REVIEW article
Front. Pediatr.
Sec. Neonatology
The Utility of Caffeine Citrate as a Neuroprotectant in the Early Life of Premature Newborns: A Literature Review of the Effects on Neurodevelopmental Outcomes
Provisionally accepted
- Oakland University William Beaumont School of Medicine, Rochester, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The incidence of prematurity-related complications has decreased due to advancements in medical preventive and supportive measures, but the rate of neurodevelopmental impairment secondary to prematurity continues to increase. Due to the high metabolic demand of the central nervous system during early development and the age-related sensitivity of the cerebral white matter, perinatal intermittent hypoxia can lead to significant cerebral pathology persisting into adulthood. Caffeine citrate is one of the mainstay medical treatments for apnea of prematurity and is widely used in many neonatal intensive care units. Caffeine citrate's benefits include reducing time on mechanical ventilation, enhancing extubation success, and decreasing the incidence of bronchopulmonary dysplasia. There is also mounting evidence that caffeine citrate benefits neurodevelopmental outcomes, attributable to its positive effect on respiratory status and other mechanisms. Research has shown that caffeine citrate exerts an anti-inflammatory effect via the antagonism of adenosine receptors, reduces the production of reactive oxygen species, and supports the plasticity of the central nervous system. This article aims to review the most up-to-date evidence on caffeine citrate's effects on neuroprotection and its role in reducing the severity of neurodevelopmental impairment associated with prematurity.
Keywords: Caffeine, preterm infants, Brain magnetic resonance imaging, Neuroprotection, Ultrasoud
Received: 09 Aug 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 PHUNG, Duong and Obeid. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: LAUREN PHUNG
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.