Oral Presentation 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Long-term effects of low dose dexamethasone and ventilation therapies: markers of inflammation and growth in preterm lamb lungs (#8)

Veena Kurup 1 , Peter B Noble 1 , Siavash Ahmadi-Noorbakhsh 1 , Paris Papagianis 2 , Amy J Wooldridge 1 , Jane Pillow 1
  1. Human Sciences, Centre for Neonatal Research and Education, UWA, Perth, WA, Australia
  2. The Ritchie Centre, Hudson Institute of Medical Research , Clayton, Victoria, Australia

Background: Bronchopulmonary dysplasia (BPD) is a chronic respiratory disorder in preterm infants characterised by alveolar and airway inflammation and arrested alveolarisation. Anti-inflammatory glucocorticoids such as dexamethasone are sometimes required for preterm infants with severe BPD. The long-term impacts of contemporary low-dose dexamethasone on development and inflammation in the preterm lung remains unclear.

Aim: To investigate the effects of ventilation strategy and low dose dexamethasone on markers of inflammation and growth in lungs of ex- lambs during infancy.

Methods: Preterm lambs (129 d) were randomised to either postnatal saline (Sal; n=13) or low-dose (DART protocol) dexamethasone (Dex; n=11) at 72 h.  Similarly hand reared term lambs (150 d, n= 8) were used as controls. Lambs were raised to 2 months corrected postnatal age using contemporary neonatal care, then euthanised. The left lung was fixed to 30 cm H2O (10 % formalin) and five lung samples were obtained. Fixed tissue was embedded, sectioned and stained with Hart’s elastin stain. Secondary septa content was determined using point counting on ImageJ. Furthermore, molecular markers of inflammation (CD45 and CD163) and markers of growth (aSMA, Sp-B and Ki67) will be determined using immunohistochemistry techniques. Positive cell counts will be conducted using ImageJ.

Results: The proportion of secondary septa was significantly higher in term lambs (10.6 ± 1.2%) than in preterm lambs (9.4 ± 1.2%) (p= 0.019). There was no difference in the proportion of secondary septa in preterm lambs allocated to either postnatal saline (9.6 ± 1.4 %) or low-dose dexamethasone (9.2 ± 0.9 %) (p= 0.381). Data for the molecular markers of inflammation and growth are pending.

Conclusion: A single course of low-dose dexamethasone has no lasting effect on secondary septation of preterm lambs. Preterm lambs managed with contemporary neonatal care have an approximately 10 % reduction in alveolar septation to term lambs.