According to the CDC,1 about 1 in every 2,800 babies born in the United States has cleft lip and 1 in every 1,700 babies is born with cleft palate. Children with this condition often have problems with feeding and speaking clearly and can have ear infections. They also might have hearing problems and problems with their teeth.
Though multiple factors can increase the chance of having a baby with an orofacial cleft, a collaborative study by Carelon Research and our research partners, published in 2014,2 found that first trimester exposure to topiramate, a medication used for the treatment of epilepsy, is associated with an increased prevalence of oral clefts.
Carelon Research’s Safety and Epidemiology team collaborated with research partners to conduct a retrospective cohort study using automated data from four sources from 1997-2011. By linking maternal records with child records, they ascertained the prevalence of oral clefts and compared the prevalence in infants of women exposed to topiramate in the first trimester (TPM cohort), infants of women formerly exposed to TPM or other antiepileptic drugs (FE cohort), and infants of women not exposed to TPM with similar medical profiles to the TPM cohort (SMP cohort).
Researchers found the birth prevalence of oral clefts was 0.36% (7/1945) in the TPM cohort, 0.14% (20/13 512) in the FE cohort, and 0.07% (9/13 614) in the SMP cohort. After adjusting for multiple factors, the increased prevalence of oral clefts remained two- to five-fold higher for TPM use in the first trimester than for each comparator group.
This research, along with other studies, supports the FDA’s warning in TPM’s package insert3 for fetal toxicity which notes that "use during pregnancy can cause cleft lip and/or palate."
Historically, pregnant women are not included in clinical trials submitted for approval of new medications. Regulators, therefore, rely on real-world data to identify potential risks. Fetuses may be susceptible to congenital effects at particular times of development.
Researchers are able to link exposures during critical periods of pregnancy to subsequent congenital anomalies, even those that are not apparent at birth but diagnosed early in childhood. By studying effects of medications on pregnancy outcomes, Carelon Research is contributing crucial evidence about safe use of medications for pregnant women to support informed medical decisions.