“I didn’t take it too seriously because I’d just never heard of it”: Experiential knowledge and genetic screening for thalassaemia in the UK

Abstract Members of the public face particular challenges when undergoing reproductive genetic screening. Lack of family history with genetic disease has been identified as a key barrier affecting screening uptake and responses to genetic risk. This study explores this obstacle using beta thalassaemia as a case study. Fifteen in‐depth qualitative interviews were conducted exploring the reproductive views and decisions of people at risk of transmitting thalassaemia. Eleven participants had thalassaemia themselves and/or were members of an affected family. Four participants were identified as thalassaemia carriers through genetic screening programmes with no family history. Notable differences were observed between these two groups. For thalassaemic individuals and families, past experience clarified and facilitated their sense of reproductive responsibility, however carriers struggled to relate to, and incorporate the information into their lives. It was witnessing their child becoming symptomatic—rather than receiving a diagnosis or genetic risk information per se that had the most substantial influence on carriers’ subsequent views and decisions. Educational resources used to support genetic screening programmes would benefit from an engagement with the experiential accounts of life with genetic disease in order to more effectively bridge the chasm in knowledge and understanding between affected families and the general public, towards whom expansive genetic screening is aimed.

the public posed by such genetic disorders becomes more substantial (Archibald et al., 2018). Indeed, recent research suggests that when combined, the prevalence of the three most common genetic disorders (Cystic Fibrosis, Fragile X syndrome and Spinal Muscular Atrophy [SMA]) is comparable to that of Down's Syndrome (Archibald et al., 2018)-a condition routinely screened for within standard NHS antenatal care. This prevalence, when considered alongside the unpredictable and variable prognoses associated with many of these genetic disorders and their relatively 20 limited treatment options all contribute to the mounting case in favour of offering carrier screening programmes to the general public (Gregg et al., 2014;Nazareth, Lazarin, & Goldberg, 2015;Plantinga et al., 2016).
Although identifying carriers of genetic conditions in the general population in either the pre-conceptual or prenatal period confers particular opportunities for the carrier couples it identifies-primarily through the extension of their (currently limited) reproductive options (HGC, 2011)-this approach also brings with it practical, ethical and social dilemmas that may surface in genetic counselling contexts.
One persistent challenge identified in the literature relates to the receptivity of the general population to the notion of their potential carrier status (Archibald et al., 2009;Beard, Amor, Pietro, & Archibald, 2016;Ioannou, Delatycki, Massie, Hodgson, & Lewis, 2015;McClaren, Delatycki, Collins, Metcalfe, & Aitken, 2008). As NHS carrier testing has typically only been reserved for families already known to be affected by genetic disease, those undergoing carrier testing have usually approached the decision in the context of their prior knowledge of the condition-a factor known to have a significant influence on reproductive decisions and attitudes (Baillergeau & Duyvendak, 2016;Etcehgary et al., 2008;Kay & Kingston, 2002;Raspberry & Skinner, 2010;Ziebland & Herxheimer, 2008). Indeed, research data have revealed key differences in the reproductive attitudes and decisions between those who have (and those who lack) prior experience of the condition being tested for (Boardman, Young, Warren, & Griffiths, 2017;Etchegary et al., 2008). Those with direct experience have been found to typically view the condition in a more favourable light than those who lack this form of insight (Boardman, Young, Warren, et al., 2017;Watson, Williamson, & Chapple, 1991), although this has been shown to vary according to the nature and impact of the condition (Kay & Kingston, 2002). Through familiarity with the challenges and opportunities associated with a particular condition, experiential knowledge may instil confidence in a person's perceived ability to cope with a child with that same condition (Boardman, 2014). By acting as a "window" into potential futures, this intimate way of knowing and experiencing genetic disease allows for the realistic envisioning, and appraisal, of different reproductive outcomes (Boardman, 2014;Etchegary et al., 2008;Markens, Browner, & Preloran, 2010) in a way that may be more challenging to those for whom genetic disease is a more removed and abstract concept (Archibald et al., 2009).
