Maternal Use of Antiepileptic Drugs and the Risk of Major Congenital Malformations: A Joint European Prospective Study of Human Teratogenesis Associated with Maternal Epilepsy

Abstract

Summary: Purpose:To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and polytherapy.Methods: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy and for 158 children of unexposed control pregnancies.Results: Overall, when comparing a subgroup of 192 children exposed to AED with 158 children of matched nonepileptic controls, there was an increased risk of major congenital malformations (MCA) in children exposed to AED during gestation [relative risk (RR) 2.3; 95% confidence interval (CI): 1.2-4.71. A significant increase in risk was found for children exposed to valproate (VPA) (RR 4.9; 95% CI: 1.6-15.0) or carbamazepine (CBZ) (RR 4.9; 95% CI: 1.3-18.0) in monotherapy. When comparing different AED regimens during all 1,221 pregnancies, risks of MCA were significantly increased for the combination of phenobarbital (PB) and ethosuximide (RR 9.8; 95% CI: 1.4-67.3) and the combination of phenytoin, PB, CBZ, and VPA (RR 11.0; 95% CI: 2.1-57.6). Offspring of mothers using >1,000 mg VPNday were at a significantly increased risk of MCA, especially neural tube defects, compared to offspring exposed G600 mg VPNday (RR 6.8; 95% CI: 1.4-32.7). No difference in risk of MCA was found between the offspring exposed to 601-1,000 mg/day and G600 mg/day.Conclusions: This reanalysis shows that VPA is consistently associated with an increased risk of MCA in babies born to mothers with epilepsy. Significant associations were also observed with CBZ. Larger prospective population-based studies are needed to evaluate the risks of many other less frequently prescribed treatment regimens, including newly marketed AEDs.

Anticonvulsant effect of the ethanol extract of Caesalpiniapulcherrima (L.) Sw., Fabaceae, leaves

“…are used as potent antiepileptic agents, but they are not free from marked side effects. Approximately 30% of the patients continue to have seizures with current antiepileptic drug therapy (Smith & Bleck, 1991;Samren et al, 1997;Poole et al, 2000). Hence, there is a need to address a potent alternative Braz.…”

Anticonvulsant Activity of Carissa carandas Linn. Root Extract in Experimental Mice

“…The current therapy of epilepsy with modern antiepileptic drugs is associated with side effects, dose-related and chronic toxicity, as well as teratogenic effects, and approximately 30% of the patients continue to have seizures with current antiepileptic drugs therapy [2][3][4] . Traditional systems of medicine are popular in developing countries and up to 80% of the population relies on traditional medicines or folk remedies for their primary health care need 5 .…”

Managing epilepsy in pregnancy

“…The effect of dose for sodium valproate in particular, may be of clinical importance in determining the size of the teratogenic risk, with the highest risk in those taking over 1000 mg per day [6,7,10].…”

“…Although there have been studies from as early as the 1960s suggesting links between major congenital malformations (MCMs) and the use of AEDs during pregnancy [6][7][8][9], the advent of the large prospective, albeit observational, epilepsy and pregnancy registries have recently added much information on the relative risks associated with the individual AEDs [5,[10][11][12][13][14][15][16][17]. The key to a successful outcome in this respect is knowledge of the individual risks and imparting these risks through preconceptual counseling, enabling women to make informed choices and allowing any alteration in therapy to be made prior to pregnancy.…”