Ethical Aspects of Prenatal DNA Testing

Abstract

Cell-free DNA (cfDNA) first-trimester screening for fetal aneuploidies, as a non-invasive, safe, and rather accurate method, has changed prenatal screening policies all over the world. Owing to aggressive marketing, cfDNA screening tests exhibit global popularity and a rapid spread in routine prenatal care. However, wide availability of the tests, together with observed difficulties in the test’s interpretation, bring to light several serious ethical concerns. To date it is vital to identify and address the most important ethical, legal, and social issues regarding prenatal screening tests. Furthermore, guidelines and restrictions in certain cfDNA screening advancements that may provide information regarding fetal genetic traits of unknown clinical significance, conditions with variable penetrance, or late-onset conditions, should be considered.

Key words

cell-free DNA - prenatal diagnosis - noninvasive prenatal testing - first trimester screening - ethics

Publication History

Received: 19 February 2022

Accepted after revision: 07 July 2022

Article published online:
29 August 2022

• References

• 1 Chandrasekharan S, Minear MA, Hung A. et al. Noninvasive prenatal testing goes global. Sci Transl Med 2014; 6: 231fs15
• 2 Alldred SK, Takwoingi Y, Guo B. et al. First trimester serum tests for Down’s syndrome screening. Cochrane Libr 2015; 30: CD011975
• 3 Chitayat D, Langlois S, Wilson RD. et al. Prenatal screening for fetal aneuploidy in singleton pregnancies. J Obstet Gynaecol Can 2011; 33: 736-750
• 4 Norton ME, Brar H, Weiss J. et al. Noninvasive chromosomal evaluation (NICE) study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012; 207: e1-e8
• 5 Palomaki GE, Deciu C, Kloza EM. et al. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Gen Med 2012; 14: 296-305
• 6 Wright C, Wei Y, Higgins J. et al. Non-invasive prenatal diagnostic test accuracy for fetal sex using cell-free DNA a review and meta-analysis. BMC Res Notes 2012; 5: 476
• 7 Gregg AR, Best R, Monaghan K. et al. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genet Med 2013; 15: 395-398
• 8 Vanstone M, King C, de Vrijer B. et al. Non-invasive prenatal testing: ethics and policy considerations. J Obstet Gynaecol Can 2014; 36: 515-526
• 9 Wright C, Burton H. The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis. Hum Reprod Update 2009; 15: 139-151
• 10 Dondorp W, De Wert G, Bombard Y. et al. Noninvasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. Eur J Hum Genet 2015; 23: 1438-1450
• 11 Kater-Kuipers A, Bunnik EM, de Beaufort ID. et al. Limits to the scope of non-invasive prenatal testing (NIPT): an analysis of the international ethical framework for prenatal screening and an interview study with Dutch professionals. BMC Pregnancy Childbirth 2018; 18: 409
• 12 Gekas J, Langlois S, Ravitsky V. et al. Non-invasive prenatal testing for fetal chromosome abnormalities: review of clinical and ethical issues. Appl Clin Genet 2016; 9: 15-26
• 13 Stapleton G, Dondorp W, Schröder-Bäck P. et al. A capabilities approach to prenatal screening for fetal abnormalities.. Health Care Anal 2019; 27: 309-321
• 14 Wertz DC, Fletcher JC, Berg K. Review of ethical issues in medical ethics: report of consultants to WHO. Geneva: World Health Organization; 2003
• 15 Marteau TM, Dormandy E, Michie S. A measure of informed choice. Health Expect 2001; 4: 99-108
• 16 Lewis C, Hill M, Skirton H. et al. Development and validation of a measure of informed choice for women undergoing non-invasive prenatal testing for aneuploidy. Eur J Hum Genet 2016; 24: 809-816
• 17 Biesecker BB, Schwartz MD, Marteau TM. Enhancing informed choice to undergo health screening: a systematic review. Am J Health Behav 2013; 37: 351-359
• 18 Gammon BL, Kraft SA, Michie M. et al. “I think we’ve got too many tests!”: Prenatal providers’ reflections on ethical and clinical challenges in the practice integration of cell-free DNA screening. Ethics Med Public Health 2016; 2: 334-342
• 19 Hui L, Bianchi DW. Noninvasive prenatal DNA testing: the vanguard of genomic medicine. Annu Rev Med 2017; 68: 459-472
• 20 UNESCO. Report of the IBC on updating its reflection on the human genome and human rights. Paris: United Nation Educational Scientific and Cultural Organization; 2015
• 21 van den Berg M, Timmermans DR, Kleinveld JH. et al. Accepting or declining the offer prenatal screening for congenital defects: test uptake and women’s reasons. Prenat Diagn 2005; 25: 84-90
• 22 García E, Timmermans DRM, van Leeuwen E. The impact of ethical beliefs on decisions about prenatal screening t searching for justification. Soc Sci Med 2008; 66: 753-764
