1. Low-dose betamethasone-acetate for fetal lung maturation in preterm sheep
- Author
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Schmidt, Augusto F, Kemp, Matthew W, Rittenschober-Böhm, Judith, Kannan, Paranthaman S, Usuda, Haruo, Saito, Masatoshi, Furfaro, Lucy, Watanabe, Shimpei, Stock, Sarah, Kramer, Boris W, Newnham, John P, Kallapur, Suhas G, and Jobe, Alan H
- Subjects
Paediatrics ,Reproductive Medicine ,Biomedical and Clinical Sciences ,Pediatric ,Lung ,Perinatal Period - Conditions Originating in Perinatal Period ,Preterm ,Low Birth Weight and Health of the Newborn ,Infant Mortality ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Reproductive health and childbirth ,ATP Binding Cassette Transporter ,Subfamily A ,Animals ,Aquaporin 5 ,Betamethasone ,Dose-Response Relationship ,Drug ,Female ,Fetal Organ Maturity ,Glucocorticoids ,Models ,Animal ,Pregnancy ,Pulmonary Surfactant-Associated Proteins ,RNA ,Messenger ,Sheep ,antenatal corticosteroids ,betamethasone ,fetal lung maturation ,prematurity ,Paediatrics and Reproductive Medicine ,Obstetrics & Reproductive Medicine ,Reproductive medicine - Abstract
BackgroundAntenatal steroids are standard of care for women who are at risk of preterm delivery; however, antenatal steroid dosing and formulation have not been evaluated adequately. The standard clinical 2-dose treatment with betamethasone-acetate+betamethasone-phosphate is more effective than 2 doses of betamethasone-phosphate for the induction of lung maturation in preterm fetal sheep. We hypothesized that the slowly released betamethasone-acetate component induces similar lung maturation to betamethasone-phosphate+betamethasone-acetate with decreased dose and fetal exposure.ObjectiveThe purpose of this study was to investigate pharmacokinetics and fetal lung maturation of antenatal betamethasone-acetate in preterm fetal sheep.Study designGroups of 10 singleton-pregnant ewes received 1 or 2 intramuscular doses 24 hours apart of 0.25 mg/kg/dose of betamethasone-phosphate+betamethasone-acetate (the standard of care dose) or 1 intramuscular dose of 0.5 mg/kg, 0.25 mg/kg, or 0.125 mg/kg of betamethasone-acetate. Fetuses were delivered 48 hours after the first injection at 122 days of gestation (80% of term) and ventilated for 30 minutes, with ventilator settings, compliance, vital signs, and blood gas measurements recorded every 10 minutes. After ventilation, we measured static lung pressure-volume curves and sampled the lungs for messenger RNA measurements. Other groups of pregnant ewes and fetuses were catheterized and treated with intramuscular injections of betamethasone-phosphate 0.125 mg/kg, betamethasone-acetate 0.125 mg/kg, or betamethasone-acetate 0.5 mg/kg. Maternal and fetal betamethasone concentrations in plasma were measured for 24 hours.ResultsAll betamethasone-treated groups had increased messenger RNA expression of surfactant proteins A, B, and C, ATP-binding cassette subfamily A member 3, and aquaporin-5 compared with control animals. Treatment with 1 dose of intramuscular betamethasone-acetate 0.125mg/kg improved dynamic and static lung compliance, gas exchange, and ventilation efficiency similarly to the standard treatment of 2 doses of 0.25 m/kg of betamethasone-acetate+betamethasone-phosphate. Betamethasone-acetate 0.125 mg/kg resulted in lower maternal and fetal peak plasma concentrations and decreased fetal exposure to betamethasone compared with betamethasone-phosphate 0.125 mg/kg.ConclusionA single dose of betamethasone-acetate results in similar fetal lung maturation as the 2-dose clinical formulation of betamethasone-phosphate+betamethasone-acetate with decreased fetal exposure to betamethasone. A lower dose of betamethasone-acetate may be an effective alternative to induce fetal lung maturation with less risk to the fetus.
- Published
- 2018