by Katie Stoll and Robert Resta
The American College of Medical Genetics and Genomics (ACMG) recently published a new Clinical Practice Resource that they proclaim recommends an “equitable approach for offering carrier screening to all individuals during pregnancy or preconception.”
We recognize the drawbacks of a screening program based solely on reported ancestry or ethnicity. And we understand that ensuring the same standard of carrier screening is available to all patients regardless of race or ethnic background addresses an important equity concern. However, the ACMG guidelines fall short in several areas:
- Addressing the benefits of carrier screening
- Questionable criteria for determining the severity of the included conditions
- A limited definition of inclusivity
- What choice patients should have in which conditions are or are not included in their personal screening.
The ACMG guidance is broad, calling for offering sequence-based population carrier screening for 113 genetic conditions to all patients who are pregnant or considering pregnancy. The rationale for expanded carrier screening according to the guideline is to allow for informed reproductive decisions. Specifically ACMG states that “reproductive decision making is the established metric for clinical utility of population-based carrier screening.”
Five reproductive options are described in the guidelines: 1) In vitro fertilization with preimplantation genetic testing for monogenic conditions 2) Use of donor gamete/embryo, 3) Adoption 4) Prenatal diagnosis using chorionic villus sampling or amniocentesis followed by a decision to either prepare for an affected child including special care after birth or to terminate the pregnancy. 5) A decision not to have children. We would add a sixth option – choice of reproductive partner, though perhaps this is more likely in situations of arranged marriages, such as with the Dor Yeshorim program.
Of these potential options, only one – prenatal diagnosis – is an option for those who undergo carrier testing during pregnancy, a fairly common occurrence. For most of the 100+ conditions included in the list, there is at best sparse evidence that prenatal preparation offers concrete medical benefits or that such knowledge enhances emotional preparation and psychological adaptation to having a child with one of these conditions. For a significant portion of patients who participate in carrier screening – those who are screened while pregnant – the only immediate benefits are either pregnancy termination or carrying to term. Therefore, the guidelines should also strongly recommend research into the specific ways that prenatal knowledge of any condition included in the panel either do or don’t enhance obstetric/neonatal management and/or parental emotional preparation and adaptation to having a child with the condition. Particularly for parents who would not consider termination or alternative reproductive pathways, we should be able to offer compelling evidence that carrier screening has measurable benefits for them and for their children if we are to claim that preparation is a benefit of screening.
ACMG states that they used “published definitions”’ to define the severity of genetic conditions considered for inclusion. The published definitions they are referring to come from one single study, published by Counsyl (now Myriad Genetics), a lab that was among the first to offer expanded carrier screening. In this study conducted in 2013, Counsyl surveyed people for whom they had emails in their internal database (presumably customers and/or staff) and asked respondents to provide their ratings of severity for five conditions that they felt represented a spectrum of health and developmental concerns. The outcome was responses from 192 genetic counselors and physicians. The opinions of these respondents is what ACMG is basing recommendations for a mass population carrier screening program.
The Counsyl study grouped severity into the following categories:
- Profound: shortened lifespan during infancy or childhood, intellectual disability;
- Severe: death in early adulthood, impaired mobility or a [disabling] malformation involving an internal organ;
- Moderate: neurosensory impairment, immune deficiency or cancer, mental illness, dysmorphic features.
It is concerning that this study puts conditions that are associated with intellectual disability in the same group as those that are associated with death in infancy/early childhood. Also, if we look across the lifespan, many, if not most of us will experience some features that could be counted in the Severe and/or Moderate buckets.
We cannot assume that this limited survey of healthcare providers is representative of the viewpoints of the US population. This survey did not include the perspectives of people who themselves have lived experience with the conditions included on the ACMG panel, or even people outside of the medical genetics community.
