One vs. two courses of antenatal corticosteroids: A secondary analysis of the MACS trial

Birth is unpredictable and many people who receive antenatal corticosteroids (ACS) for preterm birth remain pregnant. Some societies recommend rescue ACS to those who remain pregnant 14 or more days following the initial course. The main objective is to explore whether there is a difference in severe neonatal morbidity and mortality between a single vs. a second course of ACS. This is a secondary analysis of the multiple courses of ACS for preterm birth (MACS) trial. The MACS study was a randomized clinical trial conducted in 80 centers in 20 different countries from 2001 to 2006. Participants who received only one course of intervention, i.e. either a second course of ACS vs. placebo, were included in this study. The primary outcome was a composite of perinatal or neonatal mortality and severe neonatal morbidity. Two subgroup analyses were planned to address the effect of the second course of ACS on infants born before 32 weeks or within seven days from the intervention. There were 385 and 365 participants included in the ACS and placebo groups, respectively. Composite of primary outcome occurred in 24% and 20% in the ACS and placebo groups, respectively (adjusted odds ratio (aOR) 1.11, 95%CI 0.77-1.60). Newborns exposed to ACS were more likely to be smaller for gestational age, 14.9% versus 10.6% (aOR 1.58, 95%CI 1.05-2.39). Subgroup analyses of infants born before 32 weeks or infants born within seven days from the intervention did not show any benefits in terms of a composite of the primary outcome in ACS versus the placebo group, 50.5% versus 41.8% (aOR 1.18, 95%CI 0.80-1.76) and 42.3% versus 37.1% (aOR 1.05, 95%CI 0.69-1.61), respectively. Neonatal mortality and severe morbidities, including severe respiratory distress syndrome were not improved by a second course of ACS. Providers need to be thoughtful when prescribing a second course of ACS and consider what benefits are hoped to be gained from its administration not only short-term but also long-term.