title: Biomarkers for predicting spontaneous preterm birth: an umbrella systematic review.
abstract: OBJECTIVE
  To identify all systematic reviews investigating the role of maternal and fetal biomarkers for predicting spontaneous preterm birth (SPTB).
  
  
  METHODS
  Medline and Web of Sciences databases were searched electronically. Studies exploring the association between maternal biomarkers and spontaneous delivery were considered suitable for inclusion. A synthesis of the systematic reviews was performed with the umbrella methodology. Statistical measures of association (Odd ratio, OR, relative risk, RR) and predictive accuracy (sensitivity, specificity, positive and negative likelihood ratios were used to synthesize results of the included studies.
  
  
  RESULTS
  21,614 articles were identified, 542 were assessed with respect to their eligibility for inclusion and 14 systematic reviews included. Cervical fibronectin was the biomarkers which showed the highest strength of association with the occurrence of SPTB (delivery within 24 h OR 7, 95%CI 3-17; delivery <7 days (OR 12, 95%CI 8-16). Maternal serum alpha fetoprotein, was associated with an OR of 4 and 3 for early and late SPTB. C-reactive protein had an OR of 2 (95%CI 1-2) and 8 (95%CI 4-16) when detected in maternal plasma and amniotic fluid, respectively. Among cytokines, interleukin-6 had an OR and an LR + for SPTB of 2 and 12 when detected in maternal serum.
  
  
  CONCLUSIONS
  Cervical fetal fibronectin, alpha fetoprotein, C- reactive protein and interleukin 6 can have an overall good diagnostic accuracy in identifying pregnancies at risk of SPTB. Large prospective studies in different sub-set of women are needed to ascertain whether the combination of different serological and imaging marker can improve antenatal prediction of this condition.
authors.affiliation: a Department of Biomedicine and Prevention University Rome Tor Vergata , Rome , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lucaroni
authors.affiliation: a Department of Biomedicine and Prevention University Rome Tor Vergata , Rome , Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Morciano
authors.affiliation: a Department of Biomedicine and Prevention University Rome Tor Vergata , Rome , Italy.
authors.forename: Giuseppe
authors.identifier: http://orcid.org/0000-0002-5525-4353
authors.initials: G
authors.lastname: Rizzo
authors.affiliation: b Department of Clinical Medicine, Faculty of Health Sciences , UiT, The Arctic University of Norway , Tromsø , Norway.
authors.forename: Francesco
authors.initials: F
authors.lastname: D' Antonio
authors.affiliation: a Department of Biomedicine and Prevention University Rome Tor Vergata , Rome , Italy.
authors.forename: Ersilia
authors.initials: E
authors.lastname: Buonuomo
authors.affiliation: a Department of Biomedicine and Prevention University Rome Tor Vergata , Rome , Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Palombi
authors.affiliation: a Department of Biomedicine and Prevention University Rome Tor Vergata , Rome , Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Arduini
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D005260:Female; D005353:Fibronectins / Q000097:blood*; D005865:Gestational Age; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000097:blood* / Q000175:diagnosis; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D015415:Biomarkers; D005353:Fibronectins; D015850:Interleukin-6; D000509:alpha-Fetoproteins; D002097:C-Reactive Protein
keywords: Preterm birth; biomarkers; cytokines; fibronectin; systematic review