About 24,000 children in the United States are born each year to women with epilepsy and the vast majority are fine, but a national study aims to further level the playing field.
Researchers want to know if the medicines the mothers-to-be must take to control seizures have a negative, lasting impact on their babies’ developing brains.
The study will follow 285 women taking one of the three most commonly prescribed anti-seizure medications from their first trimester until their children are several years old. Researchers want to determine what impact phenytoin (Dilantin), carbamazepine (Tegretol) and valproate (Depakote) have on the children’s ability to think and learn.
"A really important aspect of this study is to find out if there is a difference between these drugs; are some of these drugs better for the child long-term than other drugs?" said Dr. Kimford J. Meador, chief of the Medical College of Georgia Section of Behavioral Neurology and principal investigator on the $6 million, five-year study funded by the National Institutes of Health. "If that’s true, then we will want women to try to use the drugs which have reduced adverse effects. It would dramatically alter how we prescribe drugs. But right now we don’t know if it’s true.
"We do know that the vast majority of women with epilepsy have healthy children," he said. "We are talking about a relatively small increased risk, but we want to reduce that risk as much as possible. We want them to have the same lack of risk other children have."
Dr. Meador emphasized that most women with epilepsy can have healthy children and that they should continue taking their medication while pregnant.
"In a woman who has significant seizures, the risk from the seizures themselves is worse than the risk of the drugs," Dr. Meador said. "The number-one reason for miscarriage late in pregnancy for women with epilepsy is trauma (resulting from a seizure)."
But he wants to objectively assess whether these drugs, which control seizures by reducing neuronal excitability in the mother, impact normal nerve growth and connections in her developing baby’s brain. "During development, that excitability may be very important in terms of how nerves grow and connect," Dr. Meador said.
Also, development may be impacted by free radicals released by these drugs which bind to protein in the body’s basic building blocks of DNA and RNA. "The body typically can repair some of this type of damage, but if it gets overloaded with damage it may not be able to and there may be long-term consequences," Dr. Meador said. "But it’s also possible that the children rebound from these drug effects and it really doesn’t have a long-term effect."
There is solid information that these types of drugs pass through the placenta from the mother to the baby where they double the 2-3 percent risk of birth defects, such as spina bifida, that occurs in the general population.
But pre-pregnancy planning, such as ensuring that women take multivitamins and folate supplements, can minimize the anatomical birth-defect risk and Dr. Meador wants to do the same for any potential neuro-developmental risks.
Studies have shown that animals exposed to lower doses of these drugs in the womb have a decreased capacity to think and learn. "They don’t learn things as fast, they don’ t respond as rapidly to cognitive tests. Our concern is that this also might be a problem for women with epilepsy and their children," Dr. Meador said.
So Dr. Meador is looking for objective data, such as the child’s IQ and predicted IQ based on the parents’ to determine any lasting impact these drugs have on the child’s ability to think and learn.
Researchers at 17 study sites in the U.S. will collect data on mothers, fathers and babies in an effort to determine the impact.
Much of the data is the type normally accumulated during pregnancy, but they will look at other parameters as well such as the mother’s seizure frequency and blood levels of the medication. They will perform IQ tests on mothers and fathers to get a predictive IQ for the baby and, beginning at about age 2, will do similar testing on children. They also will gather data on the children’s nutritional status and general health, noting milestones such as when children begin to walk and talk. Contributing risk factors, such as low socioeconomic status and poor diet, also will be considered.
The NIH-funded study will focus on women taking one of the three oldest anti-seizure medications, but Dr. Meador hopes to expand the study to include some newer drugs as well.
Enrollment for women in their first trimester of pregnancy who are taking one of the drugs begins in January. For more information, call Dr. Meador’s study coordinator at (706) 721-6260 or his office at (706) 721-2797.
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