Résumés
Abstract
Non-invasive prenatal testing (NIPT) using cell-free fetal DNA (cffDNA) from maternal blood has recently entered clinical practice in many countries, including Canada. This test can be performed early during pregnancy to detect Down syndrome and other conditions. While NIPT promises numerous benefits, it also has challenging ethical, legal and social implications (ELSI). This paper reviews concerns currently found in the literature on the ELSI of NIPT. We make four observations. First, NIPT seems to exacerbate some of the already existing concerns raised by other prenatal tests (amniocentesis and maternal serum screening) such as threats to women’s reproductive autonomy and the potential for discrimination and stigmatization of disabled individuals and their families. This may be due to the likely upcoming large scale implementation and routinization of NIPT. Second, the distinction between NIPT as a screening test (as it is currently recommended) and as a diagnostic test (potentially in the future), has certain implications for the ELSI discussion. Third, we observed a progressive shift in the literature from initially including mostly conceptual analysis to an increasing number of empirical studies. This demonstrates the contribution of empirical bioethics approaches as the technology is being implemented into clinical use. Finally, we noted an increasing interest in equity and justice concerns regarding access to NIPT as it becomes more widely implemented.
Keywords:
- non-invasive prenatal testing (NIPT),
- ethical legal and social issues (ELSI),
- reproductive autonomy,
- informed consent,
- pregnancy termination,
- discrimination,
- eugenic attitudes,
- NIPT implementation
Résumé
Le test prénatal non-invasif (TPNI) reposant sur l’utilisation de l’ADN foetal libre (cffDNA) dans le sang maternel a été introduit dans la pratique clinique dans de nombreux pays, incluant le Canada. Ce test peut être effectué tôt durant la grossesse pour détecter le syndrome de Down ainsi que d’autres conditions. Bien que le TPNI promette de nombreux avantages, il comporte aussi des enjeux éthiques, légaux et sociaux (ELS). Cet article recense les préoccupations qui se trouvent actuellement dans la littérature sur les enjeux ELS du TPNI. Nous faisons quatre observations. Tout d’abord, le TPNI semble exacerber certaines des préoccupations existantes et soulevées par d’autres tests prénataux (l’amniocentèse et le dépistage du sérum maternel), telles que les menaces à l’autonomie reproductive des femmes et la discrimination et la stigmatisation potentielles des personnes handicapées et de leurs familles. Cela peut être attribué à la probable mise en oeuvre en grande échelle et par la routinisation à venir du TPNI. Deuxièmement, la distinction entre le TPNI comme un test de dépistage (tel qu’il est actuellement recommandé) et comme un test de diagnostic (potentiellement dans le futur), présente certaines implications sur la discussion des enjeux ELS. Troisièmement, nous avons observé un changement progressif dans la littérature. Celle-ci était à l’origine composée d’analyses essentiellement conceptuelles, mais recense maintenant un nombre croissant d’études empiriques. Cela démontre la contribution des approches de la bioéthique empirique alors que la technologie est en cours d’implantation au sein de la pratique clinique. Enfin, nous avons constaté un intérêt croissant pour les questions de justice et d’équité en matière d’accès au TPNI dans la mesure où le test devient implanté à une échelle plus large.
Mots-clés :
- test prénatal non-invasif (TPNI),
- enjeux éthiques, légaux et sociaux (ELS),
- autonomie reproductive,
- consentement éclairé,
- interruption de grossesse,
- discrimination,
- attitudes eugéniques,
- implantation du TPNI
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Bibliography
- 1. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997;350(9076):485-7.
- 2. Palomaki GE, Deciu C, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, et al. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genetics in Medicine. 2012;14(3):296-305.
- 3. Bianchi DW, Platt LD, Goldberg JD, Abuhamad AZ, Sehnert AJ, Rava RP. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstetrics and Gynecology. 2012;119(5):890-901.
- 4. Salomon LJ, Alfirevic Z, Audibert F, Kagan KO, Paladini D, Yeo G, et al. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice. Ultrasound in Obstetrics & Gynecology. 2014;44(1):122-3.
