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.
21 affiliations
- 1Obstetrics and Gynecology University of Pennsylvania Philadelphia Pennsylvania USA.
- 2Obstetrics and Gynecology Lehigh Valley Health Network Allentown Pennsylvania USA.
- 3Obstetrics and Gynecology NYU Langone Health New York New York USA.
- 4Obstetrics, Gynecology and Reproductive Sciences Yale New Haven Hospital New Haven Connecticut USA.
- 5Obstetrics and Gynecology Weill Cornell Medicine New York New York USA.
- 6Obstetrics and Gynecology Icahn School of Medicine at Mount Sinai New York New York USA.
- 7Obstetrics and Gynecology Stanford Medicine Children's Health Palo Alto California USA.
- 8Emerald Coast Obstetrics and Gynecology Panama City Florida USA.
- 9Obstetrics and Gynecology St. Peter's University Hospital New Brunswick New Jersey USA.
- 10Obstetrics and Gynecology School of Medicine University of Colorado Aurora Colorado USA.
- 11Obstetrics and Gynecology Columbia University Irving Medical Center New York New York USA.
- 12Obstetrics and Gynecology University of Kansas Health System Kansas City Kansas USA.
- 13Obstetrics and Gynecology Mayo Clinic Rochester Minnesota USA.
- 14Obstetrics and Gynecology Corewell Health William Beaumont University Hospital Southfield Michigan USA.
- 15Center for Fetal Medicine and Women's Ultrasound, David Geffen School of Medicine at UCLA Los Angeles California USA.
- 16Obstetrics and Gynecology University of Michigan Ann Arbor Michigan USA.
- 17Obstetrics and Gynecology Hackensack UMC - Hackensack Meridian School of Medicine Hackensack New Jersey USA.
- 18Cedar Health Research Dallas Texas USA.
- 19Obstetrics and Gynecology Christiana Care Newark Delaware USA.
- 20Obstetrics and Gynecology Montefiore Einstein Bronx New York USA.
- 21Natera, Inc. Austin Texas USA.
Abstract
Introduction
To 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
Prospective 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
Of 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
The 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
ClinicalTrials.gov Identifier: NCT05004337.
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BibTeX
@article{dugoff2026results,
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.}},
author = {Lorraine Dugoff and Sunni L Mumford and Meredith L Rochon and Martin Chavez and Katherine Kohari and Jessica E Scholl and Jill A Berkin and Ashley S Roman and Jane Chueh and Samuel B Wolf and Kristy T S Palomares and K Joseph Hurt and Ronald J Wapner and Kelly Gorman and Myra J Wick and Zeynep Alpay Savasan and Lawrence D Platt and Marjorie C Treadwell and Abdulla Al-Khan and Jeff M Livingston and Matthew K Hoffman and Sara S Rabin-Havt and Matthew Rabinowitz and Ebad Ahmed and Jessica L Saben and Nicolas Sun and Anastasia Butskova and Wenbo Xu and Jeffrey Meltzer and Vivienne Souter},
journal = {Pregnancy (Hoboken, N.J.)},
year = {2026},
month = oct,
doi = {10.1002/pmf2.70471},
url = {https://europepmc.org/article/MED/42909945},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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.
AU - Lorraine Dugoff
AU - Sunni L Mumford
AU - Meredith L Rochon
AU - Martin Chavez
AU - Katherine Kohari
AU - Jessica E Scholl
AU - Jill A Berkin
AU - Ashley S Roman
AU - Jane Chueh
AU - Samuel B Wolf
AU - Kristy T S Palomares
AU - K Joseph Hurt
AU - Ronald J Wapner
AU - Kelly Gorman
AU - Myra J Wick
AU - Zeynep Alpay Savasan
AU - Lawrence D Platt
AU - Marjorie C Treadwell
AU - Abdulla Al-Khan
AU - Jeff M Livingston
AU - Matthew K Hoffman
AU - Sara S Rabin-Havt
AU - Matthew Rabinowitz
AU - Ebad Ahmed
AU - Jessica L Saben
AU - Nicolas Sun
AU - Anastasia Butskova
AU - Wenbo Xu
AU - Jeffrey Meltzer
AU - Vivienne Souter
PY - 2026
DA - 2026/10/21
JO - Pregnancy (Hoboken, N.J.)
DO - 10.1002/pmf2.70471
UR - https://europepmc.org/article/MED/42909945
AB - Introduction To 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 Prospective 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 Of 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 The 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 ClinicalTrials.gov Identifier: NCT05004337.
SN - 2997-9684
ER -