Considering seriousness in preconception carrier screening: a framework to support policy deliberation

Abstract

Background

The seriousness of a genetic condition has long been a central consideration in population-based screening programs. Yet, despite its widespread use in policy and practice, “serious” remains an ill-defined and multi-faceted concept. This lack of definitional clarity, complexity, and absence of guidance around how to interpret the concept has led to inconsistencies in application in policy and practice.

Objective

In this article, we use the example of preconception carrier screening (PCS) to expand on the procedural elements of our conceptual framework for considering seriousness and lay out questions to help guide and structure deliberations about gene panel composition in the context of PCS.

Main content

We argue that traditional attempts to operationalize seriousness, while useful, are insufficient for capturing the concept’s complexity in population-based interventions. Instead, our framework – by integrating clinical, contextual, and experiential dimensions – encourages deliberation that reflects and is responsive to the diverse values and needs of communities affected by genetic conditions.

Conclusions

By fostering a balanced and context-sensitive approach, our framework offers a conceptual tool to help policymakers navigate the ethical complexities of PCS and support the development of PCS programs that are ethically defensible, socially responsible, and are aligned with the goals of community genetics.

Introduction

The notion of seriousness is used across policy and practice in healthcare to triage access to and availability of treatments, support, and resources (Stenmarck et al. 2024). It is also a key consideration in both determining access to reproductive technologies such as, non-invasive prenatal testing, preimplantation genetic testing, prenatal diagnosis, and preconception carrier screening, as well as informing the decision to include specific genetic conditions as targets for these technologies. Yet, “serious” has long remained ill-defined, even by genetics professionals, as illustrated by Wertz and Knoppers (2002). This lack of definitional clarity persists today, particularly in the context of reproductive genetic technologies, with interpretations largely shaped by clinical criteria, often at the expense of the perspectives and experiences of those living with, or caring for someone with, a genetic condition (Boardman and Clark 2022; Kleiderman et al. 2019, 2025; Savell and Karpin 2008). Differences in the interpretation of seriousness or its underlying meaning may exist between healthcare professionals and policymakers – who may rely on clinical criteria or impact on the healthcare system – and the public – who may rely on personal values, experience, or cultural beliefs (Dive et al. 2023; Savell and Karpin 2008; Stenmarck et al. 2023, 2024; Wang, Scuffham et al. 2023).

The categorization of a condition as serious can also have wide-ranging consequences – both beneficial (greater access to treatment and support) or potentially harmful (greater discrimination or social stigmatization) – and these can be felt individually or at a group level (Kleiderman et al. 2025; Collier 2012). Such categorization may create perceived moral duties and obligations on prospective parents identified as carriers to follow a preferred course of action (e.g., undergo specific prenatal tests or avoid having certain kinds of children) (Dive et al. 2023; Kleiderman et al. 2025). Efforts to categorize genetic conditions based on their seriousness are complicated by the inherently subjective, multi-faceted, and elusive nature of the concept itself. This definitional complexity is further challenged by variable disease expression – ranging from lethal early-onset to mild or asymptomatic forms due to incomplete penetrance (e.g., Gaucher disease, Pompe disease) – and by advances in gene therapies (e.g., cystic fibrosis and spinal muscular atrophy), which have significantly improved outcomes (Kirk et al. 2021). As a result, conditions once considered serious may no longer carry the same implications for clinical or ethical decision-making.

The lack of definitional clarity, complexity, and absence of guidance around how to interpret seriousness can therefore lead to inconsistencies in its application, particularly in a population health context. For example, international variation in what genetic conditions are targeted by preconception carrier screening1 (PCS) can be attributed, at least in part, to different approaches to the interpretation or appraisal of seriousness. These interpretations will generally rely on high morbidity and mortality (i.e., life-limiting or life-threatening criteria) and are underpinned by Wilson & Jungner’s benchmark screening criteria2 (1968) with some more recent adaptations for genomics and/or rare diseases (Andermann et al. 2008; Dive and Newson 2021a; Molster et al. 2017; Genetic Alliance UK 2019; Rankin et al. 2025). The growing emphasis on increasing the visibility of population screening is a trend that is expected to accelerate as genomic sequencing becomes more affordable, accessible, and equitable. As the cost of sequencing continues to decline, its predictive power and precision will improve, making genetic carrier screening a more common and impactful tool for public health programs and eventual clinical decision-making, where needed. This debate on PCS is also unfolding at a time when newborn screening programs – though beyond the scope of this article – are undergoing significant transformation through advances in genomics (Jeanne and Chung 2025; Stevenson et al. 2025; Ziegler et al. 2025).

Various attempts have been made to operationalize seriousness through algorithms, taxonomies, classification systems, and decision-aids for clinical and policy decision-making (Allotey et al. 2003; Arjunan et al. 2020; Korngiebel et al. 2016; Lazarin et al. 2014). However, these approaches draw heavily on biomedical or clinical interpretations of serious, leaving less room for the contextual elements of the concept (psycho-social, cultural, environmental, lived experience) and the implications for the wider family, their community, their resources, and their setting. While some have attempted to incorporate more contextual elements and engage with the public (those impacted by decisions) (Korngiebel et al. 2016; Sajko et al. 2025), their application continues to lean towards clinical elements or the development of a definition of seriousness, both of which, we argue, are insufficient for capturing the diversity of context and lived experience, and can lead to reductive classifications of conditions. If used as a threshold or filter to access healthcare or resources, or as a key consideration in determining which conditions to screen for, there must be a common understanding of the relevant factors in the appraisal of seriousness, including a flexibility to translate this understanding to different contexts. To address this gap or these limitations, we have developed a framework for considering seriousness in reproductive decision-making, which offers a structure for reflecting on and discussing the concept in both policy and practice (Kleiderman et al. 2025).

