mProbe, Inc, Mountain View, California, USA.
Department of Cardiothoracic Surgery, Stanford University, Stanford, California, USA.
BMJ Open. 2021 Nov 25;11(11):e050963. doi: 10.1136/bmjopen-2021-050963.
This study aimed to develop a blood test for the prediction of pre-eclampsia (PE) early in gestation. We hypothesised that the longitudinal measurements of circulating adipokines and sphingolipids in maternal serum over the course of pregnancy could identify novel prognostic biomarkers that are predictive of impending event of PE early in gestation.
Retrospective discovery and longitudinal confirmation.
Maternity units from two US hospitals.
Six previously published studies of placental tissue (78 PE and 95 non-PE) were compiled for genomic discovery, maternal sera from 15 women (7 non-PE and 8 PE) enrolled at ProMedDx were used for sphingolipidomic discovery, and maternal sera from 40 women (20 non-PE and 20 PE) enrolled at Stanford University were used for longitudinal observation.
Biomarker candidates from discovery were longitudinally confirmed and compared in parallel to the ratio of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) using the same cohort. The datasets were generated by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays.
Our discovery integrating genomic and sphingolipidomic analysis identified leptin (Lep) and ceramide (Cer) (d18:1/25:0) as novel biomarkers for early gestational assessment of PE. Our longitudinal observation revealed a marked elevation of Lep/Cer (d18:1/25:0) ratio in maternal serum at a median of 23 weeks' gestation among women with impending PE as compared with women with uncomplicated pregnancy. The Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting impending event of PE with superior sensitivity (85% vs 20%) and area under curve (0.92 vs 0.52) from 5 to 25 weeks of gestation.
Our study demonstrated the longitudinal measurement of maternal Lep/Cer (d18:1/25:0) ratio allows the non-invasive assessment of PE to identify pregnancy at high risk in early gestation, outperforming the established sFlt-1/PlGF ratio test.
本研究旨在开发一种用于预测早孕期子痫前期（PE）的血液检测方法。我们假设，在妊娠过程中母体血清中循环脂肪因子和鞘脂的纵向测量可以识别新的预后生物标志物，这些标志物可预测早孕期即将发生的 PE 事件。
回顾性发现和纵向验证。
两家美国医院的产科病房。
之前有 6 项胎盘组织的研究（78 例 PE 和 95 例非 PE）被汇编用于基因组发现，来自 ProMedDx 的 15 名妇女（7 名非 PE 和 8 名 PE）的血清用于鞘脂组学发现，来自斯坦福大学的 40 名妇女（20 名非 PE 和 20 名 PE）的血清用于纵向观察。
从发现中得到的候选生物标志物通过同样的队列进行纵向确认，并与胎盘生长因子（PlGF）和可溶性 fms 样酪氨酸激酶（sFlt-1）的比值进行平行比较。数据集是通过酶联免疫吸附和液相色谱-串联质谱分析生成的。
我们的发现综合了基因组和鞘脂组学分析，确定瘦素（Lep）和神经酰胺（Cer）（d18:1/25:0）为早期评估 PE 的新生物标志物。我们的纵向观察发现，在即将发生 PE 的妇女中，中位妊娠 23 周时，母体血清中的 Lep/Cer（d18:1/25:0）比值明显升高，而与无并发症妊娠的妇女相比。Lep/Cer（d18:1/25:0）比值在预测即将发生的 PE 方面明显优于已建立的 sFlt-1/PlGF 比值，其灵敏度（85%比 20%）和曲线下面积（0.92 比 0.52）从 5 周到 25 周都有提高。
这项研究表明，母体 Lep/Cer（d18:1/25:0）比值的纵向测量可用于非侵入性评估 PE，以在早期妊娠时识别高危妊娠，优于已建立的 sFlt-1/PlGF 比值检测。
