Projects per year
Abstract
Background: Lung inflammation and impaired alveolarization precede bronchopulmonary dysplasia (BPD). Glucocorticoids are anti-inflammatory and reduce ventilator requirements in preterm infants. However, high-dose glucocorticoids inhibit alveolarization. The effect of glucocorticoids on lung function and structure in preterm newborns exposed to antenatal inflammation is unknown. We hypothesise that postnatal low-dose dexamethasone reduces ventilator requirements, prevents inflammation and BPD-like lung pathology, following antenatal inflammation. Methods: Pregnant ewes received intra-amniotic LPS (E.coli, 4 mg/mL) or saline at 126 days gestation; preterm lambs were delivered 48 h later. Lambs were randomised to receive either tapered intravenous dexamethasone (LPS/Dex, n = 9) or saline (LPS/Sal, n = 10; Sal/Sal, n = 9) commencing <3 h after birth. Respiratory support was gradually de-escalated, using a standardised protocol aimed at weaning from ventilation towards unassisted respiration. Tissues were collected at day 7. Results: Lung morphology and mRNA levels for inflammatory mediators were measured. Respiratory support requirements were not different between groups. Histological analyses revealed higher tissue content and unchanged alveolarization in LPS/Sal compared to other groups. LPS/Dex lambs exhibited decreased markers of pulmonary inflammation compared to LPS/Sal. Conclusion: Tapered low-dose dexamethasone reduces the impact of antenatal LPS on ventilation requirements throughout the first week of life and reduces inflammation and pathological thickening of the preterm lung Impact: We are the first to investigate the combination of antenatal inflammation and postnatal dexamethasone therapy in a pragmatic study design, akin to contemporary neonatal care. We show that antenatal inflammation with postnatal dexamethasone therapy does not reduce ventilator requirements, but has beneficial maturational impacts on the lungs of preterm lambs at 7 days of life. Appropriate tapered postnatal dexamethasone dosing should be explored for extuabtion of oxygen-dependant neonates.
Original language | English |
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Pages (from-to) | 931–940 |
Number of pages | 10 |
Journal | Pediatric Research |
Volume | 95 |
DOIs | |
Publication status | Published - 2024 |
Projects
- 3 Finished
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Effects of amniotic fluid ureaplasma infection, and its treatment, on brain development and
Moss, T., Dickinson, H., Zakhem, M. & Dando, S.
1/08/17 → 31/07/18
Project: Research
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Separating the adverse neurodevelopmental consequences of mechanical ventilation and postnatal steroids in preterm lambs
Pillow, J. J., Blache, D. B., Albertine, K., Noble, P. B., Gill, A. W., Black, M. & Rubenson, J.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/14 → 31/12/17
Project: Research
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NHMRC Research Fellowship
National Health and Medical Research Council (NHMRC) (Australia)
1/01/13 → 31/12/17
Project: Research