Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes. A multicenter, randomized open study of early corticosteroid treatment (OSECT) in preterm infants with respiratory illness: comparison of early and late treatment and of dexamethasone and inhaled budesonide. Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial. Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome. Early low-dose hydrocortisone in very preterm infants: a randomized, placebo-controlled trial. Early postnatal dexamethasone for the prevention of chronic lung disease in high-risk preterm infants. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia. Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy. Clinical impact of corticosteroid-induced adrenal suppression during treatment for acute lymphoblastic leukemia in children: a prospective observational study using the low-dose adrenocorticotropin test. Adrenal suppression and extubation rate after moderately early low-dose dexamethasone therapy in very preterm infants. Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema. Early dexamethasone-attempting to prevent chronic lung disease. [Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study]. Randomized controlled trial of three different doses of aerosol beclomethasone versus systemic dexamethasone to promote extubation in ventilated premature infants. Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization. Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants. Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome. Dexamethasone treatment in preterm infants at risk for bronchopulmonary dysplasia. Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary mechanics in preterm infants. Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlled trial. Dexamethasone therapy for chronic lung disease in ventilator- and oxygen-dependent infants: a controlled trial. Pulmonary effects of triiodothyronine (T3) and hydrocortisone (HC) supplementation in preterm infants less than 30 weeks gestation: results of the THORN trial--thyroid hormone replacement in neonates. A double-blind, randomized, controlled study of a "stress dose" of hydrocortisone for rescue treatment of refractory hypotension in preterm infants. Dexamethasone in the prevention of postextubation stridor in children.
In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD. To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).
                Prospective, controlled, randomized study.
                Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.
                No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.
                Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly. This study was carried out to examine the effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes (PROMs). For this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation) complicated by PROMs were evaluated prospectively during the period January 1997 to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince Zaid). Patients were allocated into two groups; Group 1 included 72 patients treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group 2 which included 67 patients whoreceived no treatment (control group). All women were examined clinically and the diagnosis of PROMs was demonstrated using vaginal speculum, nitrazine paper examination and ultrasonography. All neonates were evaluated clinically, radiologically, and by laboratory investigations. Pearson's Chi-square and Fisher's exact tests were used to assess the significance of differences between the two study groups. Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), and days of hospital stay were significantly reduced in premature infants of the corticosteroid treated women compared with the controls (p<0.04, p<0.04, p<0.04, and p<0.05, respectively). The perinatal mortality was significantly decreased among the corticosteroid treated group in the gestational subgroups 31-32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was statistically a significant factor which resulted in increased perinatal mortality in the control group (p=0.02). Regarding the occurrence of postpartum endometritis there was a statistically significant increase among the corticosteroid treated group compared with the controls (p<0.04). Conclusion: Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a positive influencing effect on premature infants between 31 and 34 weeks of gestation, decreasing significantly the perinatal morbidity and mortality. It should be used with particular relevance to the developing world where surfactant is not available or where neonatal intensive care units are lacking. To compare early (<3 days) with late (>15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease.
                Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age <30 weeks, postnatal age <72 hours, and need for mechanical ventilation and inspired oxygen concentration >30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (<72 hours) dexamethasone, early budesonide, delayed selective (>15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily.
                There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance.
                Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective. Postnatal corticosteroid therapy is controversial. The aim of this study was to determine the short-term effects of low-dose dexamethasone treatment among chronically ventilator-dependent neonates.
                Very preterm (gestational age: <28 weeks) or extremely low birth weight (birth weight: <1000 g) infants who were ventilator dependent after the first 1 week of life were eligible and were assigned randomly to receive masked dexamethasone (0.89 mg/kg over 10 days) or saline placebo. Data on ventilator and oxygen requirements and deaths were recorded.
                Seventy infants were recruited from 11 centers, at a median age of 23 days. More infants were extubated successfully by 10 days of treatment in the dexamethasone group (60%, 21 of 35 patients) than in the control group (12%, 4 of 34 patients) (odds ratio [OR]: 11.2; 95% confidence interval [CI]: 3.2-39.0). Ventilator and oxygen requirements improved substantially, and the duration of intubation was shorter. There was little evidence for a reduction in either the mortality rate (dexamethasone group: 11%; control group: 20%; OR: 0.52; 95% CI: 0.14-1.95) or the rate of oxygen dependence at 36 weeks (dexamethasone group: 85%; control group: 91%; OR: 0.58; 95% CI: 0.13-2.66). There were no obvious effects of low-dose dexamethasone on blood glucose concentrations, blood pressure, or other complications. No infant experienced intestinal perforation.
