Prediction of spontaneous preterm labour in at-risk pregnant women

Abstract

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.

New biomarkers for the prediction of spontaneous preterm labour in symptomatic pregnant women: a comparison with fetal fibronectin

“…Differentially expressed CVF proteins in women who spontaneously delivered at term (eight from Group 1) were compared with those in women who spontaneously delivered preterm (four from Group 2) utilising 2D-DIGE and MS. A comprehensive description of the protocols has been presented previously. 10 Briefly, an equal quantity of protein from each sample was pooled and precipitated. Samples were resolubilised in rehydration buffer and, in each pooled group, CVF protein was labelled with Cy3 or Cy5 DIGE Fluor minimal dye (GE Healthcare, Buckinghamshire, UK).…”

“…Two-dimensional electrophoresis and gel scanning were performed as described previously, and gels were analysed using the Progenesis SameSpots â analysis software. 10 Protein spots of interest were manually excised and processed for MS characterisation, as described in a previously published protocol. 10 Liquid chromatography-electrospray ionisation-tandem MS (LC-ESI-MS/MS) was performed using an Agilent 1100 Series high-performance liquid chromatograph coupled to an Agilent LC/MSD Trap XCT Plus mass spectrometer (Agilent, Santa Clara, CA, USA).…”

“…10 Protein spots of interest were manually excised and processed for MS characterisation, as described in a previously published protocol. 10 Liquid chromatography-electrospray ionisation-tandem MS (LC-ESI-MS/MS) was performed using an Agilent 1100 Series high-performance liquid chromatograph coupled to an Agilent LC/MSD Trap XCT Plus mass spectrometer (Agilent, Santa Clara, CA, USA). The peptide sequences from the MS/MS spectra were identified by correlation with the peptide sequences from proteins listed in the SwissProt database (version 2011_06) using the MASCOT search algorithm (Matrix Science, Boston, MA, USA).…”

“…Aside from fFN and phIGFBP-1, CVF contains a diverse range of proteins that have been previously reported to exhibit differential expression associated with term 7,8 and preterm 9,10 birth. Therefore, the aims of this study were: (1) to characterise the protein profiles of CVF collected from symptomatic women who subsequently spontaneously delivered at term or preterm, using two-dimensional gel electrophoresis and mass spectrometry (MS); (2) to validate selected candidate proteins in a larger cohort of symptomatic women; and (3) to assess the utility of these biomarkers to predict preterm birth in women with symptoms of PTL and to compare these with the current 'gold standard' fFN.…”

Quantitative body fluid proteomics in medicine — A focus on minimal invasiveness

“…The proteomic analysis of vaginal fluid can provide more information about the pathophysiological conditions affecting the female genital tract [118,119]. 63 potential biomarkers for pregnancyrelated problems such as intra-amniotic inflammation [112,120] and preterm labour/preeclampsia [121][122][123][124][125], cervical cancer [126] and HIV infection [127] were identified (Table 6) using quantitative proteomics techniques and six biomarkers were validated.…”