The accuracy of prenatal cell-free DNA screening for sex chromosome abnormalities: A systematic review and meta-analysis.

Abstract

OBJECTIVE:

Although cell-free DNA screening for sex chromosome abnormalities is increasingly used in clinical practice, its diagnostic accuracy and clinical utility remain unclear. This systematic review and meta-analysis aimed to determine the performance of cell-free DNA in the detection of sex chromosome abnormalities.

DATA SOURCES:

Medline and PubMed, Embase, and Web of Science were searched from inception to January 2022 for articles relating to cell-free DNA screening for sex chromosome abnormalities.

STUDY ELIGIBILITY CRITERIA:

Original articles, randomized control trials, conference abstracts, cohort and case-control studies, and case series with more than 10 cases with diagnostic confirmation were considered for inclusion.

METHODS:

Quality assessment of each included publication was performed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The positive predictive value was calculated as the proportion of true positive cases among those who tested positive and underwent diagnostic testing. Sensitivity and specificity were pooled, and a summary receiver operating characteristic curve was produced using bivariate models that included studies that had diagnostic confirmation for high- and low-risk women.

RESULTS:

The search identified 7553 results. Of these, 380 proceeded to the full-text screening, of which 94 articles were included in the meta-analysis with a total of 1,531,240 women tested. All studies reported a confirmatory genetic test. The pooled positive predictive value was 49.4% (95% confidence interval, 45.8-53.1). The pooled positive predictive value was 32.0% (95% confidence interval, 27.0%-37.3%) for monosomy X, 67.6% (95% confidence interval, 62.5%-72.5%) for XXY, 57.5% (95% confidence interval, 51.7%-63.1%) for XXX, and 70.9% (95% confidence interval, 63.9%-77.1%) for XYY. The pooled sensitivity and specificity of cell-free DNA for sex chromosome abnormalities were 94.1% (95% confidence interval, 90.8%-96.3%) and 99.5% (95% confidence interval, 99.0%-99.7%), respectively, with an area under the summary receiver operating characteristic curve of 0.934 (95% confidence interval, 0.907-0.989).

CONCLUSION:

Although the sensitivity and specificity of cell-free DNA for sex chromosome abnormalities are high, the positive predictive value was approximately 50%. The positive predictive value was higher for sex chromosome abnormalities with a supernumerary Y chromosome and lower for monosomy X. Clinicians should inform couples about these findings when offering cell-free DNA for sex chromosome abnormalities.

• Authors: Sofia Bussolaro, Yvette C Raymond, Melissa L Acreman, Maurizio Guido, Fabricio Da Silva Costa, Daniel L Rolnik, Ilaria Fantasia
• Journal: American journal of obstetrics & gynecology MFM (Am J Obstet Gynecol MFM) Vol. 5 Issue 3 Pg. 100844 (03 2023) ISSN: 2589-9333 [Electronic] United States
• PMID: 36572107 (Publication Type: Meta-Analysis, Systematic Review, Journal Article, Review)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Cell-Free Nucleic Acids

Topics

• Pregnancy
• Humans
• Female
• Turner Syndrome
• Noninvasive Prenatal Testing
• Sex Chromosome Aberrations
• Sensitivity and Specificity
• Cell-Free Nucleic Acids