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  • Title: Extremely preterm fetal sheep lung responses to antenatal steroids and inflammation.
    Author: Visconti K, Senthamaraikannan P, Kemp MW, Saito M, Kramer BW, Newnham JP, Jobe AH, Kallapur SG.
    Journal: Am J Obstet Gynecol; 2018 Mar; 218(3):349.e1-349.e10. PubMed ID: 29274832.
    Abstract:
    BACKGROUND: The efficacy of antenatal steroids for fetal lung maturation in the periviable period is not fully understood. OBJECTIVE: We sought to determine the lung maturational effects of antenatal steroids and inflammation in early gestation sheep fetuses, similar to the periviable period in human beings. STUDY DESIGN: Date-mated ewes with singleton fetuses were randomly assigned to 1 of 4 treatment groups (n = 8/group): (1) maternal intramuscular injection of betamethasone; (2) intraamniotic lipopolysaccharide; (3) betamethasone + lipopolysaccharide; and (4) intraamniotic + intramuscular saline (controls). Fetuses were delivered surgically 48 hours later at 94 days' gestation (63% term gestation) for comprehensive evaluations of lung maturation, and lung and systemic inflammation. RESULTS: Relative to controls, first, betamethasone increased the fetal lung air space to mesenchymal area ratio by 47% but did not increase the messenger RNAs for the surfactant proteins-B and -C that are important for surfactant function or increase the expression of pro-surfactant protein-C in the alveolar type II cells. Second, betamethasone increased expression of 1 of the 4 genes in surfactant lipid synthetic pathways. Third, betamethasone increased genes involved in epithelium sodium channel transport, but not sodium-potassium adenosine triphosphatase or Aquaporin 5. Fourth, lipopolysaccharide increased proinflammatory genes in the lung but did not effectively recruit activated inflammatory cells. Last, betamethasone incompletely suppressed lipopolysaccharide-induced lung inflammation. In the liver, betamethasone when given alone increased the expression of serum amyloid A3 and C-reactive protein messenger RNAs. CONCLUSION: Compared the more mature 125-day gestation sheep, antenatal steroids do not induce pulmonary surfactants during the periviable period, indicating a different response.
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