Short- and long-term effects of neonatal glucocorticoid therapy: is hydrocortisone an alternative to dexamethasone? M van der Heide-Jalving 1 , PJGH Kamphuis 2 , MJ van der Laan 1 , JM Bakker 1,3 , VM Wiegant 2 , CJ Heijnen 3 , S Veen 4 and F van Bel 1 Department of Neonatology 1 ; Rudolf Magnus Institute for Neurosciences 2 ; Department of Immunology 3 , University Medical Centre/ Wilhelmina Children’s Hospital, Utrecht; Department of Pediatrics 4 , Leiden University Medical Centre, Leiden, The Netherlands van der Heide-Jalving M, Kamphuis PJGH, van der Laan MJ, Bakker JM, Wiegant VM, Heijnen CJ, Veen S, van Bel F. Short- and long-term effects of neonatal glucocorticoid therapy: is hydrocortisone an alternative to dexamethasone? Acta Pædiatr 2003; 92: 827–835. Stockholm. ISSN 0803-5253 Aim: To compare short-term effects and neurodevelopmental outcome of neonatal glucocorticoid therapy between two centres. Methods: A retrospective study was performed in two centres using a tapering course of either 5 to 1 mg kg 1 hydrocortisone (HC; 22 d) or 0.5 to 0.1 mg kg 1 dexamethasone (DEX; 21 d). In both centres glucocorticoid-treated infants and control patients were matched for gestational age, birthweight, severity of infant respiratory distress syndrome and periventricular–intraventricular haemorrhage. The following short-term glucocorticoid-induced effects were investigated in 25 HC-treated and 25 control patients in centre A, and in 23 DEX- treated and 23 control patients in centre B: oxygen dependency (inspiratory oxygen fraction), arterial pressure, blood glucose and urea concentrations, weight gain and head circumference before, during and after therapy (in treated infants), or at an interval comparable to treated infants (in control infants). Neurological outcome, psychomotor development and school performance at 5–7 y of age was evaluated in all groups. Results: HC and DEX were equally potent in reducing oxygen dependency. Mean arterial pressure as well as blood glucose and urea concentrations were significantly increased during DEX, but not during HC treatment. Weight gain stopped during DEX therapy, but not during HC. Head circumference in both treatment groups was decreased after therapy compared with controls. Neonatally DEX -treated children needed special school education significantly more often (p < 0.01) than controls at 5–7 y of age. No differences between neonatally HC-treated children and controls on neurodevelopmental outcome were found at 5–7 y of age. Conclusion: Neonatal HC therapy has fewer short- and long-term adverse effects than neonatal DEX therapy. Key words: Adverse effects, dexamethasone, follow-up, hydrocortisone, neonate F van Bel, Wilhelmina Children’s Hospital, Room KE 04.123.1, Department of Neonatology, PO Box 85090, NL-3508 AB Utrecht, The Netherlands (Tel. 31 302504545, fax. 31 302505320, e-mail. F.vanBel@WKZ.AZU.NL) Neonatal glucocorticoid therapy is frequently used to prevent chronic lung disease (CLD) in very preterm infants with respiratory distress syndrome (1, 2). Be- cause of its forceful anti-inflammatory properties, dexamethasone (DEX) is almost always used for this purpose. Despite its positive effect on neonatal lung function, neonatal DEX therapy exerts several acute adverse effects, such as the induction of hypertension and left ventricular hypertrophy (LVH), and hypergly- caemia. It also negatively affects somatic growth because of its catabolic properties (3–5). These effects resolve when DEX therapy is discontinued, although there is some concern that a DEX-induced interruption of growth during neonatal life may induce long-term negative effects on somatic development (6). There is also experimental evidence that neonatal DEX therapy induces anatomical and biochemical myocardial changes in the long term (7). Finally, experimental and clinical reports point to negative effects on brain growth and on neurodevelopment after exposure to DEX during neonatal life (8–12). Because glucocorticoids significantly decrease the incidence of CLD (1, 2), it is difficult to avoid its use during neonatal life in the preterm baby. However, the above-mentioned negative effects of DEX necessitate a search for alternatives. One of the possibilities fre- quently suggested in the recent literature on this topic is the use of a less potent glucocorticoid, such as hydrocortisone (HC) (13–15). HC has a shorter half- life and a lower biological activity than synthetic glucocorticoids such as DEX (16). Moreover, the effects of glucocorticoids are mediated via two cyto-  2003 Taylor & Francis. ISSN 0803-5253 Acta Pñdiatr 92: 827±835. 2003 DOI 10.1080/08035250310002425