Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Risks associated with epilepsy and pregnancy

Steven C Schachter, MD
Section Editors
Paul Garcia, MD
Charles J Lockwood, MD, MHCM
Deputy Editor
April F Eichler, MD, MPH


Over 90 percent of women with epilepsy have a normal pregnancy. This point should be emphasized to the patient who is likely to have many fears and anxieties regarding the risks. Nonetheless, women with epilepsy are at increased risk for a range of perinatal complications compared with the general population, including preeclampsia, preterm labor, and fetal and maternal mortality. It is important for physicians and women with epilepsy to be aware of these as careful planning and management of pregnancy can increase the odds of a favorable outcome.

There are a number of important issues to be addressed by the physician when a woman with epilepsy becomes pregnant; these include:

Are antiseizure drugs necessary?

What effect do antiseizure drugs have on the fetus?

What effect does maternal epilepsy have on the fetus?


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Sep 22, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Yerby M, Koepsell T, Daling J. Pregnancy complications and outcomes in a cohort of women with epilepsy. Epilepsia 1985; 26:631.
  2. Tanganelli P, Regesta G. Epilepsy, pregnancy, and major birth anomalies: an Italian prospective, controlled study. Neurology 1992; 42:89.
  3. Richmond JR, Krishnamoorthy P, Andermann E, Benjamin A. Epilepsy and pregnancy: an obstetric perspective. Am J Obstet Gynecol 2004; 190:371.
  4. Veiby G, Daltveit AK, Engelsen BA, Gilhus NE. Pregnancy, delivery, and outcome for the child in maternal epilepsy. Epilepsia 2009; 50:2130.
  5. Borthen I, Eide MG, Daltveit AK, Gilhus NE. Obstetric outcome in women with epilepsy: a hospital-based, retrospective study. BJOG 2011; 118:956.
  6. Harden CL, Hopp J, Ting TY, et al. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): 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 American Epilepsy Society. Neurology 2009; 73:126.
  7. Harden CL, Meador KJ, Pennell PB, et al. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology 2009; 73:133.
  8. Borthen I, Eide MG, Veiby G, et al. Complications during pregnancy in women with epilepsy: population-based cohort study. BJOG 2009; 116:1736.
  9. 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.
  10. Viale L, Allotey J, Cheong-See F, et al. Epilepsy in pregnancy and reproductive outcomes: a systematic review and meta-analysis. Lancet 2015; 386:1845.
  11. Adab N, Kini U, Vinten J, et al. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry 2004; 75:1575.
  12. Edey S, Moran N, Nashef L. SUDEP and epilepsy-related mortality in pregnancy. Epilepsia 2014; 55:e72.
  13. Nakane Y, Okuma T, Takahashi R, et al. Multi-institutional study on the teratogenicity and fetal toxicity of antiepileptic drugs: a report of a collaborative study group in Japan. Epilepsia 1980; 21:663.
  14. EURAP Study Group. Seizure control and treatment in pregnancy: observations from the EURAP epilepsy pregnancy registry. Neurology 2006; 66:354.
  15. Bech BH, Kjaersgaard MI, Pedersen HS, et al. Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study. BMJ 2014; 349:g5159.
  16. Sabers A, aRogvi-Hansen B, Dam M, et al. Pregnancy and epilepsy: a retrospective study of 151 pregnancies. Acta Neurol Scand 1998; 97:164.
  17. Schmidt D. The effects of pregnancy on the natural history of epilepsy: Review of the literature. In: Epilepsy, Pregnancy and the Child, Janz D, Bossi L, Dam, M, et al (Eds), Raven, New York 1982. p.3.
  18. Vajda FJ, Hitchcock A, Graham J, et al. Seizure control in antiepileptic drug-treated pregnancy. Epilepsia 2008; 49:172.
  19. Thomas SV, Syam U, Devi JS. Predictors of seizures during pregnancy in women with epilepsy. Epilepsia 2012; 53:e85.
  20. Cagnetti C, Lattanzi S, Foschi N, et al. Seizure course during pregnancy in catamenial epilepsy. Neurology 2014; 83:339.
