Parental request for familial carrier testing in early childhood: The genetic counseling perspective

Professional guidelines generally caution against carrier testing in minors, though prior research indicates parents request and providers sometimes facilitate testing for unaffected siblings of a child affected by a genetic disorder. We investigated the perspectives of genetic counselors in North America regarding carrier testing prior to adolescence. Practicing genetic counselors (n = 177) responded to an electronic survey assessing their willingness to facilitate testing in four hypothetical scenarios and their evaluation of parental motivations. Participants did not find parental arguments for testing persuasive, and most were unwilling to facilitate carrier testing in children. A significant interaction effect indicated the presence of nonactionable carrier‐associated health risks in adulthood made participants significantly less hesitant when the mode of inheritance was X‐linked. Participants considered parental motivations that center the child's interests as significantly more persuasive. This study suggests genetic counselors are resistant to carrier testing for familial disorders in young children and tend to align with current guidelines, yet they recognize nuance in various cases. Further investigation into this topic is warranted to support genetic counselors facing these requests as the ethics of pediatric carrier testing continues to be debated.


| INTRODUCTION
3][4][5] Reviews of guidance outside North America have suggested consistency in the preference that carrier testing be deferred until the age of majority or at least until the minor can actively participate in decision-making and give proper informed consent. 6,7][10] The principle of nonmaleficence, or doing no harm, has also been invoked for advising against genetic testing in minors.The limited existing research has not, however, indicated a substantial impact of learning genetic risk information on a minor's well-being. 6,11,124][15][16] While the best interest standard places a strong emphasis on the individual, others have proposed a family-centered ethical framework, arguing that the best outcome for the family as a whole should be the focus. 17,180][21][22] These parents are largely focused on resolving uncertainty, not necessarily receiving a negative result. 23,247][28][29] Studies also report a parental desire for genetic knowledge that is equitable between siblings and complete for the family 24,30 and to facilitate life planning. 24,28,30udies show carrier testing in minors is being provided, 21,30,31 demonstrating a lack of strict adherence to policy statements by providers facing these requests. 30,321][32] Studies suggest providers may initially advise against carrier testing but may relent when parents' wishes for testing remain sustained. 21 light of increasing accessibility to genetic testing over the years, an updated understanding of genetic counseling practices is needed to better define the current standard in the field.Further, most studies surveying or interviewing genetics health professionals took place outside of North America, 21,31,32 limiting generalizability to genetic counselors working within a contrasting health care system.
Additionally, adolescent studies dominate the literature, and most others do not specify beyond "minor" or "child," terms that can encompass a wide range of ages, including adolescence.This precludes an understanding of how genetic counselors approach cases where the minor is a young child.The literature has further not examined how the presence or absence of health implications associated with carrier status affected the decision-making of genetic counselors nor has it segregated the distinct experiences of autosomal recessive (AR) carriers and X-linked (XL) carriers.
By presenting scenarios that capture more of this nuance, we sought to assess how genetic counselors approach the complexities of their cases differently in response to parental request for carrier testing of their young child.The major research questions were: All four scenarios in Section (a) in Supporting Information described a child whose sibling died from a severe childhood-onset genetic condition, prompting the parents to request carrier testing (the scenarios are available as Supporting Information accompanying the online article).The four different genetic conditions segregated the effects of two dichotomous variables: (1) XL versus AR inheritance and (2) presence versus absence of nonactionable carrier-associated health risks in adulthood.The selected conditions were infantile-onset Tay-Sachs disease (AR, no known health risks for carriers), Gaucher disease type 2 (AR, nonactionable health risks for carriers), X-linked severe combined immunodeficiency (XL, no known health risks for carriers), and X-linked adrenoleukodystrophy (XL, nonactionable health risks for carriers).Gaucher disease carrier status has been linked with a variably increased risk of Parkinson disease that could onset before the fifth decade, while carriers of XL adrenoleukodystrophy are at risk of symptoms related to progressive myelopathy and neuropathy, the frequency increasing steeply with age.The four conditions, and their associated nonactionable health risks for carriers (if applicable), were described in the scenarios, as not all participants would be expected to be sufficiently familiar with them to respond.
In addition to segregating the two dichotomous variables while introducing the fewest confounding variables, the four conditions were selected to have onset early in life.It had to be apparent without testing that an asymptomatic sibling is unaffected.Age six was selected to strike a balance between the child in the scenario being old enough that there would be no doubt they were unaffected but young enough that they could not conceivably provide informed assent.Additionally, there could not be any medical benefit to knowing carrier status for the selected conditions prior to adulthood.
Participants rated willingness to facilitate carrier testing for a 6-yearold child a four-point Likert-type scale (1 = Unwilling, 4 = Willing).Willingness was then measured for an assenting 15-year-old adolescent to allow for comparison to the body of literature predominated by middle adolescence.The order of presentation of the scenarios was randomized and counterbalanced to account for order effects.
Participants rated the persuasiveness of eight arguments put forth by parents with a five-point Likert-type scale (1 = Not persuasive, 5 = Very persuasive) in Section (b) in Supporting Information.1][32][33] The argument for pursuing carrier testing when offered at no additional cost by a laboratory was not specifically captured in the prior literature but was noted by the researchers to be an increasingly common occurrence.It may be considered a motivation stemming from convenience, which has been noted in the literature. 24 Section (c) (Supporting Information), participants shared how frequently they receive requests for carrier testing of young children in their practice.For those requests, they were asked to estimate how often they facilitate the testing and how often they refer cases for which they did not facilitate testing themselves to another site.Comparisons of sample demographics to the population were conducted with independent sample t-tests, chi-square tests, or Fisher's exact test.Two-way repeated measures analysis of variance (RM-ANOVA) and covariance (RM-ANCOVA) were used to assess whether inheritance pattern and/or carrier-associated health risks affect participants' willingness to facilitate carrier testing.Given the exploratory nature of this study, we used an exploratory model fitting process where potential covariates were added in blocks to the original independent variables (inheritance and carrier health risks).Variables with significant effects from each block were tested in a final model, which was interpreted.The same process was used to assess differences in persuasiveness ratings for parental arguments for testing and potential covariates.
All inferential tests used α = 0.05 because Type II errors at this early stage of exploration are just as problematic as Type I errors.An a priori power analysis determined 48 participants were needed to detect moderate effect sizes for within group variables at power = 0.80, α = 0.05, and no correlation between variables (the most conservative estimate).

