TY - JOUR
T1 - Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants
T2 - Results From the EPICE Cohort
AU - Norman, Mikael
AU - Piedvache, Aurelie
AU - Børch, Klaus
AU - Huusom, Lene Drasbek
AU - Bonamy, Anna-Karin Edstedt
AU - Howell, Elizabeth A
AU - Jarreau, Pierre-Henri
AU - Maier, Rolf F
AU - Pryds, Ole
AU - Toome, Liis
AU - Varendi, Heili
AU - Weber, Tom
AU - Wilson, Emilija
AU - Van Heijst, Arno
AU - Cuttini, Marina
AU - Mazela, Jan
AU - Barros, Henrique
AU - Van Reempts, Patrick
AU - Draper, Elizabeth S
AU - Zeitlin, Jennifer
AU - Effective Perinatal Intensive Care in Europe (EPICE) Research Group
PY - 2017/7
Y1 - 2017/7
N2 - Importance: 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.Objective: 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.Exposure: 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.Results: 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.
AB - Importance: 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.Objective: 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.Exposure: 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.Results: 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.
KW - Birth Intervals/statistics & numerical data
KW - Cohort Studies
KW - Europe
KW - Female
KW - Gestational Age
KW - Glucocorticoids/administration & dosage
KW - Hospital Mortality
KW - Humans
KW - Infant
KW - Infant Mortality
KW - Infant, Extremely Premature
KW - Infant, Newborn
KW - Infant, Premature
KW - Infant, Premature, Diseases/mortality
KW - Male
KW - Pregnancy
KW - Prenatal Care/methods
KW - Prospective Studies
U2 - 10.1001/jamapediatrics.2017.0602
DO - 10.1001/jamapediatrics.2017.0602
M3 - Journal article
C2 - 28505223
VL - 171
SP - 678
EP - 686
JO - JAMA Pediatrics
JF - JAMA Pediatrics
SN - 2168-6203
IS - 7
ER -