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Supplements Expanded Carrier Screening in Prenatal Care: Recent Advances and Key Considerations

Clinical Utility and Practical Implications of Carrier Screening

Technical Barriers

Laboratories offering expanded carrier screening differ in the number of conditions tested, methodologies, and result interpretation. In a comparison of expanded screening panels among 4 laboratories, only 29 of up to 210 screened conditions were common among these laboratories.22 Current laboratories screen for up to 549 diseases, and guidelines listing standardized diseases that should be included in expanded screening panels are not available.26 Some expanded screening panels include diseases of mild or moderate impact, which may pose challenges in pretest counseling and consent.22 

Different laboratories may use varying methodologies and approaches in result interpretation.22 Although some laboratories test for a predefined list of common genetic variants, others test for any variants recognized in the literature as well as novel variants.22 Testing only for a predefined list of variants reduces cost, turnaround time and variant interpretation challenges.22 However, detection of a more comprehensive list of variants, including novel variants, will identify more at-risk couples.22 An increased identification of carriers may create clinic workflow concerns.22 Hence, a robust variant curation and classification system should be followed, so that only pathogenic variants are reported.22

In addition to the National Society of Genetic Counselors, the Perinatal Quality Foundation, and the Society for Maternal-Fetal Medicine, ACMG and ACOG, issued a joint statement regarding expanded carrier screening, including recommendations for conditions to be included in expanded carrier screening panels and variant interpretation.29 However, this joint statement does not specifically recommend a list of conditions to be included or specific methodology for variant curation. Moreover, it is standard practice to not report variants of uncertain significance found by expanded carriers screening to patients.

Given the current lack of standardization of expanded carrier screening panels, some experts have recommended that clinicians and payers consider the “bottom line” measurement of a screening test’s performance, which is the ability of a test to maximize the detection of couples at risk of having an offspring affected by a severe disease.22 This concept of an “at-risk couple rate” in test performance, incorporates many important components. These consist of the severity of the diseases tested, mutation prevalence, and methodology used.22

Pre- and Posttest Management

In addition to technical laboratory challenges, there are also practical concerns with the increased frequency of identified carriers and the feasibility of adequate pretest education and posttest follow-up.22 Traditionally, only a limited set of conditions and testing information are to be discussed with patients prior to a carrier screening test.22 On the other hand, expanded carrier screening necessitates the use of a more generalized consent procedure.22 In a survey of genetic counselors, although the majority (92%) state that all patients should receive pretest counseling prior to receiving expanded carrier screening, most (67%) agree that trained providers other than genetic counselors can conduct pretest counseling. Additionally, 31% support the use of written or media alternatives for pretest counseling.21

Posttest management is of particular concern if the disease is unfamiliar.22 Genetic counseling and education should be offered for those individuals who receive positive results, but patients should also learn about residual risks when results are negative.22

Although screening male and female reproductive partners at the same time can shorten the screening process, this approach is costly.22 When an individual is screened only after the discovery of the other partner’s carrier status, the screening, results delivery, and education should be as expedient as possible.22

Based on the current availability of genetic counselors, personalized genetic counseling to accompany every positive result may not be realistic.22 Potential solutions include telephonic or online genetic counseling,22 or a combination of automated notifications, web education, and genetic counseling.30

Provider Misperceptions

In a survey study of women’s healthcare providers, 40.1% of respondents reported concerns that genetic test results may not remain confidential, and 37% were worried that positive genetic screening results may increase a patient’s insurance rates.31 Importantly, the Genetic Information Nondiscrimination Act and the Health Insurance Portability and Accountability Act offer patient protections by prohibiting health insurers from setting premiums or determining eligibility based on genetic information.31,32 Continuing education is needed to address provider misperceptions regarding insurance discrimination and confidentiality of test results.31

Taken together, although expanded carrier screening is an evolving new technology, current literature provides insights regarding potential best practices for panel selection, as well as patient pre- and posttest education and counseling.22 Research and further developments on optimizing screening panels, pre- and posttest counseling and education are expected. 22 Meanwhile, patient decision making and preferences, clinical outcomes, and optimal and efficient counseling methods are areas for further research.22 Provider education can address misperceptions regarding test result confidentiality and insurance discrimination.31

The Role of Expanded Carrier Screening in Preconception and Prenatal Care

Preconception carrier screening increases a couple’s reproductive choices and autonomy. Moreover, it may allow for earlier prenatal diagnosis and expectant management of genetic disorders.26 Expanded carrier screening overcomes limitations of conventional carrier screening based on knowledge of ancestry and family history because all individuals are offered screening for a set of conditions regardless of race or ethnicity.29 Although expanded carrier screening includes most of the genetic conditions recommended by current guidelines, they may include over a hundred genetic conditions, many of which are rare.29 The expansive list of tested conditions pose implementation challenges due to the lack of standardization in panel composition, and pre- and post-test counseling and management. 

Although ethical concerns have been raised, most can be addressed by best practices in implementation. Importantly, several health economics studies suggest that expanded carrier screening is more cost effective than conventional carrier screening in both cost per each affected birth avoided, and cost per life year gained.15,16 Importantly, the majority of reproductive couples at risk of transmitting a serious condition to their offspring will alter their reproductive decisions,14 suggesting that knowledge of the carrier status is of value to patients.

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