Teratogenic and neurodevelopmental effects of antiepileptic drugs
Sodium valproate increases the risk of spina bifida up to ten-fold (0.2 to 2%) and is associated with other serious malformations. Evidence also shows that children of mothers taking sodium valproate during pregnancy have lower intelligence and greater risk of learning difficulties than those exposed to other antiepileptic drugs. These effects are dose-related—at daily doses less than 600 to 800 mg, sodium valproate's teratogenicity and effect on cognition are similar to other antiepileptic drugs. However, a controlled cohort study1 showed that even at doses less than 800 mg daily, maternal valproate therapy was associated with an increased need for educational intervention. During pregnancy, avoid doses of sodium valproate more than 600 mg daily if possible.
Valproate is often the only drug that controls genetic (idiopathic) generalised epilepsies, including juvenile myoclonic epilepsy. Because low doses are usually sufficient, valproate therapy can continue in a female with genetic (idiopathic) generalised epilepsy planning a pregnancy, without increasing the risk of teratogenicity and neurodevelopmental adverse effects to an unacceptable level. The harms and benefits of valproate and its alternatives must be discussed with the patient. Juvenile myoclonic epilepsy is a long-lasting condition—withdrawal of sodium valproate in anticipation of pregnancy can be hazardous, because seizures are likely to recur.
For a discussion of the potential risk of neurodevelopmental disorders in children born to males taking sodium valproate, see Sodium valproate use in males of reproductive potential.
Phenytoin increases the risk of congenital abnormalities.
Lamotrigine and carbamazepine are associated with a slight and dose-related increased risk of congenital abnormalities.
Topiramate may increase the risk of congenital malformations.
Many newer antiepileptic drugs have not been taken as monotherapy in enough pregnancies to establish teratogenic risk. The limited data available for levetiracetam suggest it has a low risk of teratogenicity.