Defining Normal Citrulline Levels as a Diagnostic Tool for Screening of Gastrointestinal Disease in Premature Infants

Since the first description of citrulline as a potential marker for intestinal function in 1998, its use has been investigated in a variety of disease processes including Short Bowel Syndrome, Celiac disease, chemotherapy and radiation induced intestinal injury, infections producing intestinal cytopathic effects like Adenovirus, and predicting rejection in intestinal transplantation. The use of citrulline levels as a diagnostic tool to predict gastrointestinal disease in the premature population has not been properly addressed. The introduction of enteral nutrition in the premature infant is a process of trial and error, knowing that the immaturity of the gastrointestinal system may lead to frequent episodes of feeding intolerance. This is augmented by the fear of the development of necrotizing enterocolitis (NEC) once feeds are commenced. NEC is a condition characterized by disruption of the intestinal epithelial barrier, a pathogenic process shared with some of the conditions mentioned above for which citrulline has proven clinically useful. A normal pattern of citrulline production has not been established in the premature population. Previous studies have shown decreased levels of glutamine and arginine in premature infants up to 10 days prior to the development of necrotizing enterocolitis. Glutamine and arginine are two amino acids closely involved in the synthesis and catabolism of citrulline. The investigators therefore hypothesize that defining a normal pattern of citrulline production in the premature population may prove to be a clinically useful diagnostic tool to screen for gastrointestinal disease.