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

作     者：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 

作者机构：Department of Gynecology & Obstetrics Southwest Hospital the Third Military Medical University BGI-Shenzhen China National GeneBankBGI-Shenzhen Birth Defect Screening Project LabBGI-Shenzhen Clinical laboratories of BGI HealthBGI-Shenzhen James D.Watson Institute of Genome Sciences Laboratory of Genomics and Molecular Biomedicine Department of Biology University of Copenhagen 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2019年第62卷第2期

页      面：215-224页

核心收录：

学科分类：0710[理学-生物学] 100208[医学-临床检验诊断学] 0830[工学-环境科学与工程（可授工学、理学、农学学位）] 1002[医学-临床医学] 100211[医学-妇产科学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (81501264) Shenzhen Birth Defect Screening Project Lab (JZF No. 750) Shenzhen Municipal Government of China (JCYJ20150403101146312, JCYJ20170412153136375) Guangzhou Science and Technology Program (201604020078) 

主　　题：cell-free DNA genome-wide chromosomal abnormalities sensitivity specificity PPV 

摘      要：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%(P0.001) 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 ***-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.