Abstract
Background: Antenatal steroids promote fetal lung maturation and reduce respiratory distress and mortality in premature infants. Currently, there are no guidelines for the time-of-day administration of antenatal steroids despite a clear diurnal pattern in the release of endogenous steroids (cortisol). We aimed to understand how the diurnal timing of fetal steroid exposure impacts functional lung maturation.
Methods: Twin-pregnant Merino ewes (n = 18) received intramuscular (IM) medroxyprogesterone (150 mg/kg) at 110 days gestation and were randomised to receive two doses of IM betamethasone (11.4 mg) at 6 am or 6 pm, 48 and 24 h before delivery at 122 days gestation. The control group received two injections of IM saline at 6 am. Lambs were delivered surgically between 8-10 am and mechanically ventilated for 40 min to evaluate their lung function. The left lung was inflation-fixed at 30 cmH2O for immunohistochemical analysis of surfactant proteins. Data were analysed using one-way ANOVA or linear mixed-effect models.
Results: Both steroid groups had significantly improved lung compliance (Crs) and ventilation efficiency index (VEI) compared to the control group (Table 1). However, only the AM steroid group showed significantly higher left lung volume (p = 0.019) and increased airspace in the parenchyma (p = 0.009). Surfactant protein (SP)-B expression was elevated in both steroid groups (p < 0.05), but SP-D was significantly reduced in the PM steroid group only (p = 0.016).
Conclusions: Our data provide a first look into how the ‘time-of-day’ that steroids are administered can modulate their efficacy for lung maturation. Further investigation into the potential circadian control of lung maturation is warranted.
Oral presentation.