Clinical Practice Protocol for Management of Women of Childbearing-Age with Epilepsy

Authors

  • Margarida Ferro Serviço de Neurologia do Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal https://orcid.org/0000-0002-5128-5101
  • Miguel Serôdio Serviço de Neurologia do Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal https://orcid.org/0000-0002-5051-702X
  • Mariana Beja Serviço de Ginecologia e Obstetrícia do Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal
  • Inês Menezes Cordeiro Serviço de Neurologia do Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal
  • Joana Parra Serviço de Neurologia do Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal
  • Francisca Sá Serviço de Neurologia do Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal

DOI:

https://doi.org/10.46531/sinapse/GU/230019/2023

Keywords:

Anticonvulsants/therapeutic use, Epilepsy/drug therapy, Female, Lactation, Pregnancy

Abstract

Women of childbearing-age with epilepsy presents with challenges in prevention, planning and orientation of gestation and post-partum. Gestation in women with epilepsy represents 0.3% to 0.5% of all pregnancies, and one third of women with epilepsy is in childbearing-age. Epilepsy may be associated with serious complications in pregnant women, with a higher risk of congenital malformations, intrauterine growth restriction and neurocognitive development disorders in children, due to adverse effects of antiseizure drugs (ASD). Women should be informed that the risk of fetal congenital malformations depends on the type, number, and dosage of ASD. The choice of drugs associated with a lower incidence of congenital malformations, as well as monitoring and adjusting its dosage are essential for an adequate seizure control. Choosing the treatment for women of childbearing-age should be based on an early and shared decision between patient and doctor, and when appropriate, shared with the patient’s legal representative as well. Discussions should include careful evaluation of the risk-benefit relationship of reasonable drugs for the type of seizures/epilepsy. Women of childbearing-age and pregnant women with epilepsy should also be informed of the low risk of seizures and complications during labor. Vaginal delivery should be considered, as epilepsy is not a formal indication for cesarian delivery. A careful follow-up in post-partum is also fundamental, in which is important to check dosages of ASD, reintroduce contraceptive methods and reassure that care has been taken to minimize the risk of maternal and newborn lesions due to seizures. Follow-up should be multidisciplinary, including the attending neurologist, obstetrician, and general physician. We present a clinical practice protocol that aims to guide multidisciplinary teams managing women of childbearing-age with epilepsy, regarding contraception, fertility, pregnancy and post-partum period.

Downloads

Download data is not yet available.

References

Hernandéz S, Garcia-Penche I, Guirado L, Gómez O, Eixarch E, Carreño, et al. Protocolo: Epilepsia y Gestación. [consultado Dez 2021] . Disponível em: https://portal.medicinafetalbarcelona.org/protocolos/es/patologia-materna-obstetrica/epilepsia-y-gestacion.html

Nashef L, Tomson T. Intriguing new data on epilepsy and risks at delivery. Nat Rev Neurol. 2015;11:550-2. doi:10.1038/nrneurol.2015.176

Adab N, Chadwick DW. Management of women with epilepsy during pregnancy. Obstetrician Gynaecol. 2006;8:20-25. doi:10.1576/toag.8.1.020.27204

Edey S, Moran N, Nashef L. SUDEP and epilepsy-related mortality in pregnancy. Epilepsia. 2014;55:e72-4. doi:10.1111/epi.12621

Sazgar M. Treatment of Women With Epilepsy. Continuum. 2019;25:408-30. doi: 10.1212/CON.0000000000000713.

