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

Alessandra Familiari, Simona Boito, Georgios Rembouskos, Benedetta Ischia, Veronica Accurti, Isabella Fabietti, Paolo Volpe, Nicola Persico

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)1324-1331
JournalPrenatal Diagnosis
Volume41
Issue number10
DOIs
Publication statusPublished - 2021

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

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'Cell-free DNA analysis of maternal blood in prenatal screening for chromosomal microdeletions and microduplications: a systematic review'. Together they form a unique fingerprint.

Cite this