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Peak bone mass after exposure to antenatal betamethasone and prematurity: follow-up of a randomized controlled trial.

UNLABELLED: Small birth size is associated with reduced adult bone mass. We determined if antenatal betamethasone exposure, birth weight, or prematurity affects peak bone mass in 174 adults. Antenatal betamethasone exposure did not. Lower birth weight and prematurity predicted reduced adult height. Slower fetal growth rather than prematurity predicted lower bone mass, but this lower bone mass was appropriate for reduced adult height. INTRODUCTION: Small size at birth is reported to be associated with lower bone mass in adulthood. However, previous studies have not distinguished the relative contributions of length of gestation and fetal growth to size at birth. Fetal exposure to excess glucocorticoids has been proposed as a core mechanism underlying the associations between birth size and later disease risk. Antenatal glucocorticoids are given to pregnant women at risk for preterm delivery for the prevention of neonatal respiratory distress syndrome in their infants. We determined the relationship of antenatal exposure to betamethasone, birth weight, and prematurity to peak bone mass and femoral geometry in the adult survivors of the first randomized trial of antenatal glucocorticoids. MATERIALS AND METHODS: We studied 174 young adults (mean age, 31 years) whose mothers participated in a randomized trial of antenatal betamethasone. Mothers received two doses of intramuscular betamethasone or placebo 24 h apart. Two thirds of participants were born preterm (<37 weeks gestation). We measured indices of bone mass and size and derived estimates of volumetric density and bone geometry from DXA assessments of the lumbar spine, femur, and total body. RESULTS: There were no differences between betamethasone-exposed and placebo-exposed groups in any of the lumbar spine, femur, or total body DXA measures. There was no effect of antenatal betamethasone on adult height, although leg length was increased relative to trunk length (p = 0.002). A lighter birth weight (p <or = 0.001) and lower gestational age (p = 0.013) were associated with shorter stature (height Z scores) at age 31 years. Prematurity had no effect on peak bone mass or femoral geometry. However, lower birth weight, independent of gestational age, was associated with lower later bone mass (p < 0.001 for lumbar spine and total body, p = 0.003 for femoral neck BMC). These effects on bone mass were related to bone size and not to estimates of volumetric density. In the femur, lower birth weight, independent of gestational age, was associated with narrowing of the upper shaft and narrow neck regions. CONCLUSIONS: Antenatal betamethasone exposure does not affect peak bone mass or femoral geometry in adulthood. Birth weight and prematurity predict adult height, but it is slower fetal growth, rather than prematurity, that predicts lower peak bone mass. The lower peak bone mass in those born small is appropriate for their adult height.

Absorptiometry, Photon↗

Comparison of the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo.

It has been shown previously that topical corticosteroid treatment decreases collagen synthesis in human skin in vivo and that the adverse effects are due to reduced collagen synthesis. The aim of the present study was to evaluate the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo. Fourteen healthy male volunteers applied hydrocortisone, hydrocortisone-17-butyrate, betamethasone and vehicle twice a day for one week to four separate areas marked on their abdominal skin. The collagen synthesis rate in the skin was measured by assaying collagen propeptides from the suction blisters induced on the treated areas. Aminoterminal propeptide of type I procollagen (PINP) and aminoterminal propeptide of type III procollagen (PIIINP) were measured from skin blister fluid using radioimmunoassays. Skin thickness was measured with ultrasound. Hydrocortisone decreased the two propeptides studied in the suction blister fluids less than did hydrocortisone-17-butyrate and betamethasone, but the interindividual variation was great. Hydrocortisone-17-butyrate and betamethasone had almost similar decreasing effects on the propeptides in the suction blister fluid. Hydrocortisone decreased the concentrations of PINP and PIIINP by about 35%. In some subjects (4/14) the decline of the collagen propeptide levels was over 50%. The decline in the concentration of PINP was 63% by hydrocortisone-17-butyrate and 69% by betamethasone, while the decrease in PIIINP was 55% by hydrocortisone-17-butyrate and 62% by betamethasone. None of the treatments had any effect on skin thickness within one week. In conclusion, it seems that hydrocortisone is less atrophogenic than hydrocortisone-17-butyrate and betamethasone, as shown by radioimmunoassays for collagen propeptides. The order of inhibitory potency of the three glucocorticoids on collagen synthesis was hydrocortisone < hydrocortisone-17-butyrate < betamethasone. Thus, assay of collagen propeptides from suction blisters can be used to screen various steroids with respect to their action on collagen synthesis.

