Glucocorticoid treatment in preterm babies to prevent chronic lung disease causes myocardial hypertrophy and increased myocardial protein content. Although these changes are thought to be transient, there is evidence that dexamethasone (DEX) induces permanent myocardial abnormalities as well. We investigated whether a therapeutic course of neonatal DEX in rat pups produces anatomic and biochemical alterations in rat hearts during adult life. Twenty-four rat pups were treated with DEX on d 1, 2, and 3 (0.5, 0.3, and 0.1 g/g) of life, with doses proportional to those used in preterm babies. Twenty-four control pups were treated with saline. At d 7, wk 8, or wk 45 (n ϭ 8 per group) rats were killed. The anatomic parameters measured were body weight (Bw, in grams), heart (myocardial) weight (Hw, in milligrams), and the Hw:Bw ratio. Myocardial total protein (Prot) and DNA content were determined, and the Prot:DNA ratio was calculated. Histopathology and morphometry were performed on 45-wk-old rat hearts. In DEX-treated rat pups, at d 7, Bw and Hw were lower and the Hw:Bw ratio was increased. DNA content was lower, Prot higher, and Prot:DNA ratio was increased. In 8-wk-old rats Bw, Hw, DNA content, Prot content or Prot:DNA ratio did not differ between groups, but the Prot:DNA ratio still tended to be higher in DEX-treated rats. In 45-wk-old rats Hw and Hw:Bw ratio were significantly lower and Prot:DNA ratio higher in DEX-treated rats. Histopathologic analysis showed larger cardiomyocyte volume, length, and width, indicating hypertrophy, and increased collagen, indicating early degeneration of individual myocytes. In conclusion, neonatal DEX treatment in rat pups causes a permanent decrease in heart weight, as well as hypertrophy and early degeneration of cardiomyocytes during adulthood. (Pediatr Res 52: 900-906, 2002) Abbreviations Bw, body weight DEX, dexamethasone GC, glucocorticoid Hw, heart weight Prot, total protein SAL, saline Chronic lung disease is a common outcome in extremely preterm neonates with severe respiratory distress syndrome and carries a high incidence of morbidity and mortality. Inflammation is an important factor in its pathogenesis. Because of their antiinflammatory properties GCs, particularly DEX, resulted in an impressive decrease in chronic lung disease (1, 2). Consequently GCs are frequently used and have become indispensable in all neonatal intensive care units in the Western world, especially inasmuch as an alternative therapy is not available at present. Despite the short-term benefits of GCs, major concern has emerged now because recent experimental studies report long-lasting adverse effects of perinatal GC treatment in later life, such as lifetime changes in cardiovascular function and reprogramming of the neuroendocrine system (3-5). Benediktsson et al. (6) reported that GC exposure during the perinatal period leads to hypertension during adult life, possibly related to a GC-induced reprogramming of the hypothalamic-pituitary-adrenal axis. Neonatal GCs also altered the epinephrine a...