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

Abstract

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.

Keywords: Citrulline; Full enteral feeding; Necrotizing enterocolitis; Preterm infants; Survival; Treatment.