Phenytoin, a drug frequently used in the treatment of pregnant epileptic women, has been shown to have an embryotoxic and dysmorphogenic potential in rodents. As in children born to epileptic women, closure of the palate was found to be impaired in mice. In addition, characteristic anomalies such as necrosis, leg anomalies and malformations of the gonads were also observed. In the rat, only a small number of gross malformations were seen, but 20 to 30 % of the surviving fetuses had hydronephrosis.
Analysis of recent clinical reports has revealed a good correlation between the experimental findings and the high incidence of congenital malformations in epileptics who received anticonvulsant therapy during pregnancy. The frequency of congenital malformations in children born to treated mothers has been shown to be 2 to 3 times higher than in children born to normal mothers.
It seems therefore, that phenytoin is likely to have a dysmorphogenic potential and should be avoided in pregnant epileptic women. The mechanism of the embryotoxic and dysmorphogenic action of phenytoin is still unknown. Attempts to prevent the embryotoxic and dysmorphogenic action of the drug in rodents by administering folic acid supplements were unsuccessful. More work is necessary to elucidate this problem.
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