Unravelling the role of Pneumocystis jirovecii in utero infection in early and late pulmonary diseases of very preterm infants.

Very preterm birth represent about 1% of livebirths in Europe each year and is associated with 58% of neonatal deaths and substantial lifetime health problems. Pneumocystis jirovecii is an ubiquitous microfungus commonly known for causing a severe interstitial

pneumonia in immunosuppressed subjects. However, this could be the tip of the iceberg and compelling new evidences suggest that

this infection may be pathogenic to certain groups of infants.

In utero transmission of P. jirovecii in humans has been recently proven. The fungus has been found in the lungs of 14-25%

preterm newborns, associated with an increased risk of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia. The

ability of P. jirovecii to change the pulmonary environment has been demonstrated in other contexts, inducing a modification of the

host immune response, pulmonary dysbiosis and thickening of pulmonary alveoli. Genetic polymorphisms have also been

independently implicated in both an increased risk of preterm bi or neonatal RDS and a susceptibility to P. jirovecii.

Hence, JIROborn aims to address the impact of P. jirovecii in utero infection on the preterm infants’ lungs alteration and on the

development of subsequent early or late diseases, constructing a predictive model for monitoring preterm infants’ related

pulmonary complications.

JIROborn is a nested case control study using a prospective cohort of 596 infected and uninfected preterm infants and their mothers.

First, the clinical impact of P. jirovecii infection will be evaluated for early and later lung complications. Then, biological effects of the

infection will be studied focusing on the immune parameters, the microbiota and on surfactant and mucus production. Genetic and

epigenetic susceptibilities to P. jirovecii colonization and/or to the development of pulmonary diseases will be evaluated. Finally, all

data will be analysed to build a predictive model for the monitoring of preterm infants’ pulmonary complications.