  21. Schmidt D, Canger R, Avanzini G, et al. Change of seizure frequency in pregnant epileptic women. J Neurol Neurosurg Psychiatry 1983; 46:751.
  22. Otani K. Risk factors for the increased seizure frequency during pregnancy and puerperium. Folia Psychiatr Neurol Jpn 1985; 39:33.
  23. Bjørk MH, Veiby G, Reiter SC, 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.
  24. Kanner AM, Palac S. Depression in epilepsy: a common but often unrecognized comorbid malady. Epilepsy Behav 2000; 1:37.
  25. Meador KJ, Pennell PB, Harden CL, et al. Pregnancy registries in epilepsy: a consensus statement on health outcomes. Neurology 2008; 71:1109.
  26. Bassi V, Yerby MS, Devinsky O. Epilepsy. Adv Neurol 2002; 90:185.
  27. Holmes LB, Harvey EA, Coull BA, et al. The teratogenicity of anticonvulsant drugs. N Engl J Med 2001; 344:1132.
  28. Artama M, Auvinen A, Raudaskoski T, et al. Antiepileptic drug use of women with epilepsy and congenital malformations in offspring. Neurology 2005; 64:1874.
  29. Morrow J, Russell A, Guthrie E, et al. Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry 2006; 77:193.
  30. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000; 343:1608.
  31. Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol 2011; 10:609.
  32. Gaily E, Granström ML. Minor anomalies in children of mothers with epilepsy. Neurology 1992; 42:128.
  33. Yerby MS, Leavitt A, Erickson DM, et al. Antiepileptics and the development of congenital anomalies. Neurology 1992; 42:132.
  34. Holmes LB, Harvey EA, Brown KS, et al. Anticonvulsant teratogenesis: I. A study design for newborn infants. Teratology 1994; 49:202.
  35. Kini U, Adab N, Vinten J, et al. Dysmorphic features: an important clue to the diagnosis and severity of fetal anticonvulsant syndromes. Arch Dis Child Fetal Neonatal Ed 2006; 91:F90.
  36. Perucca E, Tomson T. Prenatal exposure to antiepileptic drugs. Lancet 2006; 367:1467.
  37. Annegers JF, Hauser WA, Elveback LR, et al. Congenital malformations and seizure disorders in the offspring of parents with epilepsy. Int J Epidemiol 1978; 7:241.
  38. Koch S, Lösche G, Jager-Romän E, et al. Major and minor birth malformations and antiepileptic drugs. Neurology 1992; 42:83.
  39. Diav-Citrin O, Shechtman S, Arnon J, Ornoy A. Is carbamazepine teratogenic? A prospective controlled study of 210 pregnancies. Neurology 2001; 57:321.
  40. Kaaja E, Kaaja R, Hiilesmaa V. Major malformations in offspring of women with epilepsy. Neurology 2003; 60:575.
  41. Meador KJ, Baker GA, Finnell RH, et al. In utero antiepileptic drug exposure: fetal death and malformations. Neurology 2006; 67:407.
  42. Holmes LB, Mittendorf R, Shen A, et al. Fetal effects of anticonvulsant polytherapies: different risks from different drug combinations. Arch Neurol 2011; 68:1275.
  43. Vajda FJ, O'Brien TJ, Lander CM, et al. Antiepileptic drug combinations not involving valproate and the risk of fetal malformations. Epilepsia 2016; 57:1048.
  44. Lindhout D, Höppener RJ, Meinardi H. Teratogenicity of antiepileptic drug combinations with special emphasis on epoxidation (of carbamazepine). Epilepsia 1984; 25:77.
  45. Kaneko S, Battino D, Andermann E, et al. Congenital malformations due to antiepileptic drugs. Epilepsy Res 1999; 33:145.
  46. Samrén EB, van Duijn CM, Koch S, et al. 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 1997; 38:981.
  47. Samrén EB, van Duijn CM, Christiaens GC, et al. Antiepileptic drug regimens and major congenital abnormalities in the offspring. Ann Neurol 1999; 46:739.
  48. Vajda FJ, Eadie MJ. Maternal valproate dosage and foetal malformations. Acta Neurol Scand 2005; 112:137.
  49. Vajda FJ, O'Brien TJ, Lander CM, et al. Teratogenesis in repeated pregnancies in antiepileptic drug-treated women. Epilepsia 2013; 54:181.
