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Study Overview
Objective. To determine whether the administration of betamethasone to women who are likely to deliver in the late preterm period would decrease respiratory and other neonatal complications.
Design. Randomized controlled trial.
Setting and participants. Participants were women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation and a high probability of delivery in the late preterm period (which extends to 36 weeks 6 days) within the 17 university-based clinical centers participating in the Maternal Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Eligible women were randomly assigned in a 1:1 ratio to a course of 2 intramuscular injections of either 12 mg betamethasone or matching placebo administered 24 hours apart. After administration of the study medications, the women were treated clinically according to local practice, including discharge to home if delivery did not occur.
Main outcome measures. The primary outcome was a composite endpoint consisting of need for respiratory support, stillbirth, or neonatal death within 72 hours after delivery. Need for respiratory support was defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation. Secondary outcomes included 2 composite outcomes: (1) respiratory distress syndrome, transient tachypnea of the newborn, or apnea; and (2) respiratory distress syndrome, intraventricular hemorrhage, or necrotizing enterocolitis.
Main results. Among 24,133 women assessed for eligibility, 2831 women underwent randomization with 1429 assigned to the betamethasone group and 1402 to the placebo group. A total of 860 (60.2%) in the betamethasone group and 826 (58.9%) in the placebo group received the prespecified 2 doses of study medication. 1083 of the 1145 women (94.6%) who did not receive a second dose delivered before 24 hours. Two women in each study group were lost to follow-up, with outcome information available for 2827 neonates.
The rate of the primary outcome was lower in the betamethasone group (11.6%) than in the placebo group (14.4%), with a relative risk of 0.80% (95% CI 0.66 to 0.97; P = 0.02); the number needed to treat was 35 women to prevent 1 case of the primary outcome. In regard to secondary outcomes, the rate of the composite outcome of severe respiratory complications was also lower in the betamethasone group than in the placebo group (8.1% vs. 12.1%; relative risk 0.67; CI 0.53 to 0.84; P < 0.001). Of note, the betamethasone group had a higher incidence of neonatal hypoglycemia when compared to the placebo group (24.0% vs. 15.0%; relative risk 1.60; 95% CI 1.37 to 1.87; P < 0.001).
Conclusion. Administration of antenatal betamethasone in women at risk for late preterm delivery significantly decreased the rate of respiratory complications in newborns.
Commentary
Use of antenatal glucocorticoids for early preterm delivery has been a widely accepted practice, with strong evidence that glucocorticoids reduce adverse neonatal outcomes when administered to women who are likely to deliver before 34 weeks of gestation [1,2]. In addition, use of glucocorticoids at the time of elective cesarean delivery at term from the results of the Antenatal Steroids for Term Elective Caesarean Section (ASTECS) trial demonstrated reduction in the rate of admission to neonatal intensive care units for respiratory complications in the betamethasone group when comparing to placebo [3]. However, the use of glucocorticoids in the late preterm period to prevent adverse neonatal respiratory outcomes remained inconclusive after 2 smaller randomized trials [4,5].
In the current study, Gyamfi-Bannerman and colleagues addressed the issue of whether the use of glucocorticoids, specifically betamethasone, in the late preterm period may prevent adverse neonatal respiratory outcomes. While only 60.2% of the betamethasone group and 58.9% of the placebo group received the proposed 2 doses of study medication, administration of betamethasone decreased the need for substantial respiratory support during the first 72 hours after birth and other respiratory complications.
There were no clinically significant adverse neonatal effects except that the betamethasone cohort babies had a 60% increased relative risk of neonatal hypoglycemia. There were no reported adverse events related to the hypoglycemia, and infants with hypoglycemia were discharged on average 2 days earlier than those without, which suggests that the condition was self-limiting. The authors suggested monitoring neonatal blood glucose after betamethasone exposure in the late preterm period. It will be important to answer questions about the long-term outcomes of this therapy, both benefits and risks, such as the potential reduction of chronic lung diseases or risk of developmental delay due to hypoglycemia [6].
