The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs

Abstract

A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research.

Prenatal exposure to antiepileptic drugs and use of primary healthcare during childhood: a population-based cohort study in Denmark

“…Our findings are in accordance with previous studies, which found prenatal valproate exposure to be associated with high risk of poor neurodevelopment in infancy and childhood 33. Furthermore, a higher risk of adverse outcomes in the children has been found for higher doses of valproate exposure 34. We have no explanation for the finding of a higher risk of GP contact for prenatal exposure to low dose, but not high dose, of oxcarbazepine.…”

Association of Prenatal Exposure to Valproate and Other Antiepileptic Drugs With Risk for Attention-Deficit/Hyperactivity Disorder in Offspring

“…For example, we found a possible risk increase associated with carbamazepine and clonazepam, which has not been previously described. 20 , 25 …”

Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study

“…Exposure to epilepsy related factors during pregnancy may further increase the risk of ADHD, over and above familial transmission. Intrauterine exposure to certain antiepileptic drugs has been associated with an increased risk of adverse neurodevelopmental outcomes, whereas evidence for a similar risk linked to seizures during pregnancy is less clear (39). Results have also been interpreted as suggestive of maternal-specific genetic transmission, however there is currently only limited evidence for such a parent-of-origin effect (40).…”