TY - JOUR
T1 - Cell-free DNA analysis of maternal blood in prenatal screening for chromosomal microdeletions and microduplications
T2 - a systematic review
AU - Familiari, Alessandra
AU - Boito, Simona
AU - Rembouskos, Georgios
AU - Ischia, Benedetta
AU - Accurti, Veronica
AU - Fabietti, Isabella
AU - Volpe, Paolo
AU - Persico, Nicola
N1 - Publisher Copyright:
© 2021 John Wiley & Sons Ltd.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - cell-free DNA
KW - fetal cells
KW - fetal diseases
KW - fetal genetic analysis
KW - fetal medicine and diagnostic procedures
KW - genetic counseling
KW - noninvasive prenatal testing
KW - nucleic acids & proteins
KW - whole genome sequencing
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U2 - 10.1002/pd.5928
DO - 10.1002/pd.5928
M3 - Review article
AN - SCOPUS:85102349001
VL - 41
SP - 1324
EP - 1331
JO - Prenatal Diagnosis
JF - Prenatal Diagnosis
SN - 0197-3851
IS - 10
ER -