Women with epilepsy planning pregnancy: we can improve outcomes by improving care.

Commentary This article is one of many reporting the outcome of the NEAD (Neurodevelopmental Effects of Antiepileptic Drugs) study, a major and important prospective evaluation of women receiving antiepileptic drugs (AEDs) during pregnancy. Epilepsy is a chronic condition that occurs throughout the lifespan. It is also a condition that can be life threatening if left untreated; typically, treatment consists of chronic antiepileptic drug (AED) therapy. All these factors contribute to the fact that many women with epilepsy will be receiving AEDs throughout their childbearing years. There has been a keen desire to protect the smallest and most vulnerable population exposed to AEDs; namely, children as yet unborn, whose mothers are receiving these drugs. As early as the 1970s, studies warned of the potential dangers of in utero exposure to AEDs. By the 1980s, physicians were being warned of the dangers of AEDs such as valproate, phenobarbital, carbamazepine and phenytoin (1). Recent pregnancy registries, which are more carefully designed than previous versions, use prospective observation and attention to confounders and have eased some earlier concerns (for BACKGROUND: Many women of childbearing potential take antiepileptic drugs, but the cognitive effects of fetal exposure are uncertain. We aimed to assess effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age. METHODS: In this prospective, observational, assessor-masked, multicentre study, we enrolled pregnant women with epilepsy on antiepileptic drug monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) between October, 1999, and February, 2004, at 25 epilepsy centres in the UK and the USA. Our primary outcome was intelligence quotient (IQ) at 6 years of age (age-6 IQ) in all children, assessed with linear regression adjusted for maternal IQ, antiepileptic drug type, standardised dose, gestational birth age, and use of periconceptional folate. We also assessed multiple cognitive domains and compared findings with outcomes at younger ages. This study is registered with ClinicalTrials.gov, number NCT00021866. FINDINGS: We included 305 mothers and 311 children (six twin pairs) in the primary analysis. 224 children completed 6 years of follow-up (6-year-completer sample). Multivari-ate analysis of all children showed that age-6 IQ was lower after exposure to valproate p=0·0006). Children exposed to valproate did poorly on measures of verbal and memory abilities compared with those exposed to the other antiepileptic drugs and on non-verbal and executive functions compared with lamotrigine (but not carbamazepine or phenytoin). High doses of valproate were negatively associated with IQ (r=-0·56, p<0·0001), …