| RESULTS
A total of 201 surveys were submitted (estimated response rate $4%).Twenty-three surveys were excluded for incompletion, and one was excluded for not meeting eligibility criteria, leaving 177 responses for data analyses.Sensitivity analysis showed 0.80 power to detect effect sizes of η 2 p = 0.02 (small effects).

| Participant demographics
Participants ranged in age from 24
A two-way RM-ANOVA assessed differences in willingness ratings as a function of inheritance pattern (AR, XL) and nonactionable carrier-associated health risks in adulthood (presence, absence).As shown in Figure 1, the ANOVA yielded a significant two-way interac-   (Continues)

| Persuasiveness of parental arguments for testing
Overall, as shown in Figure 2, participants did not find parental arguments for carrier testing persuasive, with means ranging from 1.6 to 2.5 on the 1-5 scale.The eight parental reasons for requesting carrier testing were rated very differently in terms of persuasiveness [F (7,170) = 19.12,p < 0.001, η 2 p = 0.44].Promoting adjustment and integration of carrier status into the child's self-concept and conveying information to the child before they are sexually active were rated significantly higher than the other reasons (all p < 0.001) and were most frequently selected as the most persuasive argument (Table 3).
Parents' belief they have a right/responsibility to know and parents' desire for a complete understanding of their family's genetic status  were rated significantly lower than the other reasons (p ranged from <0.001 to 0.02).Other study variables did not impact participants' evaluation of argument persuasiveness (p = 0.16-0.96;see Table S1 for full results).
Because racial/ethnic differences in willingness to facilitate was a significant covariate on its own, but not when controlling for the persuasiveness of resolving uncertainty and parental right to know arguments, we hypothesized racial/ethnic differences may exist in The parents want to be able to plan for the future 9 5.45 The parents want a complete understanding of their family's genetic status 6 3.64 The parents believe they have a right/responsibility to know 4 2.42 This study explored genetic counselors' positions and practices regarding carrier testing of young children in North America.Genetic counselors in this study were largely unwilling to facilitate such testing when approached by parents or guardians.Their caution is aligned with the consensus of national professional guidelines.Participants were most familiar with guidelines put out jointly by ACMG and AAP, 4,5 which explicitly discourage carrier testing in minors without a timely medical benefit.In the current study, over 73% of participants reported current guidelines were generally helpful, an increase from previous studies. 30idelines are not the only factor influencing providers' decisionmaking; context matters. 6,30,31A key finding of this study is the influence of aspects of a genetic condition on genetic counselors' willingness.The presence of nonactionable carrier-associated health risks in adulthood significantly increased willingness when the mode of inheritance was XL, but not when AR.
Over 15 years ago, it had been suggested the particular condition did not make an impact on decision-making because the frequency of testing facilitation did not differ greatly between indications. 30More recently, a qualitative study reported genetic health professionals seemed more likely to facilitate testing for AR conditions because they are "more straightforward" given reproductive risk is contingent on a partner also being a carrier and fewer have potential health implications associated with carrier status. 21Another study showed clinical geneticists in Europe were more willing, on average, to facilitate testing for an XL condition compared to AR, but they did not discuss the differing carrier-associated risks of the conditions surveyed. 31 is possible the interaction of these elements is borne out of scientific and/or societal underpinnings.In general, it is not surprising that positions would transform over time as the number of conditions for which genetic testing is available grows and as more is understood about the implications of carrier status.This discovery allows for a greater appreciation for nuance.Experiences of guilt, blame, and stigma based on mode of inheritance have been studied 34,35 and whether it is appropriate to call XL heterozygotes who experience related symptoms "carriers" is a recent topic of interest. 36The responses in this study may reflect an effort by genetic counselors, conscious or not, to legitimize the increasingly recognized experience and community of symptomatic XL heterozygotes.In illustration, support exists for XX individuals with XL conditions through advocacy organizations like "Remember the Girls."To our knowledge, a comparable resource is not widely available for the other types of carrier status presented in this study.Perhaps it is easier to imagine knowledge of XL carrier status with potential future health implications at a young age as empowering instead of solely burdensome when this social support exists.
