Aziz Khyzer B, Kuiper Jordan, Kilborn Alison, Kambli Hrishikesh, Jayakumar Srishti, Gerner Gwendolyn J, Tekes Aylin, Parkinson Charlamaine, Graham Ernest M, Stafstrom Carl E, Campbell Christopher, Demos Catherine, Stengelin Martin, Sigal George, Wohlstadter Jacob, Everett Allen D, Northington Frances J, Chavez-Valdez Raul
Division of Neonatology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland; Neuroscience Intensive Care Nursery Program, Johns Hopkins School of Medicine, Baltimore, Maryland; Division of General Internal Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
Department of Environmental and Occupational Health, The George Washington University Milken Institute School of Public Health, Washington, District of Columbia.
Pediatr Neurol. 2025 May;166:55-64. doi: 10.1016/j.pediatrneurol.2025.02.008. Epub 2025 Feb 21.
Understanding if neonatal seizures (Sz) worsen brain injury and outcomes would optimize treatment decisions. We hypothesized that serum central nervous system-specific biomarkers would discriminate neonates with Sz and relate to outcomes.
This is a retrospective cohort study (April 2009 to November 2019), including neonates in three groups: (1) only Sz without HIE (Sz-no HIE), (2) HIE with Sz (Sz-HIE), and (3) HIE without Sz (no Sz-HIE). Levels of glial fibrillary acidic protein (GFAP, astrocytic reactivity), Tau (neuronal injury), and neurofilament light chain (NF-L, axonal degeneration) were studied at admission/<6 h, <72 h, and 72-144 h of life against time to achieve full oral feeds and NICHD-NRN MRI score.
In 145 neonates included (61% male; 33% black), admission GFAP levels were higher in Sz-HIE than in no Sz-HIE. During the first 72 hours of life, GFAP, Tau, and NF-L levels were similar between Sz-no HIE and Sz-HIE but higher than in no Sz-HIE. After 72 hours, NF-L and Tau remained higher in both Sz groups (versus no Sz-HIE). In adjusted regression models, higher Tau and NF-L percentiles related to longer time to reach full oral feeding and higher odds of more than minimal brain injury in MRI in Sz-HIE.
Tau and NF-L levels are higher in those neonates developing Sz. Although relationships with worse brain injury may be driven by the HIE severity itself, modeling shows Sz as the most important feature, providing support to the notion that Sz may worsen brain injury in neonates with HIE even after TH.
了解新生儿惊厥（Sz）是否会加重脑损伤及影响预后，将有助于优化治疗决策。我们推测血清中枢神经系统特异性生物标志物可区分患有Sz的新生儿，并与预后相关。
这是一项回顾性队列研究（2009年4月至2019年11月），纳入三组新生儿：（1）仅患有Sz而无缺氧缺血性脑病（HIE）（Sz-无HIE），（2）患有HIE且伴有Sz（Sz-HIE），（3）患有HIE但无Sz（无Sz-HIE）。研究了入院时/<6小时、<72小时和72-144小时生命期时的胶质纤维酸性蛋白（GFAP，星形细胞反应性）、 Tau（神经元损伤）和神经丝轻链（NF-L，轴突变性）水平与实现完全经口喂养的时间及美国国立儿童健康与人类发展研究所新生儿研究网络（NICHD-NRN）MRI评分的关系。
纳入145例新生儿（61%为男性；33%为黑人），Sz-HIE组入院时GFAP水平高于无Sz-HIE组。在出生后的前72小时内，Sz-无HIE组和Sz-HIE组的GFAP、Tau和NF-L水平相似，但高于无Sz-HIE组。72小时后，两个Sz组的NF-L和Tau水平仍高于无Sz-HIE组。在调整后的回归模型中，较高的Tau和NF-L百分位数与Sz-HIE组达到完全经口喂养的时间延长及MRI显示脑损伤超过轻度的几率增加有关。
发生Sz的新生儿中Tau和NF-L水平较高。虽然与更严重脑损伤的关系可能由HIE严重程度本身驱动，但模型显示Sz是最重要的特征，这支持了即使在低温治疗后，Sz仍可能加重患有HIE的新生儿脑损伤这一观点。
