Dagmar Schmitz

An offer you can't refuse? Ethical implications of non-invasive prenatal diagnosis.

aneuploidies has been an integral part of prenatal medicine for over 30 years. It is usually performed as a combination of initial non-invasive risk screening (NIRS) strategies, and suspicious results are followed by invasive diagnostic procedures such as amniocentesis. Recently, however, several breakthroughs in non-invasive prenatal diagnosis (NIPD) indicate the upcoming clinical applicability of this procedure. In 2007, after years of largely fruitless efforts to enrich fetal cells in maternal plasma, Lo et al. reported the ability to correctly diagnose trisomy 21 in the fetus using quantitative analysis of cell-free fetal RNA in maternal blood. And in 2008, Fan et al. used shotgun sequencing of cell-free DNA in maternal blood to non-invasively diagnose fetal aneuploidy. Recently, at least two companies, using different technical approaches, have announced plans to introduce NIPD into health care: in February 2009, Lenetix, Inc. reported the launch of an Institutional Review Board-approved screening study on NIPD for Down’s syndrome, and Sequenom, Inc. has revealed that NIPD will be available for clinical use in the fourth quarter of 2009 (ref. 4). With regard to the clinical implementation of NIPD, three scenarios are possible: NIPD might replace current prenatal screening tests or be added to them; NIPD might be interposed between NIRS and invasive PND; or NIPD might replace invasive PND. Which of these options is followed will depend primarily on the technical accuracy of the NIPD strategies (in terms of sensitivity and specificity) but the third option seems to be the most attractive, especially in the long term. What will the effects be of this third option, which sees invasive methods no longer being required for routine PND of aneuploidies? Depending on the NIPD method used three effects can be anticipated, which, especially in combination, might pose serious threats to the autonomous decision making of the pregnant woman. First, prenatal (cyto)genetic diagnosis will be achieved much earlier in pregnancy. From a medical perspective this is a positive development as termination-related risks for the mother are minimized at an earlier gestational age. But it is debatable whether such a shift would be ethically desirable, because early diagnosis could increase the proportion of pregnant women opting for termination, including for non-medical reasons (such as for ‘unwanted’ fetal sex). Second, uptake rates of NIPD might become as high as they are for NIRS strategies now, which in Germany, for example, could mean up to 85%. Providing adequate pre-test counselling for such a high percentage of pregnant women would be challenging. Finally, the two-step approach of prenatal screening potentially followed by invasive diagnosis will be transformed into a one-step procedure. Although the abolishment of invasive PND has some positive aspects, as women who undergo prenatal testing would no longer have to risk fetal loss or their own health, the one-step diagnostic procedure might worsen current tendencies to neglect the reproductive autonomy of pregnant women. There will be only one contact between the pregnant woman and the physician to discuss the pros and cons of NIPD, which — if NIPD is implemented analogously to NIRS — might take place in a mass screening setting. It is therefore legitimate to ask whether this diagnostic ‘offer’ can be refused, and whether an autonomous decision-making process is still possible. Reproductive autonomy, however, is of utmost importance in PND. This is because PND differs from other diagnostic procedures in medicine insofar as most of the conditions tested cannot be cured or substantially alleviated. In these cases, the mother’s only option is to decide whether to accept the child’s impairment or to terminate the pregnancy. Consequently, the main argument for offering prenatal genetic testing is to enhance the reproductive autonomy of the pregnant woman. Studies have investigated the quality of informed consent in currently available multi-step procedures for PND. In a representative German survey, women were asked what prompted them to opt for PND: 25% stated that their physician wanted it; 36% thought that PND is an almost mandatory part of routine maternal care; and 16% had not given consent to the performed PND or could not remember giving consent. Studies in many other countries have provided similar results. In France, a survey of 305 pregnant women — most of whom had undergone maternal serum screening — revealed that nearly half of the women were uninformed about the procedure. There is already a need to improve the quality of informed consent for existing multi-step prenatal genetic examinations — a need that will be even more pressing if NIPD becomes a one-step procedure. We argue that a new organizational setting for NIPD, which from the patient’s point of view is clearly distinguishable from the setting for therapy-aimed prenatal care, could allow for a decision-making process to take place prior to NIPD and thus secure the reproductive autonomy of the pregnant woman. Women need to understand that there is a decision to be taken, that NIPD is not part of routine maternity care, and that the main aim of NIPD is to enable the pregnant woman to decide whether to live with an impaired child or to terminate the pregnancy. Therefore, a two-step approach with counselling in the first stage and decision-making and specific testing, where appropriate, in the second stage is essential for ensuring a value-consistent shared decision-making process that also takes into account the welfare of the unborn child.

