- Email: [email protected]
Unfair discrimination in prenatal aneuploidy screening using cell-free DNA?
European Journal of Obstetrics & Gynecology and Reproductive Biology 198 (2016) 27–29
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Review
Unfair discrimination in prenatal aneuploidy screening using cell-free DNA? Vasilija Rolfes, Dagmar Schmitz * Institute for History, Theory and Ethics of Medicine, University Hospital RWTH Aachen, Wendlingweg 2, 52074 Aachen, Germany
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 December 2015 Accepted 21 December 2015
Non-invasive prenatal testing on the basis of cell-free DNA of placental origin (NIPT) changed the landscape of prenatal care and is seen as superior to all other up to now implemented prenatal screening procedures – at least in the high-risk population. NIPT has spread almost worldwide commercially, but only in a few countries the costs of NIPT are covered by insurance companies. Such financial barriers in prenatal testing can lead to significant restrictions to the average range of opportunities of pregnant women and couples, which on an intersubjective level can be defined as unfair discrimination and on an individual level weakens reproductive autonomy. Given that enabling reproductive autonomy is the main ethical justification for offering prenatal (genetic) testing, these barriers are not only an issue of justice in health care, but are potentially counteracting the primary purpose of these testing procedures. ß 2016 Elsevier Ireland Ltd. All rights reserved.
Keywords: Non-Invasive Prenatal Testing Reproductive autonomy Unfair discrimination
Contents The well-known debate: reproductive autonomy The missing link: equality of opportunity . . . . . . The fallacy: high risk and reimbursement . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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In recent years the landscape of non-invasive prenatal testing has substantially changed. The analysis of cell-free (cf) DNA fragments of placental origin in the maternal blood provides currently the most accurate screening test for fetal autosomal aneuploidies in early pregnancy [1–4]. Because of lower screen positive rates, the implementation of non-invasive prenatal testing (NIPT) on the basis of cf DNA in addition led to a significant decrease in invasive diagnostic procedures like amniocentesis [5]. It has been concluded, consequently, that NIPT is in many respects superior to all other up to now implemented screening methods [6,7] and is recommended for pregnant women with an increased risk of aneuploidy [8,9]. In
* Corresponding author. Tel.: +49 2418085101. E-mail addresses: [email protected] (V. Rolfes), [email protected] (D. Schmitz). http://dx.doi.org/10.1016/j.ejogrb.2015.12.023 0301-2115/ß 2016 Elsevier Ireland Ltd. All rights reserved.
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28 28 28 29 29 29 29
more than 60 countries, NIPT for fetal aneuploidies is already available in the private sector [10]. Whether the new non-invasive prenatal testing procedures for fetal aneuploidies should be part of public health services and the costs should be reimbursed by health insurance companies, is currently discussed controversially worldwide [11–13]. In the US, coverage by private insurances and state Medicaid are inconsistent, – some state Medicaid programs do not bear any costs, some only those from certain companies [10,12]. Currently, the costs of the test are ranging from $795 to $3000 in the USA [10] and from $500 to $1500 in other countries [13,14]. Especially for pregnant woman in low- and middle-income countries, where the costs of NIPT are equal to or exceed the average monthly income per household, it is difficult to benefit from the obvious advantages of NIPT [12]. Even experts conclude that mainly economic aspects will determine how NIPT is implemented into existing clinical care pathways [15].
28
V. Rolfes, D. Schmitz / European Journal of Obstetrics & Gynecology and Reproductive Biology 198 (2016) 27–29
Essentially, two scenarios of implementation are proposed: NIPT can either (a) be offered as a first-line screening to all pregnant women or (b) as a contingent second-line screening only to those women, who are at a higher risk for fetal autosomal aneuploidies (after for example first trimester screening) [6,15]. In both options, access to NIPT can be limited by financial barriers, – either directly or indirectly. Where certain risk factors like an advanced maternal age are set as a precondition for the reimbursement of the costs of the test, every woman, who does not have any of these risk factors and still wants to have NIPT or another prenatal screening for fetal aneuploidies, will have to pay for it privately. Especially in the case of the still expensive NIPTprocedures, this might not be possible for many women. So the financial situation of a woman limits the access to prenatal aneuploidy screening, although there are no categorical restrictions to it. The ethical justifiability of this possible financial barrier, however, has not been thoroughly analyzed or debated so far, although ethical aspects of prenatal testing have always been of heightened public and scientific interest.
