New Published Guidelines Issued for Antiseizure Medications in Patients Seeking Pregnancy

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A panel of experts provided a new update on practice guidelines for prescribing antiseizure medications to patients with epilepsy who may have a pregnancy.

Alison M. Pack, MD, MPH, FAAN, FAES  (Credit: Columbia University Irving Medical Center)

Alison M. Pack, MD, MPH, FAAN, FAES

(Credit: Columbia University Irving Medical Center)

Published in Neurology, a practice guideline developed by a panel of experts provided an update on evidence-based conclusions and recommendations on effects of antiseizure medications (ASMs) in children born from patients with epilepsy.1 These issued guidelines will offer help to neurologists and other healthcare providers to identify the most effective and safe ASMs for patients with epilepsy who may become pregnant.2

This guideline, endorsed by the Child Neurology Society, slightly updates 2 of the 2009 American Academy of Neurology (AAN) and American Epilepsy Society (AES) guidelines for managing epilepsy during pregnancy. The new updates specially provide guidelines regarding folic acid supplementation on the prevalence of major congenital malformations, adverse perinatal outcomes, and neurodevelopmental outcomes in children born to patients with epilepsy of childbearing potential.

"Most children born to patients with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly because of seizures and partly because of the effects of antiseizure medications," lead author Alison M. Pack, MD, MPH, FAAN, FAES, chief of the Division of Epilepsy and Sleep Disorders and professor of neurology at Columbia University Irving Medical Center, said in a statement.1 "This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy so that doctors and patients with epilepsy can determine which treatments may be best for them.”

Top Clinical Takeaways

  • The updated guidelines recommended the use of lamotrigine, levetiracetam, or oxcarbazepine to minimize the risk of major congenital malformations.
  • The guidelines strongly advise against the use of valproic acid because of its association with neural tube defects and poor neurodevelopmental outcomes.
  • Daily folic acid supplementation of at least 0.4 mg is recommended for patients with epilepsy who may conceive to reduce the risk of neural tube defects and improve neurodevelopmental outcomes.

READ MORE: Updated Guidelines Published to Improve Care in Specialized Epilepsy Centers

Authors conducted a systematic review on all the available literature focused on impact of ASMs on children born from patients with epilepsy through August 2022. The studies used in the review included research on major congenital malformations, or birth defects, fetal growth issues and neurodevelopmental effects such as autism or lower IQ scores. Using the provided evidence, the researchers then developed practice recommendations that followed the outlined process in the 2017 edition of the AAN Clinical Practice Guideline Process Manual. Thus, the recommendations were supported by structured rationales that incorporated evidence from the systematic review, additional related evidence, the principles of care, and produced inferences from prior evidence.

The major recommendations in the new guideline include the following:

  • When clinicians are treating patients with epilepsy who may become pregnant, they should recommend their patients ASMs and doses that optimize seizure control and fetal development at the earliest possible opportunity prior to pregnancy occurring.
  • During pregnancy, clinicians should minimize the frequency of convulsive seizures, seizures with full body spasms, in patients with epilepsy who may become pregnant to minimize the potential risks to the birth parent and the unborn child.
  • Once a patient has become pregnant, clinicians should advise caution if they ever try to remove or replace an ASM that has showed significant efficacy in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures in the patient.
  • Use of lamotrigine, levetiracetam, or oxcarbazepine should be considered as treatments by clinicians for patients with epilepsy who may become pregnant appropriately according to the epilepsy syndrome, the chance of achieving seizure control, and comorbidities, for minimizing the risk of major congenital malformations.
  • Avoidance on the use of valproic acid is recommended for clinicians in treating those with epilepsy who may become pregnant to minimize risk of major congenital malformations or neural tube defects, if it is clinically feasible.
  • It is also advised that clinicians should avoid the use of valproic acid or topiramate, if clinically feasible, in patients with epilepsy who may become pregnant to lower the risk as much as possible for offspring being born small for gestational age.
  • Clinicians should avoid the use of valproic acid in patients with epilepsy who may become pregnant to reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to patients with epilepsy who may become pregnant, if clinically feasible.
  • It is recommended that clinicians prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any patients who may potentially conceive treated with an ASM to reduce the risk of neural tube defects and possibly enhance neurodevelopmental outcomes in the offspring.

Despite the guidelines providing much evidence, authors noted that more research is needed to clarify the optimal dose and timing of folic acid supplementation. In addition, authors noted that there is the need for more research about the associated risk of some medications that did not have enough evidence to be assessed among this patient population.

"Patients with epilepsy who may become pregnant want to ensure the best health of their child while still managing and minimizing their seizures," Pack said in a statement.1 "This is why it is important to discuss plans for pregnancy with your doctor before becoming pregnant and notify your doctor as soon as possible if you discover you are pregnant. Don't stop or change your medications. Talk with your doctor about any concerns you have about your medications."

REFERENCES
1. Guideline Issued for People with Epilepsy Who May Become Pregnant. News Release. American Academy of Neurology. Published May 15, 2024. Accessed May 17, 2024. https://aan.com/PressRoom/Home/PressRelease/5170?
2. Pack AM, Oskoui M, Williams Roberson S, et al. Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM. Neurology. 2024;102(11):e209279. doi:10.1212/WNL.0000000000209279
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