Effect of AAP Statement Regarding Postnatal Corticosteroids on Ongoing and Future Randomized, Controlled Trials

To the Editor.—This February the Committee on Fetus and Newborn of the American Academy of Pediatrics (AAP) and the Fetus and Newborn Committee of the Canadian Paediatric Society (CPS) advised, among other recommendations, that the postnatal use of systemic dexamethasone for the prevention or treatment of chronic lung disease should be limited to randomized, controlled trials with survival without long-term developmental impairments as the major endpoint.1 This past June, Halliday, commenting on the early use of dexamethasone, repeated the statements of the AAP and the CPS, and specifically recommended the DART study.2 The DART study is recruiting infants of either <1000 g birth weight or <28 weeks’ gestation who are ventilator-dependent after 7 years of age into a double-blind, randomized-controlled trial of low-dose dexamethasone compared with placebo. The major endpoint is survival free of major disability at 2 years of age, which will account for the potentially competing risks of mortality and cerebral palsy, among other neurosensory impairments. It is the only current study of which we are aware that is testing the therapeutic use of dexamethasone in ventilator-dependent infants with long-term outcomes as the major endpoint.The DART study has 10 centers in Australia, New Zealand, and Canada that have recruited at least 1 patient, and several other centers are ready to recruit their first patient. The total sample size is 814, and so far <10% have been recruited. In an apparent paradox, since the joint statement by AAP and the CPS in February, recruitment has dropped, not increased. Moreover, the uncertainty has not been translated into new centers wanting to join the study. Unfortunately for the infants concerned, unless the recruitment rate picks up dramatically, the DART study may have to be abandoned. Then we may never know what to do about dexamethasone in ventilator-dependent infants. We remain hopeful, however, that Halliday’s comments will not only increase interest in the DART study, but will also translate into more infants recruited, which is essential for the study to continue.Reply.—Thank you for the opportunity to reply to the letter-to-the-editor from the chief co-investigators of the DART study. I appreciate their concerns regarding the slow recruitment of study centers and thus the slow accumulation of study subjects. While acknowledging that the publication of the joint AAP/CPS statement regarding postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants could have discouraged the participation of US neonatal centers in the study, the data from the previously published studies on which the recommendations were based should not be discounted. Further, the European Association of Perinatal Medicine had earlier recommended against routine administration of postnatal corticosteroids for the prevention of chronic lung disease consequent to ventilator therapy.1The joint statement specifically did not recommend against additional trials but, as the authors note, in fact supported additional trials designed to answer the question of “long-term developmental impairments”2 definitively by the exclusion of the confounding issues of posttrial corticosteroid therapy and crossover design. The latter design requirements are essential to establish that postnatal corticosteroid (dexamethasone?) treatment alone is the key factor resulting in adverse neurodevelopmental outcomes of exposed extremely preterm infants.It is entirely appropriate and useful for those neonatologists who retain equipoise regarding postnatal corticosteroid therapy to prevent or treat chronic lung disease of prematurity to enlist subjects for the DART study, always with the informed consent of the parents. The consent process should include the most current information regarding the potential risks of such therapy.

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