Bhatia M, Adcock JE, Mackillop L. The management of pregnant women with epilepsy: a multidisciplinary collaborative approach to care. Obstetrician Gynaecol. 2017;19:279-88. doi:10.1111/tog.12413

Li Y, Meador KJ. Epilepsy and Pregnancy. Continuum Lifelong Learn Neurology. 2022;28:34-54. doi:10.1212/ con.0000000000001056

Pennell PB. Pregnancy and Reproductive Health in Patients with Epilepsy. Published online 2017. [consultado Jan 2022] Disponível em: http://upandrunningnetworks.com/files/ C41_2.pdf

Herzog AG, Mandle HB, Cahill KE, Fowler KM, Hauser WA. Differential impact of contraceptive methods on seizures varies by antiepileptic drug category: Findings of the Epilepsy Birth Control Registry. Epilepsy Behav. 2016;60:112-7. doi:10.1016/j.yebeh.2016.04.020

Pacheco A, Costa AR, Lanhoso A, Santos ATA, Rodrigues C, Rebelo C, et al. Consenso sobre Contraceção. Sociedade Portuguesa Da Contraceção. [consultado Jan 2022] Disponível em: https://www.spdc.pt/images/SPDC_ Consensos_2020_27Nov_Final_web_versao_livro_digital. pdf

Reimers A, Brodtkorb E, Sabers A. Interactions between hormonal contraception and antiepileptic drugs: Clinical and mechanistic considerations. Seizure. 2015;28:66-70. doi:10.1016/j.seizure.2015.03.006

Thangaratinam S, Fong F, McCorry D, Pirie AM, Bagary M, Greenhill L. Epilepsy in Pregnancy: Green-top Guideline No. 68. London: Royal College of Obstetricians & Gynaecologists; 2016. [consultado Jan 2022] Disponível em: https://www.rcog.org.uk/guidance/browse-all-guidance/ green-top-guidelines/epilepsy-in-pregnancy-green-top-guideline-no-68/

Arfman IJ, Heijden EAW van der, Horst PGJ ter, Lambrechts DA, Wegner I, Touw DJ. Therapeutic Drug Monitoring of Antiepileptic Drugs in Women with Epilepsy Before, During, and After Pregnancy. Clin Pharmacokinet. 2020;59:427-45. doi:10.1007/s40262-019-00845-2

Pennell PB, French JA, Harden CL, Davis A, Bagiella E, Andreopoulos E, et al. Fertility and Birth Outcomes in Women With Epilepsy Seeking Pregnancy. Jama Neurol. 2018;75(8):962. doi:10.1001/jamaneurol.2018.0646

Stephen LJ, Harden C, Tomson T, Brodie MJ. Management of epilepsy in women. Lancet Neurology. 2019;18:481-91. doi:10.1016/s1474-4422(18)30495-2

Isojärvi JIT, Taubøll E, Herzog AG. Effect of Antiepileptic Drugs on Reproductive Endocrine Function in Individuals with Epilepsy. Cns Drugs. 2005;19:207-23. doi:10.2165/00023210-200519030-00003

Viinikainen K, Heinonen S, Eriksson K, Kälviäinen R. Fertility in Women with Active Epilepsy. Neurology. 2007;69:2107-8. doi:10.1212/01.wnl.0000277451.06420.b6

Vajda FJE, Hitchcock A, Graham J, O’Brien T, Lander C, Eadie M. Seizure control in antiepileptic drug-treated pregnancy. Epilepsia. 2008;49:172-6. doi:10.1111/j.1528-1167.2007.01412.x

ACOG Comittee on Practice Bulletins--Obstetrics, Stowe ZN, Ragan K. ACOG Practice Bulletin No. 92: Use of Psychiatric Medications During Pregnancy and Lactation. Obstetrics Gynecol. 2008;111:1001-20. doi:10.1097/ aog.0b013e31816fd910

Almeida C, Costa F, Graça P, Menezes B, Mota E, Oliveira D, et al. Programa Nacional Para a Vigilância Da Gravidez de Baixo Risco. Lisboa:Direção-Geral da Saúde; 2015. [consultado Jan 2022] Disponível em: https://www.dgs. pt/em-destaque/programa-nacional-para-a-vigilancia-da-gravidez-de-baixo-risco-pdf11.aspx

Toledo M, Mostacci B, Bosak M, Jedrzejzak J, Thomas RH, Salas-Puig J, et al. Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience—a European perspective. J Neurol. 2021;268:2735-48. doi:10.1007/s00415-020-09809-0

Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:512-21. doi:10.1111/ epi.13709

