NIPT for adult-onset conditions: Australian NIPT users' views.

Noninvasive prenatal testing (NIPT) has become widely available in recent years. While initially used to screen for trisomies 21, 18, and 13, the test has expanded to include a range of other conditions and will likely expand further. This paper addresses the ethical issues that arise from one particularly controversial potential use of NIPT: screening for adult-onset conditions (AOCs). We report data from our quantitative survey of Australian NIPT users' views on the ethical issues raised by NIPT for AOCs. The survey ascertained support for NIPT for several traits and conditions including AOCs. Participants were then asked about their level of concern around implications of screening for AOCs for the future child and parent(s). Descriptive and comparative data analyses were conducted. In total, 109 respondents were included in data analysis. The majority of respondents expressed support for NIPT screening for preventable (70.9%) and nonpreventable AOCs (80.8%). Most respondents indicated concern around potential harmful impacts associated with NIPT for AOCs, including the psychological impact on the future child and on the parent(s). Despite this, the majority of participants thought that continuation of a pregnancy known to be predisposed to an AOC is ethically acceptable. The implications of these data are critically discussed and used to inform the normative claim that prospective parents should be given access to NIPT for AOCs. The study contributes to a body of research debating the ethical acceptability and regulation of various applications of NIPT as screening panels expand.

Patient Perceptions on the Advancement of Noninvasive Prenatal Testing for Sickle Cell Disease among Black Women in the United States.

BACKGROUND: Noninvasive prenatal testing (NIPT) designed to screen for fetal genetic conditions, is increasingly being implemented as a part of routine prenatal care screening in the United States (US). However, these advances in reproductive genetic technology necessitate empirical research on the ethical and social implications of NIPT among populations underrepresented in genetic research, particularly Black women with sickle cell disease (SCD). METHODS: Forty (N = 40) semi-structured interviews were conducted virtually with Black women in the US (19 participants with SCD; 21 participants without SCD) from June 2021 to January 2022. We employed a qualitative approach to examine the study participants' perceptions of the potential advancement of NIPT for screening SCD in the fetus. Data were analyzed using NVivo 12 qualitative software. RESULTS: The themes revealed the complexities involving the intersectional lived experiences of SCD, prenatal care, lack of synergy among health providers, and NIPT decision-making. The results further revealed that even when Black women have shared commonalities in their lived experiences while navigating SCD and motherhood, their perceptions of NIPT screening technologies are divergent. CONCLUSION: Expanding the ethical discourse on the social implications of NIPT is critical to fully elucidate how Black women perceive NIPT's utility, particularly as NIPT advances to screen for SCD in the fetus. Neglecting to include Black women with genetic conditions in empirical studies on NIPT may contribute to ongoing health inequities and limit and constrain reproductive choices among Black women with and without SCD.

Making use of non-invasive prenatal testing (NIPT): rethinking issues of routinization and pressure.

First mapping the main ethical issues surrounding prenatal testing, we then analyze which concerns are specific to non-invasive methods. Presupposing the privatization premise for reproductive autonomy in fundamentally liberal societies, we go on to specify common concerns about non-invasive prenatal testing (NIPT) covered by the term 'routinization', and conceptually unravel the frequently expressed worry of increasing 'pressure' to test and/or terminate affected pregnancies. We argue that mindful decision-making should be a key educational goal (not only) of NIPT counseling which could be achieved through stepwise disclosure. In addition, we identify indirect social pressure as the most plausible threat to reproductive freedom. While continuous efforts need to be made to prevent such pressure - not least by ensuring balanced availability of options -, restricting testing options, and thus freedom of choice, cannot be the answer to this concern. Lastly, we suggest abandoning the vague term 'routinization' and instead focusing on specified concerns to enable a fruitful debate.

Project Inclusive Genetics: Exploring the impact of patient-centered counseling training on physical disability bias in the prenatal setting.

PURPOSE: There is robust research examining the negative impact of racial and socioeconomic implicit bias on healthcare provider clinical decision-making. However, other under-studied important biases are likely to impact clinical care as well. The goal of this study was to explore the presence of bias against people with physical disability among a heterogeneous group of healthcare workers and trainees and to evaluate the effect of implicit association testing and an educational module on this bias. METHOD: The study was composed of a one-hour web-based survey and educational module. The survey included an explicit disability bias assessment, disability Implicit Association Tests (IATs), demographic collection, and pre- and post- module clinical vignettes of prenatal patient scenarios. In addition to providing counseling to hypothetical patients, participants also indicated their personal preferences on genetic testing and termination. The educational module focused on the principles of patient-centered counseling. RESULTS: The collected data reflects responses from 335 participants. Within this sample, there were both explicit and implicit biases towards individuals with physical disabilities. Prior to the IAT and educational module, when respondents were tasked with providing genetic testing recommendations, implicit biases and personal preferences for genetic testing and termination influenced respondents' clinical recommendations. Importantly, having previous professional experience with individuals with disabilities diminished biased clinical recommendations prior to the intervention. In response to the IAT and educational intervention, the effect of implicit bias and personal preferences on clinical recommendations decreased. CONCLUSIONS: This study demonstrates how bias against a marginalized group exists within the medical community and that personal opinions can impact clinical counseling. Importantly, our findings suggest that there are strategies that can be easily implemented into curricula to address disability bias, including formal educational interventions and the addition of professional experiences into healthcare professional training programs.

