Do premature and postterm birth increase the risk of epilepsy? An updated meta-analysis

Many studies have reported that premature birth is associated with a higher incidence of epilepsy, and postterm birth also increases the risk of epilepsy. The effects of different gestational ages (GAs) on epilepsy have become a research hotspot, but the findings of these studies remain controversial, and no systematic review has been performed until now.

The aim of this study was to evaluate the impact of different GAs on the incidence of epilepsy.

The main databases, including PubMed, Medline, Embase, Cochrane Library, and Web of Science, were searched using the terms "preterm/premature/early/postterm/postmature/late/delayed delivery/birth", "gestational age", and "epilepsy/seizure" for eligible studies published up to April 1, 2019. The search was limited to English-language articles.

Observational studies investigating the association between epilepsy and premature or postterm birth were included in this meta-analysis. We only selected studies that had clearly reported GA and the occurrence of epilepsy.

Two reviewers independently extracted the data. The quality of the included studies was examined in accordance with the Newcastle-Ottawa criteria, and the heterogeneity and publication bias were tested. We used sensitivity and subgroup analyses to determine the source of heterogeneity. A logistic randomized-effects model was used to assess the collected data when I² ≥ 50%.

The primary outcome was the odds ratio (OR) of epilepsy.

The research included eleven eligible studies with a total of 4,513,577 participants. Studies involving premature birth showed that the risk of epilepsy was 2.16 times higher in the premature birth group (<37 weeks) than in the full-term birth group (≥37 weeks) (OR [99% confidence interval [CI]] = 2.16 [1.80, 2.58]; P < 0.001). Those born before 32 weeks were associated with an increased occurrence of epilepsy when compared with those born at 32-36 weeks (OR [99% CI] = 2.73 [1.90, 3.94]; P < 0.001). However, the difference in the incidence of epilepsy between postterm children (41 weeks or more) and full-term children (37-40 weeks) was not statistically significant (OR [99% CI] = 1.05 [0.98, 1.12]; P = 0.067).

Preterm birth was closely associated with a higher risk of epilepsy throughout childhood that persisted into adulthood, and the association became stronger as GA decreased, while there was no significant difference in the risk of developing epilepsy between postterm and full-term offspring.