The predictive value of prenatal cell-free DNA testing for rare autosomal trisomies: a systematic review and meta-analysis

Melissa L. Acreman, Sofia Bussolaro, Yvette C. Raymond, Ilaria Fantasia, Daniel L. Rolnik, Fabricio Da Silva Costa

Research output: Contribution to journalReview ArticleResearchpeer-review

9 Citations (Scopus)


Objective: The diagnostic accuracy of cell-free fetal DNA in screening for rare autosomal trisomies is uncertain. We conducted a systematic review and meta-analysis aiming to determine the predictive value of cell-free DNA in screening for rare autosomal trisomies. Data Sources: PubMed, Embase, and Web of Science were searched from inception to January 2022. Study Eligibility Criteria: All studies that reported on the diagnostic accuracy of cell-free DNA in the detection of rare autosomal trisomies were included. Case series were included if they contained at least 10 cases with diagnostic test results or postnatal genetic testing. Methods: Study appraisal was completed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed using random-effects meta-analysis of double-arcsine transformed proportions of confirmed results in the fetus out of the positive tests to obtain a pooled estimate of the positive predictive value. Results: The search identified 7553 studies, of which 1852 were duplicates. After screening 5701 titles and abstracts, 380 studies proceeded to the full-text screen; 206 articles were retrieved for data extraction, of which another 175 articles were excluded. A total of 31 studies, with a total of 1703 women were included for analysis. The pooled positive predictive value of cell-free DNA for the diagnosis of rare autosomal trisomies was 11.46% (95% confidence interval, 7.80–15.65). Statistical heterogeneity was high (I2=82%). Sensitivity analysis restricted to 5 studies at low risk of bias demonstrated a pooled positive predictive value of 9.13% (95% confidence interval, 2.49–18.76). There were insufficient data to provide accurate ascertainment of sensitivity and specificity because most studies only offered confirmatory tests to women with high-risk results. Conclusion: The positive predictive value of cell-free DNA in diagnosing rare autosomal trisomies is approximately 11%. Clinicians should provide this information when offering cell-free DNA for screening of conditions outside of common autosomal trisomies.

Original languageEnglish
Pages (from-to)292-305.e6
Number of pages20
JournalAmerican Journal of Obstetrics and Gynecology
Issue number3
Publication statusPublished - Mar 2023


  • cell-free DNA
  • diagnostic accuracy
  • expanded genome testing
  • noninvasive prenatal testing
  • predictive value
  • rare autosomal trisomy

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