The well-known debate: reproductive autonomy The main ethical argument, which usually is brought forward in favor of prenatal testing, is its impact on the reproductive autonomy of the pregnant woman or the couple, on determining not only whether to have a child, but what kind of child to have [16]. It is argued that autonomy-based indications (based on the well-informed decision of the pregnant woman) should be given the same weight as beneficence-based indications in prenatal care [17]. Prenatal testing and especially non-invasive prenatal testing has the potential to support pregnant women in decisionmaking processes regarding the continuation or termination of their pregnancy effectively, safely and at an early gestational age [18]. In contrast to its frequent use, the exact meaning of ‘‘reproductive autonomy’’ (or of sometimes synonymously used terms like ‘‘reproductive freedom’’ or ‘‘procreative liberty’’) as well as its ethical grounding remains largely unclear [19]. Ronald Dworkin, an American philosopher, sees it as grounded in ‘‘a belief in individual human dignity: that people have the moral right – and the moral responsibility – to confront the most fundamental questions about the meaning and value of their own lives for themselves: answering to their own conscience and convictions’’ [20]. Understood like that reproductive autonomy represents a certain (and in the case of Dworkin) strong notion of individual autonomy, of self-determination or self-expression, which might serve as a justification for the termination of an early pregnancy, if the future child1 will for example suffer from a serious disease [19]. If prenatal testing reveals a serious disease in the embryo or fetus, this in all likelihood not only significantly affects the actual and future wellbeing of the pregnant woman or the couple, but also potentially restricts their future range of individual opportunities in a far more complex way than living with children usually does. It is argued that one should have the chance to get the information necessary to decide whether one wants to accept these foreseeable restrictions to individual opportunities or if these restrictions seem unbearable. In this argument, prenatal testing impresses as an instrument to restore the full range of individual opportunities and is, thus, necessarily linked to questions of justice.
1 An indispensable precondition for any appeal to the reproductive autonomy of pregnant women in relation to prenatal testing and subsequent termination of pregnancy, however, is to understand the embryo or fetus as not having the same rights as persons (which is increasingly controversial with a higher gestational age).
The missing link: equality of opportunity The most influential contemporary liberal approaches to social justice encompass the idea of fair equality of opportunity [21]. Norman Daniels broadened the field to ‘‘arrays of life plans persons can reasonably choose in a given society’’ [22]. If reproductive autonomy on an individual level is predominantly understood as a certain notion of individual autonomy, of selfexpression and shaping the individual future, than this intersubjectively means, that pregnant women should principally have equal access to effective means for preventing foreseeable severe restrictions to their individual autonomy, to their average range of opportunities. The idea of reproductive freedom even gains its moral importance partly through the principle of equal opportunity [16]. It is for example argued that having the possibility to choose whether to live with and care for a severely ill child would help to prevent gender inequalities (‘‘since women typically bear a disproportionate share of childrearing’’) [16]. If NIPT is in many aspects superior to other screening methods, every pregnant woman should have access to this testing procedure in order to exercise her reproductive autonomy and, thus, have the equal opportunity to create her future based on her beliefs and values. The fallacy: high risk and reimbursement Is it then justified to claim reimbursement of all costs of prenatal aneuploidy screening in a publicly funded health care