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PubMed2003

A single course of prenatal betamethasone in the rat alters postnatal brain cell proliferation but not apoptosis.

The aim of this study was to determine the effects of a clinically relevant single course of prenatal betamethasone in the rat on growth parameters with particular reference to brain cell proliferation and apoptosis. We report that administration of 170 microg kg-1 betamethasone twice within 4 h to E20 pregnant rats conveys moderate somatic growth retardation. Further, using a measure of brain cell proliferation independent of blood-brain barrier (BBB) permeability, we demonstrate for the first time that betamethasone is chronically anti-proliferative to brain cells without inducing caspase-3-mediated apoptosis. More importantly we show that there is a significant and sexually divergent rebound of neural proliferation which occurs earlier in males than in females and continues until at least 21 days of postnatal life. BBB permeability to [3H]thymidine was significantly increased by steroid treatment re-iterating the fact that tracer studies not correcting for BBB permeability, such as bromodeoxyuridine (BrdU), may be questionable in this type of study. Further, prenatal steroid treatment did not alter postnatal corticosterone levels. In summary we show that prenatal betamethasone conveys significant and long-lasting side effects and that its human clinical application in preterm labour needs more careful consideration as compared to the relative ease with which it is prescribed today.

Animals↗
PubMed1975

Effect of placebo substitution during long-term betamethasone valerate aerosol treatment in asthmatic children.

Ten children with severe asthma, who had been well controlled on maintenance betamethasone valerate aerosol for an average of 11 months, were given placebo aerosols without their knowledge. The period of placebo substitution was campared with one 28-day period of betamethasone valerate therapy beforehand, and two 28-day periods afterwards. Symptoms were increased during the placebo period, and patients did not return to their previous well-controlled state until the second month after reinstitution of therapy. Changes in the means of twice-daily peak expiratory flow readings (PEFR) followed the same pattern as changes in symptoms. The exacerbation of asthma which occurred during placebo treatment was accompanied by a widening in the diurnal variation between morning and evening PEFR. In comparison with the previous period, morning PEFR fell by a greater amount than evening PEFR. Standardized running tests suggest an increase in exercise-induced bronchoconstriction and in the Exercise Lability Index when the child was receiving only placebo treatment as compared with betamethasone valerate treatment. The trial provided further evidence of the efficacy of betamethasone valerate aerosol in the prophylatic therapy of severe childhood asthma. As 2 of these children were able to discontinue long-term therapy it is unlikely that this drug causes dependency.

Aerosols↗
PubMed1982

Induction of parturition in cows using betamethasone.

To avoid dystocia and calf mortality two groups of cows were induced to calve six or seven days prematurely. Group I consisted of none Hereford cross Friesian two-and-a-half-year-old recipient cows carrying Continental beef breed fetuses. Group 2 consisted of 10 four-year-old Continental beef breed cows carrying pure or crossbred fetuses of the same breeds. On day 280 of gestation a long-acting betamethasone formulation was injected into all 19 animals, followed five or six days later with an injection of short-acting betamethasone (15 animals) or prostaglandin F2alpha (one animal). Three cows calved before their second injection. Fourteen of the 15 animals given the short-acting betamethasone calved 26 to 70 hours later; the remaining animal was given prostaglandin at 72 hours and calved 36 hours later. The cow that received prostaglandin F2alpha instead of short-acting betamethasone calved after 11 hours. None of the calves in group I was born dead but three died within 36 hours. One calf was born dead in group 2. Cervical dilatation and slackening of pelvic ligaments were satisfactory in all animals. Although calf birthweights were between 39 and 60.5 kg, only two instances of dystocia were encountered. Thirteen of the 19 cows voided their fetal membranes within 12 hours of calving. Only two retained them for more than four days. All cows except two in group I showed good udder development and had a plentiful supply of colostrum at calving.

Animals↗
PubMed2005

Hepatic glucose regulation and metabolism in adult sheep: effects of prenatal betamethasone.