- 5. Allyse M, Minear MA, Berson E, Sridhar S, Rote M, Hung A, et al. Non-invasive prenatal testing: a review of international implementation and challenges. International Journal of Women’s Health. 2015;7:113-26.
- 6. Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews. Illustrated Glossary. Seattle (WA): University of Washington, Seattle; 1993-2016.
- 7. Dondorp W, de Wert G, Bombard Y, Bianchi DW, Bergmann C, Borry P, et al. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. European Journal of Human Genetics. 2015;23(11):1438-50.
- 8. Norton ME, Rose NC, Benn P. Noninvasive prenatal testing for fetal aneuploidy: clinical assessment and a plea for restraint. Obstetrics and Gynecology. 2013;121(4):847-50.
- 9. Wilson KL, Czerwinski JL, Hoskovec JM, Noblin SJ, Sullivan CM, Harbison A, et al. NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy. Journal of Genetic Counseling. 2013;22(1):4-15.
- 10. Gregg AR, Gross SJ, Best RG, Monaghan KG, Bajaj K, Skotko BG, et al. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genetics in Medicine. 2013;15(5):395-8.
- 11. Committee Opinion No. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstetrics and Gynecology. 2012;120(6):1532-4.
- 12. Hudecova I, Sahota D, Heung MM, Jin Y, Lee WS, Leung TY, et al. Maternal plasma fetal DNA fractions in pregnancies with low and high risks for fetal chromosomal aneuploidies. PLoS ONE. 2014;9(2):e88484.
- 13. Lench N, Barrett A, Fielding S, McKay F, Hill M, Jenkins L, et al. The clinical implementation of non-invasive prenatal diagnosis for single gene disorders: Challenges and progress made. Prenatal Diagnosis. 2013;33(6) :555-62.
- 14. Lo YM, Chan KC, Sun H, Chen EZ, Jiang P, Lun FM, et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Science Translational Medicine. 2010;2(61):61ra91.
- 15. Kitzman JO, Snyder Mw Fau - Ventura M, Ventura M Fau - Lewis AP, Lewis Ap Fau - Qiu R, Qiu R Fau - Simmons LE, Simmons Le Fau - Gammill HS, et al. Noninvasive whole-genome sequencing of a human fetus. Science Translational Medicine. 2012;4(137):137ra76
- 16. Morain S, Greene MF, Mello MM. A new era in noninvasive prenatal testing. The New England Journal of Medicine. 2013;369(6):499-501.
- 17. Pollack A. Conflict potential seen in genetic counselors. The New York Times. 2012 July 13.
- 18. Benn P, Chapman AR, Erickson K, Defrancesco MS, Wilkins-Haug L, Egan JF, et al. Obstetricians’ and gynecologists’ practice and opinions of expanded carrier testing and non-invasive prenatal testing. Prenatal Diagnosis. 2014;34(2):145-52.
- 19. Sayres LC, Allyse M, Cho MK. Integrating stakeholder perspectives into the translation of cell-free fetal DNA testing for aneuploidy. Genome Medicine. 2012;4:49.
- 20. van Schendel RV, Kleinveld JH, Dondorp WJ, Pajkrt E, Timmermans DR, Holtkamp KC, et al. Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening. European Journal of Human Genetics. 2014;22(12):1345-50.
- 21. Horsting JM, Dlouhy SR, Hanson K, Quaid K, Bai S, Hines KA. Genetic counselors’ experience with cell-free fetal dna testing as a prenatal screening option for aneuploidy. Journal of Genetic Counseling. 2014;23(3):377-400.
- 22. Kellogg G, Slattery L, Hudgins L, Ormond K. Attitudes of mothers of children with Down syndrome towards noninvasive prenatal testing. Journal of Genetic Counseling. 2014;23(5):805-13.
- 23. Shields AD, Vidosh JD. Average-risk pregnant patient perspectives on noninvasive prenatal testing. Obstetrics and Gynecology. 2014;123 Suppl 1:79S-80S.
