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Excerpt
It is recognized that both malformations and delayed development are risks for children exposed in utero to anticonvulsants. This study sought to discern the pattern of abnormalities in 57 children with various fetal anticonvulsant syndromes, the great majority of whom were accessed through the Fetal Anticonvulsant Syndrome Association. The children, from 38 families, included 32 boys and 25 girls averaging 6 1/2 years of age. Karyotyping was normal in all 51 children analyzed, and in 48 who had DNA studies, no fragile X mutation was identified. Epilepsy was idiopathic in 31 of 37 diagnosed mothers. In 15 instances there was a family history of epilepsy. Thirty-four children had been exposed to valproate alone, and 12 had been exposed to other agents in addition to valproate. In only four pregnancies was phenytoin or carbamazepine alone administered. Anticonvulsants always had been taken in the first trimester, and in all but six cases they were continued throughout pregnancy.
One-third of children had glue ear, and 70% had joint laxity, both newly noted associations. There were no external or middle ear malformations, but two infants had subglottic stenosis (one possibly because of prolonged ventilation). No cleft palate was found, but ocular abnormalities, particularly myopia, astigmatism, and strabismus, were common. Children exposed to carbamazepine or phenytoin tended to have a wide mouth and prominent eyelashes. Developmental delay or learning difficulty was found in 77% of children, and three-fourths of those at school age were receiving support or attending a special school. Major behavioral problems resembling autism were not infrequent. More than three-fourths of children older than 2 years required speech therapy; in many cases there was both expressive and receptive delay. Gross motor delay was a problem in 56% of cases, and many children had problems in coordination. Only four children were developing normally and had no behavioral problems. Nearly 40% of the group exhibited hyperactivity, trouble concentrating, or both. In the 33 families that could be appraised, there were 54 affected and 17 unaffected children. Allowing for incomplete ascertainment, the estimated risk of recurrence was 55%.
Delayed speech, myopia, autistic behaviors, and hyperactivity all are common findings in children who were exposed in utero to anticonvulsants. The high risk of recurrence, exceeding 50%, may represent a genetic predisposition.
(Epilepsy affects approximately 1.6 million Americans; of these, roughly 400,000 are women of childbearing age, which represents about 0.5% of deliveries in the United States. Compared with infants of mothers without epilepsy, infants of epileptic mothers treated with anticonvulsants have two to three times the risk of defects that might be due to genetic and/or anticonvulsant therapy: spina bifida, cleft lip, cleft palate, and heart and urogenital defects. All anticonvulsants have an increased risk for fetal malformation; therefore, the safest management strategy for epilepsy in pregnancy is to maintain the patient on the lowest protective dose of whatever drug has historically worked for her. Conflict remains as to which anticonvulsant is the most teratogenic. The animal data on newer agents such as gabapentin and lamotrigine seem encouraging, but there is insufficient human experience to know the effects of these agents on mother and fetus. Developmental delay, autistic behavior, and learning problems have been documented in children with fetal anticonvulsant syndromes, but the frequency is controversial.
