Bead‐based multiplexed immunoassays to identify new biomarkers in maternal serum to improve first trimester Down syndrome screening

Abstract

To identify new discriminative biomarkers for Down syndrome (DS) pregnancies using a bead-based multiplexed immunoassay, and to use the newly identified biomarkers to construct a prediction model for non-invasive DS screening. Maternal serum samples of 14 DS pregnancies and 15 matched controls were analyzed with a bead-based multiplexed immunoassay containing immunoassays for 90 different analytes. Potential biomarkers were selected on the basis of concentration fold ratios between DS and control samples. For these markers and the current screening markers (pregnancy-associated plasma protein-A, PAPP-A; free beta subunit of human chorion gonadotrophin (fbeta-hCG) and nuchal translucency) prediction values were obtained and used to calculate detection rates (DR) at a 5% false positive rate. Seven potential biomarkers of which the fold ratio exceeded 1.3 or -1.3 were selected for further analysis. All 14 DS cases in this study were detected using the combination of all currently used and newly identified markers. The modelled DR for all markers extrapolated to the general pregnant population was 82.5%, compared to a modelled DR of 56.2% for the current screening markers. This study demonstrates the possibility of improving the performance of the current first-trimester DS screening by addition of new biomarkers, which were identified using bead-based multiplexed immunoassays.