SIGNIFICANCE: Maternal age and parental age gap, but not paternal age, were associated with the offspring’s risk of epilepsy. Our results do not support the hypothesis that de novo mutations associated with advanced paternal age increase the risk of epilepsy in the offspring.
OBJECTIVE: This study aims to examine the association between maternal age, paternal age, and parental age difference at the time of birth and the risk of epilepsy in the offspring.
METHODS: We carried out a prospective population-based register study of all singletons born in Denmark between 1981 and 2012. Cox regression was used to estimate hazard ratios (HRs) of epilepsy and their corresponding 95% confidence intervals (CIs), adjusted for relevant confounders.
RESULTS: We followed 1,587,897 individuals for a total of ~25 million person-years and identified 21,797 persons with epilepsy during the study period. An excess risk of epilepsy was found in individuals born to mothers younger than 20 years (HR = 1.17, 95% CI = 1.07-1.29) and born to parental couples where paternal age exceeded maternal age by at least 5 years.
The risk of epilepsy increased with increasing parental age gap and was highest when the father was ?15 years older than the mother (adjusted HR = 1.28, 95% CI = 1.16-1.41). In contrast to maternal age, we found that paternal age did not independently contribute to offspring epilepsy risk, once we accounted for the parental age difference (P = .1418). The observed associations with maternal age and parental age gap were invariant to epilepsy subtypes, but were modified by age of epilepsy onset, with the effect being most pronounced in the first 10 years of the child’s life.