Prenatal dexamethasone treatment in conjunction with rescue therapy of human surfactant: a randomized placebo-controlled multicenter study. Use of ampicillin and corticosteroids in premature rupture of membranes: a randomized study. The influence of betamethasone and orciprenaline on the incidence of respiratory distress syndrome in the newborn after preterm labour. [Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study]. Antenatal glucocorticoid therapy for the prevention of respiratory distress syndrome in the premature infant. Maternal glucocorticoid in unplanned premature labor. Controlled study on the effects of betamethasone phosphate on the phospholipids of the gastric aspirate and on the adrenal cortical function of the newborn infant. Preterm premature ruptured membranes: a randomized trial of steroids after treatment with antibiotics. A randomized, placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24 to 28 weeks' gestation. Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome. The use of dexamethasone in women with preterm premature rupture of membranes--a multicentre, double-blind, placebo-controlled, randomised trial. Dexiprom Study Group. Results of a double-blind controlled study on the use of betamethasone in the prevention of respiratory distress syndrome. Premature rupture of membranes: a prospective, randomized evaluation of steroids, latent phase, and expectant management. Blood pressure at 6 years of age after prenatal exposure to betamethasone: follow-up results of a randomized, controlled trial. The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes. Antenatal administration of betamethasone to prevent respiratory distress syndrome in preterm infants: report of a UK multicentre trial. Risk of respiratory distress syndrome after prenatal dexamethasone treatment. Corticosteroid therapy for prevention of respiratory distress syndrome in severe preeclampsia.
A placebo-controlled, randomized, double-blind study was performed to determine whether prenatal dexamethasone (DEX) treatment improves the outcome of the preterm infant when exogenous surfactant is available.
                157 pregnant women at five hospitals with threatened preterm delivery and with lengths of gestation < 32 weeks received either DEX (dose 6 mg four times at 12-hour intervals) or placebo (PL). Prenatal treatment was not repeated. Preterm infants received rescue therapy of human surfactant (maximum four doses) if they required ventilatory support and at least 40% oxygen for the treatment of respiratory distress syndrome (RDS).
                Enrolled pregnant women delivered 188 live-born neonates, of whom 79 (DEX 41 and PL 38 neonates) were born 1 to 14 days after the prenatal treatment. Neonates born within 1 to 14 days after the initial DEX treatment had a lower incidence of RDS (DEX, 44%; PL, 79%; P < .01), lower requirements of surfactant (DEX, 22%; PL, 53%; P < .01), shorter duration of ventilatory support (DEX, 2.0 days; PL, 5.3 days; P < .05) and oxygen therapy (DEX, 2.0 days; PL, 7.0 days; P < .01), and a higher neonatal survival without ventilatory support (P < .05) than PL-treated neonates. DEX-treated neonates had higher mean blood pressure than PL-treated neonates during the first 3 days after birth. Among all neonates treated with DEX, there was a lower incidence of intraventricular hemorrhage or periventricular leucomalacia (DEX, 13%; PL, 33%; P < .01). Reduction in the incidence of intraventricular hemorrhage or periventricular leucomalacia in DEX-treated neonates was particularly associated with exogenous human surfactant therapy (DEX+surfactant 10%; PL+surfactant 48%; P < .01).
