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

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
6 Downloads (Pure)


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 languageEnglish
Pages (from-to)1349-1357
Number of pages9
JournalPrenatal Diagnosis
Issue number11
Early online date22 Sept 2022
Publication statusPublished - 18 Oct 2022

Bibliographical 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.

Data Availability Statement

The data gathered in this study has not been made publicly available to protect the privacy of participants. For data enquiries, please contact corresponding author Yvette Raymond.


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