JOGC

Non-invasive Prenatal Testing and the Unveiling of an Impaired Translation Process

Published:October 17, 2016DOI:https://doi.org/10.1016/j.jogc.2016.09.004

      Abstract

      Non-invasive prenatal testing (NIPT) is an exciting technology with the potential to provide a variety of clinical benefits, including a reduction in miscarriages, via a decline in invasive testing. However, there is also concern that the economic and near-future clinical benefits of NIPT have been overstated and the potential limitations and harms underplayed. NIPT, therefore, presents an opportunity to explore the ways in which a range of social pressures and policies can influence the translation, implementation, and use of a health care innovation. NIPT is often framed as a potential first tier screen that should be offered to all pregnant women, despite concerns over cost-effectiveness. Multiple forces have contributed to a problematic translational environment in Canada, creating pressure towards first tier implementation. Governments have contributed to commercialization pressure by framing the publicly funded research sector as a potential engine of economic growth. Members of industry have an incentive to frame clinical value as beneficial to the broadest possible cohort in order to maximize market size. Many studies of NIPT were directly funded and performed by private industry in laboratories lacking strong independent oversight. Physicians' fear of potential liability for failing to recommend NIPT may further drive widespread uptake. Broad social endorsement, when combined with these translation pressures, could result in the “routinization” of NIPT, thereby adversely affecting women's reproductive autonomy. Policymakers should demand robust independent evidence of clinical and public health utility relevant to their respective jurisdictions before making decisions regarding public funding for NIPT.

      Résumé

      Le dépistage prénatal non effractif (DPNE) est une technologie remarquable ayant le potentiel d'offrir une multitude d'avantages cliniques, notamment une réduction des fausses couches, grâce à la diminution du nombre d'examens invasifs. Cependant, certains soupçonnent que les avantages économiques et cliniques à court terme du DPNE ont été surévalués, et ses limites et méfaits, minimisés. Il y a donc lieu d'étudier de quelle façon les pressions sociales et les politiques influencent l'application concrète, la mise en œuvre et l'utilisation d'innovations en soins de santé comme le DPNE. Malgré les réserves quant à son rapport coût-efficacité, le DPNE est souvent présenté comme un premier palier d'examen qui devrait être offert à toutes les femmes enceintes. De nombreux facteurs ont contribué à un environnement translationnel problématique au Canada, poussant à l'adoption de cette technologie comme premier palier d'examen. Les gouvernements ont exercé des pressions pour qu'on commercialise le DPNE, en présentant le secteur de la recherche financée par les deniers publics comme un possible moteur de croissance économique. Afin d'optimiser la taille de leur marché, les acteurs du secteur ont tout avantage à défendre la valeur clinique de cette technologie pour en vanter les bienfaits pour le plus grand nombre de personnes possible. Nombre d'études sur le DPNE ont été réalisées et financées directement par le secteur privé dans des laboratoires sans supervision indépendante adéquate. Par ailleurs, la crainte pour les médecins d'être tenus responsables s'ils ne recommandent pas un DPNE à leurs patientes peut aussi provoquer l'adoption généralisée de la procédure. Combinée à ces pressions de mise en application, la forte adhésion sociale pourrait mener à une « systématisation » du DPNE et, par conséquent, nuire à l'autodétermination reproductive des femmes. C'est pourquoi les décideurs devraient, avant de prendre des décisions relativement au financement public du DPNE, exiger des preuves solides et indépendantes sur sa pertinence clinique et sanitaire dans leur province ou leur territoire.

