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PubMed1977

Effect of antepartum betamethasone treatment on cortisol levels in cord plasma, amniotic fluid, and the neonate.

Antepartum betamethasone treatment in pregnancies which terminated at less than 37 weeks of gestation resulted in a rapid and significant decrease in cord plasma cortisol levels. Mean values +/- S.E. were 5.17 +/- 0.39 microng per 100 ml. in 90 untreated cases, 2.17 +/- 0.32 microng per 100 ml. in 29 cases treated at least 24 hours prior to delivery, and 2.27 +/- 0.38 microng per 100 ml. in 18 cases in which treatment was begun within 24 hours of delivery. The mean cortisol concentration in five amniotic fluid samples obtained after betamethasone administration (0.93 +/- 0.19 microng per 100 ml.) was significantly less than in seven control samples (1.85 +/- 0.21 microng per 100 ml.) These results suggest that betamethasone suppressed endogenous cortisol production by maternal and/or fetal adrenals. However, blood cortisol levels during the first days of life of treated neonates were considerably increased in comparison to those in cord plasma, suggesting that there was rapid recovery of their adrenal function.

Amniotic Fluid↗

PubMed1978

Response of immature baboon fetal lung to intra-amniotic betamethasone.

Intra-amniotic betamethasone (6 mg.) given to six immature fetal baboons, at four and again at three days prior to delivery by cesarean section, between 147 and 158 days' gestation (term = 180 days), significantly increased the amniotic fluid lecithin/sphingomyelin (L/S) ratio. At delivery, treated animal lungs were more mature in that they had a significantly increased deflation stability and significantly decreased minimum surface tension in minced lung when compared to five control animals. Changes in maximum air distensibility lagged behind changes in deflation stability. The major molecular species of pulmonary phosphatidylcholine were analyzed by gas liquid chromatography as the diacylglycerol derivatives. The proportions of 14:0/16:0, 16:0/16:0, and 16:0/18:0, were significantly increased over control proportions while unsaturated species tended to decrease in animals exposed to intra-amniotic betamethasone. The immature fetal baboon pulmonary system responded to intra-amniotic betamethasone with a synchronous increase in the L/S ratio, improved pulmonary stability, and a more mature pulmonary lecithin composition, but did not demonstrate a synchronous increase in tissue distensibility.

Amnion↗

PubMed1988

Betamethasone effects on steroid and prostaglandin concentrations in pregnant rhesus monkeys.

Glucocorticoids delay parturition in rhesus monkeys, but the mechanism is unknown. This study was designed to determine the relationship between administration of glucocorticoids and prostaglandin levels in late pregnancy. Pregnant rhesus monkeys received intramuscular betamethasone (2 mg/day) from day 120 to day 133 of pregnancy. 13,14-Dihydro-15-keto-prostaglandin F2 alpha, progesterone, estradiol, estrone, and cortisol in amniotic fluid were measured by radioimmunoassay, and progesterone and estradiol were measured in the maternal serum. Among control animals, between 133 days and 160 days there were significant increases in adrenal size (p less than 0.05) and in amniotic fluid 13,14-Dihydro-15-keto-prostaglandin F2a metabolite, (p less than 0.005), estrone, and progesterone concentrations (p less than 0.05). The increase in adrenal size and the rise in amniotic fluid 13,14-Dihydro-15-keto-prostaglandin F2a metabolite, did not occur in betamethasone-treated monkeys. Maternal serum estradiol levels were suppressed immediately after treatment with betamethasone but recovered to control levels by day 160. Other changes in maternal serum and amniotic fluid sex steroid levels were sought but not observed. These data are consistent with the hypothesis that glucocorticoids delay primate parturition by altering intrauterine prostaglandin F2 alpha metabolism.

Amniotic Fluid↗

PubMed1992

Stereochemical analysis of betamethasone and dexamethasone by derivatization and high-performance liquid chromatography.

