{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:12:33Z","timestamp":1787987553334,"version":"build-2784847793"},"reference-count":85,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prenatal whole-genome sequencing (WGS) is a comprehensive genetic test for fetal anomalies, enabling simultaneous detection of aneuploidies, copy number variants (CNVs), single-nucleotide variants (SNVs), small insertions\/deletions, structural variants, and regions of absence of heterozygosity. However, its clinical performance, optimal sequencing strategies, and implementation challenges remain incompletely defined. We conducted a narrative review of PubMed-indexed studies (1966\u2013December 2025) evaluating prenatal WGS in fetuses with structural anomalies. Across 29 studies, diagnostic yield ranged from approximately 20% to 40%, influenced by phenotype complexity, sequencing depth, and study design. Low-coverage WGS (\u22645\u00d7) reliably detected large chromosomal abnormalities with a performance comparable to chromosomal microarray analysis. Moderate-coverage WGS (20\u201340\u00d7) additionally enabled detection of SNVs and structural variants, providing up to 30% incremental diagnostic yield after uninformative standard testing. Turnaround times were typically 14\u201321 days. Higher sequencing depth increases detection of variants of uncertain significance (0.6% to 35.7%) and secondary\/incidental findings (1.6\u201330.8%). Prenatal WGS offers meaningful diagnostic value but requires careful patient selection, multidisciplinary expertise, and structured pre- and post-test genetic counseling to ensure responsible integration into routine clinical practice, with careful consideration of clinical benefit and economic feasibility.<\/jats:p>","DOI":"10.3390\/ijms27083568","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:14:12Z","timestamp":1776352452000},"page":"3568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prenatal Whole-Genome Sequencing for Fetal Anomalies: Diagnostic Performance, Challenges, and Clinical Implications"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-1387","authenticated-orcid":false,"given":"Threebhorn","family":"Kamlungkuea","sequence":"first","affiliation":[{"name":"Fetal Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-2128","authenticated-orcid":false,"given":"Kuntharee","family":"Traisrisilp","sequence":"additional","affiliation":[{"name":"Fetal Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4838-175X","authenticated-orcid":false,"given":"Suchaya","family":"Luewan","sequence":"additional","affiliation":[{"name":"Fetal Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4992-5296","authenticated-orcid":false,"given":"Jeerawan","family":"Klangjorhor","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2329-2176","authenticated-orcid":false,"given":"Duangrurdee","family":"Wattanasirichaigoon","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7152-1952","authenticated-orcid":false,"given":"Fuanglada","family":"Tongprasert","sequence":"additional","affiliation":[{"name":"Fetal Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, Y., He, C., Yu, H., Wu, D., Liu, L., and Zhang, X. 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