Top

Published in:

01-09-2018 | Original Article

Fetal safety of levetiracetam use during pregnancy

Authors: Guray Koc, Selda Keskin Guler, Omer Karadas, Tahir Yoldas, Zeki Gokcil

Published in: Acta Neurologica Belgica | Issue 3/2018

Abstract

The aim of this study is to evaluate the effect of levetiracetam treatment during pregnancy on fetus.. The pregnant women with epilepsy (PWWE) who were exposed to levetiracetam treatment during pregnancy in the form of monotherapy or polytherapy were retrospectively evaluated. They were compared with the PWWE who did not use the antiepileptic drug (AED) during pregnancy. A total of 102 pregnancies were examined. While 35 patients never used AED during pregnancy, 30 patients received only levetiracetam therapy, and 37 patients received levetiracetam with at least one combined AED. While no major congenital malformation (MCM) was determined in the group of patients who never used AED and who received levetiracetam monotherapy, 2 MCMs were determined in the group receiving multiple AED therapy with levetiracetam. This study showed that the use of levetiracetam as monotherapy during pregnancy was at the same risk level as the group who never used AED and that the risk increased when it was used as a part of polytherapy. In conclusion, these findings support the current understanding that LEV may be a feasible option for PWWE.

Chaudhry SA, Jong G, Koren G (2014) The fetal safety of Levetiracetam: a systematic review. Reprod Toxicol 46:40–45. https://doi.org/10.1016/j.reprotox.2014.02.004 CrossRefPubMed

Mawhinney E, Craig J, Morrow J, Russell A, Smithson WH, Parsons L, Morrison PJ, Liggan B, Irwin B, Delanty N, Hunt SJ (2013) Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology 80(4):400–405. https://doi.org/10.1212/WNL.0b013e31827f0874 CrossRefPubMed

ten Berg K, Samrén EB, van Oppen AC, Engelsman M, Lindhout D (2005) Levetiracetam use and pregnancy outcome. Reprod Toxicol 20(1):175–178CrossRefPubMed

Hernández-Díaz S, Smith CR, Shen A, Mittendorf R, Hauser WA, Yerby M, Holmes LB, North American AED Pregnancy Registry; North American AED Pregnancy Registry (2012) Comparative safety of antiepileptic drugs during pregnancy. Neurology 78(21):1692–1699. https://doi.org/10.1212/WNL.0b013e3182574f39 CrossRefPubMed

Gambardella A, Labate A, Colosimo E, Ambrosio R, Quattrone A (2008) Monotherapy for partial epilepsy: focus on levetiracetam. Neuropsychiatr Dis Treat 4(1):33–38CrossRefPubMedPubMedCentral

Reimers A, Brodtkorb E (2012) Second-generation antiepileptic drugs and pregnancy: a guide for clinicians. Expert Rev Neurother 12(6):707–717. https://doi.org/10.1586/ern.12.32 CrossRefPubMed

Hovinga CA (2001) Levetiracetam: a novel antiepileptic drug. Pharmacotherapy 21(11):1375–1388CrossRefPubMed

Patsalos PN (2004) Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet 43(11):707–724CrossRefPubMed

Vajda FJ, Graham J, Roten A, Lander CM, O’Brien TJ, Eadie M (2012) Teratogenicity of the newer antiepileptic drugs—the Australian experience. J Clin Neurosci 19(1):57–59. https://doi.org/10.1016/j.jocn.2011.08.003 CrossRefPubMed

10.

Würtz AM, Rytter D, Vestergaard CH, Christensen J, Vestergaard M, Bech BH (2017) Prenatal exposure to antiepileptic drugs and use of primary healthcare during childhood: a population-based cohort study in Denmark. BMJ Open 7(1):e012836. https://doi.org/10.1136/bmjopen-2016-012836 CrossRefPubMedPubMedCentral

11.

Mølgaard-Nielsen D, Hviid A (2011) Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA 305(19):1996–2002. https://doi.org/10.1001/jama.2011.624 CrossRefPubMed

12.

EUROCAT (2005) EUROCAT Guide 1.3 and reference documents, instructions for the registration and surveillance of congenital anomalies. http://www.eurocat.ulster.ac.uk/pdf/EUROCAT-Guide-1.3.pdf. Accessed 23 Dec 2017

13.

Morrow J, Russell A, Guthrie E, Parsons L, Robertson I, Waddell R, Irwin B, McGivern RC, Morrison PJ, Craig J (2006) Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry 77(2):193–198. https://doi.org/10.1136/jnnp.2005.074203 CrossRefPubMed

14.