system? Usually, entitlements in health care are first of all linked to diseases. The easiest way to justify them is to show that they are necessary in relation to a certain disease. Differing concepts of disease, thus, are resulting in differing justified entitlements in health care. Two main groups of concepts can be distinguished in the theory of disease: normative and objective concepts [23]. Whereas normative approaches encompass a negative evaluation of bodily or mental conditions, objective approaches are value-neutral and directed toward verifiable pathological conditions. At first sight, reimbursement of prenatal aneuploidy screening seems to be a justified claim in relation to both groups of concepts. An autosomal aneuploidy like trisomy 21 is objectively as well as normatively usually understood as a disease. Objective concepts of disease are referring on measurable cognitive deficits and frequently associated malformations in trisomy 21, whereas normative concepts relate for example to the suffering of the child during necessary medical treatments or to the expected lifelong dependency of the affected person. The problem here is that not the affected fetus, but the pregnant woman is claiming health care resources and that they are not claimed in order to alleviate the suffering or restore the opportunities of the affected person. Nevertheless, the idea of reproductive autonomy is strongly linked to a fair equality of individual opportunities. Therefore, reimbursement of the costs does not seem to be a matter of justice in health care, but of social justice. Consequently, questions of distribution of scarce resources should be discussed in terms of social justice and not in terms of justice in health care. If prenatal testing is seen as an important instrument in order to restore the full individual range of opportunities, than free access to prenatal aneuploidy screening should be provided for every pregnant woman. If this is not possible in a given health care system, than it should at least be provided for women with a low income. To presuppose a higher individual risk for an aneuploidy in the fetus as a criterion for reimbursement represents in contrast a medical fallacy and leads to unfair discrimination in prenatal medicine, because it neglects the relevant aspects of social justice.
V. Rolfes, D. Schmitz / European Journal of Obstetrics & Gynecology and Reproductive Biology 198 (2016) 27–29
Summary In conclusion, questions of justice, of fair equality of opportunity, are strongly linked to the main argument for prenatal testing, – to the reproductive autonomy of pregnant women. This has to be reflected more adequately by the clinical pathways in prenatal care in order to avoid unfair discrimination against a particular group of pregnant women and, thus, give real meaning to the popular calls for reproductive autonomy. NIPT is seen as superior to all other up to now implemented prenatal screening procedures and at the same time also still is and might remain a comparably expensive medical testing procedure. Any financial barriers are therefore significant and might result in unfair discrimination of a group of pregnant women, – in particular of women with no sufficient financial resources. If a society agrees on the importance of reproductive autonomy and of prenatal testing in order to realize it, but cannot afford free access for everybody, it has to modulate the resulting inequalities as just as possible. This could for example mean that only pregnant women with a low income are granted reimbursement of the NIPT costs by health insurance companies. Conflict of interest The authors report no conflict of interest. Acknowledgements The research was funded by the German Ministry of Education and Research (BMBF) in the research project ‘‘Indication or information? The role of the physician in the context of noninvasive prenatal diagnosis’’ (ELSA funding line, grant number 01GP1201). References [1] Bianchi DW, Parker RL, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med 2014;370(9):799–808. [2] Lo YM, Tein MS, Lau TK, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998;62(4):768–75.
