The changing landscape of carrier screening: expanding technology and options?

Author:McGowan, Michelle L.
Position:New Technologies, New Challenges: Women and Prenatal Genetic Testing in the 21st Century


Carrier screening (CS) is a mechanism by which women and their partners can learn about their risks of having a child affected by a recessive genetic disorder. (1) A carrier is a healthy individual who is not affected by genetic disease but nevertheless has one copy of a genetic mutation. (2) Couples in which both individuals have a copy of the same genetic mutation are at increased risk of having a child who inherits the recessive genetic disorder. (3) Theoretically, carrier identification and education regarding the inheritance of genetic mutations can serve as a form of "genotypic prevention" by enabling couples to prevent the generational transmission of specific genetic disorders. (4)

CS typically takes place in the context of reproductive healthcare, (5) where results may be used to inform prospective parents of their options regarding family planning and prenatal diagnosis. (6) CS is typically recommended on the basis of a family history of a genetic condition and for populations that have higher incidences of recessive conditions such as the Ashkenazi Jewish population. (7) Some medical professional societies have recommended shifting away from targeting CS based on family history and ethnicity toward population-based CS for all women who are considering pregnancy or are already pregnant, (8) specifically to screen for carrier status for cystic fibrosis (CF) (9) and spinal muscular atrophy (SMA). (10)

In the last few years, CS panels (11) have expanded to evaluate large numbers of mutations associated with a range of autosomal recessive and X-chromosome-linked inherited conditions including CF, SMA, Tay-Sachs Disease, sickle cell anemia, and Fragile X syndrome. (12) Several commercial laboratories have developed these expanded CS panels and market them to reproductive healthcare providers. (13) Despite the changing technological and commercial landscape of CS in the United States, little is known about the clinical and societal implications of expanding CS efforts to include and detect much larger numbers of genetic disorders. To this end, we report results of a study of professionals with expertise in genetics regarding their attitudes toward prenatal applications of expanded carrier screening (ECS). A primary aim of this paper is to describe genetics professionals' perceptions of the benefits and challenges of expanding prenatal

CS. A secondary aim is to situate these genetics professionals' perspectives within the broader landscape of societal debates about appropriate integration of new risk assessment technologies into prenatal care. The results and following discussion demonstrate how new approaches to CS both resemble and diverge from previous prenatal surveillance technologies in ways that are likely to impact clinical practice and pregnant women's reproductive choices and perceived responsibilities.


    Medical professionals advocate CS prior to pregnancy because a wider array of reproductive options is available to prospective parents before pregnancy than during it, including deciding whether and how to conceive and considering assisted reproductive technologies such as embryonic genetic testing or donor gametes. (14) Pregnant women and their partners who receive positive CS results are limited to either (1) accepting the possible risk and continuing the pregnancy or (2) undergoing prenatal diagnosis and potentially deciding whether to terminate or continue an affected pregnancy. (15) However, preconception applications of CS are logistically challenging: nearly half of all pregnancies in the United States are unplanned, and non-pregnant patients are typically not interested in seeking population-based preconception carrier testing. (16) As a result, CS is typically offered during pregnancy by prenatal care providers, including obstetricians, nurse midwives, and family practitioners who deliver babies. (17) However, there is evidence that not all obstetricians and gynecologists adhere to professional guidelines for population-based CS. (18) To the extent that genetic counselors are involved in counseling regarding CS, their involvement tends to occur after a woman and her partner receive a positive result. (19)

    In addition to variability of CS practices across health care providers and patient populations, research has also shown that education and values impact patient willingness to consider CS in the reproductive context. Empirical research suggests that pregnancy itself is a lens through which women make decisions about whether to accept carrier testing, whereby "underlying belief systems, heightened vulnerability and personal stress management strategies" influence decision-making during pregnancy. (20) For instance, Sparbel and Williams found that pregnant women who were committed and attached to their pregnancies were less likely to accept carrier testing to avoid heightening their anxiety and stress. (21) Hence, some have argued that education and informed consent for CS should be tailored to patient values and expectations, as educational needs for making an informed decision about whether to undergo screening differ depending on patient values. (22) However, existing research assessing educational needs and values has been limited to assessing CS for single gene disorders, and little is known about how the expansion of CS panels might impact clinical practice and patient uptake.


    Despite evidence that there are multiple challenges associated with the integration of population-based approaches to CS into reproductive healthcare, several commercial laboratories are beginning to advocate ECS. The Universal Genetic Test marketed by Counsyl was the first of these products to become available through select clinics across the United States. (23) Unlike population-based CS for individual genetic disorders (e.g., CF and SMA) which is largely administered during pregnancy and CS panels targeted towards specific ethnic populations (e.g., the Ashkenazi Jewish Genetic Panel), the Universal Genetic Test was marketed as a preconception CS panel that would be universally-applicable to all ethnic populations due to the inclusion of genetic mutations that are common across ethnic groups. (24)

    Since 2009, four additional products have become available: Ambry Genetics' AmbrySCREEN, (25) GenPath's InheriGen, (26) Pathway Genomics' Pre-Pregnancy Planning Insight, (27) and 23andMe's Personal Genome Service. (28) The five currently available products screen for 47 to 164 autosomal recessive and X-chromosome-linked conditions that range in severity and age of onset from fatal, childhood-onset conditions to adult-on-set conditions. (29) With declining genotyping costs and a thriving commercial market for genetic testing products, it is reasonable to expect that the number of genetic conditions and mutations evaluated by carrier testing products will continue to increase. (30)

    These products are marketed primarily as preconception CS tools to be used by prospective mothers and fathers, (31) though there is some evidence that ECS is available to prenatal patients as well. (32) If used in the prenatal context, ECS of the mother may be followed by diagnostic testing of the fetus. (33)

    Current ECS products screen a patient-provided saliva or blood sample for known mutations at loci associated with recessive diseases. (34) The patient or physician can expect results in approximately two to three weeks. (35) Prices range from $99 to $450, which is within the range of the costs traditionally associated with evaluation of carrier status for single disorders such as CF or SMA. (36) Most products are offered only through a physician, (37) although one product is available for purchase direct-to-consumer via the Internet. (38) While one product advertises its availability at "100s of clinics across the US," (39) information regarding uptake of these products is not available currently. In addition, there are no medical consensus statements or professional-society guidelines regarding the use of ECS products in preconception or prenatal care.

  3. Focus-GROUP STUDY

    Focus-group methodology was used to examine genetics professionals' perspectives on the expansion of CS. This methodology is ideal for collecting in-depth qualitative data, as focus groups involve small gatherings of knowledgeable individuals who share a common set of interests for a moderated discussion of a chosen topic. (40) Focus-group methodology is particularly useful for producing data through social interaction that allows participants to make comparisons between each others' experiences and opinions. (41) This approach enables participants to react to and build on responses from their colleagues, resulting in novel opportunities for the production of ideas and the identification of areas of disagreement and agreement. (42) The focus-group sessions reported here comprise a component of a larger study to assess genetics professionals' perspectives on the impact of genomic tests on clinical practice. (43)

    To promote professional and specialist diversity in each focus group, a purposive sampling strategy was used to identify experts in medical genetics and genetic counseling at academic medical centers with well-established genetics programs. The research team organized focus groups in Ann Arbor, Michigan; Baltimore, Maryland; Cleveland, Ohio; Denver, Colorado; Philadelphia, Pennsylvania; and Seattle, Washington. Sites were selected based on their geographical location, training programs in medical genetics and genetic counseling, translational research programs, and clinical practice settings (e.g., pediatric vs. adult...

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