Aligning with the qualitative themes identified in Vears et al, 24 which categorized parents' reasons for wanting to know their child's carrier status, two groups emerged in this study based on which party benefits.Overall, the parental arguments genetic counselors considered the most persuasive were patient-centered: informing the child of carrier status before they are sexually active and promoting adjustment and integration of carrier status into the child's self-concept.
Some existing research supports this benefit as learning carrier status appears to be beneficial for children and adolescents, giving them the opportunity to begin considering the meaning of the information in their lives. 37,38They may incorporate their carrier status into their genetic identity and compartmentalize it as only one domain of self with greater ease than adults. 37,39The least persuasive arguments were framed as parental interests: they want a complete understanding of their family's genetics, and they believe they have a right/ responsibility to know.
In interviews with genetic health professionals, most thought parental motivations were primarily self-centered rather than childcentered, and focused on receiving reassurance of a negative result rather than resolving uncertainty. 40In fact, resolving uncertainty is salient for minors and parents, 23,24,37,38 but in this study, it was not an especially compelling reason from the perspective of genetic counselors.This suggests parents may come to these conversations assigning moral weight to rationale quite differently than their genetic counselor.
Genetic counselors of color, however, may be more aligned with parents.Even in our predominately White non-Latino sample, preliminary evidence suggests genetic counselors who do not endorse that majority identity were more willing to facilitate carrier testing for children and were more persuaded by parents asserting a right/responsibility to know.Cultural values including those influenced by collectivist backgrounds and strong hierarchical family structures may explain these differences.While the reported racial difference should not be overstated, it indicates further diversification of the field may lead to more nuanced perspectives on how to manage requests for carrier testing for minor children.

| Study limitations
A major limitation to this study is the small sample size (177) and low response rate (4%); however, the sample is generally representative of the genetic counseling field as demographic distributions are not significantly different from the 2021 PSS in problematic ways and our analyses had sufficient power.To enrich the sample for pediatric genetic counselors, members of the research team directly contacted pediatric genetic counselors, potentially introducing bias.Data analysis did not, however, reveal any effects related to specialty area.
The four conditions presented in the scenarios were carefully selected to introduce as few confounding variables as possible.All conditions could be fatal in young childhood, and it would be clear without testing that an asymptomatic child at age six is unaffected.
No two genetic conditions are the same, and there are differences between the selected familial conditions that could not be controlled for in the current study.
Further, the study design does not fully capture the nuanced views of participants who would discourage testing initially but would ultimately be willing if the family's wish for testing persists.Similarly, the study does not tease apart whether the participant has denied testing to families or if the families are amenable to deferring testing after discussion.An approximate estimation of facilitation was solicited regardless of how frequently the participant received requests in their clinical practice, so an average facilitation rate cannot represent the standard by case.

| Practice implications
It is not uncommon for genetic counselors to encounter these decisions in clinical practice.Although most seem to follow guidelines that specifically recommend testing be deferred, some genetic counselors are facilitating carrier testing for young children.
This study solely investigated genetic counselors' stances on the matter; in reality, they may not be considering these issues independently.Genetic counselors and medical geneticists often work in tandem to offer and facilitate testing in the clinical setting.The working dynamic between healthcare professionals may greatly influence or even dictate how these cases are handled.Further, institutional policies may inform genetic counselor decision-making in these matters.
Dissonance could also occur between genetic counselors and parents, who may not prioritize rationales for testing in the same way.To bridge this gap, genetic counselors must not rely on their assumptions but instead draw out parents' underlying motivations for testing.Additional studies could explore whether cultural differences or personal values impact willingness to facilitate testing or evaluation of parental arguments.The current study could be expanded upon by comparing the impact of different carrier risks on genetic counselors' willingness.For example, this could include actionable health risks in adulthood like those of hereditary cancer syndromes and the reproductive risk for miscarriage and stillbirth associated with balanced translocation carriers.Genetic testing laboratories could also be surveyed to better understand their current process for managing requests for carrier testing in minors.

