A Quantitative Analysis of Ureaplasma urealyticum and Ureaplasma parvum Compared with Host Immune Response in Preterm Neonates at Risk of Developing Bronchopulmonary Dysplasia

Abstract

Multiplex, real-time PCR for the identification of Ureaplasma urealyticum and Ureaplasma parvum was performed on nucleic acids extracted from sequential endotracheal aspirates obtained from preterm neonates born at <29 weeks of gestation and ventilated for more than 48 h admitted to two level 3 neonatal intensive care units. Specimens were obtained shortly after birth and sequentially up until extubation. One hundred fifty-two specimens (93.8%) contained material suitable for analysis. Ureaplasma spp. were identified in 5 of 13 neonates studied. In most cases, the DNA load of the detected Ureaplasma species was low and decreased over time. In addition, changes in detectable Ureaplasma species DNA did not relate to changes in the inflammatory marker C-reactive protein (CRP) or respiratory status. All but two blood samples obtained at times of suspected sepsis were culture positive for other microorganisms; the species cultured were typically coagulase-negative staphylococci and were associated with increased levels of CRP (>10 mg/liter). This study was limited by the small number of patients examined and does not have the power to support or contradict the hypothesis that postnatal lung infection with Ureaplasma parvum is causally related to bronchopulmonary dysplasia (BPD) or adverse respiratory outcomes after preterm birth. However, in this study, increases in CRP levels were not associated with patients in whom Ureaplasma parvum was detected, in contrast to the detection of other bacterial species. Bronchopulmonary dysplasia (BPD) is the most common form of chronic lung disease in premature neonates (22) and results in significant morbidity during early childhood. The role of infection, specifically by Ureaplasma spp., in relation to this condition remains controversial (3, 5-7, 9, 17).Ureaplasma spp. are among the organisms most commonly isolated from the urogenital tracts of healthy women (27). Several studies have suggested that these bacteria are associated with preterm labor, chorioamnionitis, and the development of BPD (10, 27). We recently reported the frequent identification of Ureaplasma spp. in both endotracheal (ET) and nasogastric (NG) aspirates taken from preterm neonates shortly after birth using a species-specific PCR (18). The data showed that Ureaplasma spp. were found more frequently among neonates born more prematurely. While we were able to demonstrate an association between the presence of Ureaplasma spp. in ET aspirates and adverse respiratory outcomes, this association lacked statistical significance after regression analysis taking into account the number of days of ventilation. The extent to which these bacteria are an important cause of inflammatory lung injury remains uncertain.In this further study, we have used a multiplex, real-time PCR assay to detect Ureaplasma parvum and Ureaplasma urealyticum in nucleic acids extracted from sequential ET aspirates obtained from preterm neonates intubated for more than 48 h after birth. Changes in the airway bacterial loads of Ureaplasma spp. i...

Ureaplasma Species Differentially Modulate Pro- and Anti-Inflammatory Cytokine Responses in Newborn and Adult Human Monocytes Pushing the State Toward Pro-Inflammation

“…Little is known about differences in virulence among certain serovars (Abele-Horn et al, 1997 ; Sung et al, 2011 ; Paralanov et al, 2012 ; Sweeney et al, 2017 ). While some studies reported on a predominance of U. parvum in clinical isolates (Sung et al, 2011 ; Payne et al, 2012 ; Friedland et al, 2015 ), other studies failed to designate serovars more often associated with invasive disease and adverse pregnancy outcomes than others (Xiao et al, 2011 ; Paralanov et al, 2012 ). In the present study, we did not observe significant differences between U. urealyticum serovar 8 and U. parvum serovar 3 concerning the pro-inflammatory and immunomodulatory capacity.…”

“…have been reported to be the most common organisms isolated from the amniotic fluid, cord blood, respiratory tract and the cerebrospinal fluid of preterm infants who develop bronchopulmonary dysplasia (BPD) (Goldenberg et al, 2008 ; Sung et al, 2011 ; Lowe et al, 2014 ; Viscardi, 2014 ). However, while respiratory tract colonization has been associated with BPD by several investigations (Schelonka et al, 2005 ; Viscardi and Hasday, 2009 ; Lowe et al, 2014 ), multivariable analysis did not confirm this relationship in other studies (Van Waarde et al, 1997 ; Payne et al, 2010 , 2012 ; Kacerovsky et al, 2014 ).…”

“…in pregnancy are highly variable, ranging from 15 to 88%, and seem to be inversely related to gestational age (Sánchez and Regan, 1990 ; Alfa et al, 1995 ; Chua et al, 1999 ; Kafetzis et al, 2004 ). Detection rates in initial tracheal aspirates or nasopharyngeal secretions range from 10 to 50% in term newborns (Chua et al, 1999 ; Kafetzis et al, 2004 ; Waites et al, 2005 ) and 24–52% in preterm infants <32 weeks (Chua et al, 1999 ; Kafetzis et al, 2004 ; Goldenberg et al, 2008 ; Viscardi and Hasday, 2009 ; Sung et al, 2011 ; Payne et al, 2012 ). Preterm colonization seems to be inversely proportional to gestational age, with 65% of preterm infants <26 weeks being colonized vs. 31% of preterm infants with a gestational age between 26 and 32 weeks (Sung et al, 2011 ).…”

“…As far as systemic inflammation is concerned, some studies in preterm infants indicate inflammatory cytokine responses upon neonatal Ureaplasma infection (Goldenberg et al, 2008 ; Hassanein et al, 2012 ; Viscardi, 2014 ), while others failed to correlate detection of Ureaplasma spp. with systemic inflammation (Payne et al, 2010 , 2012 ; Kacerovsky et al, 2014 ).…”

Ureaplasma urealyticum Causes Hyperammonemia in an Experimental Immunocompromised Murine Model

“…The findings reported herein raise the intriguing hypothetical possibility that Ureaplasma species may be associated with unexplained hyperammonemia in patients other than lung transplant patients. A study evaluating host immune response in preterm neonates at risk of developing bronchopulmonary dysplasia showed that Ureaplasma DNA could be detected at low levels and decreased over time [ 17 ], raising the hypothetical possibility that Ureaplasma species could explain some cases of transient hyperammonemia of the preterm infant [ 18 ]. Unexplained hyperammonemia also occurs in intensive care unit patients, raising the hypothetical possibility that it too could relate to Ureaplasma species.…”