Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Non-Invasive Prenatal Diagnosis Using Cell-Free Fetal DNA Technology: Applications and Implications

Hall A.a · Bostanci A.b · Wright C.F.a

Author affiliations

aPHG Foundation and bHughes Hall Centre for Biomedical Science in Society, Cambridge, UK

Related Articles for ""

Public Health Genomics 2010;13:246–255

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.
Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00


Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: April 15, 2010
Issue release date: April 2010

Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0

ISSN: 1662-4246 (Print)
eISSN: 1662-8063 (Online)

For additional information: https://www.karger.com/PHG

Abstract

Cell-free fetal DNA and RNA circulating in maternal blood can be used for the early non-invasive prenatal diagnosis (NIPD) of an increasing number of genetic conditions, both for pregnancy management and to aid reproductive decision-making. Here we present a brief review of the scientific and clinical status of the technology, and an overview of key ethical, legal and social issues raised by the analysis of cell-free fetal DNA for NIPD. We suggest that the less invasive nature of the technology brings some distinctive issues into focus, such as the possibility of broader uptake of prenatal diagnosis and access to the technology directly by the consumer via the internet, which have not been emphasised in previous work in this area. We also revisit significant issues that are familiar from previous debates about prenatal testing. Since the technology seems to transect existing distinctions between screening and diagnostic tests, there are important implications for the form and process involved in obtaining informed consent or choice. This analysis forms part of the work undertaken by a multidisciplinary group of experts which made recommendations about the implementation of this technology within the UK National Health Service.