Our framework consists of four core dimensions and four procedural elements (see Fig. 1) that provide a comprehensive conceptual tool to structure discussions and support decision-making around a common appraisal of seriousness (Kleiderman et al. 2025). The core dimensions encompass theoretical aspects related to the pertinent factors of seriousness, while the procedural elements illustrate how the concept can be applied across various contexts, including the elements that facilitate discussion of its core dimensions. These considerations are designed to be complementary, interrelated, and applied proportionately based on the context. Not all core dimensions or procedural elements need to be applied, and their application can vary depending on the context and circumstances.

Fig. 1.

Core dimensions and procedural elements of seriousness. This figure is based on the following source: Kleiderman, E., Boardman, F., Newson, A. J., Laberge, A. M., Knoppers, B. M., & Ravitsky, V. (2025). Unpacking the notion of “serious” genetic conditions: towards implementation in reproductive decision-making? European Journal of Human Genetics, 33(2),158–166. Licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). No changes were made

This article expands on the procedural elements of our framework for considering seriousness and lays out guiding questions and points to consider to help address the challenges around policy decisions, using the example of the offer and development of PCS in a population health context. We begin by providing an overview of the specific considerations related to PCS and the role of seriousness in this context. We argue that our framework for considering seriousness could assist in the public discussions and deliberations around which genetic conditions are most appropriate for inclusion in PCS panels, and to whom and where screening should be offered. This can be achieved by prompting multidisciplinary discussions and balanced considerations of seriousness. We consider these aspects by illustrating how our framework can help address challenges identified in the literature regarding the selection of conditions for PCS panels, where communication should be targeted, and the typology of access to effectively reach the population to be screened (Dive et al. 2023; Freeman et al. 2025). In so doing, our framework fosters an understanding of the concept that is defensible, balanced, and appropriately captures the considerations pertinent to screening in order to find asymptomatic individuals at risk. For the purpose of this article, the focus will be on screening in an adult population and within countries that have universal healthcare systems. As the framework serves as a conceptual tool, we note that further work will be required to validate its application in practice.

Framing conversations that invoke seriousness in population health

a) Preconception carrier screening (PCS)

PCS “involves testing people for their genetic carrier status in order to determine the likelihood that they could go on to have a baby with a serious recessive or X-linked genetic condition” (Dive and Newson 2021a, 202). PCS is designed to identify pathogenic variants that may be passed on to offspring (i.e., risk for future child), rather than to detect the presence of a current medical condition (Laberge and Burke 2017). Such screening is often driven by the needs of groups of parents or healthcare professionals caring for children affected by serious genetic conditions (Holtkamp et al. 2017; Van Steijvoort and Borry 2025). PCS can be undertaken during the planning or early stages of pregnancy.

As carriers typically do not exhibit symptoms of the genetic condition, no medical treatment is required (Molster et al. 2017). Instead, carrier screening identifies prospective parents at “reproductive risk” of having a child with a genetic condition. Parents who are found to be carriers through PCS are provided with relevant information to inform subsequent testing and reproductive decision-making. Decisions could include preparing to have a child with a genetic condition, avoiding having a baby, prenatal testing of a fetus during pregnancy, adoption, gamete donation, or preimplantation genetic testing (PGT). These decisions are based on the preferences, values, and circumstances of the couple (de Jong and de Wert 2015; De Wert et al. 2012; Delatycki et al. 2020; Dive and Newson 2021a; Holtkamp et al. 2017; Kater-Kuipers et al. 2018; Laberge 2023; Laberge and Burke 2017; Molster et al. 2017). They also differ in feasibility, their legal acceptability, as well as accessibility and affordability – all of which are further conditioned by geographic and cultural contexts.

Traditionally, genetic carrier screening programs were offered to specific populations or targeted groups/individuals with an increased risk of a particular genetic condition based on ethnicity or geographic location (Dive and Newson 2021a; Van Steijvoort and Borry 2025). In recent decades, with the adoption of next-generation sequencing, there has been a shift towards expanded screening that is integrated into publicly funded healthcare systems and is offered to all who wish to receive it (Cannon et al. 2019; Delatycki et al. 2020; Dive and Newson 2021a; Laberge 2023; Rowe and Wright 2020). Historically, the success of genetic carrier screening programs was measured by their ability to reduce the incidence of genetic conditions with an emphasis on public health benefits, prevention, and resource allocation, potentially prioritizing collective interests over individual autonomy and well-being. Such programs are generally implemented by governments as a public health intervention to improve the health of the population in response to a significant public health concern (Holtkamp et al. 2017). As such, population-based screening programs have typically focused on screening for common, severe or life-limiting conditions with early-onset and clearly defined phenotypes (Dive and Newson 2021a; Van Steijvoort and Borry 2025). However, positioning prevention as a form of actionability can inadvertently convey normative judgments about which kinds of lives are desirable, including the perceived acceptability of reducing the number of people with particular genetic conditions (De Wert et al. 2012; Dive and Newson 2021a; Newson 2011).

Since the early 2000s, the focus has shifted toward enhancing reproductive autonomy and supporting informed reproductive decision-making, reflecting a broader transition from a public health perspective to one centered on individualized care (Dive and Newson 2021a; Kihlbom 2016; Laberge 2023; Rowe and Wright 2020; Laberge et al. 2009). Reproductive autonomy refers to “the capacity to reflect critically on one’s values and preferences to inform decision making about reproduction […with an emphasis on] the relational context of the individual and the impact it has on their goals, values and choices” (Dive and Newson 2021a, 203). Early evidence suggests overall public support for PCS to improve reproductive decision-making by providing prospective parents with adequate information that aligns with their values, preferences, and circumstances (Dive and Newson 2021a; Rowe and Wright 2020). However, the development or expansion of such programs must also consider their implications or impact for other populations who may benefit from screening but whose needs are less visible or systematically overlooked. Screening initiatives risk becoming ethically problematic if they intentionally or inadvertently exclude these groups, or if the screening process itself results in harm (Newson 2011).

