ABSTRACT
Premature birth predisposes infants to lung diseases such as bronchopulmonary dysplasia, wheezing, and asthma that contribute to significant morbidity and mortality in the pediatric population. Outcomes in these at-risk infants are influenced by perinatal exposures including prenatal and perinatal hypoxia and inflammation, postnatal intensive care unit interventions including hyperoxia (with or without mechanical ventilation), and subsequent environmental exposures. On the one hand, hypoxia is a natural aspect of development where the fetus grows in a hypoxic environment that promotes tissue patterning and growth including of the lung. However, premature birth has significant effects on pulmonary development and health where premature exposure to room air and furthermore perinatal supplemental oxygen administration represent a hyperoxic insult that causes harm at multiple levels of the lung. Preterm infants are also subject to increased episodes of hypoxia given an immature respiratory control system superimposed on insufficient capacity of the lung to tolerate altered ventilation and perfusion, overall resulting in pulmonary damage and disease. Finally, exogenous insults such as perinatal inflammation and infection further superimpose detrimental changes in the context of hypoxia or hyperoxia. Here, we summarize current understanding of the effects of oxygen, particularly hypoxia, on the developing lung and how low vs. high oxygen may predispose to disease that extends even into adulthood. Better understanding of mechanisms of hypoxic and hyperoxic action can help lead to identify novel therapies for improved care and outcomes in this vulnerable population.
