In utero antiepileptic drug exposure: fetal death and malformations.

Full Abstract

BACKGROUND: Pregnancy outcomes following in utero exposure to antiepileptic drugs (AEDs) are uncertain, limiting an evidenced-based approach. OBJECTIVE: To determine if fetal outcomes vary as a function of different in utero AED exposures. METHODS: This ongoing prospective observational study across 25 epilepsy centers in the USA and UK enrolled pregnant women with epilepsy from October 1999 to February 2004 to determine if differential long-term cognitive and behavioral neurodevelopmental effects exist across the four most commonly used AEDs. This initial report focuses on the incidence of serious adverse outcomes including major congenital malformations (which could be attributable to AEDs) or fetal death. A total of 333 mother/child pairs were analyzed for monotherapy exposures: carbamazepine (n = 110), lamotrigine (n = 98), phenytoin (n = 56), and valproate (n = 69). RESULTS: Response frequencies of pregnancies resulting in serious adverse outcomes for each AED were as follows: carbamazepine 8.2%, lamotrigine 1.0%, phenytoin 10.7%, and valproate 20.3%. Distribution of serious adverse outcomes differed significantly across AEDs and was not explained by factors other than in utero AED exposure. Valproate exhibited a dose-dependent effect. CONCLUSIONS: More adverse outcomes were observed in pregnancies with in utero valproate exposure vs the other antiepileptic drugs (AEDs). These results combined with several recent studies provide strong evidence that valproate poses the highest risk to the fetus. For women who fail other AEDs and require valproate, the dose should be limited if possible.

Author information

Author/s: Meador, K J (KJ); Baker, G A (GA); Finnell, R H (RH); Kalayjian, L A (LA); Liporace, J D (JD); Loring, D W (DW); Mawer, G (G); Pennell, P B (PB); Smith, J C (JC); Wolff, M C (MC); NEAD Study Group;

Affiliation: Department of Neurology, University of Florida, Gainesville 32610, USA. kimford.meador(-atsign-)neurology.ufl.edu

Grants: 1 R01050659 (Agency:PHS HHS) ; 2 R01 NS038455 (Agency:NINDS NIH HHS) ; R01 NS038455-07 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Controlled Clinical Trial; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Neurology (Neurology), published in United States. (Language: eng)

Reference: 2006-Aug; vol 67 (issue 3) : pp 407-12

Dates: Created 2006/08/08; Completed 2006/09/06; Revised 2008/11/20;

PMID: 16894099, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Expert Rev Neurother. 2006 Dec;6(12):1785-7. (PMID: 17181425)

CommentIn: Neurology. 2006 Aug 8;67(3):E6-7. (PMID: 16894091)

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Abnormalities, Drug-Induced - etiology
Adult
Anticonvulsants - administration & dosage; adverse effects
Carbamazepine - adverse effects
Cognition - drug effects
Female
Fetal Death - chemically induced
Humans

Phenytoin - adverse effects
Pregnancy
Pregnancy Complications - chemically induced
Pregnancy Outcome
Prospective Studies
Triazines - adverse effects
Uterus - drug effects
Valproic Acid - adverse effects

Associated Chemicals: Anticonvulsants (0) ; Triazines (0) ; Carbamazepine (298-46-4) ; Phenytoin (57-41-0) ; lamotrigine (84057-84-1) ; Valproic Acid (99-66-1)

These are the highest related articles currently in the database: