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Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery

Men-Jean Lee, MD
Debra Guinn, MD, FACOG
Section Editors
Charles J Lockwood, MD, MHCM
Richard Martin, MD
Deputy Editor
Vanessa A Barss, MD, FACOG


In a landmark paper, Liggins and Howie showed 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 [1]. Over two dozen randomized trials have confirmed these findings [2]. Subsequent trials have also shown that antenatal corticosteroid therapy improves circulatory stability in preterm neonates, resulting in lower rates of intraventricular hemorrhage (IVH) and necrotizing enterocolitis compared with unexposed preterm neonates.

This topic will review evidence supporting the use of antenatal corticosteroids to improve neonatal outcomes in women at risk for preterm delivery, pharmacological issues, and clinical concerns about administration of this therapy.


Mechanism of action — Corticosteroid stimulation of developmentally regulated gene expression and physiologic functions result in maturation of the lungs and some other tissues [3]. Antenatal steroids accelerate development of type 1 and type 2 pneumocytes, leading to structural and biochemical changes that improve both lung mechanics (maximal lung volume, compliance) and gas exchange [4-8]. Induction of type 2 pneumocytes increases surfactant production by inducing production of surfactant proteins and enzymes necessary for phospholipid synthesis. Other effects of antenatal corticosteroids include induction of pulmonary beta-receptors, which play a role in surfactant release and absorption of alveolar fluid when stimulated [5]; induction of fetal lung antioxidant enzymes [9]; and upregulation of gene expression for the epithelial Na+ channel, which is important for absorption of lung fluid after birth [10]. 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) [5,11]. However, other beneficial effects, such as cytostructural maturation, persist (in rhesus monkeys) after steroid exposure is withdrawn [12]. (See 'Use of repeated courses of therapy' below.)

Evidence of short-term clinical efficacy

Reduction of RDS — Randomized trials performed worldwide have consistently reported a significant reduction in the incidence of RDS among infants exposed to antenatal corticosteroid therapy. In a 2017 systematic review of randomized trials comparing antenatal corticosteroid therapy versus placebo/no treatment in women at risk for preterm birth, antenatal corticosteroid therapy resulted in a [2]:


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