Elsevier

Neurologic Clinics

Volume 22, Issue 4, November 2004, Pages 799-820
Neurologic Clinics

Pregnancy in women who have epilepsy

https://doi.org/10.1016/j.ncl.2004.07.004Get rights and content

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Birth control for women taking antiepileptic drugs

Careful planning requires effective birth control. Many of the AEDs induce the hepatic cytochrome P-450 system, which also is the primary metabolic pathway of the sex steroid hormones. The resulting increased enzymatic activity can lead to rapid clearance of steroid hormones and allow ovulation in women taking oral contraceptives or other hormonal forms of birth control [4], [5]. In 1998, the recommendation in the guidelines by the American Academy of Neurology was to use an estradiol dose of

The fetal anticonvulsant syndrome

Offspring of women who have epilepsy are at an increased risk for intrauterine growth retardation, minor anomalies, major congenital malformations, cognitive dysfunction, microcephaly, and infant mortality [10], [11]. The term, “fetal anticonvulsant syndrome,” is used to include various combinations of these findings and has been described with virtually all the AEDs [12], [13].

Intrauterine growth retardation results in low birth weight (less than 2500 g) in 7% to 10% of infants born to women

Potential mechanisms

The causes of the anticonvulsant embryopathy likely are multifactorial. Recent studies, however, support that anticonvulsant drugs are the most significant offending factor, more so than actual traits carried by mothers who have epilepsy, environmental factors, or possibly seizures during pregnancy [32], [39], [61]. A recent research group reports that infants whose mothers have a history of epilepsy but took no AEDs during pregnancy do not have a higher frequency of these abnormalities

Seizures during pregnancy

The effect of pregnancy on seizure frequency is variable and unpredictable among patients. According to recent studies, approximately 20% to 33% of patients have an increase in their seizures, 7% to 25% a decrease in seizures, and 50% to 83% no significant change [85], [86], [87], [88]. Pregnancy is associated with physiologic and psychologic changes that can alter seizure frequency, including changes in sex hormone concentrations, changes in AED metabolism, sleep deprivation, and new stresses.

Antiepileptic drug management

Management of AEDs during pregnancy can be complex. Clearance of virtually all of the AEDs increases during pregnancy, resulting in a decrease in serum concentrations (Table 4) [88], [96], [97]. Clearance of most of the AEDs normalizes gradually during the first 2 to 3 postpartum months. LTG metabolism, however, undergoes an exaggerated increase throughout pregnancy and quickly converts back to baseline clearance within the first few weeks post partum [98], [99], [100].

Several physiologic

Obstetric complications

Women who have epilepsy have an increased risk for certain obstetric complications. There is an approximately twofold increased risk for vaginal bleeding, hyperemesis gravidarum, anemia, eclampsia, abruptio placentae, preterm delivery, and the need for induced labor, interventions during labor, or cesarean section [10], [104]. Weak uterine contractions are described in women taking AEDs, which may account for the twofold increase in use of interventions during labor and delivery, including

Neonatal vitamin K deficiency

Many of the AEDs can inhibit vitamin K transport across the placenta [105], [106], [107]. AEDs reported to induce a vitamin K deficiency in the fetus include CBZ, PHT, PB, ethosuximide (ESX), vigabatrin, PRM, diazepam, mephobarbital, and amobarbital [10], [108]. Other AEDs may be involved but have not yet been studied. One report of 25 women taking AEDs found that maternal vitamin K concentrations were lower and the presence of detectable protein induced by vitamin K absence of factor II

Labor and delivery

The majority of women who have epilepsy have a safe vaginal delivery without seizure occurrence. One research group reports that in their epilepsy population only 1% to 2% of women had GTCSs during labor, and an additional 1% to 2% had seizures during the first 24 hours after delivery [111]. Seizures during labor and delivery, however, may be more likely to occur in women who have primary generalized epilepsy; one study reports an occurrence rate in 12.5% compared with 0% of women who had

Postpartum care

Most of the AED levels gradually increase after delivery and plateau by 10 weeks post partum. AED levels should be followed closely during this postpartum period [6]. LTG levels, however, increase immediately and plateau within 2 to 3 weeks post partum. Adjustments in LTG doses may be needed on an anticipatory basis beginning within the first few days after delivery [99].

Perinatal lethargy, irritability, and feeding difficulties are attributed to intrauterine exposure to benzodiazepines and

Summary

Ideal, comprehensive care of women who have epilepsy during the reproductive years must include effective preconceptional counseling and preparation. The importance of planned pregnancies with effective birth control should be emphasized, with consideration of the effects of the enzyme-inducing AEDs on lowering efficacy of hormonal contraceptive medications and the need for back-up barrier methods.

Before pregnancy occurs, the patient's diagnosis and treatment regimen should be reassessed. Once

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    Funding supported by a Specialized Center of Research grant P50 MH68036 from the National Institutes of Health.

    Dr. Pennell has received speaking honoraria from GlaxoSmithKline (Durham, NC); UCB Pharma (Smyrna, GA); Novartis (Morristown, NJ); and Pfizer (Cambridge, MA); Dr. Pennell has received consulting fees from Ortho-McNeill (Raritan, NJ); Novartis, GlaxoSmithKline, and Elan Pharmaceuticals (San Diego, CA). Dr. Pennell has received research support from GlaxoSmithKline and Pfizer.

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