Antenatal Glucocorticoid Research Articles

Increased incidence of respiratory distress syndrome in neonates of mothers with abnormally invasive placentation.

BackgroundThe incidence of abnormally invasive placentation (AIP) is increasing. Most of these pregnancies are delivered preterm. We sought to characterize neonatal outcomes in AIP pregnancies.MethodsIn this retrospective case-control study (2006–2015), AIP neonates (n = 108) were matched to two controls each for gestational age, antenatal glucocorticoid exposure, sex, plurity, and delivery mode. Medical records were reviewed for neonatal and maternal characteristics/outcomes. Univariate and multivariate Poisson regressions were performed to determine relative risk ratios (RR).ResultsThere were no mortalities. All neonatal outcomes were similar except for respiratory distress syndrome (RDS), which affected 37% of AIP neonates (versus 21% of controls). AIP neonates required respiratory support (64.8% vs. 51.9%) and continuous positive airway pressure (53.7% vs. 42.1%) for a longer duration. Univariate regression yielded elevated RRs for RDS for AIP (RR 1.78, 95% CI 1.24–2.54), placenta previa (RR = 1.94, 95% CI 1.36–2.76), and placenta previa with bleeding (RR 2.29, 95% CI 1.36–3.86). One episode of bleeding had a RR of 2.43 (95% CI 1.57–3.76), 2 or more episodes had a RR of 2.95 (95% CI 1.96–4.44), and bleeding/abruption as the delivery indication had a RR of 2.57 (95% CI 1.82–3.64). A multivariate regression stratifying for AIP and evaluating the combined and individual associations of AIP, bleeding, placenta previa, and GA, resulted in elevated RRs for placenta previa alone (RR 2.16, 95% CI 1.15–4.06) and placenta previa and bleeding (RR 1.69, 95% CI 1.001–2.85).ConclusionsThe increased incidence of RDS at later gestational ages in AIP is driven by placenta previa. AIP neonates required respiratory support for a longer duration than age-matched controls. Providers should be prepared to counsel expectant parents and care for affected neonates.

The fetus at the tipping point: modifying the outcome of fetal asphyxia.

Brain injury around birth is associated with nearly half of all cases of cerebral palsy. Although brain injury is multifactorial, particularly after preterm birth, acute hypoxia-ischaemia is a major contributor to injury. It is now well established that the severity of injury after hypoxia-ischaemia is determined by a dynamic balance between injurious and protective processes. In addition, mothers who are at risk of premature delivery have high rates of diabetes and antepartum infection/inflammation and are almost universally given treatments such as antenatal glucocorticoids and magnesium sulphate to reduce the risk of death and complications after preterm birth. We review evidence that these common factors affect responses to fetal asphyxia, often in unexpected ways. For example, glucocorticoid exposure dramatically increases delayed cell loss after acute hypoxia-ischaemia, largely through secondary hyperglycaemia. This critical new information is important to understand the effects of clinical treatments of women whose fetuses are at risk of perinatal asphyxia.

Parto pré-termo

Mais de 70% da morbidade e mortalidade neonatal e infantil é secundária à prematuridade. O parto pré-termo espontâneo é uma síndrome na qual o processo da parturição pode ser iniciado por um ou mais caminhos que levam às alterações do colo uterino, ativação decidual, contrações uterinas e rotura das membranas ovulares. Os principais fatores de risco para o parto pré-termo são a história prévia de parto pré-termo e a gestação gemelar, mas a maioria das mulheres que têm filhos prematuros não apresentam fatores de riscos aparentes. Toda gravidez potencialmente possui risco. A suplementação com progesterona reduz o risco de parto pré-termo em aproximadamente 40%, em mulheres com feto único e que tiveram um parto pré-termo com feto único e em mulheres com colo curto detectado pela ultrassonografia transvaginal na gravidez atual. Outras intervenções obstétricas que reduzem a morbidade neonatal tais como, a corticoterapia antenatal, a tocólise e a antibioticoterapia profilática para o estreptococo do grupo B, são terapêuticas terciárias eficazes mas não reduzem a incidência de parto pré-termo.

Glucocorticoids, antenatal corticosteroid therapy and fetal heart maturation.

