The implementation of newborn screening (NBS) for primary immunodeficiency (PID) has led to an increasing frequency of low T cell receptor excision circle (TREC) results among preterm infants in Neonatal Intensive Care Units (NICUs). However, the diagnostic process poses significant challenges: confirmatory testing requires substantial blood volumes and notifying parents of a potential immune deficiency significantly exacerbates the anxiety of those already dealing with their infant’s fragility. These issues raise critical questions regarding the clinical benefit of early diagnosis in preterm infants and whether these dilemmas are shared across institutions.
We conducted a survey among members of the Japanese Neonatologist Association to investigate current management strategies and clinical responses to low TREC levels in preterm infants.
The survey results highlighted widespread clinical uncertainty. Respondents emphasized the urgent need for preterm-specific cutoff values, optimization of blood sampling timing, the option to defer testing during acute phases, and a deeper understanding of preterm-specific pathophysiology among clinical immunologists.
Neonatal care must account for the physiological immaturity of the immune system. While the NICU provides stringent infection control, the absence of fever does not necessarily indicate immunocompetence. Furthermore, preterm management involves unique constraints, such as limited blood volume and the frequent necessity of blood transfusions, which can complicate the interpretation of TREC results. Clinical dilemmas also extend to essential care: breastfeeding is vital for neurodevelopment and the prevention of complications like necrotizing enterocolitis, and family contact is regarded as a critical medical intervention for psychological support and parent-infant bonding. However, these may be restricted if PID is suspected. Furthermore, the timeline for clinical decision-making is tight, as the first live vaccines are typically administered around 2–3 months of corrected age.
From the perspective of neonatal medicine, we aim to advocate for a balanced screening framework that ensures the reliable detection of PID while safeguarding the specialized care and well-being of preterm infants.
