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 - 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, Mariette 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 - Funding Information:
The authors would like to thank all participating women for their contribution to the TRIDENT-2 study. Moreover, we thank all who have contributed to the set-up and execution of the study, including health professionals, laboratory staff, and other supporting staff. Staff members of RIVM/CvB, the Regional Centers for Prenatal Screening, and Peridos are acknowledged for their collaboration. Sandra van ‘t Padje is acknowledged for all her work as functional manager of the Consortium. This work was supported by a grant from the Netherlands Organization for Health Research and Development ( ZonMw, No. 543002001 ).
Publisher Copyright:
© 2019 American Society of Human Genetics
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 - CELL-FREE DNA
KW - PREGNANT-WOMEN
KW - DOWN-SYNDROME
KW - HEALTH
KW - ORGANIZATION
KW - EXPERIENCE
KW - IMPACT
U2 - 10.1016/j.ajhg.2019.10.005
DO - 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 -