- 24. Kaposy C. A disability critique of the new prenatal test for Down syndrome. Kennedy Institute of Ethics Journal. 2013;23(4):299-324.
- 25. Hill M, Fisher J, Chitty LS, Morris S. Women’s and health professionals’ preferences for prenatal tests for Down syndrome: a discrete choice experiment to contrast noninvasive prenatal diagnosis with current invasive tests. Genetics in Medicine. 2012;14(11):905-13.
- 26. Hill M, Compton C, Karunaratna M, Lewis C, Chitty L. Client views and attitudes to non-invasive prenatal diagnosis for sickle cell disease, thalassaemia and cystic fibrosis. Journal of Genetic Counseling. 2014;23(6):1012-21.
- 27. Lewis C, Silcock C, Chitty LS. Non-invasive prenatal testing for Down’s syndrome: pregnant women’s views and likely uptake. Public Health Genomics. 2013;16(5):223-32.
- 28. Silcock C, Liao L-M, Hill M, Chitty LS. Will the introduction of non-invasive prenatal testing for Down’s syndrome undermine informed choice? Health Expectations. 2015;18(5):1658-71.
- 29. Benn PA, Chapman AR. Ethical challenges in providing noninvasive prenatal diagnosis. Current Opinion in Obstetrics & Gynecology. 2010;22(2):128-34.
- 30. Hall A, Bostanci A, Wright CF. Non-invasive prenatal diagnosis using cell-free fetal DNA technology: applications and implications. Public Health Genomics. 2010;13(4):246-55.
- 31. Vanstone M, Yacoub K, Giacomini M, Hulan D, McDonald S. Women’s experiences of publicly funded non-invasive prenatal testing in Ontario, Canada: Considerations for health technology policy-making. Qualitative Health Research. 2015;25(8):1069-84.
- 32. Dixon-Woods M, Cavers D, Agarwal S, Annandale E, Arthur A, Harvey J, et al. Conducting a critical interpretive synthesis of the literature on access to healthcare by vulnerable groups. BMC Medical Research Methodology. 2006;6:35.
- 33. Deans Z, Newson AJ. Ethical considerations for choosing between possible models for using NIPD for aneuploidy detection. Journal of Medical Ethics. 2012;38(10):614-8.
- 34. Hill M, Karunaratna M, Lewis C, Forya F, Chitty L. Views and preferences for the implementation of non-invasive prenatal diagnosis for single gene disorders from health professionals in the united kingdom. American Journal of Medical Genetics Part A. 2013;161(7):1612-18.
- 35. Wright C. Cell-free fetal nucleic acids for non-invasive prenatal diagnosis. PHG Foundation, 2009.
- 36. Hewison J. Psychological aspects of individualized choice and reproductive autonomy in prenatal screening. Bioethics. 2015;29(1):9-18.
- 37. Wright CF, Burton H. The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis. Human reproduction update. 2009;15(1):139-51.
- 38. Seavilleklein V. Challenging the rhetoric of choice in prenatal screening. Bioethics. 2009;23(1):68-77.
- 39. Benn P, Cuckle H, Pergament E. Non-invasive prenatal testing for aneuploidy - current status and future prospects. Ultrasound in Obstetrics & Gynecology. 2013;42(1):15-33.
- 40. Davis DS. Opportunistic testing: the death of informed consent? Health Matrix Cleveland. 2013;23(1):35-54.
- 41. Tischler R, Hudgins L, Blumenfeld YJ, Greely HT, Ormond KE. Noninvasive prenatal diagnosis: pregnant women’s interest and expected uptake. Prenatal Diagnosis. 2011;31(13):1292-9.
- 42. Yi H, Hallowell N, Griffiths S, Leung TY. Motivations for undertaking dna sequencing-based non-invasive prenatal testing for fetal aneuploidy: a qualitative study with early adopter patients in Hong Kong. PloS One. 2013;8(11):e81794.
