Levetiracetam: more evidence of safety in pregnancy.

Commentary In utero exposure to first-generation antiepileptic drugs (AEDs) has been shown to increase the risk of congenital malforma-tions and cognitive deficits (1). The risk of major congenital malformations with AED exposure is estimated to be between 4 and 9 percent, compared with the background risk of 1 to 2 percent (2). Prenatal exposure to different older-generation AEDs has been associated with different malformations. For example, the risk of spina bifida increases with exposure to valproate, digit hypoplasia with phenytoin, oral clefts with phenobarbital, and neural tube defects with carbamazepine (3). Moreover, recent data have suggested that fetal exposure to valproate can increase the risk of autism (4) and can affect the child's cognitive abilities (1). However, until recently, data on the safety of newer-generation AEDs have been limited, except for lamotrigine (5). Indeed, for quite a few years, lamotrigine has been increasingly prescribed for women with epilepsy who are of childbearing age, while data on other new AEDs, especially levetiracetam, have been accumulating. Levetiracetam is approved as an add-on treatment of myoclonic, primary generalized, and partial-onset seizures with or without secondary generalization. Its pharmacokinetic attributes have facilitated its wide clinical use. For example, levetiracetam has linear pharmacokinetics and rapid onset of action, is totally excreted by the kidneys, does not interact with other drugs, can be loaded intravenously or orally (6), is weight neutral, has no cognitive side effects, and does not require blood-level monitoring. These attributes have made levetiracetam a preferable first line AED treatment for many physicians despite its indication as adjunctive therapy in the United States. Thus, it is of great importance to assess the safety of levetiracetam in pregnancy. Mawhinney et al. recently published important data about the safety of levetiracetam during pregnancy from the UK and Ireland Epilepsy and Pregnancy Registers, which complement other reports published since 2010 (Table). The authors collected outcome data on 671 women who became pregnant while receiving levetiracetam as monotherapy (304 pregnancies) or as part of AED polytherapy (367 pregnancies). They did not record serum AED levels or smoking and alcohol use as part of this study. In the monotherapy group, there were two cases with major congenital malformations (0.7%; 95% confidence interval [CI], 0. OBJECTIVES: Levetiracetam is a broad-spectrum antiepileptic drug (AED) which is currently licensed in the United States and the United Kingdom and Ireland for use as adjunctive treatment of focal-onset seizures and myoclonic seizures or …