National Implementation of Genome-Wide Non-Invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands

Several European countries are experimenting with the widespread introduction of NIPT (non-invasive prenatal testing) instead of standard prevalence screen. Netherlands nationwide study has also been conducted to introduce NIPT as a first-level test for all pregnant women. The experimental results indicate the high potential of this type of screening.

This study 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. The number of additional findings was 207 (0.36%); these included other , structural chromosomal aberrations and complex abnormal profiles indicative of maternal malignancies.

 “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”.

As TRIDENT-2 will continue until April 2023, we will collect and publish more relevant data on additional findings (including clinical and molecular follow-up performed both during and after pregnancy in confirmed fetal cases and cases with CPM). This will allow us to set specific guidelines for pre- and post-test counseling, and for clinical and laboratory follow-up for the most common additional findings.

The article was published in The American Journal of Human Genetics.