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.

中文翻译：

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使用嘌呤核苷诊断新生儿脑病的新方法。


背景：有证据表明，出生后早期诊断和立即开始治疗对于改善新生儿脑病（NE）后的神经发育结局至关重要。然而，目前的诊断测试主要局限于临床诊断，没有可用的分子测试。包括腺苷在内的嘌呤在缺氧等脑损伤期间释放，并且也存在于生物液中。迄今为止，尚未研究血嘌呤变化是否可用于诊断 NE。方法：使用基于血液中腺苷和腺苷代谢物电化学检测的新型护理点诊断技术 (SMARTChip) 测量新生儿缺氧和 NE 婴儿模型的血液嘌呤。结果：小鼠缺氧后，血液嘌呤浓度升高约 2-3 倍 [2.77 ± 0.48 μM（对照）与 7.57 ± 1.41 μM（缺氧后）​​，p = 0.029]。与健康对照相比，患有 NE 的婴儿的数据升高了 2-3 倍 [1.63 ± 0.47 μM（对照，N = 5）与 4.87 ± 0.92 μM（NE，N = 21），p = 0.0155]。 ROC 曲线分析表明我们识别 NE 婴儿的方法具有高敏感性 (81%) 和特异性 (80%)。此外，患有 NE 和癫痫发作的婴儿的血嘌呤浓度较高 [8.13 ± 3.23 μM（有癫痫发作，N = 5）与 3.86 ± 0.56 μM（无癫痫发作，N = 16），p = 0.044]。结论：我们的数据提供了概念验证，即通过 SMARTChip 技术测量血液嘌呤浓度可以提供小容量床边测试以支持 NE 的快速诊断。