Placing Ureaplasma within the Context of Bronchopulmonary Dysplasia Endotypes and Phenotypes

Abstract

Different pathophysiological pathways (endotypes), leading to very preterm birth may result in distinct clinical phenotypes of bronchopulmonary dysplasia (BPD). Ureaplasma is a unique player in the pathogenesis of BPD. The interaction between factors inherent to Ureaplasma (virulence, bacterial load, duration of exposure), and to the host (immune response, infection clearance, degree of prematurity, respiratory support, concomitant infections) may contribute to BPD development in a variable manner. The data reviewed herein support the hypothesis that Ureaplasma, as a representative of the infectious/inflammatory endotype, may produce pulmonary damage predominantly in parenchyma, interstitium, and small airways. In contrast, Ureaplasma may have a very limited role in the pathogenesis of the vascular phenotype of BPD. In addition, if Ureaplasma is a key factor in BPD pathogenesis, its eradication by macrolides should prevent BPD. However, various meta-analyses do not show consistent evidence that this is the case. The limitations of current definitions and classifications of BPD, based on respiratory support needs instead of pathophysiology and phenotypes, may explain this and other failures in strategies aimed to prevent BPD. The precise mechanisms through which Ureaplasma infection leads to altered lung development and how these pathways can result in different BPD phenotypes warrant further investigation.

Association between Antenatal Antibiotic Exposure and Bronchopulmonary Dysplasia: A Systematic Review and Bayesian Model-Averaged Meta-Analysis

“…Thus, the infants at greatest risk for BPD may be also the infants who receive the most antenatal antibiotics, which may lead to a false association between this exposure and the adverse outcome. Intrauterine infection is very frequently the trigger for preterm birth, particularly at early GAs where neonatal morbidity and mortality is at its greatest [3,[61][62][63][64]. Moreover, prenatal infection may have an effect on the developmental trajectory of the fetal lung, thereby altering the susceptibility to develop BPD [3,[62][63][64].…”

“…Intrauterine infection is very frequently the trigger for preterm birth, particularly at early GAs where neonatal morbidity and mortality is at its greatest [3,[61][62][63][64]. Moreover, prenatal infection may have an effect on the developmental trajectory of the fetal lung, thereby altering the susceptibility to develop BPD [3,[62][63][64]. Finally, if prenatal infection is suspected as the cause of preterm birth, the likelihood of continuing antibiotic treatment after birth increases [65,66].…”

“…The antibiotics commonly used for this purpose are not effective against Ureaplasma. Ureaplasma is recognized as a major pathogen in prenatal infection triggering preterm birth and is frequently claimed to be involved in the pathogenesis of BPD [ 64 ]. Nevertheless, there is no current evidence on a positive effect of treating maternal Ureaplasma infection/colonization on the development of BPD [ 64 ].…”