Published online December 29, 2008
PEDIATRICS Vol. 123 No. 1 January 2009, pp. 367-377 (doi:10.1542/peds.2008-0016)
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REVIEW ARTICLE

Finding the Optimal Postnatal Dexamethasone Regimen for Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Systematic Review of Placebo-Controlled Trials

Wes Onland, MDa, Martin Offringa, MD PhDa,b, Anne P. De Jaegere, MDa and Anton H. van Kaam, MD, PhDa

a Department of Neonatology, Emma Children's Hospital, Academic Medical Center, Amsterdam, Netherlands
b Center for Pediatric Clinical Epidemiology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Netherlands

CONTEXT. Postnatal dexamethasone therapy reduces the incidence of bronchopulmonary dysplasia in preterm infants but may be associated with an increased risk for adverse neurodevelopmental outcome.

OBJECTIVE. Our goal was to determine if the effects of dexamethasone on mortality and pulmonary and neurodevelopmental sequelae in preterm infants are modified by the cumulative dose given.

METHODS. Randomized, controlled trials comparing dexamethasone with placebo in ventilated preterm infants >7 days old were identified by searching the electronic databases and the abstracts from the Pediatric Academic societies and by performing manual reference searches. Two reviewers independently assessed eligibility and quality of trials and extracted data on study design, patient characteristics, and relevant outcomes. Original trialists were asked to provide additional data.

RESULTS. Sixteen trials including 1136 patients were analyzed by using meta-analysis and metaregression. Additional data were provided by 12 original trialists. Trials with a moderately early (7- to 14-day) or delayed (>3-week) postnatal treatment onset were analyzed separately. Higher dexamethasone doses reduced the relative risk for the combined outcome, mortality or bronchopulmonary dysplasia, with the largest effect in trials that used a cumulative dose of >4 mg/kg. No effect was found of doses on the risk of neurodevelopmental sequelae in the delayed treatment studies, but in the moderately-early-treatment studies the risk of mortality or cerebral palsy decreased by 6.2%, and the risk of a Mental Developmental Index below –2 SDs decreased by 6.6% for each incremental mg/kg cumulative dexamethasone dose.

CONCLUSIONS. Higher cumulative dexamethasone doses administered after the first week of life may decrease the risk for bronchopulmonary dysplasia without increasing the risk for neurodevelopmental sequelae in ventilated preterm infants. A large randomized trial is needed to confirm or refute these findings.

Key Words: glucocorticoids • systematic reviews • mortality • bronchopulmonary dysplasia • cerebral palsy • dosage schedules • cumulative dose

Abbreviations: RCT—randomized, controlled trial • BPD—bronchopulmonary dysplasia • CP—cerebral palsy • PMA—postmenstrual age • MDI—Mental Developmental Index • RR—relative risk • WMD—weighted mean difference • CI—confidence interval • DART—Dexamethasone: A Randomized Trial • CDTG—Collaborative Dexamethasone Trial Group

Accepted Apr 24, 2008.


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