Sex-Specific Patterns of Reproduction in People With Epilepsy: A Nationwide Cohort Study From Denmark.

Background and objectives: Reproduction is lower in male individuals compared with female individuals with epilepsy. The reason is unknown. We studied sex-specific reproduction in individuals with epilepsy and the role of epilepsy subtype and psychiatric comorbidity.

Methods: We conducted a population-based register study in Denmark, using data from January 1, 1982, to December 31, 2021. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) with 95% CIs for the chance of having ≥1 child. We followed all persons from 15 years of age until birth of live-born offspring, 45 years of age, emigration, death, or end of follow-up (December 31, 2021), whichever occurred first. Epilepsy status was identified from the Danish National Patient Register. The primary outcome was the occurrence of live-born children identified from the Danish Medical Birth Register among persons with and without epilepsy.

Results: We included 2,593,097 individuals (49% of female individuals), including 46,243 (1.8%) with epilepsy (mean age at diagnosis of 13.1 years [SD 9.2]). Compared with individuals without epilepsy, the aHR of having ≥1 child was reduced in both sexes with epilepsy, but lower in male individuals (0.59, 95% CI 0.57-0.60) compared with female individuals with epilepsy (0.72, 95% CI 0.71-0.74). By age 45 years, the probability of being childless was 45.9% in male individuals and 30.7% in female individuals with epilepsy, compared with 22.8% in male individuals and 14.1% in female individuals without epilepsy. Compared with persons without epilepsy, the chance of having a first child was lower in female individuals with focal epilepsy (aHR 0.61, 95% CI 0.58-0.64) than in female individuals with generalized epilepsy (aHR 0.72, 95% CI 0.69-0.75), and lower in male individuals with focal epilepsy (aHR 0.51, 95% CI 0.48-0.53) than in male individuals with generalized epilepsy (aHR 0.57, 95% CI 0.54-0.60). Reproduction was particularly low in persons with epilepsy and psychiatric comorbidity (male individuals: aHR 0.30, 95% CI 0.28-0.32; female individuals: aHR 0.51, 95% CI 0.48-0.53).

Discussion: Individuals with epilepsy were less likely to become parents than individuals without epilepsy, and the association was stronger in male individuals and those with psychiatric comorbidity and varied with epilepsy subtype.