When experiential knowledge of genetic disease becomes dislocated from the reproductive decisions that concern it, however, through the practice of genetic screening, there are significant implications not only for reproductive attitudes, but also uptake of carrier screening in various contexts (Archibald et al., 2009(Archibald et al., , 2018Ioannou et al., 2014;McClaren et al., 2008). Plantinga et al.'s (2016) study of public attitudes towards the offer of a carrier screen for 50 genetic disorders, for example, demonstrated that the most common reason for lack of interest in undergoing the screen was "not wanting to be bothered" by the knowledge that one could be a carrier for genetic disease (Plantinga et al., 2016p. 5). Similarly, Prior et al.'s (2010) study of carrier screening for SMA highlighted the most common reason for screening refusal among the 500 pregnant or pre-conceptual women offered an SMA screen was reported as a lack of concern about SMA. Lack of family history, already being a parent to healthy children, not being of advanced maternal age and viewing oneself as fit and healthy have all been identified as informing perceptions of the chances of being a genetic carrier (and consequently screening uptake) in spite of the irrelevance of these factors to actual genetic risk status (Beard et al., 2016;McClaren et al., 2008). Even for the most prevalent genetic diseases, public awareness and understanding of the nature of genetic inheritance remain demonstratively poor (Anido, Carlson, Taft, & Sherman, 2005;Braido et al., 2015;Fanos, Spangner, & Musci, 2006;Moultrie, Kish-Doto, Peay, & Lewis, 2016;Watson et al., 1991) with interest in carrier screening correspondingly low. The only exception to this trend is instances where the test is offered or recommended directly by a health care professional (Rothwell, Anderson, Swoboda, Stark, & Botkin, 2013).
The perception that genetic disease is only relevant to the subset of the population already living with them is further reflected in the reactions of shock and unpreparedness experienced by carrier couples in the wake of positive screening test results (Anido et al., 2005;Beard et al., 2016;Ioannou et al., 2015). Unlike families already living with genetic disease, screening-identified carrier couples need to quickly absorb large quantities of complex information about the condition they carry and/or make difficult decisions about pregnancy (dis)continuation, often within a compressed timeframe, presenting significant challenges to genetic counsellors (Ioannou et al., 2015).
Within the UK, the carrier screening programme for thalassaemia is currently the only prenatal genetic screening programme offered within standard NHS care. All pregnant women are screened for thalassaemia carrier status, usually before they reach 10 weeks gestation, and if found to be a carrier, are invited to have the father of the foetus tested and/or diagnostic testing of foetus, depending on the results.
Thalassaemia refers to a group of inherited recessive blood disorders that affect the production of haemoglobin within the body, affecting approximately 70,000 newborns annually and making them among the most common single trait recessive disorders worldwide (Cousens, Gaff, Metcalfe, & Delatycki, 2010).
Approaches to thalassaemia screening vary drastically in the international arena, with mandatory pre-marital screening programmes underway in countries with particularly high prevalence (e.g., Iran, Saudi Arabia, Palestinian Territories and Cyprus) (Cousens et al., 2010). Thalassaemia carriers (also known as people with thalassaemia "trait" or thalassaemia "minor") typically do not have any serious associated health problems (although may be mildly anaemic), but have the potential to pass thalassaemia on to any future children, if conceived with another thalassaemia carrier. When two thalassaemia carriers reproduce, each child born to them has a one in four chance of having thalassaemia.
The primary treatment for beta thalassaemia is regular (every 4-6 weeks) blood transfusions to treat and prevent anaemia, usually in conjunction with chelation therapy to treat any associated iron build up. The current average life expectancy (with treatment) of a person diagnosed with thalassaemia today is between 40 and 50 years old, but this is expected to increase significantly overtime as treatments improve (Telfer, 2009).
Whilst only one carrier screening programme is currently implemented at population level in the UK, shifts in the capacities of genomic technologies suggest that this model of screening provision is likely to expand in the future. Increasing numbers of would-be parents will be called upon to make decisions about the conditions they would want to know their carrier status for, and which they would not, often without any experience or knowledge of the conditions around which they are making such decisions (Plantinga et al., 2016).
It is on account of this unfamiliarity with the world of genetics that proponents of pre-conception genetic screening have highlighted the need for high quality information and support to provide the infrastructure for any screening programmes implemented (Prior et al., 2010), as well as a need to better understand the role and value of prior experience with genetic disease within reproductive decisions (Boardman, Young, Warren, et al., 2017).
In order to address this under-explored topic, this paper offers an analytic comparison of the views, experiences and reproductive decisions of 15 people at risk of transmitting thalassaemia with contrasting levels of prior experience and knowledge of the condition. Eleven participants approached their decision in the context of a family history with thalassaemia (i.e., either they had thalassaemia themselves or a member of their family did), and four participants made their reproductive decisions having been identified as a thalassaemia carrier through antenatal or newborn genetic screening, but without any prior history of, or experience with, the disease. The contrast between these two positions is illuminated in order to offer critical insight into the role that these disparities of knowledge and experience have on reproductive views and decisions, before considering their policy and practice implications.

