Abstract
Women with epilepsy that plan to become pregnant can in general look forward to uneventful pregnancies and to giving birth to normal children. However, there are certain risks associated with epilepsy and antiepileptic drug (AED) treatment, and it is likely that these risks can be reduced with appropriate prepregnancy counseling. Women with epilepsy should be informed that maintained control of tonic-clonic seizures is important for their health as well as for the well-being of the fetus; that pregnancy in general has little effect on seizure control; but that pregnancy may affect plasma concentrations of AEDs, and that drug level monitoring and dosage adjustments may be needed. They should be informed of the moderately increased risk of birth defects, and that this risk appears to be higher with the use of valproate, in particular at doses above 800 mg/day. The possibility of changing from valproate to another AED should be considered, but such changes should be tried out before conception. Withdrawing or changing an AED should generally be avoided during pregnancy. Women with epilepsy on AED treatment should be encouraged to breast-feed.
Similar content being viewed by others
References
Adab N, Kini U, Vinten J et al. (2004) The long term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry 75:1575–1583. doi:10.1136/jnnp.2003.029132
Adab N, Tudur SC, Vinten J et al. (2004) Common antiepileptic drugs in pregnancy in women with epilepsy (Cochrane review), issue 3. The Cochrane Library, Wiley, Hoboken
Artama M, Auvinen A, Raudaskoski T et al. (2005) Antiepileptic drug use of women with epilepsy and congenital malformations in offspring. Neurology 64(11):1874–1878. doi:10.1212/01.WNL.0000163771.96962.1F
Westin AA, Nakken KO, Johannessen SI et al. (2008) Serum concentration/dose ratio of topiramate during pregnancy. Epilepsia (online 30 Oct 2008)
Breen DP, Davenport RJ (2006) Teratogenicity of antiepileptic drugs. BMJ 333:615–616. doi:10.1136/bmj.38961.437639.BE
Bromley RL, Mawer G, Clayton-Smith J et al., Liverpool and Manchester Neurodevelopment Group (2008) Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology 71(23):1923–1924. doi:10.1212/01.wnl.0000339399.64213.1a
Christensen J, Sabers A, Sidenius P (2006) Oxcarbazepine concentrations during pregnancy: a retrospective study in patients with epilepsy. Neurology 67(8):1497–1499. doi:10.1212/01.wnl.0000240047.11166.0e
Crawford P (2005) Best practice guidelines for the management of women with epilepsy. Epilepsia 46(Suppl 9):117–124. doi:10.1111/j.1528-1167.2005.00323.x
Cunnington M, Ferber S, Quarteny G, the International Lamotrigine Pregnancy Registry Scientific Advisory Committee (2007) Effect of dose on frequency of major birth defects following fetal exposure to lamotrigine monotherapy in an international observational study. Epilepsia 48:1207–1210. doi:10.1111/j.1528-1167.2007.01021.x
Dolk H, Dolk H, Jentink J, Loane M, Morris J, de Jong-van den Berg LT, EUROCAT Antiepileptic Drug Working Group (2008) Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations? Neurology 71:714–722. doi:10.1212/01.wnl.0000316194.98475.d8
de Haan GJ, Edelbroek P, Segers J et al. (2004) Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study. Neurology 63(3):571–573
Eriksson K, Viinikainen K, Monkkonen A et al. (2005) Children exposed to valproate in utero: population-based evaluation of risks and confounding factors for long-term neurocognitive development. Epilepsy Res 65:189–200. doi:10.1016/j.eplepsyres.2005.06.001