                Low-dose dexamethasone treatment after the first 1 week of life clearly facilitates extubation and shortens the duration of intubation among ventilator-dependent, very preterm/extremely low birth weight infants, without any obvious short-term complications. Combined with recent evidence that infants at very high risk of bronchopulmonary dysplasia may benefit in the long term, our study reopens debate regarding the role of low-dose, late postnatal, corticosteroid therapy. To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.
                Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications.
                More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects.
                These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted. Several reports indicate a decreased cortisol response to adrenocorticotropic hormone in preterm infants developing chronic lung disease and in preterm infants with refractory hypotension. Low-dose hydrocortisone (HC) may allow for beneficial effects.
                Our aim was to assess whether HC is able to increase survival without chronic lung disease.
                We performed a double-blind, randomized, placebo-controlled trial. Fifty mechanically ventilated infants (birth weight: 500-1,249 g) were randomized to receive treatment (HC 0.5 mg/kg/12 h for 9 days, then HC 0.5 mg/kg/24 h for 3 days) or placebo. Major outcome was survival without oxygen dependence at 36 weeks of postconceptional age (O(2)-free survival).
                The basic characteristics were similar between the two groups. O(2)-free survival was higher in the HC group (64 vs. 32%). The advantage was particularly evident among infants without antenatal steroids. The mortality rate was 16% in the HC group versus 40% in the control group (difference not significant). Hypotension after recruitment was reduced by HC (0 vs. 30%). The incidence of gastrointestinal perforation and other adverse effects was similar between the two groups.
                HC prophylaxis improved O(2)-free survival and early cardiocirculatory function in our population, without important short-term effects. The neurodevelopmental outcome will be assessed at 2 years.
                Copyright (c) 2007 S. Karger AG, Basel. The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease (CLD) in high risk preterm infants and to evaluate the side effects of the early steroid administration.
                Randomised clinical trial.
                Neonatal intensive care unit.
                50 infants at high risk of CLD were randomly assigned after 72 h of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg per day for the first 3 days, 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day). The control group received no steroid treatment.
                The incidence of CLD at 28 days of life and at 36 weeks' postconceptional age was significantly lower in the dexamethasone group than in the control group (p < 0.001). Moreover, infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group (p < 0.001). Hyperglycaemia, hypertension, growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration.
                Early dexamethasone administration may be useful in preventing CLD, but its use should prudently be restricted to preterm infants at high risk of CLD. The objective of the study was to determine the efficacy and side effects of corticosteroid therapy for pregnant women with severe preeclampsia in the prevention of respiratory distress syndrome in their premature neonates.
                A prospective double-blind randomized trial enrolled 218 pregnant women with severe preeclampsia and gestational age between 26 and 34 weeks. One hundred ten received betamethasone (12 mg administered intramuscularly, repeated after 24 hours and then once a week) and 108 received placebo. Relative risks and 95% confidence intervals of respiratory distress syndrome and other neonatal and maternal complications were calculated for corticosteroid use.
                Frequency of respiratory distress syndrome was significantly reduced in the corticosteroid group (23%) with respect to the placebo group (43%), with a relative risk of 0.53 (95% confidence interval 0.35-0. 82). Relative risks of intraventricular hemorrhage, patent ductus arteriosus, and perinatal infection were significantly decreased in the corticosteroid group: 0.35 (95% confidence interval 0.15-0.86), 0.27 (95% confidence interval 0.08-0.95), and 0.39 (95% confidence interval 0.39-0.97), respectively. There was no significant difference in the frequency of stillbirth, but the neonatal mortality rate was lower in the corticosteroid group (14%) than in the placebo group (28%), with a relative risk of 0.5 (95% confidence interval 0.28-0.89). There was increased risk of gestational diabetes but of no other maternal complication after corticosteroid therapy, and mean blood pressures were similar in the 2 groups.
                Antenatal corticosteroid therapy with betamethasone for acceleration of fetal lung maturity is a safe and efficient treatment in patients with severe preeclampsia at between 26 and 34 weeks' gestation. Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. All infants received one dose of Survanta before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28. Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. Infants in the treated group had transient hyperglycemia and hypertension. There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. To substantiate our result, large randomized controlled trials are needed and warranted. To investigate how frequently adrenal function fails to recover after corticosteroid therapy in children with acute lymphoblastic leukemia and to explore the clinical impact of slow adrenal recovery without steroid substitution.
