Antiseizure Drugs in Pregnancy: Fetal Growth Risks Revealed by Global Study
A large international study from the EURAP registry indicates that antiseizure medications (ASMs) taken during pregnancy are associated with reduced fetal growth. Polytherapy poses a higher risk than monotherapy, with specific drugs like topiramate showing the greatest impact, underscoring the need for careful medication selection and monitoring.
Key Highlights
- ASMs in pregnancy linked to poor fetal growth outcomes.
- Polytherapy increases risk of small-for-gestational-age births by 50%.
- Individual ASMs show varied effects; topiramate has greatest impact.
- Lamotrigine and levetiracetam generally associated with better outcomes.
- Study emphasizes individualized treatment and close fetal monitoring.
- Poor fetal growth can lead to short-term and long-term health issues.
A significant international prospective cohort study, based on data from the EURAP (International Registry of Antiepileptic Drugs and Pregnancy) registry, has revealed a clear link between the use of antiseizure medications (ASMs) during pregnancy and an increased risk of poor fetal growth. The findings, which represent the largest prospective investigation into this topic, suggest that healthcare providers need to carefully consider treatment regimens for pregnant women with epilepsy.
The study, encompassing 15,893 offspring prenatally exposed to ASMs between 1999 and 2023, meticulously evaluated various indicators of fetal growth, including birthweight centile, small for gestational age (SGA) birth, severe SGA, and low birthweight. A crucial finding was that exposure to antiseizure medication polytherapy (multiple ASMs) was associated with significantly poorer fetal growth outcomes compared to monotherapy (a single ASM). Specifically, polytherapy was linked to approximately 50% higher risks of SGA birth, severe SGA, and low birthweight. The risk appeared to increase further with the number of concomitant antiseizure medications taken.
Beyond the number of medications, the study also highlighted substantial variations in growth effects among individual ASMs. Topiramate, in particular, was found to be associated with the greatest reduction in birthweight percentile when compared to lamotrigine. Other medications, including phenobarbital, oxcarbazepine, carbamazepine, and valproic acid, were also associated with lower birthweight centiles and increased risk of SGA. Conversely, lamotrigine and levetiracetam generally showed a more favorable profile regarding fetal growth, with lamotrigine often cited as having no association with lower birth weight or birth defects in some studies. However, it is important to note that some analyses still showed levetiracetam associated with lower birthweight compared to lamotrigine.
These findings are critical because poor fetal growth is a major contributor to perinatal morbidity and mortality, and it can predispose individuals to chronic health issues later in adulthood, such as breathing problems and heart disease. For women with active epilepsy, withholding antiseizure therapy is generally not an option due to the risks seizures pose to both the mother and the fetus. Therefore, this research provides vital information for optimizing antiseizure therapy, ideally even before conception.
The study underscores the importance of individualized ASM selection and diligent fetal growth monitoring throughout pregnancy. Healthcare providers are encouraged to discuss these risks with expectant mothers and consider the specific ASM profile when developing a treatment plan. The goal is to identify the most effective ASM regimen that minimizes risks to fetal development while effectively managing maternal epilepsy.
Corroborating previous research, a systematic review and meta-analysis published in 2024 also concluded that pregnant individuals exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes, including SGA and low birth weight, and decreased birth weight compared to unexposed individuals. This review, which included 65 studies, also found that ASM polytherapy was associated with increased risks. Furthermore, a population-based cohort study from the Nordic countries (published in 2022 but with data up to 2017) similarly identified prenatal exposure to carbamazepine, oxcarbazepine, clonazepam, and topiramate as being associated with an increased risk of being born small for gestational age.
This body of evidence reinforces the need for ongoing research, careful clinical management, and patient counseling to ensure the best possible outcomes for both mothers with epilepsy and their infants.
Frequently Asked Questions
What is the main finding of the study regarding antiseizure drugs and pregnancy?
The study found that antiseizure medications (ASMs) taken during pregnancy are linked to an increased risk of poor fetal growth, with the risk being higher when multiple ASMs (polytherapy) are used compared to a single ASM (monotherapy).
Which specific antiseizure medications are associated with the highest risk to fetal growth?
Topiramate was identified as having the greatest negative impact on birthweight percentile. Other medications like phenobarbital, oxcarbazepine, carbamazepine, and valproic acid were also associated with reduced fetal growth.
Are there any antiseizure medications considered safer for fetal growth during pregnancy?
Lamotrigine generally showed a more favorable profile regarding fetal growth and was not associated with lower birth weight or birth defects in some studies. Levetiracetam also had a better profile than many other ASMs, though some analyses still noted a difference compared to lamotrigine.
What are the implications of poor fetal growth for the baby?
Poor fetal growth is a significant cause of complications around the time of birth and can lead to short-term health issues in newborns (e.g., breathing problems, infections) and long-term health problems in adulthood (e.g., heart disease).
What should pregnant women with epilepsy do based on these findings?
Pregnant women with epilepsy should not stop their medication without consulting their doctor, as uncontrolled seizures pose risks. Instead, they should discuss these findings with their healthcare provider to review their treatment plan, optimize ASM selection, and ensure close monitoring of fetal growth throughout pregnancy.
