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However, the ability of NIPT-Plus to detect copy number variation (CNV) is debatable. Accordingly, we assessed the efficiency of NIPT-Plus to detect clinically significant fetal CNV. We performed a prospective analysis of 31,260 singleton pregnancies, included from June 2017 to December 2020. Cell-free fetal DNA was directly sequenced using the semiconductor sequencing platform for women with high-risk CNV with clinically significant results. Fetal karyotyping and chromosomal microarray analysis (or next-generation sequencing) are recommended for invasive diagnostic procedures. Women at low risk with no other abnormal results continued their pregnancies. We analyzed the expanded NIPT results, diagnostic test results, and follow-up information to evaluate its performance in detecting fetal CNV. Of the 31,260 pregnant women who received NIPT-Plus, 31,256 cases were tested successfully, a high risk of clinically significant CNV was detected in 221 cases (0.71%); 18 women refused further diagnosis; 203 women underwent invasive prenatal diagnosis; and 78 true positive cases and 125 false positive cases, with an overall positive predictive value (PPV) of 38.42% and a false positive rate of 0.40%. For known microdeletion\/microduplication syndromes (n\u2009=\u200927), the PPVs were 75% DiGeorge syndrome (DGS), 80% 22q11.22 microduplication, 50% Prader\u2013Willi syndrome, and 50% cri-du-chat. For the remaining clinically significant fetal CNVs (n\u2009=\u2009175), the combined PPVs were 46.5% (CNVs\u2009&gt;\u200910\u00a0Mb) and 28.57% (CNVs\u2009\u2264\u200910\u00a0Mb). NIPT-Plus screening for CNV has certain clinical value. NIPT-Plus yielded relatively high PPVs for 22q11.2 microduplication syndrome and DGS, and low to moderate PPVs for other CNVs.<\/jats:p>","DOI":"10.1038\/s41598-022-24337-9","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T05:04:14Z","timestamp":1668661454000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Efficiency of expanded noninvasive prenatal testing in the detection of fetal subchromosomal microdeletion and microduplication in a cohort of 31,256 single pregnancies"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-7978","authenticated-orcid":false,"given":"Huili","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aili","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangpu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"24337_CR1","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1002\/bdra.23385","volume":"103","author":"DM Webber","year":"2015","unstructured":"Webber, D. 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