Caffeine Therapy in Preterm Neonates: Mechanisms, Clinical Applications, and Long-term Outcomes – A Narrative Review

Caffeine citrate has rapidly become one of the most commonly utilized medications in neonatal intensive care units around the world, with improved outcomes on treatment for apnea of prematurity and other respiratory conditions in preterm infants. This comprehensive narrative review explores the various mechanisms of caffeine action, clinical indications, dosing strategies, and neurodevelopmental outcomes in premature infants. The primary mechanism of caffeine action is adenosine receptor antagonism, especially at A1 and A2A receptors, which leads to an increase in respiratory drive and a decrease in apneic events. In addition to respiratory effects, caffeine has demonstrated neuroprotective effects and may improve neurodevelopmental outcomes. This review describes recent evidence on optimal dosing regimens when to initiate therapy and novel indications beyond routine apnea treatment.