Administration, Topical↗

The effect of betamethasone and dexamethasone on fetal heart rate patterns and biophysical activities. A prospective randomized trial.

UNLABELLED: BACKGROUND; Contradictory findings on the effect of betamethasone versus dexamethasone on antenatal tests of fetal well-being have been reported. The purpose of this study was to compare the effects of these steroid compounds on fetal heart rate patterns and biophysical activities in a prospective. randomized trial. STUDY DESIGN: Forty-six pregnant women (gestational age range 27-34 weeks) at risk for preterm delivery were randomized to receive betamethasone or dexamethasone for enhancement of fetal lung maturity. Fetal heart rate was recorded for 60 minutes and analyzed with the Sonicaid System 8000 before (0 hours), and 48 hours and 96 hours after steroid administration. Subsequently, fetal limb, body and breathing movements were sonographically observed and quantified for 30 minutes. To account for fetal circadian rhythms, all examinations were performed between 1 p.m. and 5 p.m., at least one hour after maternal meals. RESULTS: Fetal heart rate accelerations (p<0.001; p<0.01), short-term variation (p<0.0001; p<0.05), long-term variation (p<0.01; p=NS), duration of high episodes (p<0.001; p<0.05), total movement count (p<0.001; p<0.05), and duration of breathing time (p<0.0001; p<0.0001) were substantially reduced 48 h after betamethasone and dexamethasone administration, respectively, with percent reduction being larger for the betamethasone group, except for breathing movements (p<0.05; p<0.001; p<0.001; p<0.005; p<0.05; p=NS; respectively). In 68.2%( and 45.5% of fetuses, less than 30 seconds of continuous breathing movements were found in the betamethasone and dexamethasone groups, respectively. In 71.8% and 12.5%, of fetuses, respectively, less than 2 body/limb movements were observed. Therefore five and two fetuses in the betamethasone and dexamethasone study group, respectively, had both nonreactive fetal heart rate monitors for 60 minutes and biophysical profiles of < or =4/10. All parameters returned to baseline values at 96 h. Baseline fetal heart rate and numbers of decelerations remained unchanged (p=NS). CONCLUSIONS: Both betamethasone and dexamethasone induce a profound, albeit transient, suppression of fetal heart rate characteristics and biophysical activities in the preterm fetus. However, the effect of betamethasone is more pronounced. Awareness of these phenomena might prevent unwarranted iatrogenic delivery of preterm fetuses.

Adult↗

Maternal intravenous administration of long chain n-3 polyunsaturates to the pregnant ewe in late gestation results in specific inhibition of prostaglandin h synthase (PGHS) 2, but not PGHS1 and oxytocin receptor mRNA in myometrium during betamethasone-induced labor.

OBJECTIVES: Both the onset of labor and time to delivery during betamethasone-induced delivery are delayed by omega-3 polyunsaturated fatty acid (PUFA) administration to pregnant sheep. That fatty acid also inhibits the labor-related increase in maternal plasma estradiol and maternal and fetal prostaglandin E(2). To evaluate the mechanism of inhibition of prostaglandin production and delay of onset of labor and time of delivery in PUFA-treated sheep, we determined the effect of PUFA on myometrial prostaglandin H synthase (PGHS) 1 and 2 and oxytocin receptor mRNA levels in betamethasone-induced labor. METHODS: At 124 days' gestation, a 20% emulsion of either intralipid (IL, n = 6) or PUFA (n = 6) was infused continuously (3 mL/kg per day) intravenously (IV) to the ewe. At 125 days' gestation, betamethasone was administered IV (10 microg/h over 48 hours) to fetuses of both intralipid- and PUFA-treated ewes. Myometrium was collected at necropsy either during betamethasone-induced labor as evaluated by myometrial electromyography or within 5 days of the termination of betamethasone infusion, if delivery did not occur after fetal betamethasone infusion. Total myometrial RNA was analyzed by Northern blot for oxytocin receptor and PGHS1 and 2 mRNA normalized for 18s. RESULTS: Treatment with PUFA decreased myometrial PGHS2 mRNA but did not alter myometrial PGHS1 and oxytocin receptor mRNA after betamethasone administration. CONCLUSIONS: This finding provides a mechanism whereby PUFA delays betamethasone-induced delivery in sheep and suggests a potential role of PUFA as an effective tocolytic agent in human pregnancy.

