Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: An international cross-sectional study with healthcare professionals

Celine Lewis; Jennifer Hammond; Jasmijn E. Klapwijk; Eleanor Harding; Stina Lou; Ida Vogel; Emma J. Szepe; Lisa Hui; Charlotta Ingvoldstad-Malmgren; Maria J. Soller; Kelly E. Ormond; Mahesh Choolani; Melissa Hill; Sam Riedijk

doi:10.1002/pd.5932

Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: An international cross-sectional study with healthcare professionals

Celine Lewis^*
, Jennifer Hammond
, Jasmijn E. Klapwijk
, Eleanor Harding
, Stina Lou
, Ida Vogel
, Emma J. Szepe
, Lisa Hui
, Charlotta Ingvoldstad-Malmgren
, Maria J. Soller
, Kelly E. Ormond
, Mahesh Choolani
, Melissa Hill
, Sam Riedijk

^*Corresponding author for this work

Clinical Genetics

Great Ormond Street Institute of Child Health
University College London
Aarhus University Hospital
Royal Children's Hospital Melbourne
University of Melbourne
Mercy Hospital for Women
Metro North Health
Karolinska University Hospital
Stanford University School of Medicine
National University Hospital (Singapore)
Yong Loo Lin School of Medicine

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

26 Citations (Scopus)

48 Downloads (Pure)

Abstract

Objectives: To conduct qualitative interviews with healthcare providers working in different countries to understand their experiences of dealing with uncertain results from prenatal chromosome microarray analysis (CMA) and exome sequencing (ES). Methods: Semi-structured interviews with 31 healthcare providers who report or return prenatal CMA and/or ES results (clinicians, genetic counsellors and clinical scientists) in six countries with differing healthcare systems; Australia (4), Denmark (5), Netherlands (6), Singapore (4), Sweden (6) and United Kingdom (6). The topic guide explored the main sources of uncertainty and their management. Results: There was variation in reporting practices both between and across countries for variants of uncertain significance, however, there was broad agreement on reporting practices for incidental findings. There was also variation in who decides what results are reported (clinical scientists or clinicians). Technical limitations and lack of knowledge (to classify variants and of prenatal phenotypes) were significant challenges, as were turnaround times and lack of guidelines. Conclusion: Health professionals around the globe are dealing with similar sources of uncertainty, but managing them in different ways, Continued dialogue with international colleagues on ways of managing uncertain results is important to compare and contrast the benefits and limitations of the different approaches.

Original language	English
Pages (from-to)	720-732
Number of pages	13
Journal	Prenatal Diagnosis
Volume	41
Issue number	6
Early online date	16 Mar 2021
DOIs	https://doi.org/10.1002/pd.5932
Publication status	Published - May 2021

Bibliographical note

Funding Information:
This work was supported by a Wellcome Trust Small Grant in Humanities and Social Science [211288/Z/18/Z]. C. L. is funded by an NIHR Advanced Fellowship: NIHR300099. I. V. and S. L. are funded by a grant from the Novo Nordisk Foundation no: NNF16OC0018772. L. H. was funded by an Australian National Health and Medical Research Early Career Fellowship and a Medicine, Dentistry and Health Sciences Faculty Research Fellowship from the University of Melbourne. M. H. is partially funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the UK Department of Health. The authors would like to thank all the health professionals that took part in these interviews, without whom this work would not have been possible.

Funding Information:
This work was supported by a Wellcome Trust Small Grant in Humanities and Social Science [211288/Z/18/Z]. C. L. is funded by an NIHR Advanced Fellowship: NIHR300099. I. V. and S. L. are funded by a grant from the Novo Nordisk Foundation no: NNF16OC0018772. L. H. was funded by an Australian National Health and Medical Research Early Career Fellowship and a Medicine, Dentistry and Health Sciences Faculty Research Fellowship from the University of Melbourne. M. H. is partially funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the UK Department of Health. The authors would like to thank all the health professionals that took part in these interviews, without whom this work would not have been possible.

Publisher Copyright:
© 2021 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.

