Dataset Information

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

ABSTRACT:

Background

Noninvasive prenatal testing (NIPT) allows for screening of fetal aneuploidy and copy number variants (CNVs) from cell-free DNA (cfDNA) in maternal plasma. Professional societies have not yet embraced NIPT for fetal CNVs, citing a need for additional performance data. A clinically available genome-wide cfDNA test screens for fetal aneuploidy and CNVs larger than 7 megabases (Mb).

Results

This study reviews 701 pregnancies with "high risk" indications for fetal aneuploidy which underwent both genome-wide cfDNA and prenatal microarray. For aneuploidies and CNVs considered 'in-scope' for the cfDNA test (CNVs ≥ 7 Mb and select microdeletions), sensitivity and specificity was 93.8% and 97.3% respectively, with positive and negative predictive values of 63.8% and 99.7% as compared to microarray. When including 'out-of-scope' CNVs on array as false negatives, the sensitivity of cfDNA falls to 48.3%. If only pathogenic out-of-scope CNVs are treated as false negatives, the sensitivity is 63.8%. Of the out-of-scope CNVs identified by array smaller than 7 Mb, 50% were classified as variants of uncertain significance (VUS), with an overall VUS rate in the study of 2.29%.

Conclusions

While microarray provides the most robust assessment of fetal CNVs, this study suggests that genome-wide cfDNA can reliably screen for large CNVs in a high-risk cohort. Informed consent and adequate pretest counseling are essential to ensuring patients understand the benefits and limitations of all prenatal testing and screening options.

SUBMITTER: Soster E

PROVIDER: S-EPMC10257834 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Soster Erica E Tynan John J Gibbons Clare C Meschino Wendy W Wardrop Jenna J Almasri Eyad E Schwartz Stuart S McLennan Graham G

Molecular cytogenetics 20230610 1

<h4>Background</h4>Noninvasive prenatal testing (NIPT) allows for screening of fetal aneuploidy and copy number variants (CNVs) from cell-free DNA (cfDNA) in maternal plasma. Professional societies have not yet embraced NIPT for fetal CNVs, citing a need for additional performance data. A clinically available genome-wide cfDNA test screens for fetal aneuploidy and CNVs larger than 7 megabases (Mb).<h4>Results</h4>This study reviews 701 pregnancies with "high risk" indications for fetal aneuploid ...[more]

PMID: 37301962

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Dataset Information

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

Background

Results

Conclusions

Publications

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

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