{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:18:08Z","timestamp":1791177488637,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2006,8,7]],"date-time":"2006-08-07T00:00:00Z","timestamp":1154908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A Disintegrin And Metalloprotease 12 (ADAM 12) is a glycoprotein synthesised by placenta and it has been shown to be a potential first\u2010trimester maternal serum marker for Down syndrome (DS) in two small series. Here we analyse further, the potential of ADAM 12 as a marker for DS in a large collection of first\u2010trimester serum samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The concentration of ADAM 12 was determined in 10\u201314\u2010week pregnancy sera from 218 DS pregnancies and 389 gestational age\u2010matched control pregnancies, which had been collected as part of routine prospective first\u2010trimester screening programs (DS = 105) or as part of previous research studies (DS = 113). ADAM 12 was measured using a semi\u2010automated time resolved immunofluorometric assay and median values for normal pregnancies were established by polynomial regression. These medians were then used to determine population distribution parameters for DS and normal pregnancy groups. Correlation with previously established PAPP\u2010A and free \u03b2\u2010hCG multiple of the medians (MoMs) and delta nuchal translucency (NT) were determined and used to model the performance of first\u2010trimester screening with ADAM 12 in combination with other first\u2010trimester markers at various time periods across the first trimester. The benefits of a contingent testing model incorporating early measurement of PAPP\u2010A and ADAM 12 were also explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The maternal serum concentration of ADAM 12 was significantly reduced (<jats:italic>p<\/jats:italic> = 0.0049) with an overall median MoM of 0.79 in the DS cases and a log<jats:sub>10<\/jats:sub> MoM SD of 0.3734 in the DS cases and 0.3353 in the controls. There was a significant correlation of ADAM 12 MoM in DS cases with gestational age (<jats:italic>r<\/jats:italic> = 0.375) and the median MoM increased from 0.50 at 10\u201311 weeks to 1.38 at 13 weeks. ADAM 12 was correlated with maternal weight (<jats:italic>r<\/jats:italic>(controls) = 0.283), PAPP\u2010A (<jats:italic>r<\/jats:italic>(controls) = 0.324, <jats:italic>r<\/jats:italic>(DS) = 0.251) but less so with free \u03b2\u2010hCG (<jats:italic>r<\/jats:italic>(controls) = 0.062, <jats:italic>r<\/jats:italic>(DS) = 0.049) and delta NT (<jats:italic>r<\/jats:italic>(controls) = 0.110, <jats:italic>r<\/jats:italic>(DS) = 0.151). ADAM 12 was significantly (<jats:italic>p<\/jats:italic> = 0.026) lower in smokers (0.87 <jats:italic>vs<\/jats:italic> 1.00) and elevated in Afro\u2010Caribbean women compared to Caucasian women (1.34 <jats:italic>vs<\/jats:italic> 1.00).<\/jats:p><jats:p>Population modelling using parameters from this and an earlier study showed that a combination of ADAM 12 and PAPP\u2010A measured at 8\u20139 weeks and combined with NT and free \u03b2\u2010hCG measured at 12 weeks could achieve a detection rate of 97% at a 5% false\u2010positive rate or 89% at a 1% false\u2010positive rate. PAPP\u2010A and ADAM 12 alone at 8\u20139 weeks could identify 91% of cases at a 5% false\u2010positive rate. Using this as part of a contingent\u2010screening model to select an intermediate risk group of women for NT and free \u03b2\u2010hCG at 11\u201312 weeks would enable the detection of 92% of cases with a 1% false\u2010positive rate at a cost of providing NT and free \u03b2\u2010hCG for 6% of women with 94% of women having completed screening by the 10th week of pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ADAM 12 in early first trimester is a very efficient marker of DS. In combination with existing markers, it offers enhanced screening efficiency in a two\u2010stage sequential first\u2010trimester screening program or in a contingent\u2010screening model, which may have benefits in health economies where universal access to high quality ultrasound is difficult. More data on early first\u2010trimester cases with DS are required to establish more secure population parameters by which to assess further the validity of these models. Copyright \u00a9 2006 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.1540","type":"journal-article","created":{"date-parts":[[2006,8,7]],"date-time":"2006-08-07T10:19:18Z","timestamp":1154945958000},"page":"973-979","source":"Crossref","is-referenced-by-count":57,"title":["ADAM 12 as a first\u2010trimester maternal serum marker in screening for Down syndrome"],"prefix":"10.1002","volume":"26","author":[{"given":"Jennie","family":"Laigaard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Christiansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Cowans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severin Olesen","family":"Larsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bent Norgaard","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla M.","family":"Wewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,10,9]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365510310002248"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.336"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(199910)19:10<905::AID-PD658>3.0.CO;2-Q"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j..2004.00177.x"},{"key":"e_1_2_1_6_1","article-title":"ADAM 12 as a second trimster maternal serum markers in screening for Down's syndrome","volume":"26","author":"Christiansen M","year":"2006","journal-title":"Prenat Diagn"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1987.tb03115.x"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.990"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.1.157"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.762"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000165829.65319.65"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1029"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1480"},{"key":"e_1_2_1_14_1","first-page":"91","article-title":"Proteolysis of IGFBP\u20103 may be a common regulatory mechanism of IGF action in vivo","volume":"3","author":"Lamson G","year":"1993","journal-title":"Growth Regul"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3835"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2000.tb11618.x"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(199702)17:2<101::AID-PD4>3.0.CO;2-H"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-59259-712-3","volume-title":"The IGF System. 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