| ME THODS
This study involved in-depth qualitative interviews with 15 participants who either had prior experience of thalassaemia, or encountered it through antenatal genetic screening.

| RECRU ITMENT
Participants were recruited into the study through the largest support group for thalassaemia in the UK, the UK Thalassaemia Society (UKTS). The UKTS offers support to people across the UK who are either carriers of thalassaemia, have thalassaemia themselves or have a diagnosis of thalassaemia in the family. Three separate calls were placed in the society's e-mail delivered publication between June and December 2017, requesting that potential participants get in touch with the project researcher.

| INTERVIE WS
Upon initial contact with the study team, participants were provided with an information leaflet outlining the aims of the research and what their participation might involve. They were then asked to contact the researchers to arrange an interview if they remained interested in being involved. After this point, participants were asked to sign a consent form, and interviews were carried out either faceto-face or over the telephone, depending on participant availability, health needs and preference. The majority of face-to-face interviews were carried out in participants' homes although one was conducted in the participant's workplace and another in a public space within a hotel ( Table 1).
The interview schedule was developed by reference to the relevant literature, as well as the lead researcher's previous work in this area (Boardman, 2014;Boardman, Young, Warren, et al., 2017

| DATA ANALYS IS
A modified grounded theory approach was undertaken to analyse the resulting data. Initially, one researcher conducted "open coding" (Gibbs, 2007) which was largely descriptive, before more discriminatory hierarchical coding was undertaken using qualitative data analysis software, Nvivo 11. Both researchers were involved in hierarchical coding through a process of coding and refinement of concepts (through data interpretation, reference to the literature and regular analysis meetings between the researchers). Discrepancies in coding were discussed between the researchers and following agreement, re-coding was carried out until "theoretical saturation" (i.e., no new concepts were emerging) had occurred.

| PRE S ENTATI ON OF RE SULTS
Although 15 participants were interviewed and an analysis of all of their accounts contributed to the thematic framework, four participants have been selected for detailed presentation within this paper.
These four accounts were selected on the basis of their particularly eloquent representation of the views and experiences of other participants within the two groups (those who had prior experience with thalassaemia or those who encountered it though antenatal/ newborn genetic screening) Moreover, as the concept of experiential knowledge is so critical to this analysis, a focus on the narratives of four participants allows for a more detailed and nuanced exploration of participants' stories and their relationship to their reproductive decisions and attitudes, which would not have been possible in detail for all 15 participants. To protect the identities of the four participants, all names appearing within this paper are pseudonyms.

