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

Area of Science:

• Immunology
• Neonatal Medicine
• Genetics

Background:

• The Wisconsin Newborn Screening (NBS) Program screens for severe combined immunodeficiency (SCID) using T-cell receptor excision circles (TRECs).
• A higher rate of SCID screening-positive results was observed in premature infants compared to full-term infants.

Purpose of the Study:

• To investigate the relationship between TRECs and gestational age in newborns.
• To determine if TREC levels differ significantly between preterm and full-term infants.

Main Methods:

• Analysis of de-identified SCID screening data from January 1 to June 30, 2008.
• Quantification of TRECs in DNA from dried blood NBS specimens using real-time PCR.
• Linear regression analysis to assess the correlation between TRECs and gestational age.

Main Results:

• A total of 2510 preterm newborns (23-36 weeks gestation) and 5020 full-term newborns were included.
• TRECs showed a statistically significant increase with advancing gestational age (9.60% increase per week, p ≤ 0.0001).
• The 95% confidence interval for the increase was 8.95% to 10.25%.

Conclusions:

• TREC levels increase steadily as gestational age advances in newborns.
• These findings support Wisconsin's current NBS protocol for SCID, which includes repeat screening for premature infants who test positive.
• The results provide a rationale for differentiating confirmatory testing strategies for SCID screening positives based on gestational age.