1% of the clinical dose used for antenatal steroid therapy is sufficient to induce lung maturation when administered directly to the preterm ovine fetus

Erin L Fee, Tsukasa Takahashi, Yuki Takahashi, Sean Carter, Lucy Furfaro, Michael W Clarke, Mark A Milad, Haruo Usuda, John P Newnham, Masatoshi Saito, Alan Hall Jobe, Matthew W Kemp

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
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Abstract

INTRODUCTION: Antenatal steroids (ANS) are standard of care for women at imminent risk of preterm delivery. ANS accelerate functional maturation of the preterm fetal lung. Current dosing regimens expose the mother and fetus to high steroid levels with increased risk of adverse outcomes. Using a sheep model of pregnancy, we aimed to demonstrate that direct fetal administration would be sufficient to elicit functional maturation of the fetal lung.

STUDY DESIGN: Ewes and fetuses at 122d gestation underwent recovery surgery to install a fetal jugular catheter. Animals were then immediately randomised to either: i) fetal intravenous betamethasone phosphate infusion of 2ng/ml for 26 hours (fetal low-dose group; n=16); ii) fetal intravenous saline infusion for 26 hours and two maternal intramuscular injections of 0.25mg/kg betamethasone-phosphate + betamethasone-acetate (maternal clinical treatment group; n=12); or iii) fetal intravenous saline infusion for 26 hours (negative control group; n=10). Fetuses were delivered 48 hours after surgery, ventilated for 30 min to allow collection of physiological data, and euthanised.

RESULTS: The average betamethasone dose for the fetal low-dose group was 1% (0.3mg) of that used in the maternal clinical treatment group (30mg). At 30 minutes of ventilation, arterial paCO2, pH, heart rate and VEI were significantly (p<0.05) and equivalently improved in both the fetal low-dose and maternal clinical treatment group relative to negative control.

CONCLUSION: Maternal steroid administration was not required to elicit fetal lung maturation. Targeted fetal ANS treatments may allow the use of materially reduced antenatal steroid exposures, significantly reducing the risk of adverse outcomes.

Original languageEnglish
Pages (from-to)L853-L865
JournalAmerican Journal of Physiology: Lung Cellular and Molecular Physiology
Volume322
Issue number6
DOIs
Publication statusPublished - Jun 2022

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