{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:54:38Z","timestamp":1791176078614,"version":"4.1.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate the clinical performance of expanded non-invasive prenatal testing (NIPT-plus) and compare its effectiveness in screening for chromosomal aneuploidies with that of NIPT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Screening results, confirmatory invasive testing results, and follow-up data from pregnant women who underwent either NIPT (6792 cases) or NIPT-Plus (5237 cases) testing at Luohe Central Hospital, China, from January 2019 to June 2023 were collected. The positive predictive value (PPV), sensitivity, specificity, and other indicators for different types of chromosomal abnormalities in NIPT\/NIPT-plus screening were calculated. The willingness of pregnant women with various types of abnormalities to undergo confirmatory invasive testing and the proportion of pregnancy terminations were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The average number of unique reads in NIPT-plus samples was 5.26 times greater than that in NIPT samples. There was no significant difference in the PPV or positive rate between NIPT-plus and NIPT for screening chromosomal aneuploidies. Compared with the low-risk group, the high-risk group had a greater PPV; however, in the NIPT-plus group, there was no significant disparity in the PPV between the low-risk and high-risk groups. Compared with rare autosomal aneuploidies (RAAs), pregnant women had a higher rate of confirmatory invasive testing for common trisomies, sex chromosomal abnormalities (SCAs), and copy number variations (CNVs). However, the rate of pregnancy termination for common trisomies, RAAs, and CNVs was higher than that for SCAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By enhancing sequencing data, NIPT-plus can effectively screen for CNVs as well as chromosomal aneuploidies. However, NIPT-plus does not have an advantage over standard NIPT in screening for chromosomal aneuploidies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0312184","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T13:32:21Z","timestamp":1737725541000},"page":"e0312184","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expanded non-invasive prenatal testing offers better detection of fetal copy number variations but not chromosomal 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Qu","year":"2022","journal-title":"International Journal of Environmental Research and Public Health"},{"issue":"4","key":"pone.0312184.ref002","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s12519-011-0326-0","article-title":"Birth defects surveillance in China.","volume":"7","author":"L Dai","year":"2011","journal-title":"World journal of pediatrics: WJP."},{"issue":"1","key":"pone.0312184.ref003","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13039-021-00550-5","article-title":"Clinical application of noninvasive prenatal testing in the detection of fetal chromosomal diseases.","volume":"14","author":"Y Pang","year":"2021","journal-title":"Molecular Cytogenetics"},{"issue":"2","key":"pone.0312184.ref004","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ogc.2017.02.004","article-title":"Prenatal Diagnosis: Screening and Diagnostic Tools.","volume":"44","author":"LM Carlson","year":"2017","journal-title":"Obstetrics and gynecology 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Pan","year":"2023","journal-title":"Medicine"},{"key":"pone.0312184.ref011","author":"N Eltabbakh","year":"2024","journal-title":"Advancements of non-invasive prenatal testing: the role of obstetricians"},{"issue":"30","key":"pone.0312184.ref012","doi-asserted-by":"crossref","first-page":"E1156","DOI":"10.1503\/cmaj.202456","article-title":"Performance of a universal prenatal screening program incorporating cell-free fetal DNA analysis in Ontario, Canada.","volume":"193","author":"SD Dougan","year":"2021","journal-title":"CMAJ"},{"key":"pone.0312184.ref013","doi-asserted-by":"crossref","first-page":"864076","DOI":"10.3389\/fgene.2022.864076","article-title":"Non-invasive prenatal testing for the detection of trisomy 13, 18, and 21 and sex chromosome aneuploidies in 68,763 cases.","volume":"13","author":"Y Zhang","year":"2022","journal-title":"Front Genet."},{"issue":"10","key":"pone.0312184.ref014","doi-asserted-by":"crossref","first-page":"e24660","DOI":"10.1002\/jcla.24660","article-title":"The accuracy and feasibility of noninvasive prenatal testing in a consecutive series of 20,626 pregnancies with different clinical characteristics","volume":"36","author":"Y Zheng","year":"2022","journal-title":"Journal of clinical laboratory analysis"},{"issue":"7","key":"pone.0312184.ref015","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.gim.2022.03.019","article-title":"Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies.","volume":"24","author":"NC Rose","year":"2022","journal-title":"Genetics in medicine: official journal of the American College of Medical Genetics."},{"issue":"2","key":"pone.0312184.ref016","doi-asserted-by":"crossref","first-page":"100336","DOI":"10.1016\/j.gim.2022.11.004","article-title":"Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG).","volume":"25","author":"JS Dungan","year":"2023","journal-title":"Genetics in medicine: official journal of the American College of Medical Genetics."},{"issue":"8","key":"pone.0312184.ref017","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/pd.6312","article-title":"Non-invasive prenatal testing for the detection of trisomies 21, 18, and 13 in pregnant women with various clinical indications: A multicenter observational study of 1,854,148 women in China.","volume":"43","author":"L Xiang","year":"2023","journal-title":"Prenatal diagnosis"},{"issue":"2","key":"pone.0312184.ref018","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/uog.20416","article-title":"Non\u2010invasive cell\u2010free fetal DNA testing for aneuploidy: multicenter study of 31 515 singleton pregnancies in 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mixed risk factors","volume":"32","author":"S Dan","year":"2012","journal-title":"Prenatal diagnosis"},{"issue":"9","key":"pone.0312184.ref027","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1038\/s41436-019-0467-4","article-title":"Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes.","volume":"21","author":"D Liang","year":"2019","journal-title":"Genetics in medicine: official journal of the American College of Medical Genetics."