Major changes in cardiovascular and respiratory physiology underpin the successful transition from fetal to neonatal life, and it is now apparent that lung aeration and the onset of pulmonary ventilation trigger such changes. Because preterm infants commonly have difficulty in making the transition to neonatal life, it is important to understand the mechanisms of lung aeration and how this action can be facilitated to improve the transition in these very immature infants. Recent imaging studies have demonstrated that after birth, airway liquid clearance and lung aeration are intrinsically linked and regulated primarily by transpulmonary pressures generated during inspiration. This indicates that airway liquid clearance is not solely dependent on sodium reabsorption and that a variety of mechanisms that may act before, during, and after birth are involved. The level of contribution of each mechanism likely depends on the timing and mode of delivery. Based on the knowledge that transpulmonary pressures primarily regulate airway liquid clearance after birth, it is possible to devise ventilation strategies that facilitate this process in very preterm infants. In particular, such strategies should initially focus on moving liquid rather than air through the airways because liquid has a much higher resistance and should assist in establishing and maintaining functional residual capacity. Two potential strategies are an initial sustained inflation and ventilation with a positive end-expiratory pressure.

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