Novel biomarkers for the prediction of the spontaneous preterm birth phenotype: a systematic review and meta-analysis

Abstract

Background Being able to predict preterm birth is important, as it may allow a high-risk population to be selected for future interventional studies and help in understanding the pathways that lead to preterm birth.Objective To investigate the accuracy of novel biomarkers to predict spontaneous preterm birth in women with singleton pregnancies and no symptoms of preterm labour.Search strategy Electronic searches in PubMed, Embase, Cinahl, Lilacs, and Medion, references of retrieved articles, and conference proceedings. No language restrictions were applied.Selection criteria Observational studies that evaluated the accuracy of biomarkers proposed in the last decade to predict spontaneous preterm birth in asymptomatic women. We excluded studies in which biomarkers were evaluated in women with preterm labour.Data collection and analysis Two reviewers independently extracted data on study characteristics, quality, and accuracy. Data were arranged in 2 · 2 contingency tables and synthesised separately for spontaneous preterm birth before 32, 34, and 37 weeks of gestation. We used bivariate meta-analysis to estimate pooled sensitivities and specificities, and calculated likelihood ratios (LRs).Main results A total of 72 studies, including 89 786 women and evaluating 30 novel biomarkers, met the inclusion criteria. Only three biomarkers (proteome profile and prolactin in cervicovaginal fluid, and matrix metalloproteinase-8 in amniotic fluid) had positive LRs > 10. However, each of these biomarkers was evaluated in only one small study. Four biomarkers had a moderate predictive accuracy (interleukin-6 and angiogenin, in amniotic fluid; human chorionic gonadotrophin and phosphorylated insulin-like growth factor binding protein-1, in cervicovaginal fluid). The remaining biomarkers had low predictive accuracies.Conclusions None of the biomarkers evaluated in this review meet the criteria to be considered a clinically useful test to predict spontaneous preterm birth. Further large, prospective cohort studies are needed to evaluate promising biomarkers such as a proteome profile in cervicovaginal fluid.

Low abundance plasma proteins in labour

“…The advent of reliable proteomics methodology has opened a new window of opportunity in the study of human parturition by allowing the simultaneous study of multiple proteins in complex biological samples (Pereira et al 2007, Scholl et al 2012. The need for clinically useful biomarkers to predict preterm labour remains (Conde-Agudelo et al 2011).…”

Amniotic Fluid Metabolomic Analysis in Spontaneous Preterm Birth

“…1 Several biomarker studies using maternal and fetal biological specimens have reported single or combination of biomarkers either as a predictor or as a mechanistic contributor to the preterm labor pathways. [2][3][4] Recent systematic reviews of patient metadata and PTB biomarkers have demonstrated the futility of predicting preterm labor risk using single biomarker test. 1,4 This is partly attributed to the involvement of multiple biomarkers, their redundancy in contributing to multiple PTB pathways, and unidentified risk factors that can influence the outcome, confirming the complexity of this syndrome.…”

“…[2][3][4] Recent systematic reviews of patient metadata and PTB biomarkers have demonstrated the futility of predicting preterm labor risk using single biomarker test. 1,4 This is partly attributed to the involvement of multiple biomarkers, their redundancy in contributing to multiple PTB pathways, and unidentified risk factors that can influence the outcome, confirming the complexity of this syndrome. [5][6][7] Signals to initiate labor pathways at preterm and term involve multiple maternal-fetal organ systems.…”

Rapid cervical phIGFBP-1 test in asymptomatic twin pregnancies: role in mid-pregnancy prediction of spontaneous preterm delivery

“…13 This study comprises data from different subset of pregnancies, including symptomatic and asymptomatic patients tested at different gestational ages, and high-risk and low-risk cases. In general, on the basis of published data, the phIGFBP-1 measurement in cervicovaginal fluids seems to have a moderate predictive accuracy for preterm delivery in singleton pregnancies with a high negative predictive value, especially in symptomatic cases (Table 3).…”