599 - One Size Does Not Fit All: Respiratory phenotypes within the extremes of extreme prematurity

Poster Number: 599
Publication Number: 599.1579

Background: Traditionally, all infants born 22-28 weeks’ gestation are referred to as “extremely preterm”, and management is standardised. However, this belies the substantial anatomical and physiological heterogeneity within this window of development.

Objective: The objective of this exploratory study was to characterize the impact of different degrees of extreme prematurity on the physiological and biological response to a standardized lung protective ventilation strategy.

Design/Methods: 60 min of a standardized ventilation strategy from birth was delivered to lambs at 118-120d gestation (predominantly canalicular, PretermCANALICULAR; n=7), or 127-128d gestation (predominantly saccular, PretermSACCULAR; n=8) or 139-140d gestation (Term,; n=9). Results from morphology and gene expression studies (lung tissue), SWATH-MS analysis (lung lavage), gas exchange and lung mechanics were compared between preterm and term lambs.

Results: Relative to the term group, changes in gas exchange, markers of lung injury and the lung lavage proteome were more frequent and of a greater magnitude in PretermCANALICULAR lambs compared with PretermSACCULAR lambs (Table 1, Figure 1). Bioinformatic assessment of the proteome dataset identified a PretermCANALICULAR-specific injurious phenotype characterized by proteins associated with inflammation, clotting and cell death. In PretermSACCULAR lambs proteins were predominantly associated with signal transduction, cell division and cell recycling.

Conclusion(s): Our discovery of distinct physiological and biological responses in lambs at the extremes of extreme prematurity demonstrates that a “one size fits all” approach to respiratory support fails to appreciate the developmental differences in the preterm lung, especially the increased propensity for inflammation-initiated injury in the most preterm gestations.