Glucocorticoids are essential in mammals to mature fetal organs and tissues in order to survive after birth. Hence, antenatal glucocorticoid treatment (termed antenatal corticosteroid therapy) can be life-saving in preterm babies and is commonly used in women at risk of preterm birth. While the effects of glucocorticoids on lung maturation have been well described, the effects on the fetal heart remain less clear. Experiments in mice have shown that endogenous glucocorticoid action is required to mature the fetal heart. However, whether the potent synthetic glucocorticoids used in antenatal corticosteroid therapy have similar maturational effects on the fetal heart is less clear. Moreover, antenatal corticosteroid therapy may increase the risk of cardiovascular disease in adulthood. Here, we present a narrative review of the evidence relating to the effects of antenatal glucocorticoid action on the fetal heart and discuss the implications for antenatal corticosteroid therapy.

Glucocorticoid receptor isoform-specific regulation of development, circadian rhythm, and inflammation in mice.

Glucocorticoids are primary stress hormones, and their synthetic derivatives are widely used clinically. The therapeutic efficacy of these steroids is limited by side effects and glucocorticoid resistance. Multiple glucocorticoid receptor (GR) isoforms are produced from a single gene by alternative translation initiation; however, the role individual isoforms play in tissue-specific responses to glucocorticoids is unknown. We have generated knockin mice that exclusively express the most active receptor isoform, GR-C3. GR-C3 knockin mice die at birth due to respiratory distress. Microarray analysis of fibroblasts from wild-type and GR-C3 mice indicated that most genes regulated by GR-C3 were unique to this isoform. Antenatal glucocorticoid administration rescued GR-C3 knockin mice from neonatal death. Dual-energy X-ray absorptiometry revealed no major alterations in body composition for rescued knockin mice. Rescued female, but not male, GR-C3 mice exhibited increased wheel running activity in the light portion of the day. LPS administration induced premature mortality in rescued GR-C3 knockin mice, and gene expression studies revealed a deficiency in the ability of GR-C3 to repress a large cohort of immune and inflammatory response genes. These findings demonstrate that specific GR translational isoforms can influence development, circadian rhythm, and inflammation through the regulation of distinct gene networks.-Oakley, R. H., Ramamoorthy, S., Foley, J. F., Busada, J. T., Lu, N. Z., Cidlowski, J. A. Glucocorticoid receptor isoform-specific regulation of development, circadian rhythm, and inflammation in mice.

Central Effects of Angiotensin‐(1‐7) Treatment on Medullary MAPK and PI3K Pathways of Antenatal Glucocorticoid Exposed Adult Sheep are Sex Dependent

Introduction and HypothesisFetal exposure to betamethasone (BMX) that results from the clinical administration of the glucocorticoid agonist to women threatening premature delivery may lead to deleterious long‐term effects on central autonomic regulation. In the adult offspring of pregnant sheep administered antenatal BMX, mean arterial pressure (MAP) is higher and baroreflex sensitivity (BRS) is impaired. These responses are associated with lower brain medullary expression of Angiotensin‐(1‐7) [Ang‐(1‐7)]. Moreover, we observed sex differences in two key signaling pathways implicated in cardiovascular dysfunction and stimulation of oxidative stress in the dorsal brain medulla (DMM) that include higher mitogen‐activated protein kinase (MAPK) in BMX adult male offspring and an attenuated phosphoinositide 3‐kinase (PI3K) pathway in BMX adult female offspring. To establish whether reduced central Ang‐(1‐7) tone contributes to the BMX‐induced cardiovascular effects, we assessed both MAPK and PI3K pathways in the DMM of BMX sheep following 2‐week intracerebroventricular infusion with Ang‐(1‐7) or artificial CSF (aCSF). We hypothesized that in both BMX male and female sheep, Ang‐(1‐7) therapy will correct the observed disturbances in these two pathways.ResultsAlthough presented before, two weeks of Ang‐(1‐7) administration lowered blood pressure and improved baroreflex sensitivity and heart rate variability. In BMX male sheep Ang‐(1‐7) administration was associated with a significant reduction in MAPK activation in the DMM as detected by phosphorylated ERK 1/2 compared to the aCSF‐treated BMX male controls (0.20 ± 0.07 vs 1.04 ± 0.31; p = 0.01), with no change in the PI3K pathway as determined by comparable phosphorylated Akt expression (0.25 ± 0.088 vs 0.36 ± 0.019; p = 0.34). In contrast, BMX female sheep administered Ang‐(1‐7) showed no change in either phosphorylated ERK 1/2 (0.46 ± 0.16 vs 0.70 ± 0.24; p = 0.31) or phosphorylated Akt expression (0.36 ± 0.06 vs 0.33 ± 0.05; p = 0.50) despite that BMX alone reduced PI3K expression.ConclusionCentral administration of Ang‐(1‐7) constitutes a potential therapeutic approach to improve autonomic dysfunction in both BMX exposed sheep; however, distinctly different signaling mechanisms in the DMM of male and female BMX sheep appear to be stimulated by Ang‐(1‐7).Support or Funding InformationHD 047584This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

