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The teratogenic risk of antiepileptic drug polytherapy
Author(s) -
Vajda Frank J. E.,
Hitchcock Alison A.,
Graham Janet,
O’Brien Terence J.,
Lander Cecilie M.,
Eadie Mervyn J.
Publication year - 2010
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2009.02336.x
Subject(s) - lamotrigine , medicine , pregnancy , drugs in pregnancy , relative risk , anticonvulsant , antiepileptic drug , fetus , carbamazepine , obstetrics , epilepsy , pediatrics , anesthesia , confidence interval , psychiatry , genetics , biology
Summary 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.