• 23 Crombag NM, Bensing JM, Iedema-Kuiper R. et al. Determinants affecting pregnant women’s utilization of prenatal screening for Down syndrome: a review of the literature. J Matern Fetal Neonatal Med 2013; 26: 1676-1681
• 24 Crombag NM, van Schendel RV, Schielen PCJI. et al. Present to future: what the reasons declining first-trimester combined testing tell us about accepting or declining cell-free DNA testing. Prenat Diagn 2016; 36: 587-590
• 25 Ternby E, Axelsson O, Annerén G. et al. Why do pregnant women accept or decline prenatal diagnosis for Down syndrome?. J Community Genet 2016; 7: 237-242
• 26 Vassy C, Rosman S, Rousseau B. From policy making to service use. Down’s syndrome antenatal screening in England, France and the Netherlands. Soc Sci Med 2014; 106: 67-74
• 27 Dukhovny S, Norton ME. What are the goals of prenatal genetic testing?. Semin Perinatol 2018; 42: 270-274
• 28 Akolekar R, Beta J, Picciarelli G. et al. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis. Ultrasound Obstet Gynecol 2015; 45: 16-26
• 29 Morain S, Greene MF, Mello MM. A new era in noninvasive prenatal testing. N Engl J Med 2013; 369: 499-501
• 30 Chitty LS, Hill M, White H. et al. Noninvasive prenatal testing for aneuploidy–ready for prime time?. Am J Obstet Gynecol 2012; 206: 269-275
• 31 Norton ME, Rose NC, Benn P. Noninvasive prenatal testing for fetal aneuploidy: clinical assessment and a plea for restraint. Obstet Gynecol 2013; 121: 847-850
• 32 Weaver C. Tough calls on prenatal tests. Wall Street Journal; 2013. Available from: http://www.wsj.com/articles/SB10001424127887324883604578398791568615644 Accessed November 6, 2015
• 33 Huang MC, Lin SJ, Chen CL. et al. Innovative prenatal testing: clinical applications and ethical considerations. Hu Li Za Zhi 2017; 64: 5-10
• 34 Lutgendorf MA, Stoll KA, Knutzen DM. et al. Noninvasive prenatal testing: limitations and unanswered questions. Genet Med 2014; 16: 281-285
• 35 Stetten G, Escallon CS, South ST. et al. Reevaluating confined placental mosaicism. Am J Med Genet A 2004; 131: 232-239
• 36 Ioannidis JP. Biomarker failures. Clin Chem 2013; 59: 202-204
• 37 Dyer O. The challenge of doing less. BMJ 2013; 347: f5904
• 38 Skotko BG, Allyse MA, Bajaj K. et al. Adherence of cell-free DNA noninvasive prenatal screens to ACMG recommendations. Genet Med 2019; 21: 2285-2292
• 39 Tamminga S, van Maarle M, Henneman L. et al. Maternal plasma DNA and RNA sequencing for prenatal testing. Adv Clin Chem 2016; 74: 63-102
• 40 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: 19-25
• 41 Bianchi DW. From prenatal genomic diagnosis to fetal personalized medicine: progress and challenges. Nat Med 2012; 18: 1041-1051
• 42 Arentz-Hansen H, Brurberg KG, Kvamme MK. et al. Determination of fetal rhesus D status from maternal plasma of rhesus negative women. Oslo, Norway: Knowledge Centre for the Health Services at the Norwegian Institute of Public Health (NIPH); 2014. Report from Norwegian Knowledge Centre for the Health Services (NOKC) No. 25-2014
• 43 Mone F, Quinlan-Jones E, Kilby MD. Clinical utility of exome sequencing I the prenatal diagnosis of congenital anomalies: a review. Eur J Obstet Gynecol Reprod Biol 2018; 231: 19-24
• 44 Vora NL, O’Brien BM. Noninvasive prenatal testing for microdeletion syndromes and expanded trisomies: proceed with caution. Obstet Gynecol 2014; 123: 1097-1099
• 45 Lo KK, Boustred C, Chitty LS. et al. RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy. Bioinformatics 2014; 30: 2965-2967
• 46 Crawford G, Foulds N, Fenwick A. et al. Genetic medicine and incidental findings: it is more complicated than deciding whether to disclose or not. Genet Med 2013; 15: 896-869
• 47 Nicolaides KH, Wright D, Poon LC. et al. First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood cell-free DNA testing. Ultrasound Obstet Gynecol 2013; 42: 41-50
• 48 Skirton H, Patch C. Factors affecting the clinical use of non-invasive prenatal testing: a mixed methods systematic review. Prenat Diagn 2013; 33: 532-541
• 49 Hill M, Lewis C, Jenkins L. et al. Implementing noninvasive prenatal fetal sex determination using cell-free fetal DNA in the United Kingdom. Expert Opin Biol Ther 2012; 12: S119-S126
• 50 George SM. Millions of missing girls: from fetal sexing to high technology sex selection in India. Prenat Diagn 2006; 26: 604-609
• 51 Lai-wan CC, Blyth E, Hoi-yan CC. Attitudes to and practices regarding sex selection in China. Prenat Diagn 2006; 26: 610-613
• 52 Madan K, Breuning MH. Impact of prenatal technologies on the sex ratio in India: an overview. Genet Med 2014; 16: 425-432
• 53 Haidar H, Dupras C, Ravitsky V. Non-invasive prenatal testing: review of ethical, legal and social implications. Bioéthique Online 2016; 5 Available from