Association of Antenatal Corticosteroids With Mortality and Neurodevelopmental Outcomes Among Infants Born at 22 to 25 Weeks' Gestation

Abstract

The benefits of antenatal corticosteroids in mothers with preterm labor from 24 to 34 weeks' gestational age are well established. Because of ethical issues related to periviability and the limited availability of data on the effectiveness of antenatal corticosteroids in infants born before 24 weeks' gestation, antenatal corticosteroids are not recommended for these premature infants. However, suggestions have been made that antenatal use of these agents should be considered before 24 weeks because such infants are at high risk of severe neurodevelopmental impairment, and many are receiving intensive care. This cohort study investigated whether the use of antenatal corticosteroids in mothers of infants born at 22 and 23 weeks of gestation was associated with improvement in major outcomes. Data were obtained prospectively from 10,541 infants with a birth weight between 401 and 1000 g (n = 10,541) born at 22 to 25 weeks' gestation between 1993 and 2009, at 23 academic perinatal centers. A total of 4924 (86.5%) of these infants who survived to 18 to 22 months had follow-up examinations performed by certified examiners unaware of exposure to antenatal corticosteroids. Logistic regression analysis was used to assess the relationship between antenatal exposure to corticosteroids or no exposure and outcomes, adjusting for maternal and neonatal confounding variables. The main study outcome measure was death or neurodevelopmental impairment at an 18- to 22-month follow-up. Death or neurodevelopmental impairment occurred significantly less frequently among infants who had been exposed to antenatal corticosteroids and were born at 23 weeks' gestation (exposure: 83.4% vs. no exposure: 90.5%; adjusted odds ratio [aOR], 0.58 [95% confidence interval{CI}, 0.42-0.80]), at 24 weeks' gestation (exposure: 68.4% vs. no exposure: 80.3%; aOR, 0.62 [95% CI, 0.49-0.78]), and at 25 weeks' gestation (exposure: 52.7% vs. no exposure: 67.9%; aOR, 0.61 [95% CI, 0.50-0.74]). There was no difference in outcomes for infants born at 22 weeks' gestation (90.2% with exposure vs. 93.1% without exposure; aOR, 0.80 [95% CI, 0.29-2.21]). Events occurring significantly less among infants who were born at 23, 24, and 25 weeks' gestation and exposed to antenatal corticosteroids were the following: death by 18 to 22 months, hospital death, the composite of death, intraventricular hemorrhage or periventricular leukomalacia, and the composite of death or necrotizing enterocolitis. The only outcome that occurred significantly less among infants born at 22 weeks' gestation was the composite of death or necrotizing enterocolitis (exposure: 73.5% vs. no exposure: 84.5%; the aOR was 0.54, with a 95% CI of 0.30 to 0.97. These findings show that antenatal exposure of infants born at 23 to 25 weeks' gestation to corticosteroids was associated with a lower rate of death or neurodevelopmental impairment at 18 to 22 months compared with nonexposure