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Because L-carnitine (L-CAR) is a potential substitute for neonatal dexamethasone (DEX) with respect to the prevention of long-term side effects, rats were treated on d 1, 2, and 3 after birth with saline, DEX, L-CAR, half the dose of DEX, and L-CAR + half DEX. DEX led to growth retardation, increased mortality, and severe kidney damage at 50 wk of age. L-CAR had no negative effects on growth, kidney function at 50 wk, and survival at 101 wk. Growth retardation was induced transiently by half DEX and permanently by L-CAR + half DEX, slightly reduced kidney function but no reduced life span was found in both these groups. Except for the DEX group, blood glucose levels were normal at 50 wk in all groups. A serendipitous finding was that L-CAR treatment caused one-third less food intake; however, these rats maintained normal body weight. In conclusion, L-CAR, a lower dose of DEX, and their combination caused less negative effects in later life. Because L-CAR + half DEX had a negative effect on growth, attention to monitor L-CAR levels during DEX treatment of preterm newborns seems to be justified. The finding that neonatal L-CAR caused reduced food intake in later life warrants further investigation.

Early exposure to glucocorticoids (GC) has been proposed to disturb hepatic and cardiac function in later life. In the present study, we evaluated early metabolic alterations upon GC treatment that may predispose to long-term abnormalities. Rats were injected with dexamethasone (DEX) at d 1, 2, and 3 after birth and controls received saline (SAL). Rats were killed at 2, 7, and 14 d of age. Compared with SAL, DEX induced lower plasma insulin levels, hyperglycemia, hyperketonemia, and dyslipidemia at 2 d. At the same time, DEX treatment significantly increased expression of gluconeogenic and fatty acid oxidation genes in liver and expression of genes involved fatty acid utilization in heart. At 7 d, DEX-treated rats showed insulin resistance with hyperlipidemia, whereas hepatic and cardiac gene expression patterns were largely normalized. Hyperlipidemia and a significantly increased hepatic triglyceride content in DEX-treated rats were prominent at 14 d without large differences in hepatic and cardiac gene expression patterns. Thus, neonatal DEX administration transiently affects cardiac and hepatic gene expression patterns in suckling rats associated with sustained effects on plasma glucose and lipid concentrations. Whether these early effects of DEX contribute to hepatic and cardiac abnormalities at adult age needs further evaluation.