Old and new anti-epileptic drugs in pregnancy

During the recent years, a significant number of anti-epileptic drugs have been approved for prescription in different countries. In addition, some ot her promising drugs are in various stages of development. Soon after each d rug has found its place in the therapeutic arsenal, pregnancies with exposu re occur, with an increased risk of birth defect and developmental disturba nces. As regards the possible teratogenic effect of the new anti-epileptic drugs, apart some individual reports we have only the results of pre-clinic al toxicological studies which are difficult to extrapolate to the human si tuation, because of the well-known interspecies differences in pharmacokine tics and pharmacodynamics. Furthermore, combinations of anti-epileptic drug s are not tested pre-clinically while these new drugs are prescribed as add -on medication. So, metabolic interactions between individual components of such drug combinations may induce unexpected teratogenic effects. Also as for the teratogenic effects of the "old" drugs many questions have still to be defined. The most common and more important are which anti-epileptic dr ugs or combination of drugs is most safe for a particular woman with epilep sy and if there is an association between single anti-epileptic drugs and s pecific malformations. The reason is that none of the available reports to date have studied a sufficient number of women with epilepsy exposed to ant i-epileptic drug monotherapy during pregnancy. Other questions concern dose -effect relationships, a universally accepted definition of major and minor malformations, and the lack of a thorough, exhaustive evaluation of the ot her risk factors, apart from the drugs. All these questions need to be asce rtained for both the old and the new anti-epileptic drugs. Owing to these c onsiderations, in 1998 an European Register of anti-epileptic drugs and pre gnancy was instituted. The primary objective of the study is to evaluate an d determine the degree of safety, with respect to the human foetus, of anti -epileptic drugs with reference to both old and new, and to individual drug s and drugs in combination. Secondary objectives are to establish the patte rn of abnormalities, if any, associated with anti-epileptic drugs individua lly and in combination, to delineate drug-specific syndromes, if any, to ev aluate dose-effect relationships. Tertiary objectives are to provide refere nces data for use in pre-pregnancy counselling, and for development of guid elines. The evaluation of other etiological risk factors is also considered .