Caffeine, Neurodevelopmental Outcomes in Premature Infants, and Bronchopulmonary Dysplasia

Abstract

Caffeine, a stimulant is the most widely used drug in the world in adults with increasing usage in children. It is commonly used in the treatment of apnea of prematurity in premature infants. Caffeine in a randomized trial has been shown to reduce the incidence of bronchopulmonary dysplasia in infants <1250 grams birth weight when used to treat apnea of prematurity in these infants. In the same cohort of infants, caffeine improved neurodevelopmental outcomes and survival at 18 months of age and was found to be safe without any adverse events up to 11 years of age. Caffeine is an adenosine receptor antagonist and inhibits adenosine receptors at physiologic concentrations with important effects on behavior and cognitive functions. However, higher doses of caffeine may inhibit the enzyme phosphodiesterase and affect vascular smooth muscle function. Anti-oxidant, anti-inflammatory and antiapoptotic properties of caffeine and its ability to scavenge reactive oxygen species may contribute to its lung and neuro protective effects in premature infants. Animal studies on whether caffeine is protective to the lung are not conclusive at this time. Similarly, caffeine is demonstrated to have adverse effects on brain development in animal studies. Despite the beneficial effects of caffeine in premature infants when administered in the neonatal period, the long-term effects on adult-oriented disease such as cardio-metabolic disease and neurobehavioral states in children and adults needs further study.