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[3] Chiu RW, Chan KC, Gao Y, et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci U S A 2008;105(51):20458–63. [4] 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 U S A 2008. [5] Warsof SL, Larion S, Abuhamad AZ. Overview of the impact of noninvasive prenatal testing on diagnostic procedures. Prenat Diagn 2015;35(10): 972–9. [6] Gil MM, Akolekar R, Quezada MS, Bregant B, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: meta-analysis. Fetal Diagn Ther 2014;35(3):156–73. [7] Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med 2015;372(17):1589–97. [8] Committee Opinion No. 640: cell-free DNA screening for fetal aneuploidy. Obstet Gynecol 2015;126(3):e31–7. [9] #36: prenatal aneuploidy screening using cell-free DNA. Am J Obstet Gynecol 2015;212(6):711–6. [10] Allyse M, Minear MA, Berson E, et al. Non-invasive prenatal testing: a review of international implementation and challenges. Int J Women’s Health 2015;7: 113–26. [11] Hill M, Wright D, Daley R, et al. Evaluation of non-invasive prenatal testing (NIPT) for aneuploidy in an NHS setting: a reliable accurate prenatal noninvasive diagnosis (RAPID) protocol. BMC Pregnancy Childbirth 2014;14:229. [12] Chandrasekharan S, Minear MA, Hung A, Allyse M. Noninvasive prenatal testing goes global. Sci Transl Med 2014;6(231):231fs15. [13] Benn P, Cuckle H, Pergament E. Non-invasive prenatal testing for aneuploidy: current status and future prospects. Ultrasound Obstet Gynecol 2013;42(1): 15–33. [14] Agarwal A, Sayres LC, Cho MK, Cook-Deegan R, Chandrasekharan S. Commercial landscape of noninvasive prenatal testing in the United States. Prenat Diagn 2013;33(6):521–31. [15] Bianchi DW, Wilkins-Haug L. Integration of noninvasive DNA testing for aneuploidy into prenatal care: what has happened since the rubber met the road? Clin Chem 2014;60(1):78–87. [16] Buchanan A, Brock DW, Daniels N, Wikler D. From chance to choice. In: Genetics & justice. Cambridge, New York: Cambridge University Press; 2000. [17] Chervenak FA, McCullough LB, Chervenak JL. Prenatal informed consent for sonogram: an indication for obstetric ultrasonography. Am J Obstet Gynecol 1989;161(4):857–60. [18] Deans Z, Newson AJ. Ethical considerations for choosing between possible models for using NIPD for aneuploidy detection. J Med Ethics 2012;38(10): 614–8. [19] O’Neill O. Autonomy and trust in bioethics. Cambridge, New York: Cambridge University Press; 2002. [20] Dworkin R. Life’s dominion: an argument about abortion. Euthanasia, and individual freedom. New York: Vintage Books; 1993. [21] Rawls J. A theory of justice. Oxford: Clarendon Press; 1972. [22] Daniels N. Just health: meeting health needs fairly. New York: Cambridge University Press; 2008. [23] Schramme T. Einleitung: Die Begriffe Gesundheit und Krankheit in der philosophischen Diskussion. In: Schramme T, editor. Krankheitstheorien. Berlin: Suhrkamp Verlag; 2012.
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Review
Unfair discrimination in prenatal aneuploidy screening using cell-free DNA? Vasilija Rolfes, Dagmar Schmitz * Institute for History, Theory and Ethics of Medicine, University Hospital RWTH Aachen, Wendlingweg 2, 52074 Aachen, Germany
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 December 2015 Accepted 21 December 2015
Non-invasive prenatal testing on the basis of cell-free DNA of placental origin (NIPT) changed the landscape of prenatal care and is seen as superior to all other up to now implemented prenatal screening procedures – at least in the high-risk population. NIPT has spread almost worldwide commercially, but only in a few countries the costs of NIPT are covered by insurance companies. Such financial barriers in prenatal testing can lead to significant restrictions to the average range of opportunities of pregnant women and couples, which on an intersubjective level can be defined as unfair discrimination and on an individual level weakens reproductive autonomy. Given that enabling reproductive autonomy is the main ethical justification for offering prenatal (genetic) testing, these barriers are not only an issue of justice in health care, but are potentially counteracting the primary purpose of these testing procedures. ß 2016 Elsevier Ireland Ltd. All rights reserved.
Keywords: Non-Invasive Prenatal Testing Reproductive autonomy Unfair discrimination
Contents The well-known debate: reproductive autonomy The missing link: equality of opportunity . . . . . . The fallacy: high risk and reimbursement . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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In recent years the landscape of non-invasive prenatal testing has substantially changed. The analysis of cell-free (cf) DNA fragments of placental origin in the maternal blood provides currently the most accurate screening test for fetal autosomal aneuploidies in early pregnancy [1–4]. Because of lower screen positive rates, the implementation of non-invasive prenatal testing (NIPT) on the basis of cf DNA in addition led to a significant decrease in invasive diagnostic procedures like amniocentesis [5]. It has been concluded, consequently, that NIPT is in many respects superior to all other up to now implemented screening methods [6,7] and is recommended for pregnant women with an increased risk of aneuploidy [8,9]. In
* Corresponding author. Tel.: +49 2418085101. E-mail addresses: [email protected] (V. Rolfes), [email protected] (D. Schmitz). http://dx.doi.org/10.1016/j.ejogrb.2015.12.023 0301-2115/ß 2016 Elsevier Ireland Ltd. All rights reserved.
