ADAM 12 may be used to reduce the false positive rate of first trimester combined screening for Down syndrome

Background ADAM 12 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 ADAM 12. Materials and Methods ADAM12 concentrations were determined in 28 first trimester DS and 503 control pregnancies using a novel Research Delfia(R) ADAM12 kit. Log10MoM distributions of ADAM12 and correlations with other markers were established. Population performance of screening was estimated by Monte Carlo simulation. Results ADAM 12 was significantly reduced in the first trimester in DS pregnancies with a log 10MoM of -0.1621 (equivalent to 0.68 MoM) (p < 0.001). The reduction decreased with advancing gestational age. ADAM 12 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. Conclusion 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. Copyright (C) 2009 John Wiley & Sons, Ltd.