{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:54:48Z","timestamp":1792421688831,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF16OC0018772"],"award-info":[{"award-number":["NNF16OC0018772"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNFSA170030576"],"award-info":[{"award-number":["NNFSA170030576"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp;amp; Gyne"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Our aim was to examine the prenatal profiles of pregnancies affected by an atypical chromosomal aberration, focusing on pathogenic copy\u2010number variants (pCNVs). We also wanted to quantify the performance of combined first\u2010trimester screening (cFTS) and a second\u2010trimester anomaly scan in detecting these aberrations. Finally, we aimed to estimate the consequences of a policy of using non\u2010invasive prenatal testing (NIPT) rather than invasive testing with chromosomal microarray analysis (CMA) to manage pregnancies identified as high risk by cFTS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a retrospective review of the Danish Fetal Medicine Database of all pregnant women who underwent cFTS and a risk assessment for trisomy 21 between 1 January 2008 and 31 December 2018. Chromosomal aberrations diagnosed prenatally, postnatally or from fetal tissue following pregnancy loss or termination of pregnancy were identified. Chromosomal aberrations were grouped into one of six categories: triploidy; common trisomy (13, 18 or 21); monosomy X; other sex\u2010chromosome aberration (SCA); pCNV; and rare autosomal trisomy (RAT) or mosaicism. The prevalence of each aberration category was stratified by the individual cFTS markers and trisomy 21 risk estimate, and the size of each pCNV diagnosed by CMA was calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We retrieved data on 565\u2009708 pregnancies, of which 3982 (0.70%) were diagnosed with a fetal chromosomal aberration. cFTS identified 87% of the common trisomies, but it also performed well in identifying triploidies (86%), monosomy X (92%), atypical SCAs (58%) and RATs or mosaicisms (70%). pCNVs comprised 27% (<jats:italic>n<\/jats:italic>\u2009=\u20091091) of the chromosomal aberrations diagnosed overall, and the prevalence increased during the study period, as prenatal CMA was increasingly being performed. In pregnancies with a maternal age &lt;\u200930\u2009years, nuchal translucency (NT) thickness \u2264\u200995<jats:sup>th<\/jats:sup> centile, pregnancy\u2010associated plasma protein\u2010A (PAPP\u2010A) \u2265\u20091 multiple of the median, or trisomy 21 risk of \u2264\u20091 in 1000, the prevalence of pCNVs exceeded significantly  the prevalence of trisomies 21, 18 and 13. Pregnancies affected by a pCNV had significantly increased NT and decreased levels of the maternal biomarkers PAPP\u2010A and \u03b2\u2010human chorionic gonadotropin compared with unaffected pregnancies. However, only 23% of these pregnancies screened positive on cFTS and 51% of pCNVs were not detected until after birth. Among high\u2010risk pregnancies, pCNVs comprised 14% of diagnosed aberrations, and when other atypical aberrations were considered, conventional NIPT (screening for trisomies 21, 18 and 13 and monosomy X) would miss 27% of all pathogenic aberrations diagnosed from invasive testing following a high\u2010risk cFTS result. Thus, 1 in 26 pregnancies at high risk following cFTS would be affected by a chromosomal aberration despite a normal result from conventional NIPT. In a contingent screening model using NIPT for the \u2018intermediate\u2019\u2010risk group (trisomy 21 risk of 1 in 100\u2013299), 50% of the aberrations would be missed. In our cohort, 79% of the pCNVs diagnosed were &lt;\u20095Mb and therefore not detectable using current forms of \u2018genome\u2010wide\u2019 NIPT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>As a by\u2010product of screening for trisomies 21, 18 and 13, most triploidies and the majority of atypical SCAs, RATs and mosaicisms are detected before birth. However, only 23% of pCNVs are associated with a high\u2010risk result according to cFTS and only half are diagnosed before birth. Replacing invasive testing with NIPT for high\u2010risk pregnancies would substantially decrease the first\u2010trimester detection of pathogenic chromosomal anomalies. \u00a9 2024 The Authors. <jats:italic>Ultrasound in Obstetrics &amp; Gynecology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.27667","type":"journal-article","created":{"date-parts":[[2024,4,20]],"date-time":"2024-04-20T18:13:00Z","timestamp":1713636780000},"page":"470-479","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Combined first\u2010trimester screening and invasive diagnostics for atypical chromosomal aberrations: Danish nationwide study of prenatal profiles and detection compared with <scp>NIPT<\/scp>"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1331-3503","authenticated-orcid":false,"given":"K.","family":"Gadsb\u00f8ll","sequence":"first","affiliation":[{"name":"Center for Fetal Medicine, Pregnancy and Ultrasound, Department of Gynecology, Fertility, and Obstetrics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"},{"name":"Faculty of Health and Medical Sciences, Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-0393","authenticated-orcid":false,"given":"I.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Center for Fetal Diagnostics, Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Obstetrics and Gynecology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-4738","authenticated-orcid":false,"given":"S. E.","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Center for Fetal Medicine, Pregnancy and Ultrasound, Department of Gynecology, Fertility, and Obstetrics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"},{"name":"Faculty of Health and Medical Sciences, Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-1991","authenticated-orcid":false,"given":"L. H.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-1289","authenticated-orcid":false,"given":"J.","family":"Hyett","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Western Sydney University  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8517-4082","authenticated-orcid":false,"given":"O. 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