RT Journal Article
SR Electronic
T1 Comparative safety of antiepileptic drugs during pregnancy
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 1692
OP 1699
DO 10.1212/WNL.0b013e3182574f39
VO 78
IS 21
A1 S. Hernández-Díaz
A1 C.R. Smith
A1 A. Shen
A1 R. Mittendorf
A1 W.A. Hauser
A1 M. Yerby
A1 L.B. Holmes
A1 For the North American AED Pregnancy Registry
YR 2012
UL http://n.neurology.org/content/78/21/1692.abstract
AB Objective: To assess the safety of the newer antiepileptic drugs (AEDs) during pregnancy. Methods: The study population was pregnant women who enrolled in the North American AED Pregnancy Registry between 1997 and 2011. Data on AED use and maternal characteristics were collected through phone interviews at enrollment, at 7 months' gestation, and postpartum. Malformations were confirmed by medical records. The risk of major malformations was calculated among infants exposed to specific AEDs in monotherapy during the first trimester of pregnancy and among an unexposed group. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with logistic regression. Results: The risk of major malformations was 9.3% (30 of 323) for valproate, 5.5% (11 of 199) for phenobarbital, 4.2% (15 of 359) for topiramate, 3.0% (31 of 1.033) for carbamazepine, 2.9% (12 of 416) for phenytoin, 2.4% (11 of 450) for levetiracetam, and 2.0% (31 of 1,562) for lamotrigine. Compared with lamotrigine, the RR was 5.1 (95% CI 3.0–8.5) for valproate, 2.9 (1.4–5.8) for phenobarbital, and 2.2 (1.2–4.0) for topiramate. The proportion of women with epilepsy who had seizures during pregnancy ranged from 23% for valproate to 31% for lamotrigine. Valproate was associated with a higher risk of neural tube defects, hypospadias, cardiac defects, and oral clefts and phenobarbital with a higher risk of cardiac defects and oral clefts; 5 infants exposed to topiramate (1.4%) had a cleft lip. Conclusions: AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDs such as lamotrigine and levetiracetam. Topiramate was associated with an increased risk of cleft lip compared with that of a reference population. AED=antiepileptic drug; CI=confidence interval; RR=relative risk