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

Yvette C Raymond¹, Shavi Fernando^{1

2}, Melody Menezes^{3

4}, Simon Meagher³, Ben W Mol^{1

2

5}, Andrew McLennan^{6

7}, Fergus Scott^{6

8}, Karen Mizia^{9

10}, Karen Carey⁶, Gabrielle Fleming⁹, Daniel Lorber Rolnik^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
² Monash Women's, Monash Health, Clayton, Victoria, Australia.
³ Monash Ultrasound for Women, Melbourne, Victoria, Australia.
⁴ Department of Pediatrics, The University of Melbourne, Melbourne, Victoria, Australia.
⁵ Aberdeen Centre for Women's Health Research, University of Aberdeen, Aberdeen, UK.
⁶ Sydney Ultrasound for Women, Sydney, New South Wales, Australia.
⁷ Discipline of Obstetrics, Gynaecology and Neonatology, The University of Sydney, Sydney, New South Wales, Australia.
⁸ School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
⁹ Ultrasound Care, Sydney, New South Wales, Australia.
¹⁰ Australian National University, Canberra, Australia.

PMID: 36068932
PMCID: PMC9826090
DOI: 10.1002/pd.6233

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

Yvette C Raymond et al. Prenat Diagn. 2022 Oct.

. 2022 Oct;42(11):1349-1357.

doi: 10.1002/pd.6233. Epub 2022 Sep 22.

Authors

Affiliations

¹ Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
² Monash Women's, Monash Health, Clayton, Victoria, Australia.
³ Monash Ultrasound for Women, Melbourne, Victoria, Australia.
⁴ Department of Pediatrics, The University of Melbourne, Melbourne, Victoria, Australia.
⁵ Aberdeen Centre for Women's Health Research, University of Aberdeen, Aberdeen, UK.
⁶ Sydney Ultrasound for Women, Sydney, New South Wales, Australia.
⁷ Discipline of Obstetrics, Gynaecology and Neonatology, The University of Sydney, Sydney, New South Wales, Australia.
⁸ School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
⁹ Ultrasound Care, Sydney, New South Wales, Australia.
¹⁰ Australian National University, Canberra, Australia.

PMID: 36068932
PMCID: PMC9826090
DOI: 10.1002/pd.6233

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.

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Conflict of interest statement

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.

Figures

**FIGURE 1**
Flow chart of data collection. †Parents declined either prenatal or postnatal diagnostic testing. Four RAT cases had structural/phenotype or chorionic villus sampling anomalies. ‡Participants delivered at inaccessible sites or still pregnant at the time of data collection. cfDNA, cell‐free DNA; DP, discordant positive; RAT, rare autosomal trisomy; SI, segmental imbalance; TP, true‐positive

**FIGURE 2**
Number of rare autosomal trisomies (RATs) detected, by chromosome

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources