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Understanding the risks of seizure-stopping drugs in pregnancy

Newer anti-seizure drugs have a good safety profile for the baby when used in pregnancy and breastfeeding, according to a Stanford-led study.

For women with epilepsy, pregnancy has historically been quite fraught. In generations past, epilepsy patients were discouraged from getting pregnant, as uncontrolled seizures can harm both mother and baby. Older anti-seizure medications carry a high risk of physical birth defects and cognitive deficits in children exposed during pregnancy.

But the newest anti-seizure drugs are much safer to use during pregnancy and breastfeeding, according to a Stanford-led study published June 7 in JAMA Neurology.

The study measured verbal abilities at age 2 in nearly 300 children whose mothers took newer medications for epilepsy. Their children had equal language development to those in a control group, along with moderate risks in other areas for children exposed to the highest levels of the medications before birth.

"Overall, I think the results here are positive for women with epilepsy," said lead author Kimford Meador, MD, a neurologist and an expert on managing epilepsy in pregnant women. "Based on our findings, these patients should feel better about their opportunities and options for having a child."

Prior to the 1960s, women with epilepsy were advised not to get pregnant, and many states had laws prohibiting individuals with epilepsy from getting married, Meador said.

Things changed in the '60s and '70s, thanks to social shifts and the development of effective medications to suppress seizures. But these older anti-seizure drugs, such as valproate, carry substantial risks. About 10% of babies exposed to valproate in utero developed physical birth defects, with more risk at higher doses.

Identifying impact of anti-seizure medications

Meador's research, which helped identify the risks of the older drugs, has recently expanded to assess the effects in pregnancy of newer anti-seizure medications introduced in the 1990s and 2000s, especially lamotrigine and levetiracetam, which are now widely prescribed instead of valproate.

"Most of the 30 or so drugs used in the U.S. for seizures we don't understand very well," Meador said. "We wanted to look at drugs being used now."

It was also important to measure how much of each medication was present in the mother's blood because the body clears anti-seizure medications faster during pregnancy, he said.

From 2012 to 2016, the research team enrolled pregnant women at 20 U.S. epilepsy centers, recording which anti-seizure medications they took, the dosages they used and the amounts of medications in their blood. Details about the mothers' demographics that were thought to affect children's language development and other cognitive outcomes were also recorded.

Those details included maternal IQ, education and anxiety levels, family's ethnicity, and the child's birthweight and sex. The scientists are continuing to follow all children in the study until they turn 6.

The new report, of results collected at age 2, is the first in a series of planned publications to track the children as they develop. The study compared 292 youngsters whose mothers had epilepsy with a control group of 90 whose mothers did not.

Nearly 80% of women with epilepsy in the study used a single drug to manage seizures during pregnancy, usually either lamotrigine or levetiracetam. Of those using more than one drug, 45% were taking both of these medications. Only 5 of the women in the study were using valproate to manage their seizures, showing how knowledge of its risks has changed epilepsy treatment.

Child's abilities not widely impacted

The researchers assessed the children's abilities, including their language skills, with a standardized test called the Bayley Scales of Infant and Toddler Development. As the scientists expected, demographic factors influenced language acquisition: Children in both groups whose mothers had higher IQ were more verbal, for example. Also, girls were more verbal and children with highly anxious mothers had lower language scores.

But once all these factors were statistically accounted for, "There was no difference overall between children of mothers with epilepsy and healthy moms," Meador said. "That's an important message."

Children born to women with the highest blood levels of medication, however, did face an increase in risk to motor skills and a trend toward problems in general adaptation versus children in the control group.

The findings indicate that cognitive risks of the newer drugs are smaller than for valproate treatment, Meador said, noting that his team's prior study found a loss of 10-12 IQ points in children exposed to valproate in utero, even if they did not have physical birth defects.

Meador said he is optimistic about what the findings mean for pregnant epilepsy patients, including those he works with at Stanford Health Care.

"My most important role, beyond watching patients' medicines and making sure we adjust the dosages and react to stop any seizures, is counseling them," he said. "There's some increased risk, but if they are taking the right drugs that are not dangerous, they should do fine. The vast majority of women taking the new anti-seizure drugs have normal pregnancy outcomes."

Photo by Aditya Romansa

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