      Key Words

      To read this article in full you will need to make a payment

      References

        • Lewis C.
        • Hill M.
        • Silcock C.
        • Daley R.
        • Chitty L.S.
        NIPT for trisomy 21: a cross sectional survey of service users' views and likely uptake.
        Br J Obstet Gynaecol. 2014; 121: 582-594
        • Brady P.
        • Brison N.
        • Van Den Bogaert K.
        • de Ravel T.
        • Peeters H.
        • Van Esch H.
        • et al.
        Clinical implementation of NIPT - technical and biological challenges.
        Clin Genet. 2015; 89 (Available at:) (Accessed on April 15, 2016): 523-530
        • Lewis C.
        • Choudhury M.
        • Chitty L.S.
        Hope for safe prenatal gene tests: a content analysis of how the UK press media are reporting advances in non-invasive prenatal testing.
        Prenat Diagn. 2014; 35: 420-427
        • Kamenova K.
        • Ravitsky V.
        • McMullin S.
        • Caulfield T.
        Media portrayal of non-invasive prenatal testing: a missing ethical dimension.
        Sci Comm. 2016; 15: 1-19
        • Allyse M.
        • Minear M.A.
        • Berson E.
        • Sridhar S.
        • Rote M.
        • Hung A.
        • et al.
        Non-invasive prenatal testing: a review of international implementation and challenges.
        Int J Womens Health. 2015; 7: 113-126
        • Minear M.A.
        • Lewis C.
        • Pradhan S.
        • Chandrasekharan S.
        Global perspectives on clinical adoption of NIPT.
        Prenat Diagn. 2015; 35: 959-967
        • Farrell R.M.
        • Agatisa P.K.
        • Mercer M.B.
        • Mitchum A.
        • Coleridge M.
        The use of noninvasive prenatal testing in obstetric care: educational resources, practice patterns, and barriers reported by a national sample of clinicians.
        Prenat Diagn. 2016; 36 (Available at:) (Accessed on April 15, 2016): 499-506
        • Song K.
        • Musci T.J.
        • Caughey A.B.
        Clinical utility and cost of non-invasive prenatal testing with cfDNA analysis in high-risk women based on a US population.
        J Matern Fetal Med. 2013; 26: 1180-1185
        • Okun N.
        • Teitelbaum M.
        • Huang T.
        • Dewa C.S.
        • Hoch J.S.
        The price of performance: a cost and performance analysis of the implementation of cell-free fetal DNA testing for Down syndrome in Ontario, Canada.
        Prenat Diagn. 2014; 34: 350-356
        • Benn P.
        • Curnow K.J.
        • Chapman S.
        • Michalopoulos S.N.
        • Hornberger J.
        • Rabinowitz M.
        An economic analysis of cell-free DNA non-invasive prenatal testing in the US general pregnancy population.
        PLoS One. 2015; 10: e0132313
        • Dondorp W.
        • de Wert G.
        • Bombard Y.
        • Bianchi N.W.
        • Bergmann C.
        • Borry P.
        • et al.
        Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening.
        Eur J Hum Genet. 2015; 23: 1438-1450
        • Gekas J.
        • Langlois S.
        • Ravitsky V.
        • Audibert F.
        • van den Berg D.G.
        • Haidar H.
        Non-invasive prenatal testing for fetal chromosome abnormalities: review of clinical and ethical issues.
        Appl Clin Genet. 2016; 9: 15-26
        • Yaron Y.
        The implications of non-invasive prenatal testing failures: a review of an under-discussed phenomenon.
        Prenat Diagn. 2016; 36: 391-396
        • Faas B.H.
        Prenatal genetic care: debates and considerations of the past, present and future.
        Expert Opin Biol Ther. 2015; 15: 1101-1105
        • Caulfield T.
        • Ogbogu U.
        The commercialization of university-based research: balancing risks and benefits.
        BMC Med Ethics. 2015; 16: 70
        • Norton M.E.
        • Rose N.C.
        • Benn P.
        Noninvasive prenatal testing for fetal aneuploidy: clinical assessment and a plea for restraint.
        Obstet Gynecol. 2013; 121: 847-850
        • Lo Y.M.
        • Corbetta N.
        • Chamberlain P.F.
        • Rai V.
        • Sargent I.L.
        • Redman C.W.
        • et al.
        Presence of fetal DNA in maternal plasma and serum.
        Lancet. 1997; 350: 485-487
        • Norwitz E.R.
        • Levy B.
        Noninvasive prenatal testing: the future is now.
        Rev Obstet Gynecol. 2013; 6: 48-62
      1. Swift D. Navigating the new world of non-invasive prenatal testing. The Medical Post Upfront (Canadian Health Care Network). 2014;8–9.