| RE SULTS
The calls for participants resulted in contact from 21 people which in turn led to the successful completion of 15 interviews. Six people who initially made contact with the research team were not interviewed as attempts to arrange an interview were unsuccessful. After two attempts to arrange an interview with each person, further contact was abandoned. One participant contacted the team for interview after the completion of the analysis and was accepted for interview. Their transcript was analysed using the thematic framework developed from the previous interviews.
The 15 participants who went through for interview either had thalassaemia themselves, or had at least one person diagnosed with thalassaemia in their family (see Table 2). All of the four participants who were identified as thalassaemia carriers through genetic screening went on to have at least one child with thalassaemia.
Participants ranged in age from 25 to 68, nine were parents and seven of these were parents to a child/children with thalassaemia, with one participant having multiple affected children (Jahida) (see Table 2). Only two of the nine parents had thalassaemia themselves (Bilal and Imran), both were male, and neither had gone on to have affected children themselves ( Table 2). The vast majority of participants were female (10), and all were of South-Asian, South-East Asian or Mediterranean heritage, reflecting the typical ethnic prevalence of thalassaemia (Hickman et al., 1999). All participants described themselves as belonging to a religious community (see Table 2), however, four participants described this as reflecting their social identity rather than their personal beliefs. The participants were geographically dispersed throughout England.
The results have been divided into two sections depending on participants' prior experiences with thalassaemia. First, the accounts of participants who considered their reproductive views through the lens of an established family or personal history with thalassaemia will be presented (n = 11), before contrasting these with the accounts of those who discovered the condition in their family through genetic screening (n = 4).

| 'I know exactly how hard it can become…': Experiential knowledge and reproduction in thalassaemic families
For the majority of participants within the sample (11), thalassaemia was a condition for which they had considerable experience to draw on as they considered their own reproductive views and decisions. Eight of these participants had thalassaemia themselves (with two, Giovanni and Imran, also having an affected sibling), and two were parents of an affected child who had not been identified prenatally (Jamini and Chaaya). For these participants, considering their own reproductive attitudes and decisions (both past and anticipated) was inextricably linked to the everyday reality of life with thalassaemia.
Imran was a 45 year old man at the time of his interview, and had been diagnosed with thalassaemia shortly after birth. He was living and working part-time as a taxi driver in an English city, and had five children (all carriers of thalassaemia, but without the condition themselves) born through an arranged marriage that Imran described as having since broken down. Imran described thalassaemia as a sceptre that had overshadowed much of his life, contributing to him being "overlooked" and "written off" within his family. Shakespeare (2006), among others (Boardman, Young, Warren, et al., 2017;De Wolfe, 2002), have highlighted the contrast in outlook and attitude between disabled people who have fixed, static impairments (often present from birth) and those with acquired, fluctuating or degenerative impairments which typically involve periods of pain, suffering and illness (p. 106). He has argued that people who fall within the latter group are far more likely to experience their impairment as intrusive, burdensome and entirely separate from their sense of self and identity than those whose impairments are fixed and stable.
Although thalassaemia might be considered a fluctuating impairment according to Shakespeare's categorisations, involving frequent periods of illness and medical treatment, Mahila's account demonstrates the way in which, though her condition varied, her experience of stigmatisation, of being a "tainted" person (Goffman, 1963) (Boardman, 2017).
While on the one hand giving them privileged insight into the disorder, experiential knowledge also emerged from Mahila's account as a bounded form of insight, both limited, and contoured, by the unique set of circumstances through which it was generated.
Despite its inherent limitations, there was nevertheless evidence from all of the 11 participants who had direct experience of thalassaemia in their family that their experiences served as the yardstick by which future lives could be anticipated and appraised. For some of these participants, this insight both bolstered and authenticated their views and decisions (e.g., Imran), whether this be to prevent the recurrence of thalassaemia, or a belief that thalassaemia was an insufficient justification for the use of genetic technologies and pregnancy termination. However, for the remaining participants, experience of thalassaemia introduced new layers of ambiguity and uncertainty into their reproductive views, with some unclear how they would respond if faced with selective termination decisions.
In these instances, being a member of an already affected family could serve to heighten existing tensions that surround prenatal screening and testing practices (Kelly, 2009). More specifically, the negotiation of the fine balance between managing a sense of genetic responsibility for future family members' health and a desire not to express disvalue towards affected family members, a concern that has been identified in relation to various different genetic conditions within the literature (Kay & Kingston, 2002;Kelly, 2009;Raspberry & Skinner, 2010;Shakespeare, 2006).
Although participants' experiential knowledge emerged as an influence capable of both clarifying and muddying the waters of selective reproduction, the remaining four participants in the sample however, approached their reproductive decisions from an entirely different vantage point. For these participants, thalassaemia was first encountered not through the tangible and visible processes of symptoms and diagnosis, but rather through the far more abstract pathway of genetic screening.

