{ "abstract": "Introduction\n\nTo develop and validate a single-nucleotide polymorphism (SNP)-based noninvasive prenatal cell-free DNA (cfDNA) screening algorithm capable of identifying the cfDNA signal of the living fetus in vanishing twin (VT) pregnancies and assessing that twin's aneuploidy risk.Methods\n\nProspective study enrolling participants ≥18 years old at ≥9 weeks' gestation with an ultrasound-confirmed VT at 21 US sites (August 2021 to August 2023). The study protocol specified SNP-based cfDNA screening at enrollment and at two additional 3-week intervals. Neonatal buccal swabs evaluated the SNP profile of the living fetus. Cases lost to follow-up and with missing samples were excluded. Using SNP-based technology, an algorithm to identify the living fetus was developed based on the number of fetoplacental cfDNA signals and individual fetal fraction measurements. Concordance between cfDNA in maternal plasma and newborn buccal-swab SNP profiles was used to validate the algorithm in correctly identifying the living fetus. Common aneuploidies and fetal sex were determined for the living fetus.Results\n\nOf 136 participants enrolled, 106 met criteria for the final analysis; 45 for development and 61 for validation. In the validation cohort, median gestational age was 10.7 weeks (range: 8.0-16.1 weeks) at ultrasound diagnosis of a VT. In 93.4% of validation cases, the algorithm identified the living fetus and gave an aneuploidy result; 90.2% within the first two blood draws. At the time the living fetus was identified, 39 samples had two fetoplacental signals and 18 had one. Aneuploidy results included 56 low-risk and one high-risk result for trisomy 21. Neonatal buccal swabs confirmed that the VT algorithm correctly identified the living twin and gave a correct aneuploidy result in 57/57 cases (100%; 95% confidence interval [CI]: 93.5%, 100.0%). Among 29 participants with all three blood draws and two fetoplacental signals at enrollment, two signals persisted in 93.1% at the second blood draw and 72.4% at the third.Conclusions\n\nThe SNP-based algorithm accurately identified the living fetus in VT pregnancies in this small study. Aneuploidy risk assessment was validated in all cases where the cfDNA signal for the living twin was identified, though these findings should be interpreted with caution given the limited sample size.Trial registration\n\nClinicalTrials.gov Identifier: NCT05004337.", "abstract_shown": true, "affiliations": [ "Obstetrics and Gynecology University of Pennsylvania Philadelphia Pennsylvania USA.", "Obstetrics and Gynecology Lehigh Valley Health Network Allentown Pennsylvania USA.", "Obstetrics and Gynecology NYU Langone Health New York New York USA.", "Obstetrics, Gynecology and Reproductive Sciences Yale New Haven Hospital New Haven Connecticut USA.", "Obstetrics and Gynecology Weill Cornell Medicine New York New York USA.", "Obstetrics and Gynecology Icahn School of Medicine at Mount Sinai New York New York USA.", "Obstetrics and Gynecology Stanford Medicine Children's Health Palo Alto California USA.", "Emerald Coast Obstetrics and Gynecology Panama City Florida USA.", "Obstetrics and Gynecology St. Peter's University Hospital New Brunswick New Jersey USA.", "Obstetrics and Gynecology School of Medicine University of Colorado Aurora Colorado USA.", "Obstetrics and Gynecology Columbia University Irving Medical Center New York New York USA.", "Obstetrics and Gynecology University of Kansas Health System Kansas City Kansas USA.", "Obstetrics and Gynecology Mayo Clinic Rochester Minnesota USA.", "Obstetrics and Gynecology Corewell Health William Beaumont University Hospital Southfield Michigan USA.", "Center for Fetal Medicine and Women's Ultrasound, David Geffen School of Medicine at UCLA Los Angeles California USA.", "Obstetrics and Gynecology University of Michigan Ann Arbor Michigan USA.", "Obstetrics and Gynecology