Fetal hydantoin syndrome

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Maternal hydantoin ingestion during pregnancy results in a well defined clinical entity termed "fetal hydantoin syndrome". The clinical characteristics of this syndrome includes growth retardation, and congenital anomalies. Because folic acid is essential for protein synthesis and growth, and since hydantoin interferes with intestinal transport of folic acid, we postulated that part of the fetal hydantoin syndrome may be due to inhibition of placental folic acid by maternal hydantoin. Therefore, we studied in vivo placental folate transport in a well-established model for fetal hydantoin syndrome in the rat...

In a series of experiments, prenatal administration of phenytoin to rats at non-embryotoxic and non-teratogenic doses produced offspring exhibiting large and enduring abnormalities in behavior. Plasma drug concentrations on the last day of exposure in the dams were within the human therapeutic range for anticonvulsant efficacy. The behavioral abnormalities in the offspring were hyperactivity on tests of locomotion (increased pivoting behavior and figure-8 ambulation), but decreased figure-8 rearing. As adults, the phenytoin rats exhibited no impairment in swimming ability in a straight channel, but when placed in a complex water maze showed large increases in errors compared to controls...

Sprague-Dawley rats were gavaged once daily on days 7-18 of gestation with, 100, 150, or 200 mg/kg of phenytoin. Only the highest dose of phenytoin decreased maternal weight during gestation or increased offspring mortality up to weaning. Offspring were evaluated for activity prior to weaning (pivoting and photocell) and afterwards (figure 8, open-field, and hole-board), dynamic righting development, maze learning (Biel maze), and visual discrimination (Y maze), and for startle reaction to both auditory and tactile stimuli...

No abstract text is available yet for this article.

Our recent studies of the teratogenic mechanisms of phenytoin (DPH) and glucocorticoids in mice have indicated that DPH utilizes the anti-inflammatory pathway of glucocorticoids in producing congenital defects, such as cleft palate. This pathway is influenced by H-2 and H-3 histocompatibility-linked genes in the mouse, such that congenic strains have H-2 or H-3 alleles that confer susceptibility to DPH-induced congenital defects, and susceptible H-2 congenic strains have high glucocorticoid receptor levels...

Hydantoin is an anticonvulsant drug with several side effects. A teratogenic potential has been suggested. The fetal hydantoin syndrome is an entity that consists of a broad range of morphologic and developmental disorders in children born of epileptic mothers exposed to hydantoin during pregnancy. We treated a girl in whom onychopathy was a monosymptomatic or mild form of this syndrome.

In a prospective study, 121 children of mothers with epilepsy (study group) and 105 control children were examined in a blinded fashion at age 5 1/2 years for 80 minor physical anomalies, including nine typical features previously reported characteristic of fetal hydantoin syndrome. Of the study group, 106 children had been exposed to antiepileptic drugs (82 to phenytoin) during pregnancy; 44 (36%) mothers had had generalized convulsions during pregnancy. One hundred fourteen mothers and 87 fathers of study group children and 101 mothers and 58 fathers of control children were also examined...

Four siblings are presented with a malformative syndrome. All were born to an epileptic woman treated with phenytoin and valproic acid. A considerable high fetal pathology is found. Perhaps increased teratogenic effects are related with this pharmacological association not previously described.

No abstract text is available yet for this article.

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 hepatic microsomal drug-metabolising system. 14 of the children had a "positive" assay result--ie, a significant increase in cell death associated with phenytoin metabolites...

In an attempt to determine whether and to what extent carbamazepine is teratogenic, we evaluated eight children whom we identified retrospectively as having had prenatal exposure to carbamazepine alone or in combination with a variety of anticonvulsants other than phenytoin. In addition, in a prospective study, we documented the outcome of the pregnancies of 72 women who contacted us early in pregnancy because they were concerned about the potential teratogenicity of carbamazepine. A pattern of malformation, the principal features of which are minor craniofacial defects and fingernail hypoplasia, and of developmental delay was identified in the eight children retrospectively ascertained to have been exposed to carbamazepine in utero; this pattern was subsequently confirmed through the evaluation of 48 children born alive to the women in the prospective study...

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...

A boy with dysplasia/hypoplasia of nails and fingertips is reported. He was born to a woman who had been medicated during pregnancy with hydantoin for epilepsy. The clinical and radiological features of the fetal hydantoin syndrome are described. It is suggested that hydantoinexposed fetuses should be examined by ultrasound and serum folate monitored during pregnancy.

In spite of a large body of literature suggesting that prenatal exposure to hydantoin anticonvulsant drugs can be teratogenic in humans, resulting in offspring with congenital malformations, the wide phenotypic variability of this syndrome has led many clinicians to question its very existence. Because solutions to major teratologic questions may be impossible to find within the constraints of human clinical or epidemiologic investigations, we have developed an animal model for the fetal hydantoin syndrome...

An infant with features of fetal hydantoin syndrome, born to an epileptic mother, was followed from birth to 20 months of age. Physical findings included gum hypertrophy, digitalization of the thumbs, hypoplasia of the distal phalanges and nails, epicanthal folds, pseudohypertelorism, epidermoid cyst, and geographic tongue. Available literature about the disorder is reviewed.

No abstract text is available yet for this article.

Ethanol and hydantoin are both teratogenic drugs of common usage and are associated with specific syndromes. This is a report on two children born to different heavy drinking, mentally abnormal epileptic women, that were also under treatment with 300 mg/day of hydantoin (mother of case 1 on a regular basis and that of case 2 sporadically) during pregnancy. Both infants displayed the syndrome due to both of these drugs. Particularly relevant were failure to thrive, severe mental retardation, microcephaly, blepharophimosis, hypertelorism, and long philtrum...

The well-known teratogenicity of several anticonvulsant medications is associated with an elevated level of oxidative metabolites that are normally eliminated by the enzyme epoxide hydrolase. In this study, we attempted to determine whether infants who are at risk for congenital malformations could be identified prenatally by the measurement of epoxide hydrolase activity. Before fetuses at risk could be identified, it was necessary to measure epoxide hydrolase activity in a randomly selected sample of amniocytes from 100 pregnant women...