Plasma and Cerebrospinal Fluid Candidate Biomarkers of Neonatal Encephalopathy Severity and Neurodevelopmental Outcomes
Plasma and Cerebrospinal Fluid Candidate Biomarkers of Neonatal Encephalopathy Severity and Neurodevelopmental Outcomes
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DOI：
10.1016/j.jpeds.2020.06.078
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发表时间：
2020-11-01
影响因子：
5.1
通讯作者：
Everett, Allen D.
中科院分区：
文献类型：
--
作者：
Dietrick, Barbara;Molloy, Eleanor;Everett, Allen D.
目的：从血浆和脑脊液(CSF)中寻找与新生儿脑病严重程度、癫痫发作、磁共振成像(MRI)脑损伤和15-30个月神经发育结局相关的候选生物标志物。研究设计：对新生儿脑病新生儿(N=155，出生天数0-1)和脑脊液(n=30，出生天数为0-7)进行回顾性队列研究。检测中枢神经系统坏死(胶质纤维酸性蛋白[GFAP]、神经颗粒素[NRGN]、tau)、炎症(IL-6、IL-8、IL-10)和营养(脑源性神经营养因子[BDNF]、血管内皮生长因子)蛋白。结果：新生儿脑病患者血浆NRGN、tau、IL-6、IL-8、IL-10高于对照组，而脑源性神经营养因子和血管内皮生长因子低于对照组。血浆中tau、GFAP、NRGN与脑病分级呈正相关，BDNF与脑病分级呈负相关。IL-6与癫痫发作呈负相关。Tau与MRI异常有直接关系。Tau与贝利婴幼儿发展量表III的认知和运动结果呈负相关。在脑脊液中，NRGN与认知、运动和语言测量呈负相关。GFAP、IL-6和IL-10与认知和运动结果呈负相关。IL-8与运动结果呈负相关。脑脊液候选生物标志物与脑病分级、癫痫发作或MRI异常无显著关系。结论：血浆候选生物标志物可预测15-30个月的脑病严重程度、癫痫发作、MRI异常和神经发育结局。
Objectives: To identify candidate biomarkers in both plasma and cerebrospinal fluid (CSF) that are associated with neonatal encephalopathy severity measured by encephalopathy grade, seizures, brain injury by magnetic resonance imaging (MRI), and neurodevelopmental outcomes at 15-30 months.Study design: A retrospective cohort study of plasma (N = 155, day of life 0-1) and CSF (n = 30, day of life 0-7) from neonates with neonatal encephalopathy and healthy neonates born at term (N = 30, >= 36 weeks of gestation) was conducted. We measured central nervous system necrosis (glial fibrillary acidic protein [GFAP], neurogranin [NRGN], tau), inflammatory (interleukin [IL]-6, IL-8, IL-10), and trophic (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor) proteins. Clinical outcomes were Sarnat scores of encephalopathy, seizures, MRI scores, and Bayley Scales of Infant and Toddler Development III at 15-30 months.Results: Plasma NRGN, tau, IL-6, IL-8, and IL-10 were greater, whereas BDNF and vascular endothelial growth factor were lower in patients with neonatal encephalopathy vs controls. In plasma, tau, GFAP, and NRGN were directly and BDNF inversely associated with encephalopathy grade. IL-6 was inversely related to seizures. Tau was directly related to MRI abnormalities. Tau was inversely associated with Bayley Scales of Infant and Toddler Development III cognitive and motor outcomes. In CSF, NRGN was inversely associated with cognitive, motor, and language measures. GFAP, IL-6, and IL-10 were inversely related to cognitive and motor outcomes. IL-8 was inversely related to motor outcomes. CSF candidate biomarkers showed no significant relationships with encephalopathy grade, seizures, or MRI abnormalities.Conclusions: Plasma candidate biomarkers predicted encephalopathy severity, seizures, MRI abnormalities, and neurodevelopmental outcomes at 15-30 months.