新生儿缺氧缺血性脑病的脑损伤血浆生物标志物。

Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy.

机构信息

Department of Pediatrics, The George Washington University School of Medicine and Children's National Health Systems, Washington, DC.

Department of Neurology, University of California, San Francisco, San Francisco, CA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA.

出版信息

J Pediatr. 2018 Mar;194:67-75.e1. doi: 10.1016/j.jpeds.2017.10.060.

DOI:10.1016/j.jpeds.2017.10.060

PMID:29478510

Abstract

OBJECTIVES

To evaluate plasma brain specific proteins and cytokines as biomarkers of brain injury in newborns with hypoxic-ischemic encephalopathy (HIE) and, secondarily, to assess the effect of erythropoietin (Epo) treatment on the relationship between biomarkers and outcomes.

STUDY DESIGN

A study of candidate brain injury biomarkers was conducted in the context of a phase II multicenter randomized trial evaluating Epo for neuroprotection in HIE. Plasma was collected at baseline (<24 hours) and on day 5. Brain injury was assessed by magnetic resonance imaging (MRI) and neurodevelopmental assessments at 1 year. The relationships between Epo, brain-specific proteins (S100B, ubiquitin carboxy-terminal hydrolase-L1 [UCH-L1], total Tau, neuron specific enolase), cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, IL-12P70, IL-13, interferon-gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], brain-derived neurotrophic factor [BDNF], monocyte chemoattractant protein-1), and brain injury were assessed.

RESULTS

In 50 newborns with encephalopathy, elevated baseline S100B, Tau, UCH-L1, IL-1β, IL-6, IL-8, IL-10, IL-13, TNF-α, and IFN-γ levels were associated with increasing brain injury severity by MRI. Higher baseline Tau and lower day 5 BDNF were associated with worse 1 year outcomes. No statistically significant evidence of Epo treatment modification on biomarkers was detected in this small cohort.

CONCLUSIONS

Elevated plasma brain-specific proteins and cytokine levels in the first 24 hours of life are associated with worse brain injury by MRI in newborns with HIE. Only Tau and BDNF levels were found to be related to neurodevelopmental outcomes. The effect of Epo treatment on the relationships between biomarkers and brain injury in HIE requires further study.

TRIAL REGISTRATION

ClinicalTrials.gov: 01913340.

摘要

目的

评估脑特异性蛋白和细胞因子作为缺氧缺血性脑病（HIE）新生儿脑损伤的生物标志物，并评估促红细胞生成素（Epo）治疗对生物标志物与结局关系的影响。

研究设计

在一项评估 Epo 对 HIE 神经保护作用的 II 期多中心随机试验背景下，进行候选脑损伤生物标志物的研究。在基线（<24 小时）和第 5 天采集血浆。通过磁共振成像（MRI）和 1 年的神经发育评估评估脑损伤。评估 Epo 与脑特异性蛋白（S100B、泛素羧基末端水解酶-L1[UCH-L1]、总 Tau、神经元特异性烯醇化酶）、细胞因子（白细胞介素[IL]-1β、IL-6、IL-8、IL-10、IL-12P70、IL-13、干扰素-γ[IFN-γ]、肿瘤坏死因子-α[TNF-α]、脑源性神经营养因子[BDNF]、单核细胞趋化蛋白-1）和脑损伤之间的关系。

结果

在 50 例脑病新生儿中，基线时 S100B、Tau、UCH-L1、IL-1β、IL-6、IL-8、IL-10、IL-13、TNF-α和 IFN-γ水平升高与 MRI 所示脑损伤严重程度增加相关。基线 Tau 水平升高和第 5 天 BDNF 水平降低与 1 年结局较差相关。在这个小队列中，未发现 Epo 治疗对生物标志物有统计学意义的影响。