Study: Antiepileptic drug in early pregnancy increases oral cleft risk in babies
Women taking the commonly used antiepileptic drug topiramate during early pregnancy are more likely to give birth to a baby with an oral cleft, a major US study found.
Using data from more than one million live births in the US, investigators from Brigham and Women's Hospital and the Harvard T.H. Chan School of Public Health examined the risk of oral clefts, including cleft palate or cleft lip, in newborn babies.
They compared three groups of babies: Those born to women who had taken topiramate in their first trimester; babies born to women who had taken the drug lamotrigine, an unrelated drug used to treat bipolar disorder and epilepsy; and those who had not been exposed to antiepileptic medications in utero.
It turned out that the risk of oral clefts was approximately three times higher for the topiramate group than for either the lamotrigine or the unexposed group.
Approximately one out of every 1,000 infants are born with an oral cleft, but among infants exposed to low doses of topiramate, defined as 100 mg each day, in the first trimester, that risk was 2.1 out of every 1,000 live births.
Among women taking higher doses of topiramate, defined as 200 mg each day, the risk was much higher – 12.3 for every 1,000 live births.
"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 corresponding author Sonia Hernandez-Diaz of the Harvard T.H. Chan School of Public Health.
Their results were published this week in the US journal Neurology.
"The best course may be to avoid prescribing high doses of topiramate to women of childbearing age unless the benefits clearly outweigh the risks."
Topiramate has been increasingly prescribed over the last decade not only to prevent seizures, but also to treat bipolar disorder and migraine headaches.
In addition, topiramate is a component of a recently approved drug for weight loss in the United States.