Confirmation rate of cell free DNA screening for sex chromosomal abnormalities according to the method of confirmatory testing.

OBJECTIVE To examine the positive predictive value (PPV) of cfDNA screening for sex chromosome aneuploidies (SCA) in a large series of over 90 000 patients. METHODS Retrospective study based on samples that were sent to Cenata, a private laboratory which uses the Harmony Prenatal Test. The SCA high-risk results were stratified according to the method of diagnostic testing and according to karyotype result. RESULTS The study population consisted of 144 cases. The CfDNA test indicated monosomy X, XXX, XXY, and XYY in 62, 37, 40, and 5 cases, respectively. The overall PPV was 38.9% (30.9-47.4), 29.0% (18.2-42.9) for monosomy X, 29.7% (15.9-47.9) for 47,XXX, 57.5% (40.9-73.0) for 47,XXY, and 80.0% (28.4-99.5) for 47,XYY). A total of 112 (77.8%) women with a high-risk result for SCAs opted for prenatal karyotyping. In this group, there were significant differences in the PPV if the karyotype was assessed by amniocentesis or by CVS: 29.5% vs 50.0%. This significant difference was driven by the monosomy X result which shows a significantly higher PPV in CVS (54.6% (23.4-83.3) vs 17.1% (6.6-33.6)). For the other SCAs, the differences were not significant. CONCLUSION PPV of an abnormal cfDNA test for SCAs is low, particularly for monosomy X. The confirmation rate depends on the type of confirmatory test.