Birth Defect Risk from Epilepsy Drugs Low, But Topamax Data Inconclusive

The use of newer antiepileptic drugs during pregnancy was not associated with a significantly increased risk of major birth defects, according to a new study. However, the research did not reach any conclusion about the risk of birth defects with Topamax, which was only used by a very small number of women in the study. 

The data was published online by the Journal of the American Medical Association (JAMA).

Danish researchers looked at data on 800,000 births in the study, which included 1,532 women who took a second-generation anti-seizure drug during the first month of pregnancy. However, only about 100 took Topamax, which has recently been linked to an increased risk of cleft palate and cleft lip.

Looking at the results for all second-generation epilepsy drugs, which also include Lamictal, Trileptal, Neurontin andKeppra, researchers found little difference in the rate of birth defects between women who took the drugs and those who took no medications to treat seizures. Most of the women included in the study took Lamictal (lamotrigine).

Researchers indicated that the limited number of women who used Topamax prevented them from reaching any conclusions about the risk of Topamax birth defects. Earlier this year, the FDA required new warnings about the risk of cleft palate and lip from Topamax, after data suggested that use of that second-generation epilepsy drug may be linked to a 16 times higher risk of the birth defects.

According the findings of this most recent study, only about 3.2% of the children whose mothers were given any of the newer antiepileptic drugs were born with major birth defects. That compares with about 2.4% of children born with major birth defects from women who had not taken any antiepileptic drugs while pregnant.

Older epilepsiy drugs, like Depakote and Tegretol, which have been linked to an increased risk of birth defects for years, were not included in the research. A study late last year linked Tegretol side effects to an increased risk of spina bifida, and another study found that Depakote was twice as likely as Tegretol to cause birth defects, including spina bifida and oral cleft defects.

Concerns about second-generation epilepsy drug side effects has increased since the FDA issued warnings about Topamax in March. Due to the Topamax cleft palate and lip risk, the federal drug regulatory agency urged doctors to avoid prescribing the medication to pregnant women or women of child-bearing age, as it appeared that alternative drugs to control seizures may not carry the same risk.

Topamax (topiramate) was first approved for treatment of epilepsy, which is a neurological disorder characterized by recurrent uncontrolled seizures. In 2004, the FDA approved Topamax for an additional use of treating severe headaches known as migraines. It is also used off-label by many doctors to treat bipolar disorder. Generic forms of the drug began to appear in 2006.

Cleft palate and cleft lip occur when parts of the lip or palate fail to completely fuse together. The defect results in the child being born with defects as small as a notched lip to extreme as an open groove that goes from the roof of the mouth to the nose. Cleft palate and cleft lip can cause problems eating and talking and can increase the risk of ear infections, resulting in the need for corrective surgery.

A number of women who have given birth to children with a defect or malformation after using the drug while pregnant are considering a potential Topamax lawsuit against the drug makers as a result of their failure to research the pregnancy risks associated with the medication or adequately warn about the risk of problems from the epilepsy drug.