P0733 - Enteral feed is a poor source of substrates for endogenous nitric oxide production in preterm infants – a pilot study

Background: Bronchopulmonary dysplasia (BPD) prevalence has increased with an increase in the survival of premature infants (PI). BPD associated PH (BP-PH) occurs in 1/4th of the infants with BPD due to high pulmonary vascular resistance (PVR). The endogenous NO production helps with decreasing the PVR. L-arginine (Arg) and L-citrulline (Cit) helps with the production of endogenous nitric oxide (NO). We speculate PI with BPD needs more NO to reduce PVR compared to infants without BPD which makes Arg/Cit as a semi-essential amino acid in infants with BPD-PH. TPN contains a significant amount of Arg (1mg/1mL) to metabolize ammonia via the urea cycle. Breast milk and formula have very low levels of Arg. We aimed to measure the effect of weaning TPN on serial Arg, Cit, and endogenous NO production measured by urinary nitrates and nitrites to explore an area of potential future intervention. Design/

Methods: After IRB approval, PI (≤ 30 wks and ≤1500 g) were included in the study (n=16). PI with congenital anomalies (except PDA or ASD) and necrotizing enterocolitis were excluded. Blood & urine levels of Arg and Cit were measured on days 1, 3, 7, 14, and 21 by liquid chromatography and mass spectrometry (LC-MS/MS); urinary NO and nitrite (NO ) were measured by gas chromatographic-mass spectrometer (GC-MS). Serum and urine levels of Asymmetric and Symmetric dimethylarginine (ADMA, SDMA), were also measured to know the dynamics of the Arg-NO pathway. ADMA and SDMA are antagonists of eNOS which decrease NO production. LC-MS/MS chromatogram of amino acids was quantified prior to use (Figure).

Results: Serial plasma and urinary Arg; and urinary nitrates (indicator for endogenous NO production) showed a significant decrease at all time points (Table), as TPN intake was being weaned and enteral intake was increased. ADMA and SDMA levels did not show any significant changes.Conclusion(s): There was a serial decrease in plasma and urine Arg along with urinary nitrates with the weaning of TPN. We speculate that this drop in Arg levels in PI after discontinuation of TPN can be a potential risk factor for predisposing them to develop BPD-PH. This pilot study helps to find a possible area of future intervention in PI at risk for developing BPD-PH.