A simple and economical high-performance liquid chromatographic method has been developed for the simultaneous determination of betamethasone and dexamethasone. The method is based on the derivatization of the structural epimers of betamethasone and dexamethasone with a homochiral reagent, N-carbobenzoxy-L-phenylalanine. The derivatives obtained were easily recognized by a non-chiral silica column with n-hexane-dichloromethane-isopropanol (100:100:4, v/v/v) as a mobile phase and a good separation was obtained for quantitation. The method was satisfactorily applied to the determination of betamethasone and dexamethasone in tablets.

Betamethasone↗

PubMed1995

Constriction of the fetal ductus arteriosus during prenatal betamethasone therapy.

BACKGROUND: Constriction of the fetal ductus arteriosus occurs with maternal indomethacin treatment and has been suggested with corticosteroid therapy as well. CASE: Fetal ductal constriction was diagnosed by Doppler echocardiography at 29 weeks' gestation after a third and fourth course of betamethasone was administered to a pregnant woman with placenta previa. Doppler echocardiography showed a patent ductus arteriosus 3 days after the treatment. CONCLUSION: The risk-benefit ratio of betamethasone should be assessed by large-scale studies when repeated courses or chronic maternal administration of betamethasone are required.

Adult↗

PubMed1986

Effects of betamethasone on theophylline disposition in man. Are saliva values predictive of serum theophylline levels?

The pharmacokinetic interaction between betamethasone (5 mg/day for 5 days) and theophylline (3.35 mg/kg orally before and after betamethasone treatment) was studied in 13 female patients evaluating saliva and serum theophylline concentrations by means of an enzyme multiplied immunoassay technique. Betamethasone treatment did not significantly change saliva and serum theophylline levels. As regards the potential usefulness of saliva theophylline levels in predicting the concomitant serum concentrations of the bronchodilator, in spite of the significant correlation found in our study (r = 0.758; P less than 0.001), we think that, using individual saliva values, there is a poor predictive value for serum theophylline concentrations.

Adolescent↗

PubMed1991

A double-blind, multicenter comparison between 0.05% halobetasol propionate ointment and 0.05% betamethasone dipropionate ointment in chronic plaque psoriasis.

In a double-blind, parallel-group, multicenter comparative trial on 104 evaluable patients with severe, localized plaque psoriasis, 0.05% halobetasol propionate ointment demonstrated an 88.7% success rate assessed as "healed" or "marked improvement" compared with 78.5% for 0.05% betamethasone dipropionate ointment. Healing was observed within 24 days of the start of treatment in 40% and 25% of the patients who received halobetasol propionate and betamethasone dipropionate ointments, respectively. After 4 weeks' treatment, tolerability of both ointments was good. Neither skin atrophy nor systemic adverse effects were observed. Patient acceptance of halobetasol propionate ointment, based on cosmetic acceptability and ease of application, was significantly better (p = 0.02) than that of betamethasone dipropionate ointment.

Administration, Topical↗

PubMed1987

Establishment of Ascaridia galli in betamethasone-treated chickens.

Twenty-five day-old White Leghorn chickens were each infected orally with 500 (Group I), 1000 (Group II) and 2000 (Group III) infective eggs of Ascaridia galli and were killed 30 days after the infection. A high percentage of the infecting dose (6.5%) established as adult worms in the intestine of chickens receiving the lowest level of primary infection, but as the amount of primary infection given to birds increased, there was a significant fall in the percentage establishment of adult worms in the intestine. A similar pattern of worm establishment was shown by chickens of the same age and receiving similar levels of primary infections, but which were treated with betamethasone at a dose of 2 mg/kg body weight commencing 5 days before and continuing up to 15 days after the infection. Betamethasone-treated birds, however, showed more establishment of worms in the intestine, but lower weight gains in comparison to the birds which were not treated. Different levels of primary infections given, with or without treatment with betamethasone, had no effect on the sex ratio of the resultant male/female worm populations, which became established in almost equal numbers in the intestine of chickens.

Animals↗

PubMed2006

Lowering the dose of antenatal steroids: the effects of a single course of betamethasone on somatic growth and brain cell proliferation in the rat.