- 43. van den Heuvel A, Chitty L, Dormandy E, Newson A, Deans Z, Attwood S, et al. Will the introduction of non-invasive prenatal diagnostic testing erode informed choices? An experimental study of health care professionals. Patient Education and Counseling. 2010;78(1):24-8.
- 44. Benn Pa, Chapman AR. Practical and ethical considerations of noninvasive prenatal diagnosis. Journal of American Medical Association. 2009;301(20):2154-6.
- 45. King JS. And genetic testing for all... The coming revolution in non-invasive prenatal genetic testing. Rutgers Law Journal. 2011;42:599-819.
- 46. Willems PJ, Dierickx H, Vandenakker E, Bekedam D, Segers N, Deboulle K, et al. The first 3,000 Non-Invasive Prenatal Tests (NIPT) with the Harmony test in Belgium and the Netherlands. Facts, Views & Vision in ObGyn. 2014;6(1):7-12.
- 47. Research TM. Non-Invasive Prenatal Testing (NIPT) Market: (MaterniT21 PLUS, verifi, Harmony, Panorama, NIFTY, PrenaTest and BambniTest) Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2013 - 2019.
- 48. Dondorp W, de Wert G, Bombard Y, Bianchi DW, Bergmann C, Borry P, et al. Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Summary and recommendations. European Journal of Human Genetics. 2015 Apr 1. doi: 10.1038/ejhg.2015.56
- 49. Minear MA, Alessi S, Allyse M, Michie M, Chandrasekharan S. Noninvasive prenatal genetic testing: current and emerging ethical, legal, and social issues. Annual Review of Genomics and Human Genetics. 2015;16:369-98.
- 50. Allyse MA, Sayres LC, Havard M, King JS, Greely HT, Hudgins L, et al. Best ethical practices for clinicians and laboratories in the provision of non-invasive prenatal testing. Prenatal Diagnosis. 2013;33(7):656-61.
- 51. Deans Z, Hill M, Chitty LS, Lewis C. Non-invasive prenatal testing for single gene disorders: exploring the ethics. European Journal of Human Genetics. 2013;21(7):713-8.
- 52. Hill M, Barrett AN, White H, Chitty LS. Uses of cell free fetal DNA in maternal circulation. Best Practice & Research Clinical Obstetrics & Gynaecology. 2012;26(5):639-54.
- 53. de Jong A, Dondorp WJ, de Die-Smulders CE, Frints SG, de Wert GM. Non-invasive prenatal testing: ethical issues explored. European Journal of Human Genetics. 2010;18(3):272-7.
- 54. Newson AJ. Ethical aspects arising from non-invasive fetal diagnosis. Seminars in Fetal & Neonatal Medicine. 2008;13(2):103-8.
- 55. Deans Z, Clarke AJ, Newson AJ. For your interest? The ethical acceptability of using non-invasive prenatal testing to test ‘purely for information’. Bioethics. 2015;29(1):19-25.
- 56. Menezes M, Meagher S, Costa Fda S. Ethical considerations when offering noninvasive prenatal testing. Revista Brasileira de Ginecologia e Obstetricia. 2013;35(5):195-8.
- 57. Verweij EJ, Oepkes D, de Boer MA. Changing attitudes towards termination of pregnancy for trisomy 21 with non-invasive prenatal trisomy testing: a population-based study in Dutch pregnant women. Prenatal Diagnosis. 2013;33(4):397-9.
- 58. Yagel S. Non-invasive prenatal testing: more questions than answers. Ultrasound in Obstetrics & Gynecology. 2013;42(4):369-72.
- 59. Henry T. Greely JSK. The coming revolution in prenatal genetic testing. Professional Ethics Report. 2010;23(2):3.
- 60. Skirton H, Patch C. Factors affecting the clinical use of non-invasive prenatal testing: a mixed methods systematic review. Prenatal Diagnosis. 2013;33(6):532-41.
- 61. Lewis C, Hill M, Skirton H, Chitty LS. Fetal sex determination using cell-free fetal DNA: service users’ experiences of and preferences for service delivery. Prenatal Diagnosis. 2012;32(8):735-41.
