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, Erik A Sistermans, Diane Van Opstal, Lidewij Henneman, Mireille N Bekker, Caroline J Bax, Mijntje J Pieters, Katelijne Bouman, Sonja de Munnik, Nicolette S den Hollander, Karin E M Diderich, Brigitte H W Faas, Ilse Feenstra, Attie T J I Go, Mariëtte J V Hoffer, Marieke Joosten, Fenne L Komdeur, Klaske D Lichtenbelt, Maria P Lombardi, Marike G PolakFernanda S Jehee, Heleen Schuring-Blom, Servi J C Stevens, Malgorzata I Srebniak, Ron F Suijkerbuijk, Gita M Tan-Sindhunata, Karuna R M van der Meij, Merel C van Maarle, Vivian Vernimmen, Shama L van Zelderen-Bhola, Nicolien T van Ravesteyn, Maarten F C M Knapen, Merryn V E Macville, Robert-Jan H Galjaard*, Dutch NIPT Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1140-1152
Number of pages14
JournalAmerican Journal of Human Genetics
Volume109
Issue number6
DOIs
Publication statusPublished - 2 Jun 2022

Keywords

  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Mosaicism
  • Placenta
  • Pregnancy
  • Prenatal Diagnosis/methods
  • Trisomy
  • PREECLAMPSIA
  • CELL-FREE DNA

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