Document Detail


The teratogenic risk of antiepileptic drug polytherapy.
MedLine Citation:
PMID:  19817810     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To compare the risks of fetal malformation during pregnancy associated with antiepileptic drug (AED) polytherapy and monotherapy.
METHODS: Statistical analysis of malformation rate and antiepileptic drug exposure data from the Australian Register of Antiepileptic Drugs in Pregnancy, and from the literature.
RESULTS: The calculated relative risk (RR) value for AED polytherapy compared with monotherapy was below 1.0 in only 3 of 14 literature publications. In the register, at 1 year postnatally there were fetal malformations in 5.32% of 282 AED polytherapy pregnancies, and in 7.84% of 791 AED monotherapy pregnancies, an RR of 0.68 [95% confidence interval (CI) 0.39-1.17). For pregnancies exposed to valproate, the RR of fetal malformation (0.39, 95% CI 0.20-0.89) was lower in polytherapy (7.26%) than in monotherapy (17.9%); the difference did not depend on valproate dosage. The RR values for fetal malformation were not significantly different for AED polytherapy and monotherapy when valproate was not involved. Logistic regression suggested that coadministration of lamotrigine may have reduced the malformation risk from valproate.
DISCUSSION: The fetal hazard of AED polytherapy relative to monotherapy may depend more on the degree of exposure to valproate than on the fact of polytherapy per se. Coadministration with lamotrigine may lower the fetal risk of valproate therapy.
Authors:
Frank J E Vajda; Alison A Hitchcock; Janet Graham; Terence J O'Brien; Cecilie M Lander; Mervyn J Eadie
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2009-10-08
Journal Detail:
Title:  Epilepsia     Volume:  51     ISSN:  1528-1167     ISO Abbreviation:  Epilepsia     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-06-11     Completed Date:  2010-06-29     Revised Date:  2013-08-21    
Medline Journal Info:
Nlm Unique ID:  2983306R     Medline TA:  Epilepsia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  805-10     Citation Subset:  IM    
Affiliation:
Department of Medicine and Neurosciences, Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria, Australia. perucca@unipv.it
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Drug-Induced / epidemiology,  etiology*
Anticonvulsants / adverse effects*,  therapeutic use
Australia / epidemiology
Drug Therapy, Combination / adverse effects
Female
Fetal Diseases
Fetus / abnormalities*
Humans
Infant, Newborn
Logistic Models
Maternal-Fetal Exchange
Pregnancy
Pregnancy Complications / drug therapy*,  epidemiology
Registries / statistics & numerical data
Risk
Risk Factors
Teratogens
Triazines / adverse effects
Valproic Acid / adverse effects
Chemical
Reg. No./Substance:
0/Anticonvulsants; 0/Teratogens; 0/Triazines; 99-66-1/Valproic Acid; U3H27498KS/lamotrigine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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