英国剑桥大学Ulla Sovio团队揭示孕妇血清代谢物比率预测足月胎儿生长受限（FGR）。这一研究成果发表在2020年3月11日出版的《自然-医学》杂志上。

他们使用175例足月FGR和299例来自妊娠结果预测的对照，对孕龄12、20和28周（wkGA）的孕妇血清进行了超高效液相色谱-串联质谱（UPLC-MS / MS）代谢组学（POP）研究。研究在英国剑桥进行，以鉴定预测性代谢物。使用36 wkGA样品进行的内部检验表明，两种正相关代谢物（1-（1-烯基-硬脂酰基）-2-油酰基-GPC（P-18：0/18：1）和1,5-脱水葡萄糖醇）与两种负相关代谢产物（5α-雄烷-3α，17α-二醇二硫酸盐和N1，N12-二乙酰基精胺）的相对浓度之比可预测足月FGR。

与先前开发的血管生成生物标志物7（可溶性fms样酪氨酸激酶1：胎盘生长因子（sFLT1：PlGF））之比相比，该比率具有大约两倍的分辨力（AUC 0.78比0.64，P = 0.0001）。他们对出生在英国布拉德福德人群进行的人口统计学差异研究的两个子样本中验证了代谢物比率的预测性能，该研究在英国布拉德福德进行（P = 0.0002）。使用这种代谢物比例结合36 wkGA左右的超声成像进行筛查和干预，可以通过加强胎儿监测和定向引产来合理地预防不良事件。

据了解，FGR是死产的主要原因，并且还与新生儿发病率和死亡率，童年时期的健康和教育受限以及以后的一系列疾病有关。对FGR的有效筛查和干预尚未满足临床需求。

附：英文原文

Title: A maternal serum metabolite ratio predicts fetal growth restriction at term

Author: Ulla Sovio, Neil Goulding, Nancy McBride, Emma Cook, Francesca Gaccioli, D. Stephen Charnock-Jones, Debbie A. Lawlor, Gordon C. S. Smith

Issue&Volume: 2020-03-11

Abstract: Fetal growth restriction (FGR) is the major single cause of stillbirth1 and is also associated with neonatal morbidity and mortality2,3, impaired health and educational achievement in childhood4,5 and with a range of diseases in later life6. Effective screening and intervention for FGR is an unmet clinical need. Here, we performed ultrahigh performance liquid chromatography–tandem mass spectroscopy (UPLC–MS/MS) metabolomics on maternal serum at 12, 20 and 28 weeks of gestational age (wkGA) using 175 cases of term FGR and 299 controls from the Pregnancy Outcome Prediction (POP) study, conducted in Cambridge, UK, to identify predictive metabolites. Internal validation using 36wkGA samples demonstrated that a ratio of the products of the relative concentrations of two positively associated metabolites (1-(1-enyl-stearoyl)-2-oleoyl-GPC (P-18:0/18:1) and 1,5-anhydroglucitol) to the product of the relative concentrations of two negatively associated metabolites (5α-androstan-3α,17α-diol disulfate and N1,N12-diacetylspermine) predicted FGR at term. The ratio had approximately double the discrimination as compared to a previously developed angiogenic biomarker7, the soluble fms-like tyrosine kinase 1:placental growth factor (sFLT1:PlGF) ratio (AUC 0.78 versus 0.64, P = 0.0001). We validated the predictive performance of the metabolite ratio in two sub-samples of a demographically dissimilar cohort, Born in Bradford (BiB), conducted in Bradford, UK (P = 0.0002). Screening and intervention using this metabolite ratio in conjunction with ultrasonic imaging at around 36wkGA could plausibly prevent adverse events through enhanced fetal monitoring and targeted induction of labor.

DOI: 10.1038/s41591-020-0804-9

Source: https://www.nature.com/articles/s41591-020-0804-9