| "With carriers, it's not a major thing is it? You just carry on normal…": Prenatal screening, experience and reproductive decision-making
Of the 15 participants in this study, four discovered the thalassaemia trait in their family through a genetic screening programme rather than through the illness and subsequent diagnosis of a family member. Three of these participants were informed of their carrier status following antenatal screening during their first pregnancy (Jahida, Arjun and Ameena), and one described discovering their child's thalassaemia following a heel prick test at birth (Fadwa). Of the three who discovered their carrier status through antenatal screening, two (Jahida and Arjun) had a first born child with thalassaemia. Although the identification of carriers in the antenatal period has been heralded as expanding reproductive autonomy and choice for would-be parents (Locock & Kai, 2008;Tsianakas, Atkin, Calnan, Dormandy, & Marteau, 2011), it can nevertheless be a frightening and bewildering experience for pregnant women and their partners (Beard et al., 2016;Ioannou et al., 2015;Locock & Kai, 2008). As many women are not aware that carrier screening for thalassaemia is taking place, or regard the screen as a compulsory component of high quality prenatal care (Cousens et al., 2010), the discovery of carrier couple status for a genetic condition completely unknown to them has been described as akin to entering a "new world" (McClaren et al., 2008) of genetic disease.
It was in the context of these liminal spaces that emerged through the discovery of carrier status that participants' experiences and knowledge of health and illness gained significance in the formulation of their responses to their genetic risk (Archibald et al., 2009;McClaren et al., 2008). As an autosomal recessive disorder, each "at risk" pregnancy conceived by a carrier couple has a one in four (25%) chance of being affected by thalassaemia. In the face of this uncertainty, participants looked to their family histories and those of their friends and wider communities ("I'd never seen anyone with thalassaemia before"), together with own encounters with health before. I only found out when I was first pregnant with my eldest one, I had a blood test and they told me at that point. That was the first time I actually heard of it, but to be honest I didn't really take much notice of it because I didn't think it was going to happen to me, I kind of thought, "oh, okay". And they said it's one out of four chances. And I was quite young myself and because I'd never heard of it, I didn't research into it and it turned out to be, you know, that actually she was born with it…[…]…They did call us in to do a bit of counselling and went through this condition, but to be honest I still didn't take it seriously at all because I'd just never heard of it and I thought, one in four chance, I thought, well three chances it won't happen, so I was quite positive, but you never know.
Although Jahida's daughter, Aaleyah, was diagnosed with thalassaemia at birth, her symptoms remained relatively mild and she did not require blood transfusions until she was 4 years old.
It was during this time of symptom stability and good health that Jahida and Parvez had their second child (Miras), opting not to use prenatal diagnosis: I thought, "no, well Aaleyah was fine" and we were giving her a healthy diet and she was still managing, so we kind of went into that belief that she would be okay and it won't happen to us twice and she will probably just be severely anaemic and we just need to give her a little extra support but she won't need transfusions. Due to Aaleyah's relatively good health, Jahida's perception of thalassaemia was initially largely benign, a viewpoint she reported as being upheld by her husband and wider family. Indeed, despite a confirmed diagnosis of thalassaemia, the continuation of Jahida's conviction that "it won't happen to us" is striking. It was only after the initiation of blood transfusions for both of her children, Aaleyah and Miras, that Jahida's view of thalassaemia, and consequently her perception of the genetic risk to future family members, began to change. Jahida approached her third pregnancy with a profound sense of "genetic responsibility" (Kenen, 1994;Raspberry & Skinner, 2010)  Authors such as Lippman (1999) and Katz Rothman (1986) have highlighted the burden of responsibility that the emergence of genetic technologies confers on pregnant women. The availability of such technologies, delivered under the rubric of standard antenatal care, expands ideals of responsible motherhood by subsuming within them responsibility for the (genomic) health of future generations.
As Reed has noted, the boundaries of this "genetic responsibility" are contoured through the lens of racial and gendered politics, reflecting a congruence of inequitable relations beyond the domain of reproduction (Reed, 2011). For mothers of children with genetic disorders, such as Jahida, however, this sense of genetic responsibility took on very particular meaning and significance. As Kelly (2009) discovered, mothers of children with genetic disorders often consciously side-step subsequent reprogenetic decision-making so as not to be put in the fraught position of needing to choose between continuing with an affected pregnancy or aborting a foetus with the same condition as their existing child. For Jahida, declining the CVS test was ultimately not a rejection of her sense of reproductive genetic responsibility, but rather an alternative expression of it, whereby providing her child with the opportunity to live was prioritised over her felt responsibility to prevent thalassaemia.
For both Jahida and Ameena, therefore, as well as the other two participants in the sample who discovered their thalassaemia status through a screening result, experiential knowledge of thalassaemia was pivotal to the interpretation and processing of their genetic risk information. Without grounding in their everyday realities, their carrier screening results lacked meaning and context and were consequently disregarded, a situation which Ameena regarded as common: to the intrinsic limitations of genetic risk information in the absence of an experiential "anchor" with which to ground the information in a person's everyday life.