© 2010 S. Karger AG, Basel


References

  1. Mujezinovic F, Alfirevic Z: Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstet Gynecol 2007;110:687–694.
  2. van den Berg M, Timmermans DR, Kleinveld JH, Garcia E, van Vugt JM, van der Wal G: Accepting or declining the offer of prenatal screening for congenital defects: test uptake and women’s reasons. Prenat Diagn 2005;25:84–90.
  3. Coventry PA: The dynamics of medical genetics: the development and articulation of clinical and technical services under the NHS, especially at Manchester c.1945–1979. PhD Thesis, University of Manchester, 2000.
  4. Crawfurd M: Prenatal diagnosis of common genetic disorders. BMJ 1988;297:502–506.
  5. Mandel P, Metais P: Les acides nucléiques du plasma sanguin chez l’homme. C R Acad Sci Paris 1948;142:241–243.
  6. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS: Presence of fetal DNA in maternal plasma and serum. Lancet 1997;350:485–487.
  7. Chan KC, Zhang J, Hui AB, Wong N, Lau TK, Leung TN, Lo KW, Huang DW, Lo YM: Size distributions of maternal and fetal DNA in maternal plasma. Clin Chem 2004;50:88–92.
  8. Illanes S, Denbow M, Kailasam C, Finning K, Soothill PW: Early detection of cell-free fetal DNA in maternal plasma. Early Hum Dev 2007;83:563–566.
  9. Lo YM, Zhang J, Leung TN, Lau TK, Chang AM, Hjelm NM: Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet 1999;64:218–224.
  10. Poon LL, Leung TN, Lau TK, Lo YM: Presence of fetal RNA in maternal plasma. Clin Chem 2000;46:1832–1834.
  11. Lun FM, Chiu RW, Chan KC, Leung TY, Lau TK, Lo YM: Microfluidics digital PCR reveals a higher than expected fraction of fetal DNA in maternal plasma. Clin Chem 2008;54:1664–1672.
  12. Lun FM, Tsui NB, Chan KC, Leung TY, Lau TK, Charoenkwan P, Chow KC, Lo WY, Wanapirak C, Sanguansermsri T, Cantor CR, Chiu RW, Lo YM: Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma. Proc Natl Acad Sci USA 2008;105:19920–19925.
  13. Wright CF, 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.
  14. Norbury G, Norbury CJ: Non-invasive prenatal diagnosis of single gene disorders: how close are we? Semin Fetal Neonatal Med 2008;13:76–83.
  15. Chitty L, Mistry B, Hogg J, Meaney C, Thomasson L, Norbury G, Daniels G, Finning K, Martin P: Prospective register of outcomes of free-fetal DNA testing (PROOF) – results of the first year’s audit. Newsletter of the British Society for Human Genetics 2007;37:8–9.
  16. Rijnders RJ, van der Schoot CE, Bossers B, de Vroede MA, Christiaens GC: Fetal sex determination from maternal plasma in pregnancies at risk for congenital adrenal hyperplasia. Obstet Gynecol 2001;98:374–378.
  17. Finning KM, Chitty LS: Non-invasive fetal sex determination: impact on clinical practice. Semin Fetal Neonatal Med 2008;13:69–75.
  18. Gonzalez-Gonzalez C, Trujillo-Tiebas MJ, Rodriguez de Alba M, Garcia-Hoyos M, Lorda-Sanchez I, Diaz-Recasens J, Ayuso C, Ramos C: Huntington disease – unaffected fetus diagnosed from maternal plasma using QF-PCR. Prenat Diagn 2003;23:232–234.
  19. Gonzalez-Gonzalez C, Garcia-Hoyos M, Trujillo-Tiebas MJ, Rodriguez de Alba M, Lorda-Sanchez I, Diaz-Recasens J, Gallardo E, Ayuso C, Ramos C: Prenatal detection of a cystic fibrosis mutation in fetal DNA from maternal plasma. Prenat Diagn 2002;22:946–948.
  20. Wright CF, Chitty L: Cell-free fetal DNA and RNA in maternal blood: implications for safer antenatal testing. BMJ 2009;339:161–165.
  21. van der Schoot CE, Hahn S, Chitty LS: Non-invasive prenatal diagnosis and determination of fetal Rh status. Semin Fetal Neonatal Med 2008;13:63–68.
  22. Finning K, Martin P, Summers J, Massey E, Poole G, Daniels G: Effect of high throughput RHD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women: prospective feasibility study. BMJ 2008;336:816–818.
  23. Wright C: Cell-free fetal nucleic acids for non-invasive prenatal diagnosis. Report of the UK expert working group. PHG Foundation 2009.
  24. Minon JM, Gerard C, Senterre JM, Schaaps JP, Foidart JM: Routine fetal RHD genotyping with maternal plasma: a four-year experience in Belgium. Transfusion 2008;48:373–381.
  25. Finning K, Martin P, Summers J, Daniels G: Fetal genotyping for the K (Kell) and Rh C, c, and E blood groups on cell-free fetal DNA in maternal plasma. Transfusion 2007;47:2126–2133.
  26. Lo YM, Tsui NB, Chiu RW, Lau TK, Leung TN, Heung MM, Gerovassili A, Jin Y, Nicolaides KH, Cantor CR, Ding C: Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection. Nat Med 2007;13:218–223.
  27. Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR: Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci USA 2008;105:16266–16271.
  28. Chiu RW, Chan KC, Gao Y, Lau VY, Zheng W, Leung TY, Foo CH, Xie B, Tsui NB, Lun FM, Zee BC, Lau TK, Cantor CR, Lo YM: Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci USA 2008;105:20458–20463.
  29. Lo YM, Lun FM, Chan KC, Tsui NB, Chong KC, Lau TK, Leung TY, Zee BC, Cantor CR, Chiu RW: Digital PCR for the molecular detection of fetal chromosomal aneuploidy. Proc Natl Acad Sci USA 2007;104:13116–13121.
  30. SEQUENOM announces completion of independent investigation. Press release 09/28/09.
  31. Rijnders RJ, Christiaens GC, Bossers B, van der Smagt JJ, van der Schoot CE, de Haas M: Clinical applications of cell-free fetal DNA from maternal plasma. Obstet Gynecol 2004;103:157–164.
  32. Polnay JC, Davidge A: Parental attitudes: antenatal diagnosis of cystic fibrosis. Arch Dis Child 2002;87:284–286.
  33. Seror V: What understanding of decision-making in prenatal screening could decision analysis provide? Ultrasound Obstet Gynecol 2007;30:921–923.
  34. House of Commons Science and Technology Committee: Scientific developments relating to the Abortion Act 1967. 12th Report of Session 2006–2007.
