Original Title: Pertinence de l’ajout du dépistage néonatal de l’hyperplasie congénitale des surrénales au Programme québécois de dépistage néonatal sanguin

Authors' objectives: Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive endocrine disorder affecting enzymes essential for the synthesis of steroid hormones. The estimated worldwide prevalence of classic CAH varies from 1 in 9,500 to 18,000 live births, with large regional differences, and is estimated at about 1 in 16,000 births in Québec. Although the newborn mortality rate linked to CAH is relatively low in more economically developed countries, this endocrine disorder is thought to lead to significant morbidity in the longer term, such as psychosocial problems. The Ministère de la Santé et des Services sociaux has mandated the Institut national d'excellence en santé et en services sociaux to assess the relevance of adding newborn screening for congenital adrenal hyperplasia to the blood testing platform of the provincial newborn screening program in the current Québec context.

Authors' results and conclusions: RESULTS (#1 DISEASE SEVERITY AND PROGNOSIS ARE VARIABLE): Signs of varying degrees of genital virilization in girls from birth for both forms would allow us to suspect the disease in most cases, whereas there are generally no physical signs of the disease in boys. (#2 DIAGNOSTIC METHODS AND TREATMENTS EXIST TO CONTROL THE DISEASE): • Diagnostic methods and pharmacological treatment for replacement of deficient cortisol and aldosterone are well established. (#3 THE CAH SCREENING TEST CAN BE EFFECTIVELY PERFORMED WITH A SECOND-TIER SCREEN AND BY TAKING CERTAIN PRECAUTIONS): Good screening test performance requires a complex algorithm with specific measures for premature infants and all those hospitalized in neonatal intensive care units. (#4 NEWBORN SCREENING FOR CAH APPEARS TO BE MOST EFFECTIVE IN REDUCING SHORT-TERM MORBIDITY): There is some evidence of the effectiveness of screening on longer-term outcomes: – an improvement in potential adult height for all affected men and for women with the simple virilizing form; – a downward trend in fracture rates between the pre-screening and postscreening periods for both sexes. (#5 THE SCREENING TEST CAN BE SAFE): Cases of CAH patients testing false-negative at screening appear to be rare with second-tier testing, since this allows the threshold value to be lowered, and missed cases would be mainly of the simple virilization form. (#6 UNMET NEEDS EXIST FOR CAH IF THERE IS NO NEWBORN SCREENING): Female infants with complete virilization are sometimes assigned a sex at birth that is inconsistent with their genotype, even in Québec. A diagnosis will only be made when they consult an emergency department with a salt-wasting or an adrenal crisis, or in early childhood when signs of very early puberty appear. (#7 THERE ARE ETHICAL ISSUES RELATED TO SCREENING): Newborn screening for CAH could: – increase equity in early diagnosis for all infants of both sexes, even for those without clinical signs; – accelerate the diagnosis and management of girls with complete virilization, while reducing the psychosocial impact and consequences of sex assignment at birth that is inconsistent with the newborn’s genotype. (#8 A CARE TRAJECTORY IS ESTABLISHED IN QUÉBEC, BUT ORGANIZATIONAL ADJUSTMENTS WOULD BE NECESSARY IF CAH SCREENING WERE TO BE ADDED): In Québec, it is estimated that there are between 5 and 7 cases of CAH per year. Therefore, the workload for the multidisciplinary teams in charge of their lifelong follow-up would remain the same if screening were added, and the workload for referring centres should remain within their capacity if the protocol were optimized to limit false positives (currently estimated at about 25/year); • There is a need for education, both among professionals and parents, to promote a better understanding of this rare disease. (#9 LITERATURE ON THE EFFICIENCY OF NEWBORN SCREENING RELEVANT TO THE QUÉBEC CONTEXT IS LIMITED): The cost-effectiveness of newborn screening for CAH in Québec therefore remains uncertain. The introduction of newborn screening for CAH could have a gross impact of approximately $314,215 per year, without taking into account a potential reduction linked to lower hospitalization costs, based on testing costs estimated by British Columbia. (#10 INTERNATIONAL POSITIONS ARE GENERALLY IN FAVOUR OF SCREENING): Some forty universal newborn screening programs worldwide have implemented CAH screening over the past 30 years, and favourable positions from learned societies in three countries have been published, with only one country opposed.

Authors' recommendations: In light of all the scientific, contextual, and experiential data collected, the findings and the deliberative process conducted: X INESSS is of the opinion that newborn screening for congenital adrenal hyperplasia would be clinically relevant. However, such an addition to the blood testing platform of the Québec newborn screening program would have to consider the following elements: • The delay in obtaining screening test results from the Québec newborn screening program should be improved to enable optimal therapeutic intervention for the vast majority of newborns with the severe form of the disease. – Various measures could be implemented to shorten delays in obtaining results: use of rapid courier services, involvement of birthing centres in rapid dispatch of samples to the central laboratory after collection, and extension of laboratory opening hours. • It is essential that healthcare professionals be made aware of this disease and its clinical signs, since increased vigilance during the initial physical examination of newborns would enable more suspected cases to be identified, whether or not newborn screening is available. • As this test has already been implemented in several countries, Québec should draw on the experience and success of programs that have overcome the problem of false positives and achieved good test performance. • The relevance of newborn screening for CAH could be re-evaluated using data collected in the real-life setting over several years, in order to establish the efficiency of such screening.

Authors' methods: A rapid review2, that is, a thorough and transparent synthesis of the literature, was conducted to document the parameters of interest, including screening test performance, efficacy and screening safety (the clinical dimension) and efficiency (the economic dimension). A narrative review of the scientific literature was conducted to document the populational, organizational and sociocultural dimensions. Scientific literature was retrieved from several databases and other sources, with no restrictions on study design. Contextual and experiential data were collected from an advisory committee of professionals working in the field, as well as from administrative databases.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/pertinence-de-lajout-du-depistage-neonatal-de-lhyperplasie-congenitale-des-surrenales-au-programme-quebecois-de-depistage-neonatal-sanguin.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/pertinence-de-lajout-du-depistage-neonatal-de-lhyperplasie-congenitale-des-surrenales-au-programme-quebecois-de-depistage-neonatal-sanguin.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: L'Institut national d'excellence en sante et en services sociaux (INESSS)