A systematic review and meta-analysis of cell-free DNA testing for detection of fetal sex chromosome aneuploidy

Matthew A. Shear, Kate Swanson, Ria Garg, Angie C. Jelin, John Boscardin, Mary E. Norton, Teresa N. Sparks

Research output: Contribution to journalReview articlepeer-review


Objectives: The aim was to determine the accuracy of cell-free DNA testing (cfDNA) for detecting sex chromosome aneuploidies (SCA) in singleton pregnancies. Methods: A systematic review and meta-analysis was performed to assess cfDNA accuracy for prenatal detection of 45,X, 47,XXY, 47,XXX and 47,XYY. Inclusion was restricted to studies published between January 2010 and December 2021 reporting both cfDNA and confirmatory diagnostic test results. Results: For 45,X, the sensitivity was 98.8% (95%CI 94.6%–100%), specificity 99.4% (95%CI 98.7%–99.9%) and positive predictive value (PPV) 14.5% (95%CI 7.0%–43.8%). For 47,XXY, the sensitivity was 100% (95%CI 99.6%–100%), specificity 100% (95%CI 99.9%–100%) and PPV 97.7% (95%CI 78.6%–100%). For 47,XXX, the sensitivity was 100% (95%CI 96.9%–100%), specificity 99.9% (95%CI 99.7%–100%) and PPV 61.6% (95%CI 37.6%–95.4%). For 47,XYY, the sensitivity was 100% (95%CI 91.3%–100%), specificity 100% (95% CI 100%–100%) and PPV 100% (95%CI 76.5%–100%). All four SCAs had estimated negative predictive values (NPV) exceeding 99.99%, though false negatives were reported. Conclusions: This analysis suggests that cfDNA is a reliable screening test for SCA, though both false negatives and false positives were reported. These estimates of test performance are derived from pregnancies at high pretest risk for aneuploidy, limiting the generalisability to average risk pregnancies.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalPrenatal Diagnosis
Issue number2
StatePublished - Feb 2023

ASJC Scopus subject areas

  • Genetics(clinical)
  • Obstetrics and Gynecology


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