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The last data from the TRIDENT-2 (Trial by Dutch Laboratories for Evaluation of Noninvasive Prenatal Testing-2) study, conducted by the Dutch NIPT Consortium and recently published on the American Journal of Human Genetics, demonstrates the clinical usefulness of Genome-Wide Non-Invasive Prenatal Testing (GW-NIPT), highlighting the test’s ability to detect pathogenic chromosomal abnormalities associated with diseases, sometimes severe, that cannot be revealed as a malformation on a second trimester ultrasound. Also, results show that about half of the findings that would not be detected by other, more traditional, non-invasive prenatal screenings could be associated with adverse perinatal outcomes, such as pre-eclampsia and low birth weight.

NIPT and GW-NIPT: the differences

NIPT is a method of determining the risk of genetic abnormalities in the fetus based on the analysis of cell-free DNA (cfDNA) circulating in a pregnant woman’s blood. Starting from 10 weeks of pregnancy, maternal blood contains quantities of placental DNA that are sufficient for being detected and efficiently analyzed. Since placental and fetal DNA are usually identical, analyzing cfDNA from the placenta allows for detecting genetic abnormalities in the fetus.

The primary target of NIPT are chromosomal disorders caused by an extra or missing chromosome (aneuploidies); in particular, “traditional” NIPT allows for detecting trisomy 21, trisomy 18, trisomy 13, and X and Y chromosome aneuploidies. Other approaches to NIPT include the analysis of additional chromosomal disorders; in particular, GW-NIPT enables additional findings by detecting chromosomal abnormalities other than trisomies 21, 18, 13, and X and Y aneuploidies by screening every chromosome.

The Dutch NIPT Consortium has already demonstrated the reliability and accuracy of GW-NIPT for trisomy 21, 18, and 13 detection, and its ability to unveil the origin of these less common chromosomal aberrations. In fact, detected abnormalities can be localized on maternal or fetal DNA, or even on cfDNA of exclusively placental origin – a condition, the latter, known as “confined placental mosaicism”. Newly published data highlight the clinical impact of additional information from GW-NIPT.

TRIDENT-2: the study

TRIDENT-2 is the phase 2 of an implementation study aimed at determining «whether and how NIPT should be offered within the national prenatal screening program in the Netherlands». All pregnant women in the country were offered the non-invasive prenatal testing, letting them choose between limiting the analysis to the presence of the common trisomies 21, 18, and 13 and accessing GW-NIPT.

Additional findings are received by about 1 in every 275 women who opted for GW-NIPT. Among these findings, the majority have a clinical impact. In particular:

  • fetal chromosomal aberrations are usually pathogenic, and clinical consequences are usually severe;
  • aberrations confined to the placenta (e.g.: trisomy 16 and 20) are significantly associated with adverse perinatal issues such as pre-eclampsia and low birth weight;
  • maternal findings are usually associated with maternal malignancies.

In 10.9% of cases, the origin of the additional finding could not be determined. In 1 case, the pregnancy ended in an intra-uterine fetal demise in the 1st trimester; in 2 cases, the genetic abnormalities were associated with major structural congenital abnormalities.

GW-NIPT, usefulness confirmed

As concluded by the authors of the study, «the majority of additional findings identified by GW-NIPT have clinical impact». Whether it is a fetal chromosomal abnormality associated with a pathology, an aberration confined to the placenta that should prompt sending pregnant women to tailored obstetric care to monitor for increased complication risk, or a maternal abnormality linked to a mother’s health issue, the vast majority of these additional finding can inform parents’ and clinician’s decisions about the pregnancy.

In the past, experts have highlighted how challenging it could be implementing GW-NIPT in the clinic. For example, according to Mirette Saad, Associate Professor and a Consultant Chemical Pathologist and the National Clinical Director of Molecular Genetic Pathology at Australian Clinical Labs, the test’s benefits must be balanced against the risk of discordant positives and parental anxiety. TRIDENT-2 authors also recognize that the variety of chromosome abnormalities detected by GW-NIPT adds complexity to pre- and post-test counseling. «Only a certified geneticist or an appropriately trained counselor can tell a patient how to manage such complex results», Giuseppe Mucci, Bioscience Institute CEO, comments.

Bioscience Genomics, the spin-off of the “Tor Vergata” University (Rome) participated by Bioscience Institute, offers the most validated (146,958 pregnancies, more than 3 million tests in more than 52 Countries worldwide) non-invasive prenatal test (UltraNIPT), together with pre-testing counseling and, in case of chromosome abnormalities detection, a contribution for the post-testing genetic counseling or in-depth diagnostic. «Available data show UltraNIPT works with a sensitivity greater than 99%; that means our test can correctly detect the searched genetic abnormalities in the fetus in more than 99% of cases. Only in 0.0069% of cases is impossible to have test results – the smallest “no call” for a fetal DNA test. And false positives (that is, the cases in which a high-risk result is not confirmed) are at 0.04-0.05%. UltraNIPT’s reliability is so high», Mucci concludes, «to allow us to give our customers access to a totally free insurance policy».

For more information about Bioscience Institute’s prenatal screening programs, please visit G-Test, UltraNIPT110, UltraNIPT DG, and OMNIPT web pages, contact us at info@bioinst.com, or call us at +971 (0)4 375 722: our biologist will answer your questions without commitment on your part.

References

  • van Prooyen Schuurman L et al. Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study. Am J Hum Genet. 2022 Jun 2;109(6):1140-1152. doi: 10.1016/j.ajhg.2022.04.018
  • Bilardo CM. The implementation of non-invasive prenatal testing (NIPT) in the Netherlands. J Perinat Med. 2021 Jul 13;49(8):941-944. doi: 10.1515/jpm-2021-0290
  • van der Meij KRM et al. TRIDENT-2: National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands. Am J Hum Genet. 2019 Dec 5;105(6):1091-1101. doi: 10.1016/j.ajhg.2019.10.005
  • Saad M. Targeted approach versus genome-wide non-invasive prenatal testing. Australian Clinicalabs.
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