Multiple Courses of Antenatal Corticosteroids for Preterm Birth (MACS): A Randomized Controlled Trial

Abstract

Although a single course of antenatal corticosteroids for women at risk of preterm birth reduces the risk of respiratory distress syndrome (RDS), neonatal mortality and morbidity, the benefits may diminish over time. The effects of weekly doses have been investigated but the benefits are unclear, and there is evidence of decreased fetal growth and other short-term and long-term adverse effects. MACS is an international, multicenter, double-blind, randomized controlled trial designed to determine whether multiple courses of antenatal corticosteroids provide short-term respiratory benefits and minimize the risk of neonatal morbidity and mortality. This trial enrolled 1858 women at 25 to 32 weeks' gestation who had not delivered 14 to 21 days after an initial course of antenatal corticosteroids and remained at high risk for preterm birth. The study was conducted at 80 centers in 20 countries. The study subjects were randomized to receive either antenatal corticosteroids (n = 937) or placebo (n = 921), every 14 days until week 33 or delivery, whichever came first. The primary study outcome was a composite of perinatal or neonatal mortality, or clinically significant neonatal morbidity, which was defined as severe RDS, bronchopulmonary dysplasia intraventricular hemorrhage grade III or IV, cystic periventricular leucomalacia, or necrotizing enterocolitis. All patients and caregivers were blinded as to the treatment given. No difference in primary outcomes of morbidity and mortality was found between infants receiving multiple courses of antenatal corticosteroids or placebo (150 [12.9%] vs. 143 [12.5%], P = 0.83). At birth, in comparison to the placebo, infants who received multiple courses of antenatal corticosteroids weighed less (2216 vs. 2330 g, P < 0.0026), were shorter (44.5 vs. 45.4 cm, P < 0.001), and had a smaller head circumference (31.1 vs. 31.7 cm, P < 0.001). These data show that multiple courses of antenatal corticosteroids given every 14 days are associated with decreased growth in utero and provide no neonatal benefits compared with 1 course of antenatal corticosteroids. The investigators conclude from these findings that multiple courses every 14 days are not recommended.