Therapeutic Hypothermia Modulates the Relationships Between Indicators of Severity of Neonatal Hypoxic Ischemic Encephalopathy and Serum Biomarkers.
Therapeutic Hypothermia Modulates the Relationships Between Indicators of Severity of Neonatal Hypoxic Ischemic Encephalopathy and Serum Biomarkers.
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DOI：
10.3389/fneur.2021.748150
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发表时间：
2021
影响因子：
3.4
通讯作者：
Everett AD
中科院分区：
文献类型：
--
作者：
Chavez-Valdez R;Miller S;Spahic H;Vaidya D;Parkinson C;Dietrick B;Brooks S;Gerner GJ;Tekes A;Graham EM;Northington FJ;Everett AD
目的：探讨治疗性低温（TH）暴露对新生儿缺氧缺血性脑病（HIE）严重程度的传统临床生化指标及血清生物标志物的相关性强弱变化。我们假设TH的高潮改变了HIE严重程度的传统指标与血清生物标志物之间的关系强度。方法：该研究是一项单中心观察队列研究，纳入178名接受TH治疗的新生儿HIE，并随访血清生物标志物：(i)脑源性神经营养因子（BDNF）和血管内皮生长因子（VEGF）（神经营养因子）；（ii） tau和胶质原纤维酸性蛋白（GFAP）（神经细胞损伤）；（iii）白细胞介素6 (IL-6)， IL-8和IL-10（细胞因子），在他们生命的第一周。调整后的混合效应模型测试了与TH暴露相关的HIE指标的相关性。结果：入院时，较低的Apgar评分和基础过剩（BE）以及较高的乳酸和有核红细胞（NRBC）计数与较高的Sarnat评分相关。这些HIE严重程度较差的指标，包括较高的Sarnat评分，与不同时间点较低的VEGF和较高的tau、GFAP和IL-10水平相关。在生命的最初24小时内，Sarnat评分为b>2的患者VEGF水平较低，而只有评分为3的患者GFAP和IL-10水平较高。在Sarnat评分为3分的患者中，Tau水平在TH期间升高，而在评分为2分的患者中，Tau和GFAP在TH后升高。经调整后，TH期间较低的VEGF水平和TH期间及之后较高的tau、GFAP和IL-10水平与较差的Sarnat评分相关。经TH后，Tau和GFAP与Sarnat评分的关系增强。结论：治疗性低温对传统的HIE严重程度指标与调整后的血清生物标志物之间的关系具有独立的调节作用。因此，如果在新的临床试验中提出生物标志物用于患者分层，则必须仔细考虑与TH暴露相关的生物标志物检测时间。
Objective: To determine the changes due to therapeutic hypothermia (TH) exposure in the strength of association between traditional clinical and biochemical indicators of severity of neonatal hypoxic-ischemic encephalopathy (HIE) and serum biomarkers. We hypothesized that culmination of TH changes the strength of the relationships between traditional indicators of severity of HIE and serum biomarkers. Methods: This was a single-center observational cohort study of 178 neonates with HIE treated with TH and followed with serum biomarkers: (i) brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) (neurotrophins); (ii) tau and glial fibrillary acidic protein (GFAP) (neural cell injury); and (iii) interleukin 6 (IL-6), IL-8, and IL-10 (cytokines), during their first week of life. Adjusted mixed-effect models tested associations with HIE indicators in relation to TH exposure. Results: At admission, lower Apgar scores and base excess (BE) and higher lactate and nucleated red blood cell (NRBC) count correlated with higher Sarnat scores. These indicators of worse HIE severity, including higher Sarnat score, correlated with lower VEGF and higher tau, GFAP, and IL-10 levels at different time points. Within the first 24 h of life, patients with a Sarnat score >2 had lower VEGF levels, whereas only those with score of 3 also had higher GFAP and IL-10 levels. Tau levels increased during TH in patients with Sarnat score of 3, whereas tau and GFAP increased after TH in those with scores of 2. After adjustments, lower VEGF levels during TH and higher tau, GFAP, and IL-10 levels during and after TH were associated with worse Sarnat scores. Tau and GFAP relationship with Sarnat score became stronger after TH. Conclusion: Therapeutic hypothermia exerts an independent modulatory effect in the relationships between traditional indicators of severity of HIE and serum biomarkers after adjustments. Thus, the timing of biomarker testing in relation to TH exposure must be carefully considered if biomarkers are proposed for patient stratification in novel clinical trials.
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影响因子：
1.7
作者：
Aly, Hany;Hassanein, Sahar;Atiea, Wael
通讯作者：
Atiea, Wael
影响因子：
3.7
作者：
Dalili H;Nili F;Sheikh M;Hardani AK;Shariat M;Nayeri F
通讯作者：
Nayeri F
影响因子：
2.1
作者：
Dereymaeker, Anneleen;Matic, Vladimir;Jansen, Katrien
通讯作者：
Jansen, Katrien
影响因子：
3.5
作者：
Chavez-Valdez R;Emerson P;Goffigan-Holmes J;Kirkwood A;Martin LJ;Northington FJ
通讯作者：
Northington FJ
影响因子：
5.1
作者：
Dietrick, Barbara;Molloy, Eleanor;Everett, Allen D.
通讯作者：
Everett, Allen D.