Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort

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.The research received funding from grant agreement 259882 from the European Union Seventh Framework Program (2007-2013). Additional funding in France was provided by the French Institute of Public Health Research/Institute of Public Health and its partners, including the French Health Ministry, the National Institute of Health and Medical Research, the National Institute of Cancer, and the National Solidarity Fund for Autonomy, by grant ANR-11-EQPX-0038 from the National Research Agency through the French Equipex Program of Investments in the Future, and by the PremUp Foundation; in Poland, by 2012-2015 allocation of funds for international projects from the Polish Ministry of Science and HigherEducation; and in Sweden, by regional agreementon medical training and clinical research betweenStockholm County Council and Karolinska Institutetand by the Department of Neonat al Medicine at theKarolinska University Hospital

Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort

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

Evidence-Based Neonatal Unit Practices and Determinants of Postnatal Corticosteroid-Use in Preterm Births below 30 Weeks GA in Europe. A Population-Based Cohort Study.

Postnatal corticosteroids (PNC) were widely used to treat and prevent bronchopulmonary dysplasia in preterm infants until studies showed increased risk of cerebral palsy and neurodevelopmental impairment. We aimed to describe PNC use in Europe and evaluate the determinants of their use, including neonatal characteristics and adherence to evidence-based practices in neonatal intensive care units (NICUs).3917/4096 (95,6%) infants born between 24 and 29 weeks gestational age in 19 regions of 11 European countries of the EPICE cohort we included. We examined neonatal characteristics associated with PNC use. The cohort was divided by tertiles of probability of PNC use determined by logistic regression analysis. We also evaluated the impact of the neonatal unit's reported adherence to European recommendations for respiratory management and a stated policy of reduced PNC use.PNC were prescribed for 545/3917 (13.9%) infants (regional range 3.1-49.4%) and for 29.7% of infants in the highest risk tertile (regional range 5.4-72.4%). After adjustment, independent predictors of PNC use were a low gestational age, small for gestational age, male sex, mechanical ventilation, use of non-steroidal anti-inflammatory drugs to treat persistent ductus arteriosus and region. A stated NICU policy reduced PNC use (odds ratio 0.29 [95% CI 0.17; 0.50]).PNC are frequently used in Europe, but with wide regional variation that was unexplained by neonatal characteristics. Even for infants at highest risk for PNC use, some regions only rarely prescribed PNC. A stated policy of reduced PNC use was associated with observed practice and is recommended

Specialist health care services use in a European cohort of infants born very preterm.

AIM: Children born very preterm require additional specialist care because of the health and developmental risks associated with preterm birth, but information on their health service use is sparse. We sought to describe the use of specialist services by children born very preterm in Europe. METHOD: We analysed data from the multi-regional, population-based Effective Perinatal Intensive Care in Europe (EPICE) cohort of births before 32 weeks' gestation in 11 European countries. Perinatal data were abstracted from medical records and parents completed a questionnaire at 2 years corrected age (4322 children; 2026 females, 2296 males; median gestational age 29wks, interquartile range [IQR] 27-31wks; median birthweight 1230g, IQR 970-1511g). We compared parent-reported use of specialist services by country, perinatal risk (based on gestational age, small for gestational age, and neonatal morbidities), maternal education, and birthplace. RESULTS: Seventy-six per cent of the children had consulted at least one specialist, ranging across countries from 53.7% to 100%. Ophthalmologists (53.4%) and physiotherapists (48.0%) were most frequently consulted, but individual specialists varied greatly by country. Perinatal risk was associated with specialist use, but the gradient differed across countries. Children with more educated mothers had higher proportions of specialist use in three countries. INTERPRETATION: Large variations in the use of specialist services across Europe were not explained by perinatal risk and raise questions about the strengths and limits of existing models of care. WHAT THIS PAPER ADDS: Use of specialist services by children born very preterm varied across Europe. This variation was observed for types and number of specialists consulted. Perinatal risk was associated with specialist care, but did not explain country-level differences. In some countries, mothers' educational level affected use of specialist services

Association of short antenatal corticosteroid administration-to-birth intervals with survival and morbidity among very preterm infants results from the EPICE cohort

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 outcomeswere 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 deliverymay benefit from its use