Diprolene
Antenatal glucocorticoid administration increases corticotrophin-releasing hormone in maternal plasma.

Korebrits C, Yu DH, Ramirez MM, Marinoni E, Bocking AD, Challis JR.

Department of Obstetrics and Gynaecology, University of Western Ontario, St Joseph's Health Centre, London, Canada.

OBJECTIVE: This study was designed to determine whether maternal corticotrophin-releasing hormone (CRH) concentrations are altered after maternal betamethasone administration for fetal lung maturity in women with threatened preterm labour and whether these effects are dependent on gestational age. METHODS: Our study included 49 women with threatened preterm labour who received prenatal betamethasone for fetal lung maturity between 24 and 31 weeks of gestational age and 11 women who did not. Maternal blood was taken before and after glucocorticoid administration or at 24 hours after initial sampling. Plasma CRH, adrenocorticotrophin (ACTH) and cortisol concentrations were determined by radioimmunoassays. The women were stratified into 24-25 weeks, 26-27 weeks, 28-29 weeks, and 30-31 weeks completed gestation. RESULTS: At each gestational age, maternal cortisol concentrations decreased by approximately 85% after glucocorticoid administration. Overall mean cortisol values fell from 580.0 (SD, 351.8) to 89.7 (96.6) nmol/L (n = 40, P < 0.001). Overall mean ACTH values decreased from 9.9 (4.7) to 5.0 (3.4) pmol/L (n = 43, P < 0.001), and the approximate 50% decrease was similar at each gestational age. In marked contrast, overall mean CRH values increased from 58.0 (37.0) to 87.8 (68.6) pmol/L (n = 49, P < 0.001) after betamethasone administration. There was no change in maternal cortisol, ACTH or CRH values over 24 hours in women who did not receive betamethasone. CONCLUSIONS: We conclude that maternal betamethasone administration increases maternal plasma CRH values between 24 and 31 completed weeks of gestation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9637127&dopt=Abstract betamethasone Diprolene AF



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

Gramsbergen A, Mulder EJ.

Department of Medical Physiology, University of Groningen, The Netherlands.

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9667379&dopt=Abstract betamethasone Diprolene AF



Diprolene
Effect of in utero exposure to betamethasone on motivation/anxiety testing in mice offspring.

Rayburn WF, Christensen HD, Gonzalez CL, Rayburn LA, Stewart JD.

Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA. william-rayburn uokhsc.edu

In utero exposure to a single dose of the long-acting corticosteroid betamethasone at GD 14 has been shown to induce specific differences in motivation/anxiety testing among offspring. Because multidosings are desired to enhance fetal lung maturation, our objective was to compare effects of multidosings of betamethasone with a placebo on postnatal tests of motivation and anxiety. Sixty gravid CD-1 mice were randomly assigned to receive one of six treatment regimens (n = 10) that consisted of a single or a double SC dosing of either betamethasone (Celestone soluspan 0.2 mg on GD 14; 0.1 mg on GD 13 to 16; 0.1 mg b.i.d. on GD 14 and 15; 0.1 mg b.i.d. on GD 13 to 16) or saline (0.25 ml on GD 13 to 16; 0.25 ml b.i.d. on GD 13 to 16). The percent of pups exhibiting separation vocalization was temporarily less at PND 5 after betamethasone exposure to four doses (p < 0.05) and to eight doses (p < 0.01). The percents of pups being successful in homing (PND 9) and in responding to startle stimulation (PND 12-15) were not different between the betamethasone-exposed and placebo-exposed groups. Exploratory performance in the radial arm maze revealed no delay in the activities of juvenile and adult offspring exposed to betamethasone. The percent of male offspring that fought as juveniles and as adults was not different between the betamethasone-exposed and the placebo-exposed groups. The previously reported altered responses using the elevated plus maze, among juvenile and adult offspring, after a single dose of betamethasone was not replicated in this multidose study. These data indicate that prenatal exposure to betamethasone did not affect the mouse offspring's long-term responses to motivation/anxiety testing.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9697974&dopt=Abstract betamethasone Diprolene AF



Diprolene
Placebo-controlled comparison between a single dose and a multidose of betamethasone in accelerating lung maturation of mice offspring.