- 62. Yotsumoto J, Sekizawa A, Koide K, Purwosunu Y, Ichizuka K, Matsuoka R, et al. Attitudes toward non-invasive prenatal diagnosis among pregnant women and health professionals in Japan. Prenatal Diagnosis. 2012;32(7):674-9.
- 63. King JS. Not this child: constitutional questions in regulating noninvasive prenatal genetic diagnosis and selective abortion. UCLA Law Review. 2012;60:2.
- 64. Wilkinson S. Prenatal screening, reproductive choice, and public health. Bioethics. 2015;29(1):26-35.
- 65. Haymon L. Non Invasive Prenatal Genetic Diagnosis (NIPD). Council for Responsible Genetics, 2011.
- 66. Parens E, Asch A. Disability rights critique of prenatal genetic testing: reflections and recommendations. Mental Retardation and Developmental Disabilities Research Reviews. 2003;9(1):40-7.
- 67. Kent A. Non-invasive prenatal diagnosis: public and patient perceptions. Seminars in Fetal & Neonatal Medicine. 2008;13(2):109-12.
- 68. Chachkin CJ. What potent blood: non-invasive prenatal genetic diagnosis and the transformation of modern prenatal care. American Journal of Law & Medicine. 2007;33(1):9-53.
- 69. Ma Y, Gong H, Wen Y. Nucleic acid-based non-invasive prenatal diagnosis of genetic skin diseases: are we ready? Experimental Dermatology. 2013;22(6):392-5.
- 70. Farrimond HR, Kelly SE. Public viewpoints on new non-invasive prenatal genetic tests. Public Understanding of Science. 2013;23(6):730-44.
- 71. Agarwal A, Sayres LC, Cho MK, Cook-Deegan R, Chandrasekharan S. Commercial landscape of noninvasive prenatal testing in the United States. Prenatal Diagnosis. 2013;33(6):521-31.
- 72. Fikes BJ. Illumina, Sequenom settle patent dispute. San Diego Union-Tribune. 2014; Dec. 3.
- 73. Twiss P, Hill M, Daley R, Chitty LS. Non-invasive prenatal testing for Down syndrome. Seminars in Fetal & Neonatal Medicine. 2014;19(1):9-14.
- 74. Vahanian SA, Allaf MB, Yeh C, Chavez MR, Kinzler WL, Vintzileos AM. Patient Acceptance of Non-invasive Testing for Fetal Aneuploidy via Cell-free Fetal DNA. The Journal of Maternal-Fetal & Neonatal Medicine. 2014;27(1):106-9.
- 75. Ventura W, Nazario-Redondo C, Sekizawa A. Non-invasive prenatal diagnosis from the perspective of a low-resource country. International Journal of Gynaecology and Obstetrics. 2013;122(3):270-3.
- 76. de Jong A, Dondorp WJ, Frints SG, de Die-Smulders CE, de Wert GM. Advances in prenatal screening: the ethical dimension. Nature Reviews Genetics. 2011;12(9):657-63.
- 77. Non-invasive Prenatal Testing: A Review of the Cost Effectiveness and Guidelines. Ottawa ON: 2014 Canadian Agency for Drugs and Technologies in Health. CADTH Rapid Response Reports; 2014 Feb 10.
- 78. Neyt M, Hulstaert F, Gyselaers W. Introducing the non-invasive prenatal test for trisomy 21 in Belgium: a cost-consequences analysis. BMJ Open. 2014;4(11):e005922.
- 79. Munthe C. A new ethical landscape of prenatal testing: individualizing choice to serve autonomy and promote public health: a radical proposal. Bioethics. 2015;29(1):36-45.
- 80. Chandrasekharan S, Minear MA, Hung A, Allyse M. Noninvasive prenatal testing goes global. Science Translational Medecine. 2014;6(231):231fs15.
- 81. Verweij EJ, Oepkes D, de Vries M, van den Akker ME, van den Akker ES, de Boer MA. Non-invasive prenatal screening for trisomy 21: What women want and are willing to pay. Patient Education and Counseling. 2013;93(3):641-5.