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.
Key words
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Article info
Publication history
Published online: December 23, 2022
Accepted:
December 20,
2022
Received in revised form:
November 26,
2022
Received:
August 16,
2022
Footnotes
The authors report no conflict of interest.
This study was registered in the International Prospective Register of Systematic Reviews on March 23, 2021, London (registration number CRD42021250849).
This study has been accepted as an electronic poster at the International Society of Ultrasound in Obstetrics and Gynecology 32nd World Conference on Ultrasound in Obstetrics and Gynecology, London, September 16–18, 2022.
This study received no financial support.
Identification
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