ADAM12: a novel first‐trimester maternal serum marker for Down syndrome

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Abstract
Objectives The concentration of bioavailable insulin‐like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin‐like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP‐3 takes place in human pregnancy serum; accordingly, IGFBP‐3 serum levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP‐3 and IGFBP‐5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health. Methods We developed an enzyme‐linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 µg/L. Recombinant ADAM12 was used as the standard for calibration. Results We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 µg/L at week 8 of pregnancy to 670 µg/L at 16 weeks, and reached 12 000 µg/L at term. In 18 first‐trimester Down syndrome pregnancies, the concentration of ADAM12 was decreased, thus the median multiple of mean (MoM) value was 0.14 (0.01–0.76). A detection rate for foetal Down syndrome of 82% for a screen‐positive rate of 3.2% and a 1:400 risk cut‐off was found by Monte Carlo estimation using ADAM12 and maternal age as screening markers. Conclusion ADAM12 is a promising marker for Down syndrome. Copyright © 2003 John Wiley & Sons, Ltd.