Critical appraisal of the role of Ureaplasma in the development of bronchopulmonary dysplasia with metaanalytic techniques.

BACKGROUND: Controversy exists over whether or not Ureaplasma colonization or infection of the respiratory tract contributes to the development of bronchopulmonary dysplasia (BPD). Because BPD is a major cause of morbidity and mortality in preterm infants and a potential therapeutic intervention with antimicrobials is possible, we sought to evaluate and critique the current medical literature and to document the reported association between Ureaplasma and BPD.

METHODS: We analyzed all peer-reviewed articles and previous reviews including cross-references that reported Ureaplasma respiratory tract colonization or infection and development of BPD in neonates published from January 1966 to December 2004. Inclusion criteria included a cohort limited to all neonatal intensive care unit admissions or all colonized infants, articles that did not define a numerator and a denominator for BPD and Ureaplasma or that included patients from other reports were excluded from the analysis. We evaluated BPD at 28 postnatal days (BPD28) or 36 weeks post-menstrual age (BPD36).

RESULTS: Twenty-three studies with an aggregate of 2216 infants reported BPD28, and 8 studies with 751 infants reported BPD36. Although there was significant association between Ureaplasma colonization and both BPD28 and BPD36, there was substantial heterogeneity (Q test statistic, P < 0.01). We therefore focused on describing the study characteristics associated with an increased relative proportion of BPD. The greatest contribution to effect was from the studies enrolling fewer than 100 infants.

CONCLUSION: Ureaplasma colonization is associated with higher reported rates of BPD, but the greatest reported effect is seen in small studies; reporting bias may be partially responsible for this effect.