High frequency jet ventilation in preterm infants: experience from Western Australia

Objective: To assess if high frequency jet ventilation (HFJV) is associated with reduced odds of death or discharge home on oxygen in preterm infants.Methods: A case control study (1 February 2010 – 1 June 2014) comparing the primary outcome as “death or discharge home on oxygen” in preterm infants who needed HFJV (Cases) versus those who did not (Controls). Controls were matched to cases (1:1) on gestation, birthweight, gender, place of birth, growth status, antenatal glucocorticoids, and dexamethasone as treatment for severe bronchopulmonary dysplasia (BPD). Logistic regression analysis was used to control for confounders.Results: Data on all preterm infants who needed HFJV (Cases: n = 50) and 50 controls during the study period were analysed. Primary outcome was more frequent in cases versus controls, but not significant after adjusting for mean airway pressure and adjuvant therapy (e.g. diuretics) [aOR: 1.46 (0.23–9.14), p = .687]. Death before discharge [odds ratios (OR): 6.00 (1.34–55.2), p = .013] was more frequent in cases; discharge on home oxygen [OR: 0.88 (0.27–2.76), p = 1.000] was comparable between groups. Duration of oxygen [adjusted hazard ratios (aHR): 1.23 (0.69–2.17), p = .475] and incidence of treatment warranting retinopathy of prematurity [aOR: 0.10 (0.01–1.96), p = .127] was not significant between cases versus controls.Conclusions: HFJV was not associated with reduced odds of death or discharge home on oxygen in preterm infants in our study. Adequately powered randomized trials are required to assess the efficacy and safety of HFJV in preterm infants.

Influence of Timing of Antenatal Glucocorticoid Exposure on Umbilical Cord Blood Neurotrophins Concentration in Appropriately Grown and Growth Restricted Very Preterm Infants

Influence of Timing of Antenatal Glucocorticoid Exposure on Umbilical Cord Blood Neurotrophins Concentration in Appropriately Grown and Growth Restricted Very Preterm Infants

Antenatal glucocorticoids for accelerating fetal lung maturation and its effects on parturients and offspring

Prenatal glucocorticoids(GC) therapy can effectively reduce neonatal mortality and the incidence of severe diseases without increasing the risk of chorioamnionitis, endometritis and maternal death, and it has become one of the most important prenatal interventions to improve neonatal prognosis.Chinese guideline points out that all pregnant women at risk of preterm birth between 28 to 34+ 6 weeks should be treated with a courses of GC and recent studies show that it should also be considered at 22-39 weeks if the clinical needs.Prenatal use of GC does not increase the risk of developing nervous system disorders in offspring, however, the reproductive system and immune function of the offspring may have adverse effects.In this review, the GC type, approach, gestational age, the optimal time for medicine, course of special treatment, use under special pregnancy circumstances, influence on both mothers and infants and so on are summarized. Key words: Glucocorticoids; Pregnancy; Infant, newborn

