Teratogenicity and fetotoxicity of the antiepileptics

Abstract

Pregnant women with epilepsy have more problems in maintenance of pregnancy and are under higher risk of spontaneous abort ion or occurrence of congenital fetal malformations. Use of antiepileptic drugs during pregnancy is also related to higher risk of congenital fetal malformations. The aim of our study was to determine teratogenicity and fetotoxicity of antiepileptics by performing systematic review of relevant papers. Systematic review was performed using PUBMED and Cochrane Database of Systematic Reviews. Original and review papers that relate to teratogenic effects of antiepileptic drugs were included in the analysis. Fourteen studies were found, out of which there were 7 original papers and 7 review papers. The lowest number of participants in a study was 54 and the highest 3607. Studies followed participants from 5 to 9 years. Antiepileptic drugs were used as monotherapy in 2 studies, while other studies examined both mono- and polytherapy. Doses administered varied from 600 mg (carbamazepine), 100-200 mg (lamotrigine) and 600-1000 mg (valproate), depending on kind of administration (mono or polytherapy). Among all examined antiepileptic drugs, valproate has shown the highest relation to occurrence of any degree of mental retardation or congenital malformation. Risk of congenital malformations was correlated with administration of higher drug doses and the use of polytherapy. Carbamazepine was shown to be the safest drug to use during pregnancy. Literature data do not confirm teratogenic effects of antiepileptic drugs with certainty. There are not enough studies that compare drug effects in different stages of pregnancy. Limit of presented studies is also lack of information about the degree of epilepsy and eventual comorbidity.