                Low-dose (1 microg) adrenocorticotropic hormone tests were performed before and after steroid courses and during infectious episodes in 24 children. Test results were not available during the study.
                All 13 patients tested before treatment had normal adrenal responses. Adrenal suppression was found in 8 (47%) of 17 patients 5 days after discontinuation of a 5-week induction course of prednisolone and in 1 (20%) of 5 patients 7 days after a 3-week intensification course of dexamethasone, both courses being tapered over 9 days, as well as in all 13 patients tested 2 days after a 1-week prednisolone course. Clinically significant manifestations of adrenal suppression were noted in 3 (12%) patients. Of 204 scheduled tests, 131 were performed.
                High-dose glucocorticoid therapy may cause adrenal suppression lasting more than 1 week in children with acute lymphoblastic leukemia, even after tapering the dose. We suggest steroid replacement during stress episodes within 1 to 2 weeks after discontinuation and thereafter testing adrenal function selectively in accordance with symptoms. A short course of moderately early dexamethasone therapy with a starting dose of 0.5 mg/kg/day improves lung compliance and shortens the duration of ventilatory support in preterm infants with respiratory distress syndrome (RDS). We conducted a double-blind, randomized study to evaluate whether a moderately early 14-day weaning course of low-dose dexamethasone affects adrenal function and facilitates weaning from the ventilator.
                Thirty-six preterm infants with a gestational age < or =32 weeks who required ventilatory support for RDS on days 7-14 were randomized to a 14-day treatment course with dexamethasone (0.2 mg/kg/day start, tapering doses) or placebo (equivalent amounts of normal saline). Prior to the first study treatment and the day after completion of the treatment course, adrenal function was assessed from serum cortisol levels drawn before and 30 min after intravenous administration of 0.1 mg Cortrosyn. Extubation rate during treatment in both groups was compared.
                In both groups baseline serum cortisol levels decreased significantly during treatment, but stimulated cortisol levels did not change. After the 14-day treatment course, stimulated cortisol levels increased significantly from baseline levels in both groups (p<0.001), following Cortrosyn administration. More infants in the dexamethasone group were extubated within 7-14 days of study entry than in the placebo group (p<0.05). Hyperglycemia was more frequently diagnosed in the dexamethasone group and open-label dexamethasone treatment was given more frequently in the control group.
                A moderately early 14-day weaning course of low-dose dexamethasone does not significantly suppress the adrenal function of very preterm infants with RDS, but accelerates weaning from the ventilator. We studied 50 preterm infants who had multiple or traumatic endotracheal intubations, or whose duration of endotracheal intubation was > or = to 14 days, and who were considered at high risk for airway edema. These infants were enrolled in a prospective, randomized, controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress. At study entry, both groups had similar weights, postnatal ages, methylxanthine use, ventilator settings, blood gas values, and pulmonary function test results (dynamic compliance, total respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure, minute ventilation, and peak inspiratory and expiratory flow rates). Patients underwent blood gas studies, physical examinations, and pulmonary function testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to 24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25 mg/kg per dose, at baseline, and then every 8 hours for a total of three doses; 23 infants received saline solution at corresponding times. Eighteen to twenty-four hours after extubation, total pulmonary resistance increased by 225% from baseline in the control group compared with 33% in the dexamethasone group (p < 0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants, 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients (p < 0.006). Of the 23 control patients, 4 required reintubation compared with none of the treated group (p < 0.05). We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight, high-risk preterm infants. We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results.
                Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo.
                No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively.
                This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia. The aim of the study was to determine the feasibility, the cost and the effects of antenatal maternal corticosteroid treatment on preventing respiratory distress syndrome in premature neonates of our population.
                Between January, 1, 1998 and June, 31, 1999, 118 pregnant women at 26-34 weeks' gestation and at a high risk of premature delivery, were prospectively randomized in 2 groups: group 1 received intramusculary 24 mg of betamethasone (12 mg every 24 hours), group 2 didn't receive antenatal corticosteroids. At birth, premature neonates were systematically examined by a neonatologist.
