Plasma citrulline during the first 48 h after onset of necrotizing enterocolitis in preterm infants

Background: Levels of plasma citrulline (citrulline-P), a biomarker for enterocyte function, might be useful for the monitoring the course of necrotizing enterocolitis (NEC). Our aim was to evaluate whether citrulline-P levels during the first 48 h (h) after NEC onset were associated with need for surgery, survival, and intestinal recovery. Methods: In preterm infants with NEC (Bell's stage ≥2) we measured citrulline-P levels during the first 48 h after NEC onset. Categorizing the measurements into 0–8 h, 8–16 h, 16–24 h, 24–36 h, and 36–48 h, we determined the course of citrulline-P using linear regression analyses. Next, we analyzed whether citrulline-P levels measured at 0–24 h and 24–48 h differed between conservative and surgical treatment, survivors and nonsurvivors, and equal/below and above total group's median time to full enteral feeding (FEFt). Results: We included 48 infants, median gestational age 28.3 [IQR:26.0–31.4] weeks, birth weight 1200 [IQR:905–1524] grams. Citrulline-P levels decreased the first 48 h (B per time interval: -1.40 μmol, 95% CI, −2.73 to −0.07, p = 0.04). Citrulline-P was not associated with treatment, nor with survival. Citrulline-P at 0–24 h, but not 24–48 h, was higher in infants with FEFt ≤20 days than in infants with FEFt >20 days (20.7 [IQR:19.9–25.3] µmol/L (n = 13) vs. 11.1 [IQR:8.4–24.0] µmol/L (n = 11), p = 0.049), with a citrulline-P cut-off value of 12.3 μmol/L. Conclusion: Citrulline-P levels decreased the first 48 h after NEC onset, suggesting on-going intestinal injury. In survivors, measuring citrulline-P in the first 24 h after NEC onset may provide an indication for intestinal recovery rate.