We investigated the effects of a single course of antenatal betamethasone on neonatal somatic and brain development. On day 20 of gestation, pregnant rats were injected with either with 170 microg kg(-1) body weight of betamethasone ("clinically-equivalent dose," equivalent to 12 mg twice, 24 hours apart) or half this dose or vehicle. Pups (8-11 animals per experimental group per timepoint per gender) were analyzed at 1 (P1), 2, and 21 days after birth. We report that betamethasone induced a significant dose-dependent decrease of somatic measurements in both genders. At P1 cell proliferation was affected by the "clinically equivalent dose" only in the subventricular zone in both genders and in the hippocampus in males. In summary, we show for the first time that a lower dose (equivalent to 6 mg) induces fewer and less severe effects on somatic growth, whereas it does not affect cell proliferation within the brain.

Animals↗

PubMed2005

Effect of betamethasone on neuropathic pain and cerebral expression of NF-kappaB and cytokines.

Glucocorticoids have been used to treat neuropathic pain for many years, but the underlying mechanisms are still unknown. Recent studies indicate that pathological pain states may be mediated by cytokines. We, therefore, examined the effect of betamethasone on neuropathic pain and the relationship between pain behavior and the expression of cytokines in the brain. Rats were given epidural injections of betamethasone (Diprospan) after L5 spinal nerve transection. Mechanical allodynia and thermal hyperalgesia were evaluated on post-operative days 1, 3, 7, 14 and 21 with von Frey and Hargreaves tests. Cerebral expression of NF-kappaB, TNFalpha, IL-1beta and IL-10 was quantified using electrophoretic mobility shift assay (EMSA) or enzyme-linked immunosorbent assay (ELISA). We found that spinal nerve injury caused long-lasting mechanical and thermal hyperalgesia in the hind paw and stimulated the expression of NF-kappaB, TNFalpha, IL-1beta and IL-10 in the brain. A single epidural injection of betamethasone at the time of nerve injury partially inhibited the development of neuropathic hyperalgesia and reduced the subsequent elevated levels of pro-inflammatory cytokines in the brain, while stimulating the expression of the anti-inflammatory cytokine IL-10. These data support our hypothesis that pro-inflammatory cytokines in the brain may mediate the hyperalgesic effects of spinal nerve injury and that the long-acting anti-hyperalgesic effects of epidural glucocorticoid treatment are due to an inhibitory effect on pro-inflammatory cytokine levels and a stimulatory effect on anti-inflammatory cytokine levels in the brain.

Animals↗

PubMed2005

Maternal and feto-placental prostanoid responses to a single course of antenatal betamethasone.

We tested the hypothesis that antenatal betamethasone alters prostanoid levels in the maternal and feto-placental compartments. Forty-three singleton pregnancies were studied. Group I were women treated with a single course of antenatal betamethasone and who delivered <37 weeks gestation; Group II were untreated women who delivered <37 weeks; and Group III were untreated women who delivered >38 weeks. Maternal and mixed cord blood; and placental samples were collected at delivery and analyzed for PGE2, PGF(2alpha), 6-ketoPGF(1alpha), and TxB2 levels. Antenatal betamethasone decreased maternal PGE2 levels with concomitant increases in the feto-placental compartment. Umbilical cord TxB2 levels in the treated group were significantly lower than the non-treated pre-term and term groups resulting in a higher 6-ketoPGF(1alpha):TxB2 ratio. Considering the regulatory role of PGE2 and PGI2 in fetal lung development and neonatal transition homeostasis, these results suggest a mechanism, at least in part, for the beneficial effects of antenatal steroids on fetal lung maturation and neonatal cardio-pulmonary homeostasis at birth.

Adult↗

PubMed1996

Dynamics of the fetal adrenal, cholesterol, and apolipoprotein B responses to antenatal betamethasone therapy.

