{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T22:05:55Z","timestamp":1751580355642,"version":"3.40.5"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010983","name":"Health Research Fund of Central Denmark Region","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010983","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF16OC0018772","NNFSA170030576"],"award-info":[{"award-number":["NNF16OC0018772","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":[[2024,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To examine the distribution of nuchal translucency thickness (NT), free <jats:italic>\u03b2<\/jats:italic>\u2010human chorionic gonadotropin (<jats:italic>\u03b2<\/jats:italic>\u2010hCG) and pregnancy\u2010associated plasma protein\u2010A (PAPP\u2010A) in pregnancies with a fetal 22q11.2 aberration. Furthermore, the performance of combined first\u2010trimester screening (cFTS) and a new risk algorithm targeting 22q11.2 deletions in detecting affected pregnancies was evaluated. Finally, prenatal malformations and pregnancy outcome were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a nationwide registry\u2010based cohort study of all pregnancies that underwent prenatal screening with a due date between January 2008 and December 2018 in Denmark. All cases with a fetal 22q11.2 deletion or duplication (hg19 chr22:18.9mio\u201025.0mio) diagnosed pre\u2010 or postnatally or following pregnancy loss or termination of pregnancy were retrieved from the Danish Cytogenetic Central Register and linked with pregnancy data from the Danish Fetal Medicine Database. Fetal and maternal characteristics, including cFTS results and pregnancy outcome, of pregnancies with any 22q11.2 deletion or duplication (LCR22\u2010A to \u2010H) and pregnancies with a classic deletion or duplication (LCR22\u2010A to \u2010D) diagnosed by chromosomal microarray were compared with those of a chromosomally normal reference group. A risk algorithm was developed for assessing patient\u2010specific risks for classic 22q11.2 deletions based on NT, PAPP\u2010A and <jats:italic>\u03b2<\/jats:italic>\u2010hCG. Detection rates and false\u2010positive rates at different risk cut\u2010offs were calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included data on 143 pregnancies with a fetal 22q11.2 aberration, of which 97 were deletions (54 classic) and 46 were duplications (32 classic). NT was significantly increased in fetuses with a classic deletion (mean, 1.89\u2009mm), those with any deletion (mean, 1.78\u2009mm) and those with any duplication (mean, 1.86\u2009mm) compared to the reference group (mean, 1.65\u2009mm). <jats:italic>\u03b2<\/jats:italic>\u2010hCG multiples of the median (MoM) was decreased in all 22q11.2 subgroups compared with the reference group (mean, 1.02) and reached significance in pregnancies with a classic deletion and those with any deletion (mean, 0.77 and 0.71, respectively). PAPP\u2010A MoM was significantly decreased in pregnancies with a classic duplication and those with any duplication (mean, 0.57 and 0.63, respectively), and was significantly increased in pregnancies with a classic deletion and those with any deletion (mean, 1.34 and 1.16, respectively), compared to reference pregnancies (mean, 1.01). The screen\u2010positive rate by cFTS was significantly increased in pregnancies with a classic deletion (13.7%), any deletion (12.5%), a classic duplication (46.9%) or any duplication (37.8%) compared to the reference group (4.5%). A risk algorithm targeting classic 22q11.2 deletions more than doubled the prenatal detection rate of classic 22q11.2 deletions, but with a substantial increase in the false\u2010positive rate. Structural malformations were detected in 41%, 35%, 17% and 25% of the pregnancies with a classic deletion, any deletion, classic duplication or any duplication, respectively. Pregnancy loss occurred in 40% of pregnancies with a classic deletion and 5% of those with a classic duplication diagnosed prenatally or following pregnancy loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The distribution of cFTS markers in pregnancies with a classic 22q11.2 duplication resembles that of the common trisomies, with decreased levels of PAPP\u2010A. However, classic 22q11.2 deletions are associated with increased levels of PAPP\u2010A, which likely limits early prenatal detection using the current cFTS risk algorithm. The scope for improving early detection of classic 22q11.2 deletions using targeted risk algorithms based on NT, PAPP\u2010A and <jats:italic>\u03b2<\/jats:italic>\u2010hCG is limited. This demonstrates the capability, but also the limitations, of cFTS markers in detecting atypical chromosomal anomalies, which is important knowledge when designing new prenatal screening programs. \u00a9 2023 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.27466","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T19:31:46Z","timestamp":1693337506000},"page":"34-43","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Decoding 22q11.2: prenatal profiling and first\u2010trimester risk assessment in Danish nationwide cohort"],"prefix":"10.1002","volume":"63","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 Obstetrics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-0393","authenticated-orcid":false,"given":"I.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital  Aarhus Denmark"},{"name":"Center for Fetal Diagnostics, Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-1991","authenticated-orcid":false,"given":"L. H.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Obstetrics and Gynecology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 Obstetrics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0216-9646","authenticated-orcid":false,"given":"E. 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