| D ISCUSS I ON
As genetic technologies continue to advance in their sophistication and capabilities, there are calls to expand genetic carrier screening panels for increasing numbers of genetic conditions. It has been argued that such a move will accord prospective parents-especially carrier parents-more autonomy and control over their reproductive outcomes than has previously ever been possible (Henneman et al. (ESHG)., 2016). Such shifts, however, also entail the reconfiguration of ideals of responsible parenthood and justice as reproductive outcomes which previously fell under the auspices of chance or luck come to be considered controllable and amenable to human manipulation (Denier, 2014).
Acknowledgement of the high (combined) prevalence of genetic disorders, the decreasing cost and increasing ease of genetic screening, together with the dearth of effective treatments for even the most common genetic disorders have all served to heighten these calls for their prevention through screening programmes. However, within the UK, thalassaemia remains the only genetic condition for which a prenatal carrier screening programme exists. This study, to the best of our knowledge, presents the first analytic comparison between the perspectives of those who discovered their family's thalassaemia trait through a screening programme, and those whose reproductive views emerged from their everyday stocks of knowledge acquired through being part of an affected family. A consideration of the differences, but also the similarities between the perspectives of these two groups is critical as it highlights some of the implications when reproductive decision-making is transferred from already affected families to members of the public through the use of genetic screening programmes.
For those participants whose reproductive views and decisions emerged from a rich familial or personal history with thalassaemia, experiential knowledge was critical to the way in which they formulated their perceptions of their genetic risk, envisaged future generations affected by thalassaemia and ascertained where their reproductive responsibilities lay. While for some participants (e.g., Imran) this sense of responsibility was first and foremost to prevent the transmission of thalassaemia to the next generation others presented more ambivalent views, conflicted by the inherent contradictions between their over-arching sense of responsibility to future generations (to prevent genetic disease) and their daily experience of thalassaemia, which for many was described as "not so bad" (Mahila).
First-hand experience was constructed by all of these participants, therefore, as a privileged form of insight held by thalassaemic families (Mahila) that both improved the quality and authenticity of reproductive decision-making, even as it could complicate the decisions made. Indeed, this was the case even in instances whereby its fallibility as a knowledge resource was acknowledged, or its usage led to ambiguity or conflicted understanding of parental responsibility.
For participants who discovered they were carriers of thalassaemia through prenatal or newborn genetic screening, however, perceptions of genetic risk and responsibility were constructed in entirely different ways. All four participants who discovered their carrier status in this way reported that their antenatal (or newborn) screening result was their first encounter with thalassaemia, having never heard of it before, nor met anyone with it. In the absence of this direct experience, this sub-set of participants turned to a range of different resources to make sense of, and estimate the seriousness of, their genetic risk. Experiences with personal and familial health, of community and faith practices, the stories and views of family and friends together with internet resources and medical information were all drawn upon by this group to aid the interpretation and appraisal of their genetic risk. Ultimately, three out of four of these participants decided to proceed with their first pregnancies without further testing, a process that resulted in the births of two children with thalassaemia and one child with thalassaemia trait. As Etchegary et al. (2008) have observed, in the absence of "vivid" forms of knowledge about a condition (i.e., direct experience of the condition), people facing antenatal screening typically turn to more "vague" forms of experiential knowledge (such as the stories of unknown others) to make sense of their genetic risk. However, as demonstrated by the participants in this study, vague and vivid forms of knowledge were not equally valued, nor comparable in terms of their impact on reproductive views and decisions. Rather, these forms of knowledge were hierarchically ordered, with lived experience "trumping" all other forms of knowing. Indeed, for all four participants in this group, it was the onset of serious thalassaemia symptoms in their child (rather than the thalassaemia diagnosis itself, or the concomitant provision of medical information) that had the most profound effect in the reordering of previously held beliefs and expectations of the condition.
Experiential knowledge emerged as having the most significant, and enduring, impact on genetic risk perceptions, re-calibrating participants' sense of reproductive accountability, even as this accountability could lead to entirely polarised reproductive decisions and outcomes in practice (e.g., Jahida vs. Arjun).

| CON CLUS IONS
Although uptake of thalassaemia carrier screening within the UK population is high, indeed it has been suggested that many pregnant women are not even aware it is even being carried out or consider it a mandatory part of prenatal care (Cousens et al., 2010), the reac- screening refusal more broadly (Ioannou et al., 2014). It is noteworthy that for both women, the lack of resonance that their screening results had even persisted following the diagnosis of thalassaemia in their child. Indeed, it was only following the onset of symptoms (that were serious enough to require treatment) that significant shifts occurred in the perceptions of thalassaemia, and correspondingly, in participants' estimations of their genetic risk and responsibility.
This finding underscores the centrality of direct experience to the interpretation of, and reaction to, abstract ideas such as genetic risk.
Experiential knowledge brought thalassaemia out of the realm of the hypothetical and abstract and into the everyday lives of these participants in a way that genetic risk statistics and diagnoses could not.
Research into the reactions of members of the general population to carrier screening have highlighted the difficulties in absorbing and relating to medical information about a condition that one has not directly encountered (Archibald et al., 2009;Beard et al., 2016). As such, bringing genetic disease "into the worlds" of the general public who largely view it as the domain of small groups of affected families has been identified as a key challenge in the successful implementation of carrier screening programmes (McClaren et al., 2008).

| PR AC TICE IMPLIC ATIONS
This study highlights the particular difficulties facing people who discover their carrier status through genetic screening as opposed to through the symptoms and diagnosis of a family member. As has been described elsewhere in the literature, the participants who fell into this group faced unique challenges when assessing the relevance and significance of their results in the context of the rest of their lives (Archibald et al., 2009;Beard et al., 2016;Ioannou et al., 2012;Wright et al., 2015). This was particularly the case for participants who already had healthy children and who had never before heard of thalassaemia, but also those whose experience of the condition was limited to a very mildly affected or pre-symptomatic child (e.g., Jahida).
The experiential knowledge of affected individuals and families is a significant, yet under-utilised, resource that may be harnessed in the context of genetic counselling in order to address some of these difficulties. It has been suggested that insights from affected families could be imparted to genetic counselling patients through a variety of means; for example, through personal stories, photographs, vignettes, videos and interviews, all of which may assist in humanising and "bringing to life" a genetic condition in a way that the impartation of purely clinical information often fails to do (Ahmed, Bryant, & Hewison, 2007 and support within the groups for genetic disorders, such as thalassaemia, may be explained by the relative rarity of these conditions individually, the (already strained) resources of such groups and also by the somewhat ambiguous character of carrier status. Carrier status has been described by Timmermans and Buchbinder (2010) as analogous to a liminal state, a halfway house between health and disease, the significance of which can be difficult to interpret. Carrier couples may struggle to reconcile this ambiguity in their identities which, in turn, may render them alienated from such groups, the ethos of which may also clash with their own reactions to their genetic status.

