[MODELS OF CLINICAL IMPLEMENTATION OF CELL FREE FETAL DNA IN THE MATERNAL SERUM SCREENING TEST-ANALYSIS]

Area of Science:

• Maternal-fetal medicine
• Genetics
• Diagnostic screening

Background:

• Prenatal screening identifies pregnancies at high risk for fetal damage, justifying invasive diagnostic procedures.
• Non-invasive prenatal tests (NIPT) include first-trimester combined screening, second-trimester biochemical screening, and cell-free fetal DNA (cfDNA) screening.
• cfDNA screening has been evaluated as a primary, contingent, or sequential screening method.

Purpose of the Study:

• To compare the detection rates (DR) for Trisomy 21, 18, and 13 using cfDNA screening in various applications.
• To evaluate the percentage of invasive diagnostics and the cost-effectiveness of cfDNA testing versus first-trimester combined screening.
• To establish the most suitable algorithm for cfDNA test application.

Main Methods:

• Meta-analysis of randomized multi-center clinical studies.
• Comparison of detection rates (DR) and false-positive rates (FPR) for cfDNA screening and first-trimester combined screening.
• Analysis of invasive diagnostic rates and cost-effectiveness.

Main Results:

• cfDNA screening demonstrates higher DR (99%) and lower FPR (0.4%) for Trisomy 21 compared to first-trimester screening (DR 96%, FPR 5%).
• Despite better results, the higher cost of cfDNA testing does not justify its use as a primary screening method.
• cfDNA screening has lower DR (93-95%) for Trisomy 18 and 13, making it less suitable than combined screening for these trisomies.

Conclusions:

• The optimal application of cfDNA testing is as a contingent test for pregnancies with intermediate risk (1:10 to 1:2500) after first-trimester screening.
• This approach enhances the diagnostic rate for Down syndrome (from 90% to 98%) and significantly reduces invasive procedures (from 3% to 0.7-1%).
• Contingent cfDNA screening provides an optimal balance of diagnostic accuracy, reduced invasive testing, and cost-effectiveness.