We evaluated the causality of the association between intrauterine exposure to
phenytoin and postnatal
neuroblastoma using an in vitro lymphocyte toxicity assay for
phenytoin-induced reactions in an unusual sibship. In addition, we investigated intrauterine
phenytoin exposure in a case series of infants and children with
neuroblastoma diagnosed over 17 years at our center. The response of lymphocytes from our index case with
neuroblastoma exposed in utero to
phenytoin was within the normal range, whereas the mother and a sibling with
fetal hydantoin syndrome (FHS) exhibited an intermediate toxicity. None of the 188 cases of childhood
neuroblastoma diagnosed between 1969 and 1988 had been exposed in utero to
phenytoin, indicating that, statistically, the
drug cannot be associated with
neuroblastoma in more than two cases with this
malignancy in our cohort, or in 1.5% of all cases of
neuroblastoma. Although our data do not suggest an association between
phenytoin in pregnancy and postnatal
neuroblastoma, it is still possible that there is an increased risk for
neuroblastoma in children with FHS.