Lamberink HJ, Otte WM, Geerts AT, Pavlovic M, Ramos-Lizana J, Marson AG, et al. Individualised prediction model of seizure recurrence and long-term outcomes after with-drawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis. Lancet Neurology. 2017;16:523-31. doi:10.1016/ s1474-4422(17)30114-x

Battino D, Tomson T, Bonizzoni E, Craig J, Lindhout D, Sabers A, et al. Seizure control and treatment changes in pregnancy: Observations from the EURAP epilepsy pregnancy registry. Epilepsia. 2013;54:1621-7. doi:10.1111/ epi.12302

Cagnetti C, Lattanzi S, Foschi N, Provinciali L, Silvestrini M. Seizure course during pregnancy in catamenial epilepsy. Neurology. 2014;83:339-44. doi:10.1212/ wnl.0000000000000619

Voinescu PE, Ehlert AN, Bay CP, Allien S, Pennell PB. Variations in Seizure Frequency During Pregnancy and Postpartum by Epilepsy Type. Neurology. 2022;98:e802-7. doi:10.1212/wnl.0000000000013056

Vajda FJE, O’Brien TJ, Graham JE, Hitchcock AA, Lander CM, Eadie MJ. Predicting epileptic seizure control during pregnancy. Epilepsy Behav. 2018;78:91-5. doi:10.1016/j. yebeh.2017.10.017

Reisinger TL, Newman M, Loring DW, Pennell PB, Meador KJ. Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy Behav. 2013;29:13-8. doi:10.1016/j.yebeh.2013.06.026

Boardman SG. Understanding the experiences of pregnancy in women with epilepsy. [consultado Jan 2022] Disponível em: https://ethos.bl.uk/OrderDetails.do?uin=uk. bl.ethos.613483

Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet. 2011;378:2028-38. doi:10.1016/s0140-6736(11)60176-1

Aurlien D, Larsen JP, Gjerstad L, Taubøll E. Comorbid and underlying diseases—Major determinants of excess mortality in epilepsy. Seizure. 2012;21:573-7. doi:10.1016/j.seizure.2012.05.015

Teramo K, Hiilesmaa V, Bardy A, Saarikoski S. Fetal heart rate during a maternal grand mal epileptic seizure. J Perinat Med. 1979;7:3-6. doi:10.1515/jpme.1979.7.1.3

Hiilesmaa VK, Teramo KA. Chapter 10: Fetal and Maternal Risks with Seizures. In: Harden CL, Thomas SV, Tomson T, editorss. Epilepsy in Women. London: John Wiley & Sons; 2013. p.115-27.

Tomson T, Battino D, Bromley R, Kochen S, Meador K, Pennel P, et al. Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epileptic Disord. 2019;21:497-517. doi:10.1684/epd.2019.1105

Kinney MO, Morrow J. Epilepsy in pregnancy. BMJ. 2016;353:i2880. doi:10.1136/bmj.i2880

Pennell PB, French JA, May RC, Gerard E, Kalayjian L, Penovich P, et al. Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy. New Engl J Med. 2020;383:2547-56. doi:10.1056/nejmoa2008663

Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: Changes in drug disposition and their clinical implications. Epilepsia. 2013;54:405-14. doi:10.1111/epi.12109

Pennell PB. Pregnancy, Epilepsy, and Women’s Issues. ContinLifelong Learn Neurol. 2013;19:697-714. doi:10.1212/01.con.0000431383.14061.e6

Meador K, Reynolds MW, Crean S, Fahrbach K, Probst C. Pregnancy outcomes in women with epilepsy: A systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res. 2008;81:1-13. doi:10.1016/j.eplepsyres.2008.04.022

Holmes LB, Mittendorf R, Shen A, Smith CR, Hernandez-Diaz S. Fetal Effects of Anticonvulsant Polytherapies: Different Risks From Different Drug Combinations. Arch Neurol. 2011;68:1275-81. doi:10.1001/archneurol.2011.133

Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol. 2013;12:244-52. doi:10.1016/s1474-4422(12)70323-x

Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, et al. Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Child-hood Autism. Jama. 2013;309:1696-703. doi:10.1001/ jama.2013.2270