Applications for Clinical Practice
This multicenter randomized controlled study provides strong evidence for administering antenatal glucocorticoids, such as betamethasone, in women at risk for late preterm delivery. Betamethasone administration significantly decreased the rate of respiratory complications in newborns, with the precaution to monitor for neonatal hypoglycemia.
—Ka Ming Gordon Ngai, MD, MPH
1. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. JAMA 1995;273: 413–8.
2. Leviton LC, Goldenberg RL, Baker CS, et al. Methods to encourage the use of antenatal corticosteroid therapy for fetal maturation: a randomized controlled trial. JAMA 1999;281:46–52.
3. Stutchfield PR, Whitaker, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 2005;331:662.
4. Balci O, Ozdemir S, Mahmoud AS, et al. The effect of antenatal steroids on fetal lung maturation between the 34th and 36th week of pregnancy. Gynecol Obstet Invest 2010;70:95–9.
5. Porto AM, Coutinho IC, Correia JB, Amorim MM. Effectiveness of antenatal corticosteroids in reducing respiratory disorders in late preterm infants: randomised clinical trial. BMJ 2011;342:d1696.
6. Kerstjens JM, Bocca-Tjeertes IF, de Winter AF, et al. Neonatal morbidities and developmental delay in moderately preterm-born children. Pediatrics 2012;130:e265–72.
Study Overview
Objective. To determine whether the administration of betamethasone to women who are likely to deliver in the late preterm period would decrease respiratory and other neonatal complications.
Design. Randomized controlled trial.
Setting and participants. Participants were women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation and a high probability of delivery in the late preterm period (which extends to 36 weeks 6 days) within the 17 university-based clinical centers participating in the Maternal Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Eligible women were randomly assigned in a 1:1 ratio to a course of 2 intramuscular injections of either 12 mg betamethasone or matching placebo administered 24 hours apart. After administration of the study medications, the women were treated clinically according to local practice, including discharge to home if delivery did not occur.
Main outcome measures. The primary outcome was a composite endpoint consisting of need for respiratory support, stillbirth, or neonatal death within 72 hours after delivery. Need for respiratory support was defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation. Secondary outcomes included 2 composite outcomes: (1) respiratory distress syndrome, transient tachypnea of the newborn, or apnea; and (2) respiratory distress syndrome, intraventricular hemorrhage, or necrotizing enterocolitis.
Main results. Among 24,133 women assessed for eligibility, 2831 women underwent randomization with 1429 assigned to the betamethasone group and 1402 to the placebo group. A total of 860 (60.2%) in the betamethasone group and 826 (58.9%) in the placebo group received the prespecified 2 doses of study medication. 1083 of the 1145 women (94.6%) who did not receive a second dose delivered before 24 hours. Two women in each study group were lost to follow-up, with outcome information available for 2827 neonates.
The rate of the primary outcome was lower in the betamethasone group (11.6%) than in the placebo group (14.4%), with a relative risk of 0.80% (95% CI 0.66 to 0.97; P = 0.02); the number needed to treat was 35 women to prevent 1 case of the primary outcome. In regard to secondary outcomes, the rate of the composite outcome of severe respiratory complications was also lower in the betamethasone group than in the placebo group (8.1% vs. 12.1%; relative risk 0.67; CI 0.53 to 0.84; P < 0.001). Of note, the betamethasone group had a higher incidence of neonatal hypoglycemia when compared to the placebo group (24.0% vs. 15.0%; relative risk 1.60; 95% CI 1.37 to 1.87; P < 0.001).
Conclusion. Administration of antenatal betamethasone in women at risk for late preterm delivery significantly decreased the rate of respiratory complications in newborns.
