Published online August 31, 2007
PEDIATRICS Vol. 120 No. 3 September 2007, pp. 690-691 (doi:10.1542/peds.2007-1923)

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LETTER TO THE EDITOR

The DART Study of Low-Dose Dexamethasone Therapy: In Reply

Lex W. Doyle, MD^1
1 Departments of Obstetrics and Gynaecology and Paediatrics
University of Melbourne
Melbourne 3010, Australia
Division of Newborn Services
Royal Women's Hospital
Melbourne 3053, Australia

Peter G. Davis, MD²
Colin J. Morley, MD^2
2 Division of Newborn Services
Royal Women's Hospital
Melbourne 3053, Australia

Andy McPhee, MD^3
3 Department of Neonatology
Women's and Children's Hospital
Adelaide 5006, Australia

John B. Carlin, PhD^4
4 Department of Paediatrics
University of Melbourne
Melbourne 3010, Australia
Clinical Epidemiology and Biostatistics Unit
Murdoch Children's Research Institute
Melbourne 3052, Australia

We thank Rademaker et al for their thoughtful response to our follow-up report of the DART (Dexamethasone: A Randomized Trial) study.¹ They are concerned, quite correctly, about the issue of corticosteroid exposure outside the protocol; when this occurs in the control group after enrollment, it is referred to as "contamination." Contamination was an issue for most of the >40 reported randomized, controlled trials (RCTs) of postnatal corticosteroids. The fact that some in the control group also received corticosteroids meant that the trial was less likely to find differences between the 2 groups. The DART study did show differences even after contamination, and the most plausible interpretation is that these were causally related to the randomized treatment protocol, which led 1 group to receive more corticosteroid treatment than the other during the 10-day treatment course.

Rademaker et al state, "For now, we feel that the only proper conclusion that should be drawn is that no conclusion can be drawn." We disagree; in the DART study we found that more infants were extubated successfully by 10 days, ventilator and oxygen requirements improved, and the duration of intubation was shorter after the short course of low-dose dexamethasone.² The long-term effects were consistent with other follow-up studies of RCTs of postnatal corticosteroids in infants with a high rate of chronic lung disease in the control group,³ that is, there was a reduction in the risk difference for the combination of death or cerebral palsy.¹ Hence, we concluded "that low-dose dexamethasone in these infants may have short-term benefits without substantially increasing the risk of long-term neurologic disability."¹

Rademaker at el are concerned about the effects of total exposure to corticosteroids for both groups, but the DART study was not designed to address that issue. We described the amount of all corticosteroids, before and after entry to the study, for all subjects in our original report.² The DART study is the only RCT of postnatal corticosteroids to have reported this information. The reason for including subjects who had been exposed to corticosteroid (predominantly hydrocortisone) in the first week of life was because this reflected clinical practice at the time of the study, and we did not want to exclude an important subgroup of 15% of the infants from the trial. Having reported this once, we considered it redundant to repeat the information in the follow-up study report.

The adverse effects of corticosteroids in very preterm infants probably relate to both dose and timing. In this respect, exposure in the first week after birth may be damaging, whereas later exposure may not be so bad, especially in infants at high risk of chronic lung disease,³ which itself is harmful.

We do agree with Rademaker et al that the DART study cannot answer definitively the question of overall benefits and risks of low-dose dexamethasone in ventilator-dependent infants after the first week of life, for reasons that we indicated in our reports.^1,2 Indeed, we all "still await the definitive trial."¹

REFERENCES

1. Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB; DART Study Investigators. Outcome at 2 years of age of infants from the DART study: a multicenter, international, randomized, controlled trial of low-dose dexamethasone. Pediatrics. 2007;119 :716 –721[Abstract/Free Full Text]
2. Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB; DART Study Investigators. Low-dose dexamethasone facilitates extubation among chronically ventilator-dependent infants: a multicenter, international, randomized, controlled trial. Pediatrics. 2006;117 :75 –83[Abstract/Free Full Text]
3. Doyle LW, Halliday HL, Ehrenkranz RA, Davis PG, Sinclair JC. Impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk for chronic lung disease. Pediatrics. 2005;115 :655 –661[Abstract/Free Full Text]

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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Doyle, L. W. Articles by Carlin, J. B. Search for Related Content PubMed Articles by Doyle, L. W. Articles by Carlin, J. B. Related Collections Premature & Newborn Social Bookmarking                         What's this?