Maternal Diabetes and Risk of Epilepsy in Offspring

Evidence on the association between maternal diabetes and neurodevelopmental disorders in offspring, particularly epilepsy, remains limited and heterogeneous. Moreover, most studies have not distinguished among diabetes subtypes-type 1 (T1DM), type 2 (T2DM), and gestational diabetes mellitus (GDM)-which have distinct etiologies. This study examines the association among these diabetes subtypes and epilepsy in offspring.

In a retrospective birth cohort of all in-hospital live births between 2002 and 2018 in Ontario, Canada's most populous province, linked with population maternal and child health records up until March 2020, we estimated the crude and adjusted association among T1DM, T2DM, and GDM and epilepsy in children aged younger than 18 years using Cox proportional hazards models. We examined the robustness of results using quantitative bias analyses.

Among 2 105 553 children, 160 644 (7.6%) were exposed to maternal diabetes (0.3% T1DM, 1.2% T2DM, and 6.1% GDM). Over a median follow-up of 10.2 years, 17 853 epilepsy cases were diagnosed. After adjusting for maternal socioeconomic and clinical characteristics, children exposed to maternal diabetes had an increased risk of epilepsy in all subcategories of diabetes compared with those unexposed (adjusted HR [aHR] for T2DM, 1.40; 95% CI, 1.24-1.58; aHR for T1DM, 1.32; 95% CI, 1.03-1.69; and aHR for GDM, 1.14; 95% CI, 1.07-1.22). A longer duration of T1DM or T2DM was associated with an increased risk. These results were consistent in our quantitative bias analyses.

Maternal diabetes, particularly T1DM and T2DM, is associated with an increased epilepsy risk in offspring, with longer disease duration not significantly amplifying this risk. These findings suggest that prenatal metabolic and inflammatory exposures may contribute to the development of epilepsy.