468 - Ureaplasma, Azithromycin, and varying definitions of BPD in preterm infants: challenges for clinical care and drug development

Poster Number: 468
Publication Number: 468.229

Maher Ajour, Kentucky Children's Hospital, Lexington, KY, United States; Aric Schadler, University of Kentucky College of Medicine, Lexington, KY, United States; Hong Huang, University of Kentucky College of Medicine, Lexington, KY, United States; Brandon Schanbacher, university of kentucky, lexington, KY, United States; Hubie O. Ballard, Kentucky Children's Hospital, Lexington, KY, United States; John Bauer, University of Kentucky College of Medicine, Lexington, KY, United States

Background: Bronchopulmonary dysplasia (BPD) is the major pulmonary morbidity in preterm infants; defining criteria for this condition has changed several times in the recent decade. Perinatal ureaplasma infection has been implicated in BPD risks and is known to be prevalent in NICU patient populations. Some studies have suggested that azithromycin can reduce BPD risks in ureaplasma positive cases but no formal study has yet been conducted. The goal of this effort was to conduct a secondary data analysis of a completed clinical trial, testing the hypotheses that 1-Ureaplasma is associated with worse pulmonary outcomes in preterm infants and 2-Azithromycin treatment reduces ureaplasma related pulmonary complications. A specific focus was to compare pulmonary outcomes using each of the three most recent working definitions of BPD grade.

Objective: Secondary data analysis of 220 preterm infants enrolled at birth and randomized to receive azithromycin or placebo daily for 8wks. Ureaplasma positivity (PCR testing), other major morbidities or death, pulmonary outcomes (BPD grade) were determined for each patient using three different BPD scoring systems (NIH2001; NICHD2018; Jensen et al. 2019).

Design/Methods: Categorical variables were compared using Pearson Chi-square or Fisher’s Exact tests as appropriate; p < 0.05 was considered significant.

Results: total of 76 patients enrolled were ureaplasma positive (35% overall). Using the NIH2001 BPD grading Ureaplasma positivity was associated with BPD severity (BPD moderate/severe or death vs. BPD none or mild); Azithromycin treatment in ureaplasma positive cases significantly reduced BPD outcomes. In contrast, using the two more recent BPD scoring systems showed no statistically significant differences between ureaplasma positive vs. negative cases or azithromycin benefits. The statistical conclusions were unaltered if patient deaths were excluded from analyses.Conclusion(s): The statistical hypotheses tested using this data set with 220 infants with respect to ureaplasma impact on BPD outcomes and potential benefit of azithromycin were highly dependent on the BPD grading system employed. This study illustrates how very important BPD grading is for defining potential causative agents and potential therapeutic strategies. This is a major impediment for clinical trials investigating BPD mechanisms and/or therapeutic drug development to address this major and costly medical problem. Further studies to specifically identify ureaplasma positive cases and conduct specific trials in this subgroup are clearly warranted.
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