Societal implications of expanded universal carrier screening: a scoping review

Carrier screening aims to identify couples at risk of conceiving children with a recessive condition. Until recently, carrier screening was primarily offered ancestry-based. Technological advances now facilitate expanded universal carrier screening (EUCS). This scoping review aimed to map EUCS’s potential societal implications based on both theoretical studies and empirical evidence. To this aim, we performed a CoCites search to find relevant articles, including articles describing carrier screening for at-risk populations, based on five selected query articles. Forty articles were included. Three main potential societal implications were identified: (1) unwanted medicalization, (2) stigmatization and discrimination of carriers and people affected with the conditions screened and (3) challenges in achieving equitable access. Within these themes, potential positive implications are reduction of ethnic stigmatization in ancestry-based offers and increased equity. Potential negative implications are reinforcement of disability-based stigmatization, less possibility for developing expertise in healthcare and societal pressure to partake in screening. Empirical evidence on all these implications is however scarce. In conclusion, both positive and negative potential societal implications of implementing EUCS, primarily theoretical, were identified, even in at-risk groups where evidence is mostly lacking. Empirical research in EUCS pilots is needed to identify which societal implications are likely to occur and therefore should be overcome when implementing EUCS.


INTRODUCTION
Carrier screening provides prospective parents information about their carrier status for autosomal recessive and x-linked conditions. If couples prove to be carriers, they have a 1 in 4 risk in each pregnancy of having a child with an autosomal recessive condition. For X-linked recessive conditions, there is a 50% risk for male offspring to be affected if the woman is found to be a carrier. It is estimated that approximately 1 in 100/125 couples have a risk of having a child affected with a serious recessive condition [1]. Generally, information on carrier status is provided with the aim of informing reproductive decision-making. Prior to pregnancy (i.e., preconceptionally), the range of reproductive options after testing is wider than during pregnancy and may include preimplantation genetic testing or the use of donor gametes. This contrasts with prenatal carrier screening, where the only option is having or not having prenatal diagnosis. If then the child proves to be affected, a couple may decide to terminate the pregnancy or prepare for a child with the condition identified. Although offering carrier screening preconceptionally is widely regarded as ethically preferable, couples may often only be reached once a pregnancy is already established [2].
Until recently, carrier screening for one or a few conditions was mostly offered to at-risk populations based on ancestry or geographical origin [3]. In addition to the aim of informed reproductive decision-making, many of these programs were set up to prevent suffering of children and families in communities with a high disease burden and/or to prevent the society from having insufficient healthcare budgets to take appropriate care for those affected by the condition [4,5]. Examples of these screening offers include carrier screening for Tay-Sachs disease among the Ashkenazi Jewish population, for example as part of the carriermatching program Dor Yeshorim [6], and the semi-mandatory screening offer for beta-thalassemia on Cyprus [7].
Since approximately 2011, expanded carrier screening has come into practice as a reliable, fast, and relatively affordable screening method that allows for a population-based or universal offer to all couples with a child wish, regardless of their a priori risk [5]. The term "expanded carrier screening" (ECS) consists of different elements. As a form of screening, ECS entails a routine offer of medical testing to a target population of people without necessarily having a prior indication for such testing based on elevated risk for the conditions involved. The fact that the test looks for carrier status of recessive conditions makes it a form of carrier screening. The qualification 'expanded' refers to the scope of the screening test, which allows simultaneous testing for multiple recessive conditions [8,9]. ECS can be available universally, allowing all couples with a desire to have children to partake. In several countries, such as United States, ECS is now routinely offered in a healthcare setting through use of commercial test offers [10]. Although many ECS and expanded universal carrier screening (EUCS) offers exist, including pilots carried out in several countries including the Netherlands [11] and Australia ("Mackenzie's mission") [12], EUCS has not been implemented as a population-based screening program anywhere in the world [13].
While EUCS potentially promotes reproductive autonomy for all couples planning to conceive, it also raises ethical, societal and psychological concerns, partly derived from concerns as well as experiences in at-risk populations [14]. To consider whether and how implementation of EUCS is desirable, and in what way(s) responsible implementation could be feasible, we believe it is important to map the (potential) implications of EUCS on the societal level [15,16]. To our knowledge, this has not been done systematically before. This scoping review therefore aimed to answer the following research questions: (1) which (potential) societal implications of EUCS are described in the literature?, and (2) what is the (empirical) evidence available for these societal implications?

MATERIALS AND METHODS Design
To map the literature available on societal implications of EUCS, we decided to conduct a scoping review. A scoping review instead of a systematic review was chosen because scoping reviews are more exploratory in nature, allow for a broader review of literature available with more expansive inclusion criteria and may provide directions for future research [17]. In conducting this review, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) checklist [18].

Search strategy
To perform our search, we used the citation-based method CoCites [19]. CoCites uses previously identified highly relevant scientific publications that fulfill the inclusion criteria (query articles) and performs two searches: (1) a co-citation search that retrieves the reference list of the query article and identifies which articles in this list are most often cited together with it, and (2) a citation search that finds all articles that cite or are cited by the query article. For a single query article, the citation search retrieves its citations and references. For a set of related query articles, the citation search finds articles that cite or are cited by multiple articles from the query article set. This step is performed to include articles that are recently published but not (yet) cited frequently enough to appear in the co-citation search [19]. CoCites thus differs from the traditional review approach in that it starts with identification of one or more highly relevant publications and uses these publications as the basis of the search. While it is a more efficient approach to performing a search, a limitation of this approach is that CoCites may not retrieve infrequently cited publications that themselves do not cite or are not cited by any articles from the query set, therefore potentially missing very old articles or very recently published articles [19].
To perform our search, one or more query articles needed to be defined. To this aim, authors with expertise in this field (MP, IL, LH, WD) as well as an external sociologist, discussed societal implications of EUCS they hypothesized. In this discussion, societal implications were defined as consequences of EUCS for society instead of for the individual. Based on this, the experts reached consensus on a set of five definite query articles written by a blended group of authors [2,3,14,20,21]. A set of five query articles was defined as these were thought to cover all hypothetical implications defined by the experts. We then performed analyses on these five query articles using CoCites. The search was conducted in October 2020 and updated in May 2022. Figure 1 presents the flow-chart of the article selection process. Articles that were cocited more than once were included in the selection process. We included articles that: 1) discussed potential societal implications of universal offers or reported on potential and experienced societal implications of earlier ancestry-based screening offers that could shed light on the implications of an EUCS offer, and 2) were written in English. We included all design types, both articles reporting primary data as well as expert consensus papers, opinion papers and literature reviews, as we aimed to explore all types of data and insights available on (potential) societal implications of EUCS knowing that few primary data on ECS in particular would be available.

Selection of articles
Titles and abstracts were screened for eligibility by two of the authors (LvdH and NvdB) independently, using the software program Rayyan [22]. Subsequently, full texts of the remaining articles were screened and read by LvdH and NvdB to select articles for inclusion. Any discrepancies between authors during the selection process were discussed until consensus was reached. In case of disagreement, a third author (MP) was available to reach agreement. Inter-rater reliability was assessed as high (Κ = 0.82) [23].

Data synthesis
Data synthesis was performed independently by two of the authors (LvdH and NvdB). We used a narrative synthesis strategy to summarize (potential) societal implications of an (expanded) carrier screening offer [24]. For each article, data were extracted, analyzed, and coded using a data extraction form. A codebook was based on the societal topics discussed by the authors prior to the search and was further developed based on data synthesis. As this was a scoping review, we performed no quality assessment on the included articles.

Themes
Three main themes regarding (potential) positive and negative societal implications were identified: (1) Medicalization, (2) Stigmatization and discrimination of carriers and of people affected with the conditions screened and (3) Challenges in achieving equitable access. Table 2 presents the themes addressed per article included in this review.

Supply push
The term 'supply push' was used by Bekker et al. [59] in the context of cystic fibrosis carrier testing, where the authors showed that the strongest variable associated with screening uptake was the (opportunistic) approach by healthcare professionals (HCPs) and suggested that high uptake rates more likely represent the active carrier screening approach initiated by HCPs or government rather than a response to a current demand from the general public. In the interview study of Van der Hout et al. [2], Dutch stakeholders additionally suggested that implementing EUCS as a top-down initiative prompted by the healthcare system is a matter of supply push. As a consequence, they stated that the general public might lack the initial desire to know their carrier status, either because a frame of reference is lacking or because the information EUCS provides does not respond to a problem recognized in daily practice, e.g. due to lack of awareness [2]. This was also observed in a qualitative stakeholder study with potential users from the general public, indicating that they were not aware of the availability of EUCS and therefore did not consider to participate yet [46]. Kihlbom [14] stated that resistance to partaking of EUCS may exist as well, as couples may oppose the idea of implementing an additional medical procedure in the preconception or prenatal phase. Additionally, people with certain religious beliefs or other world views may have less interest in screening that may allow for selective reproduction [44,46,50]. Prior experience or familiarity with the condition(s) screened would lead to a higher expressed need for EUCS [39,40].

Routinization
Several articles mentioned concerns regarding routinization: when screening becomes routine, as could happen when offered programmatically, it may in the end be offered and accepted without careful consideration [60]. Routinization could be worrisome for an EUCS offer as part of a reproductive screening program because this may affect informed decision-making and the freedom to choose, both key values in reproductive carrier screening, and may have unwanted consequences for people with disabilities [61]. Theoretical articles included in this review mentioned that if a universal offer becomes routine, couples may believe that partaking in EUCS is the right thing to do and may even lead to societal pressure on couples to participate in testing [3,13,14,27,34,36]. Articles stated that routinization of EUCS may specifically affect societal perspectives on reproductive responsibilities, raising the question whether couples will feel free to decline the offer or to make the decision not to intervene to prevent an affected pregnancy if they appear to be a carrier couple [6,13,14,27,32,36,45]. This concern was also expressed by HCPs and policy makers. [2,29,49,[51][52][53] Stakeholders moreover stated that if EUCS becomes routine, it may impact the perception of health in the sense that risks need to be prevented [29,52]. Ready et al. [30] reported that 33% of women's HCPs were ambivalent regarding the notion that carrier screening is socially responsible behavior. In a study exploring attitudes of the general public, 44% agreed that EUCS creates high expectations of parents to conceive a healthy child [44].
In addition, some authors argued that the organization of such an offer may reinforce the impact of routinization [3,13,32,34]. In a theoretical articles it was stated that offering ECS in a clinical setting may lead couples to compliantly accept screening, as they may believe screening is necessary or routine when clinically offered [13,34]. Authors additionally stated that governmentsponsored ECS programs, full reimbursement of ECS, using an easy and relatively non-invasive manner for sample collection, and public campaigns about the possibility of ECS may foster the notion of ECS being routine and that it is desirable to partake and perhaps even to reduce the conditions screened [3,13,32]. A survey study among Dutch Jewish participants showed that 24.1% believed that HCPs were allowed to insist that Jewish people participate in screening [38].
One article actually presented empirical data on routinization and subsequent societal pressure in case of a (semi-mandatory or mandatory) ancestry-based carrier screening offer in Israel [55]. This study on attitudes of modern-religious Ashkenazi Jewish people in Israel found that most respondents confirmed that they succumbed to societal pressure when they took part in the premarital screening program [55].
Aim for 'perfect children' Several articles included in this review also suggested that EUCS may contribute to a societal climate where having less than 'perfect children' is regarded as problematic, especially when mild conditions would be included in the test panel(s). These articles included theoretical papers [14] and stakeholder consultations. [3,29,46,[51][52][53][54] Related to this, some policy makers in Sweden expected that members of the general population might misconstrue the government's motives for ECS, considering past experiences with state-promoted eugenics policies [51]. Other stakeholders additionally shared concerns that a universal offer may indeed reinforce notions of the government restricting reproductive freedom [3,53]. However, Cowan et al. [4] argued       that the scenario of new eugenics policies occurring in Western democratic societies was considered implausible, as the considered aim of the program is to enhance reproductive autonomy at the individual level rather than to improve the health or wellbeing at population level. No articles reported experiences with actual carrier screening offers that are relevant for assessing the reality of these concerns.

Stigmatization and discrimination
Multiple aspects of genetic stigmatization (i.e. labeling a group or person with negative medical, social or psychological characteristics) and discrimination (i.e., making unjustified distinctions between groups or persons because of medical, social or psychological characteristics [62]) were brought forward as potential implications of a ECS offer [2, 3, 5, 13, 14, 20, 21, 27-30, 32, 35, 36, 38, 39, 41, 45, 47, 51-54, 58] or were reported as effects of ancestry-based preconception screening offers of the past [5,7,21,32,42,43,55,57]. Both potential positive and negative societal implications related to stigmatization and discrimination were described in theoretical articles in the context of a universal offer, as outlined below. We found no empirical evidence of stigmatization and discrimination following EUCS.

Expectations regarding stigmatization
As EUCS will be offered to all individuals in the general population regardless of ancestry, consanguinity or geographic origin, stakeholders [38,39,58], experts and authors [5,21,28,35,36,45,47] stated that such an offer could potentially reduce stigmatization of ethnic groups. Stakeholders additionally suggested that a universal offer may normalize carrier status, because 'we are all fellow mutants together' (p.169) [63] regarding carrier status for recessive conditions [29]. However, potential harms of EUCS regarding stigmatization were mentioned in multiple articles as well. First, stakeholders believed that the offer might reinforce disability-based stigmatization, [2,41,[51][52][53][54] which was also mentioned in theoretical papers [13,14,20,27,45] and an expert consensus paper [5]. They suggested that stigmatization may occur because the offer might encourage the perception that there is no place for people with disabilities in our society, or that the lives of people with genetic conditions have less value, referred to as 'the disability rights critique'. [2,5,13,14,27,32,45,[51][52][53][54] Some authors [13,27] argued that the risk of increased stigmatization depends on the screening panel, stating that it would be more ethically defensible to screen for genetic variants that cause severe childhood-onset conditions, although perceptions on severity are not entirely objectifiable.
Second, stakeholders reflected upon potential stigmatization of carriers [3,53] as well as those who opt not to undergo screening, particularly when it results in affected children [2,51,53]. This was also stated in theoretical papers [14,20,27,36]. In a study among Swedish stakeholders, it was stated that if partaking in screening may be considered a couple's reproductive responsibility, blame and guilt may become associated with declining the offer, especially when a child is affected [51]. These Swedish stakeholders [51], as well as an author [32], additionally mentioned that To present an empirical bioethics analysis of the PECS practice from the perspective of GPs.

Expanded
Two themes were identified in the analysis: (1)'Choice and its complexity' , which suggests that medical, moral, social and psychological aspects co-shape the complexity of choice regarding EUCS and (2) EUCS as prompting existential concerns' , indicating that it is not possible to analyse existential issues raised by EUCS solely on the level of the couple or family but that a societal level must be included, since these levels affect each other (referred to as 'entangled existential genetics').
Bonneau [58] 2022 France Quantitative survey article among members of the general population (N = 1568) To collect French general population opinion on the implementation of preconception genetic testing and explore the factors associated with a difference of opinion.

Expanded
In this study, 91% of participants was favorable to ECS and 57% declare to be willing to participate in screening. A medical prescription by a general practitioner or a gynecologist was considered best to offer screening for 73%, with a reimbursement from insurance. However, 19% declared not to be willing to participate because of ethic or moral convictions, and the fear that the outcome would question becoming pregnant. Otherwise, most participants considered the test medical progress despite the risk of an increased medicalization of the pregnancy.   for carriers or those opting out of screening, it may become challenging to find a partner. Furthermore, stakeholders [2,51] and authors [20] mentioned that stigmatization of affected people may lead to increased societal pressure to partake in screening.

Expectations regarding discrimination
In addition, stakeholders mentioned that an EUCS offer could lead to discrimination against carrier couples or may affect wellbeing of people living with the conditions screened for [2,3,47,52,53]. Some theoretical and expert articles [3,5,14,20,21,47] suggested that a universal offer might lower the incidence of affected births, which, in turn, could lower the incentive to develop treatments, thus disadvantaging people living with the conditions screened for. It was also expected that the societal willingness to support families with affected children could decrease as a result [2,47].
Other HCPs were worried about increases in insurance rates as well [30]. These concerns were also expressed in a theoretical article [27]. About half of French participants from the general population expressed fear of being discriminated if they were identified as a carrier [58].
Experiences with stigmatization and discrimination in carrier screening offers None of the articles reported empirical evidence regarding stigmatization and discrimination as a consequence of EUCS offers (Table 3). Multiple studies on high-risk carrier screening offers however reported on participants' experiences with aspects of stigmatization and discrimination. In the 1970s, ancestry-based sickle cell disease screening in the United States led to increased stigmatization and discrimination of carriers in access to employment and education and in the ability to obtain life insurance [5,21,32]. Stigmatization of carriers was additionally reported as a consequence of the Jewish orthodox premarital screening offer [6,55] and as a result of the semi-mandated screening offer for beta-thalassemia on Cyprus [7]. A positive carrier status resulted in restricted opportunities to marry, especially for families with affected family members [6,7,55]. In contrast, in studies reporting on ancestry-based preconception screening in the Netherlands, couples did not experience stigmatization or discrimination [42,43]. No program-related stigmatization was found in another study evaluating a preconception screening offer in Israel [57]. Participants from Israel in a study of Raz et al. [6] felt that acceptance of people with disabilities in their community increased.
Equitable access in a high-risk only versus a universal offer Multiple articles mentioned that, as it becomes increasingly difficult to assign single ethnicities to people in today's increasingly multi-cultural societies, targeted screening offers are insufficient. They argued that it is reasonable to offer ECS universally, regardless of race or ethnicity, to promote equitable access to screening [5,28,45]. In this context, HCPs mentioned that an advantage of EUCS is that it promotes equitable access as it is offered to all couples with a desire to have children [2,54]. A participant in the stakeholder interview study of Van der Hout et al. [2]. even argued that it would be unethical to deprive couples of such an offer. This was indicated by Dutch studies reporting on the perspectives of at-risk communities as well [38,42,43] and members of the general population [44], indicating a preference for carrier screening to be available to everyone. On the other hand, experts suggested that awareness amongst at-risk groups, who benefit most from ECS, may be undermined by a universal offer [5]. Therefore, Dutch stakeholders believed that EUCS should not completely replace high-risk offers [2]. We found no articles presenting data on experiences regarding this subtheme in actual carrier screening offers.
Challenges in reaching the target population Furthermore, articles suggested that reaching the target population preconceptionally might be difficult. Some articles discussed for example that, as not every pregnancy will be planned or couples do not visit HCPs before pregnancy, these individuals or couples will not receive the screening offer if limited to the preconception phase [20,34,36,37]. Cornel et al. [47]. additionally mentioned that preconception care is not systematically offered, also limiting the feasibility of offering EUCS in the preconception phase. In addition, several articles, including stakeholder consultations and theoretical papers, raised a concern about whether informed (autonomous) decision-making could actually be reached. They mentioned that successfully transferring the information on ECS to everyone may be complicated, specifically in couples with lower health literacy or educational level [5,27,29,31,32,34,36,39,52]. Some stakeholders specifically raised concerns about the knowledge and awareness in the general population, but also amongst HCPs, about genetics, screening, and reproductive options, possibly complicating informed decision-making [39]. These concerns were expressed in the theoretical article by Wilfond et al. [32] as well. Stakeholders additionally wondered whether reaching informed consent would become more complicated with larger panels of conditions [2,29]. Modra et al. [34] voiced the worry that it may specifically be complicated to reach informed decision-making in case of EUCS in a prenatal setting, because of the time pressure on making a decision. Finally, authors of a theoretical article mentioned that accessibility of EUCS in regional, rural and remote areas as well as access of culturally and linguistically diverse communities is also a point of concern [13]. None of the articles reported carrier screening participants' experiences on this subtheme.

Costs & funding of service
Other challenges in relation to equitable access had to do with costs and funding. First, several articles reported on potential societal implications of couples paying a fee for screening [5,13,27], including stakeholders. [38,46,[52][53][54] Some articles, both theoretical articles [13,32,36] and stakeholder articles [38,39,44,46], suggested that a reimbursed offer may minimize inequity and discrimination based on socioeconomic status, as compared to commercial offers, and that paying a fee for screening could potentially increase them. Relatives of patients with a severe recessive condition however mentioned that costs of screening were highly favorable compared to the costs of caring for a child affected [46]. Other stakeholders argued for partial financing, in which prospective parents would pay a certain amount for ECS themselves [39,51,54]. Some articles described funding strategies of current carrier screening programs. In the United Kingdom, carrier testing is offered free of charge as part of National Health Services [21]. In Israel, carrier testing is free of charge as well, and only a small fee is asked for additional testing for less frequent or severe conditions [21]. Only one article evaluated the costs of EUCS in an empirical study, with couples paying 650 euro for participating in screening, indicating that almost half of participants believed the costs of screening were too high [48]. Some of participants who were interviewed also believed that the costs could lead to inequality in access [48]. One article reported on funding and participation in an ancestry-based offer: Tay-Sachs disease screening in Australian high schools has been offered free of charge with a participation rate of 96% [21]. Second, multiple articles stated concerns whether healthcare resources will be fairly allocated in case of an EUCS offer. [10, 13, 25-27, 31, 36, 47, 49] Many stakeholders believed EUCS to be expensive and considered it not to be a priority in healthcare [33,39,51,53]. Other authors suggested that an offer of EUCS should not be competing with resources to provide treatment of people affected by the conditions screened [3]. Theoretical articles stated that EUCS would increase costs, as compared to a high-risk offer only [31,36], and HCPs in another article expressed concerns that EUCS implementation may negatively affect the budgets of other healthcare areas [53]. Compared to minimal or no screening, multiple articles expressed the expectation that EUCS would reduce the medical expenses for lifetime care of affected patients, which may lead to cost-effectiveness [25,26,51]. This was the case for beta-thalassemia screening in Cyprus [7]. It was also argued that in communities with a relatively high frequency of affected patients limiting (healthcare) budgets, societal impact of these diseases can be considered an argument pro EUCS [20,47]. Saving costs for society by preventing the birth of a severely affected child was also mentioned by potential users in a qualitative stakeholder analysis study [46]. However, it was additionally argued that assessing cost-effectiveness is irrelevant in case of EUCS, as increased autonomy rather than reducing birth frequency is the primary goal of the offer [13,27,36].

DISCUSSION
In this scoping review, we aimed to assess the potential societal implications of implementing EUCS described in literature. These implications were derived from publications focusing on the expected implications of offering EUCS and from relevant publications describing the theoretical as well as proven implications of non-expanded and/or ethnicity or ancestry-based carrier screening programs.
The articles identified in this review map potential positive societal implications of EUCS, including equitable access for all couples planning to conceive, normalization of carrier status (and thus reduced risk of stigmatization and discrimination) and that EUCS potentially caters to a latent need or desire of individuals or couples unaware of their reproductive risk. This review also indicates concerns about potential negative societal implications of EUCS, including routinization of reproductive screening that potentially affects freedom of choice; EUCS contributing to a society striving for the 'perfect child'; stigmatization and discrimination of couples who opt out of screening and of carriers and individuals affected by conditions screened; and challenges in promoting equitable access to screening. Importantly, we found little or no empirical evidence for both positive and negative potential implications, neither in literature on EUCS, nor in most publications on screening programs for atrisk populations (focusing on one or a few diseases). Empirical studies on EUCS are lacking, whilst insight into societal implications is important for implementation decisions. As outlined by Richardson et al. [15], defining outcome measures for studies evaluating EUCS programs is essential for proper evaluation of such programs as well for collecting empirical data. Such outcome measures should include these societal implications [15]. The few articles reporting evidence for the actual occurrence of societal implications in these settings primarily described experiences with stigmatization and discrimination. It has been stated that one way to minimize stigmatization and discrimination is to improve public knowledge by, e.g., public health campaigns, and to provide proper information and counseling [5]. In addition, as cultural and social stigmas play a role in shaping disease perception, it is important that EUCS programs are implemented in a culturalsensitive manner [64].
To implement EUCS in a socially responsible manner, it is important to consider the likelihood and impact of potential negative societal implications versus the desirability of positive societal consequences. Importantly, whether certain societal implications of EUCS will actually occur is probably dependent on the way(s) EUCS is implemented, which is dependent on the expressed aim(s) of such a program [20,45]. If EUCS is implemented with the aim of prevention only instead of reproductive autonomy, societal pressure to partake in EUCS or to choose reproductive options preventing the birth of an affected child might be higher, as might stigmatization and discrimination [13,20,45]. To limit the likelihood of negative societal implications occurring, it is important that reproductive autonomy, and thus the optional character of the offer, is clearly expressed when implementing EUCS, both with respect to partaking in screening as well as regarding reproductive options in case of carriership [5].
Despite reproductive autonomy being considered the primary aim of EUCS in most literature, articles in this review suggest that a routinized offer could reinforce the idea that it is logical or a right thing to do, with society possibly expecting couples to partake in screening or to make particular choices if they appear to be carriers. Furthermore, articles suggest that EUCS set-up may affect if, and to what extent, potential negative societal implications will occur. For example, while clinical or government-initiated offers may promote responsible implementation, including equitable access to screening, this review mapped concerns that such offers may also reinforce the notion that partaking in screening is the right thing to do, and therefore may contribute to societal pressure. Healthcare professionals offering counselling may even perpetuate this when this is not addressed in counselling. It is therefore important that healthcare professionals offering screening are aware of this and discuss the notions couples may have, so that they can adequately support informed decision-making and minimize the adverse impact of routinisation.
In addition, this review indicated the possibility that EUCS would be initiated top-down rather than bottom-up based on a need expressed by prospective parents, the latter being (sometimes) the case in high-risk communities. Literature included in this review raised concerns that couples of the general population may therefore feel opposed to screening or think it is not relevant to them. While interest and intention to partake in EUCS seem to be high when awareness is facilitated, actual uptake in the pilot studies conducted so far seems to be relatively low, as outlined in the systematic review of Steijvoort et al. [65]. Uptake is claimed to be higher when the offer is free of charge or when carrier screening is (also) offered prenatally, with the latter suggesting that awareness is still low preconceptionally, that the perceived personal relevance is higher during pregnancy and/or that relatively more pregnancies are unplanned [65,66]. Larsen et al. [67], however, reports a partly contrasting finding indicating that uptake is highest when (opportunistically) offered preconceptionally or in early pregnancy. A preconceptional offer combined with a prenatal option would also be most beneficial in terms of equitable access. To facilitate awareness and informed decision-making, proper public education about EUCS is of vital importance.
Dive and Newson [68] argue that public health values, such as equity, should be taken into account when implementing EUCS as well. Articles in the current review also voiced a concern regarding unequitable access to screening, indicating that out-of-pocket costs and inadequate information provision for those who are less (health) literate likely hamper accessibility to EUCS. An important barrier to partaking in screening perceived by members of the general population was also the limited genetic knowledge and awareness about the option of EUCS, and potentially a subsequent lack of perceived benefit among eligible couples [46]. Literature recommends no out-of-pocket costs and adequate information provision and support in decision-making (education and counseling) as ways to improve equitable access [69]. A potential relevant aspect of equitable access in EUCS lacking in the literature identified was access to reproductive options after screening, such as PGT.

LIMITATIONS
This scoping review has several limitations. First, although this review focused on the societal implications of an expanded universal offer, we also included relevant papers referring to the societal implications of high-risk carrier screening offers. We decided upon this approach as these high-risk offers may inform us about which societal implications could be expected in EUCS and we could learn from the empirical evidence from less expanded and non-universal programs. However, our search strategy focused solely on EUCS. Therefore, we probably missed some relevant articles on societal implications of small high-risk offers that would potentially further contribute to our insight into potential societal implications of EUCS, either positive or negative. Second, as this was a scoping review, we aimed to explore all types of data and insights available on societal implications of EUCS. We therefore decided not to limit our inclusion criteria to article types describing primary data. This may have complicated the interpretation of the (little) evidence of articles included in this review. However, we believe that this enabled us to provide an overview of all literature available on this subject. Finally, it was decided to perform a scoping instead of a systematic review, because this better suited our research question. Because of this, we did not perform a quality assessment of the literature reviewed.

CONCLUSIONS
This scoping review aimed to map the potential implications of implementing EUCS on societal level. Importantly, empirical evidence of the prevalence and impact of societal implications of universal offers for society is scarce. Available empirical data is derived from studies on at-risk populations and screening for just one or few disorders. Our findings indicate however several potential positive implications, including increased access for all and less stigmatization of ethnic groups, but also potential negative implications, such as unwanted medicalization of pregnancy, increased stigmatization of and discrimination against people affected with conditions in the test or couples opting out of screening and unequitable access in terms of information provision and costs. More pilot implementation studies assessing EUCS, including their consequences for society, are urgently needed to identify which societal implications occur and to what degree when implementing EUCS.