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ABSTRACT
BACKGROUND: For women at high risk of preterm delivery, it is the standard of care to administer an initial course of corticosteroids to promote lung maturity. Uncertainty remains, however, about the value of continuing treatments on a regular (weekly) schedule. This randomized controlled trial compared the efficacy of single versus weekly corticosteroids in reducing neonatal morbidity in women at high risk of preterm delivery.
POPULATION STUDIED: A total of 502 women between 24 weeks’ and 32 weeks and 6 days’ gestation at high risk for preterm delivery were recruited from 13 US academic centers. High risk was defined as preterm labor, preterm rupture of membranes, maternal medical illness, or suspected intrauterine growth restriction. Women were excluded if they needed immediate delivery, had active tuberculosis or human immunodeficiency virus infection, or if their fetuses had mature lungs or severe anomalies. Approximately equal proportions of subjects were white, Hispanic, and African American, and 67% were receiving government assistance. Also, 33% were nulliparous; 54% had preterm labor; and 14.5% had multiple gestations.
STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded trial. Women at high risk for preterm delivery who received an initial course of corticosteroids and had not delivered in 1 week were randomized to receive either betamethasone 12 mg twice in 24 hours every week until 34 weeks or similarly administered placebo. Analysis was by intention to treat, using chi-square tests and t tests with assessment of study site as a potential confounder. The study was halted after 502 of a planned 1000 patients were recruited, due to emerging evidence that weekly corticosteroids might produce long-term neurologic sequelae. The methodology of this study was strong. The major weakness was lack of statistical power.
OUTCOMES MEASURED: The primary outcome was composite neonatal morbidity (including severe RDS, BPD and IVH, periventricular leukomalacia, sepsis, NEC, or death). Secondary outcomes included each individual outcome, maternal side effects, and clinical course. Utilization, cost, and patient satisfaction were not addressed.
RESULTS: The groups were similar at baseline and follow up was 97%. There was no significant difference in composite morbidity between the weekly course group and the single-course group. Exploratory analysis showed that weekly corticosteroids decreased severe RDS (15.3% vs 24.1%; P=.01), but there also a trend toward an increased risk of severe IVH in the weekly course group (7.6% vs 2.0%; P=.06). The weekly course group had shorter time to delivery (5.0 vs 5.8 weeks; P=.02) and a trend towards more chorioamnionitis (24.1% vs 17.8%; P=.09). There was no significant difference between the 2 treatment regimens in endometritis, wound infections, hemorrhage, or length of stay.
This study provides fair evidence that there is no significant benefit and possibly an increased risk of morbidity in giving weekly corticosteroids to mothers at risk for preterm labor. In the context of studies that have suggested adverse behavior1 and delayed psychomotor development2 in children of mothers treated with repeated corticosteroids, clinicians should administer only a single course of corticosteroids and avoid weekly treatment. The burden of proof is on advocates of weekly treatments to demonstrate that benefits clearly exceed risks.
ABSTRACT
BACKGROUND: For women at high risk of preterm delivery, it is the standard of care to administer an initial course of corticosteroids to promote lung maturity. Uncertainty remains, however, about the value of continuing treatments on a regular (weekly) schedule. This randomized controlled trial compared the efficacy of single versus weekly corticosteroids in reducing neonatal morbidity in women at high risk of preterm delivery.
POPULATION STUDIED: A total of 502 women between 24 weeks’ and 32 weeks and 6 days’ gestation at high risk for preterm delivery were recruited from 13 US academic centers. High risk was defined as preterm labor, preterm rupture of membranes, maternal medical illness, or suspected intrauterine growth restriction. Women were excluded if they needed immediate delivery, had active tuberculosis or human immunodeficiency virus infection, or if their fetuses had mature lungs or severe anomalies. Approximately equal proportions of subjects were white, Hispanic, and African American, and 67% were receiving government assistance. Also, 33% were nulliparous; 54% had preterm labor; and 14.5% had multiple gestations.
STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded trial. Women at high risk for preterm delivery who received an initial course of corticosteroids and had not delivered in 1 week were randomized to receive either betamethasone 12 mg twice in 24 hours every week until 34 weeks or similarly administered placebo. Analysis was by intention to treat, using chi-square tests and t tests with assessment of study site as a potential confounder. The study was halted after 502 of a planned 1000 patients were recruited, due to emerging evidence that weekly corticosteroids might produce long-term neurologic sequelae. The methodology of this study was strong. The major weakness was lack of statistical power.