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28 28 28 29 29 29 29
more than 60 countries, NIPT for fetal aneuploidies is already available in the private sector [10]. Whether the new non-invasive prenatal testing procedures for fetal aneuploidies should be part of public health services and the costs should be reimbursed by health insurance companies, is currently discussed controversially worldwide [11–13]. In the US, coverage by private insurances and state Medicaid are inconsistent, – some state Medicaid programs do not bear any costs, some only those from certain companies [10,12]. Currently, the costs of the test are ranging from $795 to $3000 in the USA [10] and from $500 to $1500 in other countries [13,14]. Especially for pregnant woman in low- and middle-income countries, where the costs of NIPT are equal to or exceed the average monthly income per household, it is difficult to benefit from the obvious advantages of NIPT [12]. Even experts conclude that mainly economic aspects will determine how NIPT is implemented into existing clinical care pathways [15].
28
V. Rolfes, D. Schmitz / European Journal of Obstetrics & Gynecology and Reproductive Biology 198 (2016) 27–29
Essentially, two scenarios of implementation are proposed: NIPT can either (a) be offered as a first-line screening to all pregnant women or (b) as a contingent second-line screening only to those women, who are at a higher risk for fetal autosomal aneuploidies (after for example first trimester screening) [6,15]. In both options, access to NIPT can be limited by financial barriers, – either directly or indirectly. Where certain risk factors like an advanced maternal age are set as a precondition for the reimbursement of the costs of the test, every woman, who does not have any of these risk factors and still wants to have NIPT or another prenatal screening for fetal aneuploidies, will have to pay for it privately. Especially in the case of the still expensive NIPTprocedures, this might not be possible for many women. So the financial situation of a woman limits the access to prenatal aneuploidy screening, although there are no categorical restrictions to it. The ethical justifiability of this possible financial barrier, however, has not been thoroughly analyzed or debated so far, although ethical aspects of prenatal testing have always been of heightened public and scientific interest.
The well-known debate: reproductive autonomy The main ethical argument, which usually is brought forward in favor of prenatal testing, is its impact on the reproductive autonomy of the pregnant woman or the couple, on determining not only whether to have a child, but what kind of child to have [16]. It is argued that autonomy-based indications (based on the well-informed decision of the pregnant woman) should be given the same weight as beneficence-based indications in prenatal care [17]. Prenatal testing and especially non-invasive prenatal testing has the potential to support pregnant women in decisionmaking processes regarding the continuation or termination of their pregnancy effectively, safely and at an early gestational age [18]. In contrast to its frequent use, the exact meaning of ‘‘reproductive autonomy’’ (or of sometimes synonymously used terms like ‘‘reproductive freedom’’ or ‘‘procreative liberty’’) as well as its ethical grounding remains largely unclear [19]. Ronald Dworkin, an American philosopher, sees it as grounded in ‘‘a belief in individual human dignity: that people have the moral right – and the moral responsibility – to confront the most fundamental questions about the meaning and value of their own lives for themselves: answering to their own conscience and convictions’’ [20]. Understood like that reproductive autonomy represents a certain (and in the case of Dworkin) strong notion of individual autonomy, of self-determination or self-expression, which might serve as a justification for the termination of an early pregnancy, if the future child1 will for example suffer from a serious disease [19]. If prenatal testing reveals a serious disease in the embryo or fetus, this in all likelihood not only significantly affects the actual and future wellbeing of the pregnant woman or the couple, but also potentially restricts their future range of individual opportunities in a far more complex way than living with children usually does. It is argued that one should have the chance to get the information necessary to decide whether one wants to accept these foreseeable restrictions to individual opportunities or if these restrictions seem unbearable. In this argument, prenatal testing impresses as an instrument to restore the full range of individual opportunities and is, thus, necessarily linked to questions of justice.
