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. 2021 Sep;41(10):1324-1331.
doi: 10.1002/pd.5928. Epub 2021 Mar 12.

Cell-free DNA analysis of maternal blood in prenatal screening for chromosomal microdeletions and microduplications: a systematic review

Alessandra Familiari  1 , Simona Boito  2 , Georgios Rembouskos  3 , Benedetta Ischia  2 , Veronica Accurti  2 , Isabella Fabietti  2 , Paolo Volpe  3 , Nicola Persico  2   4
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Cell-free DNA analysis of maternal blood in prenatal screening for chromosomal microdeletions and microduplications: a systematic review

Alessandra Familiari et al. Prenat Diagn. 2021 Sep.

Abstract

Background and aim of the study: Scientific Societies do not recommend the use of cell-free DNA (cfDNA) testing as a first-tier screening for microdeletion and microduplication syndromes (MMs). The aim of this study was to review the current available literature on the performance of cell-free DNA as a screening for MMs.

Methods: Medline, Embase and the Cochrane Library were searched electronically from 2000 to January 2020 and articles reporting the diagnostic performance of cfDNA screening for MMs in large (>5000 cases) series were included. Between-study heterogeneity and random effect model for screen positive rate (SPR), false positive rate (FPR) and positive predictive value (PPV) were calculated.

Results: We identified 42 papers, seven included, for a total of 474,189 pregnancies and 210 cases of MMs. Diagnostic verification of positive cases was available overall in 486 (71.68 %) of 678 cases. The weighted pooled SPR, FPR and PPV were 0.19% (95% CI = 0.09-0.33), 0.07 (95% CI = 0.02-0.15) and 44.1 (95% CI = 31.49-63.07). In conclusion, the pooled PPV of cfDNA testing in screening for MMs was about 40%, ranging from 29% to 91%, for an overall FPR <0.1%.

Conclusions: No confirmatory analysis was available in cases that did not undergo invasive testing, which were the vast majority of cases with a negative test, and therefore, the DR and the negative predictive value cannot be determined.

Keywords: cell-free DNA; fetal cells; fetal diseases; fetal genetic analysis; fetal medicine and diagnostic procedures; genetic counseling; noninvasive prenatal testing; nucleic acids & proteins; whole genome sequencing.

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References

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