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Chronic lung disease (CLD) is a significant cause of neonatal morbidity and mortality despite advances in neonatal care. Ureaplasma urealyticum colonization of the lower respiratory tract has been associated with CLD, particularly in extremely low birth weight infants. Despite numerous studies demonstrating the pathogenicity of this organism, treatment remains controversial. This study examines neonates colonized with U. urealyticum in the lower respiratory tract and treated with erythromycin, as compared with noncolonized neonates.A prospective cohort study of 124 neonates weighing <1000 g at birth, requiring endotracheal intubation and ventilation. Endotracheal aspirates were cultured for U. urealyticum and conventional bacteria twice weekly for the duration of endotracheal intubation. Infants colonized with U. urealyticum were treated with intravenous erythromycin. Maximal ventilatory requirements, CLD at Day 28 and 36 weeks postconception, duration of ventilation, oxygen dependency and hospital stay were documented.Twenty-two infants (18%) were identified as being U. urealyticum colonized in endotracheal aspirates. Colonization was significantly associated with younger maternal age, prolonged rupture of membranes, premature labor and vaginal delivery. Of colonized neonates 14% were delivered by cesarean section, with intact membranes. As compared with noncolonized infants, there were no statistically significant differences in chronic lung disease, duration of oxygen therapy or time to discharge.Seven published cohort studies of similar high risk populations where U. urealyticum-colonized infants did not receive erythromycin therapy, show a consistent association with CLD (pooled relative risk + 5.21; 95% confidence interval, 2.93 to 9.64). This association was not demonstrated in the current study and adds further weight to the need for a randomized controlled trial to be performed to evaluate this treatment regimen.