Single versus multiple courses of antenatal betamethasone and neonatal outcome: a randomized controlled trial. The effect of a single remote course versus weekly courses of antenatal corticosteroids on functional residual capacity in preterm infants: a randomized trial. Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial. Randomized trial of a single repeat dose of prenatal betamethasone treatment in imminent preterm birth. Multiple versus single courses of antenatal corticosteroids for preterm birth: a pilot study. Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial. Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial.
This study compared the beneficial and adverse neonatal effects of a single versus repeated courses of antenatal betamethasone.
                Tertiary care hospital
                Open labeled, randomized controlled trial.
                Pregnant women (26-33 weeks) at risk of preterm delivery, who received one course of antenatal betamethasone and remained undelivered for 7 days. Those with uncertain gestation, major malformations and frank chorioamnionitis were excluded.
                Subjects were randomized to receive weekly antenatal betamethasone until 34 weeks or no further betamethasone.
                Primary: incidence of severe respiratory distress syndrome (RDS). Secondary: incidence of non-severe RDS and other neonatal morbidity; birth weight, length and occipito-frontal circumference (OFC); and, development and growth at 6 mo corrected age.
                38 subjects were allocated to each group. Severe RDS was similar in multiple and single course groups (7% vs. 3% respectively, P=0.34), as was incidence of other morbidity. Composite outcome of RDS and or death within 28 days tended to be less in multiple course group (P=0.07). Birth anthropometry was similar in the 2 groups. At 6 mo corrected age (n=44), weight and length were significantly lower in multiple course group (p=0.003 and P=0.007, respectively), whereas OFC was not different (P=0.1). There were no differences vis a vis neurodevelopmental outcomes.
                A single course of antenatal betamethasone was as efficacious as multiple courses, with respect to prevention of neonatal morbidity. Multiple antenatal betamethasone courses have long-term adverse effects on infant weight and length growth, but not on OFC and neurodevelopment. There are no randomized data on the effect of repeat courses of corticosteroids during pregnancy on newborn pulmonary function. Our objective was to compare the effect of a single remote course of antenatal steroids (AS) with weekly courses of AS on functional residual capacity (FRC) and respiratory compliance in preterm infants.
                Pregnant women 25 to 33 weeks' gestation, who remained undelivered 1 week after their first course of antenatal corticosteroids (two 12-mg doses of betamethasone) were randomized to weekly courses of corticosteroids versus weekly placebo until delivery or 34 weeks' gestation. FRC was measured with the nitrogen washout technique and respiratory compliance with the single breath occlusion technique within 48 hours of life.
                Thirty-seven infants (mean gestational age at delivery approximately 32.5 weeks) were studied. Maternal and infant demographics were similar. There was no significant difference in FRC (28.5 vs 27.5 mL/kg) or respiratory compliance between the infants who received a single remote course of antenatal corticosteroids and those who received weekly courses of corticosteroids until delivery. There was no significant difference in admission head circumference or birth weights between the groups.
                Our results demonstrate that weekly repetitive courses of AS do not significantly increase FRC or respiratory compliance in preterm infants when compared with a single remote course of steroids given at a mean gestational age of 29 weeks. The practice of administering weekly courses of antenatal corticosteroids to pregnant women at risk of preterm delivery is widespread, but no randomized trial has established the efficacy or safety of this practice.
                To evaluate the efficacy of weekly administration of antenatal corticosteroids compared with a single course in reducing the incidence of neonatal morbidity and to evaluate potential complications of weekly treatment.
                Randomized, double-blind, placebo-controlled intention-to-treat trial conducted in 13 academic centers in the United States from February 1996 through April 2000.
                A total of 502 pregnant women between 24 and 32 completed weeks' gestation who were at high risk of preterm delivery.
                All patients received a complete single course of antenatal corticosteroids (either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for 4 doses). Participants who had not delivered 1 week after receipt of the single course were randomly assigned to receive either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses every week until 34 weeks' gestation or delivery, whichever came first (n = 256), or a similarly administered placebo (n = 246).
                Composite neonatal morbidity (including severe respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death).
