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. 2025 Mar 11:15357597241258514.
doi: 10.1177/15357597241258514. Online ahead of print.

Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication

Practice Guideline From the AAN, AES, and SMFM; Alison M Pack, Maryam Oskoui, Shawniqua Williams Roberson, Diane K Donley, Jacqueline French, Elizabeth E Gerard, David Gloss, Wendy R Miller, Heidi M Munger Clary, Sarah S Osmundson, Brandy McFadden, Kaitlyn Parratt, Page B Pennell, George Saade, Don B Smith, Kelly Sullivan, Sanjeev V Thomas, Torbjörn Tomson, Mary Dolan O'Brien, Kylie Botchway-Doe, Heather M Silsbee, Mark R Keezer

Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication

Practice Guideline From the AAN, AES, and SMFM et al. Epilepsy Curr. .

Abstract

This practice guideline provides updated 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 neuro-developmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

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Conflict of interest statement

The American Academy of Neurology (AAN) is committed to producing independent, critical, and trustworthy clinical practice guidelines (CPGs) and evidence-based documents. Significant efforts are made to minimize the potential for conflicts of interest to influence the recommendations of this evidence-based document. Management and disclosure of document developer relationships is conducted in compliance with the 2017 AAN process manual section titled, “Implementing the AAN Conflict of Interest Policy for Guidelines and Case Definitions,” which can be viewed at aan.com.

Figures

Figure 1.
Figure 1.
Study Selection.
See this image and copyright information in PMC

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