Neonatal Intermittent Hypoxia, Reactive Oxygen Species, and Oxygen-Induced Retinopathy

Abstract

Most of the major morbidities in the preterm newborn are caused by or are associated with oxygen-induced injuries and are aptly called "oxygen radical diseases in neonatology or ORDIN". These include bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, intraventricular hemorrhage, necrotizing enterocolitis and others. Relative hyperoxia immediately after birth, immature antioxidant systems, biomolecular events favoring oxidative stress such as iron availability and the role of hydrogen peroxide as a key molecular mediator of these events are reviewed. Potential therapeutic strategies such as caffeine, antioxidants, non-steroidal anti-inflammatory drugs, and others targeted to these critical sites may help prevent oxidative radical diseases in the newborn resulting in improved neonatal outcomes.

Keywords: Intermittent hypoxia oxygen-induced retinopathy; Oxidative stress; Reactive oxygen species.

FIGURE 1. Mechanism of reactive oxygen species (ROS) and hydrogen peroxide (H₂O₂) interaction with iron to form lipid peroxidation in micro preemies

In OXPHOS, electrons are transferred down the redox enzyme complexes located within the mitochondrial inner membrane. The electrons enter at either complex I or II and are transferred through coenzyme Q to complex III, then to cytochrome c, on to complex IV, and finally to oxygen to generate H₂O. As a byproduct of OXPHOS, ROS are produced. When mitochondrial ROS production becomes excessive (as in the case of intermittent hypoxia and immature antioxidant systems) they can react with iron to cause lipid peroxidation.