Hackensack UMC - Hackensack Meridian School of Medicine Hackensack New Jersey USA.", "Cedar Health Research Dallas Texas USA.", "Obstetrics and Gynecology Christiana Care Newark Delaware USA.", "Obstetrics and Gynecology Montefiore Einstein Bronx New York USA.", "Natera, Inc. Austin Texas USA." ], "article_type": "research article", "arxiv": null, "author_total": 30, "authors": [ { "affs": [ 0 ], "name": "Lorraine Dugoff", "orcid": "0000-0003-3638-036X" }, { "affs": [ 0 ], "name": "Sunni L Mumford", "orcid": "0000-0003-0133-3176" }, { "affs": [ 1 ], "name": "Meredith L Rochon", "orcid": "0009-0004-9502-2727" }, { "affs": [ 2 ], "name": "Martin Chavez", "orcid": "0000-0003-2452-715X" }, { "affs": [ 3 ], "name": "Katherine Kohari", "orcid": "0000-0001-7008-6477" }, { "affs": [ 4 ], "name": "Jessica E Scholl", "orcid": "0000-0003-2390-3272" }, { "affs": [ 5 ], "name": "Jill A Berkin" }, { "affs": [ 2 ], "name": "Ashley S Roman" }, { "affs": [ 6 ], "name": "Jane Chueh", "orcid": "0009-0008-5179-4601" }, { "affs": [ 7 ], "name": "Samuel B Wolf" }, { "affs": [ 8 ], "name": "Kristy T S Palomares", "orcid": "0009-0001-7615-081X" }, { "affs": [ 9 ], "name": "K Joseph Hurt", "orcid": "0000-0001-6906-350X" }, { "affs": [ 10 ], "name": "Ronald J Wapner" }, { "affs": [ 11 ], "name": "Kelly Gorman" }, { "affs": [ 12 ], "name": "Myra J Wick", "orcid": "0000-0003-4126-4523" }, { "affs": [ 13 ], "name": "Zeynep Alpay Savasan" }, { "affs": [ 14 ], "name": "Lawrence D Platt", "orcid": "0000-0002-7993-760X" }, { "affs": [ 15 ], "name": "Marjorie C Treadwell", "orcid": "0000-0002-1703-3082" }, { "affs": [ 16 ], "name": "Abdulla Al-Khan", "orcid": "0009-0009-0278-3022" }, { "affs": [ 17 ], "name": "Jeff M Livingston" }, { "affs": [ 18 ], "name": "Matthew K Hoffman", "orcid": "0000-0002-2927-8693" }, { "affs": [ 19 ], "name": "Sara S Rabin-Havt" }, { "affs": [ 20 ], "name": "Matthew Rabinowitz", "orcid": "0009-0006-3109-4232" }, { "affs": [ 20 ], "name": "Ebad Ahmed" }, { "affs": [ 20 ], "name": "Jessica L Saben", "orcid": "0000-0002-9873-025X" }, { "affs": [ 20 ], "name": "Nicolas Sun" }, { "affs": [ 20 ], "name": "Anastasia Butskova" }, { "affs": [ 20 ], "name": "Wenbo Xu", "orcid": "0009-0001-0802-5240" }, { "affs": [ 20 ], "name": "Jeffrey Meltzer", "orcid": "0000-0001-8180-186X" }, { "affs": [ 20 ], "name": "Vivienne Souter" } ], "bibtex": "https://research.draconitic.com/paper/9643cnd3wen1j.bib", "cited_by": 0, "doi": "10.1002/pmf2.70471", "fulltext_url": "https://europepmc.org/articles/PMC13685661", "id": "9643cnd3wen1j", "issns": [ "2997-9684" ], "landing_url": "https://europepmc.org/article/MED/42909945", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2735|Prenatal Screening and Diagnostics" ] ], "openalex": "W7223109825", "pdf_url": "https://europepmc.org/articles/PMC13685661?pdf=render", "pmcid": "PMC13685661", "pmid": "42909945", "published": "2026-10-21", "publisher": null, "ris": "https://research.draconitic.com/paper/9643cnd3wen1j.ris", "sources": [ { "first_seen": "2026-10-30T12:20:10Z", "native_id": "MED:42909945", "source": "europepmc", "url": "https://europepmc.org/article/MED/42909945" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2735|Prenatal Screening and Diagnostics", "subfield": "reproductive-child" } ], "title": "Results from the VANISH study: A prospective multicenter study validating a single-nucleotide polymorphism-based noninvasive prenatal test to assess aneuploidy risk in surviving twins of vanishing twin pregnancies.", "title_text": "Results from the VANISH study: A prospective multicenter study validating a single-nucleotide polymorphism-based noninvasive prenatal test to assess aneuploidy risk in surviving twins of vanishing twin pregnancies.", "type": "peer-reviewed", "updated_at": "2026-10-30T12:20:10Z", "url": "https://research.draconitic.com/paper/9643cnd3wen1j", "venue": "Pregnancy (Hoboken, N.J.)", "versions": [] }