501 - Challenges in newborn screening for primary immunodeficiency among preterm infants: Clinical features of patients with low TREC/KREC values

Publication Number: 3482.501

Marika Amizuka, Saitama Medical University Hospital, General Medical Center, Saitama-shi, Saitama, Japan; Fumihiko Namba, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan; Kanako Itoh, Saitama medical center, Saitama medical university, Kawagoe, Saitama, Japan

Background: Primary immunodeficiency (PID) often presents in the neonatal period, and its early diagnosis is essential to prevent severe infections and improve outcomes. Measurement of T-cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) in newborn screening reflects newly generated T- and B-cells, respectively, providing useful markers for early detection of PID. However, preterm infants frequently exhibit low TREC and KREC values unrelated to PID, leading to high false-positive rates. The optimal timing for retesting and subsequent evaluation in preterm infants remains unclear.

Objective: To explore the clinical characteristics and temporal changes in preterm infants with low TREC/KREC values and to obtain baseline data for establishing criteria for retesting and further evaluation.

Design/Methods: This retrospective single-center study included preterm infants born at < 32 weeks’ gestation and admitted to the neonatal intensive care unit at Saitama Medical University General Medical Center between September 2024 and June 2025. The data of infants who screened positive for PID were analyzed. Screening was considered positive if TREC and KREC were < 300 or < 250 copies/μL, respectively. The patients’ perinatal and clinical characteristics (gestational age, birth weight, sex, small-for-gestational-age status, immunoglobulin administration, and hydrops) and laboratory findings [white blood cell count, lymphocyte ratio, immunoglobulin G (IgG), and IgM] were retrospectively reviewed.

Results: Nine infants screened positive for PID, including eight with low TREC value and one with low KREC value. None were ultimately diagnosed with PID. All cases were extremely preterm or extremely low birth weight infants. In seven of the eight patients with low TREC values, retesting of the same specimens confirmed that the values remained below the cutoff level.

Conclusion(s): All nine infants with positive TREC/KREC screening results in our institution were ultimately not diagnosed with PID. Nationwide data collection, including both healthy and affected infants, is needed to clarify the associations between gestational age, birth weight, and TREC/KREC values, and to develop appropriate retesting and evaluation protocols tailored for preterm infants to improve the accuracy of newborn screening for PID.