Published online July 1, 2008
PEDIATRICS Vol. 122 No. 1 July 2008, pp. 92-101 (doi:10.1542/peds.2007-2258)
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ARTICLE

Effects of Higher Versus Lower Dexamethasone Doses on Pulmonary and Neurodevelopmental Sequelae in Preterm Infants at Risk for Chronic Lung Disease: A Meta-analysis

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

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

OBJECTIVES. Systemic postnatal dexamethasone treatment reduces the risk of chronic lung disease in preterm infants but also may be associated with increased risk of neurodevelopmental impairment. Because it is not known whether these effects are modulated by the cumulative dexamethasone dose, we systematically reviewed the available randomized evidence on the effects of lower versus higher cumulative dexamethasone doses, in terms of death, pulmonary morbidity, and neurodevelopmental outcomes, in preterm infants.

METHODS. Randomized, controlled trials comparing higher- versus lower-dosage dexamethasone regimens in ventilated preterm infants were identified by searching the main electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research (from 1990 onward). Eligibility and quality of trials were assessed, and data on study design, patient characteristics, and relevant outcomes were extracted.

RESULTS. Six studies that enrolled a total of 209 participants were included; 2 studies contrasted cumulative dexamethasone doses in the higher ranges (>2.7 mg/kg in the higher-dosage regimen) and 4 in the lower ranges (≤2.7 mg/kg in the higher-dosage regimen). Meta-analysis revealed no effect of dexamethasone dose on rates of death and neurodevelopmental sequelae in these 2 subgroups. Subgroup analysis of the studies contrasting dexamethasone doses in the higher ranges showed that the higher dose of dexamethasone was more effective in reducing the occurrence of chronic lung disease than was the lower dose. Interpretation of these data was hampered by the small samples of randomly assigned children, heterogeneity of study populations and designs, use of late rescue glucocorticoids, and lack of long-term neurodevelopmental data in some studies.

CONCLUSIONS. Recommendations for optimal dexamethasone doses for preterm infants at risk for chronic lung disease cannot be based on current evidence. A well-designed, large, randomized, controlled trial is urgently needed to establish the optimal dexamethasone dosage regimen.

Key Words: chronic lung disease • cerebral palsy • glucocorticoids • systematic review • dosage regimen

Abbreviations: CLD—chronic lung disease • PMA—postmenstrual age • RCT—randomized, controlled trial • MDI—Mental Developmental Index • RR—relative risk • CI—confidence interval

Accepted Oct 31, 2007.