Commentary
Use of antenatal glucocorticoids for early preterm delivery has been a widely accepted practice, with strong evidence that glucocorticoids reduce adverse neonatal outcomes when administered to women who are likely to deliver before 34 weeks of gestation [1,2]. In addition, use of glucocorticoids at the time of elective cesarean delivery at term from the results of the Antenatal Steroids for Term Elective Caesarean Section (ASTECS) trial demonstrated reduction in the rate of admission to neonatal intensive care units for respiratory complications in the betamethasone group when comparing to placebo [3]. However, the use of glucocorticoids in the late preterm period to prevent adverse neonatal respiratory outcomes remained inconclusive after 2 smaller randomized trials [4,5].
In the current study, Gyamfi-Bannerman and colleagues addressed the issue of whether the use of glucocorticoids, specifically betamethasone, in the late preterm period may prevent adverse neonatal respiratory outcomes. While only 60.2% of the betamethasone group and 58.9% of the placebo group received the proposed 2 doses of study medication, administration of betamethasone decreased the need for substantial respiratory support during the first 72 hours after birth and other respiratory complications.
There were no clinically significant adverse neonatal effects except that the betamethasone cohort babies had a 60% increased relative risk of neonatal hypoglycemia. There were no reported adverse events related to the hypoglycemia, and infants with hypoglycemia were discharged on average 2 days earlier than those without, which suggests that the condition was self-limiting. The authors suggested monitoring neonatal blood glucose after betamethasone exposure in the late preterm period. It will be important to answer questions about the long-term outcomes of this therapy, both benefits and risks, such as the potential reduction of chronic lung diseases or risk of developmental delay due to hypoglycemia [6].
Applications for Clinical Practice
This multicenter randomized controlled study provides strong evidence for administering antenatal glucocorticoids, such as betamethasone, in women at risk for late preterm delivery. Betamethasone administration significantly decreased the rate of respiratory complications in newborns, with the precaution to monitor for neonatal hypoglycemia.
—Ka Ming Gordon Ngai, MD, MPH
Study Overview
Objective. To determine whether the administration of betamethasone to women who are likely to deliver in the late preterm period would decrease respiratory and other neonatal complications.
Design. Randomized controlled trial.
Setting and participants. Participants were women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation and a high probability of delivery in the late preterm period (which extends to 36 weeks 6 days) within the 17 university-based clinical centers participating in the Maternal Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Eligible women were randomly assigned in a 1:1 ratio to a course of 2 intramuscular injections of either 12 mg betamethasone or matching placebo administered 24 hours apart. After administration of the study medications, the women were treated clinically according to local practice, including discharge to home if delivery did not occur.
Main outcome measures. The primary outcome was a composite endpoint consisting of need for respiratory support, stillbirth, or neonatal death within 72 hours after delivery. Need for respiratory support was defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation. Secondary outcomes included 2 composite outcomes: (1) respiratory distress syndrome, transient tachypnea of the newborn, or apnea; and (2) respiratory distress syndrome, intraventricular hemorrhage, or necrotizing enterocolitis.
Main results. Among 24,133 women assessed for eligibility, 2831 women underwent randomization with 1429 assigned to the betamethasone group and 1402 to the placebo group. A total of 860 (60.2%) in the betamethasone group and 826 (58.9%) in the placebo group received the prespecified 2 doses of study medication. 1083 of the 1145 women (94.6%) who did not receive a second dose delivered before 24 hours. Two women in each study group were lost to follow-up, with outcome information available for 2827 neonates.
The rate of the primary outcome was lower in the betamethasone group (11.6%) than in the placebo group (14.4%), with a relative risk of 0.80% (95% CI 0.66 to 0.97; P = 0.02); the number needed to treat was 35 women to prevent 1 case of the primary outcome. In regard to secondary outcomes, the rate of the composite outcome of severe respiratory complications was also lower in the betamethasone group than in the placebo group (8.1% vs. 12.1%; relative risk 0.67; CI 0.53 to 0.84; P < 0.001). Of note, the betamethasone group had a higher incidence of neonatal hypoglycemia when compared to the placebo group (24.0% vs. 15.0%; relative risk 1.60; 95% CI 1.37 to 1.87; P < 0.001).
Conclusion. Administration of antenatal betamethasone in women at risk for late preterm delivery significantly decreased the rate of respiratory complications in newborns.
