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

Meij, K.R.M. van der; Sistermans, E.A.; Macville, M.V.E.; Stevens, S.J.C.; Bax, C.J.; Bekker, M.N.; Bilardo, C.M.; Boon, E.M.J.; Boter, M.; Diderich, K.E.M.; Die-Smulders, C.E.M. de; Duin, L.K.; Faas, B.H.W.; Feenstra, I.; Haak, M.C.; Hoffer, M.J.V.; Hollander, N.S. den; Hollink, I.H.I.M.; Jehee, F.S.; Knapen, M.F.C.M.; Kooper, A.J.A.; Langen, I.M. van; Lichtenbelt, K.D.; Linskens, I.H.; Maarle, M.C. van; Oepkes, D.; Pieters, M.J.; Schuring-Blom, G.H.; Sikkel, E.; Sikkema-Raddatz, B.; Smeets, D.F.C.M.; Srebniak, M.I.; Suijkerbuijk, R.F.; Tan-Sindhunata, G.M.; Ven, A.J.E.M. van der; Zelderen-Bhola, S.L. van; Henneman, L.; Galjaard, R.J.H.; Opstal, D. van; Weiss, M.M.; Dutch NIPT Consortium

doi:doi:10.1016/j.ajhg.2019.10.005

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...Show moreThe 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.Show less

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