TRIDENT-2: National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands.

Abstract

The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as a first-tier test offered to all pregnant women. This started on April 1, 2017 as the TRIDENT-2 study, licensed by the Dutch Ministry of Health. In the first year, NIPT was performed in 73,239 pregnancies (42% of all pregnancies), 7,239 (4%) chose first-trimester combined testing, and 54% did not participate. The number of trisomies 21 (239, 0.33%), 18 (49, 0.07%), and 13 (55, 0.08%) found in this study is comparable to earlier studies, but the Positive Predictive Values (PPV)-96% for trisomy 21, 98% for trisomy 18, and 53% for trisomy 13-were higher than expected. Findings other than trisomy 21, 18, or 13 were reported on request of the pregnant women; 78% of women chose to have these reported. The number of additional findings was 207 (0.36%); these included other trisomies (101, 0.18%, PPV 6%, many of the remaining 94% of cases are likely confined placental mosaics and possibly clinically significant), structural chromosomal aberrations (95, 0.16%, PPV 32%,) and complex abnormal profiles indicative of maternal malignancies (11, 0.02%, PPV 64%). The implementation of genome-wide NIPT is under debate because the benefits of detecting other fetal chromosomal aberrations must be balanced against the risks of discordant positives, parental anxiety, and a potential increase in (invasive) diagnostic procedures. Our first-year data, including clinical data and laboratory follow-up data, will fuel this debate. Furthermore, we describe how NIPT can successfully be embedded into a national screening program with a single chain for prenatal care including counseling, testing, and follow-up.

• Authors: Karuna R M van der Meij, Erik A Sistermans, Merryn V E Macville, Servi J C Stevens, Caroline J Bax, Mireille N Bekker, Caterina M Bilardo, Elles M J Boon, Marjan Boter, Karin E M Diderich, Christine E M de Die-Smulders, Leonie K Duin, Brigitte H W Faas, Ilse Feenstra, Monique C Haak, Mariëtte J V Hoffer, Nicolette S den Hollander, Iris H I M Hollink, Fernanda S Jehee, Maarten F C M Knapen, Angelique J A Kooper, Irene M van Langen, Klaske D Lichtenbelt, Ingeborg H Linskens, Merel C van Maarle, Dick Oepkes, Mijntje J Pieters, G Heleen Schuring-Blom, Esther Sikkel, Birgit Sikkema-Raddatz, Dominique F C M Smeets, Malgorzata I Srebniak, Ron F Suijkerbuijk, Gita M Tan-Sindhunata, A Jeanine E M van der Ven, Shama L van Zelderen-Bhola, Lidewij Henneman, Robert-Jan H Galjaard, Diane Van Opstal, Marjan M Weiss, Dutch NIPT Consortium
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 105 Issue 6 Pg. 1091-1101 (12 05 2019) ISSN: 1537-6605 [Electronic] United States
• PMID: 31708118 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Topics

• Adolescent
• Adult
• Chromosome Aberrations
• Down Syndrome (diagnosis, epidemiology, genetics)
• Female
• Follow-Up Studies
• Genetic Testing (methods)
• Genome, Human
• Health Plan Implementation
• Humans
• Middle Aged
• Netherlands (epidemiology)
• Pregnancy
• Pregnancy Trimester, First
• Prenatal Diagnosis (methods)
• Prognosis
• Trisomy 13 Syndrome (diagnosis, epidemiology, genetics)
• Trisomy 18 Syndrome (diagnosis, epidemiology, genetics)
• Young Adult