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      Assessing women’s preferences towards tests that may reveal uncertain results from prenatal genomic testing: Development of attributes for a discrete choice experiment, using a mixed-methods design

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          Abstract

          Prenatal DNA tests, such as chromosomal microarray analysis or exome sequencing, increase the likelihood of receiving a diagnosis when fetal structural anomalies are identified. However, some parents will receive uncertain results such as variants of uncertain significance and secondary findings. We aimed to develop a set of attributes and associated levels for a discrete-choice experiment (DCE) that will examine parents’ preferences for tests that may reveal uncertain test results. A two phase mixed-methods approach was used to develop attributes for the DCE. In Phase 1, a “long list” of candidate attributes were identified via two approaches: 1) a systematic review of the literature around parental experiences of uncertainty following prenatal testing; 2) 16 semi-structured interviews with parents who had experienced uncertainty during pregnancy and 25 health professionals who return uncertain prenatal results. In Phase 2, a quantitative scoring exercise with parents prioritised the candidate attributes. Clinically appropriate levels for each attribute were then developed. A final set of five attributes and levels were identified: likelihood of getting a result, reporting of variants of uncertain significance, reporting of secondary findings, time taken to receive results, and who tells you about your result. These attributes will be used in an international DCE study to investigate preferences and differences across countries. This research will inform best practice for professionals supporting parents to manage uncertainty in the prenatal setting.

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          Most cited references47

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          Chromosomal microarray versus karyotyping for prenatal diagnosis.

          Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down's syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.).
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            Qualitative research in health care. Assessing quality in qualitative research.

            N Mays, C Pope (2000)
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              Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study

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                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 January 2022
                2022
                : 17
                : 1
                : e0261898
                Affiliations
                [1 ] North Thames Genomic Laboratory Hub, Great Ormond Street Hospital, London, United Kingdom
                [2 ] Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
                [3 ] Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
                [4 ] Center for Fetal Diagnostics, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
                [5 ] Department of Genetics and Stanford Center for Biomedical Ethics, Stanford University School of Medicine, Stanford, CA, United States America
                [6 ] Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
                [7 ] Department of Perinatal Medicine, Mercy Hospital for Women, Heidelberg, Victoria, Australia
                [8 ] Department of Obstetrics and Gynaecology, Northern Health, Epping, VIC, Australia
                [9 ] Reproductive Epidemiology, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia
                [10 ] Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
                [11 ] Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, England, United Kindom
                [12 ] National Institute for Health Research Oxford Biomedical Research Centre, Oxford, England, United Kindom
                [13 ] Department of Clinical Genetics, Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden
                [14 ] Center for Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden
                [15 ] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
                [16 ] BSc Paediatrics and Child Health, The UCL Great Ormond Street Institute of Child Health, London, United Kingdom
                Children’s Hospital of Los Angeles, UNITED STATES
                Author notes

                Competing Interests: The authors have read the journal’s policy and have the following competing interests: JB received travel support from Illumina to attend conferences. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                [¤a]

                Current address: Health Ethics and Policy Lab, Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland

                [¤b]

                Current address: Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom

                ‡ JH and JEK share first authorship on this work. MH and CL are joint senior authors on this work.

                Author information
                https://orcid.org/0000-0002-6775-6561
                https://orcid.org/0000-0002-1033-0818
                https://orcid.org/0000-0001-7169-1521
                Article
                PONE-D-21-12941
                10.1371/journal.pone.0261898
                8797177
                35089945
                4cff967e-0999-4d0b-a0b7-bb6393d7228f
                © 2022 Hammond et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 April 2021
                : 14 December 2021
                Page count
                Figures: 1, Tables: 4, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 211288/Z/18/Z
                Award Recipient :
                CL received a Wellcome Trust Small Grant in Humanities and Social Science to conduct this work (grant number 211288/Z/18/Z). https://wellcome.org/grant-funding/schemes/small-grants-humanities-and-social-science JB received travel support from Illumina to attend conferences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Genetics
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                Medicine and Health Sciences
                Women's Health
                Maternal Health
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