Laboratory performance of genome-wide cfDNA for copy number variants as compared to prenatal microarray

Area of Science:

• Genetics
• Molecular Biology
• Prenatal Diagnostics

Background:

• Noninvasive prenatal testing (NIPT) analyzes cell-free DNA (cfDNA) for fetal aneuploidy and copy number variants (CNVs).
• Professional societies require more data before widely adopting NIPT for fetal CNVs.
• Current genome-wide cfDNA tests detect CNVs larger than 7 megabases (Mb).

Purpose of the Study:

• To evaluate the performance of genome-wide cfDNA testing for fetal CNVs.
• To compare cfDNA test results with prenatal microarray in a high-risk cohort.

Main Methods:

• Retrospective review of 701 high-risk pregnancies.
• Comparison of genome-wide cfDNA testing with prenatal microarray analysis.
• Analysis of sensitivity, specificity, and predictive values for 'in-scope' and 'out-of-scope' CNVs.

Main Results:

• For 'in-scope' CNVs (≥7 Mb), cfDNA testing demonstrated 93.8% sensitivity and 97.3% specificity versus microarray.
• Positive predictive value was 63.8%, and negative predictive value was 99.7%.
• Sensitivity decreased to 48.3% when including all 'out-of-scope' CNVs as false negatives.

Conclusions:

• Genome-wide cfDNA testing reliably screens for large fetal CNVs in high-risk populations.
• Microarray remains the most comprehensive method for fetal CNV assessment.
• Informed consent and pretest counseling are crucial for understanding NIPT limitations and benefits.