| AED | FDA pregnancy category* | Associated risks | Recommendations for use during pregnancy |
| Carbamazepine | C | Cardiac malformations | Lower teratogenic potential compared with phenobarbital and valproate |
| Gabapentin | C | No MCMs associated with monotherapy | Limited data suggest lower teratogenic risk compared with traditional AEDs† |
| Lamotrigine | C | No distinctive pattern of MCMs | Limited data suggest lower teratogenic risk compared with traditional AEDs† |
| Levetiracetam | C | Pyloric stenosis (in polytherapy with lamotrigine); spina bifida (in polytherapy with carbamazepine and valproate) | Limited data suggest lower teratogenic risk compared with traditional AEDs† |
| Oxcarbazepine | C | Urogenital malformations | Limited data suggest lower teratogenic risk compared with traditional AEDs† |
| Phenobarbital | D | Cardiac malformations | Best avoided in women of childbearing age |
| Phenytoin | D | Bradycardia and hypotension; fetal hydantoin syndrome | Best avoided in women of childbearing age |
| Topiramate | C | Hypospadias; oral clefts | Limited data suggest lower teratogenic risk compared with traditional AEDs† |
| Valproate | D | Cardiac malformations; hypospadias; limb reduction defects; neural tube defects; porencephaly; spina bifida | Best avoided in women of childbearing age |
| AED, antiepileptic drug; FDA, US Food and Drug Administration; MCMs, major congenital malformations. | |||
| *Category C indicates that human data are lacking and animal studies were positive OR not done; Category D indicates that human data have shown a teratogenic risk but the benefits may outweigh the risk. | |||
| †Traditional AEDs include carbamazepine, phenobarbital, phenytoin, and valproate. | |||
Switching (or stopping) AEDs before conception
Changes in AEDs are rarely made after conception. Any switches that patients may desire—from a potentially unsafe drug to a “safer” AED, for example—should be considered at least a year prior to planned pregnancy so good seizure control can be achieved before then.
In attempting a change in medication, start by checking the serum drug level of the patient’s effective, yet potentially unsafe, antiseizure drug. That allows you to determine the baseline therapeutic drug level and dose at which the patient is seizure-free. Then add the second, safer AED and taper it up to its therapeutic dose, 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.
What about stopping AED therapy entirely if your patient wants to get pregnant? Stopping AEDs 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, a structural brain lesion, persistently abnormal electroencephalograms, or any other finding that suggests she may have recurrent seizures, explain that the risk of discontinuing the medication is greater than the risk of fetal exposure to AEDs. It is also important to point out that more than 90% of women with epilepsy have normal, healthy children14—and that there are other steps to take to mitigate risk.13
What to consider in 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, available at http://aedpregnancyregistry.org. We recommend that physicians caring for pregnant women with epilepsy encourage them to enroll early on, 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.
Prenatal testing. We also recommend that pregnant women taking AEDs—particularly those on higher-risk drugs such as valproate—undergo a detailed first trimester ultrasound study between 16 and 20 weeks’ gestation. Amniocentesis should be avoided, if possible; if needed, however, amniotic alpha-fetoprotein levels may be determined for additional risk assessment.15