THE CHALLENGE OF TREATING EPILEPSY IN PREGNANCY: MATERNAL AND OFFSPRING PERSPECTIVES
Abstract
Epilepsy is a common medical and social disorder and usually defined as a tendency to recurrent seizures. Freedom from seizures is the ultimate goal in treatment of patients with epilepsy. At the same time, the side effects of antiepileptic drugs (AEDs) should not outweigh the benefits of treatment. This is particularly important in epileptic women who wish to become pregnant. Those women have a higher risk for pregnancy-related complications. For babies whose mothers take AEDs, the risk of birth defects is 4 to 8 percent, compared with 2 to 3 percent for controls. The risk seems to be highest when multiple AEDs are taken, but without medication, uncontrolled seizures may deprive the baby of oxygen. Seizures can also increase the risk of miscarriage or stillbirth. By working with her physicians, a woman with epilepsy can become pregnant and have a happy outcome. In the Sudan we lack national epidemiological studies using standardized definitions and case ascertainment methods on epilepsy as general and in pregnancy, but according to the WHO the number of people with epilepsy is high in most regions of the world. The mean number per 1000 population is 8.93 (SD 8.14, median 7.59). This knowledge is essential for the identification of needs and the planning of appropriate services. This a thorough review of more than 40 articles published over the last 10 years. However, it is not a complete reference for designing a protocol for the management of epilepsy in pregnant women. It aims at discussing current management of epilepsy and pregnancy, including the fetal outcome and teratogenicity of AEDs. It is part of a series mandated by the Gezira Epilepsy Care Program (GECP), to obtain baseline data for a community-adapted epilepsy education and awareness program.
References
2. Vajda FJ, O'Brien TJ, Hitchcock A, Graham J, Lander C. The Australian registry of anti-epileptic drugs in pregnancy: experience after 30 months. J Clin Neurosci. Sep 2003;10(5):543-9.
3. O'Brien MD. Management of epilepsy in women. Postgraduate Medical Journal. 2005;81:278.
4. Titze K, Koch S, Helge H, Lehmkuhl U, Rauh H, Steinhausen HC. Prenatal and family risks of children born to mothers with epilepsy: effects on cognitive development. Dev Med Child Neurol. Feb 2008;50(2):117-22.
5. Vajda FJ, Hitchcock A, Graham J, Solinas C, O'Brien TJ, Lander CM, et al. Foetal malformations and seizure control: 52 months data of the Australian Pregnancy Registry. Eur J Neurol. Jun 2006;13(6):645-54.
6. Sankar R. Teratogenicity of antiepileptic drugs: role of drug metabolism and pharmacogenomics. Acta Neurol Scand. Jul 2007;116(1):65-71.
7. Holmes GL, Harden C, Liporace J, Gordon J. Postnatal concerns in children born to women with epilepsy. Epilepsy Behav. Nov 2007;11(3):270-6.
8. Tomson T, Battino D. Teratogenic effects of antiepileptic drugs. Seizure. Mar 2008;17(2):166-71.
9. Tomson T, Battino D, French J, Harden C, Holmes L, Morrow J, et al. Antiepileptic drug exposure and major congenital malformations: the role of pregnancy registries. Epilepsy Behav. Nov 2007;11(3):277-82.
10. Tomson T, Battino D. Teratogenic effects of antiepileptic drugs. Seizure. Mar 2008;17(2):166-71.
11. Kaplan PW, Norwitz ER, Ben-Menachem E, Pennell PB, Druzin M, Robinson JN, et al. Obstetric risks for women with epilepsy during pregnancy. Epilepsy Behav. Nov 2007;11(3):283-91.
12. Artama M, Auvinen A, Raudaskoski T, Isojarvi I, Isojarvi J. Antiepileptic drug use of women with epilepsy and congenital malformations in offspring. Neurology. Jun 14 2005;64(11):1874-8.
