title: First- and second-trimester tests to predict stillbirth in unselected pregnant women: a systematic review and meta-analysis.
abstract: BACKGROUND
  Several biophysical and biochemical tests have been proposed to predict stillbirth but their predictive ability remains unclear.
  
  
  OBJECTIVE
  To assess the accuracy of tests performed during the first and/or second trimester of pregnancy to predict stillbirth in unselected women with singleton, structurally and chromosomally normal fetuses through use of formal methods for systematic reviews and meta-analytic techniques.
  
  
  METHODS
  Electronic databases, bibliographies and conference proceedings.
  
  
  METHODS
  Observational studies that evaluated the predictive accuracy for stillbirth of tests performed during the first two trimesters of pregnancy.
  
  
  METHODS
  Two reviewers selected studies, assessed risk of bias and extracted data. Summary receiver operating characteristic curves, pooled sensitivities, specificities and likelihood ratios (LRs) were generated. Data were synthesised separately for stillbirth as a sole category and for specific stillbirth categories.
  
  
  RESULTS
  Seventy-one studies, evaluating 16 single and five combined tests, met the inclusion criteria. A uterine artery pulsatility index >90th centile during the second trimester and low levels of pregnancy-associated plasma protein A (PAPP-A) during the first trimester had a moderate to high predictive accuracy for stillbirth related to placental abruption, small-for-gestational-age or pre-eclampsia (positive and negative LRs from 6.3 to 14.1, and from 0.1 to 0.4, respectively). All biophysical and biochemical tests assessed had a low predictive accuracy for stillbirth as a sole category.
  
  
  CONCLUSIONS
  Currently, there is no clinically useful first-trimester or second-trimester test to predict stillbirth as a sole category. Uterine artery pulsatility index and maternal serum PAPP-A levels appeared to be good predictors of stillbirth related to placental dysfunction disorders.
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 and Detroit, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Conde-Agudelo
authors.forename: S
authors.initials: S
authors.lastname: Bird
authors.forename: S H
authors.initials: SH
authors.lastname: Kennedy
authors.forename: J
authors.initials: J
authors.lastname: Villar
authors.forename: A T
authors.initials: AT
authors.lastname: Papageorghiou
mesh_terms: D000037:Abruptio Placentae / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011296:Prenatal Diagnosis / Q000379:methods*; D018570:Risk Assessment / Q000379:methods*; D050497:Stillbirth / Q000453:epidemiology*; D014463:Ultrasonography; D055988:Uterine Artery / Q000000981:diagnostic imaging*
chemical_list: D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human
keywords: Biomarker; meta-analysis; prediction; stillbirth; systematic review; test