were diagnosed with T1D) reported infections and medication use through repeated questionnaires from pregnancy until the children were 18 months old. Adjusted hazard ratios (aHR) for offspring T1D were estimated through Cox regression adjusted for child's sex, maternal age and parity, maternal T1D, smoking in pregnancy, education level, pre-pregnancy body mass index (BMI) and birthweight. Antibiotic use was also analysed in a population-based register cohort of 541 036 children of whom 836 developed T1D.

Results: Hospitalization for gastroenteritis during the first 18 months of life was associated with increased risk (aHR 2.27, 95% CI 1.21 - 4.29, P = 0.01) of T1D. Childhood infections not requiring hospitalization, or any kind of maternal infection during pregnancy, did not predict offspring risk of T1D. Antibiotic or acetaminophen use in pregnancy, or child`s use in early childhood, was not associated with risk of T1D.

Conclusions: Our study, which is population-based and the largest of its kind, did not find support for general early life infections, infection frequency or use of antibiotics or acetaminophen to play a major role in childhood T1D. Hospital admission for gastroenteritis was associated with T1D risk, but must be interpreted cautiously due to scarcity of cases.

Figure 1

Forest plot of antibiotic use and type 1 diabetes risk in both cohorts.* *Results from the MoBa cohort (n = 84 407) are in the top lines, marked with a square, and results from the register cohort (n = 537 460) are in the bottom line, marked with a diamond. ^†Common reference for all exposure categories in the relevant time period. ^‡Hazard ratios estimated through Cox regression adjusted for child’s sex, maternal age and parity, maternal type 1 diabetes, smoking in pregnancy, education level, pre-pregnancy BMI, prematurity, birthweight, mode of delivery, infections and acetaminophen use during the relevant time period (pregnancy, or first 6 or 18 months of life) in the MoBa cohort. The register cohort was adjusted for the same variables, with the exception of maternal pre-pregnancy BMI, smoking, acetaminophen use and infections. Adjusting for maternal smoking in the register-based cohort did not appreciably change our estimates; we present data not adjusted for maternal smoking, as there was a high proportion with missing data in the register-based cohort. Children with complete data on covariates (n = 67 718 for analysis at 0-18 months of age) were included in adjusted model for the MoBa cohort.