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Objective: Pneumatoceles are gas-filled cysts within the lung parenchyma resulting mostly from ventilator-induced lung injury and air-leak in premature infants with respiratory distress syndrome. The use of surfactant in the treatment of respiratory distress syndrome has resulted in a decrease in the incidence of air-leak disease. Our aim was to study the incidence and clinical course of pneumatoceles in the surfactant era. Study Design: A retrospective study of infants born at 30 weeks gestational age was admitted to the University of Connecticut Health Center NICU from 1998 to 2007. Pneumatoceles and other intrathoracic air-leaks were identified and comparisons were made with infants without these conditions. Result: Pneumatoceles were identified in 19 preterm infants, born at gestational age 30 weeks, needing positive pressure ventilation for respiratory distress syndrome between the years 1998 to 2007. Pneumatoceles appeared early (median, 7th day of life; range, 1st to 28th day of life) and usually resolved with decrease in mean airway pressure (median, 4 days; range, 3 to 125 days). The majority of pneumatoceles were located in the right parahilar region (18/19). Associated intrathoracic air-leaks were pulmonary interstitial emphysema (5/19), pneumothorax (10/19), and pneumomediastinum (1/19). None of the infants required any invasive procedures to alleviate the pneumatoceles. In infants who survived, most pneumatoceles resolved with a decrease in mean airway pressure or extubation (14/15). One infant had a persistent pneumatocele for 125 days without any cardiopulmonary compromise and five infants died as a result air-leaks along with other complications of prematurity. Conclusion: Pneumatoceles are a manifestation of intrathoracic air-leaks of prematurity. They are markers for ventilator-induced lung injury and are associated with significant mortality similar to other intrathoracic air-leaks. However, conservative management with reduction in mean airway pressure is effective in the resolution of this condition and interventional decompression of the pneumatocele is generally not necessary. [ABSTRACT FROM AUTHOR]