Enteral L‐Arginine Supplementation for Prevention of Necrotizing Enterocolitis in Very Low Birth Weight Neonates

Abstract

Necrotizing enterocolitis (NEC) is the most common acquired gastrointestinal disease in premature infants and has high mortality and morbidity. Endothelial nitric oxide is an important regulator of vascular perfusion and is synthetized from the amino acid L-arginine. Hypoargininemia is frequently observed in preterm neonates and may predispose them to NEC. Our objective was to determine the effect of enteral L-arginine supplementation on the incidence and severity of NEC in very low birth weight (VLBW) neonates. We conducted a parallel blind randomized pilot study, comprising VLBW neonates with birth weight ≤1500 g and gestational age ≤34 weeks. VLBW neonates were randomly assigned to receive enteral L-arginine supplementation (1.5 mmol/kg/d bid) between the 3rd and 28th day of life or placebo. Diagnosis and classification of NEC were done according to modified Bell's criteria. Eighty-three neonates were randomized to the arginine (n = 40) or placebo (n = 43) group. No adverse effects were observed in neonates receiving L-arginine supplementation. The incidence of NEC stage III was significantly lower in the arginine-supplemented group (2.5% vs 18.6%, P = .030). Enteral L-arginine supplementation of 1.5 mmol/kg/d bid can be safely administered in VLBW neonates from the 3rd to the 28th day of life. Enteral L-arginine supplementation appears to reduce the incidence of stage III NEC in VLBW infants. Larger studies are needed to further evaluate the effect of L-arginine supplementation in preventing NEC in VLBW infants.