Hromadnikova Ilona, Kotlabova Katerina, Krofta Ladislav
Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, 100 00 Prague, Czech Republic.
Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, 147 00 Prague, Czech Republic.
Biomedicines. 2022 Mar 19;10(3):718. doi: 10.3390/biomedicines10030718.
The goal of the study was to determine the early diagnostical potential of cardiovascular disease-associated microRNAs for prediction of small-for-gestational-age (SGA) and fetal growth restriction (FGR) without preeclampsia (PE). The whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation from singleton Caucasian pregnancies within the period November 2012 to March 2020. The case-control retrospective study, nested in a cohort, involved all pregnancies diagnosed with SGA ( = 37) or FGR ( = 82) without PE and 80 appropriate-for-gestational age (AGA) pregnancies selected with regard to equality of sample storage time. Gene expression of 29 cardiovascular disease-associated microRNAs was assessed using real-time RT-PCR. Upregulation of miR-16-5p, miR-20a-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, and miR-195-5p was observed in SGA or FGR pregnancies at 10.0% false positive rate (FPR). Upregulation of miR-1-3p, miR-20b-5p, miR-126-3p, miR-130b-3p, and miR-499a-5p was observed in SGA pregnancies only at 10.0% FPR. Upregulation of miR-145-5p, miR-342-3p, and miR-574-3p was detected in FGR pregnancies at 10.0% FPR. The combination of four microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) was able to identify 75.68% SGA pregnancies at 10.0% FPR in early stages of gestation. The detection rate of SGA pregnancies without PE increased 4.67-fold (75.68% vs. 16.22%) when compared with the routine first-trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation. The combination of seven microRNA biomarkers (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) was able to identify 42.68% FGR pregnancies at 10.0% FPR in early stages of gestation. The detection rate of FGR pregnancies without PE increased 1.52-fold (42.68% vs. 28.05%) when compared with the routine first-trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation. Cardiovascular disease-associated microRNAs represent promising early biomarkers with very suitable predictive potential for SGA or FGR without PE to be implemented into the routine screening programs.
本研究的目的是确定与心血管疾病相关的微小RNA在预测无先兆子痫（PE）的小于胎龄儿（SGA）和胎儿生长受限（FGR）方面的早期诊断潜力。在2012年11月至2020年3月期间，从单胎白种人妊娠的孕妇中，于妊娠10至13周内采集外周静脉血样本。该病例对照回顾性研究嵌套在一个队列中，纳入了所有诊断为SGA（n = 37）或FGR（n = 82）且无PE的妊娠，以及80例根据样本储存时间相等原则选取的适于胎龄（AGA）妊娠。使用实时逆转录聚合酶链反应评估29种与心血管疾病相关的微小RNA的基因表达。在SGA或FGR妊娠中，以10.0%的假阳性率（FPR）观察到miR-16-5p、miR-20a-5p、miR-146a-5p、miR-155-5p、miR-181a-5p和miR-195-5p上调。仅在SGA妊娠中，以10.0%的FPR观察到miR-1-3p、miR-20b-5p、miR-126-3p、miR-130b-3p和miR-499a-5p上调。在FGR妊娠中，以10.0%的FPR检测到miR-145-5p、miR-342-3p和miR-574-3p上调。四种微小RNA生物标志物（miR-1-3p、miR-20a-5p、miR-146a-5p和miR-181a-5p）的组合能够在妊娠早期以10.0%的FPR识别出75.68%的SGA妊娠。与基于胎儿医学基金会标准的常规孕早期PE和/或FGR筛查相比，无PE的SGA妊娠的检测率提高了4.67倍（75.68%对16.22%）。七种微小RNA生物标志物（miR-16-5p、miR-20a-5p、miR-145-5p、miR-146a-5p、miR-181a-5p、miR-342-3p和miR-574-3p）的组合能够在妊娠早期以10.0%的FPR识别出42.68%的FGR妊娠。与基于胎儿医学基金会标准的常规孕早期PE和/或FGR筛查相比，无PE的FGR妊娠的检测率提高了1.52倍（42.68%对28.05%）。与心血管疾病相关的微小RNA是很有前景的早期生物标志物，对无PE的SGA或FGR具有非常合适的预测潜力，有望应用于常规筛查项目。