Animals↗

[Effects of betamethasone administration on maternal-fetal Doppler velocimetry].

BACKGROUND: The effect of antenatal betamethasone on fetal parameters includes a transient reduction of fetal heart rate variation and of fetal body movements. An effect on maternal-fetal blood flow has also been shown, with non-univocal results. AIMS: To evaluate the effect of antenatal betamethasone in third trimester singleton high-risk pregnancies by Doppler technology. SUBJECTS AND METHODS: Thirty-six pregnant women who received a full course of betamethasone (12 mg i.m. two times, 24 hrs apart) were studied. The Doppler examination included the assessment of the pulsatility index (PI) of the umbilical artery (UA PI), the middle cerebral artery (MCA PI) and of resistance index of uterine arteries (Ut RI) before treatment, and 48 and 96 hrs after second dose of betamethasone. RESULTS: No significant variation was noted in UA PI through betamethasone therapy. MCA PI decreased significantly 48 hours from the last injection of betamethasone (p = 0.004), and returned to basal values at 96 hours. No difference was found for the other Doppler parameters examined. When serial Doppler studies were analyzed according to the gestational age, in the group < 32 wks' gestation, MCA PI decreased significantly after 48 hours (p < 0.006) and returned to pre-treatment values after 96 hours from the last betamethasone dose. Conversely, no difference was found in Doppler serial measurements in any of the analyzed districts in the subgroup > or = 32 wks' gestation. CONCLUSION: Betamethasone treatment is associated with an increase in end diastolic flow of the middle cerebral artery, as reflected by a significant, although transient, reduction of MCA PI, especially at gestational ages < 32 weeks.

Betamethasone↗

Inhibition of glucose-6-phosphate dehydrogenase activity by betamethasone and three of its esters with dermatological importance.

Betamethasone, betamethasone-17-valerate, betamethasone-17-benzoate, and betamethasone-17,21-diproprionate were investigated for their inhbitory action on glucose-beta-phosphate dehydrogenase (G-6-PDH) activity (pure enzyme from yeast, enzyme from human skin homogenate). Between these four compounds, marked differences were encountered which could not be attributed to the presence of an esterified or unesterified steroid. According to these data it does not seem to be justified to consider betamethasone esters simply as the transport forms of the topically inactive betamethasone but one must consider the betamethasone esters having biochemical actions of their own.

Betamethasone↗

Topical betamethasone 17-valerate is an anticorticosteroid in the rat. 2. Anti-inflammatory and anti-lymphocyte activities.

In the oxazolone-induced delayed hypersensitivity inflammation in the rat ear, betamethasone 17-valerate, in contrast to other topical corticosteroids, is incapable of suppressing oedema. When given in combination with triamcinolone acetonide, betamethasone 17-valerate competitively antagonizes the anti-inflammatory action of the active steroid. When tested in the mouse, betamethasone 17-valerate behaved as an anti-inflammatory agent 15 and 80 times as potent as betamethasone and hydrocortisone respectively. In an in vivo lymphocyte culture system in which preincubation with corticosteroids prevents subsequent phytohaemagglutinin induced DNA synthesis, betamethasone 17-valerate was less active than even hydrocortisone when rat lymph node cells were used, but with human cell preparations it was more potent than either hydrocortisone or betamethasone. Betamethasone 17-valerate behaves uniquely in the rat as an anticorticosteroid; in mouse and in man the compound behaves as a normal corticosteroid.

Administration, Topical↗

1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study.

