Effect Of Betamethasone Research Articles

Long-Term Evaluation of Low-Dose Betamethasone for Ataxia Telangiectasia

BackgroundAtaxia telangiectasia is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. Quality of life is severely impaired by neurological symptoms. However, curative options for the neurological symptoms are limited. Recent studies have demonstrated short-term improvement in neurological symptoms with betamethasone therapy. However, the long-term and adverse effects of betamethasone are unclear. The aim of this study was to evaluate the long-term effects, benefits, and adverse effects of low-dose betamethasone in ataxia telangiectasia. MethodsSix patients with ataxia telangiectasia received betamethasone at 0.02 mg/kg/day for two years. After cessation of betamethasone, the patients were observed for two additional years. Neurological assessments were performed, and adverse effects were monitored every three months throughout the four-year study period. ResultsTransient improvement of neurological symptom was observed in five of the six patients. However, after two years betamethasone treatment, only one of the six patients showed a slight improvement in the neurological score, one patient showed no change, and the neurological scores of the remaining four patients deteriorated. After the cessation of betamethasone treatment, neurological symptoms worsened in all patients. As an adverse effect of betamethasone, transient adrenal dysfunction was observed in all cases. ConclusionsAlthough these findings are in agreement with previous studies suggesting that short-term betamethasone treatment transiently benefits patients with ataxia telangiectasia, the long-term benefits and risks should be carefully considered.

Prenatal Betamethasone interferes with immune system development and alters target cells in autoimmune diabetes

Non-genetic factors are crucial in the pathogenesis of type 1 diabetes (T1D), a disease caused by autoimmunity against insulin-producing β-cells. Exposure to medications in the prenatal period may influence the immune system maturation, thus altering self-tolerance. Prenatal administration of betamethasone –a synthetic glucocorticoid given to women at risk of preterm delivery– may affect the development of T1D. It has been previously demonstrated that prenatal betamethasone administration protects offspring from T1D development in nonobese diabetic (NOD) mice. The direct effect of betamethasone on the immature and mature immune system of NOD mice and on target β-cells is analysed in this paper. In vitro, betamethasone decreased lymphocyte viability and induced maturation-resistant dendritic cells, which in turn impaired γδ T cell proliferation and decreased IL-17 production. Prenatal betamethasone exposure caused thymus hypotrophy in newborn mice as well as alterations in immune cells subsets. Furthermore, betamethasone decreased β-cell growth, reduced C-peptide secretion and altered the expression of genes related to autoimmunity, metabolism and islet mass in T1D target tissue. These results support the protection against T1D in the betamethasone-treated offspring and demonstrate that this drug alters the developing immune system and β-cells. Understanding how betamethasone generates self-tolerance could have potential clinical relevance in T1D.

Effect of betamethasone, indomethacin and fenoterol on neonatal and maternal mononuclear cells stimulated with Escherichia coli

Despite considerable progress in the field of perinatal care, infectious diseases, especially when caused by gram negative bacteria, remain a major reason for neonatal morbidity and mortality. Notably infants born prematurely and those with very low birth weight are at risk due to their immature and deficient immune system and their prolonged hospitalization which promotes nosocomial infections. In case of impending preterm birth, betamethasone is given to induce lung maturation and tocolytic agents like indomethacin or fenoterol are administered to suppress premature labor. The aim of this study was to analyze the effects of these drugs on the immune system of mothers and neonates. Therefore, mononuclear cells from cord blood and peripheral maternal blood were stimulated with Escherichia coli and incubated with betamethasone, indomethacin and fenoterol. Subsequently the effect of the treatment on cytokine production was determined. Betamethasone alone and in combination with tocolytic agents inhibited the production of pro- and anti-inflammatory cytokines. Not only does betamethasone dampen the immune response by reducing the production of cytokines, it also has a variety of other detrimental short- and long-term effects on the neonate. In conclusion we would recommend using biological markers to determine if premature labor actually leads to preterm birth and subsequently administer betamethasone only to mothers giving birth prematurely.

Mineralisation Influence of Betamethasone on Lipopolysaccharide-Stimulated Dental Pulp Cells.

