Adenosinergic modulation of respiratory activity: Developmental plasticity induced by perinatal caffeine administration

Caffeine is an adenosine receptor antagonist that is commonly used in the clinic as a respiratory stimulant to treat apnea of prematurity. A recent clinical study showed that newborns treated with caffeine present no neuro-developmental disabilities at 2 years of age in comparison to placebo-treated children [Schmidt, B., Roberts, R.S., Davis, P., Doyle, L.W., Barrington, K.J., Ohlsson, A., Solimano, A., Tin, W., 2007. Long-term effects of caffeine therapy for apnea of prematurity. N. Engl. J. Med. 357, 1893–1902]. Although neonatal caffeine administration in this population is associated with clear short- and long-term health improvements, the consequences of this treatment on basic homeostatic functions such as respiratory regulation are unknown. This article reviews evidence indicating that neonatal caffeine treatment modifies respiratory control development and that these changes persist until adulthood. The mechanisms contributing to this form of developmental plasticity are unknown but current data indicate that caffeine treatment, especially during the perinatal period, alters adenosinergic neuromodulation of the respiratory control system. While human data show that neonatal caffeine treatment is relatively safe for some aspects of neural development, the results obtained in animal studies raise important questions pertaining to the potential long-term effects of this treatment on the respiratory control system.