Fetal exposure to synthetic glucocorticoids in sheep results in increased fetal hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and corticosteroid-binding globulin (CBG) protein levels and insulin resistance in postnatal life. The aim was to determine whether these changes persisted to adulthood and whether alterations in mediators of hepatic glucocorticoid and glucose regulation contributed to changes in metabolism. Pregnant ewes or their fetuses received either repeated intramuscular saline (MS, FS) or betamethasone injections (0.5 mg/kg; M4, F4) at 104, 111, 118, and 124 days of gestation (dG), or a single betamethasone injection at 104 dG followed by saline at 111, 118, and 124 dG (M1, F1). Offspring were catheterized at 2 and 3 yr of age and given an intravenous glucose challenge (0.5 mg/kg). Hepatic tissue was collected at 3.5 yr. At 2 yr of age, basal plasma insulin was elevated in M4 offspring and at 3 yr of age was elevated in F4 offspring. Basal insulin-to-glucose ratio was significantly elevated in M4 offspring at 2 yr of age and elevated in M1, M4, and F4 offspring at 3 yr of age. All betamethasone treatments resulted in significant increases in hepatic glucose-6-phosphatase (G-6-Pase) activity. Hepatic glucocorticoid receptor protein levels were not altered in M1 and M4 offspring but were increased in F1 and F4 offspring. Hepatic CBG protein levels were lower in F4 but not F1 offspring and were unchanged from control in M1 and M4 offspring. Prenatal betamethasone exposure results in elevated hepatic G-6-Pase activity in adulthood and may contribute to long-term changes in metabolism.

Animals↗
PubMedDate not supplied

Doppler measurements in fetoplacental vessels after maternal betamethasone administration.

OBJECTIVE: To observe the influence of maternal betamethasone administration for fetal lung maturation on the arterial, venous and intracardiac blood flow of the fetus and the uterine arteries. METHODS: Twenty-seven women with singleton pregnancies were examined before the first, and 30 min and 8, 24, 48 and 72 h after the second of two single doses of 8 mg of betamethasone. We recorded blood flow velocity waveforms of the umbilical artery (UA), the middle cerebral artery, the uterine arteries, the ductus venosus, the inferior vena cava and the right hepatic vein, the pulmonary trunk, the ductus arteriosus and the right and left intraventricular inflow of the heart. RESULTS: The resistance index of the UA showed a significant transient decrease 30 min (p = 0.024) after the second betamethasone dose. The peak systolic velocity of the ductus arteriosus increased significantly 30 min after the 2nd dose (p = 0.009) and then returned to non-significant values. No significant change was observed in any of the other vessels. CONCLUSION: Betamethasone causes short-term changes in fetal blood flow. However, this effect seems to be mild and reversible and does not appear to contraindicate the use of corticosteroids to promote fetal lung maturation.

Arteries↗
PubMed1992

Comparative study of ketoconazole 2% foaming gel and betamethasone dipropionate 0.05% lotion in the treatment of seborrhoeic dermatitis in adults.

Sixty-two patients with seborrhoeic dermatitis were treated topically with a 2% ketoconazole foaming gel or with a 0.05% betamethasone dipropionate lotion in a single-blind study for 4 months. Changes in the number of Pityrosporum ovale were scored by a mycologist. The investigator rated the severity of erythema, scaling and itching of the patients' scalp, eyelashes, nasolabial folds and thorax. In addition, both the investigator and the patients evaluated the treatments globally. At the end of treatment, the response rate for ketoconazole 2% foaming gel was significantly higher than that for betamethasone dipropionate 0.05% lotion according to the global evaluation by the physician (89 vs. 62%, p less than 0.05) and the patient (89 vs. 65%, p less than 0.05). Ketoconazole was also superior to betamethasone with reference to the evolution of the symptoms, irrespective of their localization. This efficacy manifested itself by a significant reduction of the number of P. ovale on the scalp in the ketoconazole group (p less than 0.001) compared to the betamethasone group, in which the count was hardly changed during therapy. The treatment was also better tolerated in the ketoconazole group (5 vs. 16 patients with side-effects, p less than 0.001). It is concluded that ketoconazole 2% foaming gel offers an excellent alternative to local corticosteroids in the treatment of seborrhoeic dermatitis.

