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  • Clinical Research Article
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Increased mortality in infants with abnormal T-cell receptor excision circles

Pediatric Research (2024)Cite this article

Abstract

Background

T-Cell Receptor Excision Circles based newborn screening (TREC-NBS) allows for early detection of T-cell lymphopenia in infants with primary immunodeficiency disorders (PIDD). The utility of abnormal TREC-NBS in infants without PIDD is not well studied. We sought to evaluate the association of abnormal TREC-NBS with mortality.

Methods

365,207 TREC-NBS from October 2011 to December 2014 were reviewed. 467 newborns had abnormal screens and did not meet the criteria for a PIDD diagnosis. Cases were matched to controls (1:3) based on gestational age, birth weight, neonatal intensive care unit status (NICU), and race. Data were obtained through NBS, birth and death certificates records from the Michigan Department of Health and Human Services (MDHHS) databases.

Results

Infants with abnormal TREC-NBS had higher mortality even when PIDD was ruled-out. Transient abnormal TREC-NBS was not associated with higher mortality, but unresolved or late abnormal TREC-NBS was associated with higher mortality. Infants with late abnormal TREC-NBS had severe prematurity, lower birth weight, lower Apgar scores, and higher percentage of congenital anomalies.

Conclusion

Infants with abnormal TREC-NBS may be at a higher risk of morbidity and mortality and should be carefully followed, especially if discharged home before a repeat screen can be completed.

Impact

  • This study explores the risk factors and mortality for newborns with secondary T-cell lymphopenia captured on T-Cell Receptor Excision Circles based newborn screening (TREC-NBS).

  • Abnormal TREC-NBS allows for prompt life-saving interventions for primary immunological conditions such as Severe Combined Immunodeficiency (SCID), but can also be associated with non-immunologic conditions.

  • Unresolved and late abnormal TREC-NBS is associated with higher mortality even without primary immunodeficiency, likely detected in infants with more severe prematurity, lower birth weight, and congenital anomalies.

  • TREC-NBS positive infants with secondary T-cell lymphopenia require special attention and close monitoring.

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Data availability

The data that support the findings of this study are available from Michigan Department of Health and Human Services but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Michigan Department of Health and Human Services.

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Acknowledgements

We would like to thank the Michigan Primary Immunodeficiency Disorders Quality Improvement Committee (PIDQIC) members, especially Dr. Ulrich Duffner (Michigan State University/Helen DeVos Children’s Hospital), Dr. Sureyya Savasan (Children’s Hospital of Michigan/Central Michigan University College of Medicine), Dr. Nicholas Hartog (Helen DeVos Children’s), Mary Fredrickson (Children’s Hospital of Michigan) and Mary Kleyn (Michigan Department of Community Health) for their support of this project, insightful comments and review of the manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Allergy/Immunology, Children’s Hospital of Michigan, Detroit, MI, USA

    Jenny Huang, Ashwin Shankar, Divya Seth & Pavadee Poowuttikul

  2. Central Michigan University, College of Medicine, Mt. Pleasant, MI, USA

    Jenny Huang, Ronald Thomas, Divya Seth & Pavadee Poowuttikul

  3. Michigan Department of Health and Human Services, Lansing, MI, USA

    Isabel Hurden & Joseph Hill

  4. Wayne State University, School of Medicine, Detroit, MI, USA

    Elizabeth Secord

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  1. Jenny Huang
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  6. Divya Seth
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  8. Pavadee Poowuttikul
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jenny Huang, Ashwin Shankar, Isabel Hurden, Ronald Thomas and Pavadee Poowuttikul. The first draft of the manuscript was written by Jenny Huang and Ashwin Shankar, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Pavadee Poowuttikul.

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Competing interests

Drs. Pavadee Poowuttikul and Jenny Huang have research/grant support from Respiri for a project titled “The Use of Electronic Monitoring Device for Wheezing (Wheezo) and Remote Monitoring Program (RMP) to Improve Asthma Outcome in Inner-City Children” The other authors have indicated they have no potential conflicts of interest to disclose.

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Huang, J., Shankar, A., Hurden, I. et al. Increased mortality in infants with abnormal T-cell receptor excision circles. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03121-7

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  • DOI: https://doi.org/10.1038/s41390-024-03121-7

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