•  Neonatal nutrition
•  Oxidants and antioxidants
•  Total parenteral nutrition

Newborn and particularly premature infants are subjected to very reactive compounds called oxidants; this, combined with an immature antioxidant activity, accounts for a significant source of complications of prematurity. These infants often require intravenous administration of nutrients, as they are too immature to tolerate oral feeds. This is a life saving therapy. We have demonstrated that exposure of the intravenous feeding (TPN) regimen to daylight is responsible for oxidation of the nutrients. These oxidants are known to have deleterious effects on specific cells or tissues, accounting for several associated complications of prematurity. We are researching ways to protect newborn infants against the effects of oxidants by enhancing their antioxidant defenses through nutritional support and by decreasing the oxidant load. We are testing the effects of protecting nutrients from oxidants on biological outcome variables as well as on markers of clinical outcome such as length of hospitalization and decreased incidence of complications.

We are examining in animals and in babies if the mode of delivery of intravenous vitamins influences oxidant load and antioxidant defenses in premature infants. To achieve this goal we are investigating if antioxidant vitamins offer greater bioavailability and protection when given with the lipid rather than with the dextrose+amino acid component of intravenous nutrition. We are testing the relevance of specific markers of red ox status and oxidized proteins by correlating their quantification with calibrated oxidant stress induced by infused peroxides and/or hyperoxic environment. Because glutathione plays a central role as antioxidant, we plan to test if the addition of glutathione precursors to the intravenous feeding regimen decreases the harmful effects of oxidation in sick infants.

We also hope to elucidate in animals the mechanisms by which oxidant molecules formed in intravenous solutions interact with vitamin C to generate new compounds that interfere with the way the body handles sugar and fat. Also, we are assessing in newborn infants on TPN ways to administer the multivitamin preparation that will reduce metabolic perturbations induced by these new compounds that potentially alter rates of glycolysis and lipid clearance.

Given that the current mode of delivery of vitamin A administered to protect premature infants against chronic lung disease is very invasive, we are testing a new intra-tracheal modality of vitamin a supplementation mixed with exogenous surfactant. In an investigator-driven project undertaken in conjunction with an industrial partner we are investigating the effects of this preparation on the physical properties of surfactant, on the bioavailability of vitamin A, on lung mechanics and gas exchanges. Results of this study will be used to conduct preclinical work in primates and clinical trials testing the effects of this new non-invasive modality on reducing the incidence of chronic lung disease of prematurity, which consumes significant health care resources.

Lavoie JC, Chessex P, Rouleau T, Tsopmo A, Friel J. (2007) Shielding parenteral multivitamins from light increases vitamin A and E concentration in lung of newborn guinea pigs. Clinical Nutrition 26:341-7.

Khashu M, Harrison A, Lalari V, Gow A, Lavoie JC, Chessex P. (2006) Photoprotection of parenteral nutrition enhances advancement of minimal enteral nutrition in preterm infants. Seminars in Perinatology 30:139-45.

Chessex P, Friel J, Harrison A, Rouleau T, Lavoie JC. (2005) The mode of delivery of parenteral multivitamins influences nutrient handling in an animal model of total parenteral nutrition. Clinical Nutrition 24:281-7.
 
Lavoie JC, Rouleau T, Chessex P. (2004) Interaction between ascorbate and light-exposed riboflavin induces lung remodeling. Journal of Pharmacology Experimental Therapeutics 311:1-6.

Lavoie JC, Chessex P, Rouleau T, Migneault D, Comte B. (2004) Light-induced byproducts of vitamin C in multivitamin solutions. Clinical Chemistry 50: 135-40.

Chessex, P, Lavoie, JC, Rouleau, T, Brochu, P, St-Louis, P, Levy, E, Alvarez, F. (2002): Photooxidation of parenteral multivitamins induces hepatic steatosis in a neonatal guinea pig model of intravenous nutrition. Pediatric Research 52:958:963.

Lavoie, JC, Rouleau, T, Truttmann, AC, Chessex, P. (2002): Postnatal gender-dependent maturation of cellular cysteine uptake. Free Radicals Research 36:811-817.

Lavoie, JC, Rouleau, T, Gagnon, C, Chessex, P (2002): Photoprotection prevents TPN-induced lung procollagen mRNA in newborn guinea pigs. Free Radical Biology & Medicine 33:512-520.

Chessex, P, Lavoie, JC, Laborie, S, Rouleau, T. (2001): Parenteral multivitamin supplementation induces both oxidant and antioxidant responses in the liver of newborn guinea pigs. Journal of Pediatric Gastroenterology 32:316:321.

Laborie, S, Lavoie, JC, Chessex, P (2001): Increased urinary peroxides in newborn infants receiving parenteral nutrition exposed to light. The Journal of Pediatrics 136:628.

Jas Aulakh - Technician
Vikki Lalari - Clinical research assistant