Role of amino acid supplementation in the prevention of necrotizing enterocolitis in preterm neonates – a review of current evidences

Abstract

Background: Necrotizing enterocolitis (NEC) is one of the most common acute and fatal gastrointestinal emergency in very low birth weight (VLBW) preterm neonates with mortality range from 15 to 30%. NEC is likely due to multifactorial process such as oxidative injury, ischemic necrosis, and over-reactive inflammatory response to intestinal microbes.Aims: To evaluate the role of amino acid supplementation for reduction of neonatal NEC in preterm neonates.Method: The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical s Service (CAS) and other database.Results: This review included 15 RCTs that fulfilled inclusion criteria. The total neonates enrolled in these different RCT are 3424 (amino acid group 1711 and control 1713). Almost all participating neonates were of VLBW or extremely low birth weight (ELBW). In two trials, birth weight was between 1500–2000 grams. The intervention was started within first few days after birth and continued up to 30th day of postnatal age in most of the trials. In two trials, intervention was continued up to 120th day of postnatal age. Arginine, glutamine and N-acetyl cysteine (NAC) were used at the dose of 1.5 mol/kg/day (261 mg/kg/day), 0.3 grams/kg/day and 16–32 mg/kg/day, respectively.Conclusion: Role of amino acid in the prevention of neonatal NEC is not exclusively supported by the current evidence. Only three studies were able to show reduction in the incidence of NEC with amino acid supplementation (arginine, glutamine), and the remaining studies did not report any positive effect. Amino acid supplementation was not associated with significant reduction in mortality due to any causes. However, arginine supplementation was associated with significant reduction in mortality due to NEC. Two studies on glutamine were reported significant reduction in the incidence of invasive infection. Only one study reported significant positive effects on growth parameters and less time to reach full enteral feeds. None of the studies showed any effect on the duration of hospital stay.