First-Trimester Contingent Screening for Trisomy 21 by Fetal Nuchal Translucency and Maternal Serum Biomarkers and Maternal Blood Cell-Free DNA Testing

Analysis of cell-free DNA in maternal blood has been proposed as a novel screening method for evaluation of aneuploidies. The higher performance of this technique in screening of trisomies compared to all currently available methods would lead to widespread use of this technique in clinical settings. In total, 1,066,829 singleton pregnancies referred to Nilou Clinical Laboratory were screened for chromosomal trisomies during a period of 12years. First-trimester screening (FTS), Triple and Quad markers of second-trimester screening (STS) as well as integrated results have been obtained from 444,515, 34,984, 560,857 and 26,473 singleton pregnancies respectively. Non-invasive prenatal test (NIPT) using cfDNA was applied in 3500 pregnant women. Risk cutoffs, detection rates (DRs) and false positive rates (FPRs) were assessed for combinations of screening strategies to identify the most efficient strategy for contingent cfDNA testing. Contingent screening including FTS and NIPT offer to 20% of cases would lead to detection of 98% of fetuses with trisomy 21 at a total invasive testing rate of 1.1%. Contingent screening including STS and NIPT offer to 9.0% of cases would lead to detection of 95.5% of fetuses with trisomy 21 at a total invasive testing rate of 4.5%. Contingent screening including FTS or STS and cfDNA testing are efficient strategies for screening of trisomy 21.