CVF is a complex body fluid consisting of both endogenous and environmental proteins. The putative role of some of these proteins in the human reproductive tract is discussed.
Preterm labour and birth are a major cause of perinatal morbidity and mortality. Despite modern advances in obstetric and neonatal management, the rate of preterm birth in the developed world is increasing. Yet even though numerous risk factors associated with preterm birth have been identified, the ability to accurately predict when labour will occur remains elusive, whether it is at a term or preterm gestation. In the latter case, this is likely due to the multifactorial aetiology of preterm labour wherein women may display different clinical presentations that lead to preterm birth. The discovery of novel biomarkers that could reliably identify women who will subsequently deliver preterm may allow for timely medical intervention and targeted therapeutic treatments aimed at improving maternal and fetal outcomes. Various body fluids including amniotic fluid, urine, saliva, blood (serum/plasma), and cervicovaginal fluid all provide a rich protein source of putative biochemical markers that may be causative or reflective of the various pathophysiological disorders of pregnancy, including preterm labour. This short review will highlight recent advances in the field of biomarker discovery and the utility of single and multiple biomarkers for the prediction of preterm birth in the absence of intra-amniotic infection.
Objective To identify cervicovaginal fluid (CVF) biomarkers predictive of spontaneous preterm birth in women with symptoms of preterm labour.Design Retrospective cohort study.Setting Melbourne, Australia.Population Women with a singleton pregnancy admitted to the Emergency Department between 22 and 36 weeks of gestation presenting with symptoms of preterm labour.Methods Two-dimensional electrophoresis was used to analyse the CVF proteome. Validation of putative biomarkers was performed using enzyme-linked immunosorbent assay (ELISA) in an independent cohort. Optimal concentration thresholds of putative biomarkers were determined and the predictive efficacy for preterm birth was compared with that of fetal fibronectin.Main outcome measures Prediction of spontaneous preterm labour within 7 days.Results Differentially expressed proteins were identified by proteomic analysis in women presenting with 'threatened' preterm labour without cervical change who subsequently delivered preterm (n = 12 women). ELISA validation using an independent cohort (n = 129 women) found albumin and vitamin D-binding protein (VDBP) to be significantly altered between women who subsequently experienced preterm birth and those who delivered at term. Prediction of preterm delivery within 7 days using a dual biomarker model (albumin/VDBP) provided 66.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 96.7% negative predictive value (NPV), compared with fetal fibronectin yielding 66.7, 87.9, 36.4 and 96.2%, respectively (n = 64). Using the maximum number of screened samples, the predictive utility of albumin/VDBP yielded a sensitivity of 77.8%, specificity and PPV of 100% and NPV of 98.0% (n = 109).Conclusions The dual biomarker model of albumin/VDBP is more efficacious than fetal fibronectin in predicting spontaneous preterm delivery in symptomatic women within 7 days. A clinical diagnostic trial is required to test this model on a larger population to confirm these findings and to further refine the predictive values.
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