Genome-wide detection of additional fetal chromosomal abnormalities by cell-free DNA testing of 15,626 consecutive pregnant women

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Hong Yao
  • Ya Gao
  • Jia Zhao
  • Rong Zhang
  • Huixin Xu
  • Huamei Hu
  • Yanmei Luo
  • Yuying Yuan
  • Meili Fu
  • Hongyun Zhang
  • Hui Jiang
  • Wei Wang
  • Huanming Yang
  • Jian Wang
  • Zhiqing Liang
  • Fang Chen

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.

OriginalsprogEngelsk
TidsskriftScience China Life Sciences
Vol/bind62
Udgave nummer2
Sider (fra-til)215-224
ISSN1674-7305
DOI
StatusUdgivet - 2019

ID: 212852386