To evaluate the mineralisation response of lipopolysaccharide (LPS)-induced dental pulp cells (DPCs) to betamethasone and the potential benefit of betamethasone application on the recovery of injured dental pulp. The proliferation influence of betamethasone on DPCs was analysed through the cell counting kit-8 assay. To assess the anti-inflammatory effects of betamethasone, the expression levels of inflammatory factors IL-6, IL-1ß and TNF-∂ were determined by real-time polymerase chain reaction (PCR). Mineralisation was investigated through the detection of the mineralisation-related biomarkers alkaline phosphatase (ALP), dentine sialophosphoprotein (DSPP) and osteocalcin (OCN) through the ALP activity assay, immunohistochemistry staining, Alizarin Red and tissue nonspecific alkaline phosphatase (TNAP) staining, the reverse transcriptase PCR technique and western blot. A low concentration of betamethasone (1 µ/mL) promoted the proliferation of DPCs. The real-time PCR results demonstrated that inflammatory cytokines were downregulated by betamethasone treatment. The mineralisation outcome in DPCs treated with betamethasone was better than in those treated without betamethasone. Betamethasone promoted the proliferation of DPCs. Betamethasone enhanced mineralisation in LPS-stimulated DPCs.

464: Time interval from betamethasone to delivery among women at risk for late preterm delivery

Beneficial effects of betamethasone in the late preterm period are known (Gyamfi-Bannerman, C, et al NEJM 2016). The optimal time interval between betamethasone and delivery, however, is uncertain. Among women at risk of late preterm delivery, we sought to determine whether time interval (TI) between betamethasone and delivery is associated with neonatal adverse respiratory outcomes. This is a secondary analysis of a multicenter randomized trial to determine the effects of betamethasone in women at risk for late preterm delivery. The inclusion criteria for our analysis were singletons with no major anomaly, receiving betamethasone, with calculable TI between administration of last betamethasone dose and delivery. TI categories were: 1) ≤ 48 hours; 2) > 48 and ≤ 168 hours, and; 3) > 168 hours (7 days). Primary outcome was neonatal respiratory outcomes among the 3 TI groups. Primary and secondary outcomes are defined in the tables. Multivariable Poisson regression models with robust error variance were used to determine the association between TI and neonatal outcomes, while adjusting for confounders. Adjusted relative risk (aRR) with 95% confidence intervals (CI) were calculated, using TI > 48 and ≤ 168 hours as the referent group. Of the 2,831 women in the parent trial, 1,414 (50.7%) met our inclusion criteria. While 68.5% delivered in ≤ 48 hours, 15.3% were born > 48 and ≤ 168 hours and 16.2% at > 168 hrs. Factors significantly different among the three groups include: nulliparity, pre-pregnancy BMI, hypertensive disease, premature preterm rupture of membranes, number of betamethasone doses (1 versus 2), preterm delivery (gestational age < 37 weeks), labor type, and route of delivery. Among women who received betamethasone, the primary outcome was significantly less if delivery occurred > 168 hours, compared to > 48 and ≤ 168 hrs. Severe respiratory complications were also significantly lower if delivery occurred > 168 hours, compared to > 48 and ≤ 168 hours. (Table) Even when adjusted for rate of preterm birth, among women at risk for late preterm birth, the lowest rate of neonatal respiratory complication is when delivery occurred beyond 168 hrs (7 days).

Betamethasone suppresses the inflammatory response in LPS-stimulated dental pulp cells through inhibition of NF-κB

