TY - JOUR
T1 - A systematic review and meta-analysis of cell-free DNA testing for detection of fetal sex chromosome aneuploidy
AU - Shear, Matthew A.
AU - Swanson, Kate
AU - Garg, Ria
AU - Jelin, Angie C.
AU - Boscardin, John
AU - Norton, Mary E.
AU - Sparks, Teresa N.
N1 - Funding Information:
Dr. Sparks is supported by grant R01HD107190 from the NIH/NICHD, as well as by grants from the Doris Duke Charitable Foundation, the Chan Zuckerberg Biohub, and the Brianna Marie Foundation in collaboration with the Fetal Health Foundation. Dr. Norton is supported by grant U01HG009599 from the NIH/NHGRI. Dr. Jelin is supported by K23DK119949 from the NIH/NIDDK. The contents of the publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2023 John Wiley & Sons Ltd.
PY - 2023/2
Y1 - 2023/2
N2 - 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.
AB - 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.
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U2 - 10.1002/pd.6298
DO - 10.1002/pd.6298
M3 - Review article
C2 - 36588186
AN - SCOPUS:85146067972
SN - 0197-3851
VL - 43
SP - 133
EP - 143
JO - Prenatal Diagnosis
JF - Prenatal Diagnosis
IS - 2
ER -