Withdrawal of valproic acid during pregnancy in women with epilepsy

Abstract

Objective: to analyze the course of epilepsy in women after withdrawal of valproic acid (VA) during pregnancy. Material and methods. The study was conducted in the Center of paroxysmal conditions of Vitebsk Regional Clinical Diagnostic Center. The study included 58 women with epilepsy who gave birth in 2018–2020; a prospective analysis was also done using the Russian Register of Pregnancy and Epilepsy (RRPE) data. The study group included 112 women with epilepsy who were taking VA at the time of conception. In 16.1% of cases (n=18 out of 112) VA was discontinued in the first trimester (withdrawal group), in 83.9% of cases (n=94) VA therapy was continued. We analyzed the frequency of epileptic seizures depending on the use of VA during pregnancy for each trimester and for the entire pregnancy as a whole. Results. According to the Vitebsk Regional Clinical Diagnostic Center, 32 out of 58 (55.2%) patients took VA, all of them had generalized tonicclonic seizures in the structure of epileptic seizures. Seven of 32 patients (21.8%) received VA at a dose of <700 mg/day; 10 (31.3%) – 700–1000 mg/day, 15 (46.9%) – 1000–1500 mg/day. VA was canceled in two cases, in one of them a tonic-clonic seizure developed. According to the RRPE data, in 9 out of 65 (13.8%) cases VA was discontinued in the first trimester (withdrawal group), in 55 out of 65 (84.6%) cases the therapy with VA was continued, and in one case - the drug was changed. The number of women with epilepsy taking VA during pregnancy has decreased from 38.9% (275 out of 707) in 2017 to 24.9% (112 out of 450) by January 2023. According to the RRPE, the majority of patients continued VA therapy during gestation if pregnancy occurred while taking this antiepileptic drug. A high fraction of prescribing VA in patients with focal epilepsy was registered – 58.9% (66 out of 112) with continuation of VA therapy during pregnancy in 61.7% of cases. Among patients with generalized form of epilepsy, VA drugs were taken by 36.6% (41 out of 112). The majority of patients (35.1%; 33 of 94) continued to take VA throughout the entire gestation. About half of the patients took VA at a dose of >700 mg/day in the first trimester and throughout gestation. There were no statistically significant differences in the frequency of tonic-clonic and other types of epileptic seizures during pregnancy in patients who canceled VA and continued therapy, according to RRPE. Conclusion. Further prospective and controlled studies with large sample sizes are needed to determine the most effective and safe strategy for VA withdrawal.

Keywords

• valproic acid
• pregnancy
• epilepsy
• antiepileptic drugs
• generalized tonic-clonic seizures