Table_1_Novel Point-of-Care Diagnostic Method for Neonatal Encephalopathy Using Purine Nucleosides.XLSX

Background: Evidence suggests that earlier diagnosis and initiation of treatment immediately after birth is critical for improved neurodevelopmental outcomes following neonatal encephalopathy (NE). Current diagnostic tests are, however, mainly restricted to clinical diagnosis with no molecular tests available. Purines including adenosine are released during brain injury such as hypoxia and are also present in biofluids. Whether blood purine changes can be used to diagnose NE has not been investigated to date.
Methods: Blood purines were measured in a mouse model of neonatal hypoxia and infants with NE using a novel point-of-care diagnostic technology (SMARTChip) based on the summated electrochemical detection of adenosine and adenosine metabolites in the blood.
Results: Blood purine concentrations were ∼2–3-fold elevated following hypoxia in mice [2.77 ± 0.48 μM (Control) vs. 7.57 ± 1.41 μM (post-hypoxia), p = 0.029]. Data in infants with NE had a 2–3-fold elevation when compared to healthy controls [1.63 ± 0.47 μM (Control, N = 5) vs. 4.87 ± 0.92 μM (NE, N = 21), p = 0.0155]. ROC curve analysis demonstrates a high sensitivity (81%) and specificity (80%) for our approach to identify infants with NE. Moreover, blood purine concentrations were higher in infants with NE and seizures [8.13 ± 3.23 μM (with seizures, N = 5) vs. 3.86 ± 0.56 μM (without seizures, N = 16), p = 0.044].
Conclusion: Our data provides the proof-of-concept that measurement of blood purine concentrations via SMARTChip technology may offer a low-volume bedside test to support a rapid diagnosis of NE.

背景：现有研究证据表明，新生儿脑病（Neonatal Encephalopathy, NE）患儿在出生后尽早诊断并即刻启动治疗，对改善其神经发育结局至关重要。然而当前的诊断手段主要局限于临床诊断，尚无可用的分子检测方法。包括腺苷在内的嘌呤类物质会在缺氧等脑损伤过程中释放，同时也存在于生物体液中。迄今为止，尚未有研究探讨血液嘌呤水平变化能否用于新生儿脑病的诊断。
方法：本研究采用一种基于血液中腺苷及腺苷代谢物累加电化学检测的新型床旁诊断技术（SMARTChip），对新生儿缺氧小鼠模型及新生儿脑病患儿的血液嘌呤水平进行了检测。
结果：小鼠缺氧造模后，血液嘌呤浓度升高约2~3倍[对照组为2.77±0.48 μM，缺氧后组为7.57±1.41 μM，p=0.029]。新生儿脑病患儿的血液嘌呤水平较健康对照升高2~3倍[健康对照组：1.63±0.47 μM，N=5；新生儿脑病组：4.87±0.92 μM，N=21，p=0.0155]。受试者工作特征曲线（Receiver Operating Characteristic curve, ROC）分析显示，本检测方法识别新生儿脑病患儿的灵敏度达81%，特异度达80%。此外，合并癫痫发作的新生儿脑病患儿血液嘌呤水平更高[伴癫痫组：8.13±3.23 μM，N=5；无癫痫组：3.86±0.56 μM，N=16，p=0.044]。
结论：本研究结果证实了概念可行性：通过SMARTChip技术检测血液嘌呤水平，可提供一种低样本量的床旁检测手段，助力新生儿脑病的快速诊断。