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

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

doi:10.3389/fcimb.2019.00068

Abstract

Background: Controversy remains concerning the impact of Ureaplasma on preterm neonatal morbidity.Methods: Prospective single-center study in very low birth weight infants <30 weeks' gestation. Cord blood and initial nasopharyngeal swabs were screened for Ureaplasma parvum and U. urealyticum 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 Ureaplasma exposure was evaluated as risk factor for the development of bronchopulmonary dysplasia (BPD), other neonatal morbidities until discharge and systemic inflammation at admission.Results: 40/103 (39%) infants were positive for Ureaplasma in one or both specimens, with U. parvum being the predominant species. While exposure to Ureaplasma alone was not associated with BPD, we found an increased risk of BPD in Ureaplasma-positive infants ventilated ≥5 days (OR 1.64; 95% CI 0.12–22.98; p = 0.009). Presence of Ureaplasma was associated with a 7-fold risk of late onset sepsis (LOS) (95% CI 1.80–27.39; p = 0.014). Moreover, Ureaplasma-positive infants had higher I/T ratios (b 0.39; 95% CI 0.08–0.71; p = 0.014), increased levels of interleukin (IL)-17 (b 0.16; 95% CI 0.02–0.30; p = 0.025) and matrix metalloproteinase 8 (b 0.77; 95% CI 0.10–1.44; p = 0.020), decreased levels of IL-10 (b −0.77; 95% CI −1.58 to −0.01; p = 0.043) and increased ratios of Tumor necrosis factor-α, IL-8, and IL-17 to anti-inflammatory IL-10 (p = 0.003, p = 0.012, p < 0.001).Conclusions: Positive Ureaplasma 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.

Highlights

Substantial therapeutic advances have continously improved the survival of preterm infants, the incidence of neonatal morbidity and sequelae has not declined (Stoll et al, 2015)
Colonization with Ureaplasma species has been associated with increased risk of bronchopulmonary dysplasia (BPD) in preterm infants (Viscardi and Hasday, 2009; Lowe et al, 2014), and there is some evidence of additional implication in the pathogenesis of intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP) (Viscardi et al, 2008; Kasper et al, 2011; Silwedel et al, 2017)
The present study aimed to investigate whether early life exposure to Ureaplasma spp. is associated with (i) the development of BPD, (ii) the development of other neonatal morbidities until discharge, and (iii) systemic inflammation at admission in a cohort of very low birth weight infants (VLBW, i.e., birth weight < 1,500 g) born at

Summary

Introduction

Substantial therapeutic advances have continously improved the survival of preterm infants, the incidence of neonatal morbidity and sequelae has not declined (Stoll et al, 2015). Ureaplasma spp. have been frequently isolated from amniotic fluid, cord blood and respiratory tract samples of preterm infants who later developed BPD (Viscardi and Hasday, 2009). Intraamniotic detection of Ureaplasma spp. was shown to be paralleled by intrauterine and fetal inflammatory response and increased risk of adverse pulmonary and neurologic outcome in preterm infants (Berger et al, 2009; Kasper et al, 2011; Glaser and Speer, 2015; Sweeney et al, 2017). Controversy remains concerning the impact of Ureaplasma on preterm neonatal morbidity

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