{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:56:20Z","timestamp":1780667780023,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"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>Non-invasive prenatal screening (NIPS) in twin gestations has been shown to have high detection rates and low false-positive rates for trisomy 21, as seen in singleton pregnancies, although there have been few large cohort twin studies, genome-wide studies in particular, to date. In this study, we looked at the performance of genome-wide NIPT in a large cohort consisting of 1244 twin pregnancy samples collected over a two-year period in a single laboratory in Italy. All samples underwent an NIPS for common trisomies, with 61.5% of study participants choosing to undergo genome-wide NIPS for additional fetal anomalies (namely, rare autosomal aneuploidies and CNVs). There were nine initial no-call results, all of which were resolved upon retest. Based on our NIPS results, 17 samples were at high risk for trisomy 21, one for trisomy 18, six for a rare autosomal aneuploidy, and four for a CNV. Clinical follow-up was available for 27 out of 29 high-risk cases; a sensitivity of 100%, a specificity of 99.9%, and a PPV of 94.4% were noted for trisomy 21. Clinical follow-up was also available for 1110 (96.6%) of the low-risk cases, all of which were true negatives. In conclusion, we found that NIPS was a reliable screening approach for trisomy 21 in twin pregnancies.<\/jats:p>","DOI":"10.3390\/genes14050982","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T02:50:00Z","timestamp":1682563800000},"page":"982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical Experience with Genome-Wide Noninvasive Prenatal Screening in a Large Cohort of Twin Pregnancies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0553-2087","authenticated-orcid":false,"given":"Luigia","family":"De Falco","sequence":"first","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"},{"name":"Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Savarese","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"},{"name":"Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Savarese","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"},{"name":"Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Petrillo","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"},{"name":"Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Ianniello","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"},{"name":"Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"},{"name":"Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Suero","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"},{"name":"Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9079-1455","authenticated-orcid":false,"given":"Cosimo","family":"Barbato","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Mori","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ramiro","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"},{"name":"Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0584-2181","authenticated-orcid":false,"given":"Luigi","family":"Della Corte","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, 80013 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Saccone","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, 80013 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-5735","authenticated-orcid":false,"given":"Attilio","family":"Di Spiezio Sardo","sequence":"additional","affiliation":[{"name":"Department of Public Health, Gynecology Unit\u2014Federico II University Hospital of Naples, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Fico","sequence":"additional","affiliation":[{"name":"AMES, Centro Polidiagnostico Strumentale, 80013 Naples, Italy"},{"name":"Fondazione Genetica per la Vita Onlus, 80132 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/pd.5832","article-title":"International Society for Prenatal Diagnosis Position Statement: Cell free (cf) DNA screening for Down syndrome in multiple pregnancies","volume":"41","author":"Palomaki","year":"2020","journal-title":"Prenat. Diagn."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/j.1728-4457.2015.00088.x","article-title":"Twinning Rates in Developed Countries: Trends and Explanations","volume":"41","author":"Pison","year":"2015","journal-title":"Popul. Dev. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1016\/j.jogc.2017.06.015","article-title":"No. 262-Prenatal Screening for and Diagnosis of Aneuploidy in Twin Pregnancies","volume":"39","author":"Audibert","year":"2017","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/pd.5997","article-title":"Twin chorionicity and zygosity both vary with maternal age","volume":"41","author":"Sparks","year":"2021","journal-title":"Prenat. Diagn."},{"key":"ref_5","unstructured":"Committee on Practice Bulletins\u2014Obstetrics, and Society for Maternal\u2013Fetal Medicine (2016). Practice Bulletin No. 169: Multifetal Gestations: Twin, Triplet, and Higher-Order Multifetal Pregnancies. Obstet. Gynecol., 128, e131\u2013e146."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1002\/pd.5989","article-title":"Non-invasive prenatal testing in the management of twin pregnancies","volume":"41","author":"Benn","year":"2021","journal-title":"Prenat. Diagn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100499","DOI":"10.1016\/j.ajogmf.2021.100499","article-title":"Screening for aneuploidy in twins","volume":"4","author":"Hopkins","year":"2021","journal-title":"Am. J. Obstet. Gynecol. MFM"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1002\/pd.4431","article-title":"Systematic review of screening for trisomy 21 in twin pregnancies in first trimester combining nuchal translucency and biochemical markers: A meta-analysis","volume":"34","author":"Prats","year":"2014","journal-title":"Prenat. Diagn."