Intrauterine Ureaplasma is associated with small airway obstruction in extremely preterm infants

Abstract

Background: The long-term follow-up of lung function (LF) in extremely preterm (EP) infants with bronchopulmonary dysplasia (BPD) has shown a worldwide increase in small airway obstructions (SAO).Objectives: We investigated the relationships between intrauterine Ureplasma infection in EP infants and bubbly/cystic lung, BPD, and SAO at school age. Methods: Placental pathology, placental Ureaplasma DNA (pU-DNA), and cord blood immunoglobulin M (IgM) (C-IgM) were investigated in 360 EP infants born from 1981 to 2004. Maternal amniotic inflammatory response (M-AIR) scores and hemosiderin deposition (HD) were estimated in the chorioamnion. The study subjects were divided into groups based on their M-AIR scores. Their LF at school age was compared with those of 33 healthy siblings.Findings: pU-DNA and C-IgM were significantly related to SAO at school age (p < 0.012). M-AIR score 3 and pU-DNA >1000 units had an odds ratio (OR) of 35 (95% confidence interval: 10-172) and 18 (5.6-67) for bubbly/cystic lung, and 11 (3.1 − 43) and 31 (4.5-349) for severe BPD, for SAO, respectively. The ORs of surfactant treatment, BPD grade III, O 2 at 40 weeks, HD, and C-IgM >30 mg/dl for SAO were 0.21 (0.075-0.58), 5.3 (2.1-15), 2.5 (1.4-4.6), 3.6 (1.5-9.1) and 2.5 (1.0-5.2). 84% (90/107) SAO infants showed no or mild BPD in infancy, and 61% of infants had no severe CAM. Conclusion:Our long-term cohort study of LF in EP infants revealed that intrauterine Ureaplasma was associated with bubbly/cystic lung, severe BPD, and SAO at school age.

Placing Ureaplasma within the Context of Bronchopulmonary Dysplasia Endotypes and Phenotypes

“…These findings are similar to those of the interstitial BPD phenotype, which is characterized by an increase in fibrotic tissue and a widening of the interstitial spaces [8,96]. Although it is difficult to derive specific information from chest radiographs, it is noteworthy that Ureaplasma infection/colonization in extremely preterm infants has been associated with cystic-emphysematous changes [97,98]. This may be suggestive of a parenchymal BPD phenotype [8].…”

“…This may be suggestive of a parenchymal BPD phenotype [8]. Finally, Kitajima et al reported that intrauterine Ureaplasma infection in extremely preterm infants was associated with signs of moderate to severe small airway obstruction in lung function tests at school age [97]. These findings are compatible with the peripheral airway BPD phenotype [8].…”

Urine Desmosine as a Novel Biomarker for Bronchopulmonary Dysplasia and Postprematurity Respiratory Disease in Extremely Preterm or Low Birth Weight Infants

“…In our previous report, intrauterine Ureaplasma infection in EP infants was associated with longterm respiratory impairment. 32 Lung destruction may have started earlier in these infants. In the future, we need to further investigate the earlier measurement of desmosine/ creatinine levels to clarify the utility of urine desmosine as a better biomarker for early BPD detection.…”