Prenatal and childhood infections and risk of epilepsy

Infections in utero and early childhood are associated with an increased epilepsy risk; however, confounding by familial predisposition has not been adequately accounted for in previous studies. We aimed to assess the epilepsy risk attributable to infections in utero and early childhood by performing population-based and sibling-comparison analyses to account for residual and unmeasured familial confounding factors. This nationwide birth cohort study included 2,609,289 individuals born 2001-2016 in Taiwan. Maternal infection during pregnancy and early childhood infection during the first year of life were defined. Maternal pre-pregnancy infection was used as negative control. In the population analyses, offspring exposed to any maternal infection during pregnancy had an increased epilepsy risk (hazard ratio (HR) = 1.36, 95% confidence interval (CI):1.27-1.45). However, the association with maternal infection was attenuated to the null (HR = 1.11, 95% CI:0.98-1.27), except for maternal infection in sepsis (HR = 2.54, 95% CI:1.74-3.70) and central nervous system (HR = 24.59, 95% CI:3.28-184.23), in the sibling analyses. The association of maternal pre-pregnancy infection with offspring epilepsy was observed in the population analyses, but not in the sibling analyses. Individuals exposed to childhood infection had an increased epilepsy risk (HR = 1.49, 95% CI:1.45-1.54) in the population analyses; the association was still observed in the sibling analyses (HR = 1.31, 95% CI:1.23-1.40). The association between maternal infection during pregnancy and epilepsy risk in the offspring appears largely because of familial confounding factors. Infections during early childhood may play a causal role in the subsequent epilepsy risk.