Fried S, Kozer E, Nulman I et al. (2004) Malformation rates in children of women with untreated epilepsy. A meta-analysis. Drug Saf 27:197–202. doi:10.2165/00002018-200427030-00004
Gaily E, Kantola-Sorsa E, Hiilesmaa V et al. (2004) Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 62(1):28–32
Hernandez-Diaz S, Smith CR, Wyszynski DF et al. (2007) Risk of major malformations among infants exposed to carbamazepine during pregnancy. Birth Defects Res A Clin Mol Teratol 79:357
Holmes LB, Baldwin EJ, Smith CR et al. (2008) Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology 70(22 Pt 2):2152–2158. doi:10.1212/01.wnl.0000304343.45104.d6
Holmes LB, Wyszynski DF, Lieberman ES (2004) The AED (antiepileptic drug) Pregnancy Registry: a 6-year experience. Arch Neurol 61:673–678. doi:10.1001/archneur.61.5.673
Hunt S, Craig J, Russell A et al. (2006) Levetiracetam in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 67(10):1876–1879. doi:10.1212/01.wnl.0000244491.48937.55
Hunt S, Russell A, Smithson WH, Parsons L et al. (2008) Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 71(4):272–276. doi:10.1212/01.wnl.0000318293.28278.33
Kaaja E, Kaaja R, Hiilesmaa V (2003) Major malformations in offspring of women with epilepsy. Neurology 60(4):575–579
Kaneko S, Battino D, Andermann E et al. (1999) Congenital malformations due to antiepileptic drugs. Epilepsy Res 33(2–3):145–158. doi:10.1016/S0920-1211(98)00084-9
Katz O, Levy A, Wiznitzer A et al. (2006) Pregnancy and perinatal outcome in epileptic women: a population-based study. J Matern Fetal Neonatal Med 19:21–25. doi:10.1080/14767050500434096
Kooper AJ, de Bruijn D, van Ravenwaaij-Arts CM et al. (2007) Fetal anomaly scan potentially will replace routine AFAFP assays for the detection of neural tube defects. Prenat Diagn 27:29–33. doi:10.1002/pd.1614
Mazzucchelli I, Onat FY, Ozkara C et al. (2006) Changes in the disposition of oxcarbazepine and its metabolites during pregnancy and the puerperium. Epilepsia 47(3):504–509. doi:10.1111/j.1528-1167.2006.00459.x
Meischenguiser R, D’Giano CH, Ferraro SM (2004) Oxcarbazepine in pregnancy: clinical experience in Argentina. Epilepsy Behav 5:163–167. doi:10.1016/j.yebeh.2003.11.020
Montouris G (2003) Gabapentin exposure in human pregnancy: results from the Gabapentin Pregnancy Registry. Epilepsy Behav 4(3):310–317. doi:10.1016/S1525-5050(03)00110-0
Moore JL (2005) The significance of folic acid for epilepsy patients. Epilepsy Behav 7:172–181. doi:10.1016/j.yebeh.2005.05.020
Morrow JI, Russell A, Gutherie E et al. (2006) Malformation risks of anti-epileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry 77:193–198. doi:10.1136/jnnp.2005.074203
Öhman I, Vitols S, Luef G et al. (2002) Topiramate kinetics during delivery, lactation, and in the neonate: preliminary observations. Epilepsia 43(10):1157–1160. doi:10.1046/j.1528-1157.2002.12502.x
Öhman I, Vitols S, Tomson T (2000) Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation. Epilepsia 41(6):709–713. doi:10.1111/j.1528-1157.2000.tb00232.x
Öhman I, Vitols S, Tomson T (2005) Pharmacokinetics of gabapentin during delivery, in the neonatal period, and lactation: does a fetal accumulation occur during pregnancy? Epilepsia 46(10):1621–1624. doi:10.1111/j.1528-1167.2005.00251.x
Ornoy A, Zvi N, Arnon J et al. (2008) The outcome of pregnancy following topiramate treatment: a study on 52 pregnancies. Reprod Toxicol 25(3):388–389. doi:10.1016/j.reprotox.2008.03.001
Pennell PB, Newport DJ, Stowe ZN et al. (2004) The impact of pregnancy and childbirth on the metabolism of lamotrigine. Neurology 62(2):292–295
