Risk assessment of antiepileptic drug use in pregnancy

PhD ceremony: Ms. J. Boersma-Jentink, 14.30 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Risk assessment of antiepileptic drug use in pregnancy

Promotor(s): prof. L.T.W. de Jong- van den Berg, prof. H. Dolk

Faculty: Mathematics and Natural Sciences

About four to five per thousand pregnant women receive at least one antiepileptic drug from the pharmacy during pregnancy. The most frequently used antiepileptic drugs are carbamazepine, lamotrigine and valproic acid (alphabetical order).

In the thesis of Janneke Boersma-Jentink there are three case control studies presented based on data from the international EUROCAT network of congenital malformations. Here, associations between specific malformations (based on indications from literature) and first trimester exposure to carbamazepine, lamotrigine or valproic acid were investigated. The study population covered 3.8 million births including information about 98 thousand pregnancy outcomes with malformations.

For lamotrigine an indication was tested for an increased risk for orofacial clefts, but this signal was not confirmed. Combining literature, five indications were found for carbamazepine, although in the case control study only an association with spina bifida was found. For valproic acid fourteen indications were identified and six were confirmed: spina bifida, ASD, cleft palate, hypospadias, polydactyly and craniosynostosis.

Furthermore, the protective effect of folic acid on the occurrence of spina bifida was investigated among valproic acid exposed pregnancies. Additional to epidemiological studies, a comparative cost-effectiveness of carbamazepine, lamotrigine and valproic acid was conducted. In particular, carbamazepine resulted to be a relative cost-effective option based on the relative safety in terms of teratogenicity and lower costs.

In the end, best treatment option can only be chosen on an individual basis and therefore it is strongly recommended that women requiring antiepileptic drugs discuss their child wish before conception with their neurologist to decide on potential treatment changes before pregnancy.