Risks of In Utero Exposure to Valproate
Year: 2013
Type: editorial
Abstract: Antiepileptic medications are among the most commonly prescribed teratogenic drugs among women of childbearing potential.However, determining the exact number of women of childbearing age exposed to antiepileptic medications is difficult.One estimate, based on data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, suggests that from 2005-2007, there were 7 900 000 annual prescriptions for antiepileptic medications among girls and women aged 15 to 44 years, including 926 000 for valproate (12% of all antiepileptic medication prescriptions, irrespective of indication). 1 For those treated for epilepsy or seizures, there were 989 000 annual prescriptions, of which 177 000 were for valproate (18% of all prescriptions of antiepileptic medications for epilepsy or seizures). 1ter multiple pregnancy registries confirmed an increased risk of major congenital malformations following fetal valproate exposure, the American Academy of Neurology recommended avoidance of valproate during pregnancy whenever possible. 2In addition to the risk of congenital malformations, fetal valproate exposure has been associated with reduced cognitive abilities, 2,3 which led the US Food and Drug Administration to issue a warning about this risk. 4Further, several studies have suggested that fetal valproate exposure may increase the risk of autism, [5][6][7][8] although the strength of this association has been unclear because of the methodological limitations of those reports.In this issue of JAMA, Christensen and colleagues 9 report the results of a population-based study of 655 615 children born in Denmark from 1996 to 2006.Among these children, 5437 were identified as having autism spectrum disorder, including 2067 with childhood autism.When examining the relationship of fetal valproate exposure to developmental outcome, increased risks of autism spectrum disorder (absolute risk, 4.42%; adjusted hazard ratio, 2.9 [95% CI, 1.7-4.9])and childhood autism (absolute risk, 2.50%; adjusted hazard ratio, 5.2 [95% CI, 2.7-10.0])were observed among the 508 children exposed to valproate.The authors concluded that maternal use of valproate during pregnancy was associated with significantly increased risks of autism spectrum disorder and childhood autism in the offspring and that those risks remained significant after restricting the analysis to children without congenital malformations and after adjusting for parental psychiatric disease and epilepsy.This important information should be presented during the counseling of women of childbearing potential when discussing treatment options that include valproate.The investigation by Christensen et al 9 provides the strongest evidence to date that fetal valproate exposure is associated with increased risks of autism and autism spectrum disorder.Strengths of the study include that it was population-based, provided follow-up for
Source: JAMA
Authors: Kimford J. Meador, David W. Loring
Institution: Emory University
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2032734350