Published online March 1, 2005
PEDIATRICS Vol. 115 No. 3 March 2005, pp. 655-661 (doi:10.1542/peds.2004-1238)
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Impact of Postnatal Systemic Corticosteroids on Mortality and Cerebral Palsy in Preterm Infants: Effect Modification by Risk for Chronic Lung Disease

Lex W. Doyle, MD*,{ddagger}, Henry L. Halliday, MD§, Richard A. Ehrenkranz, MD||, Peter G. Davis, MD*,{ddagger} and John C. Sinclair, MD#,¶

* Division of Paediatrics, Royal Women’s Hospital, Melbourne, Australia
{ddagger} Departments of Obstetrics and Gynaecology and of Paediatrics, University of Melbourne, Melbourne, Australia
§ Department of Child Health, Queen’s University, Belfast, Northern Ireland
|| Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
# Department of Pediatrics, Center for Clinical Research and Evidence-Based Medicine, University of Texas Medical School, Houston, Texas

Objective. In preterm infants, chronic lung disease (CLD) is associated with an increased risk for cerebral palsy (CP). However, systemic postnatal corticosteroid therapy to prevent or treat CLD, although effective in improving lung function, may cause CP. The objective of this study was to determine the effect of systemic postnatal corticosteroid treatment on death and CP and to assess any modification of effect arising from risk for CLD.

Methods. Randomized, controlled trials of postnatal corticosteroid therapy for prevention or treatment of CLD in preterm infants that reported rates of both mortality and CP were reviewed and their data were synthesized. Twenty studies with data on 1721 randomized infants met eligibility criteria. The relationship between the corticosteroid effect on the combined outcome, death or CP, and the risk for CLD in control groups was analyzed by weighted meta-regression.

Results. Among all infants who were randomized, a significantly higher rate of CP after corticosteroid treatment (typical risk difference [RD]: 0.05; 95% confidence interval [CI]: 0.02, 0.08) was partly offset by a nonsignificant reduction in mortality (typical RD: –0.02; 95% CI: –0.06 to 0.02). Consequently, there was no significant effect of corticosteroid treatment on the combined rate of mortality or CP (typical RD: 0.03; 95% CI: –0.01 to 0.08). However, on meta-regression, there was a significant negative relationship between the treatment effect on death or CP and the risk for CLD in control groups. With risks for CLD below 35%, corticosteroid treatment significantly increased the chance of death or CP, whereas with risks for CLD exceeding 65%, it reduced this chance.

Conclusions. The effect of postnatal corticosteroids on the combined outcome of death or CP varies with the level of risk for CLD.

Key Words: infant • preterm • survival • cerebral palsy • corticosteroids

Abbreviations: CLD, chronic lung disease • CP, cerebral palsy • RCT, randomized, controlled trial • RR, relative risk • RD, risk difference • CI, confidence interval • IQR, interquartile range

Accepted Aug 5, 2004.




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