      2. Perinatal Services BC. Non-invasive prenatal testing (NIPT). Available at: http://www.perinatalservicesbc.ca/health-professionals/professional-resources/screening/prenatal-genetic/non-invasive-prenatal-testing-(nipt). Accessed on April 15, 2016.

      3. Children's Hospital of Eastern Ontario (CHEO) (2016). Frequently asked questions: non-invasive prenatal testing (NIPT). Available at: http://www.cheo.on.ca/en/NIPT. Accessed on March 22, 2016.

        • Langlois S.
        • Brock J.A.
        Current status in non-invasive prenatal detection of Down syndrome, trisomy 18, and trisomy 13 using cell-free DNA in maternal plasma.
        J Obstet Gynaecol Can. 2013; 35: 177-181
        • Norton M.E.
        • Jacobsson B.
        • Swamy G.K.
        • Laurent L.C.
        • Ranzini A.C.
        • Brar H.
        • et al.
        Cell-free DNA analysis for noninvasive examination of trisomy.
        N Engl J Med. 2015; 372: 1589-1597
        • Audibert F.
        • Gagnon A.
        • Society of Obstetricians and Gynaecologists of Canada Genetics Committee
        Prenatal screening for and diagnosis of aneuploidy in twin pregnancies. Joint SOGC-CCMG Clinical Practice Guideline, No. 262, July 2011.
        J Obstet Gynaecol Can. 2011; 33: 754-767
        • Dar P.
        • Curnow K.J.
        • Gross S.J.
        • Hall M.P.
        • Stosic M.
        • Demko Z.
        • et al.
        Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing.
        Am J Obstet Gynecol. 2014; 211: 527
        • Zhang H.
        • Gao Y.
        • Jiang F.
        • Fu M.
        • Yuan Y.
        • Guo Y.
        • et al.
        Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146958 pregnancies.
        Ultrasound Obstet Gynecol. 2015; 45: 530-538
        • Ogbogu U.
        • Caulfield T.
        Science powers commerce: mapping the language, justifications, and perceptions of the drive to commercialize in the context of Canadian research.
        Can J Comp & Contemp L. 2015; 1: 137-158
        • Agarwal A.
        • Sayres L.C.
        • Cho M.K.
        • Cook-Deegan R.
        • Chandrasekharan S.
        Commercial landscape of noninvasive prenatal testing in the United States.
        Prenat Diagn. 2013; 33: 521-531
      4. Natera (US). Conceive. Deliver. Available at: http://www.natera.com/reproductive-genetic-testing. Accessed on April 5, 2016.

      5. GlobeNewswire. New fetal test spares pregnant moms the risks of amniocentesis. Available at: https://globenewswire.com/news-release/2013/04/03/535659/10027308/en/New-Fetal-Test-Spares-Pregnant-Moms-the-Risks-of-Amniocentesis.html. Accessed on April 15, 2016.

