Antenatal corticosteroids (ACS) are routinely administered to pregnant mothers at risk of preterm birth to mature the fetal lung and reduce risk of neonatal respiratory disease. However, ACS also act on other fetal tissues. We hypothesised that ciclesonide (CIC), a prodrug with tissue-specific effects, matures the lung as effectively as existing ACS and examined its impact on molecular determinants of fluid transport.
Preterm lambs (~130 gestational days, gD; term, 150 gD) were delivered from Merino ewes randomised to treatment with saline (control, 48 and 24 h: n=11), betamethasone (standard clinical ACS, intramuscular (i.m.) 11.4 mg, 48 and 24 h: n=11), or CIC (i.m. 11.2 mg, 48 and 24 h: n=10, intraamniotic (i.a.) 0.5 mg/kg, 48 h: n=9, or i.a. 1 mg/kg, 48 h: n=10) before delivery, intubated and ventilated for 60 min, then humanely killed for lung tissue collection. Fetal lung fluid was collected and measured before ventilation. Markers of lung maturation: surfactant-producing type II alveolar epithelial cell (AECII) density, and gene expression of aquaporins (AQP) and epithelial sodium channel (SCNN1) subunits, were analysed by qRT-PCR. Effects of treatment and sex were analysed using mixed models in SPSS, P<0.05 were considered significant.
AECII density was higher in lambs treated with betamethasone (P<0.001) and i.a. 1 mg/kg CIC (P<0.001) than in controls, consistent with both steroids inducing lung maturation. Lung liquid volume did not differ from control lambs in betamethasone or CIC-treated groups. Expression of SCNN1G was lower in betamethasone-treated than controls in female lambs only (P=0.030), whereas expression of AQP1, AQP5, SCNN1A, and SCNN1B were unaffected by treatment.
Although CIC and betamethasone induce lung maturational changes, including increased AECII density, gene expression of key fluid transporters and lung fluid volumes were not increased by steroid treatments, likely reflecting the variability within the present cohort.