Martinez Ferri M, Peña Mayor P, Perez López-Fraile I, Escartin Siquier A, Martin Moro M, Forcadas Berdusan M, en representación del registro EURAP España (2016) Comparative study of antiepileptic drug use during pregnancy over a period of 12 years in Spain. Efficacy of the newer antiepileptic drugs lamotrigine, levetiracetam, and oxcarbazepine. Neurologia. https://doi.org/10.1016/j.nrl.2016.05.004 PubMedCrossRef

15.

Hunt S, Craig J, Russell A, Guthrie E, Parsons L, Robertson I, Waddell R, Irwin B, Morrison PJ, Morrow J (2006) Levetiracetam in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 67(10):1876–1879CrossRefPubMed

16.

Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Sabers A, Perucca E, Vajda F, EURAP study group (2011) Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol 10:609–617. https://doi.org/10.1016/S1474-4422(11)70107-7 CrossRefPubMed

17.

Battino D, Tomson T, Bonizzoni E, Craig J, Lindhout D, Sabers A, Perucca E, Vajda F, EURAP Study Group (2013) Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia 54(9):1621–1627. https://doi.org/10.1111/epi.12302 CrossRefPubMed

18.

Schachter SC (2018) Risks associated with epilepsy and pregnancy. UpToDate. https://www.uptodate.com/contents/risks-associated-with-epilepsy-and-pregnancy. Acsessed 02 Feb 2018

19.

Richmond JR, Krishnamoorthy P, Andermann E, Benjamin A (2004) Epilepsy and pregnancy: an obstetric perspective. Am J Obstet Gynecol 190(2):371–379CrossRefPubMed

20.

Vajda FJ, Hitchcock AA, Graham J, O’Brien TJ, Lander CM, Eadie MJ (2010) The teratogenic risk of antiepileptic drug polytherapy. Epilepsia 51(5):805–810. https://doi.org/10.1111/j.1528-1167.2009.02336.x CrossRefPubMed

21.

Vajda FJ, O’Brien T, Lander C, Graham J, Eadie M (2014) The efficacy of the newer antiepileptic drugs in controlling seizures in pregnancy. Epilepsia 55(8):1229–1234. https://doi.org/10.1111/epi.12711 CrossRefPubMed

22.

Pirie DA, Al Wattar BH, Pirie AM, Houston V, Siddiqua A, Doug M, Bagary M, Greenhill L, Khan KS, McCorry D, Thangaratinam S (2014) Effects of monitoring strategies on seizures in pregnant women on lamotrigine: a meta-analysis. Eur J Obstet Gynecol Reprod Biol 172:26–31. https://doi.org/10.1016/j.ejogrb.2013.10.021 CrossRefPubMed

23.

Reisinger TL, Newman M, Loring DW, Pennell PB, Meador KJ (2013) Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy Behav 29(1):13–18. https://doi.org/10.1016/j.yebeh.2013.06.026 CrossRefPubMedPubMedCentral

24.

Thomas SV, Syam U, Devi JS (2012) Predictors of seizures during pregnancy in women with epilepsy. Epilepsia 53(5):e85–e88. https://doi.org/10.1111/j.1528-1167.2012.03439.x CrossRefPubMed

25.

Harden CL, Hopp J, Ting TY, Pennell PB, French JA, Allen Hauser W, Wiebe S, Gronseth GS, Thurman D, Meador KJ, Koppel BS, Kaplan PW, Robinson JN, Gidal B, Hovinga CA, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Le Guen C, American Academy of Neurology; American Epilepsy Society (2009) Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): I. Obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 50(5):1229–1236. https://doi.org/10.1111/j.1528-1167.2009.02128.x CrossRefPubMed

Title: Fetal safety of levetiracetam use during pregnancy
Authors: Guray Koc
Selda Keskin Guler
Omer Karadas
Tahir Yoldas
Zeki Gokcil
Publication date: 01-09-2018
Publisher: Springer International Publishing
Published in: Acta Neurologica Belgica / Issue 3/2018
Print ISSN: 0300-9009
Electronic ISSN: 2240-2993
DOI: https://doi.org/10.1007/s13760-018-0996-7

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Fetal safety of levetiracetam use during pregnancy

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2018

Unusual side effects due to clobazam: a case report with edema of the extremities

Antibody profile may predict outcome in ocular myasthenia gravis

A single-center retrospective study of onabotulinumtoxinA for treatment of 245 chronic migraine patients: survey results of a real-world experience

Effects of ultrasound-guided botulinum toxin type-A injections with a specific approach in spastic cerebral palsy

Magnetic resonance imaging findings of mixed neuronal–glial tumors with pathologic correlation: a review

The course of epilepsy and seizure control in pregnant women