The standard of care for women at risk for preterm delivery between 24 and 34 weeks of gestation is 1 course of antenatal steroids, according to the National Institutes of Health Consensus Development Conference Statement published in the July 1995 issue of the American Journal of Obstetrics & Gynecology. In the June 10, 2006, issue of The Lancet, Crowther and colleagues reported that weekly antenatal steroids vs placebo resulted in decreased incidence of respiratory distress syndrome. However, as noted by Stiles in the September 20, 2007, issue of the New England Journal of Medicine, there are concerns about possible harms, including reduced in utero growth, after weekly antenatal steroid treatment.
In a March 15th online paper in the American Journal of Obstetrics & Gynecology, it is reported that when women at risk for preterm delivery receive steroids but then don't give birth in the next 7 days, a second "rescue" course of steroids improves lung function in their newborn. This randomized, double-blind trial assessed whether a rescue course of antenatal steroids vs placebo results in differences in respiratory compliance, functional residual capacity, other measures of respiratory status, survival, and growth.Findings indicate that the repeat treatment improves respiratory compliance and also leads to a lower rate of respiratory distress syndrome.
The randomized trial included 85 women, all 26 to 34 weeks pregnant and all at continued risk for preterm delivery. The researchers randomized 44 women to receive two 12-mg intramuscular injections of betamethasone 24 hours apart, and 41 to receive placebo. The women had received their first course of steroids at a mean of about 27 weeks gestation; they received the study dose at a mean of about 30 weeks. The analysis included 56 infants in each group. The authors assessed newborns' pulmonary function within 72 hours of birth and before the babies received any surfactant therapy.
The rescue group had significantly higher passive respiratory compliance compared with the placebo group (1.21 vs 1.01 mL/cm H2O/kg, p = 0.04). Pulmonary benefits were even more pronounced in infants born at 34 weeks of gestation or earlier (44 rescue, 39 placebo). A planned subgroup analysis showed respiratory compliance to be 1.17 mL/cm H2O/kg in the rescue group vs 0.90 in controls (p = 0.04).
Overall and in the subgroup analysis, significantly fewer babies in the treatment group required at least 30% oxygen or at least 40% oxygen (although this parameter was not a primary outcome). There was no difference between groups in functional residual capacity, however. Rates of respiratory distress syndrome were lower in the rescue group, with a significant difference in the subgroup analysis (34% s 56%, p < 0.05.)
Better respiratory compliance translates into improved clinical respiratory outcomes, with less oxygen requirements and a trend toward less respiratory distress syndrome. It is noted that "the enzyme system responsible for surfactant production can be repetitively induced, despite prior treatment" with antenatal steroids.
The researchers are continuing to follow their patients. In addition, based on their findings, they call for a larger controlled trial of high-risk patients, with long-term monitoring of pulmonary outcomes, growth, and neurodevelopment.
Edited From Reuters Health Information
Abstract
Am J Obstet Gynecol. 2010 Mar 12. [Epub ahead of print]
Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial.
McEvoy C, Schilling D, Peters D, Tillotson C, Spitale P, Wallen L, Segel S, Bowling S, Gravett M, Durand M. Division of Neonatology, Department of Pediatrics.
OBJECTIVE: To compare respiratory compliance and functional residual capacity in infants randomized to a rescue course of antenatal steroids vs placebo. STUDY DESIGN: Randomized, double-blinded trial. Pregnant women >/=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). RESULTS: 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 >/=30% oxygen (P < .05). Patients delivered at
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