Maternal Epilepsy and Long-term Offspring Mortality: A Nationwide Cohort Study

Abstract

Objective: We examined how maternal epilepsy and use of antiseizure medications in pregnancy was associated with offspring mortality. Methods: This population-based cohort study included all live- and stillborn singletons in Denmark between 1981 and 2016. We used nation-wide registers to retrieve information on pregnancy characteristics, epilepsy diagnoses, use of antiseizure medications, and mortality. Adjusted mortality rate ratios (MRR) were estimated using log-linear Poisson regression. Results: The cohort consisted of 1,862,474 children. In total, 12,026 live-born children died during follow-up, of whom 170 (1.4%) were offspring of mothers with epilepsy. Overall mortality was increased in offspring of mothers with epilepsy compared to offspring of mothers without epilepsy (MRR = 1.46, 95% CI: 1.23–1.71), driven by an excess mortality only in the first year of life. Mortality was increased for natural deaths (MRR = 1.50, 95% CI: 1.25–1.78) but not from unnatural deaths (MRR = 1.38, 95% CI: 0.84–2.14), and only in offspring of women with epilepsy who used antiseizure medications during pregnancy (MRR = 1.51, 95% CI: 1.00–2.17), but not in offspring of women with epilepsy who did not use antiseizure medications while pregnant (MRR = 0.97, 95% CI: 0.69–1.31). When analyses were restricted to children born from 2000 and onwards, the excess mortality that was observed in the first year of life among children of mothers with epilepsy, was no longer evident. Interpretation: During the 1981 to 1999 epoch, offspring of women with epilepsy were at increased risk of dying in the first year of life. However, this risk did not extend to children born after 2000. Future retrospective studies of the effects of maternal epilepsy on the health of the offspring should take this difference into account. ANN NEUROL 2022;91:455–465.