{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:54:20Z","timestamp":1790434460751,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To assess the value of placental insufficiency markers for estimating the risk of genetic anomalies in fetuses with isolated early\u2010onset fetal growth restriction (FGR), defined as an estimated fetal weight \u2264\u20093\n                      <jats:sup>rd<\/jats:sup>\n                      \u2009percentile diagnosed \u2264\u200928\u2009+\u20096\u2009weeks' gestation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a retrospective analysis of data collected prospectively from cases that attended Vall d'Hebron University Hospital, Barcelona, Spain, between February 2016 and December 2022. Singleton pregnancies diagnosed with isolated early\u2010onset FGR between 20\u2009+\u20090 and 28\u2009+\u20096\u2009weeks' gestation were eligible for inclusion. Cases in which a pathogenic or likely pathogenic fetal genetic abnormality was detected by chromosomal microarray (CMA) or whole\u2010exome sequencing (WES) were identified. Cases were stratified by soluble fms\u2010like tyrosine kinase\u20101 (sFlt\u20101)\/placental growth factor (PlGF) ratio (&lt;\u200938\n                      <jats:italic>vs<\/jats:italic>\n                      \u2265\u200938), PlGF level (&lt;\u2009100\n                      <jats:italic>vs<\/jats:italic>\n                      \u2265\u2009100\u2009pg\/mL), mean uterine artery (UtA) pulsatility index (PI) (&lt;\u200995\n                      <jats:sup>th<\/jats:sup>\n                      <jats:italic>vs<\/jats:italic>\n                      \u2265\u200995\n                      <jats:sup>th<\/jats:sup>\n                      \u2009percentile) and fetal Doppler (normal\n                      <jats:italic>vs<\/jats:italic>\n                      abnormal) at the time of FGR diagnosis. Abnormal fetal Doppler was defined as a PI &gt;\u200995\n                      <jats:sup>th<\/jats:sup>\n                      \u2009percentile in the umbilical artery or ductus venosus, or a middle cerebral artery PI or cerebroplacental ratio\u2009&lt;\u20095\n                      <jats:sup>th<\/jats:sup>\n                      \u2009percentile. The prevalence of genetic anomalies in each subgroup was compared with that of the overall cohort. Additionally, combinations of markers of placental insufficiency were investigated to determine whether specific combinations could improve the ability to identify cases at risk of genetic anomaly.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the total cohort of 238 cases of isolated early\u2010onset FGR, seven (2.9%) cases of genetic anomaly were detected. Of these, 2\/7 (28.6%) were detected by prenatal or postnatal CMA and 5\/7 (71.4%) by postnatal WES. Fetal Doppler alone and UtA\u2010PI alone did not identify subgroups with a significantly different prevalence of genetic abnormality compared with the overall cohort. In contrast, a sFlt\u20101\/PlGF ratio &lt;\u200938 and PlGF level \u2265\u2009100\u2009pg\/mL defined subgroups with a significantly higher prevalence of genetic abnormality, while no genetic anomalies were found in cases with a sFlt\u20101\/PlGF ratio \u2265\u200938 or PlGF level &lt;\u200945\u2009pg\/mL. Furthermore, smaller subgroups combining markers of placental insufficiency identified cases at significantly higher or lower risk of FGR\u2010related genetic anomaly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Placental insufficiency markers, particularly the sFlt\u20101\/PlGF ratio and PlGF level, may enable refined risk stratification of genetic anomalies in cases of isolated early\u2010onset FGR, which could be used to provide individualized prenatal counseling and to optimize the use of WES. Furthermore, combining markers of placental insufficiency, such as UtA\u2010PI and fetal Doppler, may improve risk stratification, potentially defining smaller subgroups with a higher prevalence of genetic anomalies, for which WES may provide greater diagnostic yield. \u00a9 2026 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.70211","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T09:33:34Z","timestamp":1774863214000},"page":"492-499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Placental insufficiency markers to assess the risk of non\u2010chromosomal genetic conditions in early\u2010onset fetal growth restriction"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-5176","authenticated-orcid":false,"given":"M.","family":"Armengol\u2010Alsina","sequence":"first","affiliation":[{"name":"Maternal\u2013Fetal Medicine Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Centres de Recerca de Catalunya (CERCA)  Barcelona Spain"},{"name":"Maternal\u2013Fetal Medicine Unit, Department of Obstetrics and Gynecology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, Department of Pediatrics, Obstetrics and Gynecology, and Preventive Medicine and Public Health  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8042-8247","authenticated-orcid":false,"given":"E.","family":"Bonacina","sequence":"additional","affiliation":[{"name":"Maternal\u2013Fetal Medicine Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Centres de Recerca de Catalunya (CERCA)  Barcelona Spain"},{"name":"Maternal\u2013Fetal Medicine Unit, Department of Obstetrics and Gynecology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7448-0862","authenticated-orcid":false,"given":"M.","family":"Dalmau","sequence":"additional","affiliation":[{"name":"Maternal\u2013Fetal Medicine Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Centres de Recerca de Catalunya (CERCA)  Barcelona Spain"},{"name":"Maternal\u2013Fetal Medicine Unit, Department of Obstetrics and Gynecology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3898-0203","authenticated-orcid":false,"given":"J.","family":"Temprado","sequence":"additional","affiliation":[{"name":"Maternal\u2013Fetal Medicine