A Blast From the Past: A Novel Complication of Bronchopulmonary Dysplasia

SESSION TITLE: Imaging SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a pulmonary complication of pre-mature birth. BPD occurs in pre-mature infants experiencing respiratory distress syndrome (RDS) treated with mechanical ventilation (MV), resulting in an inflammatory condition characterized by diverse radiographic findings and histologically by fibrosis and smooth muscle hypertrophy in the pulmonary tissues. In this case, we describe unique radiographic sequelae of BPD manifesting in adulthood. CASE PRESENTATION: A 43-year-old Caucasian female with history of premature birth, supported with MV, presented to her primary care physician for a retirement physical. She endorsed mild dyspnea on exertion, but denied chest pain, cough, or shortness of breath at rest. On physical exam, lungs were clear bilaterally with good air movement in all fields. Chest radiograph was normal except a 6mm nodular density noted in the right lower lobe. A non-contrast computed tomography scan of the chest was performed revealing a 2mm calcified granuloma. In addition, there were global, mild, and uniform paraseptal emphysematous changes throughout the pleural surfaces of the lungs and the fissures. Pulmonary work up including spirometry, carbon monoxide diffusing capacity, and testing for alpha-1 antitrypsin deficiency was normal. DISCUSSION: The long term sequelae of BPD is heterogeneous and depends on the initial degree of insult. MV of the premature infant in the setting of RDS is the predominant risk factor. Mild-moderate BPD may have no long-term effects with normal to only mildly obstructed spirometry; these patients typically go on to have normal chest radiographs by adolescence. More severe cases may demonstrate bronchial wall thickening, air trapping, lung cysts, linear interstitial opacities and emphysema. Case series suggest infants with BPD have more frequent airway hyperreactivity in adulthood and may have increased susceptibility to respiratory infections. Our patient presented with minimal symptoms, a history of MV during premature infancy and a novel, bilateral paraseptal emphysematous pattern without other underlying etiology suggesting BPD as the cause. Prevention in premature infants is key to management of this disease and centers on minimizing airway pressures during MV, antenatal glucocorticoids and exogenous surfactant therapy. CONCLUSIONS: The sequela of BPD infrequently persists into adulthood. We postulate that the diffuse and symmetric paraseptal emphysema in this adult patient with no other pulmonary risk factors is a previously undescribed manifestation of bronchopulmonary dysplasia as a premature infant. Reference #1: Howling SJ, Northway WH Jr, Hansell DM, Moss RB, Ward S, Müller NL. Pulmonary sequelae of bronchopulmonary dysplasia survivors: high-resolution CT findings. AJR Am J Roentgenol. 2000 May;174(5):1323-6. DISCLOSURE: The following authors have nothing to disclose: Tyler Church, Kyle Keinath, Whittney Warren, John Sherner No Product/Research Disclosure Information

Associations between antenatal glucocorticoid treatment and offspring early childhood developmental milestones

Reduced-intensity conditioning (RIC) and T cell depletion (TCD) through CD34+ cell selection without the use of post-transplantation immunosuppression are 2 strategies used to reduce nonrelapse mortality (NRM) in older patients after allogeneic hematopoietic cell transplantation (allo-HCT). To compare the efficacy of the RIC and TCD approaches, we evaluated the outcomes of patients age >50 years with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) who underwent allo-HCT from an HLA-matched donor with one of these strategies. Baseline characteristics were comparable in the patients receiving TCD (n = 204) and those receiving RIC (n = 151), except for a higher proportion of unrelated donors (68% versus 40%; P < .001) and a higher comorbidity burden (Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI] ≥3: 51% versus 38%; P < .001) in the TCD cohort. Analysis of outcomes at 3 years showed a higher chronic graft-versus-host disease (GVHD)/relapse-free survival (CRFS) (51% versus 7%; P < .001), lower incidences of grade II-IV acute GVHD (18% versus 46% at day +180) and chronic GVHD (6% versus 55% at 3 years; P < .001), and a lower incidence of relapse (19% versus 33% at 3 years; P = .001) in the TCD group compared with the RIC group. Relapse-free survival (RFS), overall survival (OS), and NRM were similar in the 2 groups. Combining transplantation approach (RIC versus TCD) and comorbidity burden (HCT-CI 0-2 versus ≥3), patients with an HCT-CI score of 0-2 seemed to benefit from the TCD approach. In conclusion, in this retrospective study, the use of a CD34+ cell-selected graft and a myeloablative conditioning regimen was associated with higher CRFS and similar RFS and OS compared with unmodified allo-RIC in patients age >50 years with AML and MDS.

Mid-Childhood Bone Mass After Exposure to Repeat Doses of Antenatal Glucocorticoids: A Randomized Trial.