13. Battino D, Tomson T. Management of epilepsy during pregnancy. Drugs. 2007;67(18):2727-46.
14. Katz JM, Pacia SV, Devinsky O. Current Management of Epilepsy and Pregnancy: Fetal Outcome, Congenital Malformations, and Developmental Delay. Epilepsy Behav. Apr 2001;2(2):119-123.
15. EURAP Study Group. Seizure control and treatment in pregnancy: observations from the EURAP epilepsy pregnancy registry. Neurology. Feb 14 2006;66(3):354-60.
16. Mawer G, Clayton-Smith J, Coyle H, Kini U. Outcome of pregnancy in women attending an outpatient epilepsy clinic: adverse features associated with higher doses of sodium valproate. Seizure. Dec 2002;11(8):512-8.
17. Kaplan PW, Norwitz ER, Ben-Menachem E, Pennell PB, Druzin M, Robinson JN, et al. Obstetric risks for
women with epilepsy during pregnancy. Epilepsy Behav. Nov 2007;11(3):283-91.
18. Battino D, Tomson T. Management of epilepsy during pregnancy. Drugs. 2007;67(18):2727-46.
19. Ohman I, Vitols S, Luef G, Soderfeldt B, Tomson T. Topiramate kinetics during delivery, lactation, and in the neonate: preliminary observations. Epilepsia. Oct 2002;43(10):1157-60.
20. Olafsson E, HauserA, Gudmundsson G. Fertility in patients with epilepsy. A population-based study. Neurology 1998;51:71-73.
21. Viinikainen K, Heinonen S, Eriksson K, Kalviainen R. Fertility in women with active epilepsy. Neurology. Nov 27 2007;69(22):2107-8.
22. Wide K, Winbladh B, Källén B. 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. Feb 2004;93(2):174-6.
23. Pennell PB. Antiepileptic drug pharmacokinetics during pregnancy and lactation. Neurology. Sep 1 2003;61(6 Suppl 2):S35-42.
24. BNF for children. The essential resource for clinical use of medicines in children. BMJ group (Publisher), London 2008. ISBN: 978 0 85369 780 0
25. Perucca E. Birth defects after prenatal exposure to antiepileptic drugs. Lancet Neurol. Nov 2005;4(11):781-6.
26. Thomas SV, Ajaykumar B, Sindhu K, Francis E, Namboodiri N, Sivasankaran S, et al. Cardiac malformations are increased in infants of mothers with epilepsy. Pediatr Cardiol. May 2008; 29(3):604-8.
27. Wide K, Winbladh B, Källén B. 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. Feb 2004;93(2):174-6.
28. Wide K, Henning E, Tomson T, Winbladh B. Psychomotor development in preschool children exposed to antiepileptic drugs in utero. Acta Paediatr. 2002; 91(4):409-14.
29. 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. Apr 16, 2009; 360(16):1597-1605.
30. Vajda F, Solinas C, Graham J, Hitchcock A, Eadie M. The case for lamotrigine monitoring in pregnancy. J Clin Neurosci. Jan 2006; 13(1):103-4.
31. Richmond JR, Krishnamoorthy P, Andermann E, Benjamin A. Epilepsy and pregnancy: an obstetric perspective. Am J Obstet Gynecol. Feb 2004;190 (2):371-9.
32. Pilo C, Wide K, Winbladh B. Pregnancy, delivery, and neonatal complications after treatment with antiepileptic drugs. Acta Obstet Gynecol Scand. 2006;85 (6):643-6.
33. Titze K, Koch S, Helge H, Lehmkuhl U, Rauh H, Steinhausen HC. Prenatal and family risks of children born to mothers with epilepsy: effects on cognitive development. Dev Med Child Neurol. Feb 2008;50(2):117-22.
34. Wu SP, Shyu MK, Liou HH, Gau CS, Lin CJ. Interaction between anticonvulsants and human placental carnitine transporter. Epilepsia. Mar 2004;45(3):204-10.