International guidelines vary significantly in their recommendations regarding the composition of PCS panels. For instance, the European Society of Human Genetics (ESHG) and the National Society of Genetic Counselors (NSGC) do not specify particular genes to be included in screening, instead emphasizing broader principles for panel design (Henneman et al. 2016; Peterlin and Peterlin 2025; Sagaser et al. 2023). In contrast, the Canadian College of Medical Geneticists (CCMG) recommends routinely offering pan-ethnic PCS for a specific panel of common, and yet serious, early-onset genetic conditions as part of provincial or territorial programs (Aul et al. 2025). It also recommends maintaining existing ethnicity-based and regional screening initiatives, but does not currently endorse publicly funded, population-level expanded carrier screening (Aul et al. 2025). The American College of Medical Genetics and Genomics (ACMG) advocates for a tiered approach, recommending the inclusion of 113 specific genes associated with conditions that have a carrier frequency of 1 in 200 or higher (Gregg et al. 2021). The ACMG guidelines advocate for a pan-ethnic approach to PCS – emphasizing ethnic and population neutrality – as a more equitable alternative to targeting only high-risk groups (Gregg et al. 2021). While this inclusive strategy broadens access to screening, it may not adequately address genetic conditions that are more prevalent in specific subgroups, nor does it always provide culturally tailored educational materials or counselling for those communities (Laberge 2023).

Dive and Newson (2021a) argue that by promoting plural values, PCS can have a dual mandate: (a) support reproductive autonomy and (b) attend to values of public health interventions. This differs from other traditional forms of population-based screening in that additional considerations, more focused on individual and family outcomes/decision-making – such as cultural or religious values, family context, socio-economic circumstances – ought to be taken into account not only in the implementation strategies but also in the goals of the screening program. This stands in contrast to the traditional emphasis on public health goals, such as prevention and improving population health (de Jong and de Wert 2015; Dive and Newson 2021a; Henneman et al. 2016; van der Hout et al. 2019). Therefore, PCS can be understood as integrating values from both clinical and public health paradigms, and balancing individual outcomes and population benefits (Dive and Newson 2021a; Kater-Kuipers et al. 2020).

b) The role of seriousness in preconception carrier screening

Dating back to the screening principles established by Wilson and Jungner (1968), the concept of a serious condition has been a central consideration, and plays an important role in PCS as a common consideration for gene selection (Dive et al. 2023; Holtkamp et al. 2017; Kirk et al. 2021; Molster et al. 2017). It has been argued that consensus on the genetic conditions to be included in PCS panels should extend beyond carrier frequency to include the seriousness of the condition, its clinical course, the high sensitivity/specificity of the screening test, the ease of result interpretation and communication, the availability – or lack – of effective treatment options, and its contextual framing within a particular society or culture at a particular time (Laberge 2023; Righetti et al. 2022; Wang, Kiss, et al. 2023). Furthermore, endorsement by family support groups and patient advocacy organizations, along with consensus on the importance of informing at-risk couples to support informed reproductive decision-making, are key considerations in determining the appropriateness of conditions for inclusion in PCS (Laberge 2023). PCS panels should therefore equally be informed by the perception and experiences of the population for which they are intended (Swainson et al. 2024), while recognizing that the decision to accept, decline, or act upon screening ultimately remains the decision of the individual or couple.

Variability in the offer of PCS exists worldwide, which as noted can stem from different understandings of seriousness, geographical differences in carrier frequencies of genetic conditions, local healthcare systems, availability of reproductive options and support, cultural and religious factors, as well as financial considerations (Molster et al. 2017; Rowe and Wright 2020; Van Steijvoort and Borry 2025). Population-based interventions are also likely to require a higher threshold for seriousness as the number and type of genetic conditions deemed to be serious enough to include in a PCS panel will likely be narrower than conditions for which testing may be offered in clinical care. Without established parameters around seriousness, trust in a PCS program could be affected. A greater emphasis on organizational aspects, economic considerations, and patient perspectives can help further inform public health, equity, and access (Dive and Newson 2021a; Molster et al. 2017).

In addition to seriousness, many of the concepts used to determine “screen-worthy conditions” are also subject to interpretation (Andermann et al. 2011; Johansen Taber et al. 2022). For example, concepts such as penetrance, quality of life, or impact of a condition can be widely variable and subjective to the context in which they are being considered (Boardman and Clark 2022). The inconsistent application of these concepts across different countries supports the need for a more in-depth look at how we appraise and understand seriousness. Consistency and coherence in appraisal are therefore essential to ensure equitable policy and implementation. After all, decisions are not made in isolation; they are shaped by a range of social and contextual factors, including barriers to accessing services, inadequate information, and forms of social and health inequalities (Dive and Newson 2021a; Johnston and Zacharias 2017). In the following sections, we further develop the procedural elements of our framework by outlining guiding questions and points to consider that can inform responses to challenges raised by PCS so as to foster a balanced, context-bound approach to appraising seriousness. The guiding questions and points to consider presented in Tables 1, 2, 3 and 4 are not intended to be prescriptive but to provide illustrative prompts for policymakers that can be adapted to their context. They can support exploration of the framework’s procedural elements and help structure deliberation about how seriousness is considered.

Table 1.

Guiding questions and points to consider about procedural fairness in assessing seriousness

Guiding questions
• How is seriousness assessed, and what processes ensure that assessments are transparent, evidence-based, and publicly accountable? • What measures or safeguards are in place to identify, prevent, and mitigate bias related to disability, ancestry, socio-cultural norms, geography, socio-economic status, or healthcare system structures? • How are cost, coverage, access, and communication practices evaluated to ensure appraisals of seriousness do not reinforce inequities or implicitly pressure individuals toward particular reproductive decisions?
Points to consider
Ensure transparency: Make decision-making procedures, evidence sources, and rationales publicly accessible (e.g., methodology documents, panel justification statements). Establish accountability: Define panel objectives, performance indicators, and equity measures; monitor outcomes such as participation in consultations, distribution of access, and uptake across socioeconomic groups; and establish regular review cycles to reflect new evidence and evolving social contexts. Use a multidimensional evidence base: Integrate clinical, epidemiological, and patient-reported data with lived experience to support a holistic understanding of seriousness that avoids overly medicalized interpretations. Address inequity, bias, and unintended pressure: Evaluate whether panel decisions may disproportionality affect specific populations or groups because of geography, cost, language, socio-economic circumstances, or other barriers. Ensure communication and eligibility criteria support informed choice without directing individuals towards particular reproductive decisions.

Table 2.

Guiding questions and points to consider about patient/family-centered impacts

Guiding questions
• How do individuals and families with lived experience perceive the seriousness of the condition, and what impacts does it have on their daily lives, well-being, and economic circumstances? • How might labelling a condition as serious enough to justify PCS influence stigma, identity, and societal perceptions of disability? • How should societal views about which conditions are appropriate targets for prevention be balanced with respect for diverse lived experiences and perspectives on disability? • What approaches can be used to engage the public in discussions or deliberations about which conditions should be included on screening panels (e.g., forums, surveys, deliberative panels)?
Points to consider
Consider impacts on asymptomatic carriers: Evaluate the potential benefits and harms of PCS for carriers, including effects on anxiety, uncertainty, identity, and well-being. Embed meaningful community engagement: Involve individuals with lived experience, patient advocacy groups, cultural communities, end users, and other affected stakeholders early and throughout the process to ensure diverse perspectives, evolving understandings of disability, and real-world impacts are reflected. Account for cultural, social, and political context: Consider how cultural norms, disability perspectives, and broader social and political contexts influence perceptions of seriousness and inform equitable decision-making.

Table 3.

Guiding questions and points to consider about shared decision-making (patients/families, professionals, health systems)

Guiding questions
• Is information about the offer of PCS accessible, balanced, and culturally appropriate? • Do patients understand the purpose, limitations, benefits, and possible outcomes associated with screening? • How do healthcare systems ensure PCS remains voluntary and free from coercion or pressure? • How is public understanding of PCS supported before it is offered in clinical care?
Points to consider
Provide clear, balanced, and inclusive information: Use accurate, accessible, culturally sensitive materials in multiple languages and formats, avoiding oversimplification or any suggestion that screening is expected, preferred, or socially endorsed. Promote informed and equitable choice: Ensure people of diverse literacy, linguistic, and socio-cultural backgrounds can understand their options and make autonomous decisions.

Table 4.

Guiding questions and points to consider about training and education of healthcare professionals

Guiding questions
• Are healthcare professionals involved in PCS adequately trained in genetics, risk and uncertainty communication, ethics, culturally sensitive care, and support for autonomous decisions? • Is training tailored to the diverse contexts in which PCS is offered (primary care, obstetrics, community clinics, genetics services)? • Is ongoing professional development available to address emerging evidence and technologies?
Points to consider
Provide consistent, inclusive training: Equip healthcare professionals across roles and regions to communicate accurately and sensitively with diverse populations. Embed disability perspectives, cultural humility, and sensitivity: Training should include lived disability experience, cultural awareness, and skills for communicating with people from diverse backgrounds to ensure inclusive, person-centered care. Support ongoing professional development: Invest in coordinated training to maintain trust, equity, and quality in PCS delivery.

Applying the framework for considering seriousness

Given that screening programs are generally implemented as a “one-size-fits-all” approach intended to benefit most people, there is little room for individualization, so a more generalized understanding of seriousness stemming from deliberations with those having lived experience would be required (Dive et al. 2024). Our framework allows for the shift in focus from a deeper, narrower consideration of seriousness as understood by expectant parents in the context of prenatal care (Kleiderman et al. 2026 - forthcoming) to a broader, more generalized consideration of seriousness at the policy level, beyond the individual or couple to whole or sub-populations.

In a population health context, the procedural elements (procedural fairness, patient-family-centered impacts, shared decision-making, and the assessment of training) operate alongside wider systemic considerations such as cost, equitable access, and health genomic literacy in the population. Procedural considerations must incorporate assessment of resource availability to support in-depth discussions of seriousness as they arise. As we will see, these procedural elements are likely to exert greater influence in implementation, as they establish the broader context within which decisions are made, and population-level interventions are set. Therefore, for present purposes we focus on the procedural elements which are more central to the contextual considerations relevant to PCS. The core dimensions (medical criteria, availability of treatment, availability of support, and lived experience), which intersect with the procedural elements provide additional context for their application, but will not be examined in detail as they are more integral to discussions around prenatal testing and diagnosis following PCS. It is through the interplay of its procedural elements and core dimensions that our framework aims not to define seriousness, but to enable a collaborative exploration of the concept to inform the development and implementation of PCS within a particular context or healthcare setting. In doing so, it lays a foundation on which deliberations and engagement with the public can begin.

Decisions around the development and implementation of PCS are political in nature and often fraught with competing interests that require policymakers to balance the needs of society with the different perspectives of the relevant actors (Andermann et al. 2011; Stenmarck et al. 2024). Reaching consensus may be challenging, given the diversity of actors in a policy context, each with different perceptions and understandings of seriousness. For example, while there may be agreement on which core dimensions to consider when appraising seriousness, the weight placed on each may differ based on the context or application of the technology. When considering the procedural elements, these may vary based on country, society, historical context, or healthcare system, as they account for the broader ecosystem, infrastructure, and socio-political climate within which decisions are made. In these situations, our framework can help support policymakers considering the inclusion of a specific genetic condition as a target for PCS to assess the condition’s seriousness. Our framework is designed to support a structured deliberative process in which clinical manifestations of a genetic condition are considered alongside individual and collective values, interests, and experience. Through guiding questions, the framework prompts policymakers to identify areas of convergence and tension among these considerations, examine whose perspectives are represented, and provide a transparent justification for how competing considerations are weighed. It is the intersections and possible tensions between the different elements/dimensions of our framework that help to stimulate discussion around seriousness when determining which conditions should be screened for in a given population. While we have previously elucidated the application of our framework’s core dimensions in prenatal care (Kleiderman et al. 2026 - forthcoming), for the purpose of this article on population screening practices, we are focusing on the procedural elements. These elements reflect key priorities identified in the literature, particularly in relation to ensuring fairness, equity, and responsiveness to community needs in PCS policy and program development.

a) Procedural fairness in assessing seriousness

The design, implementation, and access to PCS must be transparent, evidence-based, and incorporate diverse perspectives from the community, including those of individuals living with a genetic condition and their caregivers (Delatycki et al. 2020; Dive et al. 2023; Dive and Newson 2021a; Freeman et al. 2025; Kirk et al. 2021; Scully 2018; Vendrell et al. 2025). It is important for policymakers to be mindful of the risk of perpetuating societal views like ableism and eugenics, and consider potential repercussions of labelling a condition as serious as they develop policies affecting the population (Kleiderman et al. 2025). These potential socio-normative impacts are all the more important when PCS is publicly funded, as programs aimed at reducing the prevalence of a genetic condition can be perceived as coercive, exert undue pressure, or imply that the life of someone living with that condition is less valuable or desirable (Godard et al. 2003; Molster et al. 2017; Swainson et al. 2024; De Wert et al. 2012; Dive and Newson 2021a; Kihlbom 2016; Rowe and Wright 2020; van der Hout et al. 2019).

As population interventions typically use resources in a targeted way to reach specific groups and sub-populations, there is an emphasis on measurable outcomes and equitable resource use. Policies that attempt to clarify seriousness related to such interventions typically employ terms such as life-threatening or life-limiting with a focus on mortality and morbidity in early childhood (Henneman et al. 2016; Heritable Human Genome Editing 2020; Molster et al. 2017). Therefore, appraisals of a genetic condition’s seriousness are typically made in aggregate, based on a medical model – seriousness as the objective, quantifiable, and measurable qualifier – and applied top-down for consistent and coherent application of laws and policies (Kleiderman et al. 2025). However, we have argued that consideration of seriousness at the population level is more than an aggregate of individual cases and clinical experience so as to appropriately appraise seriousness in a context where collective interests or communal values, such as solidarity, equity, sustainability, social justice, and community participation are at play (Kleiderman et al. 2025; Knoppers et al. 2025). These communal values act on the community’s willingness or interest in making different screening programs available to all those who could benefit or for the “common good”, and involve collectivist reasoning in evaluating the risk-benefit ratio to justify the implementation of such programs (Dive and Newson 2021a; Newson 2011; Knoppers et al. 2025).

Equitable access to PCS requires that it be available to all people who want it, and this requires careful consideration of regional, cultural, and demographic factors, as well as collaborative engagement with community groups (e.g., culturally or linguistically diverse communities) to ensure that PCS, and the conditions deemed serious enough to be screened for, are implemented in a culturally appropriate manner. Some countries (e.g., Australia, Belgium, the Netherlands, Israel) are beginning to trial or implement PCS as “an opt-in population screening initiative, offered to those of reproductive age regardless of family history or ancestry” or in an ad hoc manner (Dive and Newson 2021a, 202; Rowe and Wright 2020). There is a push to offer PCS through public funding (national funded programs), where possible, so that all those who could benefit can have access (Delatycki et al. 2020; Dive and Newson 2021a; Aul et al. 2025). Yet, there remains significant international variation in access to PCS and the number or type of conditions screened (including how results are managed), as well as whether government funding is available, which can lead to concerns over inequality of access (Archibald et al. 2022; Dive and Newson 2021a; Freeman et al. 2025; Ong et al. 2018; Schuurmans et al. 2020). It is important to acknowledge the diverse socio-political contexts of individual countries and societies, and incorporate these considerations in deliberations about seriousness where inclusion and access are discussed to ensure that policy and practice remain responsive to public and communal values.

Consideration of this procedural element intersects with the core dimensions of medical factors and lived experience (i.e., personal/identity factors, psycho-social and socio-cultural factors; relationships; and built- or physical environment), which must be contextualized within the wider social and structural factors. Attending to the integrated application of procedural fairness along with these core dimensions will help to foster a more equitable approach to access and distribution of resources, ensuring that those who could benefit most will be able to do so.

It is also important to pay attention to the accessibility and affordability of further interventions that prospective parents may want to access following PCS (e.g., in vitro fertilization and PGT to avoid having an affected child; or termination of pregnancy, if already pregnant). In this instance, procedural fairness may also intersect with the core dimensions of access/availability of treatment and support, encompassing considerations such as the objectives, burden, and costs associated with treatment, as well as the allocation of resources and the financial implications for both families and the healthcare system. This creates further space for discussion about seriousness, and governments must carefully consider not only the availability of interventions for PCS but also the downstream effects and associated costs (Molster et al. 2017). For a PCS program to be effective and cost-efficient, it must include interventions that lead to improved health outcomes for individuals and couples (Laberge 2023; Molster et al. 2017). These interventions should be effective, readily available, easily accessible, and acceptable to the target population (Molster et al. 2017). See Table 1 for a list of guiding questions and points to consider related to procedural fairness in assessing seriousness.

b) Patient/family centered impacts

In a population health context, this procedural element captures the impacts and considerations related to both asymptomatic individuals/citizens (from the public), as well as patients and their families. From a programmatic perspective, this procedural element captures considerations around how society determines or influences the acceptability of screen-worthy genetic conditions and how to engage with the community on these issues prior to the implementation of PCS programs.

