 The relationship between IH, adenosine, caffeine and brain development is complex and not fully understood. At clinically effective doses, caffeine exerts effects in the brain by blocking adenosine Ado A1 and A2A receptors, resulting in respiratory stimulation and increased alertness, vigilance and arousal.44-60 Ado A1 receptor activation contributes to hypoxia-induced reduction in cerebral myelination and ventriculomegaly. Caffeine treatment attenuates the effects of hypoxia, presumably through blockade of Ado A1 receptors. It is thus reasonable to hypothesize that similar mechanisms may be active in the human preterm infant. Caffeine may thus be neuroprotective through two major mechanisms: 1 reducing incidence and severity of IH due to its respiratory stimulatory effects, and 2 reducing pre- and immature oligodendrocyte injury. 