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

Mikael Norman; Aurelie Piedvache; Klaus Børch; Lene Drasbek Huusom; Anna-Karin Edstedt Bonamy; Elizabeth A Howell; Pierre-Henri Jarreau; Rolf F Maier; Ole Pryds; Liis Toome; Heili Varendi; Tom Weber; Emilija Wilson; Arno Van Heijst; Marina Cuttini; Jan Mazela; Henrique Barros; Patrick Van Reempts; Elizabeth S Draper; Jennifer Zeitlin; Effective Perinatal Intensive Care in Europe (EPICE) Research Group

doi:10.1001/jamapediatrics.2017.0602

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

Mikael Norman, Aurelie Piedvache, Klaus Børch, Lene Drasbek Huusom, Anna-Karin Edstedt Bonamy, Elizabeth A Howell, Pierre-Henri Jarreau, Rolf F Maier, Ole Pryds, Liis Toome, Heili Varendi, Tom Weber, Emilija Wilson, Arno Van Heijst, Marina Cuttini, Jan Mazela, Henrique Barros, Patrick Van Reempts, Elizabeth S Draper, Jennifer ZeitlinEffective Perinatal Intensive Care in Europe (EPICE) Research Group

Department of Clinical Medicine

49 Citations (Scopus)

Abstract

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.

Original language	English
Journal	JAMA Pediatrics
Volume	171
Issue number	7
Pages (from-to)	678-686
Number of pages	9
ISSN	1072-4710
DOIs	https://doi.org/10.1001/jamapediatrics.2017.0602
Publication status	Published - Jul 2017

Keywords

Birth Intervals/statistics & numerical data
Cohort Studies
Europe
Female
Gestational Age
Glucocorticoids/administration & dosage
Hospital Mortality
Humans
Infant
Infant Mortality
Infant, Extremely Premature
Infant, Newborn
Infant, Premature
Infant, Premature, Diseases/mortality
Male
Pregnancy
Prenatal Care/methods
Prospective Studies

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Norman, M., Piedvache, A., Børch, K., Huusom, L. D., Bonamy, A-K. E., Howell, E. A., Jarreau, P-H., Maier, R. F., Pryds, O., Toome, L., Varendi, H., Weber, T., Wilson, E., Van Heijst, A., Cuttini, M., Mazela, J., Barros, H., Van Reempts, P., Draper, E. S., ... Effective Perinatal Intensive Care in Europe (EPICE) Research Group (2017). Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort. JAMA Pediatrics, 171(7), 678-686. https://doi.org/10.1001/jamapediatrics.2017.0602

Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants : Results From the EPICE Cohort. / Norman, Mikael; Piedvache, Aurelie; Børch, Klaus et al.

In: JAMA Pediatrics, Vol. 171, No. 7, 07.2017, p. 678-686.

Research output: Contribution to journal › Journal article › Research › peer-review

Norman, M, Piedvache, A, Børch, K, Huusom, LD, Bonamy, A-KE, Howell, EA, Jarreau, P-H, 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 & Effective Perinatal Intensive Care in Europe (EPICE) Research Group 2017, 'Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort', JAMA Pediatrics, vol. 171, no. 7, pp. 678-686. https://doi.org/10.1001/jamapediatrics.2017.0602

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abstract = "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.",

keywords = "Birth Intervals/statistics & numerical data, Cohort Studies, Europe, Female, Gestational Age, Glucocorticoids/administration & dosage, Hospital Mortality, Humans, Infant, Infant Mortality, Infant, Extremely Premature, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases/mortality, Male, Pregnancy, Prenatal Care/methods, Prospective Studies",

author = "Mikael Norman and Aurelie Piedvache and Klaus B{\o}rch and Huusom, {Lene Drasbek} and Bonamy, {Anna-Karin Edstedt} and Howell, {Elizabeth A} and Pierre-Henri Jarreau and Maier, {Rolf F} and Ole Pryds and Liis Toome and Heili Varendi and Tom Weber and Emilija Wilson and {Van Heijst}, Arno and Marina Cuttini and Jan Mazela and Henrique Barros and {Van Reempts}, Patrick and Draper, {Elizabeth S} and Jennifer Zeitlin and {Effective Perinatal Intensive Care in Europe (EPICE) Research Group}",

year = "2017",

month = jul,

doi = "10.1001/jamapediatrics.2017.0602",

language = "English",

volume = "171",

pages = "678--686",

journal = "JAMA Pediatrics",

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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

SN - 2168-6203

VL - 171

SP - 678

EP - 686

JO - JAMA Pediatrics

JF - JAMA Pediatrics

IS - 7

ER -

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

Abstract

Keywords

UN SDGs

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