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Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma arginine and citrulline levels—a pilot randomized trial

Journal of Perinatology (2023)Cite this article

Subjects

Abstract

Objective

Deficiencies of citrulline and arginine have been associated with adverse outcomes in preterm-infants and data regarding enteral supplementation in preterm infants is limited.

Study design

This randomized -trial [NCT03649932] included 42 preterm infants (gestational age ≤33 weeks) randomized to receive enteral L-citrulline in low (100 mg/kg/day), medium (200 mg/kg/day) and high-dose (300 mg/kg/day) groups for 7 days. Plasma citrulline and arginine levels were obtained pre-and-post supplementation and efficacy was determined by a significant increase in levels after supplementation. A p < 0.05 was considered significant. Safety monitoring included blood-pressure-monitoring as well as complications and death during hospitalization.

Results

A total of 40/42 (95%) of the recruits completed the 7-day supplementation with no adverse events. Plasma-citrulline levels increased significantly in all three groups while plasma-arginine levels increased significantly in the high-dose group.

Conclusion

Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma citrulline and arginine levels.

Clinical trial registration

NCT03649932 https://clinicaltrials.gov/ct2/show/NCT03649932.

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Fig. 1: Enteral L-citrulline supplementation significantly increased plasma levels of citrulline in all three groups.
Fig. 2: Enteral L-citrulline supplementation significantly increased plasma levels of arginine in and the high dose group.

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Data availability

Deidentified individual participant data (including data dictionaries) will be made available in addition to study protocols, the statistical analysis plan, and the informed consent form. The data will be made available upon publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Proposals should be submitted to skjain@utmb.edu.

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Authors and Affiliations

  1. Department of Neonatology, Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA

    Amna Qasim, Mohammad Q. Mehdi, Snigdha Bhatia, Maria E. Franco-Fuenmayor & Sunil K. Jain

  2. Department of Pediatrics, Section of Pediatric Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Amna Qasim

  3. Department of Pediatric Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Mohammad Q. Mehdi

  4. Division of Pediatric Cardiology, Department of Pediatrics, Children’s Hospital of Michigan, Central Michigan University, Detroit, MI, USA

    Snigdha Bhatia

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  1. Amna Qasim
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  4. Maria E. Franco-Fuenmayor
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  5. Sunil K. Jain
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Contributions

AQ, MQM, SB drafted the initial manuscript, and reviewed and revised the manuscript. AQ, MQM, SB, and MEF-F obtained consent, collected data, carried out the initial analyses, and reviewed and revised the manuscript. AQ and SKJ conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Sunil K. Jain.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study was approved by the Institutional Review Board at the University of Texas Medical Branch, Galveston, TX. Consent was obtained from patients prior to induction into the study. The study was in accordance with the Declaration of Helsinki.

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Qasim, A., Mehdi, M.Q., Bhatia, S. et al. Enteral L-citrulline supplementation in preterm infants is safe and effective in increasing plasma arginine and citrulline levels—a pilot randomized trial. J Perinatol (2023). https://doi.org/10.1038/s41372-023-01761-x

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  • DOI: https://doi.org/10.1038/s41372-023-01761-x

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