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

Dutch NIPT Consortium, 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 JeheeMaarten 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

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52 Citations (Scopus)

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
DOIs
Publication statusPublished - 5-Dec-2019

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