流产影响50-70%的所有概念和15-20%的临床公认的怀孕。复发性妊娠丢失(RPL,≥2次流产)影响1-5%的公认妊娠。然而,我们对RPL的病因和病理生理学的了解不完整,因此,可靠的诊断/预防工具尚不可用。这里,我们旨在定义三种胎盘蛋白对RPL的诊断价值:人绒毛膜促性腺激素游离β亚基(游离β-hCG),妊娠相关血浆蛋白A(PAPP-A),和胎盘生长因子(PlGF)。在手术时,从患有RPL的妇女(n=14)和接受选择性终止妊娠的对照组(n=30)收集血液样本。通过BRAHMSKRYPTOR分析仪测量母体血清蛋白浓度。计算每日中位数倍数(dMoM)值,以进行胎龄特异性归一化。要获取分类器,进行Logistic回归分析,并计算ROC曲线。随着健康妊娠的推进,母体血清蛋白浓度的变化存在差异。在6到13周之间,患有RPL的女性游离β-hCG的浓度和dMoMs较低,PAPP-A,和PlGF比对照。PAPP-AdMoM具有最好的判别特性(AUC=0.880)。在9到13周之间,所有dMoM蛋白的辨别特性均优异(游离β-hCG:AUC=0.975;PAPP-A:AUC=0.998;PlGF:AUC=0.924)。总之,游离β-hCG和PAPP-A是RPL的有价值的生物标志物,尤其是在9到13周之间。它们的浓度降低表明胎盘功能恶化,而较低的PlGF水平表明9周后胎盘血管生成的问题。
Miscarriages affect 50-70% of all conceptions and 15-20% of clinically recognized pregnancies. Recurrent pregnancy loss (RPL, ≥2 miscarriages) affects 1-5% of recognized pregnancies. Nevertheless, our knowledge about the etiologies and pathophysiology of RPL is incomplete, and thus, reliable diagnostic/preventive tools are not yet available. Here, we aimed to define the diagnostic value of three placental proteins for RPL: human chorionic gonadotropin free beta-subunit (free-β-hCG), pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF). Blood samples were collected from women with RPL (n = 14) and controls undergoing elective termination of pregnancy (n = 30) at the time of surgery. Maternal serum protein concentrations were measured by BRAHMS KRYPTOR Analyzer. Daily multiple of median (dMoM) values were calculated for gestational age-specific normalization. To obtain classifiers, logistic regression analysis was performed, and ROC curves were calculated. There were differences in changes of maternal serum protein concentrations with advancing healthy gestation. Between 6 and 13 weeks, women with RPL had lower concentrations and dMoMs of free β-hCG, PAPP-A, and PlGF than controls. PAPP-A dMoM had the best discriminative properties (AUC = 0.880). Between 9 and 13 weeks, discriminative properties of all protein dMoMs were excellent (free β-hCG: AUC = 0.975; PAPP-A: AUC = 0.998; PlGF: AUC = 0.924). In conclusion, free-β-hCG and PAPP-A are valuable biomarkers for RPL, especially between 9 and 13 weeks. Their decreased concentrations indicate the deterioration of placental functions, while lower PlGF levels indicate problems with placental angiogenesis after 9 weeks.