Genome-wide detection of additional fetal chromosomal abnormalities by cell-free DNA testing of 15,626 consecutive pregnant women.
2019
Cell-free DNA (cfDNA) testing for common fetal trisomies (T21,
T18, T13) is highly effective. However, the usefulness of cfDNA testing
in detecting other chromosomal abnormalities is unclear. We evaluated
the performance of cfDNA testing for genome-wide abnormalities, and
analyzed the incremental yield by reporting extra abnormalities. We
performed genome-wide cfDNA testing in 15,626 consecutive pregnancies
prospectively enrolled in this study. cfDNA testing results were reported
and counseling was given depending on the presence of extra chromosomal
abnormalities. cfDNA testing identified 190 cases (1.2%) of chromosomal
abnormalities including 100 common trisomies and 90 additional abnormalities.
By expanding the cfDNA reporting range to genome-wide abnormalities,
the false positive rate increased to 0.39% ( P <0.001)
and positive predictive value (PPV) was reduced to 65.58% ( P =0.42). However, the detection yield increased from 0.44%
to 0.65% ( P =0.014), and cfDNA testing detected 38.61%
(39/101) additional abnormalities with no ultrasound and biochemical
screening findings. cfDNA testing outperformed biochemical screening
by showing 60 times higher true positive rate and fewer false negative
results. Genome-wide cfDNA testing significantly increased the diagnostic
yield by detecting extra abnormalities, especially those without diagnostic
indications. Genome-wide cfDNA testing has fewer false positive and
false negative results compared with biochemical screening.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
37
References
7
Citations
NaN
KQI