Annals of Neurology

Fetal Growth and Premature Delivery in Pregnant Women on Anti-epileptic Drugs

Sonia Hernandez-Diaz, Thomas F McElrath, Page B Pennell, W. Allen Hauser, Mark Yerby, Lewis B Holmes for the North American AED (Antiepileptic Drug) Pregnancy Registry

Annals of Neurology Accepted manuscript online: 30 August 2017

Objective: To evaluate the effects of epilepsy and antiepileptic drugs (AED) use during pregnancy on fetal growth and preterm delivery.

Methods: This study included singleton liveborns born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (less than 37 weeks) and small-for-gestational-age (SGA) among infants exposed prenatally to AED when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariable log-binomial regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI).

Results: The study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR 1.5, 95%CI: 1.0-2.1) and 10.5% for AED-WWOE (RR 1.5: 1.0-2.4). Prenatal exposure to AED in WWE and WWOE was associated with a mean lower birth weight of 110 and 136 grams, respectively, as compared to no-AED WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR 2.0: 1.3-3.0) and 11.0% for AED-WWOE (RR 1.9: 1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate.

Interpretation: Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. This article is protected by copyright. All rights reserved.