New AAN guidelines: Medication must optimize seizure control, fetal outcomes
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Key takeaways:
- A panel of experts conducted a systematic literature review that yielded 82 articles.
- To reduce the risk of poor neurodevelopmental outcomes, clinicians must avoid use of valproic acid whenever possible.
For those with epilepsy who may become pregnant and their potential offspring, medications must optimize seizure control as well as outcomes for the fetus, according to new guidelines presented in Neurology.
“Infants born to people with epilepsy are at increased risk of major congenital malformations, adverse perinatal outcomes and adverse neurodevelopmental outcomes,” Alison M. Pack, MD, MPH, associate professor of clinical neurology at Columbia University Irving Medical Center, and colleagues wrote. “The role of folic acid supplementation in mitigating these risks is unclear.
A panel of 19 experts, recruited in March 2018, from the American Academy of Neurology, American Epilepsy Society, the Society for Maternal-Fetal Medicine, patient advocates and content experts conferred to formulate the new guideline.
They initiated a systematic literature review of evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). The review was based on the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual.
The search was commenced with articles from 2009 to scan for risk of bias, including 40 such studies, then conducted a preliminary review of newer studies in 2019. From more than 4,000 initial citations, the experts included 50 articles for analysis, then performed an updated review of all new studies in 2022, which yielded 13 additional articles from a pool of 315 search citations.
Among the major recommendations:
- When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur and must minimize the risk of seizures during pregnancy to minimize potential risks to the birth parent and fetus.
- Clinicians should exercise caution in removing or replacing an ASM proven effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures once pregnancy has occurred.
- Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on a range of factors to minimize the risk of MCMs, while avoiding valproic acid to minimize MCM risk or neural tube defects (NTDs), if clinically feasible.
- Clinicians should also avoid valproic acid or topiramate to minimize the risk of offspring being born small for gestational age and to reduce the risk of poor neurodevelopmental outcomes in children born to PWECP.
Additionally, the guidelines stated that clinicians should prescribe at least 0.4 mg of folic acid supplementation daily — both prior to conception and during pregnancy — to PWECPs treated with an ASM to decrease the risk of NTDs and potentially boost neurodevelopmental outcomes in offspring.
“There is considerable practice variation in the dosing of folic acid supplementation,” Pack and colleagues wrote. “High-quality studies, including randomized controlled trials where possible, will be required to definitively clarify the optimal dose and timing with respect to conception.”