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

Yvette C. Raymond; Shavi Fernando; Melody Menezes; Simon Meagher; Ben W. Mol; Andrew McLennan; Fergus Scott; Karen Mizia; Karen Carey; Gabrielle Fleming; Daniel Lorber Rolnik

doi:10.1002/pd.6233

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

Yvette C. Raymond^*, Shavi Fernando, Melody Menezes, Simon Meagher, Ben W. Mol, Andrew McLennan, Fergus Scott, Karen Mizia, Karen Carey, Gabrielle Fleming, Daniel Lorber Rolnik

^*Corresponding author for this work

Applied Health Sciences

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1349-1357
Number of pages	9
Journal	Prenatal Diagnosis
Volume	42
Issue number	11
Early online date	22 Sep 2022
DOIs	https://doi.org/10.1002/pd.6233
Publication status	Published - 18 Oct 2022

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@article{f8eedce6f93e47fe81843cf5a83df3b9,

title = "Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances",

abstract = "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.",

author = "Raymond, {Yvette C.} and Shavi Fernando and Melody Menezes and Simon Meagher and Mol, {Ben W.} and Andrew McLennan and Fergus Scott and Karen Mizia and Karen Carey and Gabrielle Fleming and Rolnik, {Daniel Lorber}",

note = "Funding Information: Ben W. Mol is supported by a NHMRC Investigator grant (GNT1176437). Ben W. Mol reports consultancy for ObsEva and Merck and travel support and research grants from Merck. The authors declare no conflict of interest. The authors wish to acknowledge the staff of Monash Ultrasound for Women, Sydney Ultrasound for Women, and Ultrasound Care for their diligent and compassionate care of the women involved in this study. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians. ",

year = "2022",

month = oct,

day = "18",

doi = "10.1002/pd.6233",

language = "English",

volume = "42",

pages = "1349--1357",

journal = "Prenatal Diagnosis",

issn = "0197-3851",

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TY - JOUR

T1 - Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances

AU - Raymond, Yvette C.

AU - Fernando, Shavi

AU - Menezes, Melody

AU - Meagher, Simon

AU - Mol, Ben W.

AU - McLennan, Andrew

AU - Scott, Fergus

AU - Mizia, Karen

AU - Carey, Karen

AU - Fleming, Gabrielle

AU - Rolnik, Daniel Lorber

N1 - Funding Information: Ben W. Mol is supported by a NHMRC Investigator grant (GNT1176437). Ben W. Mol reports consultancy for ObsEva and Merck and travel support and research grants from Merck. The authors declare no conflict of interest. The authors wish to acknowledge the staff of Monash Ultrasound for Women, Sydney Ultrasound for Women, and Ultrasound Care for their diligent and compassionate care of the women involved in this study. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians.

PY - 2022/10/18

Y1 - 2022/10/18

N2 - 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.

AB - 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.

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U2 - 10.1002/pd.6233

DO - 10.1002/pd.6233

M3 - Article

C2 - 36068932

AN - SCOPUS:85138557534

VL - 42

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JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

SN - 0197-3851

IS - 11

ER -

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

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