Impact of prenatal, neonatal, and postnatal factors on epilepsy risk in children and adolescents: a systematic review and meta-analysis

Background Epilepsy is a common, long-term neurological condition. Several previous case-control, cohort and cross-sectional studies have highlighted the role of prenatal, delivery and postnatal factors in the onset of epilepsy. In this systematic review, we evaluate the impact of these factors on the development of epilepsy in children and adolescents.Methods We searched PubMed and Google Scholar for literature on the relationship between prenatal, delivery and postnatal factors and the occurrence of epilepsy. The research was performed according to the PRSIMA 2020 flowchart and checklist. Data were extracted and pooled according to the ReviewManager 5.3 software using a random-effects model. Sensitivity analysis and subgroup analysis were used to evaluate the source of heterogeneity.Results We identified 25 reports, including 45,044 cases with confirmed epilepsy and 2,558,210 controls. Premature birth is significantly associated with the risk of epilepsy (pooled OR = 4.36 [95% CI: 1.26-15.09], P = 0.02). Smoking during pregnancy significantly increases this risk by 28% (pooled OR = 1.28 [95% CI:1.1-1.49], P = 0.002). Furthermore, maternal epilepsy confers a pooled OR of 2.06 [95% CI:1.26-3.36]. Eclampsia is linked to a 16.9-fold increased risk of epilepsy. In addition, both pregnancy metrorrhagia and maternal infection are significantly associated with the epilepsy risk (pooled OR = 2.24 [95% CI: 1.36-3.71] and 1.28 [95% CI: 1.17-1.41], respectively). For delivery conditions, cord prolapse (pooled OR = 2.58 [95% CI: 1.25-5.32]), prolonged labor (> 6 h) (OR = 6.74 [95% CI: 3.57-12.71]) and head trauma (pooled OR = 2.31 [95% CI: 1.54-3.48]) represent a meaningful risk of epilepsy occurrence. Moreover, birth complications (OR = 3.91 [95% CI: 2.43-6.29]), low birth weight (pooled OR = 1.83 [95% CI: 1.5-2.23]) and male birth (pooled OR = 1.18 [95% CI: 1.06-1.32]) are associated with an elevated risk of epilepsy in childhood and adolescence.Conclusions Epilepsy in children and adolescents can be attributed to a multitude of intricate factors, notably those during pregnancy, delivery and the postnatal period. These findings highlight the crucial role of prenatal and postnatal care in reducing the impact of these factors on epilepsy occurrence.