Data from: The role of plasma and urine metabolomics in identifying new biomarkers in severe newborn asphyxia: a study of asphyxiated newborn pigs following cardiopulmonary resuscitation

Background: Optimizing resuscitation is important to prevent morbidity and mortality from perinatal asphyxia. The metabolism of cells and tissues is severely disturbed during asphyxia and resuscitation, and metabolomic analyses provide a snapshot of many small molecular weight metabolites in body fluids or tissues. In this study metabolomics profiles were studied in newborn pigs that were asphyxiated and resuscitated using different protocols to identify biomarkers for subject characterization, intervention effects and possibly prognosis. Methods: A total of 125 newborn Noroc pigs were anesthetized, mechanically ventilated and inflicted progressive asphyxia until asystole. Pigs were randomized to resuscitation with a FiO2 0.21 or 1.0, different duration of ventilation before initiation of chest compressions (CC), and different CC to ventilation ratios. Plasma and urine samples were obtained at baseline, and 2 h and 4 h after return of spontaneous circulation (ROSC, heart rate > = 100 bpm). Metabolomics profiles of the samples were analyzed by nuclear magnetic resonance spectroscopy. Results: Plasma and urine showed severe metabolic alterations consistent with hypoxia and acidosis 2 h and 4 h after ROSC. Baseline plasma hypoxanthine and lipoprotein concentrations were inversely correlated to the duration of hypoxia sustained before asystole occurred, but there was no evidence for a differential metabolic response to the different resuscitation protocols or in terms of survival. Conclusions: Metabolic profiles of asphyxiated newborn pigs showed severe metabolic alterations. Consistent with previously published reports, we found no evidence of differences between established and alternative resuscitation protocols. Lactate and pyruvate may have a prognostic value, but have to be independently confirmed.研究背景：优化复苏策略对于预防围产期窒息（perinatal asphyxia）所致的并发症与死亡至关重要。窒息及复苏过程中，细胞与组织的代谢会受到严重干扰，而代谢组学（metabolomics）分析能够捕捉体液或组织中多种小分子代谢物的瞬时状态。本研究针对采用不同复苏方案处理的窒息新生仔猪开展代谢组学分析，旨在筛选可用于受试者特征分型、干预效果评估及预后预测的生物标志物（biomarker）。 研究方法：共计125头新生Noroc仔猪接受麻醉、机械通气，并施以渐进式窒息造模直至心搏停止。将仔猪随机分配至不同复苏组：吸入氧分数（FiO2）分别为0.21与1.0、胸外按压（chest compressions, CC）前通气时长各异、胸外按压与通气比例不同。分别于基线、自主循环恢复（return of spontaneous circulation, ROSC，心率≥100次/分钟）后2小时及4小时采集血浆与尿液样本。采用核磁共振波谱法（nuclear magnetic resonance spectroscopy）对样本的代谢组学特征进行分析。 研究结果：ROSC后2小时及4小时，血浆与尿液均出现与缺氧及酸中毒相符的严重代谢紊乱。基线血浆中的次黄嘌呤与脂蛋白浓度与心搏停止前持续缺氧时长呈负相关，但未观察到不同复苏方案间或不同生存结局间存在代谢应答差异的证据。 研究结论：窒息新生仔猪的代谢组学特征显示存在严重代谢紊乱。与既往发表的研究结果一致，本研究未发现标准复苏方案与备选复苏方案间存在差异的证据。乳酸与丙酮酸或具备预后评估价值，但仍需独立研究予以验证。