In Australia 8.5% of babies are born preterm (<37 weeks) and 1.6% (5000 babies) are born very preterm (>32 weeks). Complications from preterm birth account for 40% of neonatal deaths in Australia. Potent synthetic glucocorticoids (GCs) such as betamethasone or dexamethasone are routinely given antenatally to accelerate fetal lung maturation reducing both preterm infant morbidity and mortality. Synthetic GCs are up to 20x more active than endogenous GCs and risk long-term side-effects in many other organs, particularly in the developing brain of the neonate. We have assessed a novel steroid prodrug called ciclesonide for efficiency in the fetal respiratory system, compared to betamethasone and dexamethasone using both primary fetal mouse lung cells and mouse models of preterm birth in vivo. The prodrug ciclesonide is activated in vivo to an active agonist des-ciclesonide by tissue-specific carboxylesterase (CES) enzymes. We have recently demonstrated that ciclesonide is activated in vivo in most peripheral organs including the lung and in contrast to dexamethasone had no effects in the postnatal mouse brain1. To compare the regulatory effects of ciclesonide and des-ciclesonide to dexamethasone and betamethasone we treated cultured primary mouse lung fibroblasts for 6 hours. Changes in gene expression were assessed using microarray analysis and RT-qPCR. We demonstrated that des-ciclesonide, dexamethasone and betamethasone induced and repressed the expression of a similar profile of GR-regulated respiratory genes including Fkbp5, Crispld2, Tgm2 and Zbtb16. Preliminary results comparing ciclesonide to dexamethasone as an antenatal steroid treatment of pregnant mice at E15.5 and E16.5, 48 hours before birth, showed that ciclesonide in contrast to dexamethasone had no growth retardation effects on fetal pups at E18.5. Fetal mice will be analysed with markers for accelerated lung development and assessed for developmental changes in neurodevelopment.