OBJECTIVE: During the last decades, management of intertriginous psoriasis (IP) has been unsatisfactory because of the adverse effects associated with long-term corticosteroid application and the lack of alternatives. Recently, both pimecrolimus and tacrolimus have been investigated for this indication and shown to be safe and effective. So far, to our knowledge, a comparison of one of these drugs with standard regimens for IP has not been performed. DESIGN: A single-center, 4-week, double-blind, randomized, vehicle-controlled comparison study to assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone valerate in the treatment of IP. SETTING: Dermatologic hospital at Ruhr University of Bochum. PATIENTS: Eighty adults with IP. INTERVENTIONS: Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or the vehicle once daily for 28 days. MAIN OUTCOME MEASURES: Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching. RESULTS: After 4 weeks of treatment, the 3 active compounds and the vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1% betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and 21.1% for vehicle). The 0.1% betamethasone was significantly more effective than 1% pimecrolimus during the study period (P<.05). No significant difference was found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005% calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1% pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for the corticosteroid (P<.05). CONCLUSIONS: The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice.

Administration, Cutaneous↗

Analysis of betamethasone, dexamethasone and related compounds by liquid chromatography/electrospray mass spectrometry.

A reversed-phase high-performance liquid chromatography/electrospray ionisation mass spectrometry (HPLC/ESI-MS) method has been developed to conclusively differentiate the epimers betamethasone and dexamethasone and various esterification products (betamethasone and dexamethasone 21-acetate, betamethasone and dexamethasone 21-phosphate, betamethasone 17-valerate, betamethasone 21-valerate and betamethasone 17,21-dipropionate) in counterfeit drugs. Good separation with baseline resolution of all epimers or isomers was obtained on a Zorbax Eclipse XDB or Luna C8 column, using a step gradient with mobile phases of 0.05 M ammonium acetate and acetonitrile. Betamethasones can also be distinguished by the relative abundance of their m/z 279 ion in the positive electrospray tandem mass spectra. The LC/MS or LC/MS/MS method developed was successfully applied to the analysis of drug product samples, i.e. creams and tablets.

Betamethasone↗

Albumin synthesis and effect of betamethasone on albumin synthesis in perfused liver of normal and CCL4-intoxicated rats.

Synthesis of plasma albumin was studied in perfused liver of normal and CCl4-intoxicated rats, using 14C-bicarbonate method. 1. In normal liver, albumin synthesis averaged 5.6 mg/hr/100 g body weight. 2. In CCl4-intoxicated liver, albumin synthesis decreased to 4.6 mg at acute stage, but restored to 5.1 mg at non-septal fibrotic stage. At septal fibrotic, cirrhotic and cirrhotic stage with ascites, the synthesis rate averaged 4.5 mg, 4.1 mg and 3.2 mg, respectively. From these results, it is inferred that albumin synthesis rate decreases in accordance with the progress of the liver injury. 3. Effect of betamethasone on plasma albumin synthesis in perfused rat liver was investigated. Albumin synthesis rate in normal liver averaged 5.4 mg, and after addition of betamethasone, the rate averaged 4.3 mg, 3.3 mg and 2.8 mg, respectively. The rate after addition of betamethasone increased to 7.3 mg, 5.5 mg and 4.5 mg, respectively. From these results obtained, it is inferred that betamethasone increases plasma albumin synthesis in both normal and CCl4-intoxicated liver. 4. In normal liver, actinomycin-D did not inhibit basal albumin synthesis, but inhibited the increase of albumin synthesis by betamethasone, when actinomycin-D was added together with betamethasone. From these facts, it is concluded that betamethasone is able to induce albumin synthesis.

Animals↗

A randomized, placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24 to 28 weeks' gestation.

