241 - Optimal enteral citrulline supplementation dosing in preterm infants

Poster Number: 241
Publication Number: 241.222

Maria E. Franco Fuenmayor, University of Texas Medical Branch School of Medicine, Galveston, TX, United States; Snigdha Bhatia, Children’s Hospital of Michigan, Detroit, MI, United States; Mohammad Q. Mehdi, University of Texas Medical Branch School of Medicine, Galveston, TX, United States; Amna Qasim, Baylor College of Medicine/Texas Children’s Hospital, Houston, TX, United States; Sunil K. Jain, University of Texas Medical Branch School of Medicine, Galveston, TX, United States

Background: Preterm infants (PI) are at high risk for necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), BPD associated pulmonary hypertension (BPD-PH) and sepsis. Citrulline (CIT) is converted to arginine (ARG) and serves as a precursor for endogenous synthesis of nitric oxide (NO). Research suggests that lower levels of ARG and CIT are found in affected infants. A prior study has shown that levels downtrend when infants are exclusively enterally fed.  

Objective: We hypothesized that enteral CIT supplementation can safely increase plasma CIT and ARG, thus increasing endogenous NO to potentially mitigate complications.

Design/Methods: A double blinded, randomized controlled trial (NCT03649932) of 42 PI (≤32 weeks) was conducted in fully enterally fed infants using low, medium, and high doses of CIT as a 10% solution at 100, 200 and 300 mg/kg/day twice daily. Infants had not received parenteral nutrition 1 week prior to initiation. Adverse events including hypotension, NEC, BPD, BPD-PH and sepsis were monitored. Blood samples were collected prior to starting (Day 0) and at 7 days (Day 7). Plasma trough CIT and ARG levels were measured by liquid chromatography mass spectrometry.  Demographics with descriptive statistics were obtained. Data analysis was conducted using paired t-test in SPSS.

Results: 42 PI were recruited with a mean gestational age of 29.4±2 weeks and birthweight 1275 ± 388g. For infants born ≤29 weeks, arginine levels were higher than for >30 weeks irrespective of dosing (p=0.049). Plasma CIT levels increased with a mean 117umol/L (95% CI 60-175,p=0.001) in medium and mean 144umol/L (95% CI 51-238,p=0.006) in the high groups. ARG levels increased to mean 77 (95% CI 2-153,p=0.046) in medium and mean 103 (95% CI 24-181,p=0.020) in the high group. ARG levels ≤29 weeks are statistically significantly higher in the high dose group (p=0.04). There were no associated side effects with supplementation at any dosing.Conclusion(s): Enteral CIT supplementation in PI is well-tolerated and effective in increasing plasma CIT and ARG levels. ARG levels are significantly higher in preterm infants born at ≤29 weeks who receive supplementation, optimally at higher dosing and may show a benefit to ameliorate potential complications. A double blinded, placebo controlled RCT is underway to evaluate the role of enteral CIT supplementation in these complications.
MFF PAS CV 2022.pdf
Table 1: Cohort CharacteristicsThe table displays the characteristics of the infants that received citrulline supplementation.