ObjectiveThis study aimed to investigate the anti-inflammatory effect of betamethasone on LPS-stimulated human dental pulp stem cells (DPSCs) and its associated mechanism. The osteo-/odontogenic differentiation and osteoclast effect of betamethasone on DPSCs and stem cells from human exfoliated deciduous teeth (SHED) were evaluated. DesignThe proliferative effect of betamethasone on DPSCs was analyzed using a cholecystokinin octapeptide assay. The anti-inflammatory effect of betamethasone was investigated using quantitative polymerase chain reaction (qPCR) and ELISA. The anti-inflammatory mechanism was explored using qPCR, Western blot, and immunofluorescence staining. The osteo-/odontogenic differentiation and osteoclast effect of betamethasone on DPSCs and SHED were detected by qPCR. Results1 μg L-1 betamethasone was found to have the strongest effect on DPSCs proliferation. The expression of pro-inflammatory cytokines and mediators, as well as prostaglandin E2 (PGE2) were significantly decreased following treatment with betamethasone in LPS- stimulated DPSCs. They were also decreased in response to an NF-κB inhibitor, Bay 11-7082. Betamethasone and Bay 11-7082 significantly inhibited the expression of p-p65 and promoted the nuclear exclusion of p65. Gene expression associated with osteo-/odontogenic differentiation was significantly up-regulated in betamethasone and osteogenic media (OM) treated groups. The ratio of the receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) at the mRNA level was suppressed in DPSCs and elevated in SHED. ConclusionsBetamethasone has an anti-inflammatory effect on LPS- stimulated DPSCs through a blockade of NF-κB activation and exhibits an osteo-/odonto-inductive effect on DPSCs and SHED. Although betamethasone displays an osteoclast effect on SHED.

A novel model to study neonatal Escherichia coli sepsis and the effect of treatment on the human immune system using humanized mice.

Neonatal sepsis is a serious threat especially for preterm infants. As existing in vitro and in vivo models have limitations, we generated a novel neonatal sepsis model using humanized mice and tested the effect of Betamethasone and Indomethacin which are used in the clinic in case of premature birth. Humanized mice were infected with Escherichia coli (E. coli). Subsequently, the effect of the infection itself, and treatment with Betamethasone and Indomethacin on survival, recovery, bacterial burden, leukocyte populations, and cytokine production, was analyzed. The human immune system in the animals responded with leukocyte trafficking to the site of infection and granulopoiesis in the bone marrow. Treatment with Indomethacin had no pronounced effect on the immune system or bacterial burden. Betamethasone induced a decline of splenocytes. The human immune system in humanized mice responds to the infection, making them a suitable model to study neonatal E. coli sepsis and the immune response of the neonatal immune system. Treatment with Betamethasone could have potential negative long-term effects for the immune system of the child.

Effects of betamethasone on fetoplacental and maternal hemodynamics in preterm pregnancies.

To evaluate the possible effects of prenatal steroid administration onDoppler parameters of the umbilical artery, uterine artery, middle cerebral artery, and ductus venosus, the cerebroplacental ratio, and the amniotic fluid index in pretermfetuses. The present prospective observational study was performed at the Perinatology Department of Trakya University, Edirne, Turkey, between June 1, 2015, and September 1, 2016. It included patients with healthy singleton pregnancies who had received betamethasone at 24-34weeks of pregnancy. Doppler parameters were measured before (0hours) and 24, 48, and 72hours after the administration of betamethasone (two intramuscular doses of 12mg each, administered 24hours apart). There were 68 patients included. Pairwise comparisons demonstrated that, at 72hours after betamethasone administration, the umbilical artery resistance index (P=0.038), the middle cerebral artery systolic/diastolic velocity ratio (P=0.007), and the amniotic fluid index (P=0.017) were reduced, whereas the end-diastolic velocity of the middle cerebral artery was increased (P=0.012), compared with baseline values. Betamethasone had favorable effects on fetal cerebral circulation, with increased end-diastolic velocity in the middle cerebral artery; this could represent a positive effect on cerebral blood circulation and decreased flow resistance in the umbilical artery.

The influence of betamethasone on fetal heart rate variability, obtained by non-invasive fetal electrocardiogram recordings

BackgroundBetamethasone is widely used to enhance fetal lung maturation in case of threatened preterm labour. Fetal heart rate variability is one of the most important parameters to assess in fetal monitoring, since it is a reliable indicator for fetal distress. AimTo describe the effect of betamethasone on fetal heart rate variability, by applying spectral analysis on non-invasive fetal electrocardiogram recordings. Study designProspective cohort study. SubjectsPatients that require betamethasone, with a gestational age from 24 weeks onwards. Outcome measuresFetal heart rate variability parameters on day 1, 2, and 3 after betamethasone administration are compared to a reference measurement. ResultsFollowing 68 inclusions, 12 patients remained with complete series of measurements and sufficient data quality. During day 1, an increase in absolute fetal heart rate variability values was seen. During day 2, a decrease in these values was seen. All trends indicate to return to pre-medication values on day 3. Normalised high- and low-frequency power show little changes during the study period. ConclusionsThe changes in fetal heart rate variability following betamethasone administration show the same pattern when calculated by spectral analysis of the fetal electrocardiogram, as when calculated by cardiotocography. Since normalised spectral values show little changes, the influence of autonomic modulation seems minor.

