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To identify the major risk factors for the increased incidence of congenital malformations in offspring of mothers being treated for epilepsy with antiepileptic drugs (AEDs) during pregnancy and, to determine the relative teratogenic risk of AEDs, we prospectively analyzed 983 offspring born in Japan, Italy, and Canada. The incidence of congenital(More)
Folate levels in serum and red cells, as determined by a microbiological assay using Lactobacillus casei, and plasma anticonvulsant concentrations were monitored concurrently in nonpregnant (50 subjects) and pregnant (49 pregnancies in 46 subjects) epileptic women. Twenty-three (46%) nonpregnant women had subnormal serum folate levels and 4 nonpregnant(More)
Gestational folate deficiency has been associated with abnormal growth and development in both experimental animal and human studies and has been postulated as a putative mechanism for the teratogenic effects of antiepileptic drugs (AEDs). Animal studies have shown that the administration of AEDs results in folate depletion and teratogenic effects. Attempts(More)
The aim of the present study was to evaluate the risk of intrauterine growth delay in the offspring of epileptic mothers and to quantify the risks of intrauterine exposure to antiepileptic drugs (AEDs). Data concerning 870 newborns, prospectively collected in Canada, Japan and Italy, using the same study design, were pooled and analyzed. The overall(More)
Evidence accumulated over the past three decades has established AEDs as human teratogens. Important developments in the delineation of these compounds as human teratogens include: the demonstration of a consistent association between in utero exposure to AEDs and an increased occurrence of single major malformations, the description of AED-induced(More)
The prevalence of abnormal pregnancy outcomes in the offspring of 103 epileptic women, followed prospectively during pregnancy between 1982 and 1989, was compared with that in the previous study of 119 pregnancies by Dansky et al from the same institution. Our results have shown a significant decrease in the prevalence of major malformations, as compared(More)
The role of phenytoin(DPH) in causing birth defects is uncertain. Only a minority of fetuses exposed to DPH have malformations. Arene oxide metabolites(AOM) of DPH may be involved in fetal toxicity. We found genetic differences in detoxification of AOM in patients with adverse reactions to DPH. Therefore, we have explored the contribution of detoxification(More)
A direct teratogenic effect of antiepileptic drugs (AEDs) on the fetus has been postulated. However, there may also be a primary effect of AEDs on placenta, with secondary consequences to the fetus. Thirteen carefully medically controlled epileptic women were followed prenatally and perinatally. Placentas from all were investigated morphologically and in(More)
To find out whether arene oxide metabolites of phenytoin and a genetic defect in arene oxide detoxification contribute to susceptibility to phenytoin-induced birth defects, lymphocytes from 24 children exposed to phenytoin throughout gestation and from their families were challenged in a blind protocol with phenytoin metabolites generated by a murine(More)