Dexamethasone (DEX) therapy for bronchopulmonary dysplasia (BPD) is associated with poor weight gain. Neonates with BPD have increased metabolic demands and usually receive I.V. lipids (IL) as part of their hyperalimentation. Triglycerides (TG) in IL are hydrolyzed to free fatty acids(FFA) and glycerol by lipoprotein lipase. Normally FFA are oxidized for energy production and excess stored as TG. Hypertriglyceridemia (HTG) defined as a serum level > 250 mg/dl suggests impaired metabolism for energy production. DEX, by a direct pancreatotrophic effect and indirectly through hyperglycemia, leads to a hyperinsulinemic state. During hyperinsulinemia, DEX induces de novo fatty acid synthesis in the liver and FFA are channeled into TG synthesis. DEX also increases FFA levels. Elevated FFA levels may compete with bilirubin for albumin binding and may increase the risk of kernicterus. Based on animal experiments, we hypothesized that DEX induces HTG in the presence of hyperinsulinemia and also increases FFA levels. We prospectively studied neonates < 29 weeks needing DEX for BPD and receiving 3gm/kg/day IL. Neonates with active infection, prior HTG, recent surgery, on thyroid medication or on insulin were excluded. DEX therapy started with 0.5mg/kg/d divided 12 hourly for 3 days and then weaned. Blood was drawn for TG, FFA and Insulin assays before DEX (baseline) and at 24, 48, 72 and 120 hrs after start of DEX. IL infusion rate was kept constant unless HTG. If TG were 250-400mg/dl, IL was decreased to 1gm/kg/d. If TG continued to increase even on 1 gm/kg/d, IL was decreased to 0.5 gm/kg/d. If at any time TG>400 mg/dl, IL was discontinued. 10 neonates were studied to date. The sign test was used to test the null hypothesis that the median change was equal to zero. 6/10 subjects (60%) reached a state of HTG. An “exact” 95% confidence interval for the true percentage for HTG based on the binomial distribution is given by (26.2%, 87.8%). The median changes from baseline to the peak day for TG, Insulin and FFA were all statistically significant and were respectively 119.5 mg/dl (p=0.002), 35.6 μunits/ml (p=0.0039) and 192.5 μmol/liter(p=0.0156). We conclude that DEX induces HTG in the presence of hyperinsulinemia and also increases FFA levels. Neonates on DEX should be closely monitored for HTG and elevated FFA levels especially if there is a risk of kernicterus.

Supported by NIH RR0044-35A1 (GCRC).