Current Treatment Options in Neurology

, Volume 4, Issue 1, pp 31–40 | Cite as

Epilepsy in pregnant women

  • Michiko Kimura Bruno
  • Cynthia L. Harden
Article

Opinion statement

  • For women of childbearing potential with epilepsy, seizures should be controlled with the smallest dosage of anti-epileptic drug (AED). Treatment with monotherapy should be achieved, if possible.

  • The possibility of AED withdrawal should be considered in appropriate clinical setting prior to conception, and the AED treatment should be optimized prior to conception. Many pregnancies are unplanned, underscoring the need for constant vigilance in streamlining the treatment regimen.

  • Prenatal counseling becomes particularly important, in order that both the physician and patient have open communication and realistic expectations about the course and outcome of a potential pregnancy. All women of childbearing potential with epilepsy should be informed about the known rates of teratogenicity of AEDs, possibility of increased seizure frequency during pregnancy, and the risks of the pregnancy and labor.

  • All of the conventional AEDs are associated with an increased risk of major and minor anomalies in the offspring and are categorized as US Food and Drug Administration class C or D. Polytherapy increases this risk. Valproic acid and carbamazepine are each associated with an increased risk of neural tube defects, and should be avoided by women with a family history of spina bifida. This combination should be avoided, if possible.

  • When a woman with epilepsy presents with pregnancy, a monotherapy regimen should not be changed if the seizures are well controlled. Reducing the number of AEDs can be considered in case of polytherapy, if the seizures are well controlled. If seizures are poorly controlled, adequate seizure control is the primary goal.

  • Serum AED levels should be documented prior to conception, and within each trimester. More frequent monitoring may be necessary in case of poorly controlled seizures. If seizures have occurred during pregnancy, therapeutic AED levels should be documented in the late third trimester, prior to delivery. Phenytoin levels should also include an unbound fraction (“free” level); other unbound AED levels are not generally available. The dose adjustment should be made taking the whole clinical picture into account.

