Effect of prenatal phenytoin administration on postnatal development of the rat: A behavioral teratology study

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Abstract
Adult pregnant Wistar rats were treated with phenytoin (100 mg/kg) orally from day 7 to 19 of pregnancy, and a control group was pair-fed during the whole treatment period. Within 24 hours after parturition, the offspring were culled to six to eight per litter and reared by fostering or cross-fostering. The physical and behavioral development of the offspring was observed up to 90 days of age. There was a reduced survival of the offspring and a reduction in body weight which persisted to the end of the experiment, though both of these effects could be reduced by cross-fostering. Certain neurological defects were also seen in the prenatal phenytoin group. For example, there was a delay of up to 15 days in the development of the dynamic righting reflex, a decrease in ability of offspring to stay on a rotating rod, and a decrease in ability to walk along elevated parallel rods. There seemed also to be some loss of cliff avoidance. However, there was no change in the development of crawling and walking activities at 9–21 days of age, and no important changes were observed in a head dipping test or in a conditioned avoidance test at 26–34 days. There was a significant decrease in brain weight of the treated group at age 3 days which remained significantly lower than the controls even at 90 days, but no change in the brain/body weight ratio. There was no difference in cerebellar DNA content.