Second trimester maternal serum ADAM12 levels in Down's syndrome pregnancies

Objective To estimate the utility of maternal serum ADAM12 as a Down's syndrome marker. Methods Samples from 71 Down's syndrome affected pregnancies were retrieved from -20 degrees C storage together with 710 controls matched for gestation and storage time. ADAM12 was measured prior to identification of the affected pregnancies, and expressed in multiples of the gestation-specific median (MoM). Results The median ADAM12 level in the affected pregnancies was 1.36 MoM with a 10th-90th centile range of 0.90-1.94 MoM compared with 1.01 and 0.65-1.52 MoM in the unaffected control pregnancies (P = < 0.0001, two-side Wilcoxon Rank Sum Test). The Mahalanobis distance between the medians was 0.96 compared with 0.92, 1.18, 1.07 and 1.24 for alpha-fetoprotein, intact human chorionic gonadotrophin (hCG). unconjugated estriol and inhibin-A respectively in the same samples. In unaffected pregnancies there were highly statistically significant correlations between ADAM12 and each of the other markers: in the affected pregnancies the only significant correlations were with hCG (P <= 0.001) and inhibin-A (P <= 0.05). Statistical modelling predicted that ADAM12 as a fifth marker could increase the detection rate by 2-3% or reduce the false-positive rate by 0.9-1.7%. Conclusions ADAM12 is a second trimester marker of Down's syndrome, with discriminatory power similar to existing markers. It could be considered in multi-marker combinations. Copyright (C) 2008 John Wiley & Sons, Ltd.