Epilepsy in Pregnancy

Summary

Epilepsy in pregnancy increases maternal and fetal risks from seizures and antiepileptic drugs. Preconception care should emphasize monotherapy, folic acid, and adherence, with lamotrigine or levetiracetam preferred over high-risk drugs like valproate. Regular AED monitoring during pregnancy is essential, and although delivery and breastfeeding are usually safe, obstetric complications are more common, requiring close multidisciplinary care.

Introduction

Epilepsy is a common chronic neurological disorder, affecting approximately 1 in 200–250 pregnancies, with about 24,000 women with epilepsy becoming pregnant each year in the United States. Around 30% of individuals with epilepsy are of childbearing age. While pregnancy itself does not consistently alter seizure frequency—some women experience worsening, others improvement, and many no change—epilepsy in pregnancy carries significant risks. Maternal mortality is ten times higher in women with epilepsy compared with the general population, and approximately 1 in 26 maternal deaths occurs in this group. The major concerns include teratogenic effects of antiepileptic drugs (AEDs) and seizure control during pregnancy.

Epidemiology

• 1.5 million women of reproductive age in the U.S. have epilepsy.

• 1 in 200–250 pregnancies is complicated by maternal epilepsy.

• Pregnancy does not affect seizure frequency in the majority of women.

Etiology and Risk Factors for Seizure Exacerbation

Factors contributing to increased seizure frequency during pregnancy include:

• Reduced plasma concentration of AEDs due to increased renal clearance, hepatic enzyme induction (cytochrome P450 activation by estrogen), and dilutional effect from expanded plasma volume.

• Hormonal changes, particularly an increased estrogen-to-progesterone ratio.

• Sleep deprivation.

• Psychosocial stress.

• Noncompliance with AEDs due to concerns about teratogenicity.

Pre-Pregnancy Counseling and Management

Effective management should begin before conception. Key recommendations include:

• Medication adjustment: Reduce to monotherapy wherever possible, using the lowest effective dose. Divide daily doses to minimize peak serum levels.

• Seizure-free women: If seizures have been absent for ≥2 years, consider tapering and discontinuing AEDs under medical supervision.

• Folic acid supplementation: All women with epilepsy planning pregnancy should take high-dose folic acid (5 mg daily) prior to conception to reduce the risk of neural tube defects.

• Risk counseling: Discuss potential teratogenic effects of AEDs, risks of recurrent seizures, and the importance of adherence to therapy.

Antiepileptic Drugs and Teratogenicity

• Lower teratogenic risk: lamotrigine, levetiracetam.

• Higher teratogenic risk: valproate (highest), phenobarbital, topiramate, phenytoin, carbamazepine.

• Polytherapy: significantly increases risk of congenital malformations (15–25%) compared with monotherapy (5–6%).

• Common AED-associated malformations: neural tube defects, facial clefts, and cardiac anomalies.

Intrapartum exposure to teratogenic AEDs is associated with a 2–3-fold increased risk of major congenital malformations compared with the general population.

Management During Pregnancy

• Monitoring: Regular measurement of AED plasma levels is essential, as drug clearance changes during pregnancy. Adjust doses as required to maintain therapeutic concentrations.

• Seizure control: Maintaining maternal seizure freedom is crucial, as seizures may cause maternal and fetal hypoxia. In most cases, AED dosages can remain unchanged if seizures are stable. Dosage increases are warranted with breakthrough seizures.

Complications

Fetal

• Low birth weight and small-for-gestational-age infants.

• Congenital malformations and abnormal neurocognitive development due to AED exposure.

Maternal

• Increased risk of preterm delivery, cesarean section, preeclampsia, postpartum hemorrhage, and delivery-related mortality.

Delivery and Postpartum Care

• Mode of delivery: Vaginal delivery is generally safe unless seizure frequency increases significantly during pregnancy.

• Medication: Continue AED therapy during labor.

• Breastfeeding: Generally encouraged; however, feeding is best avoided for several hours after maternal AED ingestion to reduce neonatal exposure. Mothers should be counseled on safe neonatal handling.

Differential Diagnosis of Seizures in Pregnancy

Seizures during pregnancy are not always due to epilepsy and may result from:

• Eclampsia.

• CNS infections (encephalitis, meningitis).

• Intracranial pathology (tumors, tuberculomas).

• Cerebrovascular events.

• Cerebral malaria or toxoplasmosis.

• Thrombotic thrombocytopenic purpura.

• Drug or alcohol withdrawal, toxic overdose.

• Metabolic derangements (e.g., hypoglycemia).