Administration, Topical↗
PubMed1975

Glucocorticoid levels in maternal and cord serum after prenatal betamethasone therapy to prevent respiratory distress syndrome.

Serum glucocorticoid levels were determined in 20 mothers and 43 premature infants who received prenatal betamethasone therapy for prevention of respiratory distress syndrome (RDS). Maternal betamethasone peaked at 75 microg cortisol equivalents per 100 ml 1 h after injection of 12 mg steroid and declined to half by 6 h. Betamethasone in cord blood was 14.3 microg cortisol equivalents per 100 ml at 1 h, decreased to a level of 4.7 at 20 h, and was not detected 2 days after a second dose at 24 h. After the second dose, the mean level of cortisol in cord blood was 5.9 microg per 100 ml compared with 13.05 microg per 100 ml (p less than 0.001) in untreated premature infants. The unbound glucocorticoid activity in treated infants delivered 1-10 h after the second dose (mean, 8.4 microg per 100 ml) is similar to the unbound cortisol level after birth in untreated premature infants who develop RDS. These findings indicate that (a) serum glucocorticoid levels in the physiologic stress range can induce lung maturation in the human and (b) antenatal treatment with this dose of betamethasone does not expose the human fetus to potentially harmful pharmacologic levels of steroid.

Betamethasone↗
PubMed1997

Single dose of betamethasone in combined medical treatment of secretory otitis media.

With the objective of evaluating the efficacy of cefixime and the combination of cefixime and betamethasone in the treatment of secretory otitis media (SOM), we enrolled 142 children 2 to 12 years old in a randomized, double-blind, placebo-controlled study. All children suffered from SOM, verified by otomicroscopy and tympanometry, of at least 3 months' duration. Active treatment was a 10-day course of cefixime with and without a single dose of 6 mg betamethasone. On hundred forty children were available for efficacy evaluation 14 to 23 days after the start of treatment. A statistically significant treatment effect was found in the group treated with cefixime plus betamethasone (n = 59), with a 44.1% cure rate as compared to 19.7% in the cefixime-treated group (n = 61; p < .005) and 5% in the placebo group (n = 20; p < .005). Relapse rates were high and no statistically differences between groups remained at last valid visit. Adverse events possibly or probably associated with active treatment were reported in 11 cases (9.2%). One patient reported a severe adverse event. No serious events occurred. The study did not show any significant long-term effect of cefixime treatment or any long-term treatment benefit with the addition of betamethasone to the antibiotic.

Anti-Bacterial Agents↗
PubMed1987

The effect of betamethasone on neonatal neutrophil chemotaxis.

Antenatal maternal glucocorticoid administration has been widely used to accelerate fetal lung maturation. Glucocorticoids have also been used postnatally in selected neonates as antiinflammatory agents. Numerous studies have shown that glucocorticoids inhibit multiple components of the immune system including neutrophil (PMN) function in children and adults. Since PMNs are of critical importance in host defense against bacterial infection, impaired PMN function in newborn infants is thought to be an important cause of their increased morbidity and mortality from bacterial infection. Further compromise of neonatal PMN function by exogenous factors such as glucocorticoids may therefore be of significant clinical importance. A micropore filter chemotactic assay was used to determine the in vitro effect of betamethasone on the random migration and directed migration (chemotaxis) of PMNs from 18 neonates. The addition of a concentration of betamethasone (0.01 microgram/ml) similar to that found in cord blood following a standard dose administered to the mother resulted in a significant (p less than 0.01) inhibition in mean neonatal PMN random migration (-15.0 +/- 0.8%) and chemotaxis (-23.5 +/- 3.0%). A similar inhibition was not found when PMNs from 14 adults were exposed to the same concentrations of betamethasone. Betamethasone administration to pregnant women or their newborn infants may further impair PMN motility and lead to an increased morbidity and mortality from bacterial infection in neonates.

