Guidelines on epilepsy management in pregnancy

Epilepsy is a common condition affecting many women in the reproductive age group. It is estimated that about 1 million women with epilepsy in the United States are in their reproductive years. Increased fetal and maternal risks in such patients are well established. It is with this in mind that the American Academy of Neurology (AAN) and the American Epilepsy Society (AES) published Practice Parameter Updates on the pregnant woman with epilepsy in 2009. Following are guidelines taken from that report.

The effect of antiepileptic drugs (AED)

The general worldwide incidence of major structural and genetic birth anomalies is estimated to be about 3% of births. Epileptic women taking AED during the first trimester have registered a higher incidence of such defects. This becomes quite apparent when we compare these women to those epileptics not on medication, and when we consider the effects of AED on organogenesis. Valproic acid (VPA) is shown to have a higher risk amongst the AED, with polytherapy also increasing the risk compared to monotherapy.

It is recommended that VPA be avoided especially during the first trimester, preferably preconception, if not altogether during pregnancy. Patients desiring pregnancy need to be changed to alternate therapy such as lamotrigine (LTG) or levatiracetam (LVT), which happen to be 2 of the most studied AED in pregnancy.

Increased surveillance involving detailed ultrasound scans and possibly amniocentesis are essential for these patients.

The role of Folic acid (folate)

Higher dose folic acid (about 5mg) is known to prevent neural tube defects in pregnancy, if taken at least 3 months preconceptually. Certain AED such as carbamazepine, phenytoin and even LTG lower folic acid levels and may increase the risk of neural tube defects. Although no exact evidence exists regarding the correct dosage in pregnancy, 5 mg/d of folic acid supplementation for women with epilepsy of childbearing age for 3 months prior to conception and for at least 10- to 12-weeks postconception is now the standard recommendation.

The first convulsion in pregnancy

Firstly, any convulsive event in pregnancy must be confirmed as such rather than loss of consciousness or a shaking event. Differential diagnoses include metabolic alterations and medications in the first trimester, low blood pressure and syncope in the second, and eclampsia and stroke being of more dire consequence in the third trimester and postpartum period. Mass lesions and infections can occur throughout pregnancy.

Adequate inpatient investigation includes laboratory tests, lumbar puncture, electroencephalogram (EEG) and magnetic resonance imaging (MRI) of the brain.

Once an unprovoked seizure is established, appropriate first line therapy should include enough sleep and carbamazepine or LVT depending on the seizure type. Although LTG is relatively safe, therapeutic levels are hard to achieve when started in pregnancy.

The dose of medication during pregnancy

Almost all AED levels drop during pregnancy due to increased renal clearance and hepatic elimination, but return to baseline within a few weeks of delivery. Thus, most medications require a slight dose increase once pregnancy is confirmed. LTG especially undergoes a marked drop in serum levels. Monitoring of the levels of AED should be considered.

Delivery and Postpartum

Women with well-controlled epilepsy or those seizure-free for 1 year prior to pregnancy have very little risk of a fit around the time of delivery and in the immediate postpartum period. The highest risk is with those patients with active epilepsy.

The patient should be on regular medication throughout the peripartum period and adequate rest has been shown to be beneficial. Tramadol, which is known to provoke seizures, should be avoided to further decrease the risk of an epileptic fit.

Since AED levels gradually increase back to normal postpartum, it is recommended that they be closely monitored during this period, especially in the case of LTG due to the aforementioned reason.

References

1.     Harden CL, Hopp J, Ting TY, et al. American Academy of Neurology; American Epilepsy Society. 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(2).

2.     Cunnington MC, Weil JG, Messenheimer JA et al. Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology 2011;76(21):1817–1823

3.     Tomson T, Battino D. Teratogenic effects of antiepileptic medications. Neurol Clin 2009;27(4):993–1002.

4.     De Wals P, Tairou F, Van Allen MI, et al. Reduction in neural-tube defects after folic acid fortification in Canada. 
N Engl J Med 2007;357(2):135–142.

5.     Committee on Educational Bulletins of the American College of Obstetricians and Gynecologists. ACOG 
educational bulletin. Seizure disorders in pregnancy. Int J Gynaecol 
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6.     EURAP Study Group. Seizure control and treatment in pregnancy: observations from the EURAP epilepsy 
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7.     Meador KJ, Baker GA, Browning N, et al; NEAD Study Group. Effects of breastfeeding in children of women 
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