Single versus weekly courses of antenatal corticosteroids: Evaluation of safety and efficacy

Wapner, Ronald J.; Sorokin, Yoram; Thom, Elizabeth; Johnson, Francee; Dudley, Donald J.; Spong, Catherine Y.; Peaceman, Alan M.; Leveno, Kenneth J.; Harper, Margaret; Caritis, Steve N.; Miodovnik, Menachem; Mercer, Brian M.; Thorp, John M.; Moawad, Atef H.; OʼSullivan, Mary J.; Ramin, Susan M.; Carpenter, Marshall W.; Rouse, Dwight J.; Sibai, Bahaeddine M; Gabbe, Steven G.

doi:10.1016/j.ajog.2006.03.087

Cited by 257 publications

(225 citation statements)

References 13 publications

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“…Two RCTs were published after the searches were completed. 665,666 These studies were not included in the review because neither reported separate data for women with singleton pregnancies. However, both studies suggested that repeat doses of corticosteroids may be beneficial to babies at continued risk of preterm birth following initial corticosteroid treatment.…”

Section: Repeat Corticosteroid Course(s)mentioning

confidence: 99%

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

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et al. 2009

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For primary prevention, an effective, affordable and safe intervention applied to all mothers without preceding testing is likely to be the most cost-effective approach in asymptomatic women in early pregnancy. For secondary prevention among women at risk of preterm labour in later pregnancy, a management strategy based on the results of testing is likely to be more cost-effective. Implementation of a treat-all strategy with simple interventions, such as fish oils, would be premature for asymptomatic women. Universal provision of high-quality ultrasound machines in labour wards is more strongly indicated for predicting spontaneous preterm birth among symptomatic women than direct management, although staffing issues and the feasibility and acceptability to mothers and health providers of such strategies need to be explored. Further research should include investigations of low-cost and effective tests and treatments to reduce and delay spontaneous preterm birth and reduce the risk of perinatal mortality arising from preterm birth.

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Section: Repeat Corticosteroid Course(s)mentioning

confidence: 99%

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

Honest

Ca²,

Durée³

et al. 2009

Health Technol Assess

180

142

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“…The panel also suggested that animal studies were needed to examine the pathophysiological effects of the potential risks and benefits of multiple courses of glucocorticoids on the fetus (33). Recent trials comparing repeated and single courses of glucocorticoids have demonstrated better short-term outcomes after repeated courses than single courses (11,50). However, these trials raised concerns about lower birth weights (11,50), smaller head circumferences (11), and the possibility of increases in the incidence cerebral palsy (49) after the repeated courses.…”

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Maternal glucocorticoid exposure alters tight junction protein expression in the brain of fetal sheep

Sadowska

Malaeb

Stonestreet

2010

American Journal of Physiology-Heart and Circulatory Physiology

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Sadowska GB, Malaeb SN, Stonestreet BS. Maternal glucocorticoid exposure alters tight junction protein expression in the brain of fetal sheep. Am J Physiol Heart Circ Physiol 298: H179 -H188, 2010. First published October 23, 2009 doi:10.1152/ajpheart.00828.2009.-We examined the expression of tight junction (TJ) proteins in the cerebral cortex, cerebellum, and spinal cord of fetuses after maternal treatment with single and multiple courses of dexamethasone. Ewes received either single courses of four 6-mg dexamethasone or placebo injections every 12 h for 48 h between 104 and 107 days or the same treatment once a week between 76 -78 and 104 -107 days of gestation. TJ protein expression was determined by Western immunoblot analysis on tissue harvested at 105-108 days of gestation. Blood-brain barrier permeability has been previously quantified with the blood-tobrain transfer constant (K i) with ␣-aminoisobutyric acid (39). After a single course of dexamethasone, claudin-5 increased (P Ͻ 0.05) in the cerebral cortex, occludin and claudin-1 increased in the cerebellum, and occludin increased in the spinal cord. After multiple dexamethasone courses, occludin and zonula occludens (ZO)-1 increased in the cerebral cortex, and occludin and claudin-1 increased in the cerebellum. Junctional adhesion molecule-A and ZO-2 expressions did not change. Linear regression comparing K i to TJ proteins showed inverse correlations with claudin-1 and claudin-5 in the cerebral cortex after a single course and ZO-2 in the spinal cord after multiple courses and direct correlations with ZO-1 in the cerebellum and spinal cord after multiple courses. We conclude that maternal glucocorticoid treatment increases the expression of specific TJ proteins in vivo, patterns of TJ protein expression vary after exposure to single and multiple glucocorticoid courses, and decreases in blood-brain barrier permeability are associated with increases in claudin-1, claudin-5, and ZO-2 expression and decreases in ZO-1 expression. In utero glucocorticoid exposure alters the molecular composition of the barrier and affects fetal blood-brain barrier function.blood-brain barrier; dexamethasone; steroids THE BLOOD-BRAIN BARRIER is composed of a continuous layer of cerebrovascular endothelial cells connected by intercellular tight junctions (TJs) (4). TJs are composed of transmembrane and associated cytoplasmic proteins (22). The transmembrane proteins include occludin, claudins, and junctional adhesion molecules (JAMs). The proteins of the claudin family form the primary seal between adjacent endothelial cells, whereas occludin is an important support molecule that increases electrical resistance across the barrier and decreases paracellular permeability (22). JAMs regulate TJ formation and leukocyte and endothelial cell interactions (13). The associated cytoplasmic proteins zonula occuldens (ZO)-1 and ZO-2 stabilize TJs by connecting them to actin (22).Maternally administered glucocorticoids have been widely used to accelerate fetal maturation (9,12,30,34). Th...