},{"key":"pone.0312184.ref028","volume-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen).","author":"ER Riggs","year":"2020"},{"issue":"1","key":"pone.0312184.ref029","doi-asserted-by":"crossref","first-page":"19750","DOI":"10.1038\/s41598-022-24337-9","article-title":"Efficiency of expanded noninvasive prenatal testing in the detection of fetal subchromosomal microdeletion and microduplication in a cohort of 31,256 single pregnancies.","volume":"12","author":"H Xue","year":"2022","journal-title":"Sci Rep."},{"key":"pone.0312184.ref030","first-page":"354","article-title":"Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down\u2019s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units","author":"LS Chitty","year":"2016","journal-title":"BMJ (Clinical research ed)."},{"issue":"1","key":"pone.0312184.ref031","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12920-021-00955-6","article-title":"Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases","volume":"14","author":"Y Ge","year":"2021","journal-title":"BMC Med 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Wang","year":"2021","journal-title":"BMC Med Genomics"},{"issue":"16","key":"pone.0312184.ref035","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1080\/14767058.2021.1907333","article-title":"The application of expanded noninvasive prenatal screening for genome-wide chromosomal abnormalities and genetic counseling","volume":"34","author":"Y Chen","year":"2021","journal-title":"The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet."},{"key":"pone.0312184.ref036","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2147\/IJWH.S455778","article-title":"Performance Evaluation of Noninvasive Prenatal Testing in Screening Chromosome Disorders: A Single-Center Observational Study of 15,304 Consecutive Cases in China.","author":"Q Ye","year":"2024","journal-title":"International Journal of Women\u2019s Health"},{"key":"pone.0312184.ref037","doi-asserted-by":"crossref","first-page":"672211","DOI":"10.3389\/fmed.2021.672211","article-title":"Clinical Application of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies in Central China.","volume":"8","author":"G Zhao","year":"2021","journal-title":"Frontiers in medicine."},{"issue":"6","key":"pone.0312184.ref038","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s40291-023-00674-x","article-title":"Clinical Potential of Expanded Noninvasive Prenatal Testing for Detection of Aneuploidies and Microdeletion\/Microduplication Syndromes","volume":"27","author":"L. Chunyan","year":"2023","journal-title":"Molecular diagnosis & therapy"},{"issue":"1","key":"pone.0312184.ref039","doi-asserted-by":"crossref","first-page":"7767","DOI":"10.1038\/s41598-019-44018-4","article-title":"Clinical application of noninvasive prenatal screening for sex chromosome aneuploidies in 50,301 pregnancies: initial experience in a Chinese hospital.","volume":"9","author":"C Deng","year":"2019","journal-title":"Sci Rep."},{"issue":"5","key":"pone.0312184.ref040","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.tjog.2014.10.009","article-title":"Maternal mosaicism of sex chromosome causes discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing","volume":"54","author":"L Wang","year":"2015","journal-title":"Taiwanese journal of obstetrics & gynecology"},{"issue":"1","key":"pone.0312184.ref041","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13039-022-00616-y","article-title":"Prenatal diagnosis of trisomy 8 mosaicism, initially identified by cffDNA screening.","volume":"15","author":"J Hu","year":"2022","journal-title":"Molecular cytogenetics."},{"issue":"8","key":"pone.0312184.ref042","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/gim.2014.3","article-title":"Fetoplacental mosaicism: potential implications for false-positive and false-negative noninvasive prenatal screening results.","volume":"16","author":"FR Grati","year":"2014","journal-title":"Genetics in medicine: official journal of the American College of Medical Genetics."},{"issue":"1","key":"pone.0312184.ref043","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13039-024-00677-1","article-title":"Clinical outcomes of screen-positive genome-wide cfDNA cases for trisomy 20: results from the global expanded NIPT Consortium.","volume":"17","author":"E Soster","year":"2024","journal-title":"Molecular cytogenetics."},{"issue":"4","key":"pone.0312184.ref044","doi-asserted-by":"crossref","first-page":"e48","DOI":"10.1097\/AOG.0000000000004084","article-title":"Screening for fetal chromosomal abnormalities: ACOG practice bulletin, number 226.","volume":"136","author":"NC Rose","year":"2020","journal-title":"Gynecologists.Obstetrics & Gynecology."},{"issue":"14","key":"pone.0312184.ref045","doi-asserted-by":"crossref","first-page":"317","DOI":"10.21037\/atm.2019.06.57","article-title":"Clinical features and pregnancy outcomes of women with abnormal cell-free fetal DNA test results","volume":"7","author":"Q Zhou","year":"2019","journal-title":"Ann Transl Med"},{"issue":"4","key":"pone.0312184.ref046","article-title":"Performance of Cell-Free DNA Screening for Fetal Common Aneuploidies and Sex Chromosomal Abnormalities: A Prospective Study from a Less Developed Autonomous Region in Mainland China.","volume":"12","author":"Y Lai","year":"2021","journal-title":"Genes"},{"issue":"1","key":"pone.0312184.ref047","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13023-018-0976-2","article-title":"Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47,XXX and 47,XYY syndrome: a nationwide cohort study.","volume":"14","author":"A Berglund","year":"2019","journal-title":"Orphanet journal of rare diseases"},{"key":"pone.0312184.ref048","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/B978-0-444-63233-3.00024-5","article-title":"Sex chromosome aneuploidies","volume":"147","author":"D Skuse","year":"2018","journal-title":"Handbook of clinical neurology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T13:32:37Z","timestamp":1737725557000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0312184"}},"subtitle":[],"editor":[{"given":"Giuseppe","family":"Novelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,24]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0312184","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,24]]}}}