When a woman who has epilepsy is pregnant or planning for pregnancy, you face the challenge of balancing the benefits and teratogenic risks of her antiseizure medication. Here is help.
About 500,000 women of childbearing age in the United States suffer from epilepsy.1 For these patients and their physicians, family planning and pregnancy are complex and fraught with risk.
The dilemma
Infants born to women who have epilepsy have a twofold to threefold increased risk of congenital malformations, compared with infants born to women who do not have the disorder. The increased risk is mainly related to exposure to antiepileptic drugs (AEDs).2 Recent studies also suggest that children exposed to AEDs such as valproate, phenobarbital, and phenytoin in utero may have neurocognitive deficits, even when there are no major congenital malformations.1,3,4
Yet, discontinuing the drugs prior to conception or in early pregnancy is rarely a viable option. In one recent prospective study, convulsive seizures during the first trimester (the type and timing of seizure thought to have the most harmful effect on the developing fetus) were associated with malformations in 7.4% of pregnancies.2 Seizures also increase the risk of both fetal and maternal death, although the extent of that risk is unknown.5
Practice recommendations
- If feasible, women with epilepsy who are of childbearing age and taking phenobarbital, valproate, or topiramate should be switched to a safer antiepileptic drug (AED), such as lamotrigine, prior to pregnancy.
- Avoid topiramate in women with epilepsy of childbearing age. New human data show an increased risk of oral clefts, and the FDA recently placed topiramate in Pregnancy Category D.
- Avoid switching a pregnant patient to an AED that she has not taken before.
- Use the dosage of AED at which the patient is seizure-free prior to conception as a target level to adjust dosing during pregnancy.
- Start all women who have epilepsy and are of childbearing age on ≥0.4 mg folic acid daily prior to conception.
Ideally, pregnant women with epilepsy should be under the care of both an obstetrician experienced in high-risk pregnancy and a neurologist or epileptologist. In reality, those who live in areas with limited access to such specialized care or who have limited health coverage may be cared for throughout pregnancy by a generalist ObGyn. This evidence-based review was developed with that reality in mind.
Switching (or stopping) AEDs before conception
Changes in AEDs are rarely made after conception. Any switches that a patient may desire—from a potentially unsafe drug to a “safer” AED, for example—should be considered at least a year before she plans to conceive so that good seizure control can be achieved by then.
Begin by checking the serum drug level of the patient’s effective, yet potentially unsafe, antiseizure drug. That will allow you to determine the baseline therapeutic drug level and dosage at which the patient is seizure-free. Then add the second, safer AED and taper it up to its therapeutic dosage, guided by serum drug levels and the manufacturer’s recommended titration schedule. Once the new medication has reached the therapeutic serum level, begin titrating the older AED down. If the patient suffers a breakthrough seizure during the cross-taper, we recommend aborting the process and rapidly titrating the first drug back to the predetermined therapeutic level.
Is discontinuation of AED therapy advisable if a patient wants to become pregnant?
Stopping an AED is a clinical decision made by the treating physician in accordance with the patient’s wishes on a case-by-case basis and should be considered only when it is highly likely that seizures will not recur as a result. If the patient has a history of poorly controlled epilepsy despite adequate AED trials, or if she has a structural brain lesion, persistently abnormal electroencephalograms, or any other finding that suggests that she may have recurrent seizures, explain that the risk of discontinuing the medicine is greater than the risk of fetal exposure to an AED. It is also important to point out that more than 90% of women who have epilepsy have normal, healthy children14—and that there are other steps to take to mitigate risk.13
What to consider during the first trimester
Registries that aim to gather data on the outcomes of a large number of AED-exposed pregnancies are a source of reliable information regarding the risks associated with various antiseizure agents. The primary US-based registry is the AED Pregnancy Registry (http://aedpregnancyregistry.org). We recommend that physicians caring for pregnant women who have epilepsy encourage them to enroll early, before any prenatal tests are performed. Explain to your patient that by joining the registry, she will be helping others like her make informed decisions about prenatal care.