1 An indispensable precondition for any appeal to the reproductive autonomy of pregnant women in relation to prenatal testing and subsequent termination of pregnancy, however, is to understand the embryo or fetus as not having the same rights as persons (which is increasingly controversial with a higher gestational age).
The missing link: equality of opportunity The most influential contemporary liberal approaches to social justice encompass the idea of fair equality of opportunity [21]. Norman Daniels broadened the field to ‘‘arrays of life plans persons can reasonably choose in a given society’’ [22]. If reproductive autonomy on an individual level is predominantly understood as a certain notion of individual autonomy, of selfexpression and shaping the individual future, than this intersubjectively means, that pregnant women should principally have equal access to effective means for preventing foreseeable severe restrictions to their individual autonomy, to their average range of opportunities. The idea of reproductive freedom even gains its moral importance partly through the principle of equal opportunity [16]. It is for example argued that having the possibility to choose whether to live with and care for a severely ill child would help to prevent gender inequalities (‘‘since women typically bear a disproportionate share of childrearing’’) [16]. If NIPT is in many aspects superior to other screening methods, every pregnant woman should have access to this testing procedure in order to exercise her reproductive autonomy and, thus, have the equal opportunity to create her future based on her beliefs and values. The fallacy: high risk and reimbursement Is it then justified to claim reimbursement of all costs of prenatal aneuploidy screening in a publicly funded health care system? Usually, entitlements in health care are first of all linked to diseases. The easiest way to justify them is to show that they are necessary in relation to a certain disease. Differing concepts of disease, thus, are resulting in differing justified entitlements in health care. Two main groups of concepts can be distinguished in the theory of disease: normative and objective concepts [23]. Whereas normative approaches encompass a negative evaluation of bodily or mental conditions, objective approaches are value-neutral and directed toward verifiable pathological conditions. At first sight, reimbursement of prenatal aneuploidy screening seems to be a justified claim in relation to both groups of concepts. An autosomal aneuploidy like trisomy 21 is objectively as well as normatively usually understood as a disease. Objective concepts of disease are referring on measurable cognitive deficits and frequently associated malformations in trisomy 21, whereas normative concepts relate for example to the suffering of the child during necessary medical treatments or to the expected lifelong dependency of the affected person. The problem here is that not the affected fetus, but the pregnant woman is claiming health care resources and that they are not claimed in order to alleviate the suffering or restore the opportunities of the affected person. Nevertheless, the idea of reproductive autonomy is strongly linked to a fair equality of individual opportunities. Therefore, reimbursement of the costs does not seem to be a matter of justice in health care, but of social justice. Consequently, questions of distribution of scarce resources should be discussed in terms of social justice and not in terms of justice in health care. If prenatal testing is seen as an important instrument in order to restore the full individual range of opportunities, than free access to prenatal aneuploidy screening should be provided for every pregnant woman. If this is not possible in a given health care system, than it should at least be provided for women with a low income. To presuppose a higher individual risk for an aneuploidy in the fetus as a criterion for reimbursement represents in contrast a medical fallacy and leads to unfair discrimination in prenatal medicine, because it neglects the relevant aspects of social justice.
