Taking a higher dose of topiramate during the first three months of pregnancy may increase a baby’s risk of cleft lip or palate more than lower doses, according to the Harvard T.H. Chan School of Public Health. Topiramate is prescribed to prevent seizures in people with epilepsy. It also is used to prevent migraine headaches or treat bipolar disorder. In combination with phentermine, it may be prescribed for weight loss.
“While topiramate is not recommended for pregnant women, unplanned pregnancies are common, so it’s important to fully examine any possible risk,” said Sonia Hernandez-Diaz, MD, DrPH, of the school. “Our study found that when pregnant women took topiramate during the first trimester, the baby’s risk of cleft lip or palate was three times greater than if the mom was not taking the drug. The risk was higher when the mother took high doses of the drug than when she took lower doses.”
Researchers examined Medicaid data and identified nearly 1.4 million women who delivered live babies over a 10-year period. Women who filled a prescription for topiramate during their first three months of pregnancy were compared with women who did not fill a prescription for any anti-seizure drug. They also were compared to women who filled a prescription for lamotrigine, another drug used to reduce seizures in epilepsy.
There were 2,425 pregnancies in the topiramate group, 2,796 in the lamotrigine group, and more than 1.3 million in the group not taking anti-seizure drugs. The researchers then looked at how many women in each group gave birth to a baby diagnosed with cleft lip or palate.
Among the 1.3 million pregnancies in the group not taking anti-seizure drugs, 1,501 babies had cleft lip or palate, or 1.1 per 1,000. Of the mothers taking topiramate during the first trimester, the risk of cleft lip or palate was 4.1 per 1,000. The risk was 1.5 per 1,000 among the babies born to the women taking lamotrigine.
Compared to the group not taking anti-seizure medications, women with epilepsy on topiramate had an eight times greater risk of giving birth to a baby with cleft lip or palate, while the women taking the drug for other conditions had a 50% higher risk. Women with epilepsy took a higher dose of the drug than those with other conditions. The average dose for women with epilepsy was 200 mg, while the average for women without epilepsy was 100 mg.
Also, the risk of cleft lip or palate for those taking more than 100 mg for any reason was five times greater than those not taking anti-seizure drugs, while those taking less than 100 mg had a 60% greater risk than those not taking anti-seizure drugs. Results were similar when women taking topiramate were compared with those taking lamotrigine.
“Our results suggest that women with epilepsy on topiramate have the highest relative risk of giving birth to a baby with cleft lip or cleft palate, likely due to the higher doses of topiramate when used for controlling seizures,” said Hernandez-Diaz. “The best course may be to avoid prescribing high doses of topiramate to women of childbearing age unless the benefits clearly outweigh the risks.”
The researchers note that topiramate doses were not randomly assigned to patients, so women on high doses may be different from those on low doses for reasons incompletely measured by the investigators, such as severity of epilepsy. The study, “Topiramate use early in pregnancy and the risk of oral clefts: A pregnancy cohort study,” was published by Neurology.