Biochemical and molecular teratology of fetal hydantoin syndrome.
Animal and human research has clearly shown that anticonvulsants are teratogens and pose a risk for fetal malformations. In the case of dilantin it appears that fetal susceptibility correlates with the fetal level of the microsomal detoxifying enzyme epoxide hydrolase. The genetics of seizures in the parents does not predict the risk for fetal teratogenesis. The clinician must work with a mother who has seizures prior to conception to achieve the best control of seizures with a single anticonvulsant at the lowest effective dose to minimize the teratogenic potential, but even if this is done there is still a risk of fetal malformations and developmental delays. Each pregnancy in a woman on anticonvulsants is at risk, and appropriate counseling should be accomplished before conception so the family can make an informed decision. The exact risk of teratogenesis is lower than previously recorded. Dilantin poses approximately a 10% risk, tegretol less than 10%, and valproic acid causes a threefold increase in the risk of neural tube defects as well as an increased risk of other malformations. The positive aspect is that with good medical management and good prenatal care approximately 90% of infants exposed to anticonvulsants in utero will not show evidence of teratogenesis. Finally, it is important to stress that all pregnancies carry a 3% risk for a major birth defect independent of any exposures or genetic history.
Meyer Rehabilitation Institute, University of Nebraska Medical Center, Omaha.
B A
BA
Buehler
V
V
Rao
R H
RH
Finnell
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D002971:Cleft Lip / Q000139:chemically induced*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy; D005145:Face / Q000002:abnormalities*; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced*; D005333:Fetus / Q000187:drug effects; D006228:Hand Deformities, Congenital / Q000139:chemically induced*; D006628:Hirsutism / Q000139:chemically induced*; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D009264:Nails, Malformed; D010672:Phenytoin / Q000009:adverse effects*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D013577:Syndrome
D010672:Phenytoin