| CONCLUSION
This study has provided valuable insights into genetic counselors' approach to requests for carrier testing of young children.In general, (1) How willing are genetic counselors to provide carrier testing for a child based on family history?(2) How do genetic counselors weigh parents' reasons for requesting carrier testing of their unaffected child?(3) Do genetic counselors approach these requests differently based on the inheritance pattern or the presence or absence of carrier-associated health risks? 2 | MATERIALS AND METHODS Currently practicing genetic counselors in North America were invited to take a 39-item online survey.Informed consent was obtained.Participants were recruited between August 2021 and December 2021 from National Society of Genetic Counseling (NSGC) and American Board of Genetic Counselors research listservs, emails to authors who presented on pediatric topics at the 2021 NSGC Annual Conference, and social media.Participants were encouraged to forward the invitation to others who may meet inclusion criteria.The survey consisted of five sections: (a) hypothetical scenarios assessing willingness to facilitate testing in the context of four different genetic conditions; (b) persuasiveness of parental arguments for testing; (c) experience in practice; (d) familiarity with and helpfulness of four professional guidelines; and (e) demographic characteristics.Demographic items came directly from the 2021 NSGC Professional Status Survey (PSS) to facilitate analysis of sample representation.Sections (a) and (b) were presented in a counterbalanced random order to account for order effects.
Four prominent North American professional guidelines addressing carrier testing in minors were introduced in Section (d) (Supporting Information): the 2013 ACMG/AAP joint policy statement, the 2015 American Society of Human Genetics (ASHG) position statement, the American Medical Association (AMA) code of medical ethics opinion 2.2.5, and the 2003 Canadian College of Medical Geneticists (CCMG)/ Canadian Pediatric Society (CPS) joint position statement.For the guidelines with which they were familiar, participants rated their helpfulness when considering issues associated with carrier testing of children on a 0-10 scale.

For
all four scenarios, most participants (62%-77%) were more likely to facilitate testing if the patient was instead an assenting adolescent, though some said this demographic would not change their willingness.Compared to the other scenarios, participants were significantly less likely to have increased willingness for a 15-year-old child when considering testing for Gaucher disease type 2 [Cochran's Q (3) = 24.30,p < 0.001; pairwise comparison Bonferroni-adjusted p ranged from <0.001 to 0.02], an AR condition with nonactionable carrierassociated health risks in adulthood.T A B L E 1 Participant demographics a and career factors.

F
I G U R E 1 Two-way interaction for carrier testing willingness ratings by inheritance pattern and carrier-associated risk.[Colour figure can be viewed at wileyonlinelibrary.com] Improved awareness and understanding of the parental perspective may foster more productive communication when questions about carrier testing arise.Training programs and professional development efforts should encourage reflection on these issues to bolster empathy and informed decision-making when navigating requests for pediatric carrier testing.Genetic counselors are primary players in conversations with families about carrier testing of minors and should be involved in shaping professional recommendations on this topic.Professional guidelines cater to the values and preferred ethical frameworks of the people involved in their formation, therefore producing a bias: only the Western, majority group perspective is highlighted.A commitment to diversity and inclusion in the field necessitates advocating for the representation of other values in the development of guidelines and position statements.

4. 3 |
Research recommendationsThe findings described herein are considered exploratory and replication is encouraged, particularly with a larger, more diverse sample of genetic counselors.Further research would help to clarify the generalizability of the study's findings and uncover more on this topic.Qualitative research would be especially useful to elicit refined details on genetic counselors' opinions and practices related to pediatric carrier testing.Interviews with genetic counselors could reveal why they find parental arguments persuasive or not and how they do or do not use certain guidelines in their decision-making.
genetic counselors were unwilling to facilitate this testing, but they do consider the decision differently depending on aspects of the condition at hand.Two dichotomous variables, inheritance pattern and carrier-associated health risks, were shown to interact: genetic counselors were significantly more open to testing children for XL conditions (compared to AR) only when the condition has nonactionable carrier-associated health risks in adulthood.Genetic counselors seem to find child-centered parental motivations for testing more persuasive than those that primarily serve the parents' interests.An awareness of how different parties may assign different moral weights to various arguments for carrier testing in minors can inform the genetic counseling process as genetic counselors seek to maintain the patient-provider relationship while navigating these challenging conversations.