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

Abstract

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.

Keywords: Adolescents; Children; Delivery factors; Epilepsy; Postnatal factors; Prenatal factors.

Fig. 1

PRISMA flowchart showing the processes of literature search and screening for systematic review and meta-analysis

Fig. 2

Forest plot of the associations of gestational age, smoking, maternal epilepsy and eclampsia with the epilepsy risk. a Forest plot of the association between gestational age and the epilepsy risk. b Forest plot of the association between gestational age and the epilepsy risk after subgroup analysis. c Forest plot of the association between smoking during pregnancy and the epilepsy risk. d Forest plot of the association between smoking during pregnancy and the epilepsy risk after sensitivity analysis. e Forest plot of association between maternal epilepsy and the epilepsy risk. f Forest plot of the association between maternal epilepsy and the epilepsy risk after sensitivity analysis. g Forest plot of the association between eclampsia and the epilepsy risk. h Forest plot of the association between eclampsia and the epilepsy risk after subgroup analysis

Fig. 3

Forest plot of the associations of pregnancy metrorrhagia, infection, preeclampsia, gestational diabetes and hypertension, maternal age, and cord prolapse with the epilepsy risk. a Forest plot of the association between pregnancy metrorrhagia and the risk of epilepsy. b Forest plot of the relationship between maternal infection and the risk of epilepsy in children or adolescents. c Forest plot of association between gestational diabetes and the epilepsy risk. d Forest plot of the association between gestational hypertension and the epilepsy risk. e Forest plot of the association between gestational hypertension and the epilepsy risk after sensitivity analysis. f Forest plot of the association between preeclampsia and the epilepsy risk. g Forest plot of the association between maternal age and the epilepsy risk. h Forest plot of the association between maternal age and the epilepsy risk after sensitivity analysis. i Forest plot of the association between cord prolapse and the epilepsy risk

Fig. 4

Forest plot of the associations of prolonged labor, cesarean section, forceps use, and breech presentation with the risk of epilepsy. a Forest plot of the association between prolonged labor and the epilepsy risk. b Forest plot of the association between prolonged labor and the epilepsy risk after sensitivity analysis. c Forest plot of the association between cesarean section and the epilepsy risk. d Forest plot of the association between cesarean section and the epilepsy risk after sensitivity analysis. e Forest plot of the association between forceps use and the epilepsy risk. f Forest plot of the association between breech presentation and the epilepsy risk. g Forest plot of the association between breech presentation and the epilepsy risk after sensitivity analysis

Fig. 5

Forest plots of the associations of meconium, head trauma, birth complications, low birth weight and male gender with the epilepsy risk. a Forest plot of the association between meconium and the epilepsy risk. b Forest plot of the association between head trauma and the epilepsy risk. c Forest plot of the association between head trauma and the epilepsy risk after sensitivity analysis. d Forest plot of the association between birth complications and the epilepsy risk after subgroup analysis. e Forest plot of the association between low birth weight and the epilepsy risk. f Forest plot of the association between epilepsy risk and male newborns g Forest plot of the association between male gender and the epilepsy risk after sensitivity analysis