                Composite morbidity occurred in 22.5% of the weekly-course group vs 28.0% of the single-course group (unadjusted relative risk, 0.80; 95% confidence interval, 0.59-1.10). Neither group assignment nor the number of treatment courses was associated with a reduction in composite morbidity.
                Weekly courses of antenatal corticosteroids did not reduce composite neonatal morbidity compared with a single course of treatment. Weekly courses of antenatal corticosteroids should not be routinely prescribed for women at risk of preterm delivery. The purpose of this study was to determine if weekly corticosteroids improve neonatal outcome without undue harm.
                Women 23 to 32 weeks receiving 1 course of corticosteroids 7 to 10 days prior were randomized to weekly betamethasone or placebo.
                The study was terminated by the independent data and safety monitoring committee with 495 of the anticipated 2400 patients enrolled. There was no significant reduction in the composite primary morbidity outcome (8.0% vs 9.1%, P = .67). Repeated courses significantly reduced neonatal surfactant administration (P = .02), mechanical ventilation (P = .004), CPAP (P = .05), pneumothoraces (P = .03). There was no significant difference in mean birth weight or head circumference. The repeat group had a reduction in multiples of the birth weight median by gestational age (0.88 vs 0.91) (P = .01) and more neonates weighing less than the 10th percentile (23.7 vs 15.3%, P = .02). Significant weight reductions occurred for the group receiving > or = 4 courses.
                Repeat antenatal corticosteroids significantly reduce specific neonatal morbidities but do not improve composite neonatal outcome. This is accompanied by reduction in birth weight and increase in small for gestational age infants. To compare respiratory compliance and functional residual capacity in infants randomized to a rescue course of antenatal steroids vs placebo.
                Randomized, double-blinded trial. Pregnant women > or =14 days after initial antenatal steroids were randomized to rescue antenatal steroids or placebo. The primary outcomes were measurements of respiratory compliance and functional residual capacity. This study is registered with clinicaltrials.gov (NCT00669383).
                Forty-four mothers (56 infants) received rescue antenatal steroids and 41 mothers (57 infants) received placebo. There was no significant difference in birthweight, or head circumference. Infants in the rescue group had an increased respiratory compliance (1.21 vs 1.01 mL/cm H(2)O/kg; adjusted 95% confidence interval, 0.01-0.49; P = .0433) compared with placebo. 13% in the rescue vs 29% in the placebo group required > or =30% oxygen (P < .05). Patients delivered at < or =34 weeks had greater pulmonary benefits.
                Infants randomized to rescue antenatal steroids have a significantly increased respiratory compliance compared with placebo.
                Copyright 2010 Mosby, Inc. All rights reserved. A single dose of prenatal betamethasone treatment decreases neonatal morbidity rates when administered within 7 days before preterm delivery. A single repeat dose or booster dose of betamethasone before delivery has been proposed to be effective, but its efficacy has not been subjected to a randomized, blinded trial.
                Women with imminent delivery before 34.0 gestational weeks were eligible if they remained without delivery for >7 days after a single course of betamethasone. After stratification, a single repeat dose of betamethasone (12 mg) or placebo was administered. The primary outcome was survival without respiratory distress syndrome or severe intraventricular hemorrhage (grade 3 or 4).
                A total of 249 mothers had been enrolled by the time the study was discontinued. All of the 159 infants in the betamethasone group and 167 in the placebo group were born before 36 weeks of gestation. The intact survival rate was unaffected and was lower than anticipated, because the gestational age-adjusted incidence of respiratory distress syndrome was higher than the population incidence. The requirement for surfactant therapy in respiratory distress syndrome was increased in the betamethasone group. According to posthoc analysis of the data for 206 infants who were delivered within 1 to 24 hours, the betamethasone booster tended to increase the risk of respiratory distress syndrome and to decrease intact survival rates.
                According to this study, a single booster dose of betamethasone just before preterm birth may perturb respiratory adaptation. These results caution against uncontrolled use of a repeat dose of glucocorticoid in high-risk pregnancies. (1) To determine the feasibility of a multicentre, randomized, double-masked, placebo-controlled trial to investigate the effects of multiple courses of antenatal corticosteroids (ACS), more than 7 days following the initial course of ACS therapy, on perinatal or neonatal mortality or neonatal morbidity. (2) To determine the risk of complications that would require discontinuation of ACS therapy. (3) To determine if multiple courses of ACS have an effect on the concentrations of plasma cortisol and adrenocorticotropin hormone (ACTH) in cord blood and in maternal blood immediately following delivery, compared to a single course of ACS.