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Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal settingFinal published version, 309 KBLicence: CC BY

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Lewis, C., Hammond, J., Klapwijk, J. E., Harding, E., Lou, S., Vogel, I., Szepe, E. J., Hui, L., Ingvoldstad-Malmgren, C., Soller, M. J., Ormond, K. E., Choolani, M., Hill, M., & Riedijk, S. (2021). Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: An international cross-sectional study with healthcare professionals. Prenatal Diagnosis, 41(6), 720-732. https://doi.org/10.1002/pd.5932

@article{b522cd426db94564b4fe084257876771,

title = "Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: An international cross-sectional study with healthcare professionals",

abstract = "Objectives: To conduct qualitative interviews with healthcare providers working in different countries to understand their experiences of dealing with uncertain results from prenatal chromosome microarray analysis (CMA) and exome sequencing (ES). Methods: Semi-structured interviews with 31 healthcare providers who report or return prenatal CMA and/or ES results (clinicians, genetic counsellors and clinical scientists) in six countries with differing healthcare systems; Australia (4), Denmark (5), Netherlands (6), Singapore (4), Sweden (6) and United Kingdom (6). The topic guide explored the main sources of uncertainty and their management. Results: There was variation in reporting practices both between and across countries for variants of uncertain significance, however, there was broad agreement on reporting practices for incidental findings. There was also variation in who decides what results are reported (clinical scientists or clinicians). Technical limitations and lack of knowledge (to classify variants and of prenatal phenotypes) were significant challenges, as were turnaround times and lack of guidelines. Conclusion: Health professionals around the globe are dealing with similar sources of uncertainty, but managing them in different ways, Continued dialogue with international colleagues on ways of managing uncertain results is important to compare and contrast the benefits and limitations of the different approaches.",

author = "Celine Lewis and Jennifer Hammond and Klapwijk, \{Jasmijn E.\} and Eleanor Harding and Stina Lou and Ida Vogel and Szepe, \{Emma J.\} and Lisa Hui and Charlotta Ingvoldstad-Malmgren and Soller, \{Maria J.\} and Ormond, \{Kelly E.\} and Mahesh Choolani and Melissa Hill and Sam Riedijk",

note = "Funding Information: This work was supported by a Wellcome Trust Small Grant in Humanities and Social Science [211288/Z/18/Z]. C. L. is funded by an NIHR Advanced Fellowship: NIHR300099. I. V. and S. L. are funded by a grant from the Novo Nordisk Foundation no: NNF16OC0018772. L. H. was funded by an Australian National Health and Medical Research Early Career Fellowship and a Medicine, Dentistry and Health Sciences Faculty Research Fellowship from the University of Melbourne. M. H. is partially funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the UK Department of Health. The authors would like to thank all the health professionals that took part in these interviews, without whom this work would not have been possible. Funding Information: This work was supported by a Wellcome Trust Small Grant in Humanities and Social Science [211288/Z/18/Z]. C. L. is funded by an NIHR Advanced Fellowship: NIHR300099. I. V. and S. L. are funded by a grant from the Novo Nordisk Foundation no: NNF16OC0018772. L. H. was funded by an Australian National Health and Medical Research Early Career Fellowship and a Medicine, Dentistry and Health Sciences Faculty Research Fellowship from the University of Melbourne. M. H. is partially funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the UK Department of Health. The authors would like to thank all the health professionals that took part in these interviews, without whom this work would not have been possible. Publisher Copyright: {\textcopyright} 2021 The Authors. Prenatal Diagnosis published by John Wiley \& Sons Ltd.",

year = "2021",

month = may,

doi = "10.1002/pd.5932",

language = "English",

volume = "41",

pages = "720--732",

journal = "Prenatal Diagnosis",

issn = "0197-3851",

publisher = "John Wiley \& Sons Ltd.",

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Lewis, C, Hammond, J, Klapwijk, JE, Harding, E, Lou, S, Vogel, I, Szepe, EJ, Hui, L, Ingvoldstad-Malmgren, C, Soller, MJ, Ormond, KE, Choolani, M, Hill, M & Riedijk, S 2021, 'Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: An international cross-sectional study with healthcare professionals', Prenatal Diagnosis, vol. 41, no. 6, pp. 720-732. https://doi.org/10.1002/pd.5932

Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: An international cross-sectional study with healthcare professionals. / Lewis, Celine; Hammond, Jennifer; Klapwijk, Jasmijn E. et al.
In: Prenatal Diagnosis, Vol. 41, No. 6, 05.2021, p. 720-732.

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

TY - JOUR

T1 - Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting

T2 - An international cross-sectional study with healthcare professionals

AU - Lewis, Celine

AU - Hammond, Jennifer

AU - Klapwijk, Jasmijn E.

