Format

Send to

Choose Destination
Am J Hum Genet. 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.

Author information

1
Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081HV Amsterdam, the Netherlands.
2
Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081HV Amsterdam, the Netherlands. Electronic address: e.sistermans@amsterdamumc.nl.
3
Department of Clinical Genetics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, 6229HX, Maastricht, the Netherlands.
4
Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam, 1105AZ Amsterdam, the Netherlands.
5
Department of Obstetrics and Gynaecology, Utrecht University Medical Center, 3584CX Utrecht, the Netherlands.
6
Department of Obstetrics and Gynaecology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081HV Amsterdam, the Netherlands.
7
Department of Clinical Genetics, Erasmus Medical Center, 3015GD Rotterdam, the Netherlands.
8
Department of Obstetry and Gynaecology, University Medical Centre Groningen, University of Groningen, 9713GZ Groningen, the Netherlands.
9
Department of Genetics, Radboud Institute for Molecular Life Sciences, Radboud university medical Center, 6525GA Nijmegen, the Netherlands.
10
Department of Obstetrics, Leiden University Medical Center, 2333ZA Leiden, the Netherlands.
11
Department of Clinical Genetics, Leiden University Medical Center, 2333ZA Leiden, the Netherlands.
12
Department of Obstetrics and Fetal Medicine, Erasmus Medical Center, 3015GD Rotterdam, the Netherlands.
13
Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, 1105AZ Amsterdam, the Netherlands.
14
Department of Genetics, University Medical Centre Groningen, University of Groningen, 9713GZ Groningen, the Netherlands.
15
Department of Genetics, Utrecht University Medical Center, 3584CX Utrecht, the Netherlands.
16
Department of Obstetrics and Gynecology, Maastricht University Medical Center, 6229HX Maastricht, the Netherlands.
17
Department of Obstetrics and Gynecology, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands.
18
Verloskundigenpraktijk Velp, 6883AX Velp, 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:

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

PMID:
31708118
PMCID:
PMC6904791
[Available on 2020-06-05]
DOI:
10.1016/j.ajhg.2019.10.005

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center