The evidence for neonatal arginine supplementation - A narrative review

Arginine is proteomic conditionally essential amino acid in the neonatal period. As well as being necessary for protein synthesis and growth, it is a highly functional amino acid playing a key role in many metabolic pathways critical to neonatal health. These include the urea cycle and ammonia detoxification, spermidine synthesis, immune modulation and acting as the key substrate for nitric oxide synthesis. The arginine-nitric oxide (NO) pathway is an important mechanism by which hypoargininaemia may contribute to neonatal morbidity, particularly necrotising enterocolitis and potentially sepsis, pulmonary disease and post-operative recovery. The role of the inhibitory metabolite asymmetric dimethylarginine in the arginine-NO pathway has been recognised but the neonatal clinical implications have yet to be established. Neonates dependent on parenteral nutrition are particularly vulnerable to hypoargininaemia. Both parenteral and enteral arginine supplementation has been shown in a small number of clinical trials to reduce the risk of necrotising enterocolitis. This evidence has been sufficient to result in recommendations for arginine supplementation in systematic reviews and international guidelines. The potential benefits from reducing the risk of other neonatal complications such as sepsis and prolonged postoperative recovery have not been studied. No arginine side effects have been reported but the studies are not large enough to provide complete assurance. The methods of parenteral and enteral arginine supplementation also require further research to establish optimal timing, dose and target plasma level. Nevertheless, arginine supplementation relatively easy to implement in clinical practice and remains a potentially cost effective method in reducing serious neonatal morbidities.