title: Bead-based multiplexed immunoassays to identify new biomarkers in maternal serum to improve first trimester Down syndrome screening.
abstract: OBJECTIVE
  To identify new discriminative biomarkers for Down syndrome (DS) pregnancies using a bead-based multiplexed immunoassay, and to use the newly identified biomarkers to construct a prediction model for non-invasive DS screening.
  
  
  METHODS
  Maternal serum samples of 14 DS pregnancies and 15 matched controls were analyzed with a bead-based multiplexed immunoassay containing immunoassays for 90 different analytes. Potential biomarkers were selected on the basis of concentration fold ratios between DS and control samples. For these markers and the current screening markers (pregnancy-associated plasma protein-A, PAPP-A; free beta subunit of human chorion gonadotrophin (fbeta-hCG) and nuchal translucency) prediction values were obtained and used to calculate detection rates (DR) at a 5% false positive rate.
  
  
  RESULTS
  Seven potential biomarkers of which the fold ratio exceeded 1.3 or -1.3 were selected for further analysis. All 14 DS cases in this study were detected using the combination of all currently used and newly identified markers. The modelled DR for all markers extrapolated to the general pregnant population was 82.5%, compared to a modelled DR of 56.2% for the current screening markers.
  
  
  CONCLUSIONS
  This study demonstrates the possibility of improving the performance of the current first-trimester DS screening by addition of new biomarkers, which were identified using bead-based multiplexed immunoassays.
authors.affiliation: Laboratory for Infectious Diseases and Screening, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands. wendy.koster@rivm.nl
authors.forename: M P H
authors.initials: MP
authors.lastname: Koster
authors.forename: J L A
authors.initials: JL
authors.lastname: Pennings
authors.forename: S
authors.initials: S
authors.lastname: Imholz
authors.forename: W
authors.initials: W
authors.lastname: Rodenburg
authors.forename: G H A
authors.initials: GH
authors.lastname: Visser
authors.forename: A
authors.initials: A
authors.lastname: de Vries
authors.forename: P C J I
authors.initials: PC
authors.lastname: Schielen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008403:Mass Screening / Q000379:methods; D008863:Microspheres; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D015415:Biomarkers