First‐trimester Down syndrome screening using additional serum markers with and without nuchal translucency and cell‐free DNA

Abstract

This study aimed to evaluate serum-only four-marker first trimester (1T-Quad) Down syndrome screening, alone or contingently to select 10-20% with highest risk for nuchal translucency (NT) or cell-free (cf)DNA. Stored maternal serum samples (-80 °C) from 90 pregnancies with fetal Down syndrome and 1607 controls were retrieved and measured for placental growth factor, α-fetoprotein, pregnancy-associated plasma protein and free β-human chorionic gonadotropin. Samples were from singleton pregnancies (9-13 + 6 weeks), and NT was measured between 11 and 13 + 6 weeks. Markers were expressed in multiples of the normal median (MoM) for gestation. Gaussian models were fitted to the distribution of log MoMs by using observed parameters, standardized maternal age distribution (mean 27, SD 5.5) and published cfDNA results. The model-predicted detection rate (DR) for 1T-Quad was 74% [5% false-positive rate (FPR)]. When used contingently to select for NT, the DR was 89% at 5%. When used to select for cfDNA, the DR was 91% (FPR < 0.05%). The 1T-Quad test can achieve a similar DR to a second-trimester Quad test. When used contingently to select for NT, the DR is similar to the Combined test. Used contingently to select for cfDNA would achieve even higher detection.