                131 premature neonates were born (63 from group 1, 68 from group 2). The incidence and the degree of severity of respiratory distress syndrome, appeared substancially reduced (4.8% vs 27.9%) by the use of antenatal corticosteroids. Moreover, neonatal mortality due to respiratory distress syndrome was statistically less in group 1 than in group 2 (22.9% vs 57%). There was no significant difference in the occurrence of maternal or neonatal corticosteroid complications such as infection between treated group and control subjects. We estimated a potential annual savings of 21 thousands tunisian dinars, when the cost implications for antenatal corticosteroid therapy were estimated to 2 thousands tunisian dinars.
                Maternal administration of corticosteroids before preterm delivery results in a decrease in the incidence and severity of respiratory distress syndrome and a decrease in neonatal mortality rate among premature neonates born to treated versus untreated mothers at 26-34 weeks' gestation; added to an annual savings estimated to 21 thousands tunisian dinars. Our objective was to determine the safety and efficacy of aerosol beclomethasone vs. systemic dexamethasone for extubation in premature infants at high risk for chronic lung disease (CLD). Intubated preterm infants who were identified as being at high risk for moderate-severe CLD on day 14 of life were randomized to one of four groups. The control group received systemic dexamethasone and aerosol placebo, while the other three groups received either high (2.40-3.69 microg/kg/day delivered to lungs), medium (1.0-1.85 microg/kg/day), or low (0.48-0.74 microg/kg/day) dose aerosol beclomethasone and systemic placebo. Those receiving aerosol steroids who remained ventilator-dependent after 7 days were switched to standard 42-day tapering doses of systemic dexamethasone. The primary outcome was extubation within 1 week of starting steroids, using predefined criteria. Secondary variables included changes in lung function, rates of side effects, and tracheal aspirate white blood cell counts. Sixty-one infants with birth weights of 761 +/- 18 g (mean +/- SEM) and gestational ages of 25.7 +/- 0.2 weeks were randomized to one of the four groups. Seven of 15 infants in the control systemic dexamethasone group were successfully extubated compared with 3/16 in the high-dose beclomethasone group, 1/15 in the medium-dose group, and 2/15 in the low-dose group (P < 0.01). Only dexamethasone subjects demonstrated improvements in lung function over the study period. These infants also had significant increases in blood pressure and blood glucose levels, as well as a decline in their tracheal aspirate white blood cell count. In conclusion, aerosol beclomethasone at the very low doses used in this study did not facilitate extubation in intubated premature infants at high risk for moderate-severe CLD.
                Copyright 2003 Wiley-Liss, Inc. Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.
                The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.
                An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.
                Thirty-one adult CAP patients who required hospitalization were enrolled.
                Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.
                In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy. BACKGROUND. Many extremely low birth weight infants (<1000 g) show biochemical evidence of adrenal insufficiency in the first week of life, correlating with subsequent development of chronic lung disease (CLD).
                We conducted a randomized, double-masked, placebo-controlled pilot study to test whether early treatment with low-dose hydrocortisone for 12 days (1 mg/kg/day for 9 days followed by.5 mg/kg/day for 3 days), begun before 48 hours of life, would increase the likelihood of survival without CLD.
                Forty patients were enrolled at two centers. Birth weight and gestation were similar for treatment and placebo groups: 732 +/- 135 g versus 770 +/- 135 g and 25.2 +/- 1.3 weeks versus 25.4 +/- 1.5 weeks. More infants treated with hydrocortisone achieved study success, defined as survival without supplemental oxygen at 36 weeks' postconception (12/20 [60%] vs 7/20 [35%]). Lower birth weight, histologic chorioamnionitis, and preeclampsia were significant risk factors, whereas study center, prenatal steroids, sex, and ethnicity were not significant. Hydrocortisone treatment decreased days on >40% oxygen, days on >25% oxygen, days on ventilator, and oxygen at discharge. Among infants exposed to chorioamnionitis, hydrocortisone treatment also was associated with increased enteral intake during the first month of life and with increased weight at 36 weeks' postconception. Five treated infants and 6 placebo infants developed sepsis; 3 in each group died.
                First, early treatment with low-dose hydrocortisone in this population of extremely low birth weight infants increased the likelihood of survival without CLD. Second, the benefit was particularly apparent in infants with chorioamnionitis. Third, a larger multicenter trial is needed to verify the primary outcome and to better evaluate risks and benefits. To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome.
                A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities.
                The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered.
