Risks of taking epilepsy drugs while pregnant

Keep in mind ...What does the WHO recommend

Recommendation(s)

• Women with epilepsy should have seizures controlled as well as possible with the minimum dose of antiepileptic drug taken in monotherapy, wherever possible. Antiepileptic drug polytherapy should be avoided. Valproic acid should be avoided if possible.  Strength of recommendation: STRONG
• Folic acid should routinely be taken by women with epilepsy of child bearing age who are on antiepileptic drugs.  Strength of recommendation: STRONG
• Standard breast feeding recommendations remain appropriate for women with epilepsy on the antiepileptic drugs included in this review (phenobarbital, phenytoin, carbamazepine and valproic acid). Strength of recommendation: STRONG
• JR

Risks of taking epilepsy drugs while pregnant

This article discusses the various risks associated with pregnant women taking drugs for epilepsy, such as having a child with developmental delays or showing signs of autism.

Women with epilepsy who take anti-seizure medication while they are pregnant are more likely to later report delays in their child's development and autism symptoms, according to a new study from Norway.

The findings probably won't change the conversation too much between women and their doctors in terms of managing epilepsy during pregnancy, because it's already understood that the medications carry some risks, said Dr. Lewis Holmes, director of the Antiepilepsy Drug Registry at Massachusetts General Hospital, who was not involved in the research.

However, studies like this are badly needed, he added, because women are often asking about risks to their children's development, and "it hasn't really been mapped out."

The researchers could not prove that the anti-epileptic drugs are to blame, but the findings add to other evidence linking the medications to effects on children's development.

Seizure medication taken during pregnancy is already tied to a higher risk of physical malformations in the baby, and the drugs are linked with a greater chance of complications during pregnancy and childbirth.

One study from Denmark earlier this year also found that women who took the epilepsy drug valproate during pregnancy were three times more likely to have a child with an autism spectrum disorder.

"The risk of other effects on fetal development, that is, development and behavior, is less clear," said Dr. Gyri Veiby, lead author of the new study and a researcher at the University of Bergen in Norway.

She said that among all pregnancies, about three to five women out of every 1,000 use anti-epileptic drugs during pregnancy.

"It is reasonable to assume that most (anti-epileptic drugs) have the potential to harm the developing fetus. On the other hand, seizures should also be avoided during pregnancy," Veiby wrote in an email.

"In order to assess whether antiepileptic drug treatment during pregnancy is justified, we need to know as much as possible about the potential risks for the fetus," she said.

Veiby and her colleagues examined data from a large survey of mothers across Norway.

More than 108,000 women filled out a questionnaire asking about the behavior and development of their children at 18 and 36 months of age.

The survey included questions about social, physical and verbal skills, mannerisms, aggression and other traits.

Among the women in the study, 634 had epilepsy and 333 of them took epilepsy medication while they were pregnant - that translated to about 46 percent of the children of epileptic mothers having been exposed to one or more of the medications.

Children whose mothers took epilepsy drugs while pregnant were more likely to score outside the normal range on several developmental measurements, the researchers report in the journal Epilepsia.

For instance, 3.3 percent of three-year-olds whose mothers did not have epilepsy did not meet milestones for physical skills, whereas 7.5 percent of kids exposed to epilepsy drugs in utero failed to meet these milestones.

In addition, 4.8 percent of three-year-olds whose mothers did not have epilepsy scored abnormally on their ability to form sentences, while 11.2 percent of the children whose mothers took anti-seizure medication were delayed in their sentence skills.

The kids whose mothers took epilepsy medication while pregnant were also more likely to have autistic traits - 6 percent - compared to just 1.8 percent of the kids who mothers did not have epilepsy.

A mother's epilepsy itself did not appear to contribute to the heightened risk. Mothers with the condition who did not take any medication were no more likely to have a child with delays than mothers without epilepsy.

Dr. Cynthia Harden, a neurology professor at Hofstra-North Shore LIJ School of Medicine in Hempstead, New York, said it's possible the findings could be explained in part by something called "selection bias."

Mothers who take epilepsy medication while pregnant, for example, might be more concerned and therefore looking out for developmental delays, so they could be more likely to report them.

But Harden also said it's possible the drugs themselves have a negative effect on babies' development.

"There might be something real going on here, but it's possible that the magnitude of the effect is exaggerated by selection bias," said Harden, who is also the director of the Comprehensive Epilepsy Care Center at North Shore-LIJ Medical Group in Great Neck, NY.

Holmes said the findings support parents taking action on cues that their child might have a delay.

"Because there are concerns about subtle effects, I think it's smart to go ahead and think about obtaining some formal testing...as a way of making sure that everything is OK before first grade," Holmes said.

Harden agreed that the study doesn't change the discussion about epilepsy management during pregnancy too much.

Already, patients and physicians are aware of the potential hazards of the drugs, yet "seizures are dangerous, and we cannot permit our patients to have seizures during pregnancy," she said.

Physicians try to reduce the dose of the medication, trim back the treatment to one type of drug if possible, and avoid the use of valproate.

Veiby added that another way to minimize the risks during pregnancy is to plan ahead to figure out the safest treatment strategy, and to avoid unplanned pregnancies.

"Unfortunately, many women on (anti-epileptic drugs) do not receive the appropriate pre-pregnancy counseling," she said.

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