Carreras Nuria, Arnaez Juan, Valls Ana, Agut Thais, Sierra Cristina, Garcia-Alix Alfredo
Río Hortega Program, Carlos III Health Institute, Madrid, Spain.
Department of Neonatology, Hospital Sant Joan de Déu, Barcelona, Spain.
Pediatr Res. 2023 Apr;93(5):1328-1335. doi: 10.1038/s41390-022-02011-0. Epub 2022 Apr 6.
Inflammation plays a crucial role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE). The aim of this study was to measure inflammation in HIE through an analysis of CSF neopterin and β2-microglobulin and to study the association with brain injury as shown by MRI findings and neurodevelopmental outcomes.
CSF biomarkers were measured in study patients at 12 and 72 h. Brain injury was evaluated by MRI, and neurodevelopmental outcomes were assessed at 2-3 years of life. An adverse outcome was defined as the presence of motor or cognitive impairment.
Sixty-nine HIE infants were included. Median values of neopterin and β2-microglobulin paralleled the severity of HIE. Adverse outcomes were associated with early neopterin and β2-microglobulin values, late neopterin values, and the neopterin percentage change between the two samples. A cutoff value of 75% neopterin change predicted adverse outcomes with a specificity of 0.9 and a sensitivity of 0.75.
CSF neopterin and β2-microglobulin are elevated in HIE, indicating the activation of inflammation processes. Infants with adverse neurodevelopmental outcomes show higher levels of CSF neopterin and β2-microglobulin. The evolution of neopterin levels provides a better predictive capacity than a single determination.
Brain inflammation in newborns with HIE could be measurable through the analysis of CSF neopterin and β2-microglobulin, both of which are associated with neurodevelopmental outcomes. Our study introduces two inflammatory biomarkers for infants with HIE that seem to show a more stable profile and are easier to interpret than cytokines. CSF neopterin and β2-m may become clinical tools to monitor inflammation in HIE and might eventually be helpful in measuring the response to emerging therapies.
炎症在缺氧缺血性脑病（HIE）的发病机制中起关键作用。本研究的目的是通过分析脑脊液新蝶呤和β2-微球蛋白来测量HIE中的炎症，并研究其与MRI表现所示脑损伤及神经发育结局的相关性。
在研究患者12小时和72小时时测量脑脊液生物标志物。通过MRI评估脑损伤，并在患儿2至3岁时评估神经发育结局。不良结局定义为存在运动或认知障碍。
纳入69例HIE婴儿。新蝶呤和β2-微球蛋白的中位数与HIE的严重程度平行。不良结局与早期新蝶呤和β2-微球蛋白值、晚期新蝶呤值以及两个样本之间新蝶呤的百分比变化相关。新蝶呤变化75%的临界值预测不良结局的特异性为0.9，敏感性为0.75。
HIE患儿脑脊液新蝶呤和β2-微球蛋白升高，表明炎症过程被激活。神经发育结局不良的婴儿脑脊液新蝶呤和β2-微球蛋白水平更高。新蝶呤水平的变化比单次测定具有更好的预测能力。
通过分析脑脊液新蝶呤和β2-微球蛋白可测量HIE新生儿的脑炎症，二者均与神经发育结局相关。我们针对HIE婴儿引入了两种炎症生物标志物，它们似乎显示出更稳定的特征，并且比细胞因子更易于解释。脑脊液新蝶呤和β2-微球蛋白可能成为监测HIE炎症的临床工具，并最终可能有助于评估对新出现疗法的反应。