                These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants. A randomised double blind placebo controlled study was conducted to determine whether a one week course of dexamethasone could reduce the severity of bronchopulmonary dysplasia in preterm infants without compromising their adrenal function. Forty one infants with a mean birth weight of 880 g and a gestational age of 27 weeks who were ventilator dependent at 10 days of age were enrolled. At the age of 28 days pulmonary outcome was significantly better in the girls treated with dexamethasone but not in all infants. There was no difference between the groups in the long term outcome, except for a shorter duration of supplemental oxygen in dexamethasone treated female infants. After the one week dexamethasone treatment there was a significant but short lived suppression of the basal cortisol concentrations and the adrenal response to corticotrophin (ACTH). No serious side effects were observed. It is concluded that early one week dexamethasone treatment improves short term pulmonary outcome in premature infants, but there is no clear evidence of long term benefits. The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight < or = 1,250 g and gestational age < or = 32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.
                Copyright 2004 S. Karger AG, Basel Oral systemic corticosteroids are the mainstay of treatment for problematic hemangiomas; however, current information is based on anecdotal experience and retrospective studies. We aimed to determine whether systemic steroids are efficacious in proliferating hemangioma and to compare the efficacy and safety of 2 corticosteroid treatment modalities.
                Twenty patients with problematic hemangiomas of infancy were randomly assigned to either daily oral prednisolone or monthly intravenous pulses of methylprednisolone. Their clinical outcomes (improvement using a visual analog score) and adverse events were compared at 3 months from baseline and 1 year of age. Data on possible surrogate markers of angiogenesis were available for the first 3 months.
                At 3 months, orally treated patients had a median visual analog score of 70 compared with 12 in the intravenous group. This response pattern was similar at the patients' first birthday: 50.0 vs -1.5. Additional treatment beyond 3 months was needed for 65% of the patients (7 in the intravenous and 6 in the oral group). Six of 8 patients with impaired vision at enrollment had an improved function at 1 year (4 patients in the intravenous group and 3 patients in the oral group). Of the 4 surrogate markers of angiogenesis measured (plasma basic fibroblast growth factor, vascular endothelial growth factor, vascular cellular adhesion molecule 1, endoglin, and urine basic fibroblast growth factor), the only 2 that decreased over time were vascular cellular adhesion molecule 1 and endoglin. Patients in the oral group had a higher rate of adverse effects, such as hypertension (18.6% vs 13.1%), abnormal cortisol (78% vs 60%), and growth retardation.
                Systemic corticosteroids are efficacious in stopping the proliferation of hemangiomas. The oral corticosteroids offered more clinical and biological benefit than the pulse steroids with higher risk of adverse effects. To determine whether dexamethasone therapy altered the outcome of chronic lung disease in neonates, we conducted a prospective, randomized, placebo-controlled trial. Twenty-one 30-day-old oxygen- and ventilator-dependent infants were enrolled. The mean (+/- SD) birth weight was 808.1 +/- 141 gm and the mean gestational age was 26.0 +/- 1.5 weeks. There were 17 black and 12 male infants. Twelve received placebo and nine received dexamethasone. Neither severity of early illness, birth weight, gestational age, age when treated, gender and race distribution, nor frequency of diuretic therapy differed significantly between groups. The age at extubation, 57.2 days (placebo) versus 39.4 days (steroid), was significantly different. The average oxygen requirements of the steroid-treated patients was significantly lower than for placebo-treated patients during the first 10 days of treatment. There were no differences for placebo-versus steroid-treated patients in age when weaned to room air (95.5 days vs 74.9 days), age at discharge (119 days vs 111 days), or number of deaths (2 (17%) vs 1 (11%]. Dexamethasone therapy was associated with a significantly increased incidence of hyperglycemia (89% vs 8%) but did not influence the incidence of hypertension, intracranial hemorrhage, infection, or retinopathy of prematurity. The steroid-treated patients had a significant delay in weight gain during the first 3 weeks of treatment but recovered by discharge. Our results suggest that dexamethasone produces acute improvement in infants with lung disease but no long-term effect on mortality rate, duration of oxygen requirement or age at discharge. The THORN trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial to test the hypothesis that administration of triiodothyronine (T(3)) and hydrocortisone would decrease mortality and respiratory morbidity in preterm infants of less than 30 wk gestation. Two hundred fifty-three infants were randomized to receive either 6 micro g.kg(-1).d(-1) of T(3) with 1 mg.kg(-1).d(-1) of hydrocortisone or 5% dextrose (placebo) as a continuous i.v. infusion for 7 d. The dose was halved on d 5. Our first primary outcome was death or ventilator dependence at 1 wk, and the second was death or oxygen dependence at 2 wk. The overall mortality rate for both groups was 11.4%. Relative risk of death or ventilator dependence at 1 wk, treated versus placebo, was 0.87, p = 0.2, and death or oxygen dependence at 2 wk, 1.00, p = 0.9. We examined the relationship between free T(3) (FT(3)) and free thyroxine (FT(4)) levels in the first 7 d and the primary outcome death or ventilator dependence at 1 wk in all 253 babies. We found significant positive correlations of p = 0.05 for FT(3) and p = 0.002 for FT(4). Thus the higher the FT(3) and FT(4) levels, the better the outcome. No beneficial effects of T(3) and hydrocortisone were shown. In this study, although FT(3) levels were doubled by the treatment infusion, FT(4) levels were significantly suppressed. The lack of any beneficial effect of T(3) in our study may be explained by suppression of FT(4) in the treatment group. To assess the effectiveness of a "stress dose" of hydrocortisone for rescue treatment of refractory hypotension and adrenocortical insufficiency of prematurity in very low birth weight (VLBW) infants. We hypothesized that significantly more VLBW infants who were receiving dopamine > or =10 microg/kg per min could wean off vasopressor support 72 hours after treatment with hydrocortisone.
