Preventing Teratogenicity in Women with Epilepsy

Abstract

Over the last 50 years there has been a significant increase in our understanding of the issues faced by women with epilepsy, in both planning and undertaking pregnancy. The risks of teratogenicity associated with antiseizure medications have emerged slowly. The major pregnancy registers have substantially contributed to our knowledge about teratogenic risk associated with the commonly used antiseizure medications. However, there are substantial gaps in our knowledge about the potential risks associated with many third-generation drugs. The remit of the pregnancy registers and the wider research focus has moved beyond anatomical major congenital malformations. Increasingly neurodevelopmental and behavioral abnormalities have been investigated after in utero exposure to antiseizure medications. Public health approaches can help reduce the risk of teratogenicity. However, neurologists still have a vital role in reducing the risk of teratogenicity at an individual level for women attending their clinic. They also have responsibility to ensure that women with epilepsy are aware of the rationale for the different available options.

Lacosamide and pregnancy: Data from spontaneous and solicited reports

“…19 Currently, there are no substantial data available from these registries on outcomes of LCM-exposed pregnancies. 3,4,[20][21][22] According to their latest online report (October 2023), limited data have been published on LCM by the NAAPR, reporting a 0% prevalence of major malformations (95% confidence interval = 0%-5.21%) from LCM monotherapy during the first trimester, based on 88 cases. 23 Pharmacovigilance and safety databases can also provide important information on pregnancy outcomes and risks of congenital malformations for ASM-exposed pregnancies.…”

“…Prospective pregnancy registries, including EURAP, NAAPR, the UK and Ireland Epilepsy and Pregnancy Registers, and the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs, have an important role in assessing the teratogenic risk of ASMs 19 . Currently, there are no substantial data available from these registries on outcomes of LCM‐exposed pregnancies 3,4,20–22 . According to their latest online report (October 2023), limited data have been published on LCM by the NAAPR, reporting a 0% prevalence of major malformations (95% confidence interval = 0%–5.21%) from LCM monotherapy during the first trimester, based on 88 cases 23…”

“…3 Higher rates of malformations have generally been reported with ASM polytherapy compared with monotherapy. [3][4][5] However, this is dependent on the individual ASM used, as different monotherapies carry different risks 6 ; on the doses used, as some ASMs carry dose-dependent risks; and on the particular combination of ASMs used for patients on polytherapy. Some of the common major congenital malformations from ASM exposure during pregnancy include cleft lip and palate, heart defects, urogenital abnormalities, and neural tube defects.…”

“…Less is known about teratogenicity risks with newer ASMs. Prenatal exposure to certain ASMs has also been linked with poorer child neurodevelopment and other adverse outcomes, including low birth weight and being small for gestational age 3,6 . An observational study of ASM‐exposed pregnancies showed that lacosamide (LCM) was the most commonly used newer ASM 7 ; however, data are limited on pregnancy outcomes among patients taking LCM, particularly when taken as monotherapy.…”

“…Some of the common major congenital malformations from ASM exposure during pregnancy include cleft lip and palate, heart defects, urogenital abnormalities, and neural tube defects. 2,3 For ASM monotherapies used during pregnancy, statistically significant associations have been reported between valproate and spina bifida, lamotrigine and cardiac defects, and carbamazepine and urogenital anomalies. 4 Less is known about teratogenicity risks with newer ASMs.…”