  50. Campbell E, Devenney E, Morrow J, et al. Recurrence risk of congenital malformations in infants exposed to antiepileptic drugs in utero. Epilepsia 2013; 54:165.
  51. Finnell RH, Buehler BA, Kerr BM, et al. Clinical and experimental studies linking oxidative metabolism to phenytoin-induced teratogenesis. Neurology 1992; 42:25.
  52. Parman T, Chen G, Wells PG. Free radical intermediates of phenytoin and related teratogens. Prostaglandin H synthase-catalyzed bioactivation, electron paramagnetic resonance spectrometry, and photochemical product analysis. J Biol Chem 1998; 273:25079.
  53. Lindhout D, Omtzigt JG, Cornel MC. Spectrum of neural-tube defects in 34 infants prenatally exposed to antiepileptic drugs. Neurology 1992; 42:111.
  54. Lindhout D, Schmidt D. In utero exposure to valproate and neural-tube defects. Lancet 1986; 2:1932.
  55. Bromfield EB, Dworetzky BA, Wyszynski DF, et al. Valproate teratogenicity and epilepsy syndrome. Epilepsia 2008; 49:2122.
  56. Wyszynski DF, Nambisan M, Surve T, et al. Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology 2005; 64:961.
  57. Hernández-Díaz S, Smith CR, Shen A, et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology 2012; 78:1692.
  58. Jentink J, Loane MA, Dolk H, et al. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med 2010; 362:2185.
  59. Vajda FJ, O'Brien TJ, Graham JE, et al. Dose dependence of fetal malformations associated with valproate. Neurology 2013; 81:999.
  60. Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent teratogenicity of valproate in mono- and polytherapy: an observational study. Neurology 2015; 85:866.
  61. Bavoux F, Fournier-Perhilou AI, Wood C, et al. Neonatal fibrinogen depletion caused by sodium valproate. Ann Pharmacother 1994; 28:1307.
  62. Majer RV, Green PJ. Neonatal afibrinogenaemia due to sodium valproate. Lancet 1987; 2:740.
  63. Lindhout D, Meinardi H, Meijer JW, Nau H. Antiepileptic drugs and teratogenesis in two consecutive cohorts: changes in prescription policy paralleled by changes in pattern of malformations. Neurology 1992; 42:94.
  64. Kaneko S, Otani K, Kondo T, et al. Malformation in infants of mothers with epilepsy receiving antiepileptic drugs. Neurology 1992; 42:68.
  65. Satgé D, Sasco AJ, Little J. Antenatal therapeutic drug exposure and fetal/neonatal tumours: review of 89 cases. Paediatr Perinat Epidemiol 1998; 12:84.
  66. Dravet C, Julian C, Legras C, et al. Epilepsy, antiepileptic drugs, and malformations in children of women with epilepsy: a French prospective cohort study. Neurology 1992; 42:75.
  67. Holmes LB, Wyszynski DF, Lieberman E. The AED (antiepileptic drug) pregnancy registry: a 6-year experience. Arch Neurol 2004; 61:673.
  68. Jentink J, Dolk H, Loane MA, et al. Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study. BMJ 2010; 341:c6581.
  69. Rosa FW. Spina bifida in infants of women treated with carbamazepine during pregnancy. N Engl J Med 1991; 324:674.
  70. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol 2001; 153:961.
  71. FDA Drug Safety Communication: Risk of oral clefts in children born to mothers taking Topamax (topiramate). http://www.fda.gov/Drugs/DrugSafety/ucm245085.htm; U.S. Food and Drug administration, 2011.
  72. Mølgaard-Nielsen D, Hviid A. Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA 2011; 305:1996.
  73. Margulis AV, Mitchell AA, Gilboa SM, et al. Use of topiramate in pregnancy and risk of oral clefts. Am J Obstet Gynecol 2012; 207:405.e1.
  74. Hunt S, Russell A, Smithson WH, et al. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008; 71:272.
  75. Hesdorffer DC, Shinnar S, Lax DN, et al. Risk factors for subsequent febrile seizures in the FEBSTAT study. Epilepsia 2016; 57:1042.
