Betamethasone phosphate reduces the efficacy of antenatal steroid therapy and is associated with lower birthweights when administered to pregnant sheep in combination with betamethasone acetate

• DOI: 10.1016/j.ajog.2021.10.001
• Publication Date: 2021-10-07T15:42:35Z
• Authors: Tsukasa Takahashi; Erin L. Fee; Yuki Takahashi; Masatoshi Saito; Nobuo Yaegashi; Haruo Usuda; Lucy Furfaro; Sean Carter; Augusto F. Schmidt; John P. Newnham; Alan H. Jobe; Matthew W. Kemp
• Keywords: Antenatal steroid

Antenatal corticosteroid therapy is a standard of care for women at imminent risk preterm labor. However, the optimal (maximum benefit and minimal side effects) antenatal dosing strategy remains unclear. Although conveying overall when given to right patient time, treatment efficacy highly variable not risk-free. Building on earlier findings, we hypothesized that administered in combination with slow-release betamethasone acetate, phosphate high maternal-fetal concentrations it generates are redundant fetal lung maturation.Using an established sheep model prematurity postnatal ventilation lamb, aimed compare pharmacodynamic effects low-dosage acetate only against dosage as recommended by American College Obstetricians Gynecologists delivery between 24 0/7 35 6/7 weeks' gestation.Ewes carrying single fetus 122±1 days' gestation (term=150 days) were randomized receive either (1) maternal intramuscular injections sterile saline (the negative control group, n=12), (2) 2 0.25 mg/kg phosphate+betamethasone 24-hour intervals n=12); or (3) 0.125 n=11). The fetuses surgically delivered 48 hours after initiation ventilated 30 minutes determine functional maturation. euthanized ventilation, lungs collected analysis using quantitative polymerase chain reaction Western blot assays. Fetal plasma adrenocorticotropic hormone levels measured cord blood samples taken delivery.Preterm lambs defined responders nonresponders arbitrary cutoff, being PaCO2 level more extreme than deviations from mean value normally distributed group values. Compared animals groups showed significantly improved physiological responses (blood gas data) had biochemical signature (messenger RNA surfactant protein assays) consistent higher response rate group. These results strongly correlated amount A. Birthweight was lower hypothalamic-pituitary-adrenal axis suppressed greater extent group.Low-dosage solely employing sufficient elevated associated coadministration did addition improve maturation but suppression, rate, birthweight-outcomes desirable clinical setting. data warranted investigation sustained treatments avoid exposures.