Assessment of teratogenic risk

Although the association between prenatal exposure to old generation antiep ileptic drugs (AEDs) and major congenital malformations has been studied Fo r many years, it is not clear whether any specific AED, or AED combination, is more harmful than others, or whether ally pattern of malformations can be considered specific for any given drug, Relationships between dosage and plasma concentrations of AEDs and the risk of malformations also need to b e clarified. The greatest limitation of all studies performed to date is th e fact that none included a sufficiently large number of pregnancies. For n ewer generation AEDs the teratogenic risk, if any, is unknown. Large prospe ctive studies are needed, The best approach is the establishment of registr ies through international collaboration. Inclusion of non-epileptic control s and untreated women is not strictly necessary to evaluate the comparative teratogenic risk of AEDs. The modalities of data collection should be pre- defined: common protocols, sufficiently exhaustive but at the same time eas y to perform, should be shared from the beginning. Information on the prese nce or absence of major malformations or prenatal growth retardation, and o n all major factors that may affect the teratogenic endpoints should be obt ained. Study designs should ensure high duality data recording, and adequat e quality assurance and auditing procedures. Further requisites are a clear definition of congenital malformation and prolonged follow-up to detect th e occurrence of congenital malformations not detected at birth. (C) 2001 El sevier Science B.V. All rights reserved.