What is the shortest administration-to-birth interval of antenatal corticosteroids that promotes survival and decreases neonatal morbidity in very preterm infants?
In a population-based cohort of 4594 European infants born before 32 weeks’ gestation, we found that in-hospital mortality was significantly reduced when antenatal corticosteroids had been administered only a few hours prior to delivery.
Encouraging administration of antenatal corticosteroids when delivery is very imminent could result in substantial survival and health gains for very preterm infants.
Administration-to-birth intervals of antenatal corticosteroids (ANS) vary. The significance of this variation is unclear. Specifically, to our knowledge, the shortest effective administration-to-birth interval is unknown.
To explore the associations between ANS administration-to-birth interval and survival and morbidity among very preterm infants.
Design, Setting, and Participants
The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS. Data were analyzed November 2016.
Time from first injection of ANS to delivery in hours and days.
Main Outcomes and Measures
Three outcomes were studied: in-hospital mortality; a composite of mortality or severe neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis, or stage 3 or greater retinopathy of prematurity; and severe neonatal brain injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic periventricular leukomalacia.
Of the 4594 infants included in the cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the 662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of ANS was associated with an immediate and rapid decline in mortality, reaching a plateau with more than 50% risk reduction after an administration-to-birth interval of 18 to 36 hours. A similar pattern for timing was seen for the composite mortality or morbidity outcome, whereas a significant risk reduction of severe neonatal brain injury was associated with longer administration-to-birth intervals (greater than 48 hours). For all outcomes, the risk reduction associated with ANS was transient, with increasing mortality and risk for severe neonatal brain injury associated with administration-to-birth intervals exceeding 1 week. Under the assumption of a causal relationship between timing of ANS and mortality, a simulation of ANS administered 3 hours before delivery to infants who did not receive ANS showed that their estimated decline in mortality would be 26%.
Conclusions and Relevance
Antenatal corticosteroids may be effective even if given only hours before delivery. Therefore, the infants of pregnant women at risk of imminent preterm delivery may benefit from its use.
Norman M, Piedvache A, Børch K, Huusom LD, Bonamy AE, Howell EA, Jarreau P, Maier RF, Pryds O, Toome L, Varendi H, Weber T, Wilson E, Van Heijst A, Cuttini M, Mazela J, Barros H, Van Reempts P, Draper ES, Zeitlin J, for the Effective Perinatal Intensive Care in Europe (EPICE) Research Group. Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm InfantsResults From the EPICE Cohort. JAMA Pediatr. Published online May 15, 2017. doi:10.1001/jamapediatrics.2017.0602