                Women at 24 to 30 weeks' gestation, at continued increased risk of preterm birth 7 or more days following a single course of ACS, were randomized to receive weekly courses of betamethasone or placebo until 33 weeks' gestation or delivery.
                Women were recruited at two hospitals in Toronto from 01 September 1999 to 31 August 2000. Of the 78 women who were approached and were eligible for the study, 12 (15%) were recruited and 66 (85%) refused to participate. Of the 66 refusals, 38 (58%) did not feel their physicians were supportive of the study, 10 (15%) did not want to be randomized, and 4 (6%) had other personal reasons for refusing to enter the trial. Fourteen women (21%) had physicians who did not allow them to join the study. The lack of physician support was due to concerns related to the potential adverse effects of multiple courses of ACS. There were no complications requiring discontinuation of ACS. Plasma cortisol and ACTH concentrations in cord and maternal blood taken after delivery were not significantly different between ACS and placebo groups.
                A multicentre randomized controlled trial is required to determine the benefits and risks of multiple versus a single course of ACS. If the study protocols are supported by physicians and their patients, a multicentre randomized controlled trial is feasible. The efficacy and safety of repeat doses of prenatal corticosteroids remains uncertain. Our aim was to establish whether repeat prenatal corticosteroids given to women at risk of preterm birth can reduce neonatal morbidity without harm.
                In this hospital-based study, 982 women who remained at risk of preterm birth at less than 32 weeks' gestation, 7 or more days after receiving a first course of prenatal corticosteroids, were randomly assigned to receive a repeat intramuscular dose of either 11.4 mg betamethasone (as Celestone Chronodose), or saline placebo. This was repeated every week the woman remained undelivered, at less than 32 weeks' gestation, and at risk of preterm birth. Primary outcomes were occurrence and severity of neonatal respiratory distress syndrome, use and duration of oxygen and mechanical ventilation, and weight, length, and head circumference at birth and hospital discharge. Statistical analyses were on an intention to treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN48656428.
                Fewer babies exposed to repeat corticosteroids had respiratory distress syndrome (33%vs 41%; relative risk 0.82, 95% CI 0.71-0.95, p=0.01) and fewer had severe lung disease (12%vs 20%; relative risk 0.60, 95% CI 0.46-0.79, p=0.0003) than those in the placebo group. In keeping with these benefits, babies exposed to repeat corticosteroids needed less oxygen therapy (p=0.03), and shorter duration of mechanical ventilation (p=0.01). Mean weight, length, and head circumference at birth and hospital discharge did not differ between treatment groups. Z-scores for weight (p=0.04) and head circumference (p=0.03) at birth were lower in the babies who received repeat corticosteroids although at the time of hospital discharge Z-scores did not differ between treatment groups (p=0.29 for weight, p=0.48 for head circumference).
                Exposure to repeat doses of antenatal corticosteroids reduces neonatal morbidity. Pending long-term outcome results, the short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course. One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth.
                1858 women at 25-32 weeks' gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148.
                Infants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216 g vs 2330 g, p=0.0026), were shorter (44.5 cm vs 45.4 cm, p<0.001), and had a smaller head circumference (31.1 cm vs 31.7 cm, p<0.001).
                Multiple courses of antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes, and are associated with a decreased weight, length, and head circumference at birth. Therefore, this treatment schedule is not recommended.
                Canadian Institutes of Health Research.
The short-term benefits for babies of less respiratory distress and fewer serious health problems in the first few weeks after birth support the use of repeat dose(s) of prenatal corticosteroids for women still at risk of preterm birth seven days or more after an initial course. These benefits were associated with a small reduction in size at birth. The current available evidence reassuringly shows no significant harm in early childhood, although no benefit.
Further research is needed on the long-term benefits and risks for the woman and baby. Individual patient data meta-analysis may clarify how to maximise benefit and minimise harm.