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Tuesday, January 2, 2018

High Doses of Epilepsy Drug Early in Pregnancy Linked with Increased Risk of Oral Clefts in Children



Women who used topiramate (Topamax), a drug commonly prescribed for epilepsy, early in pregnancy had an increased risk of having children with oral clefts, especially if they took a high dose, according to a study published online on December 27 in Neurology.

Risks for New Mothers

Topiramate is an effective drug for controlling seizures. It is also prescribed to treat migraines and bipolar disorder. Previous research has shown that taking topiramate early in pregnancy may increase the risk of oral clefts—an opening or split in the roof of the mouth and lip—in children.

Digging through the Data

To find out more about the link between topiramate and oral clefts in children, researchers at Brigham and Women's Hospital, Harvard Medical School, and Massachusetts General Hospital in Boston, MA assessed data from the Medicaid Analytic eXtract (MAX) database, which contains information on patients who receive health insurance under the United States government's Medicaid program. They identified a total of 1,360,101 women between 12 and 55 years old who had had a live-born infant and were enrolled in Medicaid from three months before conception through one month after delivery between 2000 and 2010.

They used Medicaid records to identify women who filled at least one topiramate prescription during the first trimester (the first 90 days) of pregnancy. They divided the women into topiramate users and non-users. Then they used inpatient and outpatient codes contained in hospital medical records to identify oral clefts in infants born to these mothers.

Finally, the researchers compared the incidence of oral clefts between women who had taken topiramate during pregnancy and those who had not.

Significant Link

They found a significant association between topiramate use early in pregnancy and the risk of oral clefts. Among a total of 2,425 infants born to women who took topiramate, the risk of oral clefts at birth was 4.1 per 1,000, compared to 1.1 per 1,000 among infants born to women who did not take topiramate. Among non-topiramate users, the researchers found that those who used lamotrigine, an alternative to topiramate for controlling seizures, had the same lower risk of oral clefts as those who did not use any anticonvulsants, suggesting the risk of oral clefts is unique to topiramate.

Dose Effect

When the researchers looked at women who took topiramate for different conditions, they found that the risk of oral clefts was especially high for those who took it to treat epilepsy. The risk was still present, but less high, for women who took the drug for other conditions, such as bipolar disorder. The risk was also higher with higher doses: Women who took more than 100 mg a day were three times more likely to have children with oral clefts than those who took less than a 100 mg dose.​

These two findings may be related, the researchers noted, since women with epilepsy are likely to be prescribed higher doses than women with other conditions.