Pan Yi-Jiun, Lin Mei-Chen, Cheng Chi-Fung, Wu Chi-Shin, Liu Chia-Lin, Chen Pei-Chun, Thompson Wesley K, Fan Chun-Chieh, Wang Shi-Heng
Department of Microbiology and Immunology, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
National Center for Geriatrics and Welfare Research, National Health Research Institutes, Zhunan, Taiwan.
Eur J Epidemiol. 2025 Jun 4. doi: 10.1007/s10654-025-01256-3.
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.
子宫内感染和幼儿期感染与癫痫风险增加有关；然而，先前的研究尚未充分考虑家族易感性的混杂因素。我们旨在通过进行基于人群和同胞比较分析，以考虑残留和未测量的家族混杂因素，来评估子宫内感染和幼儿期感染导致的癫痫风险。这项全国性出生队列研究纳入了2001年至2016年在台湾出生的2,609,289人。定义了孕期母亲感染和生命第一年的幼儿期感染。孕前母亲感染用作阴性对照。在人群分析中，孕期暴露于任何母亲感染的后代癫痫风险增加（风险比（HR）=1.36，95%置信区间（CI）：1.27-1.45）。然而，在同胞分析中，除了败血症中的母亲感染（HR=2.54，95%CI：1.74-3.70）和中枢神经系统感染（HR=24.59，95%CI：3.28-184.23）外，与母亲感染的关联减弱至无效（HR=1.11，95%CI：0.98-1.27）。在人群分析中观察到孕前母亲感染与后代癫痫的关联，但在同胞分析中未观察到。在人群分析中，暴露于幼儿期感染的个体癫痫风险增加（HR=1.49，95%CI：1.45-1.54）；在同胞分析中仍观察到该关联（HR=1.31，95%CI：1.23-1.40）。孕期母亲感染与后代癫痫风险之间的关联似乎主要是由于家族混杂因素。幼儿期感染可能在随后的癫痫风险中起因果作用。
