Temporal Relationships Between Systemic Inflammatory Markers and Urinary I-FABP in Preterm Infants: Evidence that Intestinal Inflammation Precedes Systemic Inflammation

Objective: Preterm infants exhibit an aberrant inflammatory response, characterized by elevated intestinal and systemic inflammatory markers, and their relationship remains poorly understood in neonatal immunology. Our study aimed to examine the association and temporal relationship between intestinal and systemic inflammation. Study Design: This retrospective observational study included n = 74 infants who were born preterm (<34 weeks of gestation). Urine and blood samples were collected throughout the hospitalization period between 1-20 weeks of life. Urinary I-FABP (intestinal fatty acid binding protein) was measured as a marker of intestinal inflammation, and blood samples were analyzed for systemic inflammatory markers, including CRP, ICAM-1, IL-1β, IL-6, and IL-8. Unadjusted linear mixed-effects models were used to assess longitudinal trends and both concurrent and lagged associations between urinary I-FABP and systemic inflammatory markers. Results: Our longitudinal analyses revealed a significant decrease in levels of I-FABP (ß = −0.32, p < 0.001), IL-6 (ß = −0.03, p = 0.003), and IL-8 (ß = −0.11, p < 0.001), and a significant increase in levels of ICAM-1 (ß = 0.04, p < 0.001) over time. Within the same week, I-FABP was significantly associated with all systemic inflammatory markers except for CRP. Lagged associations between I-FABP levels measured one week before systemic biomarker assessment to determine whether intestinal inflammation temporally precedes systemic inflammation revealed significant positive associations with ICAM-1, IL-1β, and IL-8 (ß = 0.14, p = 0.008; ß = 0.15, p = 0.009; ß = 0.36, p < 0.001, respectively). Conclusion: Our exploratory study revealed significant associations between urinary I-FABP and systemic inflammatory markers, with intestinal inflammation preceding systemic inflammation. These findings suggest a potential temporal progression from intestinal to systemic inflammation, offering new insight into inflammatory dynamics and immune responses in preterm infants.