Bacterial Infections↗
PubMed1998

The influence of betamethasone and dexamethasone on motor development in young rats.

Synthetic corticosteroids such as dexamethasone and betamethasone are widely used in clinical practice of the perinatal period to enhance lung maturation. However, indications emerged both on the basis of investigations in humans and in experimental animals that such treatment leads to abnormal brain development. In the present study, the neurologic development and the development of locomotion were studied in two groups of rats injected either with dexamethasone or with betamethasone on their 3rd and 4th d, and this was compared with development in a group of control rats injected with saline. Each group consisted of 12 rats. Neurologic reflexes were tested daily and the rat's physical development (body weight and age at eye opening) was noted from the 4th until the 21 st d. Locomotion was recorded on videotape and analyzed during playback runs. Results indicated a growth retardation in both groups of rats treated with corticosteroids, but remarkably, the opening of the eyes was advanced by about 1 d in the dexamethasone group compared with control rats and rats treated with betamethasone. Several reflexes showed normal development, but the negative geotaxis and free-fall righting responses developed retarded. Locomotion in both experimental groups was characterized by a postural tremor and an abnormal posture during walking from the 9th until the 15th d. Although the walking pattern after this age became fluent, the gait width remained abnormally increased until the 20th d. Our results indicate that both dexamethasone and betamethasone interfere with the development of vestibular and cerebellar functions involved in complex motor patterns.

Aging↗
PubMed2001

Antenatal betamethasone administration decreases the lung hyaluronan concentration in preterm rabbit pups.

Maternal treatment with corticosteroids before preterm delivery is effective in reducing the incidence of respiratory distress syndrome and neonatal mortality. We hypothesized that corticosteroids might lower the lung hyaluronan concentration. Twenty-five rabbit dams (term = 31 d) with timed pregnancies were injected s.c. with 0.75 mg of betamethasone or saline (controls) 1 d before delivery. In addition, two dams delivered at 25 d of gestation were injected with 0.75 mg of betamethasone on two consecutive days before delivery. A total of 238 live pups were delivered by preterm cesarean section at 25, 27, 28, or 29 d of gestation and killed immediately. Their lung hyaluronan concentrations were measured with a radiometric assay, and wet/dry lung weight ratios were determined. Lungs of rabbit pups exposed antenatally to betamethasone and delivered at 25 or 27 d of gestation, but not at 28 or 29 d, displayed significantly (p = 0.001 and p = 0.008, respectively) lower hyaluronan concentrations than control pups, accompanied by less intense subepithelial staining for hyaluronan in alveolar walls. There was no significant difference in wet/dry lung weight ratio between pups exposed to one dose of betamethasone and controls. Antenatal corticosteroid exposure lowers the lung hyaluronan concentration in preterm rabbit pups delivered at 25 or 27 d of gestation, but not in those delivered at 28 or 29 d.

Animals↗
PubMed2006

Antenatal betamethasone administration has a dual effect on adult sheep vascular reactivity.

The effect of antenatal steroids on blood pressure in humans remains an unresolved question. Here we report the effects of prenatal exposure to clinically relevant doses of betamethasone on endothelial and/or vascular smooth muscle function. Pregnant sheep were randomly treated with betamethasone (0.17 mg/kg) or vehicle at 80 and 81 d of gestation. We studied arterial segments (4th-5th generation) of the right brachial artery obtained at 1-2 y of age under general anesthesia. We demonstrate that in brachial arteries of steroid exposed offspring: KCl induced contraction is increased after endothelium removal or incubation with inhibitors of nitric oxide synthase or cyclooxygenase; acetylcholine-induced relaxation is increased; sensitivity to endothelin-1 (ET-1) is increased and this effect is decreased by the ETB antagonist BQ-788. These data suggest that, in sheep treated with clinically relevant doses of betamethasone at a gestational stage when human fetuses are routinely exposed to glucocorticoids, there is a dual effect of betamethasone on the adult sheep brachial artery, i.e. endothelial dysfunction with an impairment of endothelin-1 ETB receptor-induced release of nitric oxide and an increased contribution of the ETB receptor in smooth muscle to the contractile effects of ET-1.

Acetylcholine↗
PubMed1998

Effect of maternal betamethasone administration at midgestation on baboon fetal adrenal gland development and adrenocorticotropin receptor messenger ribonucleic acid expression.

Although fetal pituitary ACTH is important to fetal adrenal growth and steroidogenesis in the second half of primate pregnancy, its role in adrenal development and function has not been established in vivo in the first half of gestation. In the present study, therefore, baboons were treated at midgestation with betamethasone to determine the effect of fetal pituitary ACTH on fetal adrenal growth, development, and ACTH receptor and P-450 enzyme messenger ribonucleic acid (mRNA) levels. The administration of betamethasone to baboon mothers on days 60-99 of gestation (term = 184 days) decreased fetal pituitary POMC mRNA levels by 54% (P < 0.01) and fetal serum ACTH levels to undetectable values (P < 0.05). The decline in ACTH was associated with decreases in fetal adrenal weight (P < 0.001), cortical cell size (P < 0.05), appearance of apoptosis and cellular disorganization, and a loss of immunocytochemically demonstrable definitive zone-specific delta5-3beta-hydroxysteroid dehydrogenase expression. The concomitant administration of ACTH and betamethasone restored these aspects of adrenal integrity to normal. Moreover, there was approximately a 95% decrease (P < 0.01) in fetal adrenal expression of ACTH receptor, P-450 cholesterol side-chain cleavage, and P-450 17alpha-hydroxylase 17/20-lyase mRNA levels after betamethasone administration. We conclude that fetal pituitary ACTH is necessary for the growth and development of fetal and definitive cortical zones and the marked coordinated increase in ACTH receptor and maintenance of P-450 cholesterol side-chain cleavage/P-450 17alpha-hydroxylase 17/20-lyase expression in the baboon fetal adrenal gland during the first half of gestation.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Occipitofrontal circumference in newborns of betamethasone treated mothers.

Celestona (betamethasone-disodiumphosphate) and Celeston (betamethasone-acetat + betamethasone-disodiumphosphate) given intramuscularly to pregnant women in order to reduce the frequency of respiratory distress syndrome does not reduce the occipitofrontal circumference of the newborn infants. Before the results from the actual work were available an impeding effect of the evolution of the brain was found in the light of animal experiments. The material is comprised of 52 newborn infants whose mothers were treated with Celestona 8 mg daily for 3 days and 46 infants treated with Celeston 12 mg daily for 3 days. The untreated population comprises 1012 newborn infants. Excluded were non-caucasian infants, twins, stillborns and cases of uncertain gestational age. The occipitofrontal circumference in normal infants and those infants treated with betamethasone were compared in Figs. 2 and 3. Focusing only upon cases in which corticoids were given more than 7 days before delivery and in which no placental dysfunction was diagnosed, no differences from the normal were found (Tabs. II and III, and Figs. 3 A and B).

Animals↗
PubMed1987

An alternative to steroids for prevention of respiratory distress syndrome (RDS): multicenter controlled study to compare ambroxol and betamethasone.