V. Rolfes, D. Schmitz / European Journal of Obstetrics & Gynecology and Reproductive Biology 198 (2016) 27–29
Summary In conclusion, questions of justice, of fair equality of opportunity, are strongly linked to the main argument for prenatal testing, – to the reproductive autonomy of pregnant women. This has to be reflected more adequately by the clinical pathways in prenatal care in order to avoid unfair discrimination against a particular group of pregnant women and, thus, give real meaning to the popular calls for reproductive autonomy. NIPT is seen as superior to all other up to now implemented prenatal screening procedures and at the same time also still is and might remain a comparably expensive medical testing procedure. Any financial barriers are therefore significant and might result in unfair discrimination of a group of pregnant women, – in particular of women with no sufficient financial resources. If a society agrees on the importance of reproductive autonomy and of prenatal testing in order to realize it, but cannot afford free access for everybody, it has to modulate the resulting inequalities as just as possible. This could for example mean that only pregnant women with a low income are granted reimbursement of the NIPT costs by health insurance companies. Conflict of interest The authors report no conflict of interest. Acknowledgements The research was funded by the German Ministry of Education and Research (BMBF) in the research project ‘‘Indication or information? The role of the physician in the context of noninvasive prenatal diagnosis’’ (ELSA funding line, grant number 01GP1201). References [1] Bianchi DW, Parker RL, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med 2014;370(9):799–808. [2] Lo YM, Tein MS, Lau TK, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998;62(4):768–75.
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[3] Chiu RW, Chan KC, Gao Y, et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci U S A 2008;105(51):20458–63. [4] 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 U S A 2008. [5] Warsof SL, Larion S, Abuhamad AZ. Overview of the impact of noninvasive prenatal testing on diagnostic procedures. Prenat Diagn 2015;35(10): 972–9. [6] Gil MM, Akolekar R, Quezada MS, Bregant B, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: meta-analysis. Fetal Diagn Ther 2014;35(3):156–73. [7] Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med 2015;372(17):1589–97. [8] Committee Opinion No. 640: cell-free DNA screening for fetal aneuploidy. Obstet Gynecol 2015;126(3):e31–7. [9] #36: prenatal aneuploidy screening using cell-free DNA. Am J Obstet Gynecol 2015;212(6):711–6. [10] Allyse M, Minear MA, Berson E, et al. Non-invasive prenatal testing: a review of international implementation and challenges. Int J Women’s Health 2015;7: 113–26. [11] Hill M, Wright D, Daley R, et al. Evaluation of non-invasive prenatal testing (NIPT) for aneuploidy in an NHS setting: a reliable accurate prenatal noninvasive diagnosis (RAPID) protocol. BMC Pregnancy Childbirth 2014;14:229. [12] Chandrasekharan S, Minear MA, Hung A, Allyse M. Noninvasive prenatal testing goes global. Sci Transl Med 2014;6(231):231fs15. [13] Benn P, Cuckle H, Pergament E. Non-invasive prenatal testing for aneuploidy: current status and future prospects. Ultrasound Obstet Gynecol 2013;42(1): 15–33. [14] Agarwal A, Sayres LC, Cho MK, Cook-Deegan R, Chandrasekharan S. Commercial landscape of noninvasive prenatal testing in the United States. Prenat Diagn 2013;33(6):521–31. [15] Bianchi DW, Wilkins-Haug L. Integration of noninvasive DNA testing for aneuploidy into prenatal care: what has happened since the rubber met the road? Clin Chem 2014;60(1):78–87. [16] Buchanan A, Brock DW, Daniels N, Wikler D. From chance to choice. In: Genetics & justice. Cambridge, New York: Cambridge University Press; 2000. [17] Chervenak FA, McCullough LB, Chervenak JL. Prenatal informed consent for sonogram: an indication for obstetric ultrasonography. Am J Obstet Gynecol 1989;161(4):857–60. [18] Deans Z, Newson AJ. Ethical considerations for choosing between possible models for using NIPD for aneuploidy detection. J Med Ethics 2012;38(10): 614–8. [19] O’Neill O. Autonomy and trust in bioethics. Cambridge, New York: Cambridge University Press; 2002. [20] Dworkin R. Life’s dominion: an argument about abortion. Euthanasia, and individual freedom. New York: Vintage Books; 1993. [21] Rawls J. A theory of justice. Oxford: Clarendon Press; 1972. [22] Daniels N. Just health: meeting health needs fairly. New York: Cambridge University Press; 2008. [23] Schramme T. Einleitung: Die Begriffe Gesundheit und Krankheit in der philosophischen Diskussion. In: Schramme T, editor. Krankheitstheorien. Berlin: Suhrkamp Verlag; 2012.