Fei He, Hou Jiebin, Wu Zhenghong, Zhang Liwen, Zhao Hongxia, Dong Xin, Chen Yaping
Department of Obstetrics and Gynaecology, The Fifth People's Hospital of Shanghai, School of Medicine, Fudan University, Shanghai, People's Republic of China.
Second Military Medical University, Shanghai, People's Republic of China.
Biomed Chromatogr. 2016 Dec;30(12):1942-1952. doi: 10.1002/bmc.3770. Epub 2016 Jul 7.
A missed abortion (MA) is an in utero death of the embryo or fetus before the 20th week of gestation with retained products of conception, and this condition is currently common in China. In order to discover novel biomarkers for MA, ultrahigh performance liquid chromatography was applied to study plasma metabolite profiles for 33 patients with MA and 29 control subjects. Thirty-seven differential plasma metabolites were found to discriminate between the two groups in the initial cohort (15 subjects with MA and 15 healthy controls). The feasibility of using these potential biomarkers to predict MA was further evaluated in the validation cohort (18 subjects with MA and 14 healthy controls) and 15 had an area under the receiver operating characteristic curve of >0.80, making them satisfactory. Tryptophan metabolism and sphingolipid metabolism were identified as important potential target pathways for MA using metabolic pathway impact analysis. Furthermore, three of the 15 satisfactory metabolites (glyceric acid, indole and sphingosine) were combined to establish a predictive model with 100% sensitivity and 100% specificity in the validation cohort. Taken together, these results suggest that MA results in significant disturbance of metabolism and those various novel biomarkers have satisfactory diagnostic and predictive power for MA.
稽留流产是指妊娠20周前胚胎或胎儿在宫内死亡且妊娠产物稽留宫腔内，目前这种情况在中国较为常见。为了发现稽留流产的新型生物标志物，采用超高效液相色谱法研究了33例稽留流产患者和29例对照者的血浆代谢物谱。在初始队列（15例稽留流产患者和15例健康对照）中发现37种差异血浆代谢物可区分两组。在验证队列（18例稽留流产患者和14例健康对照）中进一步评估了使用这些潜在生物标志物预测稽留流产的可行性，其中15种代谢物的受试者工作特征曲线下面积>0.80，结果令人满意。通过代谢途径影响分析确定色氨酸代谢和鞘脂代谢是稽留流产重要的潜在靶标途径。此外，将15种令人满意的代谢物中的3种（甘油酸、吲哚和鞘氨醇）组合起来建立了一个预测模型，该模型在验证队列中的灵敏度和特异度均为100%。综上所述，这些结果表明稽留流产会导致显著的代谢紊乱，并且这些各种新型生物标志物对稽留流产具有令人满意的诊断和预测能力。
