TY - JOUR
T1 - TRIDENT-2
T2 - National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands
AU - The Dutch NIPT Consortium
AU - van der Meij, Karuna R.M.
AU - Sistermans, Erik A.
AU - Macville, Merryn V.E.
AU - Stevens, Servi J.C.
AU - Bax, Caroline J.
AU - Bekker, Mireille N.
AU - Bilardo, Caterina M.
AU - Boon, Elles M.J.
AU - Boter, Marjan
AU - Diderich, Karin E.M.
AU - de Die-Smulders, Christine E.M.
AU - Duin, Leonie K.
AU - Faas, Brigitte H.W.
AU - Feenstra, Ilse
AU - Haak, Monique C.
AU - Hoffer, Mariëtte J.V.
AU - den Hollander, Nicolette S.
AU - Hollink, Iris H.I.M.
AU - Jehee, Fernanda S.
AU - Knapen, Maarten F.C.M.
AU - Kooper, Angelique J.A.
AU - van Langen, Irene M.
AU - Lichtenbelt, Klaske D.
AU - Linskens, Ingeborg H.
AU - van Maarle, Merel C.
AU - Oepkes, Dick
AU - Pieters, Mijntje J.
AU - Schuring-Blom, G. Heleen
AU - Sikkel, Esther
AU - Sikkema-Raddatz, Birgit
AU - Smeets, Dominique F.C.M.
AU - Srebniak, Malgorzata I.
AU - Suijkerbuijk, Ron F.
AU - Tan-Sindhunata, Gita M.
AU - van der Ven, A. Jeanine E.M.
AU - van Zelderen-Bhola, Shama L.
AU - Henneman, Lidewij
AU - Galjaard, Robert Jan H.
AU - Van Opstal, Diane
AU - Weiss, Marjan M.
AU - Dutch NIPT Consortium
N1 - Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
PY - 2019/12/5
Y1 - 2019/12/5
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Chromosome Aberrations
KW - Down Syndrome/diagnosis
KW - Female
KW - Follow-Up Studies
KW - Genetic Testing/methods
KW - Genome, Human
KW - Health Plan Implementation
KW - Humans
KW - Middle Aged
KW - NIPS
KW - NIPT
KW - Netherlands/epidemiology
KW - Pregnancy
KW - Pregnancy Trimester, First
KW - Prenatal Diagnosis/methods
KW - Prognosis
KW - Trisomy 13 Syndrome/diagnosis
KW - Trisomy 18 Syndrome/diagnosis
KW - Young Adult
KW - cfDNA
KW - common trisomies
KW - fetal trisomy
KW - first tier test
KW - genome-wide
KW - implementation study
KW - prenatal screening
KW - rare autosomal trisomies
UR - http://www.scopus.com/inward/record.url?scp=85075625045&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85075625045&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31708118
U2 - https://doi.org/10.1016/j.ajhg.2019.10.005
DO - https://doi.org/10.1016/j.ajhg.2019.10.005
M3 - Article
C2 - 31708118
SN - 0002-9297
VL - 105
SP - 1091
EP - 1101
JO - American journal of human genetics
JF - American journal of human genetics
IS - 6
ER -