ArticleJournal of clinical immunology2021
Second Tier Testing to Reduce the Number of Non-actionable Secondary Findings and False-Positive Referrals in Newborn Screening for Severe Combined Immunodeficiency.
Article in Journal of clinical immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Newborn screening for severe combined immunodeficiency in the NHS newborn blood spot screening programme: a systematic review.Health technology assessment (Winchester, England) · 2026Pooled it
- Second-tier genetics improves newborn screening accuracy for SCID and other T cell deficiencies.Journal of human immunity · 2026Article
- Nationwide TREC/KREC-based newborn screening and clinical outcomes in Japan.Journal of human immunity · 2026Article
- Improving Severe Combined Immunodeficiency and Cystic Fibrosis Newborn Screening by Replacing Current Tests with First-Tier Targeted Gene Sequencing.International journal of neonatal screening · 2026Article
- Optimizing TREC- and KREC-based newborn screening: Risk-stratified algorithms significantly reduce referrals.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- Managing non-SCID T cell lymphopenia after TREC-based newborn screening.Journal of human immunity · 2026Article
- Key Outcomes from a Stakeholder Workshop on Genomic Newborn Screening: Recommended Next Steps for the Integration of Genomics into Public Health Programs.Public health genomics · 2026Article
- Natural History of Swiss Infants with Non-SCID T-cell Lymphopenia Detected by Newborn Screening: A Cohort Study.Journal of clinical immunology · 2025Article
- Next-generation Sequencing and Other Second Tier Tests in Newborn Screening for (X-linked) Agammaglobulinemia.Journal of clinical immunology · 2025Article
- Harmonizing TREC Thresholds in Newborn Screening for SCID: Insights From Russian Validation Cohort.Journal of clinical laboratory analysis · 2025Article
- Immunological biomarkers at birth and later risk of celiac disease.BMC gastroenterology · 2025Article
- Advancing Newborn Screening in Washington State: A Novel Multiplexed LC-MS/MS Proteomic Assay for Wilson Disease and Inborn Errors of Immunity.International journal of neonatal screening · 2025Article
- Leveraging AI-enhanced digital health with consumer devices for scalable cardiovascular screening, prediction, and monitoring.NPJ cardiovascular health · 2025Review
- Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023Article
- Case report:Frontiers in immunology · 2023Article
- Future Perspectives of Newborn Screening for Inborn Errors of Immunity.International journal of neonatal screening · 2021Review
- Economic Evaluation of Different Screening Strategies for Severe Combined Immunodeficiency Based on Real-Life Data.International journal of neonatal screening · 2021Article
- First Year of TREC-Based National SCID Screening in Sweden.International journal of neonatal screening · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeNewborn screening (NBS) for severe combined immunodeficiency (SCID) is based on the detection of T-cell receptor excision circles (TRECs). TRECs are a sensitive biomarker for T-cell lymphopenia, but not specific for SCID. This creates a palette of secondary findings associated with low T-cells that require follow-up and treatment or are non-actionable. The high rate of (non-actionable) secondary findings and false-positive referrals raises questions about the harm-benefit-ratio of SCID screening, as referrals are associated with high emotional impact and anxiety for parents.
methodsAn alternative quantitative TREC PCR with different primers was performed on NBS cards of referred newborns (N = 56) and epigenetic immune cell counting was used as for relative quantification of CD3 + T-cells (N = 59). Retrospective data was used to determine the reduction in referrals with a lower TREC cutoff value or an adjusted screening algorithm.
resultsWhen analyzed with a second PCR with different primers, 45% of the referrals (25/56) had TREC levels above cutoff, including four false-positive cases in which two SNPs were identified. With epigenetic qPCR, 41% (24/59) of the referrals were within the range of the relative CD3 + T-cell counts of the healthy controls. Lowering the TREC cutoff value or adjusting the screening algorithm led to lower referral rates but did not prevent all false-positive referrals.
conclusionsSecond tier tests and adjustments of cutoff values or screening algorithms all have the potential to reduce the number of non-actionable secondary findings in NBS for SCID, although second tier tests are more effective in preventing false-positive referrals.
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