NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.
In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that
Dr. Jakob Christensen
“Because we have this large data set we were able to confirm the suspicion that’s been raised in the past that these drugs may be associated with low birth weight,” Dr. Christensen said in an interview.
The study analyzed records from population-based registers of 4.5 million births in Denmark, Finland, Iceland, Norway, and Sweden between 1996 and 2017, known as the SCAN-AED project. The researchers analyzed the association between prenatal use of antiseizure medications and birth weight, defining low birth weight as less than 5.5 pounds and small for gestational age as being in the lowest 10th percentile for sex, country, and gestational weight at birth.
The antiseizure medications and adjusted odds ratios for risk of low birth rate were:
- Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
- Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
- Topiramate, 1.60 (95% CI, 1.15-2.24).
- Pregabalin, 1.23 (95% CI, 1.02-1.48).
- Clobazam, 4.36 (95% CI, 1.66-11.45).
The odds ratios for being born small for gestational age were:
- Carbamazepine, 1.25 (95% CI, 1.11-1.41).
- Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
- Topiramate, 1.52 (95% CI, 1.20-1.91).
“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.
He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
Use with caution
This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.
“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”
She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.
The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.