AU - Harding, Eleanor

AU - Lou, Stina

AU - Vogel, Ida

AU - Szepe, Emma J.

AU - Hui, Lisa

AU - Ingvoldstad-Malmgren, Charlotta

AU - Soller, Maria J.

AU - Ormond, Kelly E.

AU - Choolani, Mahesh

AU - Hill, Melissa

AU - Riedijk, Sam

N1 - Funding Information: This work was supported by a Wellcome Trust Small Grant in Humanities and Social Science [211288/Z/18/Z]. C. L. is funded by an NIHR Advanced Fellowship: NIHR300099. I. V. and S. L. are funded by a grant from the Novo Nordisk Foundation no: NNF16OC0018772. L. H. was funded by an Australian National Health and Medical Research Early Career Fellowship and a Medicine, Dentistry and Health Sciences Faculty Research Fellowship from the University of Melbourne. M. H. is partially funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the UK Department of Health. The authors would like to thank all the health professionals that took part in these interviews, without whom this work would not have been possible. Funding Information: This work was supported by a Wellcome Trust Small Grant in Humanities and Social Science [211288/Z/18/Z]. C. L. is funded by an NIHR Advanced Fellowship: NIHR300099. I. V. and S. L. are funded by a grant from the Novo Nordisk Foundation no: NNF16OC0018772. L. H. was funded by an Australian National Health and Medical Research Early Career Fellowship and a Medicine, Dentistry and Health Sciences Faculty Research Fellowship from the University of Melbourne. M. H. is partially funded by the NIHR Biomedical Research Centre at Great Ormond Street Hospital. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the Wellcome Trust, the NHS, the NIHR, or the UK Department of Health. The authors would like to thank all the health professionals that took part in these interviews, without whom this work would not have been possible. Publisher Copyright: © 2021 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.

PY - 2021/5

Y1 - 2021/5

N2 - Objectives: To conduct qualitative interviews with healthcare providers working in different countries to understand their experiences of dealing with uncertain results from prenatal chromosome microarray analysis (CMA) and exome sequencing (ES). Methods: Semi-structured interviews with 31 healthcare providers who report or return prenatal CMA and/or ES results (clinicians, genetic counsellors and clinical scientists) in six countries with differing healthcare systems; Australia (4), Denmark (5), Netherlands (6), Singapore (4), Sweden (6) and United Kingdom (6). The topic guide explored the main sources of uncertainty and their management. Results: There was variation in reporting practices both between and across countries for variants of uncertain significance, however, there was broad agreement on reporting practices for incidental findings. There was also variation in who decides what results are reported (clinical scientists or clinicians). Technical limitations and lack of knowledge (to classify variants and of prenatal phenotypes) were significant challenges, as were turnaround times and lack of guidelines. Conclusion: Health professionals around the globe are dealing with similar sources of uncertainty, but managing them in different ways, Continued dialogue with international colleagues on ways of managing uncertain results is important to compare and contrast the benefits and limitations of the different approaches.

AB - Objectives: To conduct qualitative interviews with healthcare providers working in different countries to understand their experiences of dealing with uncertain results from prenatal chromosome microarray analysis (CMA) and exome sequencing (ES). Methods: Semi-structured interviews with 31 healthcare providers who report or return prenatal CMA and/or ES results (clinicians, genetic counsellors and clinical scientists) in six countries with differing healthcare systems; Australia (4), Denmark (5), Netherlands (6), Singapore (4), Sweden (6) and United Kingdom (6). The topic guide explored the main sources of uncertainty and their management. Results: There was variation in reporting practices both between and across countries for variants of uncertain significance, however, there was broad agreement on reporting practices for incidental findings. There was also variation in who decides what results are reported (clinical scientists or clinicians). Technical limitations and lack of knowledge (to classify variants and of prenatal phenotypes) were significant challenges, as were turnaround times and lack of guidelines. Conclusion: Health professionals around the globe are dealing with similar sources of uncertainty, but managing them in different ways, Continued dialogue with international colleagues on ways of managing uncertain results is important to compare and contrast the benefits and limitations of the different approaches.

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U2 - 10.1002/pd.5932

DO - 10.1002/pd.5932

M3 - Article

C2 - 33724493

AN - SCOPUS:85103371594

SN - 0197-3851

VL - 41

SP - 720

EP - 732

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 6

ER -

Dealing with uncertain results from chromosomal microarray and exome sequencing in the prenatal setting: An international cross-sectional study with healthcare professionals

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