Sick neonates, e.g. those with congenital heart disease, usually require TPN during the course of their illness and until their ability to tolerate enteral feeds is well established. Sick newborns are at risk of both disturbed glucose metabolism and inadequate energy intake. In an effort to prevent hypoglycemia and to provide a sufficient energy intake, some of these neonates are routinely receiving glucose infusion at rates twice their normal glucose turn over rate (6-8mg/kg/min.), a regimen frequently leading to hyperglycemia. The purpose of this project is to determine the effects of various glucose infusion rates on glucose, lipid, and protein metabolism in newborn infants with congenital heart disease.  Knowledge about the physiology of glucose metabolism in these sick neonates is important and will help us design nutritional strategies that render these infants normoglycemic while providing them with a sufficient energy intake

1) Hyperglycemia is more likely to occur during routine TPN (usually providing glucose at rates corresponding about twice the normal glucose turnover rate) than during a TPN providing glucose at 6 mg/kg/min (normal glucose turnover rate).

2) Newborn infants with congenital heart disease are able to maintain normoglycemia during a 6mg/kg/min glucose infusion rate (while maintaining the infusion rates of parenteral lipids and amino acids unchanged).

3) Glucose production, particularly gluconeogenesis, is not completely suppressed in infants with congenital heart disease while receiving a routine TPN providing glucose at twice normal turnover rate.

4) Whole-body protein synthesis is reduced in sick infants receiving TPN providing glucose at 6mg/kg/min.

The infants will be studied on one occasion during their first 7 days of life.At start of the study (time zero), infusions of compounds labeled with stable, non-radioactive, naturally occurring isotopes, [U-13C]glucose, [2-13C]glycerol, [1-13C]leucine and [15N2]urea will be started and continued at constant rates for 15 h. During the first 5 study hours, TPN will be administered at the pre-study rate as ordered by the physician on service (2 mg/kg min of the glucose will be replaced by [U-13C]glucose, which is metabolically equivalent to natural glucose). After 5 h, the glucose infusion rate will be reduced to 6 mg/kg min (i.e. corresponding to the average normal glucose turnover rate of infants) and then to 3 mg/kg min for 5 h (2 mg/kg min of this glucose will be replaced by [U-13C]glucose throughout the study). Blood samples will be obtained at start of the study (just prior to start of the infusion of the stable isotope solutions), and then at study hours 4.5; 5; 10.5 and 11 h. Thus, a total of 5 blood samples of 0.5-1 mL each during the entire study period. The total blood volume withdrawn will not exceed 3 ml/kg body weight i.e., within the guidelines established by the IRB. In addition, blood glucose will be checked hourly at the bedside using a glucometer requiring only drops of blood. If  in the unlikely event of blood glucose concentrations of 40 mg/dL or less would occur, the glucose infusion rate will be increased to maintain blood glucose above this level.Thus, using the compounds labeled with stable isotopes we will determine the effect of the glucose infusion rate on glucose production, gluconeogenesis, protein breakdown, protein oxidation, protein synthesis and lipolysis. We will also measure insulin and inflammatory cytokines and chemokines and determine whether these factors are involved in the regulation of glucose metabolism.

12

Infants born after 34 weeks or more of gestation and who have been antenataly or neonataly diagnosed with congenital heart disease (diagnosis assessed and confirmed by echocardiography) and with a postnatal age of 7 days or less. Further, the infants must have an UVC or peripheral vein catheter, and an UAC or a peripheral artery catheter in place for clinical care purposes. Infants with parenchymal lung disease (IRDS, meconium aspiration syndrome, pneumothorax) proven bacterial sepsis or requiring ECMO or Nitric oxide treatment will be excluded

One baby has been studied. Analyses are ongoing.