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Antiepileptic Drugs, Epileptic Seizures and the Foetus

  • MJ Eadie
  • FJE Vajda

Abstract

This chapter deals with two main issues, viz. the possible effects of pregnancy on the course of maternal epileptic seizure disorders and the effects of seizure disorders on pregnant women and their foetuses.

The little information that is available suggests that pregnancy tends to increase the risk of loss of seizure control in women whose epilepsy is untreated. The interpretation of the more extensive literature concerning antiepileptic drug-treated epilepsy in pregnancy is confounded by the effect of pregnancy in tending to decrease circulating concentrations of antiepileptic drugs relative to drug dose. It appears that, in the majority of instances, seizure control does not deteriorate during antiepileptic drug-treated pregnancy but that, if seizure control changes, it is more likely to worsen than to improve. However, when attention has been given to maintaining satisfactory pre-pregnancy circulating concentrations of antiepileptic drugs throughout pregnancy, the impaired seizure control seems to be avoided.

There is little published evidence of maternal injury from epileptic seizures during pregnancy or of significantly increased pregnancy complications such as spontaneous abortion or stillbirth, though neonates born to women taking antiepileptic drugs tend to be a little premature, smaller and of lower birth weight for gestation age than would be expected. Seizures during pregnancy do not seem to be a significant cause of foetal damage.

