Expanded Carrier Screening for Reproductive Risk Assessment
Summary of Recommendations
- Expanded carrier screening (ECS) presents an ethnicity-based carrier screening alternative which does not rely on race-based medicine; therefore, ECS should be offered to all who are currently pregnant, considering pregnancy, or might otherwise biologically contribute to pregnancy. Gatekeeping ECS to only those persons with access to medical care who know to ask about ECS, and furthermore only those who are perceived to be able to handle the potential stress of results, upholds systemic inequalities in medicine by ensuring that individuals with fewer medical resources and/or lower health literacy levels will encounter more difficulties in obtaining information about their genetic code.
- Barriers to the broad implementation of ECS should be identified and addressed so that test performance for carrier screening will not depend on social constructs such as race.
- The final decision to pursue carrier screening should be directed by shared decision-making, which takes into account specific features of patients as well as their preferences and values.
- Informed consent for ECS is essential and should be accessible for all. Informed consent methods and tools may take many forms, depending on the needs of the population.
- Informed consent for ECS should emphasize the universal nature of AR and XL disease carrier status, and that the ultimate determinant of risk for AR disease is the shared carrier status of both individuals in the reproductive pair. Patients should be counseled that individual “abnormal” or “positive” results from ECS are expected and will usually not have an impact on one's own health status. Informed consent should also note that ECS may uncover incidental findings, such as a possible diagnosis and/or health risks.
- Expanded carrier screening panel composition should result in a useful carrier pair yield for AR diseases, although the frequency of at-risk reproductive pairs may vary. Conditions included for screening by ECS should be reasonably expected to pose changes to reproductive planning, which should be considered to broadly encompass all elements of family planning and early neonatal evaluation. The actionability and clinical utility of ECS should not be determined by the healthcare provider alone, as the healthcare provider should not impose their own values regarding appropriate, reasonable, and/or accessible family planning strategies upon the patient.
- Sequencing assays for ECS are recommended to achieve the goal of equitable testing and care. The risk of mild variant identification through sequencing is preferable to the risk of variant non-identification through genotyping.
- Likely pathogenic variants identified through ECS should be treated clinically as potentially disease-causing until evidence is provided disputing that variant's pathogenicity. ECS laboratory reports should comprehensively detail variant classification rationale, cite scientific publications, and provide links to genomic databases containing the identified variant.
- If VUS reporting should become a standard feature in ECS panels for all genes included on the panel, counseling on VUSs will need to be included in the informed consent process. At present, we do not recommend the routine inclusion of VUSs on ECS reports.
- Patients should be informed of the possibility for updated variant interpretations over time. Clinicians should be aware of the variant upgrade/downgrade processes and patient re-contact protocols at the labs they use for ECS.
- Patients should be counseled that a consecutive testing strategy for ECS will delay receipt of final results when compared to simultaneous testing, and therefore, simultaneous ECS is ideal, especially in the context of pregnancy.
- Insurance reimbursement for ECS is critically important. Collaboration between ECS stakeholders is necessary to identify and implement solutions that improve ECS cost-effectiveness and access to comprehensive risk assessment. Payers and providers should continue to be educated on AR/XL disease to underscore that all individuals, including those without personal or family history of genetic disease, stand to benefit from payer coverage of ECS.
- The perspectives of those in the disability community should be solicited and amplified during discussions of ECS panel composition, disease severity, and whether the aim of ECS centers upon disease prevention or autonomy in decision-making.
- Advocacy efforts are needed to ensure equitable access to disability resources, maternal and child welfare programs, and other crucial reproductive justice initiatives. Without access to these resources, the benefits of ECS will not be actualized in an equitable and just manner.
Expanded Carrier Screening for Reproductive Risk Assessment
February 13, 2023
Last Updated Month/Year
September 11, 2023
Country of Publication
Expanded carrier screening (ECS) intends to broadly screen healthy individuals to determine their reproductive chance for autosomal recessive (AR) and X-linked (XL) conditions with infantile or early-childhood onset, which may impact reproductive management (Committee Opinion 690, Obstetrics and Gynecology, 2017, 129, e35). Compared to ethnicity-based screening, which requires accurate knowledge of ancestry for optimal test selection and appropriate risk assessment, ECS panels consist of tens to hundreds of AR and XL conditions that may be individually rare in various ancestries but offer a comprehensive approach to inherited disease screening. As such, the term "equitable carrier screening" may be preferable. This practice guideline provides evidence-based recommendations for ECS using the GRADE Evidence to Decision framework (Guyatt et al., BMJ, 2008, 336, 995; Guyatt et al., BMJ, 2008, 336, 924). We used evidence from a recent systematic evidence review (Ramdaney et al., Genetics in Medicine, 2022, 20, 374) and compiled data from peer-reviewed literature, scientific meetings, and clinical experience. We defined and prioritized the outcomes of informed consent, change in reproductive plans, yield in identification of at-risk carrier pairs/pregnancies, perceived barriers to ECS, amount of provider time spent, healthcare costs, frequency of severely/profoundly affected offspring, incidental findings, uncertain findings, patient satisfaction, and provider attitudes. Despite the recognized barriers to implementation and change in management strategies, this analysis supported implementation of ECS for these outcomes. Based upon the current level of evidence, we recommend ECS be made available for all individuals considering reproduction and all pregnant reproductive pairs, as ECS presents an ethnicity-based carrier screening alternative which does not rely on race-based medicine. The final decision to pursue carrier screening should be directed by shared decision-making, which takes into account specific features of patients as well as their preferences and values. As a periconceptional reproductive risk assessment tool, ECS is superior compared to ethnicity-based carrier screening in that it both identifies more carriers of AR and XL conditions as well as eliminates a single race-based medical practice. ECS should be offered to all who are currently pregnant, considering pregnancy, or might otherwise biologically contribute to pregnancy. Barriers to the broad implementation of and access to ECS should be identified and addressed so that test performance for carrier screening will not depend on social constructs such as race.
Health Care Settings
Ambulatory, Laboratory services
Genetics, nurse, nurse practitioner, physician, physician assistant
Assessment and screening, Prevention
D006580 - Genetic Carrier Screening, D016742 - Preconception Care
preconception, reproductive risk assessment, genetic screening, carrier screening, genetic carrier screening, carrier testing
Sagaser KG, Malinowski J, Westerfield L, Proffitt J, Hicks MA, Toler TL, Blakemore KJ, Stevens BK, Oakes LM. Expanded carrier screening for reproductive risk assessment: An evidence-based practice guideline from the National Society of Genetic Counselors. J Genet Couns. 2023 Feb 9. doi: 10.1002/jgc4.1676. Epub ahead of print. PMID: 36756860.