Hypoxic-Ischemic Encephalopathy (HIE) is one of the most relevant contributors to neurological disability in term infants. We hypothesized that clinical outcomes of newborns with (HIE) can be associated with changes at plasma metabolic level enabling the detection of brain injury. Plasma samples of a cohort of 55 asphyxiated infants who evolved to moderate/severe HIE were collected between birth and completion of therapeutic hypothermia (TH). Samples were analyzed employing a quantitative gas chromatography–mass spectrometry method for the determination of lactate and pyruvate and an untargeted liquid chromatography–time-of-flight mass spectrometry method for metabolic fingerprinting. Brain injury was assessed employing magnetic resonance imaging (MRI). A critical assessment of the usefulness of lactate, pyruvate, and pyruvate/lactate for outcome prediction was carried out. Besides, metabolic fingerprinting identified a dynamic perturbation of eleven metabolic pathways, including amino acid and purine metabolism, and the steroid hormone biosynthesis, in newborns with pathologic MRI outcomes. Although data suggest the usefulness of lactate and pyruvate monitoring during 72 h for discerning outcomes, only the steroid hormone biosynthesis pathway was significantly altered in early plasma samples (i.e., before the initiation of TH). This study highlights pathways that might potentially be targeted for biomarker discovery or adjuvant therapies to be combined with TH.

中文翻译：

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缺氧缺血性脑病的代谢表型与正常与病理磁共振成像结果的关系

缺氧缺血性脑病（HIE）是足月儿神经系统残疾最相关的因素之一。我们假设（HIE）新生儿的临床结局可能与血浆代谢水平的变化有关，从而可以检测出脑损伤。在出生至治疗性体温过低（TH）期间，收集了55名窒息婴儿的血浆样本，这些婴儿演变为中度/重度HIE。样品采用定量气相色谱-质谱法测定乳酸和丙酮酸，无目标液相色谱-飞行时间质谱法分析代谢指纹。使用磁共振成像（MRI）评估脑损伤。对乳酸，丙酮酸，丙酮酸/乳酸盐用于结果预测。此外，代谢指纹图谱在患有病理性MRI结局的新生儿中发现了11种代谢途径的动态扰动，包括氨基酸和嘌呤代谢以及类固醇激素的生物合成。尽管数据表明在72 h内进行乳酸和丙酮酸监测对于确定结局有用，但在早期血浆样品中（即在TH开始之前）仅甾体激素生物合成途径发生了显着改变。这项研究突出了可能与TH结合使用的生物标志物发现或辅助疗法的潜在途径。和具有病理MRI结局的新生儿中的甾体激素生物合成。尽管数据表明在72 h内进行乳酸和丙酮酸监测对于识别预后很有帮助，但在早期血浆样品中（即在TH开始之前）仅甾体激素生物合成途径发生了显着改变。这项研究突出了可能与TH结合使用的生物标志物发现或辅助疗法的潜在途径。和具有病理MRI结局的新生儿中的甾体激素生物合成。尽管数据表明在72 h内进行乳酸和丙酮酸监测对于识别预后很有帮助，但在早期血浆样品中（即在TH开始之前）仅甾体激素生物合成途径发生了显着改变。这项研究突出了可能与TH结合的生物标志物发现或辅助疗法的潜在途径。