Genetic Variability in Fetal Response to Anticonvulsants

  • D. Lindhout
Conference paper


Since the discovery of thalidomide embryopathy in 1961, many other drugs and chemicals have been recognized as potential teratogens. Observations during the last three decades have shown that thalidomide is still the strongest teratogen, causing malformations in 20%–50% of fetuses that are exposed during the critically sensitive embryonic period [20]. Only the retinoic acid congeners isotretinoin and etretinate and the obsolete trimethadiones induce severe anomalies in a similarly large proportion of exposed fetuses [13, 26, 31]. Most other teratogenic drugs are associated with malformations in a much smaller proportion of exposed fetuses. This is also the case with the anticonvulsant drugs phenytoin, phenobarbitone, primidone, valproate, and carbamazepine. The use of these drugs during the first trimester of pregnancy is associated with, on the average, a twofold risk of congenital malformation. High maternal serum levels of the parent drug seem to be of some significance [4, 12], but they cannot explain by themselves the occurrence of malformations because many unaffected infants were born after documented exposure to equally high maternal drug levels.


Pyrene Carbamazepine Epoxide Halothane Anthracene 


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Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • D. Lindhout
    • 1
  1. 1.Department of Clinical GeneticsErasmus UniversityRotterdamThe Netherlands

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