Efficacy and safety of antenatal steroids

Matthew W Kemp, Alan H Jobe, Haruo Usuda, Peter W Nathanielsz, Cun Li, Anderson Kuo, Hillary F Huber, Geoffrey D Clarke, Masatoshi Saito, John P Newnham, Sarah J Stock

Antenatal steroids (ANS) are among the most important and widely utilised interventions to improve outcomes for preterm infants. A significant body of evidence demonstrates improved outcomes in preterm infants (24-34 weeks) delivered between 1 and 7 days after the administration of a single course of antenatal steroids (ANS). Moreover, ANS have the advantage of being widely available, low cost, and easily administered via maternal intramuscular injection. The use of ANS to mature the fetal lung is, however, not without contention. Their use in pregnancy is not FDA approved and treatment doses and regimens remain largely un-optimized. Their mode of use varies considerably between countries, and there are lingering concerns regarding the safety of exposing the fetus to high doses of exogenous steroids. A significant proportion of women deliver outside of the 1-7 day therapeutic window after ANS treatment, and this delay may be associated with an increased risk of adverse outcomes for both mother and baby. Today, animal-based studies are one means by which key questions of dosing and safety relating to ANS may be resolved, allowing for further refinement/s of this important therapy. Complementary approaches using non-human primates, sheep and rodents have provided invaluable advances to our understanding of how exogenous steroid exposure impacts fetal development. Focussing on these three major model groups, this review highlights the role of three key animal models (sheep, non-human primates, rodents) in the development of antenatal steroid therapy, and provides an up-to-date synthesis of current efforts to refine this therapy.