[Application analysis of noninvasive prenatal testing for fetal chromosome copy number variations in Chinese...

Objective: To investigate the general situation, detection range, testing reagents, and clinical performance of non-invasive prenatal testing (NIPT) for fetal chromosomal copy number variations (CNVs) in Chinese laboratories. Methods: The National Center for Clinical Laboratories of the National Health Commission designed a questionnaire for the detection of CNVs by NIPT, which included the investigation of whether the laboratory has carried out NIPT to detect CNVs and its testing scope, reagents/platforms, intended uses, screening populations and clinical performance. The questionnaires were distributed to 355 laboratories in 31 provinces, autonomous regions, and municipalities across the country on October, 2020. Further, the feedbacks were statistical analyzed. Results: Two hundred and twenty-eight laboratories had performed NIPT to detect CNVs, including 116 types of CNVs, and more than 95% of laboratories chose to detect the CNVs of 5p15 deletion, 22q11.2 deletion, 1p36 deletion, and 15q11.2 deletion. All testing reagents used were laboratory-developed tests and were based on massive parallel sequencing, the minimum amount of sequencing data was 3-15 M reads, the detection limit of fetal fraction was 3%-5%, and the minimum size of variants that can be detected was 1-5 Mb. The proportion of laboratories that apply CNVs testing for daily project, voluntary requirements of patients, and scientific research were 58.8% (134/228), 57.5% (131/228), and 20.6% (47/228), respectively. One hundred and thirty-four laboratories were fully or partially aware of the clinical performance of NIPT to detect microdeletion/microduplication syndromes, and the laboratories' declared sensitivity of NIPT for Cri du Chat syndrome, 22q11.2 deletion syndrome, 1p36 deletion syndrome, and Angelman syndrome were 50.0%-100%, 60.0%-100%, 50.0%-100%, and 33.3%-100%, and the positive predictive values were 9.0%-50.0%, 18.0%-100%, 20.0%-30.0%, and 20.0%. Conclusion: The detection of CNVs by NIPT in Chinese laboratories need to be standardized. Laboratories should detect CNVs with clear clinical significance in accordance with the guidelines, conduct performance validation of the reagents, then perform NIPT test and provide adequate interpretation after mastering the clinical performance sufficiently.