Commentary
Use of antenatal glucocorticoids for early preterm delivery has been a widely accepted practice, with strong evidence that glucocorticoids reduce adverse neonatal outcomes when administered to women who are likely to deliver before 34 weeks of gestation [1,2]. In addition, use of glucocorticoids at the time of elective cesarean delivery at term from the results of the Antenatal Steroids for Term Elective Caesarean Section (ASTECS) trial demonstrated reduction in the rate of admission to neonatal intensive care units for respiratory complications in the betamethasone group when comparing to placebo [3]. However, the use of glucocorticoids in the late preterm period to prevent adverse neonatal respiratory outcomes remained inconclusive after 2 smaller randomized trials [4,5].
In the current study, Gyamfi-Bannerman and colleagues addressed the issue of whether the use of glucocorticoids, specifically betamethasone, in the late preterm period may prevent adverse neonatal respiratory outcomes. While only 60.2% of the betamethasone group and 58.9% of the placebo group received the proposed 2 doses of study medication, administration of betamethasone decreased the need for substantial respiratory support during the first 72 hours after birth and other respiratory complications.
There were no clinically significant adverse neonatal effects except that the betamethasone cohort babies had a 60% increased relative risk of neonatal hypoglycemia. There were no reported adverse events related to the hypoglycemia, and infants with hypoglycemia were discharged on average 2 days earlier than those without, which suggests that the condition was self-limiting. The authors suggested monitoring neonatal blood glucose after betamethasone exposure in the late preterm period. It will be important to answer questions about the long-term outcomes of this therapy, both benefits and risks, such as the potential reduction of chronic lung diseases or risk of developmental delay due to hypoglycemia [6].
Applications for Clinical Practice
This multicenter randomized controlled study provides strong evidence for administering antenatal glucocorticoids, such as betamethasone, in women at risk for late preterm delivery. Betamethasone administration significantly decreased the rate of respiratory complications in newborns, with the precaution to monitor for neonatal hypoglycemia.
—Ka Ming Gordon Ngai, MD, MPH
1. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. JAMA 1995;273: 413–8.
2. Leviton LC, Goldenberg RL, Baker CS, et al. Methods to encourage the use of antenatal corticosteroid therapy for fetal maturation: a randomized controlled trial. JAMA 1999;281:46–52.
3. Stutchfield PR, Whitaker, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 2005;331:662.
4. Balci O, Ozdemir S, Mahmoud AS, et al. The effect of antenatal steroids on fetal lung maturation between the 34th and 36th week of pregnancy. Gynecol Obstet Invest 2010;70:95–9.
5. Porto AM, Coutinho IC, Correia JB, Amorim MM. Effectiveness of antenatal corticosteroids in reducing respiratory disorders in late preterm infants: randomised clinical trial. BMJ 2011;342:d1696.
6. Kerstjens JM, Bocca-Tjeertes IF, de Winter AF, et al. Neonatal morbidities and developmental delay in moderately preterm-born children. Pediatrics 2012;130:e265–72.
1. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. JAMA 1995;273: 413–8.
2. Leviton LC, Goldenberg RL, Baker CS, et al. Methods to encourage the use of antenatal corticosteroid therapy for fetal maturation: a randomized controlled trial. JAMA 1999;281:46–52.
3. Stutchfield PR, Whitaker, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ 2005;331:662.
4. Balci O, Ozdemir S, Mahmoud AS, et al. The effect of antenatal steroids on fetal lung maturation between the 34th and 36th week of pregnancy. Gynecol Obstet Invest 2010;70:95–9.
5. Porto AM, Coutinho IC, Correia JB, Amorim MM. Effectiveness of antenatal corticosteroids in reducing respiratory disorders in late preterm infants: randomised clinical trial. BMJ 2011;342:d1696.
6. Kerstjens JM, Bocca-Tjeertes IF, de Winter AF, et al. Neonatal morbidities and developmental delay in moderately preterm-born children. Pediatrics 2012;130:e265–72.