{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:55:57Z","timestamp":1786978557025,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100016337","name":"Department for the Economy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate: (i) the performance of the National Health Service (NHS)\u00a0phenotypic eligibility criteria for prenatal exome sequencing (pES); (ii) the diagnostic yield of individual NHS criteria; (iii) the diagnostic yield when one or multiple NHS criteria were met; and (iv) the performance of the NHS criteria compared with that of phenotypic eligibility criteria used in other countries\/regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An online survey was circulated to healthcare professionals in 120 countries to gather information on whether pES is offered in their country and how case selection is performed. Five predefined sets of phenotypic eligibility criteria from England, Greece, Canada (British Columbia and Ontario) and Spain were tested on a virtual historical cohort of 1054 \u2018unselected\u2019 structurally abnormal fetuses undergoing pES, derived from a published systematic review. The performance of the current and previous gene panels used in the NHS pES service was assessed in the unselected cohort. The sensitivity and specificity with 95%\u2009CI for each set of criteria in relation to diagnostic yield for pathogenic and likely pathogenic variants were calculated, along with the area under the summary receiver\u2010operating\u2010characteristics curve (AUC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The electronic survey received 261 responses from 63\/120 countries. Where deducible, 81.8% (45\/55) of the countries surveyed offered pES. Where stated, most (90.3% (28\/31)) cases were selected for pES on a case\u2010by\u2010case basis, according to fetal phenotype and the likelihood of an association with a monogenic condition, rather than on the basis of predetermined phenotypic criteria. The total diagnostic yield of the NHS criteria when applied to all relevant cases for pES was 27.8% (69\/248), with pooled sensitivity, pooled specificity and AUC of 49.8% (95%\u2009CI, 31.7\u201367.9%), 80.7% (95%\u2009CI, 59.6\u201392.2%) and 0.66 (95%\u2009CI, 0.53\u20130.74), respectively. The diagnostic yield was highest for isolated short long bones (58.3% (7\/12)). The likelihood of a monogenic diagnosis did not increase significantly as the number of NHS criteria met increased. There was a significant increase in the diagnostic yield of the current (2024)\n                      <jats:italic>vs<\/jats:italic>\n                      original (2020) gene panel adopted by the NHS (129\/135 (95.6%)\n                      <jats:italic>vs<\/jats:italic>\n                      118\/135 (87.4%);\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.017). The four other sets of phenotypic criteria used in other countries\/regions performed moderately well, with the best performance seen for the British Columbia criteria, which had a pooled sensitivity of 70.5% (95%\u2009CI, 43.7\u201388.1%), pooled specificity of 68.9% (95%\u2009CI, 37.5\u201389.1%) and AUC of 0.73 (95%\u2009CI, 0.58\u20130.79).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In the majority of countries for which there was a survey response, pES was offered on a case\u2010by\u2010case basis, according to fetal phenotype and the likelihood of an underlying monogenic condition. Existing phenotypic eligibility criteria for pES performed modestly. \u00a9 2025 The Author(s).\n                      <jats:italic>Ultrasound in Obstetrics &amp; Gynecology<\/jats:italic>\n                      published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/uog.29290","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T13:37:47Z","timestamp":1752068267000},"page":"282-289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Performance of international phenotypic criteria for prenatal exome sequencing: systematic review and comparative diagnostic accuracy study using historical individual participant data"],"prefix":"10.1002","volume":"66","author":[{"given":"K.","family":"Reilly","sequence":"first","affiliation":[{"name":"Centre for Public Health Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2263-3592","authenticated-orcid":false,"given":"D. L.","family":"Rolnik","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Monash University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Allen","sequence":"additional","affiliation":[{"name":"West Midlands Regional Genetics Laboratory Birmingham Women's and Children's NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0876-5596","authenticated-orcid":false,"given":"A.","family":"Sotiriadis","sequence":"additional","affiliation":[{"name":"Second Department of Obstetrics and Gynecology, Faculty of Medicine Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ong","sequence":"additional","affiliation":[{"name":"Centre for Fetal Medicine, Royal Jubilee Maternity Service, Belfast Health and Social Care Trust  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Sonner","sequence":"additional","affiliation":[{"name":"Centre for Public Health Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. V.","family":"Blayney","sequence":"additional","affiliation":[{"name":"Centre for Fetal Medicine, Royal Jubilee Maternity Service, Belfast Health and Social Care Trust  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Fernando","sequence":"additional","affiliation":[{"name":"King's College London Medical School  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-6905","authenticated-orcid":false,"given":"T.","family":"Van Mieghem","sequence":"additional","affiliation":[{"name":"Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynaecology Mount Sinai Hospital, University of Toronto  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4304-4797","authenticated-orcid":false,"given":"A.","family":"Borrell","sequence":"additional","affiliation":[{"name":"Barcelona Centre for Maternal\u2013Fetal and Neonatal Medicine (BCNatal), Hospital Cl\u00ednic Barcelona Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Langlois","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0718-7547","authenticated-orcid":false,"given":"F.","family":"Mone","sequence":"additional","affiliation":[{"name":"Centre for Public Health Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Collaborators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2023.100915"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.26301"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6115"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2022.09.045"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.23652"},{"key":"e_1_2_7_7_1","unstructured":"PanelApp. Genomics England.https:\/\/panelapp.genomicsengland.co.uk\/[Accessed 1st December 2024]."},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2024-109878"},{"key":"e_1_2_7_9_1","unstructured":"Hellenic Society of Ultrasound in Obstetrics and Gynecology.Guidelines for the application of next\u2010generation sequencing in prenatal screening [translated]. 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