  • Vitamin K 10 mg per day orally should be administered in the last 4 weeks of pregnancy for women taking hepatic enzyme-inducing AEDS (phenytoin, phenobarbital, primidone, carbamazepine, topiramate, and oxcarbazepine). The newborn should receive vitamin K 1 mg intravenously or intramuscularly regardless of maternal AED exposure.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Practice Parameter: Management issues for women with epilepsy (summary statement). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1998, 51:944–948. Comprehensive guide for treatment of women with epilepsy.Google Scholar
  2. 2.
    Morrell MJ: Epilepsy in women: the science of why it is special. Neurology 1999, 53(suppl):S42-S48.PubMedGoogle Scholar
  3. 3.
    Nulman I, Laslo D, Koren G: Treatment of epilepsy in pregnancy. Drugs 1999, 57:535–544.PubMedCrossRefGoogle Scholar
  4. 4.
    Zahn CA, Morrell MJ, Collins SD, et al.: Management issues for women with epilepsy. Neurology 1998, 51:949–956.PubMedGoogle Scholar
  5. 5.
    Olafsson E, Hallgrimsson JT, Hauser WA, et al.: Pregnancies of women with epilepsy: a populationbased study in Iceland. Epilepsia 1998, 39:887–892.PubMedCrossRefGoogle Scholar
  6. 6.
    Holmes LB, Harvey EA, Coull BA, et al.: The teratogenicity of anticonvulsant drugs. N Engl J Med 2001, 344:1132–1138. This large retrospective study supports the teratogenicity of anti-epileptic drugs.PubMedCrossRefGoogle Scholar
  7. 7.
    Kaneko S, Battino D, Andermann E, et al.: Congenital malformations due to antiepileptic drugs. Epilepsy Res 1999, 33:145–158.PubMedCrossRefGoogle Scholar
  8. 8.
    Samren 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, 38:981–990.PubMedCrossRefGoogle Scholar
  9. 9.
    Arpino C, Brescianini S, Robert E, et al.: Teratogenic effects of antiepileptic drugs: use of an International Database on Malformations and Drug Exposure (MADRE). Epilepsia 2000, 41:1436–1443.PubMedCrossRefGoogle Scholar
  10. 10.
    Canger R, Battino D, Canevini MP, et al.: Malformations in offspring of women with epilepsy: a prospective study. Epilepsia 1999, 40:1231–1236.PubMedCrossRefGoogle Scholar
  11. 11.
    Moore SJ, Turnpenny P, Quinn A, et al.: A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet 2000, 37:489–497.PubMedCrossRefGoogle Scholar
  12. 12.
    Scolnik D, Nulman I, Rovet J, et al.: Neurodevelopment of children exposed in utero to phenytoin and carbamazepine monotherapy. JAMA 1994, 271:767–770.PubMedCrossRefGoogle Scholar
  13. 13.
    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, 40:1237–1243.PubMedCrossRefGoogle Scholar
  14. 14.
    Gaily E, Granstrom ML: Minor anomalies in children of mothers with epilepsy. Neurology 1992, 42(suppl):128–131.PubMedGoogle Scholar
  15. 15.
    Lindhout D, Hoppener RJ, Meinardi H: Teratogenicity of antiepileptic drug combinations with special emphasis on epoxidation (of carbamazepine). Epilepsia 1984, 25:77–83.PubMedGoogle Scholar
  16. 16.
    Buehler BA, Delimont D, van Waes M, Finnell RH: Prenatal prediction of risk of the fetal hydantoin syndrome. N Engl J Med 1990, 322:1567–1572.PubMedCrossRefGoogle Scholar
  17. 17.
    Schmidt D, Canger R, Avanzini G, et al.: Change of seizure frequency in pregnant epileptic women. J Neurol Neurosurg Psychiatry 1983, 46:751–755.PubMedCrossRefGoogle Scholar
  18. 18.
    Tomson T, Lindbom U, Ekqvist B, Sundqvist A: Epilepsy and pregnancy: a prospective study of seizure control in relation to free and total plasma concentrations of carbamazepine and phenytoin. Epilepsia 1994, 35:122–130.PubMedCrossRefGoogle Scholar
  19. 19.
    Yerby MS: Quality of life, epilepsy advances, and the evolving role of anticonvulsants in women with epilepsy. Neurology 2000, 55(suppl):S21-S31.PubMedGoogle Scholar
  20. 20.
    Minkoff H, Schaffer RM, Delke I, Grunebaum AN: Diagnosis of intracranial hemorrhage in utero after a maternal seizure. Obstet Gynecol 1985, 65(suppl):22S-24S.PubMedGoogle Scholar
  21. 21.
    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.PubMedCrossRefGoogle Scholar
  22. 22.
    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(suppl):94–110.PubMedGoogle Scholar
  23. 23.
    Centers for Disease Control and Prevention: Recommendation for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR CDC Surveilll Summ 1992, 41:1–7.Google Scholar
  24. 24.
    Wegner C, Nau H: Alteration of embryonic folate metabolism by valproic acid during organogenesis: implications for mechanism of teratogenesis. Neurology 1992, 42(suppl):17–24.PubMedGoogle Scholar
  25. 25.
    Hernandez-Diaz, Werler MM, Walker AM, Mitchell AA: Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000, 343:1608–1614. This study demonstrated that adding folic acid did not change the risk of neural tube defects, and suggests that teratogenicity of AED is not necessarily related to folic acid deficiency.PubMedCrossRefGoogle Scholar
  26. 26.
    Seale CG, Morell MJ, Nelson L, Druzin ML: Analysis of prenatal and gestational care given to women with epilepsy. Neurology 1998, 51:1039–1045. This study shows that despite various recommendations and interest in the topic of pregnancy and epilepsy, the actual care of pregnant women with epilepsy may be still far from ideal.PubMedGoogle Scholar
  27. 27.
    Fairgrieve SD, Jackson M, Jonas P, et al.: Population based, prospective study of the care of women with epilepsy in pregnancy. BMJ 2000, 321:674–675.PubMedCrossRefGoogle Scholar
  28. 28.
    Practice Parameter: A guideline for discontinuing antiepileptic drugs in seizure-free patients-summary statement. Report of the Quality Standard Subcommittee of the American Academy of Neurology. Neurology 1996, 47:600–602.Google Scholar
  29. 29.
    Delgado-Escueta AV, Janz D: Consensus guidelines: preconception counseling, management, and care of the pregnant woman with epilepsy. Neurology 1992, 42(suppl):149–160.PubMedGoogle Scholar
  30. 30.
    Lindhout D, Schmidt D: In-utero exposure to valproate and neural tube defects. Lancet 1986, 1:1392–1393.PubMedCrossRefGoogle Scholar
  31. 31.
    Rosa FW: Spina bifida in infants of women treated with carbamazepine during pregnancy. N Engl J Med 1991, 324:674–677.PubMedCrossRefGoogle Scholar
  32. 32.
    Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA: Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol 2001, 153:961–968.PubMedCrossRefGoogle Scholar
  33. 33.
    Yerby MS, Friel PN, McCormick K: Antiepileptic drug disposition during pregnancy. Neurology 1992, 42(suppl):12–16.PubMedGoogle Scholar
  34. 34.
    Committee on Nutrition of the American Academy of Pediatrics: Vitamin K compounds and their water soluble analogues: use in therapy and prophlaxis in pediatrics. Pediatrics 1961, 8:501–507.Google Scholar
  35. 35.
    Cornelissen M, Steegers-Theunissen R, Kollee L, et al.: Increased incidence of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. Am J Obstet Gynecol 1993, 168:923–928.PubMedGoogle Scholar
  36. 36.
    Lundburg YW, Greer KA, Zhao J: Mapping of a chromosomal locus for valproic acid-induced neural tube defects. Am J Human Genet 2000, 67(suppl):20.Google Scholar
  37. 37.
    Morrell MJ: The new antiepileptic drugs and women: efficacy, reproductive health, pregnancy, and fetal outcome. Epilepsia 1996, 37(suppl):S34-S44. This article gives an overview of the gender-specific issues on new AEDs.PubMedCrossRefGoogle Scholar
  38. 38.
    Topiramate prescribing information [package insert]. Raritan, NJ: Ortho-McNeil Pharmaceutical, Inc.; 1999.Google Scholar
  39. 39.
    Reiff-Eldridge R, Heffner CR, Ephross SA, et al.: Monitoring pregnancy outcomes after prenatal drug exposure through prospective pregnancy registries: a pharmaceutical company commitment. Am J Obstet Gynecol 2000, 182:159–163.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2002

Authors and Affiliations

  • Michiko Kimura Bruno
  • Cynthia L. Harden
    • 1
  1. 1.Comprehensive Epilepsy CenterWeill Medical College of Cornell UniversityNew YorkUSA

Personalised recommendations