OBJECTIVE: Prior studies suggest that fetal plasma cholesterol is regulated in part by the rate of uptake and utilization of low-density lipoprotein cholesterol by the fetal adrenals for use in steroid biosynthesis. Direct evidence for this phenomenon and the kinetics of this process is, however, virtually impossible to obtain in a controlled experiment in the developing human. In the current study we sought to take advantage of the anticipated transient inhibition of the hypothalamic-pituitary-adrenal axis that occurs after antenatal therapy with glucocorticosteroids, to evaluate the temporal relationship between fetal adrenal steroids and plasma lipoprotein cholesterol levels in umbilical cord blood at delivery. STUDY DESIGN: Umbilical cord serum was obtained at delivery from 136 infants (30.5 +/- 2.7 weeks' gestation) who previously had been treated in utero with betamethasone, 12 mg per 12 or 24 hours for one or two doses and from 308 preterm infants (30.5 +/- 2.1 weeks) who had not been exposed to such therapy. We quantified the concentrations of dehydroepiandrosterone sulfate and cortisol as representative fetal adrenal steroids and also measured the total cholesterol and apolipoprotein B; the relationship between the steroids and lipids as a function of the interval between initial treatment and delivery was analyzed. RESULTS: Umbilical cord levels of dehydroepiandrosterone sulfate and cortisol were significantly reduced within the first 24 hours after initial treatment and remained significantly lower than in control infants through 4 days after initial treatment. In contrast, serum levels of cholesterol were significantly increased 3 to 4 days after treatment but fell on day 5. Serum levels of apolipoprotein B generally followed the same pattern as cholesterol. Cholesterol levels also were higher than normal in infants delivered >1 week after initial betamethasone treatment. CONCLUSIONS: The results of this study are consistent with the view that the plasma cholesterol pool in the fetus is regulated, at least in part, by the rate of uptake of low-density lipoprotein cholesterol and utilization by the fetal adrenals as substrate for steroidogenesis. Betamethasone also may influence cholesterol and lipoprotein synthesis in the fetus.

Apolipoproteins B↗

PubMed1975

Betamethasone 17 valerate aerosol and disodium chromoglycate in severe childhood asthma.

Eleven children with severe perennial asthma and a poor clinical response to disodium cromoglycate were studied in a 4-month, double blind trial involving 1 month's treatment with placebo, disodium cromoglycate, betamethasone 17 valerate, and both drugs combined according to a predetermined random design. Each drug apparently reduced symptoms and improved daily peak flow and fortnightly spirometric measurements compared with placebo, but the improvement after betamethasone 17 valerate was greater in part because of the way this group of patients was selected. There did not appear to be any additional benefit when both drugs were used together. Betamethasone 17 valerate was not compared with beclomethasone diproprionate aerosol and there is no reason to believe it may be superior. Corticosteroid aerosols have potential hazards which may prove to equal those of long-term systemic steroids, but they offer the prospect of satisfactory control of symptoms without the risk of growth suppression in children with severe asthma. Disodium cromoglycate remains the drug of choice in severe childhood asthma and the use of corticosteroid aerosols should be confined to those children who fail to respond satisfactorily to disodium cromoglycate.

Adolescent↗

PubMed1982

Treatment with intermittent high dose methylprednisolone or intermittent betamethasone for antisperm antibodies: preliminary communication.

Thirty-four men received steroid therapy in an attempt to overcome antisperm antibodies. Fifteen men received intermittent methylprednisolone (MP), 7 men received intermittent betamethasone following a failed course of MP, and 12 men received intermittent betamethasone. The pregnancy rate following steroid treatment, when compared with the expected pregnancy rate for patients with similar duration of infertility, was significantly improved. The titers of antibodies fell during steroid treatment. There were steroid side effects in all groups, although these were less marked in the group that received betamethasone alone. This work provides evidence that steroid treatment alters the expected prognosis and indicates that there is justification for a randomized trial in spite of the risks of treatment.

Autoantibodies↗

PubMed1980

Fetal sex and prenatal betamethasone therapy.

