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

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 ADAM 2 in serum. The assay range was 42 to 667 mug/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 mug/L at week 8 of pregnancy to 670 mug/L at 16 weeks, and reached 12000 mug/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 (C) 2003 John Wiley Sons, Ltd.