Commentary: No risk, no objections? Ethical pitfalls of cell-free fetal DNA and RNA testing

At first glance, the prospect of achieving a definite prenatal diagnosis with no obvious procedure related risks is compelling. Implementation of non-invasive prenatal diagnosis will save the lives of healthy fetuses that would have been lost as a rare “side effect” of established invasive procedures like amniocentesis. But, as Wright and Chitty are well aware, a closer look shows that this technique may have “side effects” of a different kind, most importantly problems with autonomy.nnFrom an ethical point of view, the main justification for prenatal diagnosis is to support the reproductive autonomy of the pregnant woman or couple, because the typical goal of …

A new era in prenatal testing: are we prepared?

Prenatal care and the practice of prenatal genetic testing are about to be changed fundamentally. Due to several ground-breaking technological developments prenatal screening and diagnosis (PND) will soon be offered earlier in gestation, with less procedure-related risks and for a profoundly enlarged variety of targets. In this paper it is argued that the existing normative framework for prenatal screening and diagnosis cannot answer adequately to these new developments. In concentrating on issues of informed consent and the reproductive autonomy of the pregnant women the ethical debate misses problems related to the clinical pathway as a whole and to implicit normative attributions to clinical actions or the function of health care professionals. If, however, ethical debate would focus on the clinical context and on the ends of PND to a larger extent, it would be able to provide a more comprehensive analysis of the ethical challenges especially of the new technologies in order to be more adequately prepared for their implementation.

Möglichkeiten und Grenzen von Beratung bei (späten) Schwangerschaftsabbrüchen

ZusammenfassungDie in den vergangenen Monaten auf den Weg gebrachten Initiativen zur Änderung des Schwangerschaftskonfliktgesetzes in Deutschland betonen den grundsätzlichen Stellenwert der Schwangerenberatung vor und nach Pränataldiagnostik und damit auch die Bedeutung der Entscheidung der Schwangeren. Vorstellbar und zum Teil auch bereits eingerichtet sind darüber hinaus Beratungsstrukturen für die in einen Abbruch involvierten Ärzte. Die vorliegende Arbeit untersucht die Möglichkeiten und Grenzen von Beratung für die Schwangere wie auch für die beteiligten Ärzte bei (späten) Schwangerschaftsabbrüchen. Die umfassende Beratung der Schwangeren kann sowohl der Sicherung selbstbestimmter Entscheidungen als auch dem Schutz des ungeborenen Lebens dienen. Die hypothetisch-stellvertretenden Entscheidungen der zur Arztberatung eingerichteten Kommissionen aber lassen nicht nur Zweifel an ihrer Legitimation, sondern ebenso an dem grundsätzlichen Umgang mit der medizinischen Indikation aufkommen. Gesetzesinitiativen in diesem Bereich müssen sich deshalb auch mit der medizinischen Indikation befassen, wenn eine umfassende und konsequente Regelung angestrebt wird.AbstractDefinition of the problem Current legislative initiatives that are aiming to change the German abortion law emphasise the importance of counselling for the pregnant woman before and after a prenatal diagnosis. By stating this they are also strengthening the impact of a woman’s decision. Furthermore, several counselling structures have been suggested or established in order to support the decision-making-process of the physicians who are involved in an abortion after a prenatal diagnosis. This article addresses opportunities and limitations of counselling for the physician as well as for the pregnant woman before (late) termination of pregnancy. Arguments and conclusion Comprehensive counselling of a pregnant woman before prenatal testing and termination of pregnancy can be an effective tool to enable autonomous choices as well as to secure the rights of the unborn child. Counselling committees, established to support the certifying physician, perform a kind of hypothetical surrogate decision-making, which is difficult to legitimise, – either legally or ethically. Furthermore, they illuminate fundamental difficulties attached to the current interpretation and use of the medical indication for termination of pregnancy in Germany, which therefore should also be addressed, if a consistent revision of the abortion law is intended.

Unfair discrimination in prenatal aneuploidy screening using cell-free DNA?

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.

Intrauterine Growth Restriction. Guideline of the German Society of Gynecology and Obstetrics (S2k-Level, AWMF Registry No. 015/080, October 2016)

Aims The aim of this official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG) was to provide consensus-based recommendations obtained by evaluating the relevant literature for the diagnostic treatment and management of women with fetal growth restriction. Methods This S2k guideline represents the structured consensus of a representative panel of experts with a range of different professional backgrounds commissioned by the Guideline Committee of the DGGG. Recommendations Recommendations for diagnostic treatment, management, counselling, prophylaxis and screening are presented.