Non-invasive prenatal testing (NIPT): does the practice discriminate against persons with disabilities?

The most well-known goal of non-invasive prenatal testing (NIPT) is still to determine whether or not a fetus has trisomy 21. Since women often terminate the pregnancy upon a positive result, there is concern that the use of NIPT contributes to discrimination against persons with disabilities. If this concern is justified, it could have an impact on the wider social acceptability of existing testing practices and their potential further expansion. This paper demonstrates four different versions of the discrimination worry, indicates how international policy papers have reacted to them, and identifies the ethically most relevant feature of the concern.

The implementation of non-invasive prenatal testing (NIPT) in the Netherlands.

In the Netherlands prenatal screening is offered as a mean to increase reproductive choices of couples. All women are counseled on the existing options by trained midwives. The government puts a great emphasis on informed choice and on womens' opinions and reactions to screenings options. Since 2017 non-invasive prenatal testing (NIPT, cf-DNA) is offered as first tier screening for aneuploidies in the genome-wide (GW) variant at the cost of 175 Euro's. Uptake is around 50%. This screenings offer is perceived as unconventional for the traditionally cautious Dutch system.

Should prenatal screening be seen as 'selective reproduction'? Four reasons to reframe the ethical debate.

There are a number of problems with the classification of prenatal screening as a form of 'selective reproduction' that has become an increasingly dominant classification scheme in the last decade. (1) Since the term 'selection' implies choosing one out of several (at least two), it misdescribes the decision to terminate a pregnancy. (2) Deciding whether to have this child is a decision taken within the relationships that constitute the pregnancy. (3) 'Selection' is a loaded term, connecting prenatal diagnosis to negative eugenics or to population genetics. (4) Deciding against the birth of a child who would suffer or would not be able to flourish is a decision taken within a negotiation of personal responsibilities and social constraints. The characterization of prenatal screening as selective reproduction is, in a very narrow way, defensible to reconstruct why prenatal screening is permissible in a liberal state and should not be banned, but it needs to be rejected as a general frame for understanding the substance of the ethical issues around prenatal diagnosis and screening. Ethics should rather attempt to create a respectful space of mutual understandings and reflect how women and couples, who are ultimately responsible for these decisions, perceive their responsibilities in care.

Do non-invasive prenatal tests promote discrimination against people with Down syndrome? What should be done?

By implementation of non-invasive prenatal testing (NIPT) for the diagnosis of Down syndrome (DS) in maternity care, an ethical debate is newly inflamed how to deal with this information. Fears of the consequences of an increased use of NIPT are justified with the same arguments when amniocentesis and preimplantation genetic diagnosis (PGD) were introduced decades ago. It can be expected that the prevalence of people with DS would significantly increase in Western societies as a result of the increasing age of pregnant women and the improved medical care for people with DS. The net effect as to whether an increasing uptake of NIPT will result in more abortions of fetuses with trisomy 21 cannot be reliably estimated. This holds true since more and more couples will use results of NIPT for information only, but will not opt for termination of pregnancy. Although parents love their children with DS, in a society where reproductive autonomy is seen as an achievement, access to NIPT cannot be limited. On this background, comprehensive and qualified pretest counseling is vital, also to avoid possible stigmatization of people with DS and as the resulting consequence to avoid feared deterioration in their living conditions, for which, however, there is no evidence to date. The personal view of a mother of a child with DS illustrates the complexity in dealing with NIPT, which does not allow simple answers and must be understood as a challenge for society as a whole.

Non-invasive prenatal diagnostics (NIPD) in the system of medical care. Ethical and legal issues.

The procedures of prenatal and preimplantation diagnostics are discussed critically again and again in our community. In addition to the permanently controversial issues of embryo protection and abortion, considerations that discrimination on the basis of disability could occur with problematic consequences also for already born people with disabilities and their relatives now play a central role.

Moral ambivalence. A comment on non-invasive prenatal testing from an ethical perspective.

