Avoiding the prenatal programming effects of glucocorticoids: are there alternative treatments for the induction of antenatal lung maturation?

J Perinat Med. 2015 Sep;43(5):503-23. doi: 10.1515/jpm-2014-0295.

Abstract

Background: The long-term outcomes of antenatal glucocorticoids (GCs) vary between reports, and have generated controversy in terms of repeated and single-course events, causing irreversible effects on endocrine set points.

Aim: This study aimed to assess the effects of alternative therapeutic agents other than synthetic glucocorticoid GC administration for fetal lung maturation.

Methods: A review of literature from PubMed, EMBASE, Cochrane Library, and Google Scholar was conducted to assess the use of alternative therapies to synthetic GCs using recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). End points included the rates of respiratory distress syndrome (RDS), mRNA expression for pneumocyte type II, concentration of surfactant proteins in alveolar lavage, morphological differences, histological proof of lung maturation, and angiogenesis or quantification of the surfactant pool.

Results: In all 41 studies examined, we found that ambroxol showed positive effects on lung maturation, but it has yet to be analyzed with sufficient significance in humans. Interleukins and TNF-alpha produce accelerated lung maturation, but have only been evaluated in basic research/experimental studies. Growth factors promote structural and functional growth in all phases of lung maturation, but little is known about their reciprocal effects and exact mechanisms as therapeutics. Thyroid releasing hormone or vitamin A cause detrimental side effects or were less effective for lung maturation.

Conclusions: The efficacy and safety of these alternative agents are differentiated and none up to now can be recommended as an alternative to GCs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ambroxol / adverse effects
  • Ambroxol / therapeutic use
  • Animals
  • Female
  • Fetal Organ Maturity / drug effects*
  • Glucocorticoids / adverse effects*
  • Glucocorticoids / therapeutic use*
  • Growth Substances / adverse effects
  • Growth Substances / therapeutic use
  • Humans
  • Infant, Newborn
  • Inflammation Mediators / adverse effects
  • Inflammation Mediators / therapeutic use
  • Lung / drug effects*
  • Lung / embryology*
  • Pregnancy
  • Respiratory Distress Syndrome, Newborn / prevention & control
  • Thyrotropin / adverse effects
  • Thyrotropin / therapeutic use
  • Vitamin A / adverse effects
  • Vitamin A / therapeutic use

Substances

  • Glucocorticoids
  • Growth Substances
  • Inflammation Mediators
  • Vitamin A
  • Ambroxol
  • Thyrotropin