Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia.
Reproduction. 2013 Aug 21;146(4):335-45. doi: 10.1530/REP-13-0175. Print 2013 Oct.
The ability to recognise women who are at-risk of preterm labour (PTL) is often difficult. Over 50% of women who are identified with factors associated with an increased risk of preterm birth will ultimately deliver at term. The cervicovaginal fluid (CVF) comprises a range of proteins secreted by gestational tissues, making it an ideal candidate for the screening of differentially expressed proteins associated with PTL. CVF samples were collected from at-risk asymptomatic women. Two-dimensional gel electrophoresis techniques were used to examine the CVF proteome of women who spontaneously delivered preterm 11-22 days later compared with gestation-matched women who delivered at term. Five candidate biomarkers were selected for further validation in a larger independent cohort of asymptomatic women. Thioredoxin (TXN) and interleukin 1 receptor antagonist (IL1RN) concentrations in the CVF were found to be significantly reduced up to 90 days prior to spontaneous PTL compared with women who subsequently delivered at term. TXN was able to predict spontaneous PTL within 28 days after sampling with a high positive predictive value (PPV) and negative predictive value (NPV) of 75.0% and 96.4% respectively. IL1RN also showed comparable PPV and NPV of 72.7% and 95.7% respectively. The discovery of these differentially expressed proteins may assist in the development of a new predictive bedside test in identifying asymptomatic women who have an increased risk of spontaneous PTL.
识别有早产风险(PTL)的女性的能力通常很困难。超过 50%的被识别出与早产风险增加相关因素的女性最终会足月分娩。宫颈阴道分泌物(CVF)包含一系列由妊娠组织分泌的蛋白质,使其成为筛查与 PTL 相关的差异表达蛋白的理想候选物。从有风险的无症状女性中采集 CVF 样本。二维凝胶电泳技术用于检查在 11-22 天后自然早产的女性与在足月分娩的妊娠匹配女性的 CVF 蛋白质组。选择了五个候选生物标志物在更大的无症状女性独立队列中进行进一步验证。与随后足月分娩的女性相比,在自发性 PTL 发生前 90 天,CVF 中的硫氧还蛋白(TXN)和白细胞介素 1 受体拮抗剂(IL1RN)浓度显著降低。TXN 能够在采样后 28 天内预测自发性 PTL,其阳性预测值(PPV)和阴性预测值(NPV)分别高达 75.0%和 96.4%。IL1RN 的 PPV 和 NPV 也分别为 72.7%和 95.7%,具有可比性。这些差异表达蛋白的发现可能有助于开发新的预测床边测试,以识别有自发性 PTL 风险增加的无症状女性。