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.
Authors
Ram Ram, Corbin Corbin, Eng Eng, Kvalsvig Kvalsvig, Baker Baker, 't Mannetje 't Mannetje, Davies Davies, Douwes Douwes
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