                Prenatal DEX treatment combined with exogenous human surfactant therapy in preterm infants decreases pulmonary morbidity and cerebral complications, and increases survival without severe morbidity. A randomized study was conducted to investigate the effects of antenatal corticosteroids and ampicillin in the management of preterm pregnancies under 34 weeks complicated by premature rupture of membranes. Patients with documented lecithin/sphingomyelin (L/S) ratios of less than 2.0 and a singleton gestation were eligible to participate in the study. One hundred sixty-five patients qualified and were randomized, using sealed envelopes, to four study groups. All patients were followed expectantly. Group I (41 patients) received neither ampicillin nor corticosteroids. Group II (43 patients) received 24 mg of antenatal betamethasone. Group III (37 patients) received 2 g of intravenous ampicillin every 6 hours, with discontinuation of antibiotic therapy if cultures were negative for pathogenic bacteria. Group IV (44 patients) received both corticosteroids and ampicillin as described for groups II and III, respectively. Compared with patients not receiving corticosteroids, those administered antenatal corticosteroids experienced a reduction in the incidences of respiratory distress syndrome (53 versus 26%), bronchopulmonary dysplasia (23 versus 9%), severe grades of intracranial hemorrhage (15 versus 3%), and patent ductus arteriosus (18 versus 6%), with no difference in the incidence of maternal or neonatal infection. Compared with patients not receiving antenatal antibiotics, the group of patients treated with ampicillin on admission had a lower incidence of clinical chorioamnionitis (4 versus 26%) and neonatal sepsis (5 versus 10%). This reduction in infectious morbidity by antenatal ampicillin was restricted to those patients (28.4% of the study population) colonized with group B streptococci.(ABSTRACT TRUNCATED AT 250 WORDS) In a randomized double-blind trial on antenatal corticosteroid treatment for the prevention of respiratory distress syndrome (RDS) a corticosteroid related beneficial effect was found. Possibly of more significance was the finding that the children born within 12 hours of their mother's admission to hospital showed a higher incidence of RDS than those born between 12 hours and one week after admission even in the placebo and untreated groups. Bèta-adrenergic drugs seemed to exert no other influence on the occurrence of RDS than can be explained by the delay of delivery. Prolonged ruptured membranes appeared to decrease the incidence of RDS to the same extent as other symptoms of threatened preterm labour. 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. A double-blind study was designed to investigate the effects of antenatal glucocorticoids on the incidence of respiratory distress syndrome (RDS) in 128 premature human infants. There was a significant reduction (P less than 0.05) in the incidence of RDS in the betamethasone-treated infants to 8.7% compared to an incidence of 22.6% in the saline-treated controls and 25.0% in infants whose mothers received methylprednisolone. The effectiveness of betamethasone in reducing RDS was limited to premature infants delivered to mothers with intact fetal membranes and with an initial L/S ratio less than 2.0. The time between administration of the glucocorticoid and delivery did not significantly affect the incidence of RDS in this study. The failure of methylprednisolone to reduce the development of RDS in premature infants suggests its potential use in maternal therapy during pregnancy with minimal effects on fetal maturation. The effects of betamethasone on surfactant composition and neonatal adrenal function were compared with placebo in a double-blind study, which included 74 patients at risk for premature delivery. The overall incidence of respiratory distress syndrome was low, and no differnce was observed between the betamethasone and placebo groups. The phospholipid pattern (lecithin/sphingomyellin ratio, acetone precipitated lecithin, phosphatidylinositol/sphingomyelin ratio, and phosphatidylglycerol/sphingomyelin ratio) from gastric aspirates of newborn infants was similar in the betamethasone and placebo groups, suggesting a similarity in lung surfactant. The responsiveness of the adrenal cortex of the newborn infants, evaluated by a 2-hr adrenocorticotropic hormone test at the age of 24 hr, did not differ between infants whose mothers had received either betamethasone or placebo. The low incidence of respiratory distress syndrome in the betamethasone and placebo groups was ascribed in part to a high incidence of prolonged rupture of fetal membranes. Our results do not exclude the possibility that antenatal maternal administration of betamethasone could prevent respiratory distress syndrome in other defined high-risk infants. To assess the effectiveness of corticosteroids in patients with preterm premature rupture of membranes (PROM) after treatment with a broad-spectrum antibiotic, ampicillin-sulbactam.
                A randomized clinical trial of corticosteroids in patients with preterm PROM was undertaken after treating these patients for a minimum of 12 hours with ampicillin-sulbactam. No digital vaginal examinations were performed on these patients. Antibiotics were continued for 7 days and the steroids were repeated weekly. No tocolytics were used. The primary outcome measure was the incidence of respiratory distress syndrome (RDS). Secondary outcome measures included latency period and neonatal and maternal infectious morbidity.
