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

The Dutch NIPT Consortium, Dutch NIPT Consortium

Research output: Contribution to JournalArticleAcademicpeer-review

125 Citations (Scopus)

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

Keywords

  • Adolescent
  • Adult
  • Chromosome Aberrations
  • Down Syndrome/diagnosis
  • Female
  • Follow-Up Studies
  • Genetic Testing/methods
  • Genome, Human
  • Health Plan Implementation
  • Humans
  • Middle Aged
  • NIPS
  • NIPT
  • Netherlands/epidemiology
  • Pregnancy
  • Pregnancy Trimester, First
  • Prenatal Diagnosis/methods
  • Prognosis
  • Trisomy 13 Syndrome/diagnosis
  • Trisomy 18 Syndrome/diagnosis
  • Young Adult
  • cfDNA
  • common trisomies
  • fetal trisomy
  • first tier test
  • genome-wide
  • implementation study
  • prenatal screening
  • rare autosomal trisomies

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