                A double-blind, randomized, controlled study was conducted in a university neonatal center. Forty-eight VLBW infants who had refractory hypotension and required dopamine > or =10 microg/kg per min were randomly assigned to receive a stress dose of hydrocortisone (1 mg/kg every 8 hours for 5 days; n = 24) or an equivalent volume of the placebo solution (isotonic saline; n = 24).
                The baseline clinical characteristics were similar between the groups. Serum cortisol concentrations were very low immediately before randomization in both groups of infants. Significantly more VLBW infants who were treated with hydrocortisone weaned off vasopressor support 72 hours after starting treatment. The use of volume expander, cumulative dose of dopamine, and dobutamine were significantly less in hydrocortisone-treated infants compared with control infants. In addition, the median duration of vasopressor treatment was halved in hydrocortisone-treated patients. Two versus 11 infants in the hydrocortisone and control groups required a second vasopressor for treatment of refractory hypotension. The trend (linear and quadratic) of the mean arterial blood pressure was also significantly and consistently higher in hydrocortisone-treated infants.
                A stress dose of hydrocortisone was effective in treating refractory hypotension in VLBW infants. Although routine and prophylactic use of systemic corticosteroids could not be recommended because of their potential adverse effects, this relatively low dose of hydrocortisone would probably be preferable to high-dose dexamethasone for treatment of refractory hypotension in emergency and life-threatening situations. To assess whether there is any advantage in the use of corticosteroid to prevent postextubation stridor in children, we conducted a prospective, randomized, double-blind trial of dexamethasone versus saline solution. The patients were evaluated and then randomly selected to receive either dexamethasone or saline solution according to a stratification based on risk factors for postextubation stridor: age, duration of intubation, upper airway trauma, circulatory compromise, and tracheitis. Dexamethasone, 0.5 mg/kg, was given every 6 hours for a total of six doses beginning 6 to 12 hours before and continuing after endotracheal extubation in a pediatric intensive care setting. There was no statistical difference in incidence of postextubation stridor in the two groups; 23 of 77 children in the placebo group and 16 of 76 in the dexamethasone group had stridor requiring therapy (p = 0.21). We conclude that the routine use of corticosteroids for the prevention of postextubation stridor during uncomplicated pediatric intensive care airway management is unwarranted.
The benefits of early postnatal corticosteroid treatment (≤ 7 days), particularly dexamethasone, may not outweigh the known or potential adverse effects of this treatment. Although early corticosteroid treatment facilitates extubation and reduces the risk of chronic lung disease and patent ductus arteriosus, it causes short-term adverse effects including gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure. Long-term follow-up studies report an increased risk of abnormal neurological examination and cerebral palsy. However, the methodological quality of the studies determining long-term outcomes is limited in some cases; the surviving children have been assessed predominantly before school age, and no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes. There is a compelling need for the long-term follow-up and reporting of late outcomes, especially neurological and developmental outcomes, among surviving infants who participated in all randomised trials of early postnatal corticosteroid treatment. Hydrocortisone in the doses and regimens used in the reported RCTs has few beneficial or harmful effects and cannot be recommended for prevention of CLD.