Previous randomized controlled studies of corticosteroids for the reduction of respiratory distress syndrome have failed to demonstrate benefit in very early premature gestational age groups. A randomized, double-blind, placebo-controlled clinical trial of betamethasone given to mothers with intact membranes and threatened premature delivery between 24 and 28 weeks of pregnancy was conducted. Thirty-six patients were randomized to receive betamethasone, two doses of 12 mg, 24 hours apart, and 41 received placebo. No difference was found in the overall incidence of respiratory distress syndrome between the two groups (betamethasone vs placebo 0.55 vs 0.66) or in the incidence of respiratory distress syndrome in babies delivered between 1 and 7 days after the first dose of drug (betamethasone vs placebo 0.78 vs 0.88). Nor were there any differences observed in any measure of severity of respiratory distress syndrome between the groups. The neonatal death rates were also similar (betamethasone vs placebo 0.25 vs 0.24). The only difference seen was an unexpected reduction in the betamethasone group in the incidence of grades 3 and 4 intraventricular hemorrhage (betamethasone vs placebo 1/31 vs 9/36, p = 0.01). Therefore this study was unable to demonstrate any beneficial effect of corticosteroids in reducing respiratory distress syndrome at less than 28 weeks' gestation in spite of a sample size that had an 80% likelihood of detecting a 50% reduction in the incidence of respiratory distress syndrome with p = 0.05, which is the minimum reduction seen in virtually all randomized trials in other gestational age groups.

Adult↗

The effect of betamethasone and fetal sex on the synthesis and maturation of lung surfactant phospholipids in rabbits.

In the present study we investigated the maturation of the surfactant phospholipids and the role of fetal sex on the effect of betamethasone in male and female rabbit fetuses. Betamethasone was administered to the doe (0.2 mg/kg intramuscularly) 42 and 18 h prior to killing. The fetuses were studied at 27 and 28 days from conception. Results from the alveolar lavage show that male fetuses tended to have a lower disaturated phosphatidylcholine/sphingomyelin ratio and lower levels of phosphatidylinositol. Phosphatidylglycerol was detected in trace amounts. This was apparently due to the high extracellular levels of myo-inositol inhibiting the synthesis of surfactant phosphatidylglycerol while increasing the synthesis of surfactant phosphatidylinositol. Betamethasone increased the recovery of disaturated phosphatidylcholine and phosphatidylinositol from the lung lavage in both sexes. As studied in lung slices in vitro, the betamethasone treatment decreased the incorporation of glucose into phospholipids, including into the fatty acid moiety of disaturated phosphatidylcholine, although it had no significant effect on the incorporation of glucose into the glycerol moiety of disaturated phosphatidylcholine. However, the addition of palmitate increased the incorporation of glucose into the glycerol moiety of disaturated phosphatidylcholine. The betamethasone treatment did not increase the incorporation of [1-14C]pyruvate into disaturated phosphatidylcholine. Following betamethasone administration, the availability of fatty acids may become rate-limiting for the synthesis of surfactant phospholipids. Betamethasone increased the activities of phosphatidic acid phosphohydrolase and phosphatidate cytidyltransferase in a fraction of microsomal membranes. The present evidence suggests that the glucocorticoid-induced lung maturation and the maturation of the normal lung are associated with an increase in the activity of the enzymes which are involved in metabolizing phosphatidic acid to neutral and acidic surfactant secretion of the male fetus was not explained by possible sex-related differences in the biosynthesis of the phospholipids.

Aging↗

Effect of simultaneous administration of betamethasone and triiodothyronine (T3) on the development of functional pulmonary maturation in fetal rabbit.

Recent experimental evidence suggests that a combination of glucocorticoid and thyroid hormone may be more effective than either hormone alone in accelerating morphologic as well as biochemical mammalian fetal lung maturation. We have demonstrated that IM administration of T3 to the rabbit doe is associated with enhanced functional fetal lung maturation. We investigated the effect of simultaneous administration of T3 and betamethasone on the development of functional fetal lung maturation and the duration of survival after premature delivery. On day 25 and 26 of pregnancy, T3 (175 micrograms/kg/dose) betamethasone (85 micrograms/kg/dose), T3 plus betamethasone or the appropriate amount of the vehicles were injected. The functional fetal pulmonary maturity and the duration of survival after premature delivery were assessed on day 27 of gestation. Although enhanced functional fetal lung maturation was observed after T3 or betamethasone administration, there was no additive effect after simultaneous administration of both. The duration of survival on premature delivery was enhanced in betamethasone but not T3 or T3 plus betamethasone group when compared to control. Further animal experimentation seems necessary before a clinical trial of T3 plus betamethasone therapy is considered.

Animals↗

Antigen presentation is inhibited in vivo by betamethasone.