        • Haute Autorité de Santé
        Les performances des tests ADN libre circulant pour le dépistage de la trisomy 21 foetale [The performance of free circulating DNA tests for the detection of fetal trisomy 21].
        Haute Autorité de Santé, Saint-Denis, France2015
        • United Kingdom National Screening Committee
        Consultation for cell-free DNA testing in the first trimester in the Fetal Anomaly Screening Programme.
        United Kingdom National Screening Committee, London2016
        • Canadian Agency for Drugs and Technologies in Health
        Non-invasive prenatal testing: a review of the cost effectiveness and guidelines.
        Canadian Agency for Drugs and Technologies in Health, Ottawa2014
        • Gekas J.
        • Langlois S.
        • Ravitsky V.
        • Audibert F.
        • van den Berg D.G.
        • Haidar H.
        • et al.
        Identification of trisomy 18, trisomy 13, and down syndrome from maternal plasma.
        Appl Clin Genet. 2014; 7: 127-131
        • Piechan J.L.
        • Hines K.A.
        • Koller D.L.
        • Stone K.
        • Quaid K.
        • Torres-Martinez W.
        • et al.
        NIPT and informed consent: an assessment of patient understanding of a negative NIPT result.
        J Genet Couns. 2016; 25 (Accessed April 1, 2016.): 1127-1137
        • Sahlin E.
        • Nordenskjöld M.
        • Gustavsson P.
        • Wincent J.
        • Georgsson S.
        • Iwarsson E.
        Positive attitudes towards non-invasive prenatal testing (NIPT) in a Swedish cohort of 1,003 pregnant women.
        PloS One. 2016; 11: e0156088
        • Morris S.
        • Karlsen S.
        • Chung N.
        • Hill M.
        • Chitty L.S.
        Model-based analysis of costs and outcomes of non-invasive prenatal testing for Down's syndrome using cell free fetal DNA in the UK National Health Service.
        PLoS One. 2014; 9: e93559
        • Hulstaert F.
        • Neyt M.
        • Gyselaers W.
        Belgian Health Care Knowledge Center (KCE), The non-invasive prenatal test (NIPT) for trisomy 21 – health economic aspects.
        Health Technol Assess. 2014; (KCE Report 222.)
        • Fairbrother G.
        • Burigo J.
        • Sharon T.
        • Song K.
        Prenatal screening for fetal aneuploidies with cell-free DNA in the general pregnancy population: a cost-effectiveness analysis.
        J. Matern Fetal Neonatal Med. 2016; 29: 1160-1164
      6. Warren N. Manderson L. Reframing disability and quality of life: a global perspective. Springer Science & Business Media, Berlin2013
        • Goldhaber-Fiebert J.D.
        • Brandeau M.L.
        Evaluating cost-effectiveness of interventions that affect fertility and childbearing how health effects are measured matters.
        Med Decis Making. 2015; 35: 818-846
        • Levesque M.
        • Kim J.R.
        • Isasi R.
        • Knoppers B.M.
        • Joly Y.
        Stem cell research funding policies and dynamic innovation: a survey of open access and commercialization requirements.
        Stem Cell Rev. 2014; 10: 455-471
        • Institute of Medicine
        Evolution of translational omics: lessons learned and the path forward.
        The National Academies Press, Washington2012
        • Roseman M.
        • Milette K.
        • Bero L.A.
        • Coyne J.C.
        • Lexchin J.
        • Turner E.H.
        • et al.
        Reporting of conflicts of interest in meta-analyses of trials of pharmacological treatments.
        J Am Med Assoc. 2011; 305: 1008-1017
        • Lumbreras B.
        • Parker L.A.
        • Porta M.
        • Pollán M.
        • Ioannidis J.P.A.
        • Hernández-Aguado I.
        Overinterpretation of clinical applicability in molecular diagnostic research.
        Clin Chem. 2009; 55: 786-794
        • Bell C.M.
        • Urbach D.R.
        • Ray J.G.
        • Bayoumi A.
        • Rosen A.B.
        • Greenberg D.
        • et al.
        Bias in published cost effectiveness studies: systematic review.
        Br J Med. 2006; 332: 699-703
        • Petersen A.
        • Krisjansen I.
        Assembling ‘the bioeconomy’: exploiting the power of the promissory life sciences.
        J Sociol. 2015; 51: 28-46
        • Lundh A.
        • Sismondo S.
        • Lexchin J.
        • Busuioc O.A.
        • Bero L.
        Industry sponsorship and research outcome. Outcome reporting among drug trials registered in ClinicalTrials.gov.
        Cochrane Database Syst Rev. 2012; 12: MR000033
        • Fugh-Berman A.
        How basic scientists help the pharmaceutical industry market drugs.
        PLoS Biol. 2013; 11: e1001716
        • Tsilidis K.K.
        • Panagiotou O.A.
        • Sena E.S.
        • Aretouli E.
        • Evangelou E.
        • Howells D.W.
        • et al.
        Evaluation of excess significance bias in animal studies of neurological diseases.
        PLoS Biol. 2013; 11: e1001609
        • Lexchin J.
        Those who have the gold make the evidence: how the pharmaceutical industry biases the outcomes of clinical trials of medications.
        Sci Eng Ethics. 2012; 18: 247-261
        • Stamatakis E.
        • Weiler R.
        • Ioannidis J.
        Undue industry influences that distort healthcare research, strategy, expenditure and practice: a review.
        Eur J Clin Invest. 2013; 43: 469-475
        • Dachis B.
        • Chesterley N.
        • Jacobs A.
        • Brydon R.
        Measuring innovation in Canada: the tale told by patent applications.
        C.D. Howe Institute, Toronto2014: 191 (Available at:) (Accessed on April 15, 2016)
        • Bessen J.
        • Meurer M.J.
        Patent failure.
        Princeton University Press, Princeton2008
        • Bubela T.M.
        • Caulfield T.
        Role and reality: technology transfer at Canadian universities.
        Trends Biotechnol. 2010; 28: 447-451
        • Morain S.
        • Greene M.F.
        • Mello M.M.
        A new era in noninvasive prenatal testing.
        N Engl J Med. 2013; 369: 499-501
      7. MarketersMedia. Non-invasive prenatal testing (NIPT) market expected to reach USD 2.38 billion in 2022: transparency market research. 2015. Available from: http://marketersmedia.com/non-invasive-prenatal-testing-nipt-market-expected-to-reach-usd-2-38-billion-in-2022-transparency-market-research/87584. Accessed on April 15, 2016.

