AUTHOR=Glaser Kirsten , Gradzka-Luczewska Anna , Szymankiewicz-Breborowicz Marta , Kawczynska-Leda Natalia , Henrich Birgit , Waaga-Gasser Ana Maria , Speer Christian P. 

TITLE=Perinatal Ureaplasma Exposure Is Associated With Increased Risk of Late Onset Sepsis and Imbalanced Inflammation in Preterm Infants and May Add to Lung Injury

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2019.00068

DOI=10.3389/fcimb.2019.00068

ISSN=2235-2988

ABSTRACT=<p><bold>Background:</bold> Controversy remains concerning the impact of <italic>Ureaplasma</italic> on preterm neonatal morbidity.</p><p><bold>Methods:</bold> Prospective single-center study in very low birth weight infants &lt;30 weeks' gestation. Cord blood and initial nasopharyngeal swabs were screened for <italic>Ureaplasma parvum</italic> and <italic>U. urealyticum</italic> using culture technique and polymerase chain reaction. Neonatal outcomes were followed until death or discharge. Multi-analyte immunoassay provided cord blood levels of inflammatory markers. Using multivariate regression analyses, perinatal <italic>Ureaplasma</italic> exposure was evaluated as risk factor for the development of bronchopulmonary dysplasia (BPD), other neonatal morbidities until discharge and systemic inflammation at admission.</p><p><bold>Results:</bold> 40/103 (39%) infants were positive for <italic>Ureaplasma</italic> in one or both specimens, with <italic>U. parvum</italic> being the predominant species. While exposure to <italic>Ureaplasma</italic> alone was not associated with BPD, we found an increased risk of BPD in <italic>Ureaplasma</italic>-positive infants ventilated ≥5 days (OR 1.64; 95% CI 0.12–22.98; <italic>p</italic> = 0.009). Presence of <italic>Ureaplasma</italic> was associated with a 7-fold risk of late onset sepsis (LOS) (95% CI 1.80–27.39; <italic>p</italic> = 0.014). Moreover, <italic>Ureaplasma</italic>-positive infants had higher I/T ratios (<italic>b</italic> 0.39; 95% CI 0.08–0.71; <italic>p</italic> = 0.014), increased levels of interleukin (IL)-17 (<italic>b</italic> 0.16; 95% CI 0.02–0.30; <italic>p</italic> = 0.025) and matrix metalloproteinase 8 (<italic>b</italic> 0.77; 95% CI 0.10–1.44; <italic>p</italic> = 0.020), decreased levels of IL-10 (<italic>b</italic> −0.77; 95% CI −1.58 to −0.01; <italic>p</italic> = 0.043) and increased ratios of Tumor necrosis factor-α, IL-8, and IL-17 to anti-inflammatory IL-10 (<italic>p</italic> = <italic>0.0</italic>03, <italic>p</italic> = 0.012, <italic>p</italic> &lt; 0.001).</p><p><bold>Conclusions:</bold> Positive <italic>Ureaplasma</italic> screening was not associated with BPD. However, exposure contributed to BPD in infants ventilated ≥5 days and conferred an increased risk of LOS and imbalanced inflammatory cytokine responses.</p>