Evaluating the Clinical Utility of Genomic Sequencing After Perinatal Death

Date

2025

Authors

Schubert, C.M.
Jackson, M.R.
Barnett, C.P.
Scott, H.S.
Sullivan, T.
Goodall, S.
Merlin, T.
Genomic Autopsy Study Research Network,

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Clinical Genetics, online, 2025; online(1)

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Camille M. Schubert, Matilda R. Jackson, Christopher P. Barnett, Hamish S. Scott, Thomas Sullivan, Stephen Goodall, Tracy Merlin, the Genomic Autopsy Study Research Network

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Abstract

Following termination of pregnancy for fetal anomaly or unexplained perinatal death (PND), clinical geneticists advise on possible genetic causes and likelihood of recurrence, often with limited use of molecular analysis. In the Australian Genomic Autopsy Study (GAS) cases that were unresolved following standard-of-care investigations underwent exome and/or genome sequencing (ES/GS). This diagnostic before-and-after study measured the changes in clinical management, in terms of the effect on clinical counselling that was provided to parents following ES/GS. Clinicians were surveyed before and after receiving sequencing results about the likelihood of recurrence and the reproductive planning advice they would provide to families. 161 pairs of before-and-after surveys were completed. Clinician estimates regarding PND recurrence changed for 45% (73/161) of families after receiving test results, despite a genetic diagnosis being found in only 19%. Families with an 'unknown likelihood' of recurrence reduced from 26% to 15% (p = 0.01). The information provided to parents about recurrence and reproductive planning increased significantly, both with and without a diagnosis, and clinicians reported that most parents expressed value was obtained from the investigation. The utility of genomic autopsy for clinical management is not restricted to families with a genetic finding.

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First published: 09 August 2025.\ OnlinePubl

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© 2025 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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