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, 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. Jehee, Maarten F.C.M. Knapen & 21 others 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, The Dutch NIPT Consortium

Research output: Contribution to journalArticleAcademicpeer-review

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
Early online date31 Oct 2019
DOIs
Publication statusPublished - 5 Dec 2019

Cite this

van der Meij, Karuna R.M. ; Sistermans, Erik A. ; Macville, Merryn V.E. ; Stevens, Servi J.C. ; Bax, Caroline J. ; Bekker, Mireille N. ; Bilardo, Caterina M. ; Boon, Elles M.J. ; Boter, Marjan ; Diderich, Karin E.M. ; de Die-Smulders, Christine E.M. ; Duin, Leonie K. ; Faas, Brigitte H.W. ; Feenstra, Ilse ; Haak, Monique C. ; Hoffer, Mariëtte J.V. ; den Hollander, Nicolette S. ; Hollink, Iris H.I.M. ; Jehee, Fernanda S. ; Knapen, Maarten F.C.M. ; Kooper, Angelique J.A. ; van Langen, Irene M. ; Lichtenbelt, Klaske D. ; Linskens, Ingeborg H. ; van Maarle, Merel C. ; Oepkes, Dick ; Pieters, Mijntje J. ; Schuring-Blom, G. Heleen ; Sikkel, Esther ; Sikkema-Raddatz, Birgit ; Smeets, Dominique F.C.M. ; Srebniak, Malgorzata I. ; Suijkerbuijk, Ron F. ; Tan-Sindhunata, Gita M. ; van der Ven, A. Jeanine E.M. ; van Zelderen-Bhola, Shama L. ; Henneman, Lidewij ; Galjaard, Robert Jan H. ; Van Opstal, Diane ; Weiss, Marjan M. ; The Dutch NIPT Consortium. / TRIDENT-2 : National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands. In: American journal of human genetics. 2019 ; Vol. 105, No. 6. pp. 1091-1101.
@article{2b2b29d185a54bcba68ead64fa39ec42,
title = "TRIDENT-2: National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands",
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 = "cfDNA, common trisomies, fetal trisomy, first tier test, genome-wide, implementation study, NIPS, NIPT, prenatal screening, rare autosomal trisomies",
author = "{van der Meij}, {Karuna R.M.} and Sistermans, {Erik A.} and Macville, {Merryn V.E.} and Stevens, {Servi J.C.} and Bax, {Caroline J.} and Bekker, {Mireille N.} and Bilardo, {Caterina M.} and Boon, {Elles M.J.} and Marjan Boter and Diderich, {Karin E.M.} and {de Die-Smulders}, {Christine E.M.} and Duin, {Leonie K.} and Faas, {Brigitte H.W.} and Ilse Feenstra and Haak, {Monique C.} and Hoffer, {Mari{\"e}tte J.V.} and {den Hollander}, {Nicolette S.} and Hollink, {Iris H.I.M.} and Jehee, {Fernanda S.} and Knapen, {Maarten F.C.M.} and Kooper, {Angelique J.A.} and {van Langen}, {Irene M.} and Lichtenbelt, {Klaske D.} and Linskens, {Ingeborg H.} and {van Maarle}, {Merel C.} and Dick Oepkes and Pieters, {Mijntje J.} and Schuring-Blom, {G. Heleen} and Esther Sikkel and Birgit Sikkema-Raddatz and Smeets, {Dominique F.C.M.} and Srebniak, {Malgorzata I.} and Suijkerbuijk, {Ron F.} and Tan-Sindhunata, {Gita M.} and {van der Ven}, {A. Jeanine E.M.} and {van Zelderen-Bhola}, {Shama L.} and Lidewij Henneman and Galjaard, {Robert Jan H.} and {Van Opstal}, Diane and Weiss, {Marjan M.} and {The Dutch NIPT Consortium}",
note = "Copyright {\circledC} 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = "12",
day = "5",
doi = "10.1016/j.ajhg.2019.10.005",
language = "English",
volume = "105",
pages = "1091--1101",
journal = "American journal of human genetics",
issn = "0002-9297",
publisher = "Cell Press",
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van der Meij, KRM, Sistermans, EA, Macville, MVE, Stevens, SJC, Bax, CJ, Bekker, MN, Bilardo, CM, Boon, EMJ, Boter, M, Diderich, KEM, de Die-Smulders, CEM, Duin, LK, Faas, BHW, Feenstra, I, Haak, MC, Hoffer, MJV, den Hollander, NS, Hollink, IHIM, Jehee, FS, Knapen, MFCM, Kooper, AJA, van Langen, IM, Lichtenbelt, KD, Linskens, IH, van Maarle, MC, Oepkes, D, Pieters, MJ, Schuring-Blom, GH, Sikkel, E, Sikkema-Raddatz, B, Smeets, DFCM, Srebniak, MI, Suijkerbuijk, RF, Tan-Sindhunata, GM, van der Ven, AJEM, van Zelderen-Bhola, SL, Henneman, L, Galjaard, RJH, Van Opstal, D, Weiss, MM & The Dutch NIPT Consortium 2019, 'TRIDENT-2: National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands' American journal of human genetics, vol. 105, no. 6, pp. 1091-1101. https://doi.org/10.1016/j.ajhg.2019.10.005

TRIDENT-2 : National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands. / van der Meij, Karuna R.M.; Sistermans, Erik A.; Macville, Merryn V.E.; Stevens, Servi J.C.; Bax, Caroline J.; Bekker, Mireille N.; Bilardo, Caterina M.; Boon, Elles M.J.; Boter, Marjan; Diderich, Karin E.M.; de Die-Smulders, Christine E.M.; Duin, Leonie K.; Faas, Brigitte H.W.; Feenstra, Ilse; Haak, Monique C.; Hoffer, Mariëtte J.V.; den Hollander, Nicolette S.; Hollink, Iris H.I.M.; Jehee, Fernanda S.; Knapen, Maarten F.C.M.; Kooper, Angelique J.A.; van Langen, Irene M.; Lichtenbelt, Klaske D.; Linskens, Ingeborg H.; van Maarle, Merel C.; Oepkes, Dick; Pieters, Mijntje J.; Schuring-Blom, G. Heleen; Sikkel, Esther; Sikkema-Raddatz, Birgit; Smeets, Dominique F.C.M.; Srebniak, Malgorzata I.; Suijkerbuijk, Ron F.; Tan-Sindhunata, Gita M.; van der Ven, A. Jeanine E.M.; van Zelderen-Bhola, Shama L.; Henneman, Lidewij; Galjaard, Robert Jan H.; Van Opstal, Diane; Weiss, Marjan M.; The Dutch NIPT Consortium.

In: American journal of human genetics, Vol. 105, No. 6, 05.12.2019, p. 1091-1101.

Research output: Contribution to journalArticleAcademicpeer-review

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, 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 - The 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 - cfDNA

KW - common trisomies

KW - fetal trisomy

KW - first tier test

KW - genome-wide

KW - implementation study

KW - NIPS

KW - NIPT

KW - prenatal screening

KW - rare autosomal trisomies

UR - http://www.scopus.com/inward/record.url?scp=85075625045&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2019.10.005

DO - 10.1016/j.ajhg.2019.10.005

M3 - Article

VL - 105

SP - 1091

EP - 1101

JO - American journal of human genetics

JF - American journal of human genetics

SN - 0002-9297

IS - 6

ER -