In a landmark paper, Liggins and Howie demonstrated that a single course of antenatal corticosteroid therapy administered to women at risk for preterm delivery (PTD) reduced the incidence and severity of respiratory distress syndrome (RDS) and mortality in offspring . Over a dozen randomized trials have subsequently confirmed these findings . In addition, antenatal corticosteroid therapy improves circulatory stability in preterm neonates, resulting in less intraventricular hemorrhage (IVH) or necrotizing enterocolitis compared with unexposed preterm neonates.
The National Institutes of Health (NIH) [3,4], the American College of Obstetricians and Gynecologists (ACOG) , the Royal College of Medicine (RCP) , and other major organizations have recommended antenatal corticosteroid treatment for women at risk for preterm delivery prior to 34 weeks of gestation to reduce the morbidity and mortality associated with preterm birth.
This topic will review the evidence supporting the use of antenatal corticosteroids to improve neonatal outcomes in women at risk for preterm delivery, pharmacological issues associated with this therapy, and other clinical concerns from administration of antenatal corticosteroids.
MECHANISM OF ACTION
Antenatal corticosteroid therapy leads to architectural and biochemical changes that improve both lung mechanics (maximal lung volume, compliance) and gas exchange. These changes are primarily the result of accelerated morphologic development of type 1 and type 2 pneumocytes [7-11]. Type 1 pneumocytes are responsible for gas exchange in the alveoli, while type 2 pneumocytes are responsible for production and secretion of surfactant (figure 1). Antenatal corticosteroids also alter production of surfactant binding proteins and enhance fetal lung antioxidant enzymes. For these changes to occur, however, the lungs need to have reached a stage of development that is biologically responsive to corticosteroids (see 'Gestational age at administration' below).
The biologic rationale for repeating antenatal corticosteroid therapy is based upon the observation that biochemical stimulation of surfactant production appears to be reversible in cell culture models (eg, surfactant protein mRNA levels decline to control levels after cortisol is removed) [8,12]. However, other beneficial effects, such as cytostructural maturation, persist (in rhesus monkeys) after steroid exposure is withdrawn .