Early life antibiotic-use and risk of childhood type 1 diabetes: a nationwide cohort study utilising data linkage.

Antibiotic use in early life is associated with autoimmune diseases like Type 1 diabetes (T1D), but evidence is inconsistent. We examined associations of prenatal and early-childhood (0-5 years) antibiotic use and T1D in New Zealand, a country with high antibiotic consumption. Using linked data, we identified antibiotic use during pregnancy and the first 5 years for all children born between 2005 and 2010 (n = 315,789), followed until 2021. Associations were assessed using Cox proportional hazard regression, adjusted for parental and perinatal factors. For prenatal exposure, we assessed associations with T1D-diagnosis from birth; for early-childhood exposure, associations were assessed with T1D-diagnosis from age 5. Antibiotic use (≥ 1 course) was 29.2% for pregnant mothers and 96.3% for children aged 0-5 years. T1D was diagnosed in 0.36% (n = 1,131), with 0.28% (n = 906) diagnosed after age 5 years. Antibiotic use during pregnancy was associated with T1D, both expressed as a continuous variable (HR 1.05, 95% CI 1.03-1.08) and as a dichotomous variable (0 vs ≥ 1 course; HR 1.20, 1.05-1.38). When categorised into 0, ≤ 1, ≤ 2, and ≥ 3 courses, a significant (p = 0.0008) positive trend was observed. For postnatal exposure, the HR was 1.02 (1.02-1.03) and 1.62 (1.00-2.63), respectively; when categorised into 0, ≤ 4, ≤ 7, ≤ 12, and ≥ 13 courses, a significant dose-response trend (p = 0.0017) was shown. Strongest associations were found for moderate and broad-spectrum antibiotics in both periods. Prenatal penicillin and cephalosporins/cephamycins-use, and postnatal exposure to all antibiotic classes except tetracyclines were associated with a higher risk of T1D. In conclusion, antibiotic use during both prenatal and early childhood is associated with an increased risk of T1D.