New insights into anti-tuberculosis drugs during pregnancy

Two common antiseizure medications, lamotrigine and levetiracetam, are safe to use during pregnancy, according to a study by Stanford Medicine.

The research, published online Nov. 25 in JAMA Neurologyis the first to examine the long-term effects of drugs on children born to mothers who took one or both anti-epileptic drugs during pregnancy. Studies confirm that these two medications provide a safer alternative to older antiseizure medications such as valproate, which are known to be harmful to unborn babies.

The main finding of the study is that the ability to speak at age 6 was normal in children whose mothers used one or both drugs during pregnancy. This study also measured other different cognitive and cognitive outcomes in 6-year-old children and there was no statistically significant difference.

“For these new drugs, lamotrigine and levetiracetam, the results look very good,” said the lead author of the study, Kimford Meador, MD, professor of psychiatry and neuroscience.

We did not see a difference between the children of women with epilepsy who took the new medicine and the children of healthy women, which is very encouraging. “

Kimford Meador, MD, Professor, Neurology and Neurological Sciences, Stanford Medicine

Women with epilepsy need the attention of neurologists and physicians who have the expertise to manage the disease during pregnancy, Meador said, adding that with proper care, “More than 90% of women with with epilepsy will have normal pregnancies and normal children.”

Meador is also the clinical director of the Stanford Comprehensive Epilepsy Center.

Amazing history

Historically, people with epilepsy were very depressed -; if not prohibited by law -; from having children.

“There were laws in the 1950s, in 18 states in the US, to ban women and men with epilepsy,” Meador said. “It was part of the eugenics movement.”

As a medical student in the 1970s, Meador cared for an epilepsy patient who had received a hysterectomy, decades earlier, for this reason. Seeing the patient interacting with his extended family during his time in the hospital, young Meador was struck by the sense of loss his patient had experienced.

“It was clear to me that he loved kids,” Meador said. “She had poured so much of her life into her nieces and nephews and was denied the opportunity to have children because of ignorance, basically.”

Treatment problems

It is important to prevent as many inclinations as possible during pregnancy, as falls can injure both the mother and the fetus. But managing epilepsy is difficult. Studies by Meador and colleagues in the 1990s showed that the anti-seizure drug valproate was a poor choice during pregnancy because it posed a significant risk to children. for conditions such as autism and low IQ as well as impairment of other mental abilities. These findings have led to federal warnings for valproate. In addition, studies conducted by others have shown that valproate increased birth defects. After the research was published, the use of valproate during pregnancy decreased.

Patients changing antiseizure medications may have more seizures during the transition to a new medication, so changing treatment regimens during pregnancy is also not appropriate. Even when women use the same drugs throughout pregnancy, their bodies change. Pregnancy speeds up metabolism, doubling the rate at which most of these drugs are removed from the body and thus reducing the amount of drugs in the blood. In order to prevent epilepsy, doctors should carefully monitor the medication and increase the dose to keep it stable.

In terms of long-term results

For the study, researchers enrolled women during pregnancy, followed them and their children for several years, and examined many outcomes for mothers and their children. The latest documents data from 6 years from 298 children of women with epilepsy and a comparison group of 89 children of healthy women. The team previously recorded the data of the same children aged 2, 3 and 4.5 years.

The women in this study were pregnant between 2012 and 2016. Those with epilepsy were being treated at 20 epilepsy centers around the United States; they received care that they and their doctors chose and that followed the normal course of the disease. During pregnancy, most women with epilepsy were taking lamotrigine (43.6%) or levetiracetam (34.5%), or a combination of these drugs; others were taking various anti-fall medications. During the first trimester of pregnancy, most of the women in this study also took folate, a B vitamin known to reduce the risk of certain birth defects in the general population.

The researchers monitored the mothers’ blood levels of anti-seizure medications throughout pregnancy, especially during the third trimester, when the baby’s brain is developing rapidly. They wanted to see if a child’s high exposure to antiseizure medication during the third trimester of pregnancy was related to their later speech ability.

The researchers were particularly concerned about the ability to speak at age 6 because previous studies have shown that verbal skills can be affected by exposure to antiseizure drugs. They measured verbal ability with standardized tests.

The children also completed standard tests of other neurological and cognitive abilities, including general intelligence, visual acuity, memory, executive function, motor skills, processing speed and behavior.

The ability to speak is preserved

The researchers found no difference in vocabulary between female children with and without epilepsy at age 6. This remained true after adjusting for many that can influence children’s speaking skills. Key variables included mother’s IQ, age and education level; whether the baby was exposed in utero to acetaminophen (commonly known as Tylenol); and the child’s gender, race and whether they were small for gestational age when they were born.

The ability to speak was somewhat influenced by the level of drugs in the mother’s blood during the three-month period, depending on which drug the mother used, the study found.

“It seemed to have a positive effect [on verbal ability] Meador said: “For levetiracetam, we saw a negative effect: In high orders, and not the highest dose of lamotrigine. [verbal] performance is down. These findings should be considered carefully because the study did not assign patients to take drugs, so the findings need to be replicated,” he added.

The study also found links between exposure to acetaminophen during pregnancy and adverse neurodevelopmental outcomes. “This is a drug that was considered very safe during pregnancy,” Meador said, adding that other recent studies have also shown similar risks.

Folate in early pregnancy has been found to be helpful. Women are often told to take folate supplements during pregnancy to prevent major birth defects such as spina bifida, but new research, including this study, also shows that folate supplementation has and other benefits for children of women with epilepsy. “We found that folic acid supplementation improved cognition and behavior at age 6,” Meador said.

Ways of the future

There are many epilepsy drugs on the market whose risks are unknown. It’s important that scientists continue to discover how they influence the developing brain, Meador said. Finding medications that control a patient’s anxiety can take trial and error, and lamotrigine and levetiracetam do not work for everyone.

“The next choice is to use a drug that we know has a high risk or to use a drug where we don’t know the risk,” Meador said. “And it’s a very bad situation. It’s a clear difference in health care.”

He emphasized the need for more research to understand which genes make patients more vulnerable to the adverse effects of antiseizure medications. “Drugs that cause birth defects work in a dose-dependent manner, so the higher the dose, the worse it is, but it also works on the more susceptible genotype, and we still don’t understand that what genes in people put you more at risk.”