Acknowledging the deeply personal nature of reproductive decisions informed by PCS results, the determination of what genetic conditions to include in a screening panel requires a judgment around seriousness, which should be informed by lived experience and the potential impact of a given condition on an individual, their family, and their community (Dive et al. 2022; Freeman et al. 2025). For example, lived experience can capture aspects such as what it means to be a carrier, to live with the condition, or to care for someone living with that condition (Van Steijvoort and Borry 2025; Boardman et al. 2018). Our framework for considering seriousness encourages a balanced approach that incorporates both objective factors (medical factors, treatment options, and prevalence), as well as contextual factors (cultural values, physical environments, and family experiences with the condition). This means evaluating not just how serious the condition is in clinical terms but also how it is perceived and experienced by different communities and populations.

Decisions regarding the inclusion of genes or conditions on PCS panels involve a diverse range of stakeholders, including policymakers, patients (prospective parents), healthcare professionals, ethicists, researchers, health economists, as well as individuals living with and advocacy groups representing populations with different genetic conditions (Korngiebel et al. 2016). As such, PCS must acknowledge and respond to this diversity of perspectives, while remaining responsive to community values, attitudes, and expectations (Kirk et al. 2021). Given the range of interests and experiences represented among stakeholders, different strategies to appraising seriousness may be necessary at both the policy and program development levels. Such an approach can support more inclusive policies (Gollust et al. 2005). Importantly, views on what aspects of a condition are most significant, and how clinical and lived impacts should be measured, may differ across individuals and communities. Lived experiences will also vary both within and across conditions, particularly where disability is considered identity-constituting, demonstrating the complexities of the experience of disability and some of the existing misconceptions (Beard et al. 2016; Boardman and Hale 2018; Shakespeare 1998).

The question of societal readiness or desirability – whether the general population actually wants publicly funded access to PCS – remains pertinent (Holtkamp et al. 2017; Molster et al. 2017). Therefore, it is important to consider ways to build in broad community consultation, engagement, and deliberation about the seriousness of genetic conditions with those living with the conditions, those who may be offered screening, healthcare professionals, policymakers, ethicists, and the general public to ensure the offer meets the needs of the population (Freeman et al. 2025; Gollust et al. 2005). For example, workshops, surveys, focus groups, and interviews with members of relevant communities and patient advocacy groups could significantly inform the development and implementation of PCS (Alarcón Garavito et al. 2023; Major and Juengst 2025). The Australian Reproductive Genetic Carrier Screening Project (Mackenzie’s Mission) research initiative is an example that incorporated community perspectives into the development of a PCS panel (Kirk et al. 2021). They clearly articulate the importance of involving “communities who live (or care for someone) with a genetic condition […] to ensure that the program will be acceptable to those whom it is intended to serve” and acknowledge the existence of country-specific considerations that may influence the assessment of a genetic condition’s seriousness (Kirk et al. 2021, 2). These ought to be taken into account when developing an inclusive offer of PCS.

This procedural element supports the incorporation of personalized experiences and perspectives through its intersection with the core dimensions of availability of treatment, availability of support, and lived experience. This includes considerations around an individual’s close environment and capacity to deal with important changes in life, as well as notions of perceived quality of life, community/identity, and ability to thrive or impact on the household (Kleiderman et al. 2025). Incorporating these perspectives in the design and implementation of PCS acknowledges diverse cultural and social understandings of seriousness, without aggregating or collapsing experiences into a single narrative (Kleiderman et al. 2025). This leads into the next procedural element, reflecting the advocacy principle, “Nothing about us, without us.” See Table 2 for a list of guiding questions and points to consider related to patient/family-centered impacts.

c) Shared decision-making between patients/families, healthcare professionals and healthcare systems

Population-based programs must effectively communicate to the entire population that screening is available as an offer (i.e., voluntary). This offer encompasses not only the initial screening process but also subsequent confirmatory testing and access to appropriate clinical and/or other forms of care. In a population health context, this procedural element highlights the importance of public awareness and the manner in which information about the offer and implementation of PCS is communicated to individuals (prospective parents), groups, and communities. Enhancing public awareness is essential for improving genetic literacy and ensuring that these end users are informed, empowered, and prepared to meaningfully participate in consultations and discussions related to PCS (Alarcón Garavito et al. 2023; Holtkamp et al. 2017; Kleiderman et al. 2025). This includes the provision of accessible and appropriate public education and information (e.g., interactive e-learning tools, decision aids, workshops, courses, media campaigns) (Holtkamp et al. 2017). Miscommunication or misinformation on the meaning of being a carrier can have social implications, such as shifts in societal norms or perpetuation of epistemic injustices like ableism or eugenics, leading to stigmatization (Laberge 2023). Educational materials should be evidence-based, incorporate the experiences of affected individuals and caregivers, clearly communicate program aims and explain the benefits, risks, and uncertainties of genetics and PCS, including the broad implications for society (Gollust et al. 2005; Molster et al. 2017).

Experts also advocate for a shift from the current model, which relies on a group of individuals making such decisions, toward integrating the richness and diversity of broader perspectives. This shift aims to foster more accountable policymaking that is reflective of the realities and lived experiences of those for whom population-based interventions are most relevant (Williams et al. 2002). Such an approach in turn can lead to greater support for PCS that reflects the diverse perspectives of the population that could benefit from screening. This is demonstrated through the interplay of shared decision-making and the core dimensions of lived experience (e.g., education, psycho-social factors, living circumstances, as well as the historical, legal, and political context); availability of treatment (e.g., burden – physical, financial, interpersonal); and the availability of support (e.g., social, familial, financial). Considering these elements provides structure for reflections around panel composition.