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“…The widespread adoption of antenatal corticosteroid therapy has improved outcomes for thousands of preterm babies (2), but the benefits are not consistent. Antenatal corticosteroids reduce the risk of RDS by approximately 50%, but the protection against the development of bronchopulmonary dysplasia (BPD) (3,4) does not occur after a single course of treatment, although repetitive treatment causes may be protective (5). The possibility of augmenting the maturational effects of antenatal corticosteroids has been the subject of many studies, but, to date, there is no other proven effective therapy (6).…”

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confidence: 99%

“…However, the studies presented in the Cochrane Review did not start steroid treatment until 2 wk after birth, and antenatal application was not assessed. Although the effects of prolonged or repeated systemic exposure of corticosteroids on the fetus are contentious (5,(37)(38)(39), this study did not assess betamethasone or budesonide concentrations in the fetal circulation or the effects of these corticosteroids on other developing organ systems. We demonstrate that IA administration of betamethasone or budesonide did not confer any additional pulmonary structural maturational benefits beyond that achieved with maternal administration.…”

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Maternal and Intra-amniotic Corticosteroid Effects on Lung Morphometry in Preterm Lambs

et al. 2007

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ABSTRACT:We investigated the effects of intra-amniotic (IA) betamethasone or budesonide injections on lung structure 2 or 7 d after treatment in preterm fetal sheep. Pregnant ewes received intra-amniotic betamethasone (2 mg/kg fetal weight), budesonide (2 mg/kg), saline or maternal intramuscular betamethasone (0.5 mg/kg maternal weight), or saline. Lambs were delivered 2 or 7 d later at 124 d of gestation. Morphometric analysis was conducted on the right upper lung lobe. Intra-amniotic corticosteroids, 2 or 7 d before delivery, resulted in higher average alveolar volumes than controls (2 d: 25%-35%, 7d: 15%-25%). All corticosteroid treatments resulted in thinning of alveolar walls 7 d after treatment and a higher proportion of alveolar ducts and a lower alveolar wall fraction relative to controls 2 or 7 d after treatment. The changes in structural lung indices correlated with the improved lung function at 2 d. Structural lung indices and increased surfactant correlated with the improved lung function at 7 d. Similar structural changes induced by intra-amniotic corticosteroids and maternal intramuscular betamethasone were associated with improvements in lung function at 2 and 7 d. A ntenatal corticosteroids are used routinely to induce fetal lung maturation and prevent respiratory distress syndrome (RDS) in preterm infants (1,2). The widespread adoption of antenatal corticosteroid therapy has improved outcomes for thousands of preterm babies (2), but the benefits are not consistent. Antenatal corticosteroids reduce the risk of RDS by approximately 50%, but the protection against the development of bronchopulmonary dysplasia (BPD) (3,4) does not occur after a single course of treatment, although repetitive treatment causes may be protective (5). The possibility of augmenting the maturational effects of antenatal corticosteroids has been the subject of many studies, but, to date, there is no other proven effective therapy (6).Our observations that IA endotoxin induces preterm lung maturation by direct contact of endotoxin with the fetal lung (7,8) led us to investigate the maturational potential of IA corticosteroids. IA administration would reduce the risks to the fetus associated with direct fetal i.m. injection and minimize the unwanted and potentially harmful effects of systemic maternal administration, particularly for women with diabetes mellitus. Although IA corticosteroids were shown to mature the fetal lungs (9,10), we wanted to verify that the changes to lung maturation were similar to those previously described by other routes. Due to the possible systemic take up of corticosteroids by the fetus (10,11), we also investigated the maturational effects of budesonide, a corticosteroid preparation designed to be administered by inhalation in postnatal life, that has low systemic bioavailability (6%) due to rapid effective clearance from plasma (12,13).IA betamethasone or budesonide (0.5 or 2 mg/kg estimated fetal body weight) improved preterm lung function 2 d after treatment, equivalent to that induced by ma...

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Single versus weekly courses of antenatal corticosteroids: Evaluation of safety and efficacy

Cited by 257 publications

References 13 publications

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

Maternal glucocorticoid exposure alters tight junction protein expression in the brain of fetal sheep

Maternal and Intra-amniotic Corticosteroid Effects on Lung Morphometry in Preterm Lambs

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