Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA.
Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA.
Biol Reprod. 2024 Mar 13;110(3):548-557. doi: 10.1093/biolre/ioad162.
To assess performance and discriminatory capacity of commercially available enzyme-linked immunosorbent assays of biomarkers for predicting first trimester pregnancy outcome in a multi-center cohort.
In a case-control study at three academic centers of women with pain and bleeding in early pregnancy, enzyme-linked immunosorbent assays of biomarkers were screened for assay performance. Performance was assessed via functional sensitivity, assay reportable range, recovery/linearity, and intra-assay precision (%Coefficient of Variation). Top candidates were analyzed for discriminatory capacity for viability and location among 210 women with tubal ectopic pregnancy, viable intrauterine pregnancy, or miscarriage. Assay discrimination was assessed by visual plots, area under the curve with 95% confidence intervals, and measures of central tendency with two-sample t-tests.
Of 25 biomarkers evaluated, 22 demonstrated good or acceptable assay performance. Transgelin-2, oviductal glycoprotein, and integrin-linked kinase were rejected due to poor performance. The best biomarkers for discrimination of pregnancy location were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 1, insulin-like growth factor binding protein 1, kisspeptin (KISS1), pregnancy-specific beta-1-glycoprotein 3, and beta parvin (PARVB). The best biomarkers for discrimination of pregnancy viability were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 3, EH domain-containing protein 3, KISS1, WAP four-disulfide core domain protein 2 (HE4), quiescin sulfhydryl oxidase 2, and pregnancy-specific beta-1-glycoprotein 1.
Performance of commercially available enzyme-linked immunosorbent assays was acceptable for a panel of novel biomarkers to predict early pregnancy outcome. Of these, six and seven candidates demonstrated good discriminatory capacity of pregnancy location and viability, respectively, when validated in a distinct external population. Four markers demonstrated good discrimination for both location and viability.
评估商业上可获得的生物标志物酶联免疫吸附测定在多中心队列中预测早孕结局的性能和区分能力。
在三个学术中心的早期妊娠疼痛和出血的妇女中进行病例对照研究，筛选生物标志物酶联免疫吸附测定的测定性能。通过功能灵敏度、可报告的测定范围、恢复/线性和室内精密度（%变异系数）评估性能。对 210 例输卵管异位妊娠、活宫内妊娠或流产的妇女进行了具有生存能力和位置区分能力的候选物分析。通过视觉图、95%置信区间的曲线下面积和两样本 t 检验的中心趋势度量评估测定的区分能力。
在评估的 25 种生物标志物中，有 22 种表现出良好或可接受的测定性能。由于性能不佳，转胶蛋白-2、输卵管糖蛋白和整合素连接激酶被拒绝。用于区分妊娠位置的最佳生物标志物是妊娠特异性β-1-糖蛋白 9、妊娠特异性β-1-糖蛋白 1、胰岛素样生长因子结合蛋白 1、KISS1、妊娠特异性β-1-糖蛋白 3 和β-parvin（PARVB）。用于区分妊娠活力的最佳生物标志物是妊娠特异性β-1-糖蛋白 9、妊娠特异性β-1-糖蛋白 3、EH 结构域蛋白 3、KISS1、WAP 四硫键核心域蛋白 2（HE4）、静止硫氧还蛋白氧化酶 2 和妊娠特异性β-1-糖蛋白 1。
商业上可获得的酶联免疫吸附测定的性能可用于预测早孕结局的一组新型生物标志物。在一个独立的外部人群中验证时，其中六个和七个候选物分别显示出良好的妊娠位置和活力的区分能力。四个标志物在位置和活力方面均具有良好的区分能力。
