Ten Years of Newborn Screening for Severe Combined Immunodeficiency (SCID) in Massachusetts

Hale, Jaime E.; Platt, Craig D.; Bonilla, Francisco A.; Hay, Beverly N.; Sullivan, John L.; Johnston, Alicia; Pasternack, Mark S.; Hesterberg, Paul E.; Meissner, H. Cody; Cooper, Ellen; Barmettler, Sara; Farmer, Jocelyn R.; Fisher, Donna; Walter, Jolán E.; Yang, Nancy; Sahai, Inderneel; Eaton, Roger B.; DeMaria, Alfred; Notarangelo, Luigi D.; Comeau, Anne Marie

doi:10.1016/j.jaip.2021.02.006

Cited by 26 publications

(21 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to our study, PPV SCID in other reports using the TREC assay without a secondtier method was consistently below 10% [28,[35][36][37][38]. Gizewska et al obtained a TREC-based PPV SCID of approximately 17% with a two-step referral procedure, according to which requesting a second screening card due to low but detectable TRECs was not counted as a referral [26].…”

Section: Discussionsupporting

confidence: 88%

“…During the first year of screening, 73 children with low TREC values were referred for clinical examination, resulting in a referral rate of 0.063%. Other screening programs have reported referral rates between 0.02% and 0.17% using either proprietary methods or commercial systems from different manufacturers [11,15,26,28,[33][34][35][36]. The comparatively high referral rate in our study can be explained by the fact that only one referral cut-off was used leading to contact with a specialist care centre without delay, independent of gestational age.…”

Section: Discussionmentioning

confidence: 55%

“…The comparatively high referral rate in our study can be explained by the fact that only one referral cut-off was used leading to contact with a specialist care centre without delay, independent of gestational age. Other programs requested a second screening card for result verification in cases of TRECs below cut-off but detectable or for premature children with abnormal results [15,28,[34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

First Year of TREC-Based National SCID Screening in Sweden

Göngrich

Ekwall

Sundin

et al. 2021

IJNS

View full text Add to dashboard Cite

Screening for severe combined immunodeficiency (SCID) was introduced into the Swedish newborn screening program in August 2019 and here we report the results of the first year. T cell receptor excision circles (TRECs), kappa-deleting element excision circles (KRECs), and actin beta (ACTB) levels were quantitated by multiplex qPCR from dried blood spots (DBS) of 115,786 newborns and children up to two years of age, as an approximation of the number of recently formed T and B cells and sample quality, respectively. Based on low TREC levels, 73 children were referred for clinical assessment which led to the diagnosis of T cell lymphopenia in 21 children. Of these, three were diagnosed with SCID. The screening performance for SCID as the outcome was sensitivity 100%, specificity 99.94%, positive predictive value (PPV) 4.11%, and negative predictive value (NPV) 100%. For the outcome T cell lymphopenia, PPV was 28.77%, and specificity was 99.95%. Based on the first year of screening, the incidence of SCID in the Swedish population was estimated to be 1:38,500 newborns.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

First Year of TREC-Based National SCID Screening in Sweden

Göngrich

Ekwall

Sundin

et al. 2021

IJNS

View full text Add to dashboard Cite

show abstract

“…In the United States screening was first implemented in Wisconsin in 2008, and in all 50 states by 2018. This has allowed for earlier diagnosis and treatment, typically with hematopoietic stem cell transplant, gene therapy, or enzyme replacement, and has led to improved survival of infants with SCID (2)(3)(4)(5)(6). These outcomes are highlighted in a study from the Primary Immune Deficiency Treatment Consortium which found 94% survival among infants who were transplanted by 3.5 months age, versus 50% survival among those who had active infection and were transplanted later than 3.5 months age (7).…”

Section: Introductionmentioning

confidence: 99%

Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S.

et al. 2021

View full text Add to dashboard Cite

The implementation of severe combined immunodeficiency (SCID) newborn screening has played a pivotal role in identifying these patients early in life as well as detecting various milder forms of T cell lymphopenia (TCL). In this study we reviewed the diagnostic and clinical outcomes, and interesting immunology findings of term infants referred to a tertiary care center with abnormal newborn SCID screens over a 6-year period. Key findings included a 33% incidence of non-SCID TCL including infants with novel variants in FOXN1, TBX1, MYSM1, POLD1, and CD3E; 57% positivity rate of newborn SCID screening among infants with DiGeorge syndrome; and earlier diagnosis and improved transplant outcomes for SCID in infants diagnosed after compared to before implementation of routine screening. Our study is unique in terms of the extensive laboratory workup of abnormal SCID screens including lymphocyte subsets, measurement of thymic output (TREC and CD4TE), and lymphocyte proliferation to mitogens in nearly all infants. These data allowed us to observe a stronger positive correlation of the absolute CD3 count with CD4RTE than with TREC copies, and a weak positive correlation between CD4RTE and TREC copies. Finally, we did not observe a correlation between risk of TCL and history of prenatal or perinatal complications or low birth weight. Our study demonstrated SCID newborn screening improves disease outcomes, particularly in typical SCID, and allows early detection and discovery of novel variants of certain TCL-associated genetic conditions.

show abstract

“…In 2013, Ward et al reported that premature infants posed a challenge to population-based screening due to their immature immune systems [ 31 ]. In the last few years, several NBS programs have published their experience in screening the premature infant population for SCID and the difficulties of balancing false-positive results with ensuring screening catches true SCID cases in the premature infant population [ 32 , 33 , 34 , 35 , 36 ]. Here, we report our study results assessing the relationship between TREC copy numbers and gestational age in weeks.…”

Section: Introductionmentioning

confidence: 99%

Newborn Screening for Severe Combined Immunodeficiency: Do Preterm Infants Require Special Consideration?

Atkins¹,

Cogley²,

Baker

2021

IJNS

View full text Add to dashboard Cite

The Wisconsin Newborn Screening (NBS) Program began screening for severe combined immunodeficiency (SCID) in 2008, using real-time PCR to quantitate T-cell receptor excision circles (TRECs) in DNA isolated from dried blood NBS specimens. Prompted by the observation that there were disproportionately more screening-positive cases in premature infants, we performed a study to assess whether there is a difference in TRECs between full-term and preterm newborns. Based on de-identified SCID data from 1 January to 30 June 2008, we evaluated the TRECs from 2510 preterm newborns (gestational age, 23–36 weeks) whose specimens were collected ≤72 h after birth. The TRECs from 5020 full-term newborns were included as controls. The relationship between TRECs and gestational age in weeks was estimated using linear regression analysis. The estimated increase in TRECs for every additional week of gestation is 9.60%. The 95% confidence interval is 8.95% to 10.25% (p ≤ 0.0001). Our data suggest that TRECs increase at a steady rate as gestational age increases. These results provide rationale for Wisconsin’s existing premature infant screening procedure of recommending repeat NBS following an SCID screening positive in a premature infant instead of the flow cytometry confirmatory testing for SCID screening positives in full-term infants.

show abstract

Ten Years of Newborn Screening for Severe Combined Immunodeficiency (SCID) in Massachusetts

Cited by 26 publications

References 24 publications

First Year of TREC-Based National SCID Screening in Sweden

First Year of TREC-Based National SCID Screening in Sweden

Immunological Findings and Clinical Outcomes of Infants With Positive Newborn Screening for Severe Combined Immunodeficiency From a Tertiary Care Center in the U.S.

Newborn Screening for Severe Combined Immunodeficiency: Do Preterm Infants Require Special Consideration?

Contact Info

Product

Resources

About