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February 25, 2003

Major malformations in offspring of women with epilepsy

February 25, 2003 issue
60 (4) 575-579


Background: The offspring of women with epilepsy are at an increased risk of major congenital malformations, but the impact of the various contributing factors remains unresolved.
Method: In 1980 through 1998, the authors prospectively followed up 970 pregnancies in women with epilepsy at a single maternity clinic. Of their 979 offspring, 740 were exposed to maternal antiepileptic drugs (AED) during the first trimester of pregnancy and 239 were not exposed. Maternal AED levels and serum folate concentrations were measured at the end of the first trimester. Logistic regression analysis was applied to identify factors associated with the occurrence of major malformations in the fetuses and newborns.
Results: Major malformations were detected in 28 fetuses (3.8%) exposed to maternal AED and in 2 (0.8%) not exposed (p = 0.02). After logistic regression analysis, the occurrence of major malformations was independently associated with use of carbamazepine (adjusted OR 2.5; 95% CI 1.0 to 6.0), use of valproate (4.1; 1.6 to 11), use of oxcarbazepine (10.8; 1.1 to 106), low serum folate concentration (5.8; 1.3 to 27), and low maternal level of education (3.0; 1.3 to 6.8). Major malformations were not associated with seizures during the first trimester (0.6; 0.1 to 2.9).
Conclusions: Major malformations in the offspring of mothers with epilepsy are associated with use of AED during early pregnancy, and also with low serum folate concentrations and a low level of education.

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Information & Authors


Published In

Volume 60Number 4February 25, 2003
Pages: 575-579
PubMed: 12601095

Publication History

Received: July 1, 2002
Accepted: October 11, 2002
Published online: February 25, 2003
Published in print: February 25, 2003


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Affiliations & Disclosures

Erja Kaaja, MSc(pharm)
From the Department of Obstetrics and Gynecology (E. Kaaja and Drs. R. Kaaja and Hiilesmaa), Helsinki University Central Hospital; and Division of Pharmacology and Toxicology (E. Kaaja), Department of Pharmacy, University of Helsinki, Finland.
Risto Kaaja, MD PhD
From the Department of Obstetrics and Gynecology (E. Kaaja and Drs. R. Kaaja and Hiilesmaa), Helsinki University Central Hospital; and Division of Pharmacology and Toxicology (E. Kaaja), Department of Pharmacy, University of Helsinki, Finland.
Vilho Hiilesmaa, MD PhD
From the Department of Obstetrics and Gynecology (E. Kaaja and Drs. R. Kaaja and Hiilesmaa), Helsinki University Central Hospital; and Division of Pharmacology and Toxicology (E. Kaaja), Department of Pharmacy, University of Helsinki, Finland.


Address correspondence and reprint requests to Dr. Vilho Hiilesmaa, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, P.O. Box 140, 00029 HUCH, Finland; e-mail: [email protected]

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