SCIENCE CHINA Life Sciences, Volume 62 , Issue 2 : 215-224(2019) https://doi.org/10.1007/s11427-017-9344-7

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

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  • ReceivedMay 11, 2018
  • AcceptedJun 21, 2018
  • PublishedAug 2, 2018


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.

Funded by

the National Natural Science Foundation of China(81501264)

Shenzhen Birth Defect Screening Project Lab(JZF,No.,[2016],750)

Shenzhen Municipal Government of China(JCYJ20150403101146312)


The authors would like to thank all the pregnant women who participated in this work and their family. Thank also goes to all laboratory personnel and medical staffs who could not be listed as authors. The authors also would like to thank Dr. Dev Sooranna, Imperial College London, and Prof. Lars Bolund, Aarhus University for editing the manuscript. This work was supported by the National Natural Science Foundation of China (81501264), Shenzhen Birth Defect Screening Project Lab (JZF No. [2016] 750), Shenzhen Municipal Government of China (JCYJ20150403101146312, JCYJ20170412153136375) and Guangzhou Science and Technology Program (201604020078).

Interest statement

The author(s) declare that they have no conflict of interest.



Figure S1 Schematic illustration of the reporting workflow and two-stage genetic counseling in this study.

Table S1 Summaries of atypical and extra abnormalities identified by genome-wide cfDNA testing, and their clinical information and confirmation results

Table S2 Comparison of FPRs and PPVs for detecting additional abnormalities and different cfDNA reporting strategies

Table S3 Comparison of biochemical screening and cfDNA testing of chromosomal abnormalities in a subgroup of pregnant women with both test results shown

The supporting information is available online at http://life.scichina.com and https://link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Figure 1

    Enrollment and genome-wide cfDNA testing outcomes of 15,626 study participants.

  • Figure 2

    Clinical utility of cfDNA testing was affected by different reporting ranges.

  • Figure 3

    Comparison of biochemical screening and cfDNA testing in a selected subgroup of 7,548 pregnancies with both testing results shown.

  • Table 1   Demographic characteristics of pregnancy women undergoing genome-wide cfDNA testing service


    Total population (n=15,612)

    Maternal age (years)


    18–24 years

    2,145 (13.74%)

    25–29 years

    5,648 (36.18%)

    30–34 years

    4,067 (26.05%)

    35–40 years

    3,604 (23.08%)

    >40 years

    148 (0.95%)

    Gestational age (weeks)


    1st trimester (10–13 weeks)

    848 (5.43%)

    2nd trimester (14–27 weeks)

    14,270 (91.40%)

    3rd trimester (³28 weeks)

    494 (3.16%)

    Previous ultrasound screening tests


    Abnormal USG

    1,472 (9.43%)

    Normal USG

    14,123 (90.46%)

    No test

    17 (0.11%)

    Previous biochemical tests


    High risk

    5,548 (35.54%)

    Low risk

    1,890 (12.11%)

    No test

    8,174 (52.36%)

  • Table 2   Performance of genome-wide cfDNA testing in detecting T21, T18, T13 in pregnancies with outcome data


    TP (n)

    FP (n)

    TN* (n)

    FN (n)

    Sensitivity (% (95% CI))

    Specificity (% (95% CI))

    PPV (% (95% CI))






    100.00 (92.00–100.00)

    99.93 (99.86–99.96)

    84.85 (73.06–91.99)






    100.00 (62.88–100.00)

    99.99 (99.94–100.00)

    81.82 (47.76–96.79)






    100.00 (31.00–100.00)

    99.96 (99.90–99.98)

    33.33 (9.04–69.08)






    100.00 (93.34–100.00)

    99.87 (99.79–99.92)

    79.07 (68.69–86.80)

    T21/T18/T13 lower boundary





    100.00 (93.34–100.00)

    99.76 (99.67–99.84)

    68.00 (57.82–76.78)

    T21/T18/T13 upper boundary





    100.00 (94.42–100.00)

    99.87 (99.79–99.92)

    82.00 (72.78–88.70)

    TN, true negative; *, True negative was calculated as the sum of karyotyping confirmed normal and normal live birth and birth defects not caused by T21/T18/T13.