USE OF VALPROIC ACID IN WOMEN WITH EPILEPSY DURING PREGNANCY
Objective: to evaluate the use of valproic acid in treatment of epilepsy during pregnancy.
Material and Methods. The maternal and obstetric outcomes of 601 pregnancies in women with epilepsy in the Samara region were reviewed. The incidence rates of fetal major congenital malformations (MCM) in women with epilepsy were analyzed; the data were obtained from the Samara regional MCM registry and from EURAP – the European epilepsy and pregnancy registry (report dated November, 2016). The development of intelligence (IQ) in 23 children born to women with epilepsy and 10 children of healthy women was assessed.
Results. Among the 601 pregnant women with epilepsy, 219 (36.4±2.0%) received no antiepileptic drugs (AED), 290 patients (48.3±2.0%) received AED monotherapy, and 92 patients (15.3±1.5%) – AED polytherapy. Fetal MCM were diagnosed in 19 of 601 women with epilepsy (3.2±0.7%); of those five MCM cases were attributed to monogenic and chromosomal abnormalities. The reported incidence of MCM in the population of the Samara region is 2.7%. However, within the present study we found deviations from the standard protocol of MCM registration; therefore, we assume that the real MCM incidence rate in the regional population is higher. The rate of fetal MCM in women exposed to AED monotherapy was 3.1±1.0%, with polytherapy – 4.3±2.1%, and in the untreated women – 0.5±0.5%. The rate of MCM was relatively higher after exposure to valproic acid monotherapy (4.7±1.7%) than that for carbamazepine monotherapy (3.1±2.2%); these figures were still considered to be within the limits of low genetic risk. Notably, the present rates of MCM incidence for the Samara region were lower than those reported in EURAP. Among the children born to the women with epilepsy, the general, verbal and non-verbal IQ averaged at 128.8; 116.5 и 133.3 points (respectively), which did not significantly differ from the IQ values in children born to the women without epilepsy. Likewise, no significant differences were found between the IQs of children exposed in their fetal period to valproate or carbamazepine and those who were not exposed to antiepileptic drugs.
Conclusion. If good seizure control is reached with valproic acid, this drug can be used during pregnancy at the lowest effective dose.
About the AuthorsA. V. Yakunina
PhD, Associate Professor at the Department of Neurology and Neurosurgery, the Samara State Medical University. Address: ul. Chapaevskaya, 89, Samara, Russia, 443099. Tel.: +7(846)9561684
I. E. Poverennova
MD, Head of the Department of Neurology and Neurosurgery, the Samara State Medical University. Address: ul. Chapaevskaya, 89, Samara, Russia, 443099. Tel.: +7(846)9561684
V. A. Kalinin
MD, Professor at the Department of Neurology and Neurosurgery, the Samara State Medical University. Address: ul. Chapaevskaya, 89, Samara, Russia, 443099. Tel.: +7(846)9561684
S. A. Nenasheva
physician-geneticist at the Regional Medical Genetic Center, the Samara Regional Clinical Hospital named after V. D. Seredavina. Address: ul. Tashkentskaya, 159, Samara, Russia, 443095. Tel.: +7(846)3725157
1. Karlov V. A., Vlasov P. N., Petrukhin V. A. Krasnopol’skii V. I. Features of epilepsy during pregnancy. Methodical recommendations of the Ministry of Health of the Russian Federation [Osobennosti terapii epilepsii vo vremya beremennosti. Metodicheskie rekomendatsii Ministerstva zdravookhraneniya RF (in Russian)]. Moscow. 2001; 1-15.
2. Petrukhin V. A., Grishin V. L., Mel’nikov A.P., Vlasov P. N., Drozhzhina G. R. Nevrologiya, neiropsikhiatriya, psikhosomatika. 2011; 3 (2): 47-49.
3. Epilepsy and pregnancy. Ed. L. S. Logutova [Epilepsiya i beremennost’. Pod red. Logutovoi L. S.] Moscow. 2012; 485-532.
4. Kiang T., Ho P., Anari M., Tong V., Abbott F., Chang T. Contribution of CYP2C9, CY-P2A6, and CYP2B6 to valproic acid metabolism in hepatic microsomes from individuals with the CYP2C9*1/CYP2C9*1 genotype.Toxicological Sciences. 2006; 94 (2): 261-271. DOI: 10.1093/toxsci/kfl096.
5. Shnaider N. A., Sychev D. A., Pilyugina M. S., Dmitrenko D. V., Bochanova E. N., Shapovalova E. A. Zhurnal nevrologii i psikhiatrii im. S. S. Korsakova. 2011; 111 (5-2): 31-37.
6. Dmitrenko D. V., Shnaider N. A., Govorina Yu.B., Murav’eva A.V., Gazenkampf K. A. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian). 2014; 6 (4): 16-22.
7. Adamchik A. S., Panchenko D. I. Akusherstvo, ginekologiya i reproduktsiya / Obstetrics, gynecology and reproduction (in Russian). 2015; 9 (1): 59-62. DOI: 10.17749/2313-7347.2015.9.1.059-062.
