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. 2022 Jun 2;109(6):1140-1152.
doi: 10.1016/j.ajhg.2022.04.018.

Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study

Lisanne van Prooyen Schuurman  1 , Erik A Sistermans  2 , Diane Van Opstal  3 , Lidewij Henneman  2 , Mireille N Bekker  4 , Caroline J Bax  5 , Mijntje J Pieters  6 , Katelijne Bouman  7 , Sonja de Munnik  8 , Nicolette S den Hollander  9 , Karin E M Diderich  3 , Brigitte H W Faas  8 , Ilse Feenstra  8 , Attie T J I Go  10 , Mariëtte J V Hoffer  9 , Marieke Joosten  3 , Fenne L Komdeur  2 , Klaske D Lichtenbelt  11 , Maria P Lombardi  2 , Marike G Polak  12 , Fernanda S Jehee  11 , Heleen Schuring-Blom  11 , Servi J C Stevens  13 , Malgorzata I Srebniak  3 , Ron F Suijkerbuijk  7 , Gita M Tan-Sindhunata  2 , Karuna R M van der Meij  2 , Merel C van Maarle  2 , Vivian Vernimmen  13 , Shama L van Zelderen-Bhola  2 , Nicolien T van Ravesteyn  14 , Maarten F C M Knapen  10 , Merryn V E Macville  13 , Robert-Jan H Galjaard  15 ; Dutch NIPT consortium
Affiliations

Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study

Lisanne van Prooyen Schuurman et al. Am J Hum Genet. .

Erratum in

  • Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study.
    van Prooyen Schuurman L, Sistermans EA, Van Opstal D, Henneman L, Bekker MN, Bax CJ, Pieters MJ, Bouman K, de Munnik S, den Hollander NS, Diderich KEM, Faas BHW, Feenstra I, Go ATJI, Hoffer MJV, Joosten M, Komdeur FL, Lichtenbelt KD, Lombardi MP, Polak MG, Jehee FS, Schuring-Blom H, Stevens SJC, Srebniak MI, Suijkerbuijk RF, Tan-Sindhunata GM, van der Meij KRM, van Maarle MC, Vernimmen V, van Zelderen-Bhola SL, van Ravesteyn NT, Knapen MFCM, Macville MVE, Galjaard RH; Dutch NIPT consortium. van Prooyen Schuurman L, et al. Am J Hum Genet. 2022 Jul 7;109(7):1344. doi: 10.1016/j.ajhg.2022.06.003. Am J Hum Genet. 2022. PMID: 35803237 Free PMC article. No abstract available.

Abstract

In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight <2.3rd percentile (13.6% [24/177] vs 2.5% [3,892/155,491]; RR 5.5) were significantly increased compared to the general obstetric population. Of the 90 maternal findings, 12 (13.3%) were malignancies and 32 (35.6%) (mosaic) pathogenic copy number variants, mostly associated with mild or no clinical phenotypes. Data from this large cohort study provide crucial information for deciding if and how to implement GW-NIPT in screening programs. Additionally, these data can inform the challenging interpretation, counseling, and follow-up of additional findings.

Keywords: NIPS; NIPT; cfDNA; common trisomies; confined placental mosaicism; fetal trisomy; first tier test; genome-wide; prenatal screening; rare autosomal trisomies.

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Conflict of interest statement

Declaration of interests E.A.S. was one of the applicants of the ZonMW grant and is a member of the GenQA advisory board (unpaid) and the associate editor of Extracellular Vesicles and Circulating Nucleic Acids. D.V.O. is a member of the project group NIPT additional findings and Project group NIPT Laboratories of the National Institute for Public Health & Environment (RIVM) – Center for Population Screening (CvB). L.H. was one of the applicants of the ZonMW grant. M.N.B. is a member of the project group NIPT additional findings, of the RIVM-CvB (unpaid). C.J.B. is a member of the project group NIPT additional findings, of the RIVM-CvB (unpaid). M.J.P. is a member of the Project group NIPT Quality, and Project group NIPT additional findings, all of the RIVM-CvB (unpaid). M.V.E.M. is a member of the Program Committee Prenatal Screening, Project group NIPT Quality, and Project group NIPT Laboratories, all of the RIVM-CvB (unpaid). Part of the ZonMW grant was paid to his institution for TRIDENT-2 bio-informatic research. R.-J.H.G. was one of the applicants of the ZonMW grant, and he is a member of the Program Committee Prenatal Screening, Project group NIPT Quality, and Project group NIPT additional findings, all of the RIVM-CvB (unpaid).

Figures

Figure 1
Figure 1
Origin of additional findings per chromosome Rare autosomal trisomies (upper panel) and structural chromosome aberrations (lower panel). CPM, confined placental mosaicism; SA, structural aberration; T, trisomy.
See this image and copyright information in PMC

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