Keywords

Antiepileptic Drug Epileptic Seizure Seizure Control Seizure Disorder Antiepileptic Drug Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Annegers JF, Baumgartner KB, Hauser WA, Kurland LT (1988) Epilepsy, antiepileptic drugs, and the risk of spontaneous abortion. Epilepsia 29:451–458CrossRefPubMedGoogle Scholar
  2. Artama M, Gissler M, Malm L, Rilvanen A, the Drug and Pregnancy Group (2013) Effect of maternal epilepsy and antiepileptic drugs during pregnancy on personal health of offspring: national retrospective cohort study in Finland. Drug Saf 36:359–369CrossRefPubMedGoogle Scholar
  3. Bardy AH (1987) Incidence of seizures during pregnancy, labor and the puerperium in epileptic women: a prospective study. Acta Neurol Scand 75:356–360CrossRefPubMedGoogle Scholar
  4. Barroso FV, Araujo Júnior E, Guazelli CA, Santana EF, Rolo LC, Martins MD, Moron AF (2014) Perinatal outcomes from the use of antiepileptic drugs during pregnancy: a case–control study. J Matern Fetal Neonatal Med 10:1–6CrossRefGoogle Scholar
  5. Battino D, Tomson T (2007) Management of epilepsy during pregnancy. Drugs 67:2727–2746CrossRefPubMedGoogle Scholar
  6. Battino D, Tomson T, Bonizzoni E et al (2013) Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia 54:1621–1627CrossRefPubMedGoogle Scholar
  7. Bech BH, Kjaersgaard MI, Pedersen HS et al (2014) Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study. Br Med J 349:g5159CrossRefGoogle Scholar
  8. Béraud R (1884) De l’épilepsie dans ses rapports avec la grossesse et l’accouchment bromuration pendant la grossesse. Delahays et Lecrosnier, ParisGoogle Scholar
  9. Borthen I, Gilhus NE (2012) Pregnancy complications in patients with epilepsy. Curr Opin Obstet Gynecol 24:78–83CrossRefPubMedGoogle Scholar
  10. Borthen I, Eide MG, Dalveit AK, Gilhus NE (2011) Obstetric outcome in women with epilepsy: a hospital-based, retrospective study. Br J Obstet Gynaecol 118:956–965CrossRefGoogle Scholar
  11. Cangetti C, Lattanzi S, Foschi N, Provincili L, Silvestrini M (2014) Seizure course during pregnancy in catamenial epilepsy. Neurology 83:339–344CrossRefGoogle Scholar
  12. Chen Y, Chiou HY, Lin HC, Lin HL (2009) Effect of seizures during gestation on pregnancy outcomes in women with epilepsy. Arch Neurol 66:979–984CrossRefPubMedGoogle Scholar
  13. Eadie MJ (2012) Potassium bromide and Sir Charles Locock. J R Coll Physicians Edinb 42:274–279CrossRefPubMedGoogle Scholar
  14. Edey S, Moran N, Nashef L (2013) SUDEP and epilepsy-related mortality in pregnancy. Epilepsia 55:72–74CrossRefGoogle Scholar
  15. Fuchs U (1965) Epilepsie und Schwangerschaft. Inaugural Dissertation. Heidelberg. Cited by Schmidt D (1982) loc cit Google Scholar
  16. Gjerde IO, Strandjord RE, Ulstein M (1988) The course of epilepsy during pregnancy: a study of 78 cases. Acta Neurol Scand 78:198–205CrossRefPubMedGoogle Scholar
  17. Gowers WR (1881) Epilepsy and other chronic convulsive disorders, 1st edn. J & A Churchill, LondonGoogle Scholar
  18. Harden C, Hopp J, Ting TY et al (2009) Management issues for women with epilepsy - Focus on pregnancy (an evidence-based review): 1. Obstetrical complications and change in seizure frequency. Epilepsia 50:1229–1236CrossRefPubMedGoogle Scholar
  19. Herkes GK, Eadie MJ, Sharbrough F, Moyes T (1993) Patterns of seizure occurrence in catamenial epilepsy. Epilepsy Res 15:47–52CrossRefPubMedGoogle Scholar
  20. Herpin T (1867) Des accès incomplets d’épilepsie. Ballière, ParisGoogle Scholar
  21. Herzog AG (2009) Hormone therapies. Progesterone. Neurotherap 6:383–391CrossRefGoogle Scholar
  22. Janz D, Fuchs U (1964) Are anti-epileptic drugs harmful when given during pregnancy? Ger Med Mon 9:20–22Google Scholar
  23. Katz O, Levy A, Wiznitzner A, Sheiner E (2006) Pregnancy and perinatal outcome in epileptic women: a population-based study. J Matern Fetal Neonatal Med 19:21–25CrossRefPubMedGoogle Scholar
  24. Kilic D, Pedersen H, Kjaersgaard MI et al (2014) Birth outcomes after prenatal exposure to antiepileptic drugs - A population-based study. Epilepsia 55:1714–1721CrossRefPubMedGoogle Scholar
  25. Knight AH, Rhind EG (1975) Epilepsy and pregnancy: a study of 153 pregnancies in 59 patients. Epilepsia 16:99–110CrossRefPubMedGoogle Scholar
  26. Lin HL, Chen YH, Lin HC, Lin HC (2009) No increase in adverse pregnancy outcomes for women receiving antiepileptic drugs. J Neurol 256:1742–1749CrossRefPubMedGoogle Scholar
  27. Mawer G, Briggs M, Baker GA et al (2010) Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study. Seizure 19:112–119PubMedCentralCrossRefPubMedGoogle Scholar
  28. McPherson JA, Harper LM, Odibo AO, Roehl KA, Cahill AG (2013) Maternal seizure disorder and risk of adverse pregnancy outcomes. Am J Obstet Gynecol 208:378.e1–378.e5CrossRefGoogle Scholar
  29. Morrell MJ (2002) Epilepsy in women. Am Fam Physician 66:1489–1494PubMedGoogle Scholar
  30. Otani K (1985) Risk factors for the increased seizure frequency during pregnancy and puerperium. Folia Psychiatr Neurol Jpn 39:33–41PubMedGoogle Scholar
  31. Ottman R, Annegers JF, Hauser WA, Kurland LT (1988) Higher risk of seizures in offspring of mothers than of fathers with epilepsy. Am J Hum Genet 43:257–264PubMedCentralPubMedGoogle Scholar
