Randomized Trial on Efficacy and Safety of the Antenatal Rescue Course of Glucocorticoids in Threatened Premature Birth (ACG Trial)

RANDOMIZED TRIAL ON EFFICACY AND SAFETY OF THE ANTENATAL RESCUE COURSE OF GLUCOCORTCOID IN THREATENED PREMATURE BIRTH (ACG trial)

Introduction

Prematurity is the main cause of neonatal mortality and morbidity. Immature infants have many serious diseases such as respiratory distress syndrome (RDS), intracranial hemorrhage (ICH), chronic lung disease (CLD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). Corticosteroids have the maturational effects on fetal cardiovascular, respiratory, nervous and gastrointestinal systems (1). Antenatal corticosteroids (ANC) have been widely used for prevention of RDS and other serious diseases in preterm infants since 1972's, when the controlled trial of antepartum glucocorticoid treatment was published. Administration of s of 12 mg of betamethasone given twice intramuscularly 24 hours apart has shown to be effective (2,3,4,39). Strong evidence exists for neonatal benefits from a complete course of ANC starting at 24 hours and lasting up to 7 days after treatment (2,39). Betamethasone and dexamethasone have similar biological activity and both are associated with a significant reduction in the risk of RDS, but only betamethasone with a significant decrease of the neonatal mortality. The clinical benefit had not been documented beyond 7 days after the onset of ANC therapy. (1,2)

Several randomized studies have shown that a single course of antenatal corticosteroid treatment improves the survival of preterm infants born at 24-34 weeks gestation and decreases the incidence of RDS, ICH and NEC. ANC therapy reduces the incidence of RDS by approximately 50%.(1,2) ANC treatment also reduces the need of exogenous surfactant (4). The protective effect against RDS is thought to be due to the structural maturation of the lungs, increased surfactant synthesis, improved resistance to lung injury and improved cardiovascular adaptation. Glucocorticoid speeds up the normal thinning of the gas-exchange walls with double capillary loops between the air sacs. ANC thus accelerates the structural development of the respiratory airways, but reduces the number of alveoli. Glucocorticoid increases surfactant synthesis by enhancing maturation of the surfactant- producing type II pneumocytes and stimulating the secretion of surfactant complex (1,6,7,8,9,40). Serial doses of ANC may possibly downregulate steroid receptors resulting in decreased or disordered surfactant production.(ref) ANC has not been shown to decrease the incidence of CLD at 28 days of age either in the meta-analysis or in the recent retrospective studies (2,13,14,15).

ANC treatment is associated with maturation of the cardiovascular system and normalisation of the low blood pressure in the small premature infant at birth.(ref) This influence was evident after administration of surfactant.(4) According to meta-analysis, ANC had no effect on the incidence of PDA. However in several studies, use of ANC was associated with increased spontaneous closure of PDA(2,3,4, ).