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Antenatal betamethasone depresses maternal and fetal aldosterone levels.

ABSTRACT: Antenatal glucocorticoids are used to mature lung function in fetuses at risk for preterm delivery, but they also suppress cortisol synthesis in both pregnant women and their fetuses. We recently discovered in pregnant rabbits that even though exogenous betamethasone is not a mineralocorticoid, it also suppresses production of aldosterone. Lower aldosterone levels were linked to reduced P450 side chain cleavage(P450scc) messenger RNA levels in the rabbit maternal and fetal adrenal cortex. To establish whether this occurs in humans, we assayed aldosterone levels in women and newborns treated with antenatal betamethasone for preterm labor. In mothers treated with betamethasone, maternal cortisol depression after 48 hours was accompanied by aldosterone depression. Both pregnant women and their newborns treated with betamethasone showed depressed aldosterone levels in a 1- to 3-day period after the first betamethasone dose. We conclude that suppression of aldosterone biosynthesis is a side effect of antenatal steroids that has been largely overlooked, but may be clinically relevant at a time when the newborn is learning to control plasma electrolytes and blood volume.

SUBMITTER: Kessel JM

PROVIDER: S-EPMC3883983 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Antenatal betamethasone depresses maternal and fetal aldosterone levels.

Kessel Julie M JM Cale Jackie M JM Verbrick Erin E Parker C Richard CR Carlton David P DP Bird Ian M IM

Reproductive sciences (Thousand Oaks, Calif.) 20090101 1

Antenatal glucocorticoids are used to mature lung function in fetuses at risk for preterm delivery, but they also suppress cortisol synthesis in both pregnant women and their fetuses. We recently discovered in pregnant rabbits that even though exogenous betamethasone is not a mineralocorticoid, it also suppresses production of aldosterone. Lower aldosterone levels were linked to reduced P450 side chain cleavage(P450scc) messenger RNA levels in the rabbit maternal and fetal adrenal cortex. To est ...[more]

PMID: 18997118

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Project description:BackgroundInfants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities.MethodsWe conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery.ResultsThe primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001).ConclusionsAdministration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications. (Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.).

Project description:Importance:Repeated doses of antenatal betamethasone are recommended for women at less than 32 weeks' gestation with ongoing risk of preterm birth. However, concern that this therapy may be associated with adverse neurocognitive effects in children with fetal growth restriction (FGR) remains. Objective:To determine the influence of FGR on the effects of repeated doses of antenatal betamethasone on neurocognitive function in midchildhood. Design, Setting, and Participants:This preplanned secondary analysis of data from the multicenter Australasian Collaborative Trial of Repeat Doses of Corticosteroids (ACTORDS) included women at less than 32 weeks' gestation with ongoing risk of preterm birth (<32 weeks) at least 7 days after an initial course of antenatal corticosteroids who were treated at 23 hospitals across Australia and New Zealand from April 1, 1998, through July 20, 2004. Participants were randomized to intramuscular betamethasone or saline placebo; treatment could be repeated weekly if the woman was judged to be at continued risk of preterm birth. All surviving children were invited to a midchildhood outcome study. Data for this study were collected from October 27, 2006, through March 18, 2011, and analyzed from June 1 through 30, 2018. Interventions:At 6 to 8 years of corrected age, children were assessed by a pediatrician and psychologist for neurosensory and cognitive function, and parents completed standardized questionnaires. Main Outcomes and Measures:The prespecified primary outcomes were survival free of any disability and death or survival with moderate to severe disability. Results:Of 1059 eligible children, 988 (55.0% male; mean [SD] age at follow-up, 7.5 [1.1] years) were assessed at midchildhood. The FGR rate was 139 of 493 children (28.2%) in the repeated betamethasone treatment group and 122 of 495 (24.6%) in the placebo group (P?=?.20). Primary outcome rates were similar between treatment groups for the FGR and non-FGR subgroups, with no evidence of an interaction effect for survival free of any disability (FGR group, 108 of 144 [75.0%] for repeated betamethasone treatment vs 91 of 126 [72.2%] for placebo groups [odds ratio [OR],?1.1; 95% CI, 0.6-1.9]; non-FGR group, 267 of 335 [79.7%] for repeated betamethasone vs 283 of 358 [79.0%] for placebo groups [OR,?1.0; 95% CI, 0.7-1.5]; P?=?.77) and death or moderate to severe disability (FGR group, 21 of 144 [14.6%] for repeated betamethasone treatment vs 20 of 126 [15.9%] for placebo groups [OR,?0.9; 95% CI, 0.4-1.9]; non-FGR group, 29 of 335 [8.6%] for repeated betamethasone vs 36 of 358 [10.0%] for placebo [OR,?0.8; 95% CI, 0.4-1.3]; P?=?.84). Conclusions and Relevance:In this study, repeated antenatal betamethasone treatment compared with placebo was not associated with adverse effects on neurocognitive function at 6 to 8 years of age, even in the presence of FGR. Physicians should use repeated doses of antenatal corticosteroids when indicated before preterm birth, regardless of FGR, in view of the associated neonatal benefits and absence of later adverse effects. Trial Registration:anzctr.org.au Identifier: ACTRN12606000318583.

Project description:In humans and other species, Longlong-term hypoxia (LTH) during pregnancy can lead to intrauterine growth restriction with reduced body/brain weight, dysregulation of cerebral blood flow (CBF), and other problems in humans and rodents. In contrast, sheep appear to undergo relatively successful acclimatization, not demonstrating any of the above-mentioned problems except at extremely high altitude. To identify the signal transduction genetic pathways and those critical molecules, which may be involved in acclimatization to high altitude LTH, we conducted microarray with advanced bioinformatic analysis on carotid arteries (CA) from the normoxic near-term ovine fetus at sea-level and those acclimatized to high altitude for 110+ days during gestation. In response to LTH acclimatization, in fetal CA we identified, mRNA from 38 genes upregulated (> 2 fFold; (P < 0.05) and 9 genes downregulated (> 2-f Fold; (P < 0.05). The major genes with upregulated mRNA were SLC1A3, Insulin-like growth factor (IGF) binding protein 3, IGF type 2 receptor, transforming growth factor (TGF) Beta-3, and genes involved in the AKT and BCL2 signal transduction networks. The majority of genes with upregulated mRNA have a common motif for Pbx/Knotted homeobox in the promoter region, and Sox family binding sites in the 3M-bM-^@M-^Y un -translated region (UTR). Genes with downregulated mRNA included those involved in the P53 pathway and 5-lipoxygenase activating proteins. The promoter region of all genes with downregulated mRNA, had a common 49 bp region, with a binding site for DOT6 and TOD6, components of the RPD3 histone deacetylase complex RPD3C(L). We also identified miRNA complementary to a number of the altered genes. Thus, the present study identified molecules in the ovine fetus, which may help it to play a role in the acclimatizatione successfully response to high-altitude associated LTH. In these series of experiments we examined changes in gene expression in sheep carotids. Pregnant sheep and non-pregnant adult sheep were exposed to 110 days of hypoxia at 3801 meters of altitude. Carotid arteries from fetuses from non-pregnant adult from sea-level controls and those from high-altitude were compared by Agilent ovine custom array

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Antenatal betamethasone depresses maternal and fetal aldosterone levels.

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Antenatal betamethasone depresses maternal and fetal aldosterone levels.

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