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. 2019 Dec 5;105(6):1091-1101.
doi: 10.1016/j.ajhg.2019.10.005. Epub 2019 Nov 7.

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  1 , Erik A Sistermans  2 , Merryn V E Macville  3 , Servi J C Stevens  3 , Caroline J Bax  4 , Mireille N Bekker  5 , Caterina M Bilardo  6 , Elles M J Boon  1 , Marjan Boter  7 , Karin E M Diderich  7 , Christine E M de Die-Smulders  3 , Leonie K Duin  8 , Brigitte H W Faas  9 , Ilse Feenstra  9 , Monique C Haak  10 , Mariëtte J V Hoffer  11 , Nicolette S den Hollander  11 , Iris H I M Hollink  7 , Fernanda S Jehee  7 , Maarten F C M Knapen  12 , Angelique J A Kooper  13 , Irene M van Langen  14 , Klaske D Lichtenbelt  15 , Ingeborg H Linskens  6 , Merel C van Maarle  13 , Dick Oepkes  10 , Mijntje J Pieters  16 , G Heleen Schuring-Blom  15 , Esther Sikkel  17 , Birgit Sikkema-Raddatz  13 , Dominique F C M Smeets  9 , Malgorzata I Srebniak  7 , Ron F Suijkerbuijk  13 , Gita M Tan-Sindhunata  1 , A Jeanine E M van der Ven  18 , Shama L van Zelderen-Bhola  1 , Lidewij Henneman  1 , Robert-Jan H Galjaard  7 , Diane Van Opstal  7 , Marjan M Weiss  1 ; Dutch NIPT Consortium
Affiliations

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 et al. Am J Hum Genet. .

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.

Keywords: NIPS; NIPT; cfDNA; common trisomies; fetal trisomy; first tier test; genome-wide; implementation study; prenatal screening; rare autosomal trisomies.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
NIPT Flow and Numbers for the Open and Targeted Cohorts n, number.
Figure 2
Figure 2
Distribution of Rare Autosomal Trisomies NIPT, non-invasive prenatal test; RAT, rare autosomal trisomy; T, trisomy
Figure 3
Figure 3
Distribution of Structural Chromosomal Aberrations NIPT, non-invasive prenatal test; SA, structural chromosomal aberration
See this image and copyright information in PMC

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