Extremely preterm fetal sheep lung responses to antenatal steroids and inflammation

Kevin Visconti, Paranthaman Senthamaraikannan, Matthew W. Kemp, Masatoshi Saito, Boris W. Kramer, John P. Newnham, Alan H. Jobe, Suhas G. Kallapur

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)349.e1-349.e10
JournalAmerican Journal of Obstetrics and Gynecology
Volume218
Issue number3
DOIs
Publication statusPublished - Mar 2018

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