Aim of the present study was to assess whether betamethasone, a synthetic glucocorticoid used as immunosuppressant, could modify in vivo the antigen presentation by antigen presenting cells (APC). Interleukin-2 (IL-2) production by a T cell hybridoma specific for the hen egg white lysozyme (HEL) cultured in the presence of HEL and APC from treated or control mice was utilized as read out. Betamethasone induced a dose-dependent inhibition of antigen presentation. Fifty percent maximal response was observed with 1152 (95% confidence interval: 948-1419) resident peritoneal macrophages from untreated animals, and 5843 (4700-7445, 21, 235 (12,857-43,705), 28,313 (20,847-40,955) macrophages from mice injected for 3 days with betamethasone 10, 25, and 50 mg/kg respectively. Similar findings were obtained with spleen cells. When given for 3 days at 25 mg/kg, betamethasone reduced the number of cells recovered from the peritoneum by approximately half and from the spleen by one order of magnitude. One day vs. 3 days treatment resulted in similar recovery of cells but lower inhibition of APC function. In the experimental conditions utilized, no carryover of betamethasone with APC could be demonstrated and no reversal of inhibition was observed by increasing the antigen concentration. The data here presented demonstrate that short curses of high dose betamethasone specifically impair antigen presentation. Thus, this mechanism appears to be involved in the immunosuppressant activity of betamethasone.

Animals↗

Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris.

The therapeutic efficacy and tolerability of calcipotriol ointment and betamethasone valerate ointment in psoriasis were compared in a multicentre, prospective, randomised, double-blind, right/left trial. 345 inpatients and outpatients with psoriasis vulgaris of symmetrical distribution were treated twice daily for 6 weeks with calcipotriol ointment 50 micrograms/g and betamethasone ointment 0.1% randomly assigned to opposite sides of the body. The main outcome measures--the psoriasis area and severity index (PASI), the investigators' assessments of erythema, thickness, and scaling, and the patients' own assessments of the overall response to treatment--were sought at weeks 2, 4, and 6. Both treatments significantly reduced the PASI scores and the investigator's assessment scores, but at each visit the PASI score was significantly (p less than 0.001) lower with calcipotriol than with betamethasone. At 6 weeks the mean PASI reduction was 68.8% with calcipotriol and 61.4% with betamethasone (95% confidence interval for difference 5.1-9.8, p less than 0.001). The scores for erythema, thickness, and scaling were significantly (p less than 0.001) lower with calcipotriol than with betamethasone at the end of treatment. The patients considered that 82.1% of calcipotriol-treated sides and 69.3% of betamethasone-treated sides had improved greatly or cleared up by the end of treatment (p less than 0.001). 57 adverse events were reported by 52 patients (15.1%). The most common adverse event, lesional/perilesional skin irritation, was slightly but not significantly (p = 0.12) more common with calcipotriol treatment. 15 (4.3%) patients were withdrawn from the study, 3 because of local adverse events. There were no changes in serum calcium during the study. Thus, calcipotriol ointment was superior to betamethasone valerate ointment in psoriasis vulgaris. Though long-term results are not yet available, calcipotriol holds great promise as an antipsoriatic agent.

Administration, Topical↗

Effects of betamethasone and thyroid releasing hormone on fetal lung maturation: an experimental and morphometric study.

OBJECTIVE: To determine the effects of betamethasone and thyroid releasing hormone (TRH) on morphologic fetal rabbit lung maturation when administered separately and in combination. MATERIAL AND METHODS: Twenty-five pregnant rabbits were divided into five groups. Study groups were as follows: TRH or betamethasone alone (between 24 and 27th days of gestation), TRH + betamethasone or betamethasone + TRH (second dose of drugs were added in the last 2 days), and the control. The pregnancies were terminated on the 27th day of gestation. Weights and volumes of the fetal lungs were determined and the results were compared. RESULTS: Mean lung weights in all treatment groups were significantly heavier than controls (P < 0.05). The differences between mean lung weights of TRH alone, TRH + betamethasone, and betamethasone alone groups were not statistically significant (P > 0.05), but the mean lung weight of betamethasone + TRH group was significantly lower than the other treatment groups (P < 0.05). Mean lung volume of TRH alone group was significantly higher than control group; however, there were no significant differences between other treatment groups and the control. No correlation was found between the lung weights and volumes in all groups (r = 0.1, P > 0.05). CONCLUSION: Only TRH alone treatment produced a significant increase in both fetal lung volume and weight compared to the control group. Administering TRH alone can lead to increased lung maturation. Combining TRH to corticosteroid treatment significantly decreased mean fetal lung weight, instead of an increase. According to these results combined used of these two substances probably counteract each others effect, instead of having a synergism.