Das Verbot der pränatalen Diagnostik spätmanifestierender Erkrankungen im deutschen Gendiagnostikgesetz – eine Diskussion medizinischer und rechtlicher Aspekte und deren Implikation für die medizinethische Diskussion

ZusammenfassungAm 1. Februar 2010 ist das Gendiagnostikgesetz (GenDG) in Kraft getreten. Die Debatte um einige Regelungsbereiche, wie beispielsweise das Neugeborenenscreening, reißt nicht ab. Ein Aspekt des Gesetzes ist im Rahmen der Debatte um die Präimplantationsdiagnostik (PID) in Deutschland unter neuen Vorzeichen zu diskutieren: Das – international bislang einzigartige – Verbot der pränatalen Diagnostik so genannter spätmanifestierender Erkrankungen, die erst nach der Vollendung des 18. Lebensjahres ausbrechen. In diesem Beitrag möchten wir Hinweise zur differenzierten Diskussion dieser in §xa015(2) GenDG bestimmten Verbotsnorm liefern. Obgleich Argumente, insbesondere das Recht auf Nichtwissen des geborenen Kindes, für ein solches Verbot sprechen, kommen wir aufgrund der medizinischen Sachlage und nach einer Analyse der Pro- und Kontraargumente aus ethischer und rechtlicher Sicht zu dem Schluss, dass ein generelles Verbot der pränatalen Diagnostik spätmanifestierender Erkrankungen im Sinne der Zielsetzung womöglich insuffizient ist sowie in der Begründung Inkonsistenzen zum bereits bestehenden Regelwerk aufweist, und lenken daher den Blick auf unter Umständen bessere Alternativen.AbstractDefinition of the problem The German Genetic Diagnosis Act (Genetic Diagnosis Act, GenDG) became effective on February 1, 2010. Although this act was welcomed by many, the debate surrounding some regulatory areas, for example, screening newborns, continues. One aspect of this new legislation, however, has received little attention: the prohibition of prenatal diagnosis of so-called late-onset diseases—where first symptoms only develop after completion of the 18th year of life—constitutes an internationally unique prohibition. In this publication, we would like to contribute to a more differentiated discussion of §xa015(2) GenDG that sanctions this diagnosis. Arguments and conclusion There are arguments supporting this prohibition (especially the right of the child not to know). However, based on medical concerns as well as an analysis of ethical and legal pros and cons, we conclude that maintaining this general prohibition of diagnosing late-onset diseases might be insufficient as well as inconsistent with other regulations; thus, possible alternatives are discussed.

Ethics rounds: affecting ethics quality at all organisational levels

Clinical ethics support (CES) services are experiencing a phase of flourishing and of growing recognition. At the same time, however, the expectations regarding the acceptance and the integration of traditional CES services into clinical processes are not met. Ethics rounds as an additional instrument or as an alternative to traditional clinical ethics support strategies might have the potential to address both deficits. By implementing ethics rounds, we were able to better address the needs of the clinical sections and to develop a more comprehensive account of ethics quality in our hospital, which covers the level of decisions and actions, and also the level of systems and processes and aspects of ethical leadership.

Lost in Translation? Ethical Challenges of Implementing a New Diagnostic Procedure.

Since cell-free DNA (cfDNA) fragments of placental origin can be isolated and analyzed from the blood of pregnant women. Applications of this finding have been developed and implemented in clinical care pathways worldwide at an unprecedented pace and manner. Implementation patterns, however, exhibit considerable insufficiencies. Different motors of implementation processes, like the market or various regulatory institutions, can be identified at a national level. Each motor entails characteristic ethical challenges which are exemplified impressively by a rising number of case reports.Empirical data demonstrate that there are significant losses in the respective translational processes, especially when the results from clinical research are to be translated into the clinical reality of NIPT (the so called second roadblock (T2)). These losses are perceived in the fields of knowledge transfer, professional standardization and ethical debate. Recommendations of professional organizations often fail to reach general practitioners. Blindsided by the new diagnostic procedure in their clinical practice, professionals in prenatal care express their insecurities with regard to its handling. Ethical debate appears to adhere to pre-existing (and partly already proven to be insufficient) normative frameworks for prenatal testing. While all of these deficits are typical for the implementation processes of many new molecular diagnostic procedures, especially in NIPT, they show a high variability between different nations.A critical assessment of the preferred strategy of implementation against the background of already existing national ethical frameworks is indispensable, if potential adverse effects are to be diminished. The described translational losses seem to be significantly reducible by granting the translational process in roadblock T2 more time.

Intensivmedizin und demographische Entwicklung

Zusammenfassend wird es wichtig sein, bei den in Zukunft aufgrund der demographischen Entwicklung zunehmend auf Intensivstationen zu behandelnden alteren und hochbetagten Patienten eine besonders sorgfaltige individuelle Indikationsstellung vorzunehmen, die einerseits das Patientenwohl im Kampf um einzelne Organfunktionen nicht aus dem Blick verliert, andererseits aber auch Patienten nicht aufgrund ihres Alters benachteiligt.