Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea.
Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Seongnam-si, Kyeonggido, 463-707, South Korea.
Reprod Sci. 2020 May;27(5):1187-1196. doi: 10.1007/s43032-019-00114-4. Epub 2020 Jan 6.
We aimed to identify novel biomarkers in maternal plasma that predict spontaneous preterm delivery (SPTD) in women with preterm labor (PTL) using an antibody microarray and to develop the best prediction model for SPTD based on these biomarkers in combination with clinical and ultrasound factors. This retrospective cohort study included 215 women with singleton pregnancies and PTL (23-33 weeks) who gave plasma samples. In a nested case-control study design, plasma proteomes from SPTD (case subjects, n = 15) and term delivery (control subjects, n = 15) groups were differentially profiled using a membrane-based antibody microarray. Six candidate biomarkers of interest were validated by enzyme-linked immunosorbent assay (ELISA) in the total cohort (n = 215). Cervical lengths were also measured. The primary outcome measure was SPTD within 48 h after sampling. Twenty of the molecules studied displayed significant intergroup differences. Validation by ELISA confirmed significantly higher levels of plasma endostatin and lipopolysaccharide binding protein (LBP) in women who had SPTD within 48 h than in those delivering after 48 h. However, plasma macrophage inflammatory protein (MIP)-1α levels were significantly lower in women who delivered within 48 h. A combined model was developed to predict SPTD within 48 h using a stepwise regression procedure, which included plasma endostatin and LBP levels, nulliparity, and cervical length (area under the curve = 0.920). Plasma LBP, endostatin, and MIP-1α are potential new biomarkers for predicting imminent SPTD and a combined noninvasive model based on these biomarkers and clinical and ultrasound factors can accurately predict imminent SPTD in women with PTL.
我们旨在使用抗体微阵列鉴定母体血浆中的新型生物标志物,以预测有早产迹象(PTL)的孕妇自发性早产(SPTD),并根据这些生物标志物结合临床和超声因素开发最佳的 SPTD 预测模型。这项回顾性队列研究纳入了 215 名单胎妊娠和 PTL(23-33 周)的孕妇,并采集了血浆样本。在嵌套病例对照研究设计中,使用基于膜的抗体微阵列对 SPTD(病例组,n=15)和足月分娩(对照组,n=15)组的血浆蛋白质组进行差异分析。通过酶联免疫吸附试验(ELISA)在总队列(n=215)中验证了 6 个候选生物标志物。还测量了宫颈长度。主要观察指标是采样后 48 小时内发生的 SPTD。在所研究的 20 种分子中,有 20 种显示出组间的显著差异。ELISA 验证显示,在采样后 48 小时内发生 SPTD 的女性血浆中,内皮抑素和脂多糖结合蛋白(LBP)的水平明显高于在 48 小时后分娩的女性。然而,在 48 小时内分娩的女性中,血浆巨噬细胞炎性蛋白(MIP)-1α水平明显较低。通过逐步回归程序,使用包括血浆内皮抑素和 LBP 水平、初产妇和宫颈长度在内的综合模型,建立了预测 48 小时内 SPTD 的模型(曲线下面积为 0.920)。血浆 LBP、内皮抑素和 MIP-1α是预测即将发生 SPTD 的潜在新型生物标志物,基于这些生物标志物和临床及超声因素的综合非侵入性模型可以准确预测 PTL 孕妇即将发生的 SPTD。