Animals↗

Influence of a single course of antenatal betamethasone on the maternal-fetal insulin-IGF-GH axis in singleton pregnancies.

OBJECTIVE: We examined the hypothesis that a single course of antenatal betamethasone influences the maternal-fetal insulin-IGF-GH axis. DESIGN: A prospective, observational, pilot study consisting of four groups of pregnant women: (I) received betamethasone and delivered <2 weeks post treatment; (II) received betamethasone and delivered >2 weeks post treatment; (III) untreated women who delivered <37 weeks (preterm controls); (IV) untreated women who delivered >37 weeks (term controls). Maternal and mixed umbilical cord blood was collected at delivery and analyzed for insulin, glucose, IGF-I, IGF-II, IGFBP-1, IGFBP-3, GH, and GHBP. RESULTS: Betamethasone increased maternal insulin, glucose and IGF-I levels without affecting IGFBPs. In the fetal compartment, betamethasone treatment was associated with a delayed suppressive effect on GH and a sustained suppressive effect on IGF-II levels. There were no differences in infant size or neonatal morbidities between patients who delivered <2 weeks or >2 weeks post betamethasone treatment. In Group IV, birth weight correlated positively with cord IGF-I levels (r2=0.41, p=0.0098) and negatively with cord IGFBP-1 levels (r2=0.51, p=0.0039), and ponderal index correlated negatively with cord IGFBP-1 levels (r2=0.27, p<0.05). CONCLUSIONS: A single course of antenatal betamethasone influences the maternal-fetal insulin-IGF-GH axis, particularly fetal IGF-II levels, without measurable anthropometric changes at birth. Whether these effects have implications beyond the neonatal period remains to be determined.

Betamethasone↗

Betamethasone cream for the treatment of pre-pubertal labial adhesions.

PURPOSE: We evaluated the efficacy of 0.05% betamethasone cream for the treatment of pre-pubertal labial adhesions. METHODS: We retrospectively reviewed the records of 19 children with labial adhesions who were treated with betamethasone cream from 6/2001 to 3/2003. Children were treated with 1 to 3 courses of twice-daily 0.05% betamethasone cream for 4 to 6 weeks. Successful lysis of adhesions was assessed by clinical exam or parental phone contact and outcomes were defined as: (1) success--complete separation of labia, (2) partial success--greater than 75% separation, (3) progression to surgical lysis, and (4) lost to follow-up. RESULTS: Nineteen patients with an average age of 58 months (range 12 to 132 months) were treated. Four of the 19 patients had never been treated previously and 1 had been treated previously with surgical lysis of adhesions only. Fourteen of the 19 patients had been previously treated with conjugated estrogen (Premarin) cream. Two of these fourteen patients had also undergone surgical lysis of adhesions. Severity of adhesions ranged from 33% to 99% labial closure. Betamethasone cream was successful in treating 13/19 (68%) pre-pubertal labial adhesions. Eleven (85%) of these 13 patients had complete resolution of labial adhesions with 1 course of treatment, 1 (7.5%) had resolution with 2 courses of treatment and 1 (7.5%) had resolution with 3 courses of treatment. One patient had a partial success with 3 courses of betamethasone cream. Two (11%) patients underwent surgical lysis of adhesion after 1 and 2 courses of betamethasone cream respectively. Three (16%) patients were lost to follow-up. Average follow-up was 7 months (range 1-24 months). No adverse outcomes or untoward effects were noted in any of the patients treated. CONCLUSIONS: Betamethasone 0.05% cream appears to be a safe and effective treatment of pre-pubertal labial adhesions as primary therapy or in patients that have failed previous therapies and it may avoid the undesirable side effects of breast budding and hyperpigmentation that can be associated with Estrogen creams.

Administration, Topical↗