Neurology, Children's National Hospital, Washington, DC, USA.
Diagnostic Imaging and Radiology, Children's National Hospital, Washington, DC, USA.
Pediatr Res. 2021 Dec;90(6):1228-1234. doi: 10.1038/s41390-021-01405-w. Epub 2021 Mar 2.
Neonatal encephalopathy (NE) is a major cause of long-term neurodevelopmental disability in neonates. We evaluated the ability of serially measured biomarkers of brain injury to predict adverse neurological outcomes in this population.
Circulating brain injury biomarkers including BDNF, IL-6, IL-8, IL-10, VEGF, Tau, GFAP, and NRGN were measured at 0, 12, 24, 48, 72, and 96 h of cooling from 103 infants with NE undergoing TH. The biomarkers' individual and combinative ability to predict death or severe brain injury and adverse neurodevelopmental outcomes beyond 1 year of age was assessed.
Early measurements of inflammatory cytokines IL-6, 8, and 10 within 24 HOL (AUC = 0.826) and late measurements of Tau from 72 to 96 HOL (AUC = 0.883, OR 4.37) were accurate in predicting severe brain injury seen on MRI. Late measurements of Tau were predictive of adverse neurodevelopmental outcomes (AUC = 0.81, OR 2.59).
Tau was consistently a predictive marker for brain injury in neonates with NE. However, in the first 24 HOL, IL-6, 8, and 10 in combination were most predictive of death or severe brain injury. The results of this study support the use of a serial biomarker panel to assess brain injury over the time course of disease in NE.
While recent studies have evaluated candidate brain injury biomarkers, no biomarker is in current clinical use. This study supports the use of a serial biomarker panel for ongoing assessment of brain injury neonates with NE. In combination, IL6, IL8, and IL10 in the first 24 h of cooling were more predictive of brain injury by MRI than each cytokine alone. Individually, Tau was overall most consistently predictive of adverse neurological outcomes, particularly when measured at or after rewarming.
新生儿脑病（NE）是新生儿长期神经发育残疾的主要原因。我们评估了连续测量脑损伤生物标志物在该人群中预测不良神经结局的能力。
在接受 TH 的 103 例 NE 婴儿中，于冷却后 0、12、24、48、72 和 96 小时测量循环脑损伤生物标志物，包括 BDNF、IL-6、IL-8、IL-10、VEGF、Tau、GFAP 和 NRGN。评估了这些生物标志物单独和联合预测死亡或严重脑损伤以及 1 岁以上不良神经发育结局的能力。
在 24 小时内早期测量炎症细胞因子 IL-6、8 和 10（AUC=0.826）和在 72 至 96 小时内晚期测量 Tau（AUC=0.883，OR 4.37）可准确预测 MRI 上的严重脑损伤。晚期 Tau 测量值可预测不良神经发育结局（AUC=0.81，OR 2.59）。
Tau 一直是 NE 新生儿脑损伤的预测标志物。然而，在最初的 24 小时内，IL-6、8 和 10 的组合对死亡或严重脑损伤最具预测性。这项研究支持使用连续生物标志物组来评估 NE 中疾病的时间过程中的脑损伤。
尽管最近的研究已经评估了候选脑损伤生物标志物，但没有生物标志物目前在临床使用。本研究支持使用连续生物标志物组来对患有 NE 的脑损伤新生儿进行持续评估。在最初的 24 小时内，联合使用 IL6、IL8 和 IL10 比单独使用每种细胞因子更能预测 MRI 脑损伤。总体而言，Tau 是最一致地预测不良神经结局的标志物，特别是在复温后或之后测量时。