                Seventy-seven patients were enrolled and data about their pregnancies were analyzed. No statistically significant difference in latency period was noted (14.7 days in the steroid group, 15.8 days in the no-steroid group). Both neonatal and maternal infectious morbidity were similar. A significant reduction in the incidence of RDS (18.4 versus 43.6%, P = .03) were observed in the steroid group.
                These data suggest that treating preterm PROM patients with a broad-spectrum antibiotic before corticosteroids decreases RDS without apparent adverse sequelae. 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. A double-blind, collaborative, randomized trial was initiated in 1976 to evaluate dexamethasone administered to mothers as a method of preventing neonatal respiratory distress syndrome (RDS). Five centers enrolled 696 women at risk for premature delivery. Up to 20 mg of dexamethasone phosphate (5 mg every 12 hours) or a placebo was administered intramuscularly. The overall incidence of RDS was different between control subjects (18.0%) and steroid-treating mothers (12.6%) (P less than 0.05). The effect was, however, mainly attributable to discernible differences among singleton female infants (P less than 0.001), whereas no treatment effect was observed in male infants (P = 0.96). Non-Caucasians were improved whereas Caucasians showed little benefit. Fetal and neonatal mortality and maternal postpartum infection rates were not different. Neurologic examination at 40 weeks' gestation demonstrated no significant difference in the rate of abnormal outcomes in the neonatal steroid group (P = 0.2). To assess whether administration of dexamethasone in women with preterm premature rupture of membranes (PPROM) has an effect on the prevalence of maternal sepsis, neonatal respiratory distress syndrome (RDS), perinatal mortality and neonatal sepsis in a developing country.
                Six public hospitals in South Africa that deal mainly with indigent women.
                A multicentre, double-blind, placebo-controlled, randomised trial was performed on women with PPROM and fetuses of 28-34 weeks' gestation or clinically estimated fetal weight between 1,000 and 2,000 g if the gestational age was unknown. Women were randomised to receive either dexamethasone 24 mg intramuscularly or placebo in two divided doses 24 hours apart. All women received amoxycillin and metronidazole and were managed expectantly. Hexoprenaline was administered if contractions occurred within the first 24 hours after admission to the trial.
                The maternal outcome measures were clinical chorio-amnionitis and postpartum sepsis. The outcome measures for infants were perinatal death, RDS, mechanical ventilation, necrotising enterocolitis, and neonatal infection within 72 hours.
                One hundred and two women who delivered 105 babies were randomised to the dexamethasone group and 102 women who delivered 103 babies, to the placebo group. The groups were well balanced with regard to clinical features. There was a trend towards fewer perinatal deaths in the dexamethasone group: 4 compared with 10 (P = 0.16, odds ratio 0.37, 95% confidence intervals 0.09-1.34). A subanalysis of mothers who delivered more than 24 hours after admission to the study and their infants revealed a significant reduction in perinatal deaths; 1 death in the dexamethasone group and 7 in the placebo group, P = 0.047 (Fisher's exact test). No woman in either group developed severe sepsis, and the incidence of sepsis in the women did not differ significantly. Eleven infants in each group developed sepsis.
                This is the first randomised trial in women with PPROM to compare the effects of the use of corticosteroids with placebo, where all women received prophylactic antibiotics concomitantly with the corticosteroids. A trend towards an improved perinatal outcome was demonstrated in the women who received dexamethasone. There was no increased risk of infection in the women or their infants where dexamethasone was administered. Administration of corticosteroids to women with PPROM has more advantages than disadvantages in developing countries. A double-blind controlled study on the prenatal use of betamethasone in the prevention of respiratory distress syndrome (RDS) was carried out on 137 patients from 24 to 34 weeks' gestation. The incidence of RDS was less in the treated group (5%) than in control group (17%). The neonatal mortality rate was lower in the treated group (5%) than in the control group (18%) due to an excess of neonatal deaths in the placebo group. A prospective, randomized study was conducted comparing the use of betamethasone and early delivery, early delivery alone, and expectant management in patients in the 28th to 34th week of pregnancy with premature rupture of the membranes (PROM). Tocolytic drugs were used to delay delivery until 24 hours had elapsed after the first dose of steroid or 24 to 48 hours of latent period had elapsed in the second group. There were no significant differences in maternal age, gestation at PROM, maximum maternal temperature, birth weights, maternal hospital days, respiratory distress, maternal sepsis, or delivery routes in the three groups. Comparisons with one other similar prospective, randomized study support the concept that expectant management offers less risk from tocolytic side effects. To determine whether prenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) alters blood pressure in childhood.