Periapical injection of betamethasone to control postoperative pain in emergency endodontic care - a randomized double blind clinical trial

Aim: the objective of this study was to evaluate the effect of betamethasone in the control of postoperative pain in patients undergoing endodontic treatment. Methods: patients of both genders (n = 120), after being submitted to emergency endodontic treatment, received a single dose of betamethasone solution (0.05 mg / body weight) or sterile saline solution intramucosally, in the periapical region of the treated tooth. The study evaluated the intensity of pain experienced by the patient and the number of analgesics consumed during periods of 4, 24 and 48 hours after endodontic treatment. To compare the level of pain among the groups and the use of analgesics the Fisher’s Exact Test was used, adopting a significance level of 95%. Results: patients who received betamethasone felt less pain in 4 hours (p = 0.0177) and 24 hours (p = 0.0012) compared to those who received the placebo. Conclusions: betamethasone at a dose of 0.05 mg / body weight administered in the periapical region is a advantageous protocol due to its effectiveness, and also because of the comfort it provides to patients in the prevention or control of inflammatory pain in endodontics.

Effect of Betamethasone on Fetal Pulmonary and Umbilical Artery Doppler Velocimetry and Relationship With Respiratory Distress Syndrome Development.

Respiratory distress syndrome (RDS) is a major cause of neonatal morbidity and mortality. It is primarily a disease of premature neonates. The aim of this study was to evaluate the impact of maternal betamethasone administration on the fetal pulmonary arteries (PAs) and umbilical arteries (UAs) and the correlation between RDS development and PA Doppler results. Forty singleton pregnancies between 24 and 34 gestational weeks with a diagnosis of preterm birth were included prospectively. They received corticosteroids to enhance fetal lung maturity. Fetal PA and UA Doppler parameters were evaluated before and 48 to 72 hours after steroid administration. Maternal records were matched to neonatal charts, and demographic and outcome data were abstracted. There were no differences between groups for maternal age, body mass index, mode of delivery, and mean GA at steroid administration. Apgar scores at 1 and 5 minutes were significantly lower for neonates who developed RDS (P < .05). There were no statistically significant differences in PA Doppler results between fetuses who developed RDS and those who did not, and there were no significant differences in PA Doppler results before and after steroid administration for both groups. The UA pulsatility and resistive indices were significantly lower after steroid administration for the neonates who developed RDS (P < .05). There were no significant differences in PA Doppler indices for fetuses with or without RDS after steroid administration.

The Effect of Betamethasone on Middle Cerebral Artery Doppler Flow in Fetuses With Elevated Peak Systolic Velocities [27Q

INTRODUCTION: Administration of betamethasone (BMZ) has been shown to decrease the morbidity and mortality associated with preterm birth, and is given to patients with a variety of complications such as preterm labor, PPROM, fetal growth restriction, and alloimmunization, among others. As middle cerebral artery (MCA) Dopplers are used to monitor fetal hemodynamics in patients with many of these conditions, we sought to determine if administration of betamethasone is associated with changes in MCA Doppler parameters in fetuses with an abnormally elevated MCA peak systolic velocity (PSV). METHODS: A retrospective longitudinal study was conducted including women with a fetal MCA PSV greater than 1.3 MoM that had an MCA Doppler assessment within one week before and one week after betamethasone administration. Pre- and post-BMZ MCA PSV were compared using a repeated measures t-test. RESULTS: 20 fetuses met inclusion criteria with diagnoses of alloimmunization (13), parvovirus infection (3), fetal growth restriction (2), and twin-twin transfusion (2). The pre-BMZ PSV of 1.60±0.16 MoM was significantly lower than the post-BMZ PSV of 1.41±0.16 MoM (p &lt; 0.0001). 13 of the 20 fetuses had a second post-BMZ MCA Doppler performed with a PSV of 1.5±0.24 MoM which was not significantly different from the initial post-BMZ MCA PSV (p=0.231). CONCLUSION: Our data suggest that maternal betamethasone administration lowers the MCA PSV in fetuses with an initially elevated MCA PSV. This should be taken into account when using MCA Dopplers to monitor fetal hemodynamics in patients receiving BMZ.

