From the Department of Neurology (A.M.P.), Columbia University, New York City; Departments of Pediatrics and Neurology & Neurosurgery (M.O.), McGill University, Montreal, Quebec, Canada; Departments of Neurology (S.W.R.), Biomedical Engineering (S.W.R.), and Obstetrics and Gynecology (S.S.O.), Vanderbilt University Medical Center, Nashville, TN; Northern Michigan Neurology and Munson Medical Center (D.K.D.), Traverse City, MI; Department of Neurology (J.F.), NYU Grossman School of Medicine, New York City; Feinberg School of Medicine (E.E.G.), Northwestern University, Chicago, IL; The NeuroMedical Center (D.G.), Baton Rouge, LA; Epilepsy Foundation (W.R.M.), Bowie, MD; Department of Neurology (H.M.M.C.), Wake Forest University School of Medicine, Winston-Salem, NC; My Epilepsy Story (B.M.), Nashville, TN; Institute of Clinical Neurosciences (K.P.), Royal Prince Alfred Hospital, Sydney, Australia; Department of Neurology (P.B.P.), University of Pittsburgh School of Medicine, PA; Department of Ob-Gyn (G.S.), Eastern Virginia Medical School, Norfolk; Department of Neurology (D.B.S.), University of Colorado School of Medicine, Aurora; Department of Biostatistics, Epidemiology, and Environmental Health Sciences (K.S.), Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro; Department of Neurology (S.V.T.), Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India; Department of Clinical Neuroscience (T.T.), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; American Academy of Neurology (M.D.O.B., K.B.-D., H.M.S.), Minneapolis, MN; and Centre Hospitalier de l'Université de Montréal Research Centre (CRCHUM) (M.R.K.), Quebec, Canada.
Neurology. 2024 Jun;102(11):e209279. doi: 10.1212/WNL.0000000000209279. Epub 2024 May 15.
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 neurodevelopmental 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.
本实践指南提供了更新的循证结论和建议，涉及抗癫痫药物 (ASM) 和叶酸补充对育龄期癫痫患者 (PWECP) 所生孩子的主要先天畸形 (MCM) 患病率、围产期不良结局和神经发育结局的影响。一个多学科小组按照 2017 年版美国神经病学学会临床实践指南制作过程手册中的流程进行了系统评价并制定了实践建议。系统评价包括截至 2022 年 8 月的研究。建议得到了结构化理由的支持，这些理由整合了系统评价中的证据、相关证据、护理原则以及从证据中推断出的内容。以下是一些主要建议。在治疗 PWECP 时，临床医生应在最早的可能机会即孕前推荐既能控制癫痫发作又能优化胎儿结局的 ASM 和剂量。临床医生必须尽量减少 PWECP 在怀孕期间发生癫痫发作，以尽量降低对母婴的潜在风险，并降低胎儿的潜在风险。一旦 PWECP 已经怀孕，临床医生在试图去除或替换有效控制全面强直阵挛或局灶性双侧强直阵挛发作的 ASM 时应谨慎行事。临床医生必须根据患者的癫痫综合征、控制癫痫发作的可能性和合并症，在适当的情况下考虑在 PWECP 中使用拉莫三嗪、左乙拉西坦或奥卡西平，以降低 MCM 的风险。如果临床可行，临床医生必须避免在 PWECP 中使用丙戊酸，以降低 MCM 或神经管缺陷 (NTD) 的风险。如果临床可行，临床医生必须避免在 PWECP 中使用丙戊酸或托吡酯，以降低胎儿出生时体重不足的风险。为了降低 PWECP 所生孩子神经发育不良结局（包括自闭症谱系障碍和智商较低）的风险，如临床可行，临床医生必须避免在 PWECP 中使用丙戊酸。临床医生应在孕前和怀孕期间为任何接受 ASM 治疗的 PWECP 开具至少 0.4 毫克叶酸补充剂，以降低 NTD 风险，并可能改善后代的神经发育结局。