Treatment of women at risk for preterm birth with repeat doses of glucocorticoids reduces neonatal morbidity, but could have adverse effects on skeletal development. We assessed whether exposure to repeat antenatal betamethasone alters bone mass in children whose mothers participated in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids. Women were randomized to a single dose of betamethasone or placebo, ≥7 days after an initial course of glucocorticoids, repeated each week that they remained at risk for preterm birth at <32 weeks' gestation. In this follow-up study, children underwent whole-body dual-energy radiograph absorptiometry at 6 to 8 years' corrected age. Of 212 eligible childhood survivors, 185 were studied (87%; 91 repeat betamethasone group; 94 placebo [single course] group). Children exposed to repeat antenatal betamethasone and those exposed to placebo had similar whole-body bone mineral content (median repeat betamethasone: 553 g, interquartile range: 442-712 g; placebo: 567 g, interquartile range: 447-750 g; geometric mean ratio: 0.99; 95% confidence interval: 0.94-1.03, P = .55) and bone area (median repeat betamethasone 832 cm2, interquartile range: 693-963 cm2; placebo: 822 cm2, interquartile range: 710-1020 cm2; geometric mean ratio: 0.99, 95% confidence interval: 0.92-1.07, P = .75). Exposure to repeat doses of antenatal betamethasone compared with a single course of glucocorticoids does not alter bone mass in mid-childhood.

Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia

Antenatal glucocorticoid therapy significantly improves the short-term systemic outcomes of prematurely born infants, but there is limited information available on their impact on neurodevelopmental outcomes in at-risk preterm babies exposed to perinatal asphyxia. Preterm fetal sheep (0.7 of gestation) were exposed to a maternal injection of 12 mg dexamethasone or saline followed 4 h later by asphyxia induced by 25 min of complete umbilical cord occlusion. In a subsequent study, fetuses received titrated glucose infusions followed 4 h later by asphyxia to examine the hypothesis that hyperglycemia mediated the effects of dexamethasone. Post-mortems were performed 7 days after asphyxia for cerebral histology. Maternal dexamethasone before asphyxia was associated with severe, cystic brain injury compared to diffuse injury after saline injection, with increased numbers of seizures, worse recovery of brain activity, and increased arterial glucose levels before, during, and after asphyxia. Glucose infusions before asphyxia replicated these adverse outcomes, with a strong correlation between greater increases in glucose before asphyxia and greater neural injury. These findings strongly suggest that dexamethasone exposure and hyperglycemia can transform diffuse injury into cystic brain injury after asphyxia in preterm fetal sheep.

Chronic Activation of the MAP Kinase Pathway in Isolated Proximal Tubules of Adult Male Sheep with Antenatal Glucocorticoid Exposure

