{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:48:04Z","timestamp":1774028884979,"version":"3.50.1"},"reference-count":19,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Non-invasive prenatal testing (NIPT) based on cell-free fetal DNA (cfDNA) in maternal blood has revolutionized prenatal screening for trisomies 21, 18, and 13. This approach, based on next-generation sequencing (NGS), usually allows the detection of other chromosomal abnormalities; however, their clinical value in routine practice requires further evidence. Objectives: This study aimed to assess the experience and clinical utility of genome-wide NIPT in pregnant women at intermediate risk in the autonomous communities of Arag\u00f3n and Valencia, Spain. Methods: For this purpose, a retrospective cohort study was conducted between 2020 and 2024 across two public hospitals. Pregnant women at intermediate risk for trisomies 21, 18, or 13, were included, as well as those meeting specific clinical criteria. Participants were offered either basic or expanded NIPT, and positive results were confirmed by invasive prenatal testing or placental analysis. Results: Among 9,059 expanded NIPT tests, 132 (1.45%) indicated a high-risk result for less common chromosomal anomalies, comprising 60 rare autosomal aneuploidies (RAAs), 39 copy number variants (CNVs), 23 sex chromosome aneuploidies (SCAs), and 10 multiple abnormalities. The positive predictive value (PPV) was 5.5% for RAAs in the fetus, 12.8% for CNVs (31% for deletions), and 58% for SCAs. Conclusions: Several confirmed anomalies were clinically significant and would not have been detected through conventional screening. Opportunistic use of expanded NIPT enables the detection of additional clinically relevant abnormalities, potentially improving obstetric management without substantially increasing invasive testing.<\/jats:p>","DOI":"10.3390\/genes16111344","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T11:41:47Z","timestamp":1762515707000},"page":"1344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Utility of Opportunistic Genome-Wide cfDNA Prenatal Screening in Intermediate-Risk Pregnancies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1817-4549","authenticated-orcid":false,"given":"S.","family":"Menao Guill\u00e9n","sequence":"first","affiliation":[{"name":"Department of Genetics, Hospital Cl\u00ednico Universitario Lozano Blesa, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-6124","authenticated-orcid":false,"given":"L.","family":"Pedrola","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hospital Universitario La Fe, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-5859","authenticated-orcid":false,"given":"C.","family":"Orellana","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hospital Universitario La Fe, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9234-2953","authenticated-orcid":false,"given":"M.","family":"Rosell\u00f3","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hospital Universitario La Fe, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Arruebo","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Lahuerta Pueyo","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Sobreviela Laserrada","sequence":"additional","affiliation":[{"name":"Obstetrics Department, Gynecological Center Bolonia, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Marcos","sequence":"additional","affiliation":[{"name":"Obstetrics Department, Hospital Universitario La Fe, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5869-4450","authenticated-orcid":false,"given":"J.","family":"Pascual Mancho","sequence":"additional","affiliation":[{"name":"Obstetrics Department, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8252-1106","authenticated-orcid":false,"given":"J. V.","family":"Cervera","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hospital Universitario La Fe, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Tajada","sequence":"additional","affiliation":[{"name":"Obstetrics Department, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4562-3319","authenticated-orcid":false,"given":"R.","family":"Quiroga","sequence":"additional","affiliation":[{"name":"Obstetrics Department, Hospital Universitario La Fe, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S0140-6736(97)02174-0","article-title":"Presence of fetal DNA in maternal plasma and serum","volume":"350","author":"LLo","year":"1997","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/pd.4945","article-title":"Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. 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