      8. PRNewswire. Non-invasive prenatal testing (NIPT) market expected to reach USD 3.68 billion globally in 2019: transparency market research. 2014. Available at: http://www.prnewswire.com/news-releases/non-invasive-prenatal-testing-nipt-market-expected-to-reach-usd-362-billion-globally-in-2019-transparency-market-research-238824411.html. Accessed on April 15, 2016.

      9. MarketWatch. Global non-invasive prenatal test (NIPT) market is expected to grow at 17.6% CAGR during 2015-2020. 2015. Available at: http://www.marketwatch.com/story/global-non-invasive-prenatal-testing-nipt-market-is-expected-to-grow-at-176-cagr-during-2015–-2020-2015-11-19-82033153. Accessed on April 15, 2016.

      10. Heger M. Sequenom eyes low-risk NIPT market; inks contract with Aetna. GenomeWeb 2014. Available at: https://www.genomeweb.com/sequencing/sequenom-eyes-low-risk-nipt-market-inks-contract-aetna. Accessed on April 15, 2016.

        • Lefkowitz R.B.
        • Tynan J.A.
        • Liu T.
        • Wu Y.
        • Mazloom A.R.
        • Almasri E.
        • et al.
        Clinical validation of a noninvasive prenatal test for genomewide detection of fetal copy number variants.
        Am J Obstet Gynecol. 2016; 215: 227.e1-227.e16
        • Hui W.W.I.
        • Chiu R.W.K.
        Noninvasive prenatal testing beyond genomic analysis: what the future holds.
        Curr Opin Obstet Gynecol. 2016; 28: 105-110
      11. Regalado A. Prenatal DNA sequencing. MIT Technology Review. 2013. Available at: https://www.technologyreview.com/s/513691/prenatal-dna-sequencing/. Accessed on April 15, 2016.

      12. Young RS. A brave new world of prenatal sequencing. MIT Technology Review. 2013. Available at: https://www.technologyreview.com/s/510181/a-brave-new-world-of-prenatal-dna-sequencing/. Accessed on April 15, 2016.