OUTCOMES MEASURED: The primary outcome was composite neonatal morbidity (including severe RDS, BPD and IVH, periventricular leukomalacia, sepsis, NEC, or death). Secondary outcomes included each individual outcome, maternal side effects, and clinical course. Utilization, cost, and patient satisfaction were not addressed.
RESULTS: The groups were similar at baseline and follow up was 97%. There was no significant difference in composite morbidity between the weekly course group and the single-course group. Exploratory analysis showed that weekly corticosteroids decreased severe RDS (15.3% vs 24.1%; P=.01), but there also a trend toward an increased risk of severe IVH in the weekly course group (7.6% vs 2.0%; P=.06). The weekly course group had shorter time to delivery (5.0 vs 5.8 weeks; P=.02) and a trend towards more chorioamnionitis (24.1% vs 17.8%; P=.09). There was no significant difference between the 2 treatment regimens in endometritis, wound infections, hemorrhage, or length of stay.
This study provides fair evidence that there is no significant benefit and possibly an increased risk of morbidity in giving weekly corticosteroids to mothers at risk for preterm labor. In the context of studies that have suggested adverse behavior1 and delayed psychomotor development2 in children of mothers treated with repeated corticosteroids, clinicians should administer only a single course of corticosteroids and avoid weekly treatment. The burden of proof is on advocates of weekly treatments to demonstrate that benefits clearly exceed risks.
ABSTRACT
BACKGROUND: For women at high risk of preterm delivery, it is the standard of care to administer an initial course of corticosteroids to promote lung maturity. Uncertainty remains, however, about the value of continuing treatments on a regular (weekly) schedule. This randomized controlled trial compared the efficacy of single versus weekly corticosteroids in reducing neonatal morbidity in women at high risk of preterm delivery.
POPULATION STUDIED: A total of 502 women between 24 weeks’ and 32 weeks and 6 days’ gestation at high risk for preterm delivery were recruited from 13 US academic centers. High risk was defined as preterm labor, preterm rupture of membranes, maternal medical illness, or suspected intrauterine growth restriction. Women were excluded if they needed immediate delivery, had active tuberculosis or human immunodeficiency virus infection, or if their fetuses had mature lungs or severe anomalies. Approximately equal proportions of subjects were white, Hispanic, and African American, and 67% were receiving government assistance. Also, 33% were nulliparous; 54% had preterm labor; and 14.5% had multiple gestations.
STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded trial. Women at high risk for preterm delivery who received an initial course of corticosteroids and had not delivered in 1 week were randomized to receive either betamethasone 12 mg twice in 24 hours every week until 34 weeks or similarly administered placebo. Analysis was by intention to treat, using chi-square tests and t tests with assessment of study site as a potential confounder. The study was halted after 502 of a planned 1000 patients were recruited, due to emerging evidence that weekly corticosteroids might produce long-term neurologic sequelae. The methodology of this study was strong. The major weakness was lack of statistical power.
OUTCOMES MEASURED: The primary outcome was composite neonatal morbidity (including severe RDS, BPD and IVH, periventricular leukomalacia, sepsis, NEC, or death). Secondary outcomes included each individual outcome, maternal side effects, and clinical course. Utilization, cost, and patient satisfaction were not addressed.
RESULTS: The groups were similar at baseline and follow up was 97%. There was no significant difference in composite morbidity between the weekly course group and the single-course group. Exploratory analysis showed that weekly corticosteroids decreased severe RDS (15.3% vs 24.1%; P=.01), but there also a trend toward an increased risk of severe IVH in the weekly course group (7.6% vs 2.0%; P=.06). The weekly course group had shorter time to delivery (5.0 vs 5.8 weeks; P=.02) and a trend towards more chorioamnionitis (24.1% vs 17.8%; P=.09). There was no significant difference between the 2 treatment regimens in endometritis, wound infections, hemorrhage, or length of stay.
This study provides fair evidence that there is no significant benefit and possibly an increased risk of morbidity in giving weekly corticosteroids to mothers at risk for preterm labor. In the context of studies that have suggested adverse behavior1 and delayed psychomotor development2 in children of mothers treated with repeated corticosteroids, clinicians should administer only a single course of corticosteroids and avoid weekly treatment. The burden of proof is on advocates of weekly treatments to demonstrate that benefits clearly exceed risks.