  76. Hernández-Díaz S, Mittendorf R, Smith CR, et al. Association between topiramate and zonisamide use during pregnancy and low birth weight. Obstet Gynecol 2014; 123:21.
  77. Cunnington M, Tennis P, International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Lamotrigine and the risk of malformations in pregnancy. Neurology 2005; 64:955.
  78. Glaxo SmithKline. The Lamotrigine Pregnancy registry. Interim report: 1 September 1992 through 30 September 2008; Issued January 2008. http://pregnancyregistry.gsk.com/lamotrigine.html (Accessed on March 31, 2008).
  79. Cunnington MC, Weil JG, Messenheimer JA, et al. Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology 2011; 76:1817.
  80. Cunnington M, Ferber S, Quartey G, International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Effect of dose on the frequency of major birth defects following fetal exposure to lamotrigine monotherapy in an international observational study. Epilepsia 2007; 48:1207.
  81. Holmes LB, Baldwin EJ, Smith CR, et al. Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology 2008; 70:2152.
  82. Dolk H, Jentink J, Loane M, et al. Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations? Neurology 2008; 71:714.
  83. Dolk H, Wang H, Loane M, et al. Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies. Neurology 2016; 86:1716.
  84. Mawhinney E, Craig J, Morrow J, et al. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology 2013; 80:400.
  85. Shallcross R, Bromley RL, Irwin B, et al. Child development following in utero exposure: levetiracetam vs sodium valproate. Neurology 2011; 76:383.
  86. Shallcross R, Bromley RL, Cheyne CP, et al. In utero exposure to levetiracetam vs valproate: development and language at 3 years of age. Neurology 2014; 82:213.
  87. https://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.
  88. Winterfeld U, Merlob P, Baud D, et al. Pregnancy outcome following maternal exposure to pregabalin may call for concern. Neurology 2016; 86:2251.
  89. Pennell PB, Meador KJ. A common medication for neuropsychiatric illnesses may cause common problems in pregnancy. Neurology 2016; 86:2224.
  90. Morrell MJ. The new antiepileptic drugs and women: efficacy, reproductive health, pregnancy, and fetal outcome. Epilepsia 1996; 37 Suppl 6:S34.
  91. Fujii H, Goel A, Bernard N, et al. Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study. Neurology 2013; 80:1565.
  92. Montouris G. Gabapentin exposure in human pregnancy: results from the Gabapentin Pregnancy Registry. Epilepsy Behav 2003; 4:310.
  93. Hill RM, Vernaius WM, Retting GM, et al. Relationship of antiepileptic drug exposure of the infant and developmental potential. In: Epilepsy, pregnancy, and the child, Janz D, Dam M, Richens A (Eds), Raven, New York 1982.
  94. Gaily E, Kantola-Sorsa E, Granström ML. Specific cognitive dysfunction in children with epileptic mothers. Dev Med Child Neurol 1990; 32:403.
  95. Thomas SV, Sukumaran S, Lukose N, et al. Intellectual and language functions in children of mothers with epilepsy. Epilepsia 2007; 48:2234.
  96. Vinten J, Bromley RL, Taylor J, et al. The behavioral consequences of exposure to antiepileptic drugs in utero. Epilepsy Behav 2009; 14:197.
  97. Oyen N, Vollset SE, Eide MG, et al. Maternal epilepsy and offsprings' adult intelligence: a population-based study from Norway. Epilepsia 2007; 48:1731.
  98. Forsberg L, Wide K, Källén B. School performance at age 16 in children exposed to antiepileptic drugs in utero--a population-based study. Epilepsia 2011; 52:364.
  99. Cummings C, Stewart M, Stevenson M, et al. Neurodevelopment of children exposed in utero to lamotrigine, sodium valproate and carbamazepine. Arch Dis Child 2011; 96:643.
  100. McVearry KM, Gaillard WD, VanMeter J, Meador KJ. A prospective study of cognitive fluency and originality in children exposed in utero to carbamazepine, lamotrigine, or valproate monotherapy. Epilepsy Behav 2009; 16:609.
