Article summary
An analysis of pregnancies in women with epilepsy found an association between monotherapy with two antiepileptic drugs, valproic acid and topiramate, with a two-fold increase in the risk of major congenital malformations in the child. rice field.
The choice and dosage of antiepileptic drugs (ASMs) for women who are pregnant or planning to become pregnant are of great importance given the teratogenic potential of certain treatments. Both concerns are now clarified by the results of a large population-based study comparing the safety and potential risks of her ASM to fetal development for major congenital malformations.
Analysis published online Nov. 26 Neurological Annalsfound that both valproic acid and topiramate monotherapy were associated with a two-fold increased risk of major congenital malformations. The risk of topiramate was less clear, although exposed children showed a three-fold higher risk of developing congenital malformations. This suggests that it may not be
The study also confirmed data from previous studies showing that lamotrigine and levetiracetam lowered the risk of major congenital malformations, while carbamazepine and oxcarbazepine were relatively safe with respect to the risk of major congenital malformations. .
Survey details
Using National Health Register data from 1996 to 2020 from five Nordic countries: Denmark, Finland, Iceland, Norway, and Sweden, researchers investigated the comparative safety of common ASMs. We constructed a population-based cohort of nearly 5 million pregnancies. Approximately 16,000 women (0.3%) used her ASM monotherapy during the first trimester of pregnancy, compared with her 4,866,362 women who did not use ASM at all.
Most women were treated with lamotrigine monotherapy (8,339). Other treatments included carbamazepine (2,674 women), valproic acid (2,031), oxcarbazepine (1,313), levetiracetam (1,040), and topiramate (509). The study did not include gabapentin or pregabalin, or older drugs such as phenytoin and phenobarbital, which are no longer frequently used in Nordic countries.
Investigators received lamotrigine monotherapy after adjusting for confounding factors such as country, year of delivery, maternal age, indications for ASM, and other chronic conditions, including diabetes, and other drug use during early pregnancy. No difference was found between women who received ASM and those who did not. , and indicators of pre-pregnancy health care use.
Researchers compared the safety of lamotrigine monotherapy with carbamazepine, valproic acid, oxcarbazepine, levetiracetam, and topiramate monotherapy. They also stratified the monotherapy groups by dose and compared each to low-dose lamotrigine.
Both valproate and topiramate dose-dependently increased the risk of congenital malformations by 2-fold compared with lamotrigine monotherapy. Both agents were associated with a possible increased risk of multiple malformations. Valporate has been associated with heart and nervous system malformations, as well as cleft mouth, clubfoot, and hypospadias.
This study found no increased risk of congenital malformations with carbamazepine, oxcarbazepine, and levetiracetam monotherapy compared with lamotrigine monotherapy.
“Based on our study, we found no significant differences in the risk of major congenital malformations between these drugs,” said the study’s lead author, head of the Department of Chronic Diseases and Fertility Center. said senior researcher Jacqueline Cohen, Ph.D. Health at the Norwegian Institute of Public Health in Oslo. Given that Dr. Cohen was based on a higher number of infants exposed to carbamazepine prenatally than those assessed in previous studies, she is in favor of finding a comparable safety to carbamazepine. He said he was relieved.
“In relation to previous studies, our findings suggest that neurologists should not use valproic acid and topiramate in people of childbearing potential unless other treatment options are ineffective or unacceptable. It suggests that we should avoid prescribing it,” Dr. Cohen said.
“Although oxcarbazepine has not reached the number to confidently assess its structural risk, an analysis of more than 1,000 exposed pregnancies showed that it was equally safe for lamotrigine and levetiracetam. It has been confirmed.”—DR. Paula Voinescu
“The best time to counsel women with epilepsy of childbearing age is at least six months before conception. It can simplify your seizure treatment plan.”—DR. Mona Sazgar
“Severe congenital malformations occur very early in pregnancy, so it’s best for patients to consider these risks before they become pregnant,” she said. All patients of childbearing potential should use effective contraception and be well informed about the risks associated with using the drug during pregnancy.”
clinical perspective
Paula Voinescu, MD, PhD, a neurologist and director of the Women’s Epilepsy Program at Brigham and Women’s Hospital in Boston, found that lamotrigine and levetiracetam were associated with the best structural outcomes during pregnancy. He said research was corroborating.
What she’s excited about, she added, is that this study proves that oxcarbazepine is a safe drug as well.
“Although oxcarbazepine has not reached the numbers to confidently assess its structural risk, an analysis of over 1,000 exposed pregnancies showed that it is equally safe for lamotrigine and levetiracetam. It is now confirmed that there is,” Dr. Voinescu said.
She also emphasized that the study emphasized that valproic acid should be “a last resort for women planning a pregnancy, given the highest incidence of congenital malformations.” She said it also supports previous suspicions that topiramate has significant risks and should be avoided.
The results showing that carbamazepine was associated with lower rates of congenital malformations than previously shown should be “consolation” for women who are pregnant or planning to become pregnant, adds Dr. Voinescu. rice field.
Mona Sazgar, M.D., Ph.D., a neurologist in the Comprehensive Epilepsy Program at UC Irvine Health, said the results of the study are consistent with prospective pregnancy registry data from around the world, including the North American Antiepileptic Drug Pregnancy Registry. I said I would reassure her.
“The results have increased my confidence in counseling women with epilepsy,” said Dr. Sazgar.
She advises pregnant women to continue using ASM because uncontrolled seizures during pregnancy can pose a risk to the fetus.
“We try to simplify dosing regimens, aim for monotherapy where possible, and choose drugs with more favorable side effect profiles,” Dr. Sazgar said. “Fortunately, most of these drugs are considered safe, at least as monotherapy, and most women with epilepsy have healthy babies.”
Dr. Sazgar noted that lamotrigine, oxcarbazepine, and levetiracetam (all included in the current study) have similar risk profiles to the general population. When using zonisamide, gabapentin, and lacosamide, she will have monthly blood draws to check baseline pregnancy levels and guide medications during pregnancy.
In line with research findings and previous findings, she avoids valproate and topiramate, as well as phenobarbital. Try to use doses of less than 700 mg for valproic acid and less than 150 mg for phenobarbital to minimize .
Dr. Sazgar emphasized that gaps remain in understanding the safety of myriad new ASMs, including perampanel, brivaracetam, clobazam, escricarbazepine, lacosamide, senobamate, and cannabidiol. Many women use these treatments to control seizures, but there are not enough data on their safety during pregnancy.
Counseling Pregnant Women
Dr. Sazgar said he tries to discuss the risks of ASM during pregnancy before patients conceive. “The best time to counsel women with epilepsy of childbearing age is at least six months before conception. Medications can simplify seizure mediation regimens,” she said.
Once a woman becomes pregnant, it’s usually not safe to reduce her medication or simplify her antiepileptic drug regimen, she said. to keep both of them healthy.”
In addition to using drugs with a lower risk of birth defects, Prachi Parikh, M.D., an assistant professor of neurology at Duke University School of Medicine, says it’s important to check blood levels of drugs before and every month after pregnancy. “Medicine levels usually drop in early and mid-pregnancy and can lead to breakthrough seizures if not accounted for,” she said.
Disclosure:
Doctor. Cohen and Sazgar had no disclosures. Dr. Voinescu has received speaker fees from Neurodiem, Stony Brook University, and Physicians’ Education Resources..
