154 - Exploring the Relationship Between SGA and Abnormal SCID Tests in State-Mandated Screening of Newborns

Publication Number: 154.4896

Humza Zaidi, University of Connecticut School of Medicine, Avon, CT, United States; Brooke Onwenu, University of Connecticut School of Medicine, West Bloomfield, MI, United States; Hassan El Chebib, Connecticut Children's Medical Center, Hartford, CT, United States; Naveed Hussain, Connecticut Children's Medical Center, Farmington, CT, United States

Background: Severe Combined Immunodeficiency (SCID) is a genetic condition characterized by the near absence of T, B, and NK cells, rendering affected infants highly susceptible to infections. Early detection is imperative to reduce mortality risks. Newborn SCID screening measures T-cell receptor excision circles (TRECs), a reliable biomarker for mature T-cell production, where low TREC counts may indicate SCID. It is postulated that small for gestational age (SGA) infants may trigger a false-positive result due to poor fetal growth compromising thymic function.

Objective: This study aims to evaluate the association between TREC count, reported as abnormal SCID screening results, and SGA status.

Design/Methods: This retrospective study analyzed data from 380 infants admitted to Connecticut (CT) Children’s NICU between January 5, 2017 - October 19, 2023. Infants were classified as SGA or non-SGA based on birth weight nomograms. SCID screening results were obtained from the CT newborn screening program, with abnormal results confirmed through repeat and confirmatory tests. False-positive SCID screens were identified, and a chi-square analysis assessed differences in false-positive rates between SGA and non-SGA infants. Multiple logistic regression analysis was subsequently performed to adjust for variables such as birth weight, gestational age, premature rupture of membranes (PPROM), and sex.

Results: Among the 380 infants, 64 SGA and 281 non-SGA infants had normal SCID results, while 19 SGA and 16 non-SGA infants had false-positive results. The false-positive rate for SCID screening was higher in SGA infants (22.89%) when compared to non-SGA infants (5.38%). Chi-square analysis confirmed a significant association between SGA status and false-positive SCID results (χ² = 33.999, p < 0.001). This association remained significant (p < 0.05) after controlling for birth weight, gestational age, PPROM, and sex using multiple logistic regression analysis.

Conclusion(s): These findings suggest that SGA infants are at an elevated risk for false-positive SCID screening results. Further research will evaluate potential confounding factors, such as maternal steroid use and hypertension. Investigating the relationship between abnormal TREC counts and recent thymic emigrants (RTE cells) may also enhance our understanding of thymic involvement in low TREC results, especially in SGA or intrauterine growth-restricted (IUGR) neonates.

SCID Screening Results by Gestational Age Group
Distribution of initial SCID screening outcomes among small for gestational age (SGA) and appropriate/large for gestational age (AGA/LGA) infants in the study cohort. A total of 35 infants initially screened positive for SCID, with 19 false positives observed in the SGA group and 16 in the AGA/LGA group. This table illustrates the disproportionate rate of false-positive results among SGA infants, supporting the observed association between SGA status and an elevated risk of false-positive SCID outcomes, as discussed in the results section.

False-Positive SCID Rates by Group
Comparison of false-positive SCID screening rates between small for gestational age (SGA) and appropriate/large for gestational age (AGA/LGA) infants. SGA infants demonstrated a significantly higher false-positive rate (22.89%) compared to AGA/LGA infants (5.38%), suggesting an association between SGA status and increased likelihood of false-positive SCID results.