        • Nicolaides K.H.
        • Syngelaki A.
        • Ashoor G.
        • Birdir C.
        • Touzet G.
        Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population.
        Am J Obstet Gynecol. 2012; 207: 374.e1-374.e6
        • Bayindir B.
        • Dehaspe L.
        • Brison N.
        • Brady P.
        • Ardui S.
        • Kammoun M.
        • et al.
        Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management.
        Eur J Hum Genet. 2015; 23: 1286-1293
        • Straver R.
        • Oudejans C.B.M.
        • Sistermans E.A.
        • Reinders M.J.T.
        Calculating the fetal fraction for non invasive prenatal testing based on genome-wide nucleosome profiles.
        Prenat Diagn. 2016; 36: 614-621
        • Dan S.
        • Wang W.
        • Ren J.
        • Li Y.
        • Hu H.
        • Xu Z.
        • et al.
        Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11 105 pregnancies with mixed risk factors.
        Prenat Diagn. 2012; 32: 1225-1232
        • Chen E.Z.
        • Chiu R.W.
        • Sun H.
        • Akolekar R.
        • Chan K.A.
        • Leung T.Y.
        • et al.
        Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing.
        PloS One. 2011; 6: e21791
        • Chiu R.W.
        • Akolekar R.
        • Zheng Y.W.
        • Leung T.Y.
        • Sun H.
        • Chan K.A.
        • et al.
        Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study.
        BMJ. 2011; 342: c7401
        • Chiu R.W.
        • Chan K.A.
        • Gao Y.
        • Lau V.Y.
        • Zheng W.
        • Leung T.Y.
        • et al.
        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
        • Takoudes T.
        • Hamar B.
        Performance of non-invasive prenatal testing when fetal cell-free DNA is absent.
        Ultrasound Obstet Gynecol. 2015; 45: 112
        • Gil M.M.
        • Quezada M.S.
        • Revello R.
        • Akolekar R.
        • Nicolaides K.H.
        Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis.
        Ultrasound Obstet Gynecol. 2015; 45: 249-266
        • Lutgendorf M.A.
        • Stoll K.A.
        Why 99% may not be as good as you think it is: limitations of screening for rare diseases.
        J Matern Fetal Neonat Med. 2016; 29: 1187-1189
        • Thumm N.
        Strategic patenting in biotechnology.
        Technology Analysis & Strategic Management. 2004; 16: 529-538
        • Caulfield T.
        Biotechnology and the popular press: hype and the selling of science.
        Trends Biotechnol. 2004; 22: 337-339
        • Bubela T.M.
        • Li M.D.
        • Hafez M.
        • Bieber M.
        • Atkins H.
        Is belief larger than fact: expectations, optimism and reality for translational stem cell research.
        BMC Med. 2012; 10: 1
        • Kamenova K.
        • Caulfield T.
        Stem cell hype: media portrayal of therapy translation.
        Sci Transl Med. 2015; 7: 278ps4
        • Bubela T.M.
        • Caulfield T.
        Do the print media “hype” genetic research? A comparison of newspaper stories and peer-reviewed research papers.
        Can Med Assoc J. 2004; 170: 1399-1407
      13. Karow J. Noninvasive prenatal testing diversifies in 2015, migrates toward average-risk market. GenomeWeb 2016. Available at: https://www.genomeweb.com/molecular-diagnostics/noninvasive-prenatal-testing-diversifies-2015-migrates-toward-average-risk. Accessed on April 15, 2016.

        • Norton M.E.
        • Rink B.D.
        Changing indications for invasive testing in an era of improved screening.
        Semin Perinatol. 2016; 40: 56-66
        • Lo K.K.
        • Karampetsou E.
        • Boustred C.
        • McKay F.
        • Mason S.
        • Hill M.
        • et al.
        Limited clinical utility of non-invasive prenatal testing for subchromosomal abnormalities.
        Am J Hum Genet. 2016; 98: 34-44
        • Hill M.
        • Lewis C.
        • Chitty L.S.
        Stakeholder attitudes and needs regarding cell-free fetal DNA testing.
        Curr Opin Obstet Gynecol. 2016; 28: 125-131
        • Vanstone M.
        • King C.
        • de Vrijer B.
        • Nisker J.
        Non-invasive prenatal testing: ethics and policy considerations.
        J Obstet Gynaecol Can. 2014; 36: 515-526
        • Lewis C.
        • Hill M.
        • Skirton H.
        • Chitty L.S.
        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
        • van Schendel R.V.
        • Dondorp W.J.
        • Timmermans D.R.
        • Hugte E.J.
        • Boer A.
        • Pajkrt E.
        • et al.
        NIPT-based screening for Down syndrome and beyond: what do pregnant women think?.
        Prenat Diagn. 2015; 35: 598-604
        • Devaney S.
        • Palomaki G.
        • Scott J.
        • Bianchi D.
        Noninvasive fetal sex determination using cell-free fetal DNA: a systematic review and meta-analysis.
        JAMA. 2011; 306: 627-636
        • Stern A.M.
        Eugenic nation: faults and frontiers of better breeding in modern America.
        University of California Press, Berkeley2015
        • Chachkin C.J.
        What potent blood: non-invasive prenatal genetic diagnosis and the transformation of modern prenatal care.
        Am J Law Med. 2007; 33: 9-53
        • Ma Y.
        • Gong H.
        • Wen Y.
        Nucleic acid-based non-invasive prenatal diagnosis of genetic skin diseases: are we ready?.
        Exp Dermatol. 2013; 22: 392-395
        • Toews M.
        • Caulfield T.
        Physician liability and non-invasive prenatal testing.
        J Obstet Gynaecol Can. 2014; 36: 907-914
        • van Schendel R.V.
        • Kleinveld J.H.
        • Dondorp W.J.
        • Pajkrt E.
        • Timmermans D.R.
        • Holtkamp K.C.
        • et al.
        Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening.
        Eur J Hum Genet. 2014; 22: 1345-1350
        • Farrell R.M.
        • Mercer M.B.
        • Agatisa P.K.
        • Smith M.B.
        • Philipson E.
        It's more than a blood test: patients' perspectives on noninvasive prenatal testing.
        J Clin Med. 2014; 3: 614-631
      14. Canada NewsWire. Medcan is the first Canadian clinic to provide verinata non-invasive prenatal testing (NIPT) to pregnant women. 2013. Available at: http://www.newswire.ca/news-releases/medcan-is-the-first-canadian-clinic-to-provide-verinata-non-invasive-prenatal-testing-nipt-to-pregnant-women-512195581.html. Accessed on April 15, 2016.

      15. Press Association. Non-invasive test for Down's syndrome recommended for high-risk women. The Guardian 2016. Available at: http://www.theguardian.com/society/2016/jan/15/non-invasive-test-for-downs-syndrome-recommended-for-high-risk-women. Accessed on April 15, 2016.

      16. What to Expect. Noninvasive prenatal testing (NIPT). 2015. Available from: http://www.whattoexpect.com/pregnancy/pregnancy-health/noninvasive-prenatal-testing. Accessed on April 16, 2016.

        • Seavilleklein V.
        Challenging the rhetoric of choice in prenatal screening.
        Bioethics. 2009; 23: 68-77
        • Rothman B.K.
        The tentative pregnancy; how amniocentesis changes the experience of motherhood.
        WW Norton and Company, New York1993
        • Favre R.
        • Moutel G.
        • Duchange N.
        • Vayssière C.
        • Kohler M.
        • Bouffet N.
        • et al.
        What about informed consent in First-trimester ultrasound screening for Down Syndrome?.
        Fetal Diagn Ther. 2008; 23: 173-184
        • 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 Educ Couns. 2010; 78: 24-28