Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts.

PURPOSE

To conduct a systematic review and meta-analysis to quantify the incidence of congenital malformations (CMs) and other pregnancy outcomes as a function of in utero anti-epileptic drug (AED) exposure.

METHODS

We performed a systematic literature review to identify all published registries and cohort studies of births from pregnant women with epilepsy (WWE) that reported incidence of CMs. Overall incidences were calculated using a random effects model.

RESULTS

The review included 59 studies that met inclusion/exclusion criteria, involving 65,533 pregnancies in WWE and 1,817,024 in healthy women. The calculated incidence of births with CM in WWE [7.08%; 95% CIs 5.62, 8.54] was higher than healthy women [2.28%; CIs 1.46, 3.10]. Incidence was highest for AED polytherapy [16.78%; CIs 0.51, 33.05]. The AED with the highest CM incidence was valproate, which was 10.73% [CIs 8.16, 13.29] for valproate monotherapy.

CONCLUSIONS

Results of this systematic literature review suggest that the overall incidence of CMs in children born of WWE is approximately threefold that of healthy women. The risk is elevated for all AED monotherapy and further elevated for AED polytherapy compared to women without epilepsy. The risk was significantly higher for children exposed to valproate monotherapy and to polytherapy of 2 or more drugs when the polytherapy combination included phenobarital, phenytoin, or valproate. Further research is needed to delineate the specific risk for each individual AED and to determine underlying mechanisms including genetic risk factors.