With the shift towards expanded screening comes the likelihood that more individual carriers relative to carrier couples will be identified (Aul et al. 2025). This raises the question about how results from PCS are communicated to couples or individuals. Different programs approach it differently. In this context, prioritizing couple-based rather than individual-based PCS may better support informed reproductive decision-making and promote a more just allocation of limited resources (Dive and Newson 2021b; Laberge 2023; Plantinga et al. 2019; Schuurmans et al. 2019). Policymakers must also recognize that access to interventions for couples identified as carriers is not always equitable, so the utility of the information provided must be considered to ensure resources are allocated where they will have the most impact (Laberge 2023). See Table 3 for a list of guiding questions and points to consider related to shared decision-making.

d) Assessment of training of healthcare professionals

Similar to the need for public education, governments and healthcare systems should ensure appropriate training and education is available to healthcare professionals. As we have seen, the seriousness of a genetic condition must be able to respond to or resonate with diverse perspectives and experiences of genetic conditions. Currently, resource limitations – particularly in the provision of genetic counselling – pose significant challenges (Wang, Kiss, et al. 2023; Allyse et al. 2015; Bayefsky et al. 2016; Hoskovec et al. 2018). Recent trends indicate that an increasing number of women or couples are being screened by a wider range of healthcare professionals. However, not all healthcare professionals possess the appropriate training or preparation to deliver PCS and related counselling, including conversation about the seriousness of a genetic condition (Laberge 2023).

To support the transition to expanded PCS, there is a recognized need for practical tools, such as structured practice guides or schematic overviews, that not only convey essential knowledge and assist in interpreting laboratory results but also provide concrete examples of how to deliver counselling in a non-directive manner (Holtkamp et al. 2017). Moreover, there should be greater emphasis on genetics and carrier screening within medical education, including the integration of these topics into undergraduate medical curricula as well as postgraduate training for healthcare professionals (Holtkamp et al. 2017). Our framework can support such initiatives by serving as one such tool to enable structured, multi-dimensional discussions and deliberations around seriousness both in the selection of conditions to include in expanded PCS panels. See Table 4 for a list of guiding questions and points to consider related to training and education of healthcare professionals.

Moving forward

As genomic technologies continue to evolve and expand, the need for ethically grounded, context-sensitive approaches to population-based screening will only grow. Seriousness remains a central consideration across all contexts, as societies must reflect on how reproductive decisions shape who comes into the world. The challenge in designing population screening programs is in integrating individuals’ experiential knowledge to better understand how seriousness is understood at the population level. The scientific understanding behind PCS, and population-based screening in general, must be informed by this experiential knowledge, but we recognize that it cannot be dictated by it given that population interventions have different goals and distinct scientific methodologies (e.g., epidemiology, biostatistics, health services, social and public policy analysis, population health management, health impact assessment). The collective decision to pay for, implement, and offer a screening program should align with the prevailing values of a population that endorses and recognizes the importance of identifying asymptomatic individuals through publicly funded initiatives (i.e., at the cost of the State, on behalf of the population). Such programs serve a measurable indicator of a society’s commitment to preventive care and should be acknowledged as a distinct component of the public health system. With the increasing use of high-throughput screening technologies, this space will only become more complex for policymakers. Better methods are needed for determining not only what constitutes a serious genetic condition, but also what constitutes a “result” deemed serious enough to be shared.

Our framework offers a foundation for such efforts, supporting the development of screening programs that are equitable, respectful of lived experience, and aligned with the goals of community genetics. The authors recognize that discussions and deliberations regarding a common understanding of seriousness are an iterative process that will require a certain flexibility to adapt to different contexts and situations (i.e., no firm lines drawn in the sand). Advancements in medical science, including the development of new treatments and therapies, can lead to an evolving perception or understanding of seriousness of specific genetic conditions over time (Wang, Scuffham, et al. 2023). Use of our framework encourages the integration of contextual considerations and lived experience in policy discussions about seriousness, as these aspects directly affect the perception of the concept, including societal perceptions of genetic conditions labelled as such.

Importantly, our framework cautions against an overreliance on clinical/medical factors, and interpreting these devoid of context, when determining a condition’s suitability for inclusion in PCS. The emphasis is on the emergence of seriousness through deliberation among policymakers with input from relevant stakeholders and end users (i.e., those with experiential knowledge of the conditions being discussed). The framework provides structure for these discussions and a way to incorporate lived experience. This approach helps ensure that technological interventions are used responsibly, while also acknowledging the wide variability that may exist within any given genetic condition. It also avoids labelling conditions – and people living with those conditions – and instead sheds critical light on the circumstances surrounding the person, including the impacts of their experiences of the world. While our framework accounts for contextual factors, differences in policies and population programs are still expected due to variations in socio-political environments, healthcare systems, and jurisdictional structures. However, the resulting policy decisions would be informed by a similar approach to appraising seriousness. It is the characteristics of the context and our framework’s ability to respond to and address different aspects (individual versus population) that may lead to different decisional outcomes. Our framework also supports the need for adaptability to regional differences in prevalence and availability of treatments and/or resources, including considerations of the potential impacts for the affected individual and for society. For example, funding for and equitable access to screening, treatments, or to social support. Therefore, different countries may reach different conclusions about which genetic conditions are considered sufficiently serious to warrant inclusion in PCS. The framework highlights that seriousness is not self-evident, despite its frequent use in everyday discourse. It invites critical reflection and creates space for ethical deliberation by providing policymakers with a structured yet flexible set of common considerations. In doing so, it may expose certain fault lines in the debate about seriousness, particularly where there are tensions between its core dimensions and procedural elements. Although it is designed to facilitate constructive deliberation, we recognize that its use may also give rise to more complex discussions and polarized viewpoints. Yet this very complexity is essential for a meaningful unpacking of what constitutes a serious genetic condition. These crucial deliberations will influence how and which of the core dimensions and/or procedural elements will be applied based on those most relevant to the question/objective under consideration, and shaped by the socio-cultural, political, historical, and healthcare contexts of each jurisdiction. It is within this framing that considerations of seriousness should be situated.

