# Intrauterine exposure to maternal diabetes and the risk of developing epilepsy in children: a national cohort study of 2.3 million children

## TL;DR

Maternal type 1 or type 2 diabetes during pregnancy is linked to a higher risk of epilepsy in children, partly due to preterm birth and birth asphyxia.

## Contribution

This study is the first to show a significant association between maternal pre-existing diabetes and childhood epilepsy in a large national cohort.

## Key findings

- Children exposed to maternal type 1 diabetes had a 30% higher risk of epilepsy.
- Maternal type 2 diabetes was linked to a 41% increased risk of epilepsy in children.
- Preterm birth and birth asphyxia partially mediated the increased risk from maternal diabetes.

## Abstract

Approximately half of the epilepsy cases lack a documented cause. Despite growing evidence linking maternal diabetes to pregnancy complications and impaired child neurodevelopment, little is known about its potential association with child epilepsy. This study aims to determine whether intrauterine exposure to maternal pre-existing type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), or gestational diabetes mellitus (GDM) increases the risk of epilepsy in children.

This study included live-born children without major malformations in Sweden from 1998 to 2021. Children were followed from birth until epilepsy diagnosis, death, emigration, or October 2023. Child epilepsy, maternal T1DM, T2DM, GDM, and a comprehensive set of covariates were identified through linked national health registers. Multivariable Cox proportional hazards regression was used to examine the association between maternal diabetes and child epilepsy, estimating adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Analyses also included paternal T1DM and T2DM as negative control exposures to assess potential genetic confounding. Preeclampsia, preterm birth, and birth asphyxia were evaluated as mediators, using a sequential mediation approach.

Of the 2,305,051 children, 14,283 (0.6%) were exposed to maternal T1DM, 3,833 (0.2%) to T2DM, and 36,388 (1.6%) to GDM. Over a median follow-up of 13 years (range 0 to 25.8 years), 18,968 were diagnosed with epilepsy, corresponding to an incidence rate of 63.7 per 100,000 person-years. Compared with no maternal diabetes, maternal T1DM and T2DM were associated with increased hazards of epilepsy in children, with aHRs of 1.30 (95% CI 1.11–1.52) and 1.41 (95% CI 1.01–1.97), respectively. Preterm birth and birth asphyxia jointly mediated nearly half of the total effect of T1DM (HRIndirect Effect:1.14, 95% CI: 1.11, 1.17) and 30% of the total effect of T2DM (HRIndirect Effect:1.11, 95% CI: 1.04, 1.18). Paternal T1DM and T2DM, as well as maternal GDM, were not associated with epilepsy risk.

In this large cohort study, maternal T1DM and T2DM were associated with an increased risk of epilepsy in children. These associations are likely influenced by intrauterine mechanisms and were partially mediated by preterm birth and asphyxia-related conditions at birth.

The online version contains supplementary material available at 10.1186/s12916-026-04696-0.