Ventilation-Induced Brain Injury in Preterm Neonates: A Review of Potential Therapies

Samantha K. Barton, Mary Tolcos, Suzanne L. Miller, Charles Christoph Roehr, Georg M. Schmölzer, Timothy J.M. Moss, Stuart B. Hooper, Euan M. Wallace, Graeme R. Polglase

Mechanical ventilation is a risk factor for cerebral inflammation and brain injury in preterm neonates. The risk increases proportionally with the intensity of treatment. Recent studies have shown that cerebral inflammation and injury can be initiated in the delivery room. At present, initiation of intermittent positive pressure ventilation (IPPV) in the delivery room is one of the least controlled interventions a preterm infant will likely face. Varying pressures and volumes administered shortly after birth are sufficient to trigger pathways of ventilation-induced lung and brain injury. The pathways involved in ventilation-induced brain injury include a complex inflammatory cascade and haemodynamic instability, both of which have an impact on the brain. However, regardless of the strategy employed to deliver IPPV, any ventilation has the potential to have an impact on the immature brain. This is particularly important given that preterm infants are already at a high risk for brain injury simply due to immaturity. This highlights the importance of improving the initial respiratory support in the delivery room. We review the mechanisms of ventilation-induced brain injury and discuss the need for, and the most likely, current therapeutic agents to protect the preterm brain. These include therapies already employed clinically, such as maternal glucocorticoid therapy and allopurinol, as well as other agents, such as erythropoietin, human amnion epithelial cells and melatonin, already showing promise in preclinical studies. Their mechanisms of action are discussed, highlighting their potential for use immediately after birth.