Unit, Department of Obstetrics and Gynecology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2350-6058","authenticated-orcid":false,"given":"I.","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Department Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"},{"name":"Genetics Medicine Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Centres de Recerca de Catalunya (CERCA)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Codina\u2010Sol\u00e0","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Department Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"},{"name":"Genetics Medicine Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Centres de Recerca de Catalunya (CERCA)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Vi\u00f1as\u2010Jornet","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Genetics Department Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"},{"name":"Genetics Medicine Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Centres de Recerca de Catalunya (CERCA)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8801-5677","authenticated-orcid":false,"given":"C.","family":"Rod\u00f3","sequence":"additional","affiliation":[{"name":"Maternal\u2013Fetal Medicine Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Centres de Recerca de Catalunya (CERCA)  Barcelona Spain"},{"name":"Maternal\u2013Fetal Medicine Unit, Department of Obstetrics and Gynecology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-3833","authenticated-orcid":false,"given":"M.","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Maternal\u2013Fetal Medicine Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Centres de Recerca de Catalunya (CERCA)  Barcelona Spain"},{"name":"Maternal\u2013Fetal Medicine Unit, Department of Obstetrics and Gynecology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, Department of Pediatrics, Obstetrics and Gynecology, and Preventive Medicine and Public Health  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Collaborators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000357592"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2017.11.577"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-017-4341-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5635"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5160"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000452217"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.05.035"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6339"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.29195"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000004251"},{"key":"e_1_2_7_12_1","unstructured":"Small\u2010for\u2010Gestational\u2010Age Fetus and a Growth Restricted Fetus Investigation and Care (Green\u2010top Guideline No. 31). RCOG. Accessed September 1 2025.https:\/\/www.rcog.org.uk\/guidance\/browse\u2010all\u2010guidance\/green\u2010top\u2010guidelines\/small\u2010for\u2010gestational\u2010age\u2010fetus\u2010and\u2010a\u2010growth\u2010restricted\u2010fetus\u2010investigation\u2010and\u2010care\u2010green\u2010top\u2010guideline\u2010no\u201031\/."},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2022.09.045"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2004.02.003"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2012.01.022"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.20350"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2021.12.003"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.14032"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.24888"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2024.39.e70"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(85)90298-4"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.5402"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2006.12.015"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.5315"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpme.1990.18.3.165"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0705.1994.04050381.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.20"},{"key":"e_1_2_7_28_1","unstructured":"Dosage Sensitivity Curations. Accessed September 3 2025.https:\/\/search.clinicalgenome.org\/kb\/gene\u2010dosage?page=1&size=25&search="},{"key":"e_1_2_7_29_1","unstructured":"LiH.Aligning sequence reads clone sequences and assembly contigs with BWA\u2010MEM.arXiv. 2013.10.48550\/arXiv.1303.3997"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0244-x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1005"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6157"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5169"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1159\/000479506"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu002"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.11.1357"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmab009"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-020-00253-4"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189762"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2005.06.031"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2019.1575357"}],"container-title":["Ultrasound in Obstetrics &amp; Gynecology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/uog.70211","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/uog.70211","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/uog.70211","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T12:37:13Z","timestamp":1778935033000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/uog.70211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/uog.70211"],"URL":"https:\/\/doi.org\/10.1002\/uog.70211","archive":["Portico"],"relation":{},"ISSN":["0960-7692","1469-0705"],"issn-type":[{"value":"0960-7692","type":"print"},{"value":"1469-0705","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]},"assertion":[{"value":"2025-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}