Pennell PB, Peng L, Newport DJ et al. (2008) Lamotrigine in pregnancy. Clearance, therapeutic drug monitoring and seizure frequency. Neurology 70(222):2130–2136. doi:10.1212/01.wnl.0000289511.20864.2a
Petrenaite V, Sabers A, Hansen-Schwartz J (2005) Individual changes in lamotrigine plasma concentrations during pregnancy. Epilepsy Res 65(3):185–188. doi:10.1016/j.eplepsyres.2005.06.004
Richmond JR, Krishnamoorthy P, Andermann E et al. (2004) Epilepsy and pregnancy: an obstetric perspective. Am J Obstet Gynecol 190:371–379. doi:10.1016/j.ajog.2003.09.020
Samren EB, van Duijn CM, Christiaens GC et al. (1999) Antiepileptic drug regimens and major congenital abnormalities in the offspring. Ann Neurol 46:739–746. doi:10.1002/1531-8249(199911)46:5<739::AID-ANA9>3.0.CO;2-2
Samren EB, van Duijn CM, Koch S et al. (1997) Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy. Epilepsia 38:981–990. doi:10.1111/j.1528-1157.1997.tb01480.x
Schmidt D (1982) The effect of pregnancy on the natural history of epilepsy. In: Janz D, Dam M, Bossi L, Helge H, Richens A, Schmidt D (eds) Epilepsy, pregnancy, and the child. Raven, New York, pp 3–14
Stokes T, Juarez-Garcia A, Camosso-Stefinovic J et al. (2004) Clinical guidelines and evidence review for the epilepsies: diagnosis and management in adults and children in primary and secondary care. Royal College of General Practitioners, London
Teramo K, Hiilesmaa V (1982) Pregnancy and fetal complications in epileptic pregnancies. In: Janz D, Dam M, Bossi L, Helge H, Richens A, Schmidt D (eds) Epilepsy, pregnancy, and the child. Raven, New York, pp 53–59
TheEURAP Study Group (2006) Seizure control and treatment in pregnancy: observations from the EURAP Epilepsy Pregnancy Registry. Neurology 66:354–360. doi:10.1212/01.wnl.0000195888.51845.80
Tomson T, Battino D (2007) Pharmacokinetics and therapeutic drug monitoring of newer antiepileptic drugs during pregnancy and the puerperium. Clin Pharmacokinet 46:209–219. doi:10.2165/00003088-200746030-00002
Tomson T, Battino D (2005) Teratogenicity of antiepileptic drugs: state of the art. Curr Opin Neurol 18:135–140. doi:10.1097/01.wco.0000162854.67767.06
Tomson T, Hiilesmaa V (2007) Epilepsy in pregnancy. BMJ 335:769–773. doi:10.1136/bmj.39266.473113.BE
Tomson T, Palm R, Kallen K et al. (2007) Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation. Epilepsia 48(6):1111–1116. doi:10.1111/j.1528-1167.2007.01032.x
Tomson T (2005) Gender aspects of pharmacokinetics of new and old AEDs: pregnancy and breast-feeding. Ther Drug Monit 27:718–721. doi:10.1097/01.ftd.0000179843.63515.8f
Tran TA, Leppik IE, Blesi K et al. (2002) Lamotrigine clearance during pregnancy. Neurology 59(2):251–255
Vajda FJ, Hitchcock A, Graham J et al. (2007) The Australian Register of Antiepileptic Drugs in Pregnancy: the first 1002 pregnancies. Aust NZ J Obstet Gynaecol 47:468–474. doi:10.1111/j.1479-828X.2007.00781.x
Vajda FJE, Hitchcock A, Graham J et al. (2008) Seizure control in antiepileptic drug-treated pregnancy. Epilepsia 49(1):172–176
Wide K, Winbladh B, Kallen B (2004) Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population-based register study. Acta Paediatr 93(2):174–176. doi:10.1080/08035250310021118
Wyszynski DF, Nambisan M, Surve T et al. (2005) Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology 64:961–965
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tomson, T., Battino, D. Pregnancy and epilepsy: what should we tell our patients?. J Neurol 256, 856–862 (2009). https://doi.org/10.1007/s00415-009-5062-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-009-5062-1