Abstract
BackgroundLevels 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. MethodsIn 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). ResultsWe 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. ConclusionCitrulline-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.
Highlights
One of the cornerstones of the treatment for necrotizing enterocolitis is a nil per mouth (NPO) regimen [1,2]
We identified 120 preterm infants with suspected necrotizing enterocolitis (NEC) who were eligible for inclusion, of whom 48 infants were diagnosed with proven NEC (Bell’s stage ≥ 2) (Fig. 1)
We found higher median citrulline-P levels during the first 24 h after NEC onset in infants with FEFt of 20 days or less than in those with FEFt more than 20 days (20.7 [interquartile range (IQR): 17.9–25.3] micromoles per litre (μmol/L) (n = 13) vs. 11.1 [IQR: 8.4–24.0) μmol/L (n = 11), p = 0.049)
Summary
One of the cornerstones of the treatment for necrotizing enterocolitis is a nil per mouth (NPO) regimen [1,2]. Establishing a suitable biomarker to indicate which NEC infants are ready for the reintroduction of enteral feeding is very relevant. One of these potential biomarkers is plasma citrulline (citrulline-P), which is a marker for enterocyte function [7,8,9,10,11,12,13]. Citrulline is a non-protein amino acid and a metabolic intermediate of the urea cycle It is synthesized from glutamine and glutamate in both liver and small intestine [14,15]. Levels of plasma citrulline (citrulline-P), a biomarker for enterocyte function, might be useful for the monitoring the course of necrotizing enterocolitis (NEC). Results: We included 48 infants, median gestational age 28.3 [IQR:26.0–31.4] weeks, birth weight 1200
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