title: ADAM 12 may be used to reduce the false positive rate of first trimester combined screening for Down syndrome.
abstract: BACKGROUND
  ADAM12 has been shown to be an efficient maternal serum marker for Down syndrome (DS) in the first trimester; but recent studies, using a second generation assay, have not confirmed these findings. We examined the efficiency of a second generation assay for ADAM12.
  
  
  METHODS
  ADAM12 concentrations were determined in 28 first trimester DS and 503 control pregnancies using a novel Research Delfia ADAM12 kit. Log10MoM distributions of ADAM12 and correlations with other markers were established. Population performance of screening was estimated by Monte Carlo simulation.
  
  
  RESULTS
  ADAM12 was significantly reduced in the first trimester in DS pregnancies with a log10MoM of -0.1621 (equivalent to 0.68 MoM) (p < 0.001). The reduction decreased with advancing gestational age. ADAM12 used with PAPP-A + hCG beta + NT (CUB screening) increased the detection rate (DR) from 86% to 89% for a false positive rate (FPR) of 5%. When used for a fixed DR of 90%, the addition of ADAM12 resulted in a 25% reduction of the FPR.
  
  
  CONCLUSIONS
  ADAM12 is a moderately effective DS marker. It is not a cost-effective addition to CUB screening, but may be used to reduce the FPR in selected high-risk cases.
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark. mic@ssi.dk
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.forename: Kasper
authors.initials: K
authors.lastname: Pihl
authors.forename: Paula L
authors.initials: PL
authors.lastname: Hedley
authors.forename: Anne-Cathrine
authors.initials: AC
authors.lastname: Gjerris
authors.forename: Pia Ø
authors.initials: PØ
authors.lastname: Lind
authors.forename: Severin Olesen
authors.initials: SO
authors.lastname: Larsen
authors.forename: Lone
authors.initials: L
authors.lastname: Krebs
authors.forename: Torben
authors.initials: T
authors.lastname: Larsen
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000072199:ADAM12 Protein; D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D004314:Down Syndrome / Q000097:blood* / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008403:Mass Screening; D008565:Membrane Proteins / Q000097:blood*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011295:Prenatal Care
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human