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

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

doi:10.1016/j.ajhg.2022.06.003

Cited by 15 publications

(31 citation statements)

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“…This should include an assessment of the proportion of abnormal cells in cases with, and without, adverse outcomes. [28][29][30][31] The PPV for SI was consistent with previous studies. [26][27][28] We found that 2/7 confirmed SI were benign because the imbalance was present in the genome of an apparently normal mother.…”

Section: Discussionsupporting

confidence: 91%

“…[28][29][30][31] The PPV for SI was consistent with previous studies. [26][27][28] We found that 2/7 confirmed SI were benign because the imbalance was present in the genome of an apparently normal mother. In addition, in 13.8% (4/29), the high-risk results were attributable to a genetic imbalance present only in the maternal genome and not in the fetus.…”

Section: Discussionsupporting

confidence: 91%

“…This PPV was higher than previously reported (4%-6%) in a study where the genome-wide approach was applied as nationwide first-tier non-invasive prenatal screening. [26][27][28] Most of the confirmed RATs in our study showed a mosaic fetal karyotype, which is typically associated with a high level of uncertainty due to the -1583…”

Section: Discussionmentioning

confidence: 64%

“…Confirmation of a RAT, even in AF cells, is not necessarily indicative of an abnormal phenotype. 28 Our survey did not seek phenotype information for these pregnancies. Moreover, non-mosaic RATs identified by NIPT would be expected to spontaneously abort and generally, not come to our attention.…”

Section: Discussionmentioning

confidence: 99%

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Positive predictive values and outcomes for uninformative cell‐free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study)

Grati¹,

Bestetti

Siero³

et al. 2022

Prenatal Diagnosis

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Objectives To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories. Methods Prenatal diagnostic test results obtained by Italian laboratories between 2013 and March 2020 were compiled for women with positive non‐invasive prenatal tests (NIPT), without an NIPT result, and cases where there was sex discordancy between the NIPT and ultrasound. PPV and other summary data were reviewed. Results Diagnostic test results were collected for 1327 women with a positive NIPT. The highest PPVs were for Trisomy (T) 21 (624/671, 93%) and XYY (26/27, 96.3%), while rare autosomal trisomies (9/47, 19.1%) and recurrent microdeletions (8/55, 14.5%) had the lowest PPVs. PPVs for T21, T18, and T13 were significantly higher when diagnostic confirmation was carried out on chorionic villi (97.5%) compared to amniotic fluid (89.5%) (p < 0.001). In 19/139 (13.9%), of no result cases, a cytogenetic abnormality was detected. Follow‐up genetic testing provided explanations for 3/6 cases with a fetal sex discordancy between NIPT and ultrasound. Conclusions NIPT PPVs differ across the conditions screened and the tissues studied in diagnostic testing. This variability, issues associated with fetal sex discordancy, and no results, illustrate the importance of pre‐ and post‐test counselling.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

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Positive predictive values and outcomes for uninformative cell‐free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study)

Grati¹,

Bestetti

Siero³

et al. 2022

Prenatal Diagnosis

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“…The clinical utility of cfDNA screening for SIs is complex. Although suggested improvements for the provision of genome‐wide cfDNA screening include restricting referrals for invasive diagnostic testing to high‐risk results accompanied by ultrasound anomalies due to the lower PPV for rare anomalies, this approach risks misclassifying clinically significant true‐positive results as many SIs may not present with abnormal ultrasound findings, as demonstrated in the current study 37 . However, even when successfully identified, the variable phenotypic consequences are a challenge for genetic counselling 38,39 …”

Section: Discussionmentioning

confidence: 85%

Cell‐free DNA screening for rare autosomal trisomies and segmental chromosome imbalances

et al. 2022

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Objective: To assess the outcomes of pregnancies at high-risk for rare autosomal trisomies (RATs) and segmental imbalances (SIs) on cell-free DNA (cfDNA) screening.Method: A retrospective study of women who underwent cfDNA screening between September 2019 and July 2021 at three ultrasound services in Australia.Positive predictive values (PPVs) were calculated using fetal chromosomal analysis.Results: Among 23,857 women screened, there were 93 high-risk results for RATs (0.39%) and 82 for SIs (0.34%). The PPVs were 3.8% (3/78, 95% CI 0.8%-10.8%) for RATs and 19.1% (13/68, 95% CI 10.6%-30.5%) for SIs. If fetuses with structural anomalies were also counted as true-positive cases, the PPV for RATS increased to 8.5% (7/82, 95% CI 3.5%-16.8%). Among 85 discordant cases with birth outcomes available (65.4%), discordant positive RATs had a significantly higher proportion of infants born below the 10th and 3rd birthweight percentiles than expected (19.6% (p = 0.022) and 9.8% (p = 0.004), respectively), which was not observed in the SI group (2.9% < 10th (p = 0.168) and 0.0% <3rd (p = 0.305)). Conclusion:The PPVs for SI and RAT results are low, except when a structural abnormality is also present. Discordant positive RATs are associated with growth restriction. Key points What is already known about this topic?� Prenatal cell-free DNA (cfDNA) screening has high accuracy in screening for trisomies 21, 18 and 13. � The positive predictive values of cfDNA screening for rare autosomal. Trisomies rare autosomal trisomies (RATs) and segmental imbalances (SIs) are lower than that for common autosomal trisomies. � Fetal exclusion of chromosomal anomaly following high-risk cfDNA screen may indicate confined placental involvement.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Issues associated with possible implementation of Non‐Invasive Prenatal Testing (NIPT) in first‐tier screening: A rapid scoping review

et al. 2023

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In recent years, as the implementation and use of Non‐Invasive Prenatal Testing (NIPT) have increased, the cost of the test has been decreasing. The cost of NIPT is expected to fall further in the upcoming years. As a result of the decreasing cost of NIPT, many jurisdictions may change their prenatal screening policies toward abandoning serum‐based screening and instead, implement and support NIPT as the first‐tier screening for all women. There are several concerns in replacing first‐trimester screening with NIPT. In this scoping review, we aimed to map the existing knowledge about possible issues in the systematic implementation of NIPT as the primary method of first‐tier screening and to assess if any jurisdiction has altered its policy and discontinued serum‐based prenatal screening in exchange for NIPT. The Medline database (Ovid) and Google Scholar was searched and all the studies discussing, investigating, or reporting on the systematic implementation of NIPT as the primary method of first‐tier screening were included. All the studies went through a two‐stage screening process and included full‐text articles were reviewed. We did not find any articles indicating a country or region that replaced traditional prenatal screening by NIPT. The included articles were charted, and the data about the possible issues in the systematic implementation of NIPT as the primary method of first‐tier screening are summarized narratively and presented in tables in four categories. The findings of this scoping review may be informative for stakeholders and policymakers regarding recent changes in NIPT implementation policies around the world and may aid with developing policy for NIPT implementation with a broader perspective.

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

Cited by 15 publications

References 0 publications

Positive predictive values and outcomes for uninformative cell‐free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study)

Positive predictive values and outcomes for uninformative cell‐free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study)

Cell‐free DNA screening for rare autosomal trisomies and segmental chromosome imbalances

Issues associated with possible implementation of Non‐Invasive Prenatal Testing (NIPT) in first‐tier screening: A rapid scoping review

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