title: 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.
  
  
  METHODS
  Electronic searches in PubMed, Embase, Cinahl, Lilacs, and Medion, references of retrieved articles, and conference proceedings. No language restrictions were applied.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  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.
authors.affiliation: Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Conde-Agudelo
authors.forename: A T
authors.initials: AT
authors.lastname: Papageorghiou
authors.forename: S H
authors.initials: SH
authors.lastname: Kennedy
authors.forename: J
authors.initials: J
authors.lastname: Villar
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002582:Cervix Mucus / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; C501532:IGFBPL1 protein, human; D018969:Insulin-Like Growth Factor Binding Proteins; D015850:Interleukin-6; D020543:Proteome; D025521:Tumor Suppressor Proteins; D011388:Prolactin; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D020784:Matrix Metalloproteinase 8