Association of Ureaplasma Urealyticum Colonization with Chronic Lung Disease of Prematurity: Results of a Metaanalysis

Objectives: We performed a metaanalysis to determine whether there is an association between Ureaplasma urealyticum and chronic lung disease of prematurity (CLD); most studies involved small sample sizes, and the reported lack of statistical significance could have been due to inadequate power.

Methods: Articles were identified from the literature through a search of MEDLINE, Excerpta Medica, and Reference Update, with the search terms "Ureaplasma urealyticum," "CLD," and "bronchopulmonary dysplasia." The search was initially conducted in June 1994 and updated in March 1995. Abstracts were identified through a hand search of proceedings from two meetings for the years 1987 through 1994. Summary data on frequency of CLD in U. urealyticum-colonized and uncolonized babies were independently determined by the three authors. Preterm and term neonates were included. Colonization required recovery of U. urealyticum from a respiratory or surface specimen. The presence of CLD at 28 or 30 days was determined.

Results: Seventeen publications comprising 13 full publications and 4 abstracts were included in the analysis. The estimates for relative risk (RR) exceeded one in all studies, although the lower confidence interval included one in seven studies. The RR for the development of CLD in colonized neonates was 1.72 (95% confidence interval, 1.5 to 1.96) times that for uncolonized neonates. The RR was not significantly different for abstracts versus full publications; studies focusing on extremely premature, low birth weight neonates versus studies including all neonates; and studies in which only endotracheal aspirates were used to define colonization versus others. The RR since surfactant use was somewhat lower than in studies in which receipt of surfactant was unknown.

Conclusions: This metaanalysis supports a significant association between U. urealyticum colonization and subsequent development of CLD. A randomized, controlled trial showing a reduction in CLD through the use of an antibiotic effective against U. urealyticum would provide further support of a causative role for this agent.