Chronic lung disease of prematurity : a study of selected causative factors and preventive measures

Abstract: Chronic lung disease of prematurity (CLD) is the most common chronic lung disorder in infants. With the increase in survival of preterm infants in recent years, many immature infants are surviving with CLD. Care of preterm babies with CLD is a major clinical problem in neonatal intensive care. We studied the population of very-low-birth-weight infants (n = 687) in Stockholm County from 1988-1993 to evaluate the use of nasal continuous airway pressure (NCPAP) and mechanical ventilation, and the effects on respiratory morbidity, including the incidence of CLD. We found that infants with gestational ages > 26 weeks can often be cared for at level II neonatal units without mechanical ventilation by using early NCPAP. On the other hand, infants with a gestational age of < 26 weeks need transfer to level III neonatal units, since they will often need mechanical ventilation. Failure of NCPAP is related to the presence of respiratory distress syndrome. CLD increased with decreasing gestational age in mechanically ventilated infants. The incidence of Ureaplasma urealyticum colonization and relationship to CLD was investigated in two studies (n = 93 and 155). Colonization with Ureaplasma urealyticum was inversely related to gestational age and only seen in infants < 30 weeks gestation. Colonization is significantly related to vaginal delivery, prolonged rupture of membranes and chorioamnionitis in the mother. Colonized infants developed CLD more frequently, but immaturity was the strongest determinant for this outcome. Oxygen requirement at 36 weeks postconceptual age was most strongly related to the presence of chorioamnionitis in the mother, and sepsis and/or persisting ductus arteriosus after the first week of life. Erythromycin treatment reduced colonization, but not time with supplemental oxygen. Cytokine levels in relation to CLD development were examined in two studies (n = 38 and 69). Levels of proinflammatory cytokines were elevated in tracheobronchial aspirate fluid during the first days of life in preterm infants who developed CLD. Production of downregulatory cytokines was irregular or absent in preterm infants who developed CLD, while levels of cytokines leading to the development of fibrosis remained elevated. An imbalance in the pulmonary cytokine network may contribute to the development of CLD. We studied the effects of an inhaled steroid (budesonide) in 30 infants at high risk for development of CLD. Inhaled budesonide decreased the need for mechanical ventilation similar to intravenous dexamethasone, but without significant side effects.