  32. Pennell PB, Peng L, Newport DJ et al (2008) Lamotrigine in pregnancy: clearance, therapeutic drug monitoring, and seizure frequency. Neurology 70:2130–2136PubMedCentralCrossRefPubMedGoogle Scholar
  33. Pennell PB, Klein AM, Browning N et al (2012) Differential effects of antiepileptic drugs on neonatal outcomes. Epilepsy Behav 24:449–456PubMedCentralCrossRefPubMedGoogle Scholar
  34. Pirie DAJ, Wattar BHA, Pirie AM et al (2013) Effect of monitoring strategies on seizures in pregnant women on lamotrigine: a meta-analysis. Eur J Obstet Gynecol Reprod Biol 172:26–31CrossRefPubMedGoogle Scholar
  35. Rauchenzaue M, Ehrensberger M, Prieschl M et al (2013) Generalised tonic clonic seizures and antiepileptic drugs during pregnancy: a matter of importance for the baby? J Neurol 260:484–488CrossRefGoogle Scholar
  36. Reddy DS (2010) Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives. Expert Rev Clin Pharmacol 3:183–192PubMedCentralCrossRefPubMedGoogle Scholar
  37. 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 29:13–18PubMedCentralCrossRefPubMedGoogle Scholar
  38. Richmond JR, Krishnamoorthy P, Andermann E, Benjamin A (2004) Epilepsy and pregnancy: an obstetric perspective. Am J Obstet Gynecol 190:371–379CrossRefPubMedGoogle Scholar
  39. Rosciszewska D, Buntner B, Guz I, Zawiaza L (1986) Ovarian hormones, anticonvulsant drugs, and seizures during the menstrual cycle in women with epilepsy. J Neurol Neurosurg Psychiatry 49:47–51PubMedCentralCrossRefPubMedGoogle Scholar
  40. Sabers A, Dam M (1990) Pregnancy, delivery and puerperium. In: Gram L, Dam M (eds) Comprehensive epileptology. Raven Press, New York, pp 299–307Google Scholar
  41. Sabers A, Petrenaite V (2009) Seizure frequency in pregnant women treated with lamotrigine monotherapy. Epilepsia 50:2163–2166CrossRefPubMedGoogle Scholar
  42. Schmidt D (1982) The effect of pregnancy on the natural history of epilepsy: review of the literature. In: Janz D, Bossi L, Dam M, Helge H, Richens A, Schmidt D (eds) Epilepsy, pregnancy, and the child. Raven, New York, pp 3–14Google Scholar
  43. Schmidt D, Canger R, Avanzini G et al (1983) Change in seizure frequency in pregnant epileptic women. J Neurol Neurosurg Psychiatry 46:751–755PubMedCentralCrossRefPubMedGoogle Scholar
  44. Schupf N, Ottman R (1997) Reproduction among individuals with idiopathic/cryptogenic epilepsy: risk factors for spontaneous abortion. Epilepsia 38:824–829CrossRefPubMedGoogle Scholar
  45. Shavit AG, Lermann P, Korczyn AD, Kivity S, Bechar M, Gitter S (1984) Phenytoin pharmacokinetics in catamenial epilepsy. Neurology 34:959–961CrossRefPubMedGoogle Scholar
  46. Speidel BD, Meadow SR (1972) Maternal epilepsy and abnormalities of the fetus and newborn. Lancet 2:839–843CrossRefPubMedGoogle Scholar
  47. Tanganelli P, Regesta G (1992) Epilepsy, pregnancy, and major birth anomalies; an obstetric perspective. Neurology 42:89–98PubMedGoogle Scholar
  48. Teramo K, Hillesmaa VK (1982) Pregnancy and fetal complications in epileptic pregnancies: review of the literature. In: Janz D, Bossi L, Dam M, Helge H, Richens A, Schmidt D (eds) Epilepsy, pregnancy and the child. Raven, New York, pp 53–59Google Scholar
  49. Teramo K, Hillesmaa VK, Bardy A, Saarikoski S (1979) Fetal heart rate during a maternal grand mal epileptic seizure. J Perinat Med 7:3–6CrossRefPubMedGoogle Scholar
  50. The EURAP Study Group (2006) Seizure control and treatment in pregnancy. Observations from the EURAP Epilepsy Pregnancy Registry. Neurology 66:354–360CrossRefGoogle Scholar
  51. Thomas SV, Sindhu K, Ajaykumar B, Sulekha Devi PB, Sujamol J (2009) Maternal and obstetric outcome of women with epilepsy. Seizure 18:63–66CrossRefGoogle Scholar
  52. Thomas SV, Syam U, Devi JS (2012) Predictors of seizures during pregnancy in women with epilepsy. Epilepsia 53:e85–e88CrossRefPubMedGoogle Scholar
  53. Vajda FJE, Hirchcock A, Graham J, O’Brien T, Lander C, Eadie M (2008) Seizure control in antiepileptic drug-treated pregnancy. Epilepsia 49:172–175CrossRefPubMedGoogle Scholar
  54. Veiby G, Daltveit AK, Engelsen BA, Gilhus NE (2009) Pregnancy, delivery, and outcome for the child in maternal epilepsy. Epilepsia 50:30–39CrossRefGoogle Scholar
  55. Wegner I, Edelsbroek P, de Haan G-J, Lindhout D, Sander JW (2010) Drug monitoring of lamotrigine and oxcarbazepine combinations during pregnancy. Epilepsia 51:2500–2502CrossRefPubMedGoogle Scholar
  56. Wilks S (1861) Bromide and iodide of potassium in epilepsy. Med Times Gaz ii:635–636Google Scholar
  57. Yerby MS (2008) Pregnancy and the mother with epilepsy. In: Pedley TA, Engel J (eds) Epilepsy. A comprehensive textbook. Wolters Kluwer Lippincott Williams & Wilkins, Philadelphia, pp 2067–2074Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • MJ Eadie
    • 1
  • FJE Vajda
    • 2
  1. 1.Clinical Neurology and NeuropharmacologyUniversity of Queensland, and Honorary Consultant Neurologist, Royal Brisbane and Women’s HospitalBrisbaneAustralia
  2. 2.Department of Medicine and Neurology Director of the Australian Epilepsy and Pregnancy RegisterUniversity of Melbourne and Royal Melbourne HospitalMelbourneAustralia

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