  35. American Psychological Association Task Force: Report of the APA Task Force on mental health and abortion. 2008.
  36. Katz Rothman B: The Tentative Pregnancy: Prenatal Diagnosis and the Future of Motherhood. London, Pandora, 1988.
  37. Royal College of Obstetricians and Gynaecologists: The care of women requesting induced abortion: evidence-based clinical guideline #7, 2004.
  38. Hall A, Bostanci A, John S: Ethical, legal and social issues arising from cell-free fetal DNA technologies. Appendix III to the report: Cell-free fetal nucleic acids for non-invasive prenatal diagnosis. PHG Foundation 2009;1–45.
  39. Dormandy E, Michie S: Informed choice in antenatal Down syndrome screening: a cluster randomised trial of combined versus separate visit testing. Patient Educ Couns 2006;61:56–64.
  40. O’Connor A, O’Brien-Pallas L: Decisional conflict; in McFarlane G, McFarlane E (eds): Nursing Diagnosis and Intervention: Planning for Patient Care. St Louis, Mosby, 1996, pp 486–489.
  41. Marteau T, Dormandy E, Michie S: A measure of informed choice. Health Expect 2001;4:99–108.
  42. Edwards AG, Evans R, Dundon J, Haigh S, Hood K, Elwyn GJ: Personalised risk communication for informed decision making about taking screening tests. Cochrane Database Syst Rev 2006;4:CD001865.
  43. Dormandy E, Mitchie S, Hooper R, Marteau TM: Low uptake of prenatal screeing for Down syndrome in minority ethnic groups and socially deprived groups: a reflection of women’s attitudes or a failure to facilitate informed choices? Int J Epidemiol 2005;34:346–352.
  44. Seavilleklein V: Challenging the rhetoric of choice in prenatal screening. Bioethics 2009;23:68–77.
  45. Schmitz D, Netzer C, Henn W: An offer you can’t refuse? Ethical implications of non-invasive prenatal diagnosis. Nat Rev Genet 2009;10:515.
  46. Newson AJ: Ethical aspects arising from non-invasive fetal diagnosis. Semin Fetal Neonatal Med 2008;13:103–108.
  47. van den Berg M, Timmermans DR: Are counsellors’ attitudes influencing pregnant women’s attitudes and decisions on prenatal screening? Prenat Diagn 2007;27:518–524.
  48. Sumner W: Abortion and Moral Theory. Princeton, Princeton University Press, 1981.
  49. UK Parliament: The Abortion Act. 1967. (c.87) as amended by the Human Fertilisation and Embryology Act 1990 (c. 37, SIF 83:1).
  50. Scott R: Prenatal testing, reproductive autonomy and disability interests. Camb Q Healthc Ethics 2005;14:65–82.
  51. Bustamante-Aragones A, Rodrigez de Alba M, Gonzalez-Gonzalez C, Trujillo-Tiebas MJ, Diego-Alvarez D, Vallespin E, Plaza J, Ayuso C, Ramos C: Foetal sex determination in maternal blood from the seventh week of gestation and its role in diagnosing haemophilia in foetuses of female carriers. Haemophilia 2008;14:593–598.
  52. Special Non-Invasive Advances in Fetal and Neonatal Evaluation Network. Available at www.safeoe.org. 2009.
  53. Lucast EK: Informed consent and the misattributed paternity problem in genetic counselling. Bioethics 2007;21:41–50.
  54. National Down Syndrome Cytogenetic Register: Annual Report. 2006.
  55. National Down Syndrome Cytogenetic Register: Annual Report. 2008.
  56. Morris JK, Alberman E: Trends in Down’s syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008: analysis of data from the National Down Syndrome Cytogenetic Register. BMJ 2009;339:B3794.
  57. Mansfield C, Hopfer S, Marteau TM: Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anecephaly, and Turner and Klinefelter syndromes: a systematic literature review. Prenat Diagn 1999;19:808–812.
  58. Loeben S, Marteau T, Wilford B: Mixed messages: presentation of information in cystic fibrosis screening pamphlets. Am J Hum Genet 1998;63:1181–1189.
  59. Hall S, Chitty L: Undergoing prenatal screening for Down syndrome; presentation of choice and information in Europe and Asia. Eur J Hum Genet 2007;15:563–569.
  60. van den Heuvel A, Chitty L, Dormandy E, Newson AJ, Deans Z, Marteau TM: Informed choice in prenatal testing: a survey among obstetricians and gynaecologists in Europe and Asia. Prenat Diagn 2008;28:1238–1244.
  61. van den Heuvel A, Chitty L, Dormandy E, Newson AJ, Deans Z, Attwood S, Haynes S, Marteau TM: Will the introduction of non-invasive prenatal diagnostic testing erode informed choices? An experimental study of health care professionals. Patient Educ Couns 2009;78:24–28.
  62. George SM: Millions of missing girls: from fetal sexing to high technology sex selection in India. Prenat Diagn 2006;26:604–609.
  63. Chan CL, Blyth E, Chan CH: Attitudes to and practices regarding sex selection in China. Prenat Diagn 2006;26:610–613.
  64. van Balen F: Attitudes towards sex selection in the Western world. Prenat Diagn 2006;26:614–618.
  65. Gesetzesbeschluss des Deutschen Bundestages: Gesetz über genetische Untersuchungen bei Menschen (Gendiagnostikgesetz – Gen DG). Bundesrat Drucksache 2009;374/09.
  66. Human Genetics Commission: A Common Framework of Principles for direct-to-consumer genetic testing services. Principles and Consultation Questions, 2009.
  67. Christianson A, Modell B: Medical genetics in developing countries. Annu Rev Genomics Hum Genet 2004;5:219–265.
  68. Ballantyne A, Newson AJ, Luna F, Ashcroft R: Prenatal diagnosis and abortion for congenital abnormalities: is it ethical to provide one without the other? Am J Bioeth 2009;9:48–56.
  69. de Jong A, Dondorp WJ, de Die-Smulders CEM, Frints SGM, de Wert GMWR: Non-invasive prenatal testing: ethical issues explored. Eur J Hum Genet 2010;18:272–277.

Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: April 15, 2010
Issue release date: April 2010

Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0

ISSN: 1662-4246 (Print)
eISSN: 1662-8063 (Online)

For additional information: https://www.karger.com/PHG


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.