The Use of Caffeine Citrate in the Management of Neonatal Apnea in Low- and Middle-Income Countries: A Rapid Systematic Review

Background and Aims: Caffeine citrate is an example of a methylxanthine approved for managing apnea of prematurity (AOP). However, there is limited evidence of its use in low- and middle-income countries (LMICs). This rapid systematic review aims to appraise the literature on using caffeine citrate in managing neonatal apnea in LMICs. Methods: A comprehensive search was conducted on literature reporting the treatment of AOP in LMICs. The search was based on a population, intervention, comparison, and outcome format using medical subject heading terms. The PRISMA and PRISMA extension for scoping reviews guidelines were meticulously followed. PubMed, Science Direct, and Scopus were among the bibliographic databases searched. Initially, 2638 articles were identified based on the keywords used. However, after eliminating duplicates and implementing advanced options (only full-text, language, and year), the articles were further screened by abstract and title, ensuring a rigorous selection process. Results: The evaluation of 10 studies involving 1010 preterm infants provided compelling evidence. Our findings demonstrated that caffeine citrate, compared to aminophylline, had fewer adverse effects. The adverse effects, including feeding intolerance, tachycardia, central nervous system derailment, and hyperglycemia, were significantly reduced with caffeine citrate. Furthermore, data from the included studies revealed that caffeine citrate had a lower risk of recurrent apnea and was less likely to fall out of the recommended therapeutic range than aminophylline. These results unequivocally establish caffeine citrate's safety, efficacy, and cost-effectiveness in treating prematurity apnea in LMICs, providing a reliable and beneficial intervention for neonatal care in these regions. Conclusion: Caffeine may be a preferred option in managing AOP in LMICs. However, high drug prices and lack of availability of caffeine may be factors limiting its use in these settings.