Original Title: Avis: Évaluation de la pertinence du dépistage néonatal du déficit immunitaire combiné sévère (SCID)

Authors' objectives: Severe combined immunodeficiency (SCID) is a category of primary immune deficiency consisting of a group of very serious inherited disorders characterized by the insufficient production of functional peripheral T cells in the newborn. This deficiency is caused by a broad spectrum of mutations in different genes involved in the development and function of the cells of the adaptive immune system. The worldwide prevalence of severe combined immunodeficiency is approximately 1 in 50,000 live births. Its prevalence in Québec is uncertain. Severe combined immunodeficiency usually manifests during the first few months of life as nonspecific conditions and signs, such as severe infections due to opportunistic organisms, delayed growth or chronic diarrhea. All children with severe combined immunodeficiency who are not treated usually die by the age of 1 to 2 years from an infection. The Ministère de la Santé et des Services sociaux (MSSS) asked the Institut national d'excellence en santé et en services sociaux (INESSS) to evaluate the relevance of newborn screening for severe combined immunodeficiency in the current Québec context.

Authors' results and conclusions: RESULTS: (1. Poor prognosis in children who are not treated): • SCID is a group of very serious inherited disorders that usually manifest during the first few months of life as nonspecific conditions and signs. •All children with SCID who are not treated have a poor prognosis and usually die before the age of 1 to 2 years. (2. Urgent care is required): • Suspected SCID should be considered an urgent clinical condition, and reducing diagnostic delay is important in order to obtain treatment as soon as possible. Timely diagnosis is a critical issue for affected newborns. (3. Treatments are available): •There are different supportive treatments that prolong survival, and there are curative treatments, of which the gold standard is hematopoietic stem cell transplantation. •According to an expert consensus, curative treatment is more effective when the transplant is performed before the age of 3.5 months and the child has not previously had an infection. (4. There is a reliable and validated screening test:): • The TREC test has the potential to improve the detection of SCID before the infant contracts an infection. • The TREC test’s sensitivity for detecting SCID is very high, its specificity and referral rate for a diagnostic workup are quite variable, and its positive predictive value is generally low. • The identification of non-SCID T-cell lymphopenia by the TREC test confirms the importance of establishing a population-specific threshold value to limit these cases, which would outnumber SCID cases. (5. A safe screening): Psychosocial risks associated with false-positive detection do exist, as in any other neonatal screening, but the tests that infants with a false-positive screening result undergo are generally not very invasive. (6. An equitable offer of screening and a multifunctional platform): Given the uncertainty regarding the actual prevalence of SCID in Québec, offering screening to all Québec newborns seems to be a fair option.

Authors' recommendations: Based on all the findings and a deliberative process with the Comité délibératif permanent – Approches diagnostiques et dépistage: INESSS recommends adding severe combined immunodeficiency screening to the blood platform in Québec’s neonatal screening program. Given the following considerations: • The need for the facility entrusted with this screening to establish performance standards for this test and a population-specific TREC‘s threshold value to limit the identification of non-SCID T-cell lymphopenia. • Guidance will be needed for the disclosure of incurable incidental findings sometimes identified by the TREC test, such as ataxia-telangiectasia. • Premature newborns and those admitted to neonatal intensive care units should also be screened before discharge from hospital, and a specific algorithm for these infants should be developed. • The administration of the live attenuated bacille Calmette-Guérin (BCG) tuberculosis vaccine to newborns in Nunavik communities should be postponed for a few weeks so that one can first obtain the SCID screening result. • The dissemination of information about the disease and the screening test should be promoted to alleviate the fear of molecular screening in the general population and especially among future parents.

Authors' methods: To evaluate the relevance of newborn screening for severe combined immunodeficiency, we conducted a comprehensive search of the scientific literature across several databases, with no limitations on study design and with the inclusion of the grey literature for all the aspects examined. Contextual and experiential data were collected from professionals practicing in pediatrics (pediatrician, immunologist and neonatologist) and medical genetics, from a representative of an association of patients and parents or caregivers of affected children, and from clinical administrative databases. Additionally, we determined the transferability of the results of the economic studies identified to the Québec clinical context and performed a budget impact analysis. All the data (scientific, contextual and experiential) were presented to the members of the deliberative committees so that they could deliberate on the clinical relevance of this screening and on the relevance of implementing it in the Québec context, taking into account the organizational aspect and the economic impact. The result of these deliberations served as the basis for developing the final recommendation.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/evaluation-de-la-pertinence-du-depistage-neonatal-du-deficit-immunitaire-combine-severe-scid.html

Year Published: 2022

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/evaluation-de-la-pertinence-du-depistage-neonatal-du-deficit-immunitaire-combine-severe-scid.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec