Dataset Information

First Universal Newborn Screening Program for Severe Combined Immunodeficiency in Europe. Two-Years' Experience in Catalonia (Spain).

ABSTRACT: Severe combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TRECs) in dried blood spot (DBS) samples. Early detection of this condition speeds up the establishment of appropriate treatment and increases the patient's life expectancy. Newborn screening for SCID started in January 2017 in Catalonia, the first Spanish and European region to universally include this testing. The results obtained in the first 2 years of experience are evaluated here. All babies born between January 2017 and December 2018 were screened. TREC quantification in DBS (1.5 mm diameter) was performed with the Enlite Neonatal TREC kit from PerkinElmer (Turku, Finland). In 2018, the retest cutoff in the detection algorithm was updated based on the experience gained in the first year, and changed from 34 to 24 copies/?L. This decreased the retest rate from 3.34 to 1.4% (global retest rate, 2.4%), with a requested second sample rate of 0.23% and a positive detection rate of 0.02%. Lymphocyte phenotype (T, B, NK populations), expression of CD45RA/RO isoforms, percentage and intensity of TCR ?? and TCR ??, presence of HLA-DR+ T lymphocytes, and in vitro lymphocyte proliferation were studied in all patients by flow cytometry. Of 130,903 newborns screened, 30 tested positive, 15 of which were male. During the study period, one patient was diagnosed with SCID: incidence, 1 in 130,903 births in Catalonia. Thirteen patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 10,069 newborns (43% of positive detections). Nine patients were considered false-positive cases because of an initially normal lymphocyte count with normalization of TRECs between 3 and 6 months of life, four infants had transient lymphopenia due to an initially low lymphocyte count with recovery in the following months, and three patients are still under study. The results obtained provide further evidence of the benefits of including this disease in newborn screening programs. Longer follow-up is needed to define the exact incidence of SCID in Catalonia.

SUBMITTER: Argudo-Ramirez A

PROVIDER: S-EPMC6818460 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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First Universal Newborn Screening Program for Severe Combined Immunodeficiency in Europe. Two-Years' Experience in Catalonia (Spain).

Argudo-Ramírez Ana A Martín-Nalda Andrea A Marín-Soria Jose L JL López-Galera Rosa M RM Pajares-García Sonia S González de Aledo-Castillo Jose M JM Martínez-Gallo Mónica M García-Prat Marina M Colobran Roger R Riviere Jacques G JG Quintero Yania Y Collado Tatiana T García-Villoria Judit J Ribes Antonia A Soler-Palacín Pere P

Frontiers in immunology 20191022

Severe combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TRECs) in dried blood spot (DBS) samples. Early detection of this condition speeds up the establishment of appropriate treatment and increases the patient's life expectancy. Newborn screening for SCID started in January 2017 in Catalonia, the first Spanish and European region to universally include this testing. The results obtained i ...[more]

PMID: 31695692

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Project description:IntroductionSevere Combined Immunodeficiency (SCID) is generally fatal if untreated; it predisposes to severe infections, including disseminated Bacille-Calmette-Guerin (BCG) disease from BCG vaccination at birth. However, delaying BCG vaccination can be detrimental to the population in tuberculosis-endemic regions. Early diagnosis of SCID through newborn screening followed by pre-emptive treatment with anti-mycobacterial therapy may be an alternative strategy to delaying routine BCG vaccination. We report the results of the first year of newborn SCID screening in Singapore while continuing routine BCG vaccination at birth.MethodNewborn screening using a T-cell receptor excision circle (TREC) assay was performed in dried blood spots received between 10 October 2019 to 9 October 2020 using the Enlite Neonatal TREC kit. Patients with low TREC had lymphocyte subset analysis and full blood count performed to determine the severity of lymphopenia and likelihood of SCID to guide further management.ResultsOf the 35888 newborns screened in 1 year, no SCID cases were detected, while 13 cases of non-SCID T-cell lymphopenia (TCL) were picked up. Using a threshold for normal TREC to be >18 copies/μL, the retest rate was 0.1% and referral rate to immunologist was 0.04%. Initial low TREC correlated with low absolute lymphocyte counts (ALC), and subsequent normal ALC corresponded with increases in TREC, thus patients with normal first CD3+ T cell counts were considered to have transient idiopathic TCL instead of false positive results. 7/13 (54%) had secondary TCL (from sepsis, Trisomy 21 with hydrops and stoma losses or chylothorax, extreme prematurity, or partial DiGeorge Syndrome) and 6/13 (46%) had idiopathic TCL. No cases of SCID were diagnosed clinically in Singapore during this period and for 10 months after, indicating that no cases were missed by the screening program. 8/9 (89%) of term infants with abnormal TREC results received BCG vaccination within the first 6 days of life when TREC and ALC were low. No patients developed BCG complications after a median follow-up of 17 months.ConclusionNewborn screening for SCID can be implemented while continuing routine BCG vaccination at birth. Patients with transient TCL and no underlying primary immunodeficiency are able to tolerate BCG vaccination.

Project description:BackgroundThis study aimed to estimate potential undetected cancers over the first 2 years of the COVID-19 pandemic in Catalonia.MethodsCancer incidence was compared between pre-pandemic (2019) and pandemic (March 2020-January 2022) periods in the Catalan Pathology Registry (CPR) according to sex, age, and tumor site. The correlation between cancer diagnosis and COVID-19 health care workload was also evaluated by means of the Pearson's correlation coefficient (R). The expected incident cancers (E) during the pandemic were estimated by applying 2019 CPR cancer incidence specific rates by sex and 5-year age groups to the 2020 and 2021 Catalan population pyramids. CPR incident cancers were considered observed (O). Standardized incidence ratios (SIR) and 95% confidence intervals (CIs) were calculated using the O/E ratio.ResultsAfter two pandemic years, cancer diagnosis decreased by 12% (SIR 0.88, 95% CI 0.87-0.89), or ∼7700 undetected cancers (13 000 with nonmelanoma skin cancer). Without nonmelanoma skin cancer, 72% of the cancer underdiagnosis was generated in 2020. Diagnoses decreased more in men (whole pandemic -14%; 2020 -21%; 2021 -8%) than in women (-9%, -19%, -3%, respectively), dropping significantly overall in all pandemic waves but the fifth (first -37%, second -16%, third -8%, fourth -6%, fifth -2%, sixth -6%), and across all adult age groups. In the first wave, CPR cancer diagnosis was inversely correlated with COVID-19 caseload in primary care (R -0.91, 95% CI -0.97 to -0.75) and occupancy in conventional hospital wards (R -0.91, 95% CI -0.99 to -0.48) and intensive care (R -0.91, 95% CI 95% -0.98 to -0.70).ConclusionsOur study evaluated the overall pandemic impact on cancer diagnosis on a large scale and with minimal selection bias, showing that as of February 2022, cancer detection in Catalonia had not yet recovered to pre-pandemic levels. Pending cancer incidence data from population-based cancer registries, early CPR data could inform the development of Spanish cancer control plans.

Project description:BackgroundPublic health newborn screening (NBS) programs continuously evolve, taking advantage of international shared learning. NBS for severe combined immunodeficiency (SCID) has recently been introduced in many countries. However, comparison of screening outcomes has been hampered by use of disparate terminology and imprecise or variable case definitions for non-SCID conditions with T-cell lymphopenia.ObjectivesThis study sought to determine whether standardized screening terminology could overcome a Babylonian confusion and whether improved case definitions would promote international exchange of knowledge.MethodsA systematic literature review highlighted the diverse terminology in SCID NBS programs internationally. While, as expected, individual screening strategies and tests were tailored to each program, we found uniform terminology to be lacking in definitions of disease targets, sensitivity, and specificity required for comparisons across programs.ResultsThe study's recommendations reflect current evidence from literature and existing guidelines coupled with opinion of experts in public health screening and immunology. Terminologies were aligned. The distinction between actionable and nonactionable T-cell lymphopenia among non-SCID cases was clarified, the former being infants with T-cell lymphopenia who could benefit from interventions such as protection from infections, antibiotic prophylaxis, and live-attenuated vaccine avoidance.ConclusionsBy bringing together the previously unconnected public health screening community and clinical immunology community, these SCID NBS deliberations bridged the gaps in language and perspective between these disciplines. This study proposes that international specialists in each disorder for which NBS is performed join forces to hone their definitions and recommend uniform registration of outcomes of NBS. Standardization of terminology will promote international exchange of knowledge and optimize each phase of NBS and follow-up care, advancing health outcomes for children worldwide.

Dataset Information

First Universal Newborn Screening Program for Severe Combined Immunodeficiency in Europe. Two-Years' Experience in Catalonia (Spain).

Publications

First Universal Newborn Screening Program for Severe Combined Immunodeficiency in Europe. Two-Years' Experience in Catalonia (Spain).

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