Supplementary parenteral arginine corrects hypoargininaemia and rebalances plasma amino acid profiles in very preterm infants receiving parenteral nutrition: A prospective study.

Arginine-supplemented PN significantly increased plasma arginine levels in very preterm infants compared to standard PN by day 10.

• Median day 10 plasma arginine level was 85 (52-146) µmol/L for 18 g/100 g AA arginine vs 41 (28-54) µmol/L for control (P < 0.0001).
• Standard PN contained 6.3 g/100 g AA arginine; supplemented PN contained 18 g/100 g AA arginine.
• The highest mean daily arginine intake was on day 7: 521 mg/kg/day (SD 142 mg/kg/day) at the 18 g arginine/100 g parenteral AA dose.
• VPIs were at less than 30 weeks' gestation and allocated according to intervention PN availability.

Arginine-supplemented PN significantly reduced total essential amino acid (EAA) plasma levels compared to standard PN.

• Median day 10 total EAA levels were 896 (750-1142) µmol/L for 18 g/100 g AA arginine vs 1220 (1031-1428) µmol/L for control (P < 0.05).
• Standard PN-dependent VPIs showed overprovision of essential AA alongside arginine deficiency.
• The arginine-supplemented formulation rebalanced the plasma AA profile by both correcting hypoargininaemia and reducing excess EAA.

Blood ammonia levels did not differ significantly between arginine-supplemented and standard PN groups.

• Median blood ammonia levels were 46 (24-65) µmol/L vs 51 (40-62) µmol/L for supplemented vs control groups respectively (P = 0.28).
• Point-of-care testing was used to measure ammonia levels.
• Blood ammonia levels were not useful in identifying individual arginine deficiency.

Higher plasma arginine levels achieved through parenteral supplementation were not sustained once parenteral arginine was discontinued.

• Plasma AA levels were measured on days 3, 10, and 30 using ion exchange chromatography.
• The loss of elevated arginine levels after PN discontinuation suggests enteral nutrition alone does not maintain the same arginine concentrations achieved by supplemented PN.
• This finding has potential implications for growth and immune/inflammatory responses in very preterm infants.

Standard PN for very preterm infants consistently showed overprovision of essential amino acids and arginine deficiency.

• Standard PN contained 6.3 g/100 g AA arginine, which was associated with hypoargininaemia.
• Plasma AA profiles in PN-dependent VPIs consistently show overprovision of EAA and arginine deficiency.
• This imbalance may have implications for growth and immune/inflammatory responses.
• The final PN AA formulation design containing 18 g/100 g AA was derived through a series of separate physiological studies.