The administration of antenatal glucocorticoids is a well‐accepted therapeutic approach to improve the survivability of infants; an estimated 100,000 women annually who are in jeopardy of premature delivery are treated with steroids. Although antenatal steroid treatment has clear benefit for pulmonary development and improved mortality of the newborn, the long‐term consequences of glucocorticoid exposure during a critical period in fetal development for the adult offspring are not clear. We established a model of fetal programming in the sheep whereby pregnant ewes are exposed to the same dose of glucocorticoids and at the same period of gestation as that applied clinically. The betamethasone‐exposed (BMX) offspring exhibit indices of cardiovascular dysregulation including elevated blood pressure, a reduced baroreflex response and an imbalance in the kidney and brain renin‐angiotensin systems (RAS). The adult exposed males also exhibit a reduced capacity to excrete a sodium (Na+) load that may contribute to the sustained increase in blood pressure. In this regard, isolated proximal tubule cells from male BMX sheep show an enhanced basal increase in Na+ uptake and an exaggerated Na+ response to angiotensin II (Ang II); however, the natriuretic response to Ang‐(1‐7) is blunted suggesting that antenatal steroid exposure impairs the regulation of Na+ in the proximal tubules of adult males. The present study investigated the downstream signaling events in isolated proximal tubules that may reflect the altered expression of the Ang II‐AT1 receptor and Ang‐(1‐7)‐AT7/Mas receptor pathways by antenatal steroid exposure. Proximal tubules (PTs) were isolated from kidneys of control and BMX adult male sheep (~1.2 years of age) and the soluble PT extracts were initially analyzed by a multiplex intracellular signaling array (Cell Signaling, Danvers MA). The array data revealed that components of the MAP kinase pathway [ERK1/2, p38, JNK] were elevated in the PT extracts from the BMX sheep. We then sought to confirm that the MAP kinase pathway was activated in the PTs of exposed sheep using individual antibodies for the phosphorylated (phospho) and total isoforms for each kinase. The MAP kinase phospho‐ERK1/2 was increased 3.7‐fold in the BMX PTs as compared to the non‐exposed controls [2.28±0.57 vs. 0.62±0.07; n = 4 per group, p&lt;0.05]. The phospho‐p38 isoform was increased 2.6‐fold in the PTs from the exposed BMX sheep as compared to the non‐exposed group [1.46±0.24 vs. 0.57±0.22; n = 4 per group, p&lt;0.05]. The chronic activation of the MAP kinase pathway in the BMX PTs may reflect an attenuated expression of cellular phosphatases. One potential target involved in the regulation of both ERK1/2 and p38 is the dual specificity phosphatase DUSP‐1; however, immunoblot analysis did not reveal a difference in the expression of DUSP‐1 between the BMX and control sheep. In summary, the present data demonstrate that the MAP kinase pathway is chronically stimulated in the tubules of BMX male sheep. We suggest that both an activated Ang II‐AT1 receptor axis and an attenuated Ang‐(1‐7)‐AT7/Mas receptor pathway contribute to the long‐term alteration of the MAP kinase system within the renal tubules that potentially accounts for the altered Na+ handling in this model of glucocorticoid‐dependent fetal programming.Support or Funding InformationNICHD HD084227, HD‐047584 and HD‐017644

Confirming the Most Effective Strategy for Improving Neonatal Outcomes in Threatened Preterm Birth

Despite the known survival benefits of antenatal glucocorticoids, administration before 24 weeks' gestation is still based on consensus. To determine

Effect of glucocorticoids on mechanisms of placental angiogenesis

The benefits of antenatal glucocorticoid (GC) treatment to promote human fetal lung maturation are well established. However, reports have emerged indicating that maternal exposure to high concentrations of circulating GCs alters placental and fetal development. Because many adult-onset metabolic and cardiovascular disorders have their origins in utero, the importance of prenatal conditions should be considered in detail. Therefore, this review aims to present an overview of the GC effect on placental and fetal development, specifically with regard to mechanisms of placental angiogenesis.We assumed that GC overexposure affects fetal development by altering placental angiogenesis. Disturbances in the development of the villous tree and pathological changes in the villous vascular system with insufficient uteroplacental blood flow have been linked to the pathogenesis of intrauterine growth retardation. Moreover, low birth weight is a serious risk factor known to correlate with an increased risk of adult-onset diseases. Although there have been many circumstances in which maternal GCs are elevated, we focused on exogenous synthetic GCs that are applied for therapeutic reasons. However, some questions about the use of steroids remain unanswered, which will require further studies that lead us to review alterations in placental angiogenesis under the perspective of GC overexposure.

The effects of antenatal glucocorticoid exposure on fetal and neonatal skin maturation.

The use of antenatal glucocorticoids in women with preterm labor has dramatically improved outcomes for premature infants. The most commonly used antenatal glucocorticoids are betamethasone and dexamethasone. Glucocorticoids accelerate fetal lung growth by several mechanisms, including the maturation of type II pneumocytes enabling surfactant production. Furthermore, the lipids in the lung share similarity with those in the skin. Therefore, antenatal administration of glucocorticoids may have effects on the structure and function of the developing epidermal barrier in fetuses and neonates. We performed a systematic review to characterize these effects, identifying 11 studies (six animal and five human studies). Five out of the six animal studies used a rodent model for investigating the effects of antenatally administered glucocorticoids, while the other used an ovine model. Antenatally administered glucocorticoids accelerated skin maturation in animal studies, but studies of human fetuses found conflicting results. None of the reviewed studies compared the effects of different types of glucocorticoids. More human studies are needed to fully understand the effects of antenatal steroids. However, as the antenatal use of glucocorticoids in preterm pregnancies has become part of standard clinical practice, it would be unethical to carry out a large randomized controlled trial. We may have to rely on animal models to improve our understanding of the effects of antenatal glucocorticoid exposure on the fetal and neonatal skin maturation.

