A focused guideline update “Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After in Utero Exposure to Antiseizure Medication” was released by the American Academy of Neurology (AAN), the American Epilepsy Society (AES), and the Society for Maternal-Fetal Medicine (SMFM) on May 15, 2024. The new guideline updates the previous 2009 guideline for “Management Issues for Women with Epilepsy—Focus on Pregnancy: Teratogenesis and Perinatal Outcomes”. Today we’ll take a look at what’s changed since that 2009 guideline, as well as some of the key takeaways from the new 2024 recommendations for managing potential sequelae secondary to in utero antiseizure medication exposure. Before we dive in, if you’re looking to save time but get all the pertinent clinical decision support recommendations in a quick reference format, you can access the AAN/AES/SMFM Guidelines Pocket Guide available for online and in the Guideline Central mobile apps which can be found here.

It has been approximately 15 years since the last guidelines were issued, and significant advancements have occurred in that time. Below, we will outline the major revisions, key takeaways, and provide insight into potential future guideline updates in the management and care of patients with in utero antiseizure medication exposure. Please be aware that this list does not encompass all changes made to the guidelines but rather serves to highlight some of the key new developments in recommended patient care plans. For a comprehensive comparison of the new recommendations, we encourage you to refer to the full text guideline or the pocket guide available through the provided links.

Now, without further ado, let’s explore the 2024 guideline updates!

Comparing the 2024 vs 2009 Guideline: Key Changes and Takeaways

  • The 2009 guidelines referred to the affected population as “women with epilepsy,” failing to acknowledge the distinction between biological and sociocultural gender. In this updated version, gender-neutral language is used to refer to the affected population as “people with epilepsy of childbearing potential” (PWECP). This change is intended to be more inclusive and respectful of all individuals affected by epilepsy, regardless of their gender identity.
  • The 2009 guidelines were unable to assess the risk associated with commonly used anti-seizure medications (ASMs), such as levetiracetam or topiramate, due to a lack of evidence.
    • In contrast, the 2024 guideline advises against clinicians using topiramate in PWECP to reduce the likelihood of offspring being born small for gestational age, if clinically feasible.
    • Furthermore, the 2024 guideline suggests that clinicians consider utilizing levetiracetam in PWECP when appropriate, taking into account factors such as the patient’s epilepsy syndrome, likelihood of achieving seizure control, and comorbidities. This recommendation aims to minimize the risk of major congenital malformations (MCMs).

  • The authors of the 2009 study determined that using valproic acid as a treatment for epilepsy poses a greater risk of MCMs in the children of affected women compared to using carbamazepine, phenytoin, and phenobarbital, especially when used in combination therapy. Additionally, the study found that valproic acid treatment was associated with the highest likelihood of adverse cognitive outcomes in the offspring of women with epilepsy when compared to carbamazepine. 
    • However, the study did not address the risk of autism spectrum disorder (ASD) as this association had not yet been reported in the existing literature.
    • The 2024 guideline also recommends that healthcare providers avoid prescribing valproic acid to pregnant women with epilepsy in order to decrease the chances of their offspring being born small for gestational age, if it is feasible based on clinical considerations.
    • The 2024 guideline also points to mitigating the risk of negative neurodevelopmental outcomes, such as autism spectrum disorder and lower IQ, in children born to pregnant women with epilepsy; healthcare providers must avoid the use of valproic acid in this population, if it is clinically feasible.

Future Guideline Updates

The 2024 guideline has identified several areas of research that need to be explored further in order to enhance reproductive outcomes for PWECP. Specifically, there is a need for more research on the risks of MCMs and adverse perinatal outcomes associated with newer and less studied antiseizure medications (ASMs) such as lacosamide, zonisamide, clobazam, and perampanel.

Moving forward, it is important that future guidelines take into consideration the potential risks and benefits of even newer ASMs, including cenobamate and fenfluramine, which were not included in this guideline update. 

There you have it – a rundown of some of the bigger “Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After in Utero Exposure to Antiseizure Medication” guideline changes, 15 years in the making!  For more information about this guideline, as well as access to our full library of clinical practice guidelines, articles, and clinical decision support tools, make sure to Sign up for alerts to stay informed on the latest published guidelines and articles.

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