Genome-Wide Cell-Free DNA Test for Fetal Chromosomal Abnormalities and Variants: Unrestricted Versus Restricted...

Area of Science:

• Prenatal Diagnostics
• Genetics
• Maternal-Fetal Medicine

Background:

• Genome-wide cell-free DNA (cfDNA) testing is a common prenatal screening method for chromosomal abnormalities.
• The reporting of additional findings, beyond common trisomies, in cfDNA testing has evolved.
• Understanding the impact of reporting policies on screening performance is crucial for clinical practice.

Purpose of the Study:

• To compare the screening performance of genome-wide cfDNA testing between periods with and without reporting of additional findings.
• To evaluate the effect of reporting policies on concordance rates, detection rates, and false-positive rates.
• To assess the impact on no-result rates in cfDNA screening.

Main Methods:

• Retrospective analysis of cfDNA testing data from 3981 pregnant women with singleton pregnancies (≥10 weeks gestation) from 2015-2019.
• Comparison of screening performance metrics (concordance, detection, false-positive rates) between two reporting periods.
• Calculation of no-result rates for both reporting scenarios.

Main Results:

• No-result rates were similar across both reporting periods (2.04% vs. 2.08%).
• Concordance rates for Trisomy 21 and 18 were 100%. Sex chromosome aneuploidy (SCA) and rare autosomal trisomy detection rates were 90% and 13.3% respectively.
• Restricting additional findings significantly reduced the combined false-positive rate from 0.93% to 0.17% (p=0.002).

Conclusions:

• Restricting the reporting of additional findings in genome-wide cfDNA analysis significantly reduces the false-positive rate.
• This policy change does not negatively impact the no-result rate.
• The findings support a more focused reporting strategy for cfDNA screening to improve test specificity.