BACKGROUND: Non-invasive prenatal testing (NIPT) has been available for almost 10 years. In many countries the test attracted considerable criticism from the start. While most critical comments in this context deal with the (alleged) problem of eugenic selection, I will concentrate on a somewhat broader issue. CONTENT: I will argue that NIPT clearly has the potential to increase reproductive autonomy and benefit expectant parents. However, NIPT can also put people in a situation that is morally overwhelming for them and from which there is no easy way out. In this sense, such tests can have a dilemma-generating effect. SUMMARY AND OUTLOOK: I will conclude that this can be adequately described by the term "moral ambivalence".

Ethical, Legal and Social Issues (ELSI) Associated with Non-Invasive Prenatal Testing: Reflections on the Evolution of Prenatal Diagnosis and Procreative Choices.

New technologies such as non-invasive prenatal testing (NIPT), capable of analyzing cell-free fetal DNA in the maternal bloodstream, have become increasingly widespread and available, which has in turn led to ethical and policy challenges that need addressing. NIPT is not yet a diagnostic tool, but can still provide information about fetal genetic characteristics (including sex) very early in pregnancy, and there is no denying that it offers valuable opportunities for pregnant women, particularly those at high risk of having a child with severe genetic disorders or seeking an alternative to invasive prenatal testing. Nonetheless, the ethical, legal and social implications (ELSI) include multiple aspects of informed decision-making, which can entail risks for the individual right to procreative autonomy, in addition to the potential threats posed by sex-selective termination of pregnancy (in light of the information about fetal sex within the first trimester), and the stigmatization and discrimination of disabled individuals. After taking such daunting challenges into account and addressing NIPT-related medicolegal complexities, the review's authors highlight the need for an ethically and legally sustainable framework for the implementation of NIPT, which seems poised to become a diagnostic tool, as its scope is likely to broaden in the near future.

Non-invasive prenatal testing (NIPT): societal pressure or freedom of choice? A vignette study of Dutch citizens' attitudes.

The introduction of the accurate and procedurally easy non-invasive prenatal test (NIPT) raises ethical concerns that public attitudes towards prenatal screening may change, leading to societal pressure to participate in aneuploidy screening. This study examined Dutch citizens' attitudes towards a pregnant woman's decision to (1) decline NIPT in the context of two different funding policies and (2) to terminate or continue a pregnancy affected by different disorders. The attitudes of 1096 respondents were assessed with the contrastive vignette method, using two pairs of vignettes about declining NIPT and termination of pregnancy. Most respondents either agreed with a woman's decision to decline NIPT or were neutral about it, stating that this decision should be made independently by women, and does not warrant judgement by others. Interestingly, funding policies did influence respondents' attitudes: significantly more respondents disagreed with declining NIPT when it was fully reimbursed. Respondents had similar attitudes to the vignettes on termination and continuation of pregnancy in case of Down's syndrome. In case of Edwards' or Patau's syndrome, however, significantly more respondents disagreed with continuation, citing the severity of the disorder and the child's best interests. This study demonstrates broad acknowledgement of women's freedom of choice in Dutch society; a finding that may help to rebut existing concerns about societal pressure for pregnant women to participate in prenatal screening. As the reimbursement policy and the scope of NIPT may influence people's attitudes and elicit moral judgements, however, maintaining freedom of choice warrants sustained efforts by health professionals and policy makers.

Discouraging Elective Genetic Testing of Minors: A Norm under Siege in a New Era of Genomic Medicine.

Consistently, the field of genetic counseling has advocated that parents be advised to defer elective genetic testing of minors until adulthood to prevent a range of potential harms, including stigma, discrimination, and the loss of the child's ability to decide for him- or herself as an adult. However, consensus around the policy of "defer-when-possible" obscures the extent to which this norm is currently under siege. Increasingly, routine use of full or partial genome sequencing challenges our ability to control what is discovered in childhood or, when applied in a prenatal context, even before birth. The expansion of consumer-initiated genetic testing services challenges our ability to restrict what is available to minors. As the barriers to access crumble, medical professionals should proceed with caution, bearing in mind potential risks and continuing to assess the impact of genetic testing on this vulnerable population.

Understanding attitudes and behaviors towards cell-free DNA-based noninvasive prenatal testing (NIPT): A survey of European health-care providers.

