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

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. KnapenAngelique 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, The Dutch NIPT Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1091-1101
Number of pages11
JournalAmerican journal of human genetics
Volume105
Issue number6
Early online date31 Oct 2019
DOIs
Publication statusPublished - 5 Dec 2019

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