Antenatal Corticosteroid Administration for Reducing the Risk of Neonatal Morbidities from Prematurity Corticosteroide antenatal para redução das complicações neonatais da prematuridade

Prematurity continues to be the most important cause of neonatal complications, with more-severe outcomes with lower gestational age at birth. A recently published multicenter study conducted in the United States analyzed births that occurred between 2000 and 2011 and found that one in every four extreme preterms (< 28 weeks) died before hospital discharge.1 Deaths that occurred in the first 12h were attributed to generalized immaturity; between 12h and 14 days of life, to respiratory distress syndrome (RDS); and between 15 days and 60 days of life, to necrotizing enterocolitis. This emphasizes the important contribution of prematurity to more-severe outcomes. Even today, the prevention of prematurity is a major challenge not only because of its multifactorial nature but also because the various causes are not subject to prevention. Thus, when premature delivery is inevitable, the use of antenatal corticosteroids is the only effective intervention for reducing neonatal complications such as RDS, intracranial hemorrhage, necrotizing enterocolitis, and death. However, many misconceptions arise in this area, and hasty conclusions and contradictory information are frequent. These often arise from studies that do not allow to draw the conclusions that are proclaimed. The first evidence in humans that corticosteroids could be used to accelerate fetal lungmaturity came from the study of Liggins and Howie2 in 1972, in which betamethasone was compared with a placebo. In this study, 6 mg of betamethasone sodium phosphate and 6 mg of betamethasone acetate (total 1⁄4 12 mg) were administered by intramuscular injection. After 24h, a second identical injectionwas applied if the first one had no effect. It should be stressed that this is currently themost commonly used scheme.When compared with the placebo group, the treated group displayed a significant reduction in the incidence of RDS and neonatal mortality rate. Further studies with betamethasone or dexamethasone confirmed the initial results and demonstrated not only fetal pulmonary maturation but also improvement in other neonatal results. A meta-analysis that included 21 controlled and randomized studies (n 1⁄4 4,269 newborns) revealed a significant reduction in the incidences of RDS (relative risk [RR] 1⁄4 0.66), intracranial hemorrhage (RR 1⁄4 0.54), necrotizing enterocolitis (RR 1⁄4 0.46), and neonatal death (RR 1⁄4 0.69), without increased incidences ofmaternal and neonatal infections.3 In the same study, beneficial results were observed in cases of preterm premature rupture of membranes. Corticosteroids act by promoting the expressions of proteins that accelerate the functional and structuralmaturityof pulmonary cells and other organs.4 The physiological effects on the lungs result from the production of proteins and enzymes involved in the production of phospholipids by type 2 pneumocytes. The physiological effects include improvement of pulmonary expansion, reduction in vascular permeability, improvement of respiratory function, and response to postnatal surfactants. Betamethasone and dexamethasone are equally effective in promoting the acceleration of lung maturation. Dexamethasone should be administered intramuscularly at 4 doses of 6 mg, with 12-hour intervals between applications. However, in most studies, the use of betamethasone is preferred because long-term follow-up data of fetuses exposed to dexamethasone are still limited. Briefly, some authors started to suggest weekly courses of corticosteroids between the 24 and 34 weeks of life. After multiple courses of corticosteroids have been applied in clinical practice for several years, several studies questioned Editorial