AED Therapy & Pregnancy
It is estimated that 6.1 per 1,000 pregnancies are among women with epilepsy. During pregnancy, seizures are the most common major neurological disorder requiring continuous treatment. It is known that offspring of women taking anti-seizure medications drugs (AEDs), including phenytoin, carbamazepine, and sodium valproate, are at higher risk of congenital malformation or developmental delay.
Dr. David Lloyd and colleagues at the Department of Neonatal Medicine, Aberdeen Maternity Hospital (Aberdeen, Scotland) investigated the general health and neurodevelopment of 293 children borne of 149 women taking AEDs in the greater Aberdeen area between 1976 and 2000. Of these children, 38 were not exposed to AEDs because their mothers either were not taking AEDs or had not been diagnosed with epilepsy at the time.
The researchers conclude that the risk of congenital malformation or developmental delay in their offspring is tripled by AED therapy during pregnancy.
The data show that 31% of children exposed to these AEDs had either major malformations or developmental delay: 52% had facial dysmorphism (compared with 25% of children who were not exposed); 31% had childhood medical problems (compared with 13% of non-exposed siblings); and 20% had behavioural disorders (compared with 5% of non-exposed siblings). Of infants exposed to AEDs, 20% presented symptoms of neonatal withdrawal, including feeding difficulties, low blood glucose levels, and seizures. Excluding children from families with a history of developmental delay, 19% of exposed children had such problems (compared with 3% of non-exposed siblings). Hernia was more common, and rates of cleft palate, heart disease, hip dislocation, and abnormal genital development, were 3-times more common among the children exposed to AEDs. Joint laxity and behavioural disorders were associated with exposure to sodium valproate and carbamazepine. Although developmental disorders may have a multifactorial etiology, monotheraly with carbamazepine, phenytoin and valproate was associated with a "substantial risk of developmental delay, even when possible genetic factors are excluded". A dose/response effect was shown for carbamazepine and developmental delay.
Despite the teratogenic risk, many women must continue to take AEDs during pregnancy. The researchers point out that the only alternative includes the development of safer drugs, and call for further research into susceptibility factors, and into the impairment of mother-child interaction in early years (because of maternal epilepsy or its treatment). They advise appropriate counselling and medical management women living with epilepsy. The study also also shows a higher frequency of later childhood complications associated with maternal epilepsy and its treatment.
Sources
Journal of Medical Genetics 2002;39:251-9. "Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth"
http://jmg.bmjjournals.com/cgi/content/abstract/39/4/251
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