An Zhuoling, Zhao Rui, Han Feifei, Sun Yuan, Liu Yanping, Liu Lihong
Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Department of Clinical Nutrition, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, Beijing, China.
Front Pharmacol. 2022 Jul 8;13:915935. doi: 10.3389/fphar.2022.915935. eCollection 2022.
Premature rupture of the fetal membranes (PROM) is a common and important obstetric complication with increased risk of adverse consequences for both mothers and fetuses. An accurate and timely method to predict the occurrence of PROM is needed for ensuring maternal and fetal safety. Untargeted metabolomics was applied to characterize metabolite profiles related to PROM in early pregnancy. 41 serum samples from pregnant women who developed PROM later in gestation and 106 from healthy pregnant women as a control group, were analyzed. Logistic regression analysis was adjusted to analyze a PROM prediction model in the first trimester. A WISH amniotic cell viability assay was applied to explore the underlying mechanisms involved in PROM, mediated by C8-dihydroceramide used to mimic a potential biomarker (Cer 40:0; O). Compared with healthy controls, 13 serum metabolites were identified. The prediction model comprising four compounds (Cer 40:0; O2, sphingosine, isohexanal and PC O-38:4) had moderate accuracy to predict PROM events with the maximum area under the curve of a receiver operating characteristics curve of approximately 0.70. Of these four compounds, Cer 40:0; O2 with an 1.81-fold change between PROM and healthy control serum samples was defined as a potential biomarker and inhibited the viability of WISH cells. This study sheds light on predicting PROM in early pregnancy and on understanding the underlying mechanism of PROM. This study protocol has been registered at www.ClinicalTrials.gov, CT03651934, on 29 August 2018 (prior to recruitment).
胎膜早破（PROM）是一种常见且重要的产科并发症，母亲和胎儿出现不良后果的风险都会增加。为确保母婴安全，需要一种准确且及时的方法来预测PROM的发生。采用非靶向代谢组学来表征与孕早期PROM相关的代谢物谱。分析了41例妊娠后期发生PROM的孕妇血清样本以及106例健康孕妇血清样本作为对照组。采用逻辑回归分析来分析孕早期的PROM预测模型。应用Wish羊膜细胞活力测定法来探究由用于模拟潜在生物标志物的C8 - 二氢神经酰胺（神经酰胺40:0；O）介导的PROM潜在机制。与健康对照组相比，鉴定出13种血清代谢物。由四种化合物（神经酰胺40:0；O2、鞘氨醇、异己醛和PC O - 38:4）组成的预测模型预测PROM事件具有中等准确性，受试者工作特征曲线下的最大面积约为0.70。在这四种化合物中，PROM与健康对照血清样本之间变化倍数为1.81倍的神经酰胺40:0；O2被定义为潜在生物标志物，并抑制了Wish细胞的活力。本研究为孕早期预测PROM以及理解PROM的潜在机制提供了线索。本研究方案已于2018年8月29日（招募前）在www.ClinicalTrials.gov上注册，注册号为CT03651934。
