Teratogenicity of antiepileptic drugs: role of drug metabolism and pharmacogenomics

The approach to clinical decision-making pertaining to the use of antiepileptic drugs (AEDs) during pregnancy has relied on previous accumulated experience and, since the 1990s, on data from pregnancy registries. The limitations of this process are that no information regarding the chemical attributes of the AED under consideration, nor the role of a number of enzyme systems that are known to interact with foreign compounds to modify their potential for harm, are included. The role of the hepatic mixed function oxidase system may be especially important in conferring teratogenic risk. However, systems such as epoxide hydrolase, glutathione reductase, superoxide dismutase and other toxin-scavenging systems may be important modifiers that lower the risk. Knowledge is also accumulating on the interactions of AEDs with molecular targets such as histone deacetylase and peroxisome proliferator-activated receptors that may play important roles in teratogenesis. While our knowledge of these factors are incomplete, progress can be achieved by beginning to include these concepts in our discussion on the topic and by promoting research that may improve our ability to individualize the analysis of risk for a specific patient with regards to specific AEDs.