Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Summary and recommendations

European Journal of Human Genetics (2015), 1–3 & 2015 Macmillan Publishers Limited All rights reserved 1018-4813/15 www.nature.com/ejhg POLICY Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Summary and recommendations Wybo Dondorp*,1, Guido de Wert1, Yvonne Bombard2, Diana W Bianchi3, Carsten Bergmann4,5, Pascal Borry6, Lyn S Chitty7, Florence Fellmann8, Francesca Forzano9, Alison Hall10, Lidewij Henneman11, Heidi C Howard12, Anneke Lucassen13, Kelly Ormond14, Borut Peterlin15, Dragica Radojkovic16, Wolf Rogowski17, Maria Soller18, Aad Tibben19, Lisbeth Tranebjærg20,21,22, Carla G van El11 and Martina C Cornel11 on behalf of the European Society of Human Genetics (ESHG) and the American Society of Human Genetics (ASHG) European Journal of Human Genetics advanced online publication, 1 April 2015; doi:10.1038/ejhg.2015.56 INTRODUCTION This paper contains a summary and the recommendations of a joint European Society of Human Genetics (ESHG)/American Society of Human Genetics (ASHG) position statement on responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). This statement was drafted by the Public and Professional Policy Committee of the ESHG and the Social Issues Committee of the ASHG, and endorsed by the boards of both societies in December 2014. The statement is also endorsed by the Human Genetics Society of Australasia, the Australasian Association of Clinical Geneticists, the British Society for Genetic Medicine, the Czech Medical Genetics Society, and the PHG Foundation (Cambridge, UK). The full document with extensive references is published separately.1 SUMMARY OF THE ESHG/ASHG POSITION STATEMENT This ESHG/ASHG position statement takes as its starting point the internationally endorsed normative framework for prenatal screening, stressing that the aim of the practice should be to facilitate informed reproductive choices rather than preventing the birth of children with specific abnormalities, and that the benefits for those tested should clearly outweigh any harms. Moreover, when screening is offered as a public health programme, societal and justice aspects need to be taken into account. This includes possible consequences for other individuals and groups (including those living with the relevant conditions), as well as cost-effectiveness of publicly funded services. In the past few years, professional bodies and policy authorities have recommended offering NIPT for common aneuploidies to women who belong to a higher risk group, either based on maternal age or a positive combined first trimester screening test (cFTS). With recent publications suggesting equally good test performance in lower-risk populations, and depending on the health care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible, including NIPT as an alternative first-tier test. The greater accuracy and lower invasive follow-up testing rate that can thus be achieved, has the potential of helping prenatal screening better achieve its aim, provided that balanced pre-test information and non-directive counseling are available as part of the screening offer. Concerns have been raised that as a result of these same features (greater accuracy and lower invasive follow-up testing rate), prenatal screening may increasingly be regarded both by professionals and pregnant women as a routine procedure that as such would not require much reflection. This may have the consequence that women or couples are insufficiently prepared for the possible eventual diagnosis of a fetus with a serious disorder. Avoiding such ‘routinisation’ effects may well be the greatest ethical challenge of NIPT-based prenatal screening. Depending on the use of targeted or non-targeted analysis and on the level of resolution, NIPT for common autosomal aneuploidies may 1 Department of Health, Ethics & Society, Research Schools CAPHRI and GROW, Maastricht University, Maastricht, The Netherlands; 2Li Ka Shing Knowledge Institute of St. Michael’s Hospital & Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto,Toronto, ON, Canada; 3Department of Pediatrics, Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA, USA; 4Center for Human Genetics Bioscientia, Ingelheim, Germany; 5Department of Medicine, University Freiburg Medical Center, Freiburg, Germany; 6Department of Public Health and Primary Care, Centre for Biomedical Ethics and Law, Leuven University, Leuven, Belgium; 7Clinical and Molecular Genetics Unit, UCL Institute of Child Health, Great Ormond Street Hospital and UCLH NHS Foundations Trusts, London, UK; 8Service of Medical Genetics, University Hospital of Lausanne, Lausanne, Switzerland; 9Medical Genetics Unit, Ospedali Galliera, Genova, Italy; 10PHG Foundation, Cambridge, UK; 11Section Community Genetics, Department of Clinical Genetics and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; 12Centre for Research Ethics and Bioethics, Uppsala University, Uppsala, Sweden; 13Department of clinical ethics and law (CELS), University of Southampton and Wessex Clinical Genetic Service, Southampton, UK; 14Department of Genetics and Stanford Center for Biomedical Ethics, Stanford University School of Medicine, Stanford, CA, USA; 15Clinical Institute of Medical Genetics, Ljubljana University Medical Centre, Ljubljana, Slovenia; 16Laboratory for Molecular Biology, Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, Belgrade, Serbia; 17Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum, München, Germany; 18Division Clinical Genetics, University and Regional Laboratories Region Skåne, Lund University Hospital, Lund, Sweden; 19Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands; 20Department of Audiology, Bispebjerg Hospital/Rigshospitalet, Copenhagen, Denmark; 21Department of Clinical Genetics/The Kennedy Center, University of Copenhagen, Copenhagen, Denmark; 22Institute of Cellular and Molecular Medicine, ICMM, University of Copenhagen, Copenhagen, Denmark *Correspondence: Dr W Dondorp, Department of Health, Ethics & Society, Research Schools CAPHRI and GROW, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands. Tel: +31 43 3881712; Fax: +31 43 3670932; E-mail: Received 23 December 2014; revised 15 February 2015; accepted 19 February 2015 Responsible innovation in prenatal screening. Summary W Dondorp et al 2 lead to findings of abnormalities in other chromosomes, including submicroscopic abnormalities. This is not a new problem: such findings also emerge at follow-up testing after positive cFTS. However, at the NIPT stage, they precede decision making about invasive testing. This may entail putting the pregnancy at risk for confirming findings that not only have a (...truncated)