Repeat doses of antenatal betamethasone and risk factors for cardiometabolic disease at early school age.

Commentary on: McKinlay CJ, Cutfield WS, Battin MR, Dalziel SR, Crowther CA, Harding JE, ACTORDS Study Group. Cardiovascular risk factors in children after repeat doses of antenatal glucocorticoids: an RCT. Pediatrics 2015; 135: e405–15. McKinlay et al. 1 provides new evidence regarding some aspects of long-term safety with the use of repeated courses of antenatal corticosteroids. The original aim of the ACTORDS study was to evaluate short-term outcomes, and it has shown reduced neonatal morbidity after repeated courses of antenatal corticosteroids without an associated increase in neurologic disability at two years of corrected age or at mid-childhood 2. In the context of cardiometabolic health, the associations between preterm birth and later hypertension, diabetes, stroke and even death from cardiovascular disease 3 – boosted by animal data – have generated worries about glucocorticoid exposure in foetal life, especially if repeated. The central worry is that this glucocorticoid exposure might be in the causal pathway towards cardiometabolic disease in adult life. Previously, there had been some conflicting observational data 4-9. The long-term evaluation by McKinlay et al. carries an important message; that is, there were no adverse cardiovascular and metabolic outcomes in children exposed to repeat dose(s) of antenatal betamethasone. Although reassuring, there are some, as always, remaining questions and limitations. First, extremely preterm infants were few in the ACTORDS study. The average gestational age at study entry was >28 weeks. It cannot be excluded that extremely low gestational age at exposure may exert long-standing effects on glucose metabolism. Secondly, although six to eight years of follow-up most be considered as long term from a neonatologist's perspective, it may be too short for the outcomes addressed. Finally, the authors state that they will report other outcomes separately. These include neurologic function, lung function, general intellectual ability, specific cognitive skills, behaviour, general health and health-related quality of life. I look forward to coming reports. So what should the attending obstetrician and neonatologist recommend? The latest Cochrane review of 10 randomised trials comparing single and repeat courses of antenatal glucocorticoids for neonatal morbidity favours repeat courses. And although repeated courses have been associated with lower birthweight and small reductions in head circumference, data on long-term safety outcomes are so far generally reassuring 2. According to ACOG present guidelines, a single rescue course of antenatal corticosteroids may be considered if the antecedent treatment was given more than two weeks prior, the gestational age is less than 32 weeks and the women are judged by the clinician to be likely to give birth within the next week. The ACTORDS follow-up studies – the one reviewed herein and others 2 – add further support for such recommendation. https://ebneo.org/2015/05/repeat-doses-of-antenatal-betamethasone-and-risk-factors-for-cardio-metabolic-disease-at-early-school-age/ None. None.

Influence of antenatal synthetic glucocorticoid administration on pyramidal cell morphology and microtubule-associated protein type 2 (MAP2) in rat cerebrocortical neurons.

.Previous animal studies have indicated that excessive prenatal circulating glucocorticoid (GC) levels induced by the antenatal administration of synthetic GC (sGC) significantly alter neuronal development in the cerebellar and hippocampal neurons of the offspring. However, it is unknown whether antenatal sGC administration results in long-term neocortical pyramidal cell impairment. In the current study, we examined whether an equivalent therapeutic dose of antenatal betamethasone phosphate (BET) in pregnant rats alters the Golgi-stained basilar dendritic length and histochemical expression of dendritic microtubule-associated protein 2 (MAP2) of neocortical pyramidal cells in infant, adolescent, and young adult offspring. The results obtained showed that in utero BET exposure resulted in a significant reduction in the basilar dendritic length per neuron and a transient reduction in histochemical MAP2 immunoreactivity. Consistent with previous hippocampal and cerebellar data, the present findings suggest that prenatal BET administration alters the dendritic growth of cerebrocortical pyramidal cells.

Antenatal glucocorticoid administration significantly reduced the immunohistochemical expression of synaptophysin and locomotor behaviour in adolescent rats

Antenatal glucocorticoid administration significantly reduced the immunohistochemical expression of synaptophysin and locomotor behaviour in adolescent rats