A condition that comes up frequently with expanded carrier screening is related to GJB2-related DFNB1 nonsyndromic hearing loss. GJB2 is included on the recommended ACMG panel on the basis of population frequency (second only to CFTR on the basis of current US-wide population frequencies) and in that it is considered of “moderate” severity based on the Counsyl study. Many in the Deaf community do not consider hearing loss a disability or disease, and we imagine many people who are homozygous for GJB2 mutations would not classify their hearing loss as a moderately severe condition.
We need to recognize that as much as we might try to avoid bringing our own biases into the way we counsel patients, or how we define the severity of a condition, the mere act of offering a prenatal test is not value neutral. There are negative associations implied for any condition we are including on a prenatal testing panel that by definition has a clinical utility metric of influencing reproductive decisions. We need to recognize our responsibility in that it is us in the medical genetics community who determine what is included on genetic screens, and we are also who defines what these conditions are in how we describe them to patients (be that in how we write a summary on a lab report or counsel people in clinic).
Stakeholder perspectives beyond the genetics community should be involved in development of these guidelines including what is included on screening panels and how we define these conditions for our patients. Perspectives from people with intellectual disabilities, the Deaf community and those living with cystic fibrosis, sickle cell anemia, spinal muscular atrophy, and other conditions being considered for inclusion on a carrier panel should have their voices included.
ACMG has been called to task previously on the issue of not including patient voices in the development of guidelines; see Nothing About Us Without Us: Guidelines for Genetic Testing. And the National Council on Disability specifically recommended that “Professional standards of care for offering NIPS and other prenatal genetic tests should be established through consensus negotiations that include genetic counselors, obstetrics and gynecology care providers, and representatives from affected disability communities.”
Another concern not addressed in the guidelines is whether patients have a choice to not include certain conditions in a screen. For example, someone may wish not to screen for a specific condition given historical negative experiences of racial stigma and bias (see this interview and article to learn more about problems encountered when carrier testing for sickle cell was introduced in the 1970s). Someone may wish to limit screening only to conditions for which we have a high degree of certainty of outcome, or only to conditions for which death in infancy/childhood is expected and for which there are no effective treatments. As Lisa Dive and Ainsely Newson point out in a recent thoughtful paper on reproductive carrier screening, some may find screening for life-limiting conditions to be acceptable and prefer not to screen for all conditions on a panel. If the goal of carrier screening is to support informed and autonomous choices, patients should be able to decide what is included on their screening.
Concerns regarding how conditions were defined and about the lack of diverse stakeholder perspectives, including those with disabilities and genetic conditions, were raised with ACMG during the development of this guideline and no actions were taken to address them. In ACMG’s email announcement to members about the new Practice Resource, lead author Anthony R. Gregg, MD, MBA was quoted as saying, “The benefits of carrier screening are clear. The greatest benefits can be achieved by accepting the challenge that all women be offered carrier screening not during pregnancy, but as they move from being pediatric patients to patients requiring well-women care. Professional organizations must respond to this call.” At the same time, ACMG is pushing state legislatures to not allow genetic counselors to order genetic testing. For many patients, genetic counselors are a common point of contact in preconception planning and during pregnancy. It is hard to see how such a policy enhances equity and access to testing if a genetic counselor cannot order a genetic test.
We will be waiting to see how professional organizations respond to this call. While it is too late for change to come with ACMG’s publication, other professional organizations including the American College of Obstetricians and Gynecologists (ACOG) and the National Society of Genetic Counselors (NSGC) can do better and demonstrate a genuine commitment to advancing equity and inclusion for all people by including diverse stakeholder voices, including those with genetic conditions and disabilities, in the development of guidelines related to carrier screening.
As the healthcare providers charged with the responsibility of guiding care, it is imperative that we do the important work of inviting all marginalized stakeholder populations to the table, hear their concerns, and address them before releasing guidelines that shape policies that will affect all of us. Equity extends beyond access to health services. As explained by Dr. Richard Besser at the Robert Wood Johnson Foundation:
Health equity cannot be achieved without actual lived experiences informing and advancing policies, regulations, laws and initiatives that address disability rights, accessibility and inclusion.