Stewart JD, Sienko AE, Gonzalez CL, Christensen HD, Rayburn WF.

Section of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

OBJECTIVE: Our purpose was to determine, in a placebo-controlled manner with a mouse model, whether a multidose of betamethasone is more beneficial than a single dose in accelerating fetal lung maturation. STUDY DESIGN: Ninety gravid CD-1 mice were randomly assigned to 1 of 3 groups (n = 30) to receive either a placebo (0.25 mL subcutaneously) or betamethasone (0.1 mg subcutaneously) as a single dose on gestational day 14 or as a multidose twice daily on gestational day 14 and 15. Ten pregnancies in each group were terminated at gestational day 16.5 to observe the neonatal breathing pattern (scale 0 to 5; 5 is unlabored breathing) and the lung histologic findings (scale 0 to 5; 5 is alveolar budding). The lungs of the offspring belonging to the remaining 20 pregnancies in each group were removed and weighed at postnatal day 1, 3, 5, or 120. RESULTS: Fetuses exposed to a multidose of betamethasone displayed a higher breathing score at gestational day 16.5 than either to a single dose or to the placebo (mean score 4.6 vs 3.8 or 1.3; P <. 001). Alveolar development was greater after exposure to a multidose of betamethasone than after a single dose or after a placebo (mean score 4.4 vs 3.5 or 1.6; P <.001). The lung weights at gestational day 16.5 were less after a multidose of betamethasone than after a single dose of either betamethasone or a placebo (18.3 +/- 1.0 g vs 21.4 +/- 1.3 g or 23.3 +/- 1.3 g; P <.02). The lung/body weight ratio was similarly affected. This reduced weight of the lungs persisted postnatally into adulthood. CONCLUSIONS: With a CD-1 mouse model, a multidose of antenatal betamethasone accelerated fetal lung maturation more than after a single dose but was accompanied with a decrease in lung weight that persisted into adulthood.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9822509&dopt=Abstract betamethasone Diprolene AF



Diprolene
Betamethasone-induced resistance to neuromuscular blockade: a comparison of atracurium and vecuronium in vitro.

Robinson BJ, Lee E, Rees D, Purdie GL, Galletly DC.

Department of Community Health, Wellington School of Medicine, New Zealand.

Steroids induce resistance to neuromuscular blocking drugs. Betamethasone-induced resistance to vecuronium has been demonstrated in vitro, and a presynaptic site of interaction has been suggested. This study investigated whether atracurium is similarly affected. Rat phrenic nerve-hemidiaphragm preparations were bathed in a physiologic solution, and one-half were exposed to betamethasone (1 mumol/L). Dose responses were recorded for atracurium (8-13 mumol/L) and vecuronium (2-12 mumol/L) for control and betamethasone-treated preparations. In comparison to control, the betamethasone groups had significantly less depression of muscle contraction force at all concentrations of atracurium (P = 0.0004) and vecuronium (P = 0.002). The calculated ED50 (50% depression of muscle contraction force, expressed as mean +/- SEM) for atracurium was 8.83 +/- 0.62 mumol/L for controls and 11.19 +/- 0.54 mumol/L for betamethasone-treated preparations. The calculated ED50 for vecuronium was 4.72 +/- 0.41 mumol/L for controls and 6.84 +/- 0.66 mumol/L for betamethasone-treated preparations. Betamethasone therefore increased the ED50 for atracurium by 27% and vecuronium by 45%; however, the magnitudes of these differences were not significant (P = 0.74) between the neuromuscular blocking agents. These results indicate that betamethasone-induced resistance to nondepolarizing neuromuscular blockade affects both atracurium and vecuronium to similar degrees in vitro.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1348914&dopt=Abstract betamethasone Diprolene AF