This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective: To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs).
Methods: The EURAP registry is an observational international cohort study primarily designed to determine the risk of major congenital malformations (MCMs) after prenatal AED exposure. Using EURAP data, we prospectively monitored pregnancies exposed to the 6 most common AED monotherapies and to polytherapy. Intrauterine death (spontaneous abortion and stillbirth combined) was the primary endpoint.
Results: Of 7,055 pregnancies exposed to monotherapy with lamotrigine (n = 1,910), carbamazepine (n = 1,713), valproic acid (n = 1,171), levetiracetam (n = 324), oxcarbazepine (n = 262), or phenobarbital (n = 260), and to polytherapy (n = 1,415), 632 ended in intrauterine deaths (592 spontaneous abortions and 40 stillbirths). Rates of intrauterine death were similar across the different monotherapies (8.2%; 95% confidence interval [CI] 7.5%–8.9%), higher with polytherapy (12.1%; 95% CI 10.5%–13.9%), but showed no relationship with AED dose in monotherapy at conception. Multivariable analysis including 11 covariates in addition to the different AED exposures showed that the risk was greater with polytherapy vs monotherapy (risk ratio [RR] 1.38; 95% CI 1.14–1.66), parental history of MCMs (RR 1.92; 1.20–3.07), maternal age (RR 1.06; 1.04–1.07), and number of previous intrauterine deaths (RR 1.09; 1.00–1.19). The risk was greater with early enrollment and decreased with later gestational week at enrollment (RR 0.84; 0.82–0.86).
Conclusions: The most important risk factors for intrauterine death in pregnancies of women with epilepsy include maternal exposure to AED polytherapy and the presence of MCMs in at least one of the parents.
GLOSSARY
- AED=
- antiepileptic drug;
- CBZ=
- carbamazepine;
- CI=
- confidence interval;
- EURAP=
- International Registry of Antiepileptic Drugs and Pregnancy;
- LTG=
- lamotrigine;
- MCM=
- major congenital malformation;
- RR=
- risk ratio;
- VPA=
- valproic acid
Footnotes
↵* These authors contributed equally to this work.
EURAP Study Group coinvestigators and contributors are listed on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received November 19, 2014.
- Accepted in final form March 20, 2015.
- © 2015 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
More Online
Topics Discussed
Alert Me
Recommended articles
Declining malformation rates with changed antiepileptic drug prescribing
Dose-dependent teratogenicity of valproate in mono- and polytherapy
Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy
Unintended pregnancy, prenatal care, newborn outcomes, and breastfeeding in women with epilepsy