Validity and Utility of Non-Invasive Prenatal Testing for Copy Number Variations and Microdeletions: A Systematic Review

Valid data on prenatal cell-free DNA-based screening tests for copy number variations and microdeletions are still insufficient. We aimed to compare different methodological approaches concerning the achieved diagnostic accuracy measurements and positive predictive values. For this systematic review, we searched the Scopus and PubMed databases and backward citations for studies published between 2013 and 4 February 2022 and included articles reporting the analytical and clinical performance of cfDNA screening tests for CNVs and microdeletions. Of the 1810 articles identified, 32 met the criteria. The reported sensitivity of the applied tests ranged from 20% to 100%, the specificity from 81.62% to 100%, and the PPV from 3% to 100% for cases with diagnostic or clinical follow-up information. No confirmatory analysis was available in the majority of cases with negative screening results, and, therefore, the NPVs could not be determined. NIPT for CNVs and microdeletions should be used with caution and any developments regarding new technologies should undergo strict evaluation before their implementation into clinical practice. Indications for testing should be in correlation with the application guidelines issued by international organizations in the field of prenatal diagnostics.

Automated summary

Sufficient data on prenatal cell-free DNA-based screening tests for copy number variations and microdeletions are still lacking. Different methodological approaches show variations in diagnostic accuracy measurements and positive predictive values. Caution should be exercised in using NIPT for CNVs and microdeletions, and any new technologies should undergo strict evaluation before implementation. Testing indications should be in line with international guidelines in the field of prenatal diagnostics.