The results are reported of a multicenter randomized study of the effectiveness of maternal administration of betamethasone versus ambroxol, a substance of the group of the benzylamines, for prevention of RDS in preterm infants. Women of 27 to 34 weeks gestation with threatened premature delivery or planned premature delivery were admitted to the trial. Between September 1981 and November 1984 a total of 288 randomized patients delivered 315 neonates. The incidence of RDS was assessed in 169 viable neonates born before the 37th week. Of these 86 were born of 76 mothers treated with beta-methasone and 83 of 76 mothers treated with ambroxol. The overall incidence of RDS was significantly (P less than 0.05) higher in the betamethasone group (31%) than the ambroxol group (13%). Ambroxol was significantly more effective than betamethasone in twin births, in infants born before the 31st week, when ROM to delivery time was more than 48 hours, when treatment to delivery time was between 2 and 7 days and in female infants. The neonatal infection rate was significantly higher (P less than 0.05) in the group of betamethasone treated infants (18% with four fatalities) than in the group of ambroxol treated infants (9% with one fatality). These results suggest that ambroxol may be a valid alternative to steroids for prevention of RDS.

Ambroxol↗
PubMed1986

Randomized trial of oral naproxen or local injection of betamethasone in lateral epicondylitis of the humerus.

A randomized pilot study, comparing oral naproxen and a single betamethasone injection, was carried out in 21 patients suffering from lateral epicondylitis of the humerus ("tennis elbow"). The naproxen dosage was 250 mg per day for two weeks. Six milligrams of betamethasone in a long-acting form was given as a local injection. To achieve "blindness," the patients receiving naproxen were also given an injection of saline into the area of maximal tenderness at the epicondyle, while the patients getting the betamethasone-injection were given oral placebo tablets. At a clinical control after two weeks, five of the ten patients receiving naproxen and five of the 11 patients receiving betamethasone injection were improved. Thus, no apparent difference in effect could be noted at an evaluation after two weeks' treatment. No significant side effects were noted with any of the treatments.

Administration, Oral↗
PubMed1999

Multiple vs. single betamethasone therapy. Neonatal and maternal effects.

OBJECTIVE: To identify potential neonatal benefits and possible neonatal and maternal complications associated with repeated use of antenatal corticosteroids. STUDY DESIGN: A retrospective chart review was done on all gravidas < 34 weeks who were hospitalized and received antenatal betamethasone at our institution between January 1, 1992 and April 30, 1996. Regression analysis was performed to investigate the relationship between single vs. multiple course of betamethasone and multiple variables. RESULTS: After controlling for significant covariates, multiple courses of betamethasone were associated with a decrease in oxygen use (P < .01). A nonsignificant decline in respiratory distress syndrome and assisted ventilation was noted. No effect on birth weight or maternal or neonatal infection was seen. CONCLUSION: Repeated use of betamethasone is associated with a significant decrease in oxygen use in the preterm neonate. No significant maternal or neonatal complications were found. A prospective, randomized trial is necessary.

Adult↗
PubMed2000

Evaluation of safety and efficacy of supirocin-B (mupirocin 2% + betamethasone dipropionate 0.05%) in infected dermatoses--a post marketing study.

The aim of the present post marketing study was to study the safety and efficacy of supirocin-B ointment (mupirocin 2% + betamethasone dipropionate 0.05%) in the treatment of infected dermatoses. For this purpose physicians from different parts of India were requested to keep the clinical records prospectively as per a specially designed proforma over a follow-up period of 7 days, whenever they prescribed supirocin-B ointment (mupirocin 2% + betamethasone dipropionate 0.05%) for local application, three times a day, to their patients having either primary infection complicated by dermatoses or dermatoses infected secondarily. From the analysis of 251 clinical records contributed by 27 physicians, it was evident that in clinical practice, supirocin-B ointment (mupirocin 2% + betamethasone dipropionate 0.05%) was found to be safe and very effective by physicians in the treatment of infected dermatoses in 94.8% of the patients. Similarly 92.4% of the patients reported more than 70% improvement in their symptoms after 7 days of treatment. No adverse effects were reported during the treatment period by any of the patients except worsening of skin lesions by one patient. Thus from this study, supirocin-B ointment (mupirocin 2% + betamethasone dipropionate 0.05%) seems to be safe and effective in the treatment of infected dermatoses.

Betamethasone↗