Epilepsy in Pregnancy-Management Principles and Focus on Valproate

• Published in: International journal of molecular sciences Vol. 23; no. 3; p. 1369
• Main Authors: Błaszczyk, Barbara, Miziak, Barbara, Pluta, Ryszard, Czuczwar, Stanisław J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.01.2022; MDPI
• Subjects: Abnormalities, Drug-Induced - drug therapy; Age; Anticonvulsants - therapeutic use; Antiepileptic agents; antiepileptic drugs; Attention Deficit Disorder with Hyperactivity - chemically induced; Attention deficit hyperactivity disorder; Autism; Autism Spectrum Disorder - chemically induced; Birth defects; Cell cycle; Cell differentiation; Childbirth & labor; Children & youth; Congenital defects; Congenital diseases; congenital malformations; Contraindications; Convulsions & seizures; Cytokines; Differentiation (biology); Drug dosages; Drug therapy; Epilepsy; Epilepsy - complications; Epilepsy - drug therapy; Female; Fertility; Fetuses; Folic acid; Folic Acid - therapeutic use; Gene expression; Genes; Gynecology; Hippocampus; histone deacetylase; Histone Deacetylase Inhibitors - adverse effects; Histone Deacetylase Inhibitors - pharmacology; Histones; Humans; Infertility; Metabolism; Neural Tube Defects; Neurodevelopmental disorders; Oxidative stress; Population studies; Pregnancy; Pregnancy Complications - drug therapy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects - chemically induced; Review; Social behavior; valproate; Valproic acid; Valproic Acid - adverse effects; Valproic Acid - therapeutic use; Womens health; United States > US; antiepileptic drugs; valproate; congenital malformations; histone deacetylase; neurodevelopmental disorders; pregnancy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031369

An estimated 60 million people worldwide suffer from epilepsy, half of whom are women. About one-third of women with epilepsy are of childbearing age. The childbirth rate in women with epilepsy is about 20-40% lower compared to that of the general population, which may be partly due to a lower number of these women being in relationships. Lower fertility in women with epilepsy may be linked to the disease itself, but it is mainly a result of the treatment provided. Valproate, as an antiepileptic drug inhibiting histone deacetylases, may affect the expression of genes associated with cell cycle control and cellular differentiation. Evidently, this drug is associated with the risk of malformations although other antiepileptic drugs (AEDs) may also trigger birth defects, however, to a lower degree. Valproate (and to a certain degree other AEDs) may induce autism spectrum disorders and attention deficit hyperactivity disorder. The main mechanism responsible for all negative effects of prenatal exposure to valproate seems inhibition of histone deacetylases. Animal studies show a reduction in the expression of genes involved in social behavior and an increase in hippocampal cytokines. Valproate-induced oxidative stress may also contribute to neural tube defects. Interestingly, paternal exposure to this AED in mice may trigger neurodevelopmental disorders as well although a population-based cohort study does not confirm this effect. To lower the risk of congenital malformations and neurodevelopmental disorders, a single AED at the optimal dose and supplementation with folic acid is recommended. VPA should be avoided in women of childbearing age and especially during pregnancy.