Shallcross R, Bromley RL, Cheyne CP, García-Fiñana M, Irwin B, Morrow J, et al. In utero exposure to levetiracetam vs valproate. Neurology. 2014;82:213-21. doi:10.1212/ wnl.0000000000000030

Vajda FJE, O’Brien TJ, Lander CM, Graham J, Roten A, Eadie MJ. Teratogenesis in repeated pregnancies in antiepileptic drug-treated women. Epilepsia. 2013;54:181-6. doi:10.1111/j.1528-1167.2012.03625.x

Rajiv KR, Radhakrishnan A. Status epilepticus in pregnancy – Can we frame a uniform treatment protocol? Epilepsy Behav. 2019;101:106376. doi:10.1016/j.yebeh.2019.06.020

Rajiv KR, Radhakrishnan A. Status epilepticus in pregnancy: Etiology, management, and clinical outcomes. Epilepsy Behav. 2017;76:114-19. doi:10.1016/j.yebeh.2017.07.002

MacDonald SC, Bateman BT, McElrath TF, Hernández-Díaz S. Mortality and Morbidity During Delivery Hospitalization Among Pregnant Women With Epilepsy in the United States. Jama Neurol. 2015;72:981-8. doi:10.1001/jamaneurol.2015.1017

Hernández-Díaz S, McElrath TF, Pennell PB, Hauser WA, Yerby M, Holmes LB. Fetal growth and premature delivery in pregnant women on antiepileptic drugs. Ann Neurol. 2017;82:457-65. doi:10.1002/ana.25031

Bech BH, Kjaersgaard MIS, Pedersen HS, Howards PP, Sørensen MJ, Olsen J, et al. Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study.BMJ. 2014;349:g5159. doi:10.1136/bmj.g5159

Thomas SV, Syam U, Devi JS. Predictors of seizures during pregnancy in women with epilepsy. Epilepsia. 2012;53:e85-8. doi:10.1111/j.1528-1167.2012.03439.x

Pennell PB, Peng L, Newport DJ, Ritchie JC, Koganti A, Holley DK, et al. Lamotrigine in pregnancy. Neurology. 2008;70:2130-6. doi:10.1212/01.wnl.0000289511.20864.2a

Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, et al. Effects of breastfeeding in children of women taking antiepileptic drugs (e–Pub ahead of print) (Patient Page). Neurology. 2010;75:1954-60. doi:10.1212/wnl.0b013e3181ffe4a9

Chen L, Liu F, Yoshida S, Kaneko S. Is breast-feeding of infants advisable for epileptic mothers taking antiepileptic drugs? Psychiat Clin Neuros. 2010;64:460-8. doi:10.1111/ j.1440-1819.2010.02126.x

Turner K, Piazzini A, Franza A, Marconi AM, Canger R, Canevini MP. Epilepsy and postpartum depression. Epilepsia. 2009;50:24-7. doi:10.1111/j.1528-1167.2008.01965.x

Bjørk MH, Veiby G, Reiter SC, Berle JØ, Daltveit AK, Spigset O, et al. Depression and anxiety in women with epilepsy during pregnancy and after delivery: A prospective population-based cohort study on frequency, risk factors, medication, and prognosis. Epilepsia. 2015;56:28-39. doi:10.1111/epi.12884

Galanti M, Newport DJ, Pennell PB, Titchner D, Newman M, Knight BT, et al. Postpartum depression in women with epilepsy: Influence of antiepileptic drugs in a prospective study. Epilepsy Behav. 2009;16:426-30. doi:10.1016/j. yebeh.2009.07.009

Published

2023-07-18

How to Cite

1.
Ferro M, Serôdio M, Beja M, Menezes Cordeiro I, Parra J, Sá F. Clinical Practice Protocol for Management of Women of Childbearing-Age with Epilepsy. Sinapse [Internet]. 2023 Jul. 18 [cited 2024 Dec. 21];23(2):111-24. Available from: https://sinapse.pt/index.php/journal/article/view/25

Issue

Section

Guidelines

Most read articles by the same author(s)