},{"key":"ref_9","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":"Lo","year":"1997","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/pd.3892","article-title":"DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations","volume":"32","author":"Canick","year":"2012","journal-title":"Prenat. Diagn."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.gim.2022.03.019","article-title":"Systematic evidence-based review: The application of noninvasive prenatal screening us-ing cell-free DNA in general-risk pregnancies","volume":"24","author":"Rose","year":"2022","journal-title":"Genet. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100336","DOI":"10.1016\/j.gim.2022.11.004","article-title":"ACMG Board of Directors, Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)","volume":"25","author":"Dungan","year":"2023","journal-title":"Genet. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.ajhg.2022.04.018","article-title":"Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study","volume":"109","author":"Sistermans","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists (ACOG), and Society for Maternal-Fetal Medicine (SMFM) (2020). Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin Summary, Number 226. Obstet. Gynecol., 136, 859\u2013867.","DOI":"10.1097\/AOG.0000000000004107"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.jogc.2017.01.032","article-title":"No. 348-Joint SOGC-CCMG Guideline: Update on Prenatal Screening for Fetal Aneuploidy, Fetal Anomalies, and Adverse Pregnancy Outcomes","volume":"39","author":"Audibert","year":"2017","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/gim.2016.97","article-title":"Noninvasive prenatal screening for fetal aneuploidy, 2016 update: A position statement of the American College of Medical Genetics and Genomics","volume":"18","author":"Gregg","year":"2016","journal-title":"Genet. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1136\/jmg.31.11.864","article-title":"Counselling following diagnosis of a fetal abnormality: The differing approaches of obstetricians, clinical geneticists, and genetic nurses","volume":"31","author":"Marteau","year":"1994","journal-title":"J. Med. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"La Verde, M., De Falco, L., Torella, A., Savarese, G., Savarese, P., Ruggiero, R., Conte, A., Fico, V., Torella, M., and Fico, A. (2021). Performance of cell-free DNA sequencing-based non-invasive prenatal testing: Experience on 36,456 singleton and multiple pregnancies. BMC Med. Genom., 14.","DOI":"10.1186\/s12920-021-00941-y"},{"key":"ref_19","unstructured":"Illumina, Inc. (2022, December 01). VeriSeq NIPT Solution v2 Package Insert. Available online: https:\/\/support.illumina.com\/downloads\/veriseq-nipt-solution-v2-package-insert-1000000078751.html."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1093\/clinchem\/hvab067","article-title":"Performance of a Paired-End Sequencing-Based Noninvasive Prenatal Screening Test in the Detection of Genome-Wide Fetal Chromosomal Anomalies","volume":"67","author":"Pertile","year":"2021","journal-title":"Clin. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1007\/s00404-020-05856-0","article-title":"Analysis of cell-free DNA in a consecutive series of 13,607 routine cases for the detection of fetal chromosomal aneuploidies in a single center in Germany","volume":"303","author":"Borth","year":"2021","journal-title":"Arch. Gynecol. Obs."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/S0140-6736(01)06183-9","article-title":"Development and implementation of a new rapid aneuploidy diagnostic service within the UK National Health Service and implications for the future of prenatal diagnosis","volume":"358","author":"Mann","year":"2001","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/(SICI)1097-0258(19980430)17:8<857::AID-SIM777>3.0.CO;2-E","article-title":"Two-sided confidence intervals for the single proportion: Comparison of seven methods","volume":"17","author":"Newcombe","year":"1998","journal-title":"Stat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"975987","DOI":"10.3389\/fgene.2022.975987","article-title":"Multisite assessment of the impact of cell-free DNA-based screening for rare autosomal aneuploidies on pregnancy management and outcomes","volume":"13","author":"Mossfield","year":"2022","journal-title":"Front. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"79.e1","DOI":"10.1016\/j.ajog.2021.01.005","article-title":"Non-invasive Prenatal Screening in Twin Pregnancies with cell-free DNA using the IONA Test: A prospective multicentre study","volume":"225","author":"Khalil","year":"2021","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/uog.23648","article-title":"Cell-free DNA testing of maternal blood in screening for trisomies in twin pregnancy: Updated cohort study at 10\u201314 weeks and meta-analysis","volume":"58","author":"Judah","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/uog.17484","article-title":"Analysis of cell-free DNA in maternal blood in screening for aneuploidies: Updated meta-analysis","volume":"50","author":"Gil","year":"2017","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1002\/pd.5797","article-title":"Cell-free DNA screening in twin pregnancies: A more accurate and reliable screening tool","volume":"40","author":"Chibuk","year":"2020","journal-title":"Prenat. Diagn."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1097\/AOG.0000000000004385","article-title":"Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations","volume":"137","author":"Brison","year":"2021","journal-title":"Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1093\/humupd\/dmab009","article-title":"Confined placental mosaicism and the association with pregnancy outcome and fetal growth: A review of the literature","volume":"27","author":"Eggenhuizen","year":"2021","journal-title":"Hum. Reprod. 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