Cell-free DNA-based noninvasive prenatal testing (cfDNA) is a relatively new screening tool that analyzes cfDNA circulating in maternal plasma to screen for aneuploidies. Since its introduction, cfDNA has been rapidly adopted by health care providers (HCPs). This rapid adoption, as well as progressive developments in the technology, requires professional societies to continuously update their guidelines to indicate the broadening scope both in terms of test indications and patient populations for whom it has become the appropriate primary test. CfDNA testing, initially applied to high-risk patients, is now largely considered an option for all patients. For HCPs, the rapid introduction of cfDNA into clinical practice has come with the requirement to stay up-to-date and accurately informed. We performed a survey to understand the current practices and views of European HCPs on the use of cfDNA. European HCPs were surveyed on several topics such as familiarity with cfDNA-based noninvasive prenatal testing (NIPT), current usage, patient counseling, test menu expansion, and future perspectives. The results of this survey demonstrate increasing usage and awareness of cfDNA-based NIPT in five European countries (UK, France, Germany, Spain and Italy). Major barriers to implementation include cost and a lack of physician education on NIPT.

Considerations for whole exome sequencing unique to prenatal care.

Whole exome sequencing (WES) is increasingly being used in the prenatal setting. The emerging data support the clinical utility of prenatal WES based on its diagnostic yield, which can be as high as 80% for certain ultrasound findings. However, detailed practice and laboratory guidelines, addressing the indications for prenatal WES and the surrounding technical, interpretation, ethical, and counseling issues, are still lacking. Herein, we review the literature and summarize the most recent findings and applications of prenatal WES. This review offers specialists and clinical genetic laboratorians a body of evidence and expert opinions that can serve as a resource to assist in their practice. Finally, we highlight the emerging technologies that promise a future of prenatal WES without the risks associated with invasive testing.

Pandora's pregnancy: NIPT, CMA, and genome sequencing-A new era for prenatal genetic testing.

OBJECTIVES: We delineate in this article a shift from the "traditional" technologies of karyotyping in PND to the current phase of advanced genetic technologies including noninvasive prenatal testing (NIPT), chromosomal microarray analysis (CMA), and whole-exome sequencing (WES) with their higher detection rate and related abundance of uncertain data. METHODS: Conceptual analysis based on seminal works that shaped the socioethical discourse surrounding the experiences of parents as well as professionals with prenatal diagnosis in the last 30 years. RESULTS: We consider the implications of this new era of PND for patients and health professionals by drawing on previous studies documenting how probability and uncertainty affect informed consent/choice, health risks communication, customer satisfaction and decision making, and parent-child bonding. CONCLUSIONS: We argue that these changes move us beyond the idioms and realities of the tentative pregnancy and moral pioneering, to uncertainty, probability-based counseling, and moral/translational gambling. We conclude by discussing what is needed to maintain hope in the era of Pandora's pregnancy.

Maternal copy-number variations in the DMD gene as secondary findings in noninvasive prenatal screening.

PURPOSE: Noninvasive prenatal screening (NIPS) using genome sequencing also reveals maternal copy-number variations (CNVs). Those CNVs can be clinically actionable or harmful to the fetus if inherited. CNVs in the DMD gene potentially causing dystrophinopathies are among the most commonly observed maternal CNVs. We present our experience with maternal DMD gene CNVs detected by NIPS. METHODS: We analyzed the data of maternal CNVs detected in the DMD gene revealed by NIPS. RESULTS: Of 26,123 NIPS analyses, 16 maternal CNVs in the DMD gene were detected (1/1632 pregnant women). Variant classification regarding pathogenicity and phenotypic severity was based on public databases, segregation analysis in the family, and prediction of the effect on the reading frame. Ten CNVs were classified as pathogenic, four as benign, and two remained unclassified. CONCLUSION: NIPS leverages CNV screening in the general population of pregnant women. We implemented a strategy for the interpretation and the return of maternal CNVs in the DMD gene detected by NIPS.

Just choice: a Danielsian analysis of the aims and scope of prenatal screening for fetal abnormalities.

Developments in Non-Invasive Prenatal Testing (NIPT) and cell-free fetal DNA analysis raise the possibility that antenatal services may soon be able to support couples in non-invasively testing for, and diagnosing, an unprecedented range of genetic disorders and traits coded within their unborn child's genome. Inevitably, this has prompted debate within the bioethics literature about what screening options should be offered to couples for the purpose of reproductive choice. In relation to this problem, the European Society of Human Genetics (ESHG) and American Society of Human Genetics (ASHG) tentatively recommend that any expansion of this type of screening, as facilitated by NIPT, should be limited to serious congenital and childhood disorders. In support of this recommendation, the ESHG and ASHG cite considerations of distribution justice. Notably, however, an account of justice in the organization and provision of this type of screening which might substantiate this recommendation has yet to be developed. This paper attempts to redress this oversight through an investigation of Norman Daniels' theory of Just health: meeting health needs fairly. In line with this aim, the paper examines what special moral importance (for Just health) screening for the purpose of reproductive choice might have where concerning serious congenital and childhood disorders in particular. The paper concludes that screening for reproductive choice where concerning serious congenital and childhood disorders may be important for providing women with fair opportunity to protect their health (by either having or not having an affected child).