title: ADAM 12 as a second-trimester maternal serum marker in screening for Down syndrome.
abstract: BACKGROUND
  ADAM 12 is a placenta-derived glycoprotein that is involved in growth and differentiation. The maternal serum concentration of ADAM 12 is a potential first-trimester maternal serum marker of Down syndrome (DS). Here we examine the potential of ADAM 12 as a second-trimester maternal serum marker of DS.
  
  
  METHODS
  The concentration of ADAM 12 was determined in gestational week 14-19 in 88 DS pregnancies and 341 matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and the distribution of log(10) MoM ADAM 12 values in DS pregnancies and controls determined. Correlations with alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (free beta-hCG) were established and used to model the performance of maternal serum screening with ADAM 12 in combination with other second-trimester serum markers.
  
  
  RESULTS
  The ADAM 12 maternal serum concentration was significantly increased with a median MoM of 1.85 and a mean log(10) MoM (SD) of 0.268 (0.2678) compared to a mean log(10) MoM (SD) of 0.013 (0.4318) in controls. ADAM 12 correlated with maternal weight and ethnicity (with the serum concentration increased in Afro-Caribbeans), but neither with maternal age nor gestational age, and only marginally with AFP (r(DS) = 0.078, r(controls) = 0.093) and free beta-hCG (r(DS) = 0.073, r(controls) = 0.144. The increase in detection rate-for a false positive rate of 5%--by adding ADAM 12 to the double test (AFP + free beta-hCG) was 4%, similar to that of adding uE3 to the double test.
  
  
  CONCLUSIONS
  ADAM 12 is an efficient second-trimester marker for DS. Further studies should be conducted to determine whether it may be a useful additional or alternative marker to those currently used in the second-trimester.
authors.affiliation: Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.forename: Kevin
authors.initials: K
authors.lastname: Spencer
authors.forename: Jennie
authors.initials: J
authors.lastname: Laigaard
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Cowans
authors.forename: Severin Olesen
authors.initials: SO
authors.lastname: Larsen
authors.forename: Ulla M
authors.initials: UM
authors.lastname: Wewer
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000072199:ADAM12 Protein; D015415:Biomarkers / Q000097:blood; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008403:Mass Screening; D008565:Membrane Proteins / Q000097:blood*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood*
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human