Antiepileptic drugs during pregnancy: What is known and which AEDs seem to be safest?

Abstract

SUMMARY Most infants born to women with epilepsy are healthy, but there are increased risks related to in utero antiepileptic drug (AED) exposure and seizures. Emerging data from pregnancy registries and other studies allow us to better balance the anatomic teratogenic and neurodevelopmental effects of AEDs against the need to maintain maternal seizure control. Several large prospective pregnancy registries demonstrate a consistent pattern of increased risk for major congenital malformations (MCMs) with valproate (VPA) use as monotherapy, compared to nonexposed populations and to other AEDs used in monotherapy. AED polytherapy likely increases risk for MCMs, but the risk is more pronounced if VPA is included. Reduced cognitive outcomes have been reported with AED polytherapy, and with use of VPA, phenobarbital (PB), and PHT as monotherapy. Dose-dependent risk has been demonstrated with VPA for MCMs and cognitive consequences. CBZ groups show normal neurodevelopment. Increased clearance of most of the AEDs occurs during pregnancy. Use of therapeutic drug monitoring during pregnancy with LTG reduces the risk for seizure worsening. The consistent findings of increased teratogenic risk for VPA should discourage use of this medication as first-line treatment in women of childbearing age.

Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

“…However, some AEDs are endowed with unfavourable safety profiles, such as hepatotoxicity, toxicity to central nervous system (CNS) and show complex drug/drug interactions (Johannessen Landmark and Patsalos, 2010;Loring et al, 2007;Pennell, 2008). In recent years, pharmaceutical companies have developed new AEDs with improved safety profiles than the previously available ones.…”

Antiepileptic drug use by pregnant women enrolled in Florida Medicaid

“…[4][5][6] The risk of MCMs increases to 4% to 9% after in utero exposure to the first-generation AEDs. 5,7 The percentage of MCMs was reported as 6.5% for phenobarbital, 8 3.7% for phenytoin, 9 and 2.2% for carbamazepine. 10 Valproate has shown a greater risk (6.2%-20.3%) of MCM, 9,[11][12][13] which is 7.3-fold higher than that of nonexposed, and 4-fold higher than in those exposed to other AEDs.…”

Avaliação do ciclo estral, tecido ovariano e uterino e parâmetros fetais de ratas Wistar tratadas com Topiramato

“…Many studies in animals and human have suggested teratogenic effect of TPM, but further investigation is still necessary (PENNEL, 2008;FOUNTAIN, 2009;HERNÁNDEZ-DÍAZ et al, 2012). TPM, gabapentin and leveracetam, newer-generation antiepileptic drugs, do not appear to be major teratogens, but their risks should not be disregarded (MOLGAARD-NIELSEN, HVIID, 2011).…”