From the Department of Pediatrics (H.M.A.), King Abdullah bin Abdulaziz University Hospital, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; Department of Pediatrics (E.F.P.), Centre Hospitalier Universitaire Sainte-Justine and the University of Montreal, Quebec; Neurosciences and Mental Health Program (M.-A.T., J.P.V., E.W., C.D.H., E.W.Y.T.), Hospital for Sick Children Research Institute; Department of Paediatrics (C.I.S.C., D.K., E.W., L.L., C.D.H., E.W.Y.T.), Department of Radiology (E.W.), and Department of Psychology (E.M.), The Hospital for Sick Children and the University of Toronto, Ontario, Canada; and Epilepsia Helsinki (P.N.), Department of Clinical Neurophysiology, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Finland.
Neurology. 2023 May 9;100(19):e1976-e1984. doi: 10.1212/WNL.0000000000207202. Epub 2023 Mar 29.
Seizures are common during neonatal encephalopathy (NE), but the contribution of seizure burden (SB) to outcomes remains controversial. This study aims to examine the relationship between electrographic SB and neurologic outcomes after NE.
This prospective cohort study recruited newborns ≥36 weeks postmenstrual age around 6 hours of life between August 2014 and November 2019 from a neonatal intensive care unit (NICU). Participants underwent continuous electroencephalography for at least 48 hours, brain MRI within 3-5 days of life, and structured follow-up at 18 months. Electrographic seizures were identified by board-certified neurophysiologists and quantified as total SB and maximum hourly SB. A medication exposure score was calculated based on all antiseizure medications given during NICU admission. Brain MRI injury severity was classified based on basal ganglia and watershed scores. Developmental outcomes were measured using the Bayley Scales of Infant Development, Third Edition. Multivariable regression analyses were performed, adjusting for significant potential confounders.
Of 108 enrolled infants, 98 had continuous EEG (cEEG) and MRI data collected, of which 5 were lost to follow-up, and 6 died before age 18 months. All infants with moderate-severe encephalopathy completed therapeutic hypothermia. cEEG-confirmed neonatal seizures occurred in 21 (24%) newborns, with a total SB mean of 12.5 ± 36.4 minutes and a maximum hourly SB mean of 4 ± 10 min/h. After adjusting for MRI brain injury severity and medication exposure, total SB was significantly associated with lower cognitive (-0.21, 95% CI -0.33 to -0.08, = 0.002) and language (-0.25, 95% CI -0.39 to -0.11, = 0.001) scores at 18 months. Total SB of 60 minutes was associated with 15-point decline in language scores and 70 minutes for cognitive scores. However, SB was not significantly associated with epilepsy, neuromotor score, or cerebral palsy ( > 0.1).
Higher SB during NE was independently associated with worse cognitive and language scores at 18 months, even after adjusting for exposure to antiseizure medications and severity of brain injury. These observations support the hypothesis that neonatal seizures occurring during NE independently contribute to long-term outcomes.
新生儿脑病（NE）期间常发生癫痫发作，但癫痫发作负荷（SB）对结局的影响仍存在争议。本研究旨在探讨 NE 后脑电图 SB 与神经结局的关系。
本前瞻性队列研究于 2014 年 8 月至 2019 年 11 月在新生儿重症监护病房（NICU）招募胎龄≥36 周的新生儿，生后 6 小时内入组。参与者接受至少 48 小时的连续脑电图检查，生后 3-5 天内行脑 MRI 检查，并在 18 个月时进行结构化随访。由 board-certified 神经生理学家识别脑电图痫性发作，并将其量化为总 SB 和最大每小时 SB。根据 NICU 住院期间给予的所有抗癫痫药物计算药物暴露评分。根据基底节和分水岭评分对脑 MRI 损伤严重程度进行分类。采用贝利婴幼儿发育量表第三版测量发育结局。采用多变量回归分析，调整了显著的潜在混杂因素。
在 108 名入组婴儿中，98 名婴儿完成了连续脑电图（cEEG）和 MRI 数据采集，其中 5 名婴儿失访，6 名婴儿在 18 个月前死亡。所有中重度脑病患儿均完成了亚低温治疗。cEEG 确诊的新生儿癫痫发作发生于 21 名（24%）新生儿中，总 SB 平均为 12.5±36.4 分钟，最大每小时 SB 平均为 4±10 分钟/小时。在校正 MRI 脑损伤严重程度和药物暴露后，总 SB 与 18 个月时的认知功能（-0.21，95%CI-0.33 至-0.08， =0.002）和语言功能（-0.25，95%CI-0.39 至-0.11， =0.001）评分显著相关。SB 达到 60 分钟与语言评分下降 15 分，达到 70 分钟与认知评分下降 15 分相关。然而，SB 与癫痫、神经运动评分或脑瘫无显著相关性（ > 0.1）。
NE 期间更高的 SB 与 18 个月时的认知和语言评分更差独立相关，即使在校正抗癫痫药物暴露和脑损伤严重程度后也是如此。这些观察结果支持了这样的假设，即 NE 期间发生的新生儿癫痫发作独立影响长期结局。
