Maternal Autoimmune Diseases During Pregnancy and Offspring Type 1 Diabetes

IMPORTANCE Maternal autoimmune diseases during pregnancy may influence the long-term risk of immune-mediated diseases in offspring, but the relative contributions of prenatal and familial factors to offspring type 1 diabetes (T1D) remain unclear. OBJECTIVE To investigate the association between a broad spectrum of maternal autoimmune diseases during pregnancy and offspring T1D, and to compare the associations of maternal and paternal autoimmune diseases with offspring T1D. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study included children identified from national health registers who were born in Sweden between 2001 and 2014, and were followed up from birth until T1D diagnosis, death, emigration, or December 31, 2023. These data were analyzed from November 2025 to June 2026. EXPOSURE Parental autoimmune diseases diagnosed before or during pregnancy, identified from national health registers. MAIN OUTCOMES AND MEASURES The primary outcome was incident T1D in offspring. Hazard ratios (HRs) and 95% CIs for offspring T1D were estimated using Cox proportional hazard regression models. Associations of maternal and paternal autoimmune diseases before childbirth with offspring T1D were directly compared, and cousin analyses were performed to assess the potential role of shared familial factors. RESULTS During a median follow-up of 15.3 years, 10 273 (0.71%) of the 1 455 645 included individuals (51.4% male and 48.6% female; median [IQR], age 15.3 [11.9-19.0] years) developed T1D. Maternal autoimmune disease during pregnancy was associated with an increased risk of offspring T1D (adjusted HR, 1.57; 95% CI, 1.46-1.68); paternal autoimmune disease before childbirth showed a similar association (adjusted HR, 1.51; 95% CI, 1.37-1.67). No overall difference was observed in maternal-paternal comparisons (ratio of HR, 1.04; 95% CI, 0.92-1.17), but heterogeneity was observed across specific disease categories. A clear gradient in T1D risk was observed according to parental T1D status, with the highest risk among offspring with both parents affected, followed by paternal T1D only and maternal T1D only. In cousin analyses, the association with maternal autoimmune disease was attenuated but persisted (HR, 1.27; 95% CI, 1.08-1.50). CONCLUSIONS AND RELEVANCE In this population-based cohort study, maternal autoimmune diseases during pregnancy were associated with an increased risk of offspring T1D. Comparable associations of maternal and paternal autoimmune diseases with offspring T1D suggest a role of shared familial susceptibility, while disease-specific differences indicate that some conditions could have parental-specific effects, suggesting contributions from shared familial susceptibility and potential intrauterine mechanisms.