We examined the influence of fetal sex on the occurrence of respiratory distress syndrome in premature infants after maternal treatment with betamethasone. Among treated infants of 1,251 to 1,750 gm birth weight, the incidence of RDS was 40.9% in 22 males and 7.1% (P = 0.03) in 14 females. Cord serum levels of betamethasone were similar for infants of both sexes, and there was no sex difference in suppression of serum cortisol, dehydroepiandrosterone sulfate, and growth hormone after treatment. These findings suggest that prenatal corticosteroid therapy is less effective in male infants than in female infants. This effect is not due to a difference in transfer or metabolism of betamethasone, nor is it reflected in the responsiveness of the fetal hypothalamic-pituitary-adrenal axis to synthetic glucocorticoid.

Betamethasone↗

PubMed1981

An enzyme immunoassay for plasma betamethasone.

A sensitive enzyme immunoassay for plasma betamethasone was developed using betamethasone-3-(O-carboxymethyl)oxime-beta-D-galactosidase conjugate as a labelled antigen and 4-methylumbelliferyl-beta-D-galactoside as a fluorescence substrate. The performances of the enzyme immunoassay were compared with that of a radioimmunoassay using 3H-betamethasone and the same antiserum. The minimal detectable level for the enzyme immunoassay was 0.15 pg/tube or 0.15 ng/ml of plasma, which was remarkably more sensitive than the radioimmunoassay level of 10 pg/tube or 2 ng/ml of plasma. The specificity was sufficient, in particular, the cross reactivity of cortisol as 0.008%. However, the precision of the enzyme immunoassay was inferior to that of the radioimmunoassay.

Betamethasone↗

PubMed1981

Correlation between metabolism of betamethasone 17,21-dipropionate and adrenal hypertrophy in rat fetuses.

The effects of metabolites of betamethasone 17,21-dipropionate (BMDP) on the hypothalamo-pituitary-adrenocortical axis were assessed by measurements of adrenal weights, after studying the metabolism of BMDP in vivo and in vitro in pregnant rats and mice. After BMDP was injected intravenously at a dose of 5 mg/kg into rats and mice in late stages of pregnancy, it disappeared rapidly from the plasma and brain stages of pregnancy, it disappeared rapidly from the plasma and brain in both mothers and fetuses while betamethasone 17-propionate (BMP) was detected as the main metabolite followed by betamethasone (BM). In vitro studies demonstrated that BMDP was metabolized to BMP in maternal and fetal tissues (plasma, liver, brain and placenta) of both species. The subcutaneous administration of BMP to rats in the late stages of pregnancy induced adrenal hypertrophy in fetuses, though the adrenals of the mothers became atrophic. In the case of mice, both maternal and fetal adrenals became atrophic. Administration of BM produced adrenal atrophy in mothers and fetuses of both species. The subcutaneous administration of 6 beta-hydroxybetamethasone 17-propionate (6 beta-OH-BMP) to rat fetuses in utero produced adrenal hypertrophy and 6 beta-hydroxybetamethasone (6 beta-OH-BM) showed no effect. These data suggest that BMP is transferred across the placental barrier to produce marked adrenal hypertrophy in rat fetuses.

Adrenal Glands↗

PubMed1993

Protective effects of disodium etidronate and pamidronate against the biomechanical repercussion of betamethasone-induced osteopenia in growing rat femurs.

To assess the protective effect of bisphosphonates on the biomechanical repercussion of glucocorticoid-induced osteopenia, intraperitoneal doses of 1 or 10 mg/kg/d of disodium etidronate or 1 or 50 mg/kg/day of pamidronate were given to groups of 6 growing rats simultaneously receiving subcutaneous doses of 4.8 mg/kg/day of betamethasone for 20 days. Betamethasone impaired strength and stiffness of femur diaphyses through a reduction of geometric properties, abnormally enhancing bone ability to absorb energy. Both bisphosphonates partially prevented betamethasone effects on diaphyseal stiffness (but not strength) through positive, dose-related effects on material modulus of elasticity and slighter improvements in diaphyseal geometry, avoiding the enhancement of energy-absorbing ability and the subsequent tendency to production of comminute fractures. These results and others obtained treating normal rats with (pamidronate) APD suggest that the sign of bisphosphonate effects on bone biomechanics may depend not only on the type of compound but also on eventual interactions with concomitant treatments.

Animals↗