                Prospective follow-up study of a randomized, double-blind, placebo-controlled trial.
                National Women's Hospital (Auckland, New Zealand).
                Two hundred twenty-three 6-year-old children of mothers who presented with unplanned premature labor and took part in a randomized, controlled trial of prenatal betamethasone therapy for the prevention of neonatal RDS.
                Mothers received 2 doses of betamethasone (12 mg) or placebo, administered through intramuscular injection, 24 hours apart.
                Systolic and diastolic blood pressure at 6 years of age.
                Children exposed prenatally to betamethasone (n = 121) did not differ in systolic or diastolic blood pressure from children exposed to placebo (n = 102) (mean difference: systolic: -1.6 mm Hg; 95% confidence interval: -4.1 to 0.8 mm Hg; diastolic: -0.3 mm Hg; 95% confidence interval: -2.5 to 1.8 mm Hg).
                Prenatal exposure to betamethasone for prevention of neonatal RDS does not alter blood pressure at 6 years of age. 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. In a prospective, randomized, double-blind, multicentre trial the effect of antenatal treatment with betamethasone phosphate was compared with placebo in the prevention of the respiratory distress syndrome (RDS) in preterm infants. The dose of betamethasone was 4 mg every 8 h for six doses, unless delivery occurred. The 251 women who were enrolled gave birth to 262 liveborn infants, 130 in the beta-methasone and 132 in the placebo group; the two groups were evenly matched in most respects. The diagnosis of RDS in the newborn was confirmed by two independent assessors. Seven of the 130 infants in the betamethasone group and 16 of the 132 in the placebo group developed RDS. In infants whose mothers had received at least three injections, RDS was also less frequent in the steroid group than in the placebo group (3/104 and 10/104 respectively; P less than 0.05). There was a significant reduction of RDS in those born between 24 h and 6 days after entry into the trial (0/30 and 8/45 respectively; P less than 0.05). The largest difference in frequency of RDS occurred in the subgroup of infants born before 34 weeks gestation, within 8 days of trial entry, and whose mothers had received at least three injections (0/27 steroid group and 7/32 placebo group; P = 0.03), and there were also significantly fewer neonatal deaths (2/27 and 13/32, respectively; P less than 0.01) in this subgroup. Betamethasone did not provoke earlier delivery. Premature rupture of the membranes and maternal hypertension did not seem to contraindicate the use of steroids: there was no increase in maternal or neonatal sepsis nor in stillbirth in hypertensive pregnancies in the steroid group. Neonatal jaundice was significantly less frequent in the steroid (55/129) than in the placebo group (81/127; P less than 0.01) but not in the subgroups born before 34 completed weeks gestation. A prospective double-blind randomized clinical trial was carried out to determine whether glucocorticoid treatment reduces the risk of respiratory distress syndrome (RDS) in prematurely born infants. There were 127 infants born to 122 mothers who received either steroid (dexamethasone phosphate) or placebo. No differences between groups occurred in risk factors for RDS (eg, prepartum asphyxia, male sex, cesarean section). When those who received a full course of dexamethasone therapy were compared with those who received placebo, a significant reduction was found in risk, severity, and deaths due to RDS. An increased incidence of infection in mothers treated with steroid was evident, particularly after premature rupture of membranes. We conclude that steroids are effective in reducing risk of RDS, but safer and more efficacious approaches for the prevention of RDS should be sought. 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.
The evidence from this new review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids should be considered routine for preterm delivery with few exceptions. Further information is required concerning optimal dose to delivery interval, optimal corticosteroid to use, effects in multiple pregnancies, and to confirm the long-term effects into adulthood.
[Note: The 16 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]