Clinical Neuroscience, UCL-Great Ormond Street Institute of Child Health, London, UK.
Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Epilepsia. 2023 Oct;64(10):2550-2570. doi: 10.1111/epi.17745. Epub 2023 Sep 1.
Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.
新生儿癫痫发作较为常见，但治疗方法存在较大差异。国际抗癫痫联盟（ILAE）新生儿工作组根据 ILAE 标准，就新生儿抗癫痫药物（ASM）管理制定了循证推荐意见。该工作组共提出了 6 个优先问题，进行了系统的文献回顾和荟萃分析，并根据 PRISMA（系统评价和荟萃分析的首选报告项目）2020 标准报告了结果。使用 Cochrane 工具和非随机干预研究的偏倚风险（ROBINS-I）评估偏倚，并使用推荐分级、评估、制定与评价（GRADE）评估证据质量。如果证据不足，则采用 Delphi 共识方法征求专家意见。推荐意见的强度根据 ILAE 临床实践指南制定工具确定。主要有 6 项推荐意见。首先，苯巴比妥应作为一线 ASM（循证推荐），无论病因如何（专家一致同意），除非通道病可能是癫痫发作的原因（例如，由于家族史），在这种情况下应使用苯妥英或卡马西平。其次，对于一线 ASM 治疗无效的癫痫发作新生儿，可使用苯妥英、左乙拉西坦、咪达唑仑或利多卡因作为二线 ASM（专家一致同意）。对于存在心脏疾病的新生儿，左乙拉西坦可能是首选二线 ASM（专家一致同意）。第三，在没有新生儿期癫痫发作证据的情况下，急性诱发性癫痫发作停止后，无论磁共振成像或脑电图检查结果如何，都应在出院前停止使用 ASM（专家一致同意）。第四，亚低温治疗可能会降低缺氧缺血性脑病新生儿的癫痫发作负担（循证推荐）。第五，治疗新生儿癫痫发作（包括仅有脑电图改变的癫痫发作）以降低癫痫发作负担可能与改善结局相关（专家一致同意）。第六，对于有维生素 B6 依赖性癫痫临床特征和二线 ASM 治疗无效的癫痫发作新生儿，可尝试试用吡哆醇（专家一致同意）。此外，每个新生儿病房都应制定新生儿癫痫发作管理的标准化流程，并告知家长/监护人有关癫痫发作的诊断和初始治疗方案。