A structured, multi-dimensional framework for considering seriousness can enrich the screening criteria set out by Wilson and Jungner by incorporating experiential knowledge, real-world impact, value judgments, and implementation readiness. It can also help clarify the notion of “important health problem” by combining clinical severity with personal and social dimensions to identify those conditions that truly warrant population screening. In so doing, the combination of our framework and Wilson and Jungner’s longstanding criteria can be complementary and ensure that screening initiatives are medically sound, ethically robust, and responsive to the lived experiences of those affected. Takahashi et al. (2025) demonstrate that our framework has been shown to be useful when exploring Japan’s approach to PGT-M, as the act of balancing core dimensions and procedural elements encourages deliberations that are more inclusive and highlights areas of tension or undervalued perspectives, while enhancing reproductive autonomy and disability justice in genetics.

Although designed with public healthcare systems in mind, the framework is grounded in broader ethical principles, building on long-standing debates and foundational concepts in reproductive ethics. It acknowledges that individuals and families have varied levels of access to healthcare resources, and these differences are built into its structure. As such, the framework is adaptable and can be applied within different contexts/healthcare models, including privatized systems. When applied in privatized healthcare systems, the framework may take a different form, with certain core dimensions and procedural elements gaining prominence depending on the priorities and structures of that system. Importantly, frameworks of this kind can also serve a regulatory function by guiding genetics companies in determining which conditions should be included in screening panels, thereby discouraging the practice of offering excessively broad or ethically unanchored testing options. Consequently, for multi-stakeholder governance – particularly within privatized systems where no single entity sets priorities – the framework provides a shared language for considering seriousness across insurers, pharmaceutical companies, healthcare professionals, patient advocacy groups, employers, and regulators. The framework’s application in contexts beyond publicly funded healthcare systems will require further reflection and validation, as it is beyond the scope of this article.

We acknowledge that a single definition is not attainable (or desirable) and recognize that serious may nonetheless remain an essentially contested concept or that alternative parameters for setting the scope of assisted reproductive technologies may be more appropriate than seriousness (Dive et al. 2024; Taylor-Sands et al. 2024). Others have argued that different criteria or concepts (e.g., clinical utility or prevalence of a genetic condition) may be more appropriate as a primary consideration and help circumvent some of the ethical complexities raised by serious (Dive et al. 2024; Williams et al. 2002). For example, a condition may be extremely prevalent but not serious or decisions about the usefulness of information provided by an intervention may lead to a judgment about the seriousness of a condition (even if implicit). Yet, we argue against doing away with seriousness altogether. Rather than being seen as an intrinsic element of a genetic condition, seriousness captures how a condition is experienced in the world; and this is where the discussions and deliberations need to occur. The concept has inherent value and meaning given its widespread use in policy and practice. When framed appropriately, seriousness can serve as an important safeguard against the inappropriate use of technology, particularly in contexts that risk veering into eugenics or human enhancement – it helps establish ethical boundaries for understanding and evaluating the degree of human suffering. Without a shared understanding of what constitutes a serious genetic condition, there are no meaningful parameters to guide ethical decision-making. That being said, we recognize that serious is but one of the factors to consider and encourage further reflection on how seriousness and clinical utility, for example, may be able to work together to provide greater clarity and guidance in this space.

Limitations:

While the framework’s flexibility accommodates diverse and context-sensitive interpretations of seriousness, its deliberate avoidance of fixed thresholds or hierarchies among dimensions does not eliminate the underlying normative ambiguity of the concept and may reduce its utility in contexts that require clear, consistent criteria for decision-making. Similarly, its intentionally non-prescriptive design offers limited guidance on how dimensions should be weighted or prioritized in practice, potentially resulting in variability across applications. However, even in contexts that demand consistency and accountability, the framework may serve as a useful tool for structuring deliberation, making relevant considerations, values, and assumptions explicit, and supporting more transparent decision-making. Further empirical work is needed to test and validate the framework’s operationalization and effectiveness across different regulatory and policy contexts

Beyond these limitations, the framework may have broader relevance across a range of policy and clinical contexts in which appraisals of seriousness play a role. Although PCS is used as the example in this article, similar considerations would take effect wherever seriousness informs access to other assisted reproductive technologies or healthcare interventions, including non-invasive prenatal testing (NIPT), PGT, prenatal diagnosis, human somatic / germline gene editing, late-term abortions, and treatment or resource allocation decisions. The framework may also support deliberation in other ethically complex contexts, such as access to last resort medications / treatments, withdrawal of neonatal care, and disclosure of genetic information to family members. We acknowledge that further work is required to validate our framework for considering seriousness and to facilitate its practical application. This includes exploring its use in other settings, as well as how it might fit with diverse understandings of health and illness. There is also the possibility that our framework could support the creation of binning systems or the categorization of conditions in policy, where appropriate, by enabling more nuanced reflections around seriousness that account for diverse perspectives, including the context within which policy discussions occur.

Author contributions

All authors were involved in the conception and design of this manuscript. EK was responsible for writing the original draft of the manuscript. AML, LD, VR, BMK, and FB provided support, comments, and critical revision and edits to several versions of the manuscript. All authors read and approved the final version of the manuscript.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval

This article does not contain any studies with human participants or animals performed by the any of the authors.

Conflict of interest

The authors declare they have no conflict of interest.