Extremely preterm fetal sheep lung responses to antenatal steroids and inflammation

Kevin Visconti, Paranthaman Senthamaraikannan, Matthew W. Kemp, Masatoshi Saito, John P. Newnham

Research output: Contribution to journalArticleResearchpeer-review

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

Keywords

  • Chorioamnionitis
  • Fetal inflammation
  • Fetal lung maturation
  • Respiratory distress syndrome
  • Surfactant

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