  101. Bromley RL, Mawer G, Love J, et al. Early cognitive development in children born to women with epilepsy: a prospective report. Epilepsia 2010; 51:2058.
  102. Meador KJ, Baker GA, Browning N, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 2009; 360:1597.
  103. Meador KJ, Baker GA, Browning N, et al. Effects of fetal antiepileptic drug exposure: outcomes at age 4.5 years. Neurology 2012; 78:1207.
  104. Gaily E, Kantola-Sorsa E, Hiilesmaa V, et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 2004; 62:28.
  105. Nadebaum C, Anderson VA, Vajda F, et al. Language skills of school-aged children prenatally exposed to antiepileptic drugs. Neurology 2011; 76:719.
  106. Thomas SV, Ajaykumar B, Sindhu K, et al. Motor and mental development of infants exposed to antiepileptic drugs in utero. Epilepsy Behav 2008; 13:229.
  107. Bromley RL, Mawer G, Clayton-Smith J, et al. Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology 2008; 71:1923.
  108. Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol 2013; 12:244.
  109. Bromley R, Weston J, Adab N, et al. Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child. Cochrane Database Syst Rev 2014; :CD010236.
  110. Baker GA, Bromley RL, Briggs M, et al. IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study. Neurology 2015; 84:382.
  111. Bromley RL, Calderbank R, Cheyne CP, et al. Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate. Neurology 2016.
  112. Moore SJ, Turnpenny P, Quinn A, et al. A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet 2000; 37:489.
  113. Rasalam AD, Hailey H, Williams JH, et al. Characteristics of fetal anticonvulsant syndrome associated autistic disorder. Dev Med Child Neurol 2005; 47:551.
  114. Bromley RL, Mawer GE, Briggs M, et al. The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs. J Neurol Neurosurg Psychiatry 2013; 84:637.
  115. Christensen J, Grønborg TK, Sørensen MJ, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 2013; 309:1696.
  116. Koch S, Titze K, Zimmermann RB, et al. Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents. Epilepsia 1999; 40:1237.
  117. Reinisch JM, Sanders SA, Mortensen EL, Rubin DB. In utero exposure to phenobarbital and intelligence deficits in adult men. JAMA 1995; 274:1518.
  118. Thorp JA, O'Connor M, Jones AM, et al. Does perinatal phenobarbital exposure affect developmental outcome at age 2? Am J Perinatol 1999; 16:51.
  119. Meador KJ, Baker GA, Browning N, et al. Foetal antiepileptic drug exposure and verbal versus non-verbal abilities at three years of age. Brain 2011; 134:396.
  120. Holmes LB, Coull BA, Dorfman J, Rosenberger PB. The correlation of deficits in IQ with midface and digit hypoplasia in children exposed in utero to anticonvulsant drugs. J Pediatr 2005; 146:118.
  121. Teramo K, Hiilesmaa V, Bardy A, Saarikoski S. Fetal heart rate during a maternal grand mal epileptic seizure. J Perinat Med 1979; 7:3.
  122. Nei M, Daly S, Liporace J. A maternal complex partial seizure in labor can affect fetal heart rate. Neurology 1998; 51:904.
  123. Chen YH, Chiou HY, Lin HC, Lin HL. Affect of seizures during gestation on pregnancy outcomes in women with epilepsy. Arch Neurol 2009; 66:979.
  124. Ottman R, Annegers JF, Hauser WA, Kurland LT. Higher risk of seizures in offspring of mothers than of fathers with epilepsy. Am J Hum Genet 1988; 43:257.
  125. Holmes GL, Weber DA. Effect of seizures during pregnancy on seizure susceptibility in offspring. Epilepsia 1985; 26:421.
  126. Schupf N, Ottman R. Risk of epilepsy in offspring of affected women: association with maternal spontaneous abortion. Neurology 2001; 57:1642.
  127. Tsuboi T, Endo S. Incidence of seizures and EEG abnormalities among offspring of epileptic patients. Hum Genet 1977; 36:173.
  128. Peljto AL, Barker-Cummings C, Vasoli VM, et al. Familial risk of epilepsy: a population-based study. Brain 2014; 137:795.