What the Research Shows: Pregnancy

Between 1992 and 1999, pregnancy registries have been established in the U.S. and overseas to study the fetal effects of anticonvulsant drugs and are now beginning to report their results. The North American Pregnancy Registry (funded by a consortium of pharmaceutical companies which manufacture anticonvulsants), the Australian Pregnancy Registry, the United Kingdom Pregnancy Registry, and some academic centers have recently reported that while all anticonvulsant medications carry some risk to a developing child, one of the older drugs — sodium valproate — is consistently associated with an increased risk of birth defects and developmental disorders, ranging from 6.1 percent to 16.7 percent. The North American Pregnancy Registry has also reported an elevated risk of malformations (6.5 percent) in children of mothers who took phenobarbital during pregnancy.

While physical malformations can be identified at birth or shortly after, effects on a child’s neurological, intellectual, and behavioral development take longer to emerge and require follow up for several years. The long term NEAD study is finding some of these effects following prenatal exposure to carbamazepine (8 percent), lamotrigine (1 percent), phenytoin (10 percent) or valproate (25 percent) while other studies have linked valproate during pregnancy to cognitive effects in offspring.

Although these studies currently trend towards the conclusion that valproate is not a good first choice for women during pregnancy, the experts are quick to urge caution and point out that, with epilepsy, seizure control is still paramount. Valproate has been a highly successful drug in the treatment of epilepsy and other disorders. For some women, it may be the only drug that prevents seizures. Even less is known about the comparative risks for birth defects of valproate and other drugs used to treat disorders such as bipolar disorder. And as already noted, seizures during pregnancy carry risk to both mother and child. Similarly, women with some types of pain, mood disorders, migraine or other neuropsychiatric conditions may continue to need valproate for relief. It is also important to remember that the vast majority of women who take this medication during pregnancy deliver healthy infants.

There is far less information from research concerning the effects of the newer anticonvulsants on the offspring of women treated with them during pregnancy. One company-sponsored report comes from the U.K based International Lamotrigine Pregnancy Registry, which is funded by GlaxoSmithKline, the pharmaceutical company that manufactures lamotrigine. This registry reported on the rate of major malformations in infants of women who took lamotrigine as a single drug to be 2.9 percent. A few reports have been published on other newer medications, including gabapentin, levetiracetam, oxcarbazepine, zonisimide and topiramate; however, the very small number of patients involved in these studies prevents any conclusions at this time.

Pregnancy, however, is not the only issue about which women on anticonvulsants need to be informed. A key factor in the Epilepsy Foundation’s decision to mount a new Call to Action campaign targeted to women and their healthcare providers is the stream of new research concerning other physical effects associated with women’s long term use of some of these medications. Bone loss, weight gain, hormonal and cognitive/behavioral effects are among those identified so far.