The role of prenatal steroids at 34–36 weeks of gestation

A recent multicentre, double-blind, randomised, placebo-controlled trial has demonstrated that administration of betamethasone to women with threatened preterm delivery at 34–36 weeks of gestational age reduces the risk of neonatal...

Fetal and Neonatal Outcomes After Term and Preterm Delivery After Betamethasone Administration in Twin Pregnancies

(Abstracted from Int J Gynaecol Obstet 2016;134:329–335) Prenatal betamethasone administration in singleton pregnancies is associated with a dose-dependent decrease in birth weight. This study aimed to determine the effects of betamethasone overall, and at different doses on fetal growth and neonatal outcomes in twin pregnancies based on fetal sex, chorionicity, and severity of prematurity.

Predictors of the Usefulness of Corticosteroids for Cancer-Related Fatigue in End-of-Life Patients

Although some studies have examined the use of corticosteroids, their effectiveness in treating cancer-related fatigue (CRF) has yet to be established. Therefore, this retrospective study attempted to identify factors that would predict the usefulness of corticosteroids in treating CRF. We examined 87 hospitalized end-of-life cancer patients who were given betamethasone for relief of CRF at our hospital between January 2008 and January 2014. We evaluated the effect of betamethasone at 3days after administration and performed a multivariate logistic regression analysis designed to identify predictive factors for the usefulness of corticosteroids. Threshold measurements were examined using a receiver operating characteristic (ROC) curve. This analysis identified the initial daily dose of betamethasone [odds ratio (OR)=1.662], days from the start date of betamethasone administration to the date of death (OR=1.05), administration of fentanyl (OR=0.206) and age (OR=1.055) as significant factors related to the effect of betamethasone. ROC curve analysis of the effect of the betamethasone showed that the threshold for the initial daily dose of betamethasone was above 4mg, the threshold for the days from the start date of the betamethasone administration to the date of death was above 16days and the threshold for age was above 60years old. The initial daily dose of betamethasone, days from the start date of the betamethasone administration to the date of death, non-administration of fentanyl and advanced age were shown to be predictive factors for the usefulness of corticosteroids for CRF in end-of-life patients.

Abnormal cell-clearance and accumulation of autophagic vesicles in lymphocytes from patients affected with Ataxia-Teleangiectasia

Ataxia-Teleangiectasia (A-T) is a neurodegenerative disorder due to mutations in ATM gene. ATM in the nucleus ensures DNA repair, while its role in the cytosol is still poorly clarified. Abnormal autophagy has been documented in other neurodegenerative disorders, thus we evaluated whether alteration in this process may be involved in the pathogenesis of A-T by analyzing the autophagic vesicles and the genes implicated in the different stages of autophagy. Through transmission electron microscopy (TEM) and immunofluorescence analysis we observed an accumulation of APs associated with a LC3 puncta pattern, and a reduced number of ALs. We also documented an increased expression of genes involved in AP and lysosome biogenesis and function, and a decrease of Vps18 expression, involved in their vesicular trafficking and fusion. mTORC1-controlled proteins were hyperphosphorylated in A-T, in keeping with an increased mTOR inhibitory influence of autophagy. Betamethasone is able to promote the degradation of SQSTM1, a biomarker of autophagy. Collectively, our results indicate that in cells from A-T patients, the APs maturation is active, while the fusion between APs and lysosomes is inappropriate, thus implying abnormalities in the cell-clearance process. We also documented a positive effect of Betamethasone on molecules implicated in autophagosome degradation.

Development of somatosensory-evoked potentials in foetal sheep: effects of betamethasone.

