Prenatal Exposure to Some Anti-Seizure Drugs Linked With Low Birth Weight

Prenatal exposure to some anti-seizure drugs was associated with adverse birth weight outcomes, a preliminary analysis of SCAN-AED registry data suggested.

In a study of nearly 4.5 million children born in Denmark, Finland, Iceland, Norway, and Sweden, carbamazepine (Tegretol), oxcarbazepine (Trileptal), and topiramate (Topamax) were associated with low birth weight and an increased risk of being born small for gestational age, reported Jakob Christensen, MD, DSc, PhD, of Aarhus University Hospital in Denmark, at the American Epilepsy Society annual meeting.

Low birth weight is linked with long-term health, Christensen noted. “For example, low birth rate has been associated with cardiovascular risk later on,” he said in an interview with MedPage Today.

“What came out of this study was that oxcarbazepine and carbamazepine seemed to be associated with an increased risk of lower birth weight, meaning less than 2,500 grams [about 5.5 pounds],” he added. “I don’t know that this is really a new finding, but it confirms smaller studies and makes us more sure that this is a real observation.”

Women with epilepsy usually require anti-seizure medication during pregnancy. In the U.S., the prevalence of anti-epileptic drug use is up to 34.5 per 1,000 pregnancies.

Prenatal exposure to anti-seizure drugs has been linked with several adverse outcomes, including risks of autism and intellectual disability or major congenital malformations with certain agents. The most effective and safest anti-seizure medication depends on a woman’s response to treatment and whether it’s possible to switch medications before pregnancy, Christensen observed.

SCAN-AED is the largest study to look at epilepsy drug exposure and birth weight. Christensen and co-authors analyzed data for 4,494,920 children who were either exposed or unexposed to anti-seizure medication during pregnancy between 1996 and 2017. About half (51.3%) of the infants were male.

The researchers defined small for gestational age as children with a z-score under the 10% percentile for birth weight according to sex, country, and gestational week at birth. Estimates were adjusted for potential confounding factors, including maternal age, smoking, substance abuse, cohabitation, income, education, parity, maternal psychiatric disorders, maternal use of psychotropic medication, and maternal epilepsy. Analyses of birth weight and low birth weight were adjusted for gestational age.

Anti-seizure drugs assessed included lamotrigine (Lamictal; taken by 8,760 women), carbamazepine (taken by 3,420 women), oxcarbazepine (taken by 1,590 women), and topiramate (taken by 680 women).

Compared with no exposure, exposure to anti-seizure drugs as monotherapy during pregnancy was associated with lower birth weight in children exposed to carbamazepine, oxcarbazepine, and topiramate, but not in children exposed to lamotrigine.

“There have been other studies in the past that have looked at other outcomes like congenital malformation and neurodevelopment. In all of these studies, lamotrigine has come out favorably,” Christensen pointed out.

“For most of the drugs, especially the newer ones, the evidence is low because few women have used them during pregnancy — meaning we found no significant association of low birth weight because only a few infants have been exposed — and therefore they cannot be considered safe,” Christensen stated in a press release.

“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,” he said.