| RE S E ARCH RECOMMENDATIONS
Further research is indicated to explore understandings of, and reactions to, genetic risk among the general population, particularly in relation to different types of genetic screening programme (pre-conceptual, prenatal, newborn) and for contrasting conditions.
Anticipating (and responding appropriately to) the information and support needs of the screened population has been described as paramount to the successful implementation of screening programmes.
This is especially the case, as has been demonstrated by this study and others (e.g., Evers-Kiebooms, Denayer, & Berghe, 1990; Hershberger et al., 2012), where information needs fluctuate across the couple's decision-making trajectory and use of genetic technologies is inconsistent across pregnancies (e.g., Jahida). Unlike screening for non-heritable disorders like Down's Syndrome where a positive result is typically a "one off" event (and therefore contact with the support group may be fleeting), genetic risk for conditions like thalassaemia recurs (assuming the same reproductive partner for each pregnancy), suggesting a need for ongoing forms of information and support that are tailored to its unique, and expanding, challenges.
Additional research could also explore the format and content

| S TUDY LIMITATI ON S
Recruiting participants through the UKTS may have introduced bias to the sample as its members have typically received a diagnosis of thalassaemia in the family. Indeed, all four participants who discovered their thalassaemia carrier status through prenatal screening went on to have affected children. The perspectives of those who received a negative prenatal test result, or who terminated their pregnancy following a positive result, therefore, are missing.
Although such individuals may be recruited through antenatal clinics, there are ethical concerns with undertaking interviews in the (typically highly strained and short) time between receiving a positive screening result and undergoing a prenatal diagnosis/selective pregnancy termination. However, as the focus of this analysis was not on the outcomes of the reproductive views and decisions per se, but rather on the processes and resources with which participants arrived at them, it was felt that the exclusion of these participants did not detract significantly from the utility of its findings.

INFORMED CONS ENT
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

AUTHOR S HIP CONTRIBUTIONS
Dr Felicity Boardman designed the study, was responsible for the study set up and oversight of the data collection and led on both the data analysis, table creation and paper writing. She also provided final approval for manuscript submission. Dr Rachel Hale conducted all of the interviews, contributed to the interpretation and analysis of the data, and provided critical input to the writing of the paper. She also provided approval for manuscript submission.

ACK N OWLED G EM ENTS
The authors would like to acknowledge with gratitude the participants who offered their time and stories for this project, as well as Elaine Miller and the UKTS who assisted with recruitment. This study was funded by a Wellcome Trust Society and Ethics Investigator Award (203384/Z/16/Z). The authors confirm that this work was not completed as part of a degree requirement and is not eligible for the student paper award.