6 responses to “ACMG Carrier Screening Guidelines: Falling Short On Equity and Inclusion”
Really good paper. But as Diane & I argued, the very sound principle “Health equity cannot be achieved without actual lived experiences informing and advancing policies, regulations, laws and initiatives that address disability rights, accessibility and inclusion » depends on who provides the « actual live experience »— in practice who the « legitimate » spokespersons for people living with a given condition or their parents are. I am writing on Zika now — trying to finish my book on Zika in Brazil- and recently listened in to forum organized by LSE to one of my -progressive – Brazilian colleagues explaining that in Brazil it is not possible to argue in favor or legalization of abortion following an ultrasound diagnosis of a severe congenitial Zika syndrome -CZS (and this is a really severe neurological condition) because mothers of children with CZS strongly oppose it. It so happens that the charismatic leader and self appointed spokesperson of the most important association of mothers of children with CZS (called Union of Mothers of Angels -UMA, name that is already a program) , Germana Soares, is evangelical, and is strongly opposed to abortion for CZS, although even she modulated her initial opinion. Germana Soares, is very articulate, political savvy, and has excellent links with the press. From an anecdotal evidence, this view is not the only one among mothers of children with CZS, but there is no data on this topic; it is not sure what other mothers active in UMA think, even less what think the majority of mothers of children with CZS who are not linked with any association, and who as a rule are poor, and non-white. All best Ilana
Excellent point (as always). I agree that reaching out only to select people who may or may not represent a majority opinion of a group, or ignore a plurality of opinions is a shortcoming. But, as a start, it’s better than not reaching out to them, while still acknowledging that their views may not be representative or the final word. In addition, if our call for more research about the benefits of testing beyond termination for pregnant women is heeded, there is a good chance that such research would reach people beyond those involved with support groups and would result in the collection of a wider range of insights.
“…the mere act of offering a prenatal test is not value neutral.”
While true, neither is having disability advocates determining which conditions should be tested for on a carrier screening panel.
While I understand the point of view of equity and inclusion in this post, I question the paternalistic nature of limiting the conditions tested for on such a panel. I also believe there is a concerning parallel between this argument and conservative governments limiting abortion rights, especially in laws restricting abortion based on genetic abnormality.
I don’t know the right answer, but with ethical questions like this, I tend to try to remember who our patients are.
As a disability/patient advocate who’s long been involved with the genetic counseling community, I’ve been very fortunate to participate in many conversations about best practices for delivering a diagnosis and developing patient education materials, and I’m very grateful for the many thoughtful, sensitive genetic counselors who have become valued colleagues and friends. I think an important element to consider is that people with disabilities belong to a historically marginalized population that is increasingly being included as a cultural minority in Diversity, Equity, and Inclusion initiatives. While no one can certainly speak as the definitive authority for any minority population, I do think there are thoughtful leaders who could be invited to the table, people like Dr. Kara Ayers who is an esteemed academic with Osteogenesis Imperfecta who also publishes on these issues and leads the Center for Dignity in Healthcare for People with Disabilities or Alice Wong, a thoughtful disability rights activist with spinal muscular atrophy and leader of the Disability Visibility Project. There are many leaders in the advocacy/academic community who live with disabilities or whose loved ones have disabilities, who are academics in the field of disability studies, who respect the autonomy of women, and who specifically examine prenatal testing and disability. We would not and should not consider any initiative in society with broad implications for people of color without consulting with leaders of those communities as critical stakeholders, and I think the same is true for any other historically marginalized population including women, people who are LGBTQ, and people with disabilities. I’m not asserting that in the case of prenatal screening these advocates should be the sole deciding voices at the table—in fact they are usually far outweighed by medical professionals when an invitation is extended, but they should have a meaningful presence to participate as part of the conversation. Otherwise it seems somewhat culturally tone deaf, like when we see a group of men making reproductive policies that primarily impact women.
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