The efficacy of antenatal steroid therapy is dependent on the duration of low-concentration fetal exposure: evidence from a sheep model of pregnancy

American Journal of Obstetrics and Gynecology
Matthew W KempA H Jobe

Abstract

Antenatal corticosteroids are among the most important and widely used interventions to improve outcomes for preterm infants. Antenatal corticosteroid dosing regimens remain unoptimized and without maternal weight-adjusted dosing. We, and others, have hypothesized that, once a low concentration of maternofetal steroid exposure is achieved and maintained, the duration of the steroid exposure determines treatment efficacy. Using a sheep model of pregnancy, we tested the relationship among steroid dose, duration of exposure, and treatment efficacy. The study was conducted to investigate the relative importance of duration and magnitude of fetal corticosteroid exposure to mature the preterm fetal ovine lung. Ewes with single fetuses at 120 days gestation received an intravenous bolus (loading dose) followed by a maintenance infusion of betamethasone phosphate to target 12-hour fetal plasma betamethasone concentrations of (1) 20 ng/mL, (2) 10 ng/mL, or (3) 2 ng/mL. In a subsequent experiment, fetal plasma betamethasone concentrations were targeted at 2 ng/mL for 26 hours. Negative control animals received sterile saline solution. Positive control animals received 2 intramuscular injections of 0.25 mg/kg Celestone Chronodose (betamet...Continue Reading

Citations

Aug 1, 2019·Pediatric Research·Augusto F SchmidtMatthew W Kemp
Sep 20, 2019·PloS One·Augusto F SchmidtAlan H Jobe
Apr 10, 2020·F1000Research·Katie WynneHenry Murray
Mar 28, 2019·Current Pharmaceutical Design·Lenka HrabalkovaSarah J Stock
Oct 24, 2020·The New England Journal of Medicine·UNKNOWN WHO ACTION Trials CollaboratorsHarish K Chellani
Nov 13, 2020·Pediatric Research·Alan H JobeMark Milad
Jun 22, 2021·American Journal of Obstetrics & Gynecology MFM·Moti GulersenEran Bornstein
Sep 11, 2021·The Journal of Physiology·Jessica R IvyKaren E Chapman

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