Antiepileptic drugs and pregnancy outcomes

The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy (WWE) require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs (AEDs) is a risk that needs to be carefully addressed. Antiepileptic medications are also used to treat an ever broadening range of medical conditions such as bipolar disorder, migraine prophylaxis, cancer, and neuropathic pain. Despite the fact that the majority of pregnancies of WWE who are receiving pharmacological treatment are normal, studies have demonstrated that the risk of having a pregnancy complicated by a major congenital malformation is doubled when comparing the risk of untreated pregnancies. Furthermore, when AEDs are used in polytherapy regimens, the risk is tripled, especially when valproic acid (VPA) is included. However, it should be noted that the risks are specific for each anticonvulsant drug. Some investigations have suggested that the risk of teratogenicity is increased in a dose-dependent manner. More recent studies have reported that in utero exposure to AEDs can have detrimental effects on the cognitive functions and language skills in later stages of life. In fact, the FDA just issued a safety announcement on the impact of VPA on cognition (Safety Announcement 6-30-2011). The purpose of this document is to review the most commonly used compounds in the treatment of WWE, and to provide information on the latest experimental and human epidemiological studies of the effects of AEDs in the exposed embryos.