Antenatal glucocorticoids are used to accelerate foetal lung maturation in babies threatened with premature labour. We examined the influence of glucocorticoids on functional and structural maturation of the central somatosensory pathway in foetal sheep. Somatosensory-evoked potentials (SEP) reflect processing of somatosensory stimuli. SEP latencies are determined by afferent stimuli transmission while SEP amplitudes reveal cerebral processing. After chronic instrumentation of foetal sheep, mothers received saline (n=9) or three courses of betamethasone (human equivalent dose of 2×110μgkg-1 betamethasone i.m. 24h apart, n=12) at 0.7, 0.75 and 0.8 of gestational age. Trigeminal SEP were evoked prior to, 4 and 24h after each injection and at 0.8 of gestational age before brains were histologically processed. Somatosensory-evoked potentials were already detectable at 0.7 of gestation age. The early and late responses N20 and N200 were the only reproducible peaks over the entire study period. With advancing gestational age, SEP latencies decreased but amplitudes remained unchanged. Acutely, betamethasone did not affect SEP latencies and amplitudes 4 and 24h following administration. Chronically, betamethasone delayed developmental decrease in the N200 but not N20 latency by 2weeks without affecting amplitudes. In parallel, betamethasone decreased subcortical white matter myelination but did not affect network formation and synaptic density in the somatosensory cortex. Somatosensory stimuli are already processed by the foetal cerebral cortex at the beginning of the third trimester. Subsequent developmental decrease in SEP latencies suggests ongoing maturation of afferent sensory transmission. Antenatal glucocorticoids affect structural and functional development of the somatosensory system with specific effects at subcortical level.

Effect of betamethasone on patch test reactivity in patients with parthenium dermatitis.

Effect of betamethasone on patch test reactivity in patients with parthenium dermatitis.

Effect of betamethasone, surfactant, and positive end-expiratory pressures on lung aeration at birth in preterm rabbits.

Antenatal glucocorticoids, exogenous surfactant, and positive end-expiratory pressure (PEEP) ventilation are commonly provided to preterm infants to enhance respiratory function after birth. It is unclear how these treatments interact to improve the transition to air-breathing at birth. We investigated the relative contribution of antenatal betamethasone, prophylactic surfactant, and PEEP (3 cmH2O) on functional residual capacity (FRC) and dynamic lung compliance (CDL) in preterm (28 day GA) rabbit kittens at birth. Kittens were delivered by cesarean section and mechanically ventilated. FRC was calculated from X-ray images, and CDL was measured using plethysmography. Without betamethasone, PEEP increased FRC recruitment and CDL Surfactant did not further increase FRC, but significantly increased CDL Betamethasone abolished the benefit of PEEP on FRC, but surfactant counteracted this effect of betamethasone. These findings indicate that low PEEP levels are insufficient to establish FRC at birth following betamethasone treatment. However, surfactant reversed the effect of betamethasone and when combined, these two treatments enhanced FRC recruitment irrespective of PEEP level.

Fetal and neonatal outcomes after term and preterm delivery following betamethasone administration in twin pregnancies

ObjectiveTo investigate effects of betamethasone on fetal growth and neonatal outcomes in twins. MethodsA retrospective cohort study was conducted of twins delivered at one center in Berlin, Germany, between 1993 and 2011. The betamethasone group included twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to betamethasone between 23+5 and 33+6 weeks. The control group included twin pregnancies with no betamethasone exposure matched for length at delivery. Fetal growth and neonatal anthropometric data were analyzed by twin-pair structure, dose, and gestational age (linear mixed model). ResultsOverall, 1922 live-born twin pairs (653 betamethasone group, 1269 controls) were included. Compared with controls, late-preterm twins exposed to betamethasone were lighter (mean difference –126g), had a smaller head circumference (–0.4cm), and a shorter body length (–0.8cm) after adjustment for confounders (P<0.05). Female neonates from mixed or same-sex twin pairs had a lower birth weight than controls (betamethasone ≤16mg: –114g; betamethasone 24mg: –124g; betamethasone >24mg: –187g), with no detectable improvement in neonatal morbidity (hyperbilirubinemia, respiratory distress, asphyxia) or mortality. ConclusionBetamethasone reduced birth weight, head circumference, and length of female preterm neonates in twin pairs in a dose-dependent manner. The neonatal mortality and morbidity were not improved by betamethasone.