8. Bitsadze V. O., Samburova N. V., Makatsariya N. A., Mishchenko A. L. Akusherstvo, ginekologiya i reproduktsiya / Obstetrics, gynecology and reproduction (in Russian). 2016; 10 (1): 38-48. DOI:10.17749/2313-7347.2015.10.1.038-048.
9. Bushtyreva I. O., Kuznetsova N. B., Kovaleva A. V., Barinova V. V., Sundeeva A. G. Akusherstvo, ginekologiya i reproduktsiya / Obstetrics, gynecology and reproduction (in Russian). 2015; 9 (2): 13-18. DOI:10.17749/2070-4968.2015.9.2.013-018.
10. Harden C., Meador K., Pennell P. et al. Management issues for women with epilepsy – Focus on pregnancy (an evidence-based review): II. Teratogenesis and perinatal outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2009; 73: 133-141. DOI:10.1212/wnl.0b013e3181a6b312.
11. Tomson T., Battino D., Bonnizoni E., Craig G., Lindhout D., Sabers A., Perucca E., Vajda F. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. The Lancet Neurology. 2011; 10 (7): 609-617. DOI: 10.1016/s1474-422(11)70107-7.
12. Hernandez-Diaz S., Smith C. R., Shen A., Mittendorf R., Hauser W. A., Yerby M., Holmes L. B. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012; 78: 1692-1699. DOI: 10.1212/wnl.0b013e3182574f39.
13. Meador K., Baker G., Browning N., Cohen M., Bromley R., Clayton-Smith J., Kalayjian L., Ranner A., Liporace J., Pennel P., Privitera M., Loring D. NEAD Study Group. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. The Lancet Neurology. 2013; 12(3): 244- 252. DOI: 10.1016/s1474-4422(12)70323-x.
14. Novye dannye po bezopasnosti lekarstvennykh preparatov, soderzhashchikh val’proat natriya, val’proevuyu kislotu, val’proat seminatriya i val’promid. URL: https://www.vidal.ru/novosti/5614. Accessed: 10.07.2017
15. Vlasov P. N. Zhurnal nevrologii i psikhiatrii im. S. S. Korsakova (in Russian). 2015; 115 (4): 36-40. DOI: 10.17116/jnevro20151154136-40.
16. Instructions for the use of medicinal products for medical use Depakin- Chronosphere [Instruktsiya po primeneniyu lekarstvennogo preparata dlya meditsinskogo primeneniya Depakinkhronosfera (in Russian)]. URL: http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=d16ee912-a3c1-444faee3-ad4d026c24f5&t=. Accessed: 22.03.2017.
17. Karlov V. A. Epilepsy in children and adult women and men: a guide for Doctors [Epilepsiya u detei i vzroslykh zhenshchin i muzhchin: rukovodstvo dlya Vrachei (in Russian)]. Moscow. 2010; 720 s.
18. Herzog A. Disorders of reproduction in patients with epilepsy: Primary neurological mechanisms. Seizure. 2008; 17 (2): 101-110. DOI: 10.1016/j.seizure.2007.11.025
19. Mula M., Kanner A., Schmitz B., Schachter S. Antiepileptic drugs and suicidality: An expert consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology. Epilepsia. 2012; 54 (1): 199-203. DOI: 10.1111/j.1528-1167.2012.03688.x.
20. Vlasov P. N., Orekhova N. V., Filatova N. V. Le onova M. V. Epilepsiya u vzroslykh v aspekte stoimosti zabolevaniya. Zhurnal nevrologii i psikhiatrii im. S. S. Korsakova (in Russian)]. 2010; 3 (2): 44-47.
21. Eurep. An International Antiepileptic Drugs and Pregnancy Registry: Interim Report, November 2016. URL: http://www.eurapinternational.org/registry/reports/index.php. Accessed: 22.03.2017.
22. Poverennova I. E., Yakunina A. V., Kalinin V. A., Kuznetsova T. V., Kordonskaya I. S. [Saratovskii nauchnomeditsinskii zhurnal (in Russian)]. 2012; 8 (2): 505-509.
23. Otchet informatsionno-analiticheskogo tsentra Federal’nogo geneticheskogo registra i monitoringa VPR. URL: http://old.pedklin.ru/Defects/VPR.html. Accessed: 22.03.2017.
24. Clinical genetics. Genomics and proteomics of hereditary pathology. Ed. G. R. Mutovin [Klinicheskaya genetika. Genomika i proteomika nasledstvennoi patologii. Pod red. G. R. Mutovina (in Russian)] Moscow. 2010; 764-783.
For citation: Yakunina A.V., Poverennova I.E., Kalinin V.A., Nenasheva S.A. USE OF VALPROIC ACID IN WOMEN WITH EPILEPSY DURING PREGNANCY. Epilepsia and paroxyzmal conditions. 2017;9(3):22-31. https://doi.org/10.17749/2077-8333.2017.9.3.022-031
- There are currently no refbacks.