Continuous but not pulsed low-dose fetal betamethasone exposures extend the durability of antenatal steroid therapy

Antenatal steroid (ANS) therapy is standard care for women at imminent risk of preterm labor. Despite extensive and long-standing use, 40-50% of babies exposed antenatally to steroids do not derive benefit; remaining undelivered 7d or more after ANS treatment is associated with a lack of treatment benefit, and increased risk of harms. The study used a pregnant sheep model to evaluate the impact of continuous vs. pulsed ANS treatments on fetal lung maturation at an extended, eight-day treatment to delivery interval. Continuous low-dose ANS treatments for more than 72 hours in duration improved fetal lung maturation at eight days after treatment initiation. If fetal ANS exposure was interrupted, the beneficial ANS effect was lost. Truncated treatments, including that simulating the current clinical treatment regimen, did not improve lung function. Variable fetal lung maturation was correlated to the amount of saturated phosphatidylcholine present in the lung fluid. These data demonstrate that: i) the durability of ANS therapy may be enhanced by employing an extended, low-dose treatment regimen with reducing total dose; and ii) interrupting the continuity of fetal exposure by allowing it to fall below a minimal threshold was associated with comparably poor functional maturation of the preterm ovine lung.