In Preterm Infants the Tpn Modality Can Be Used to Modulate the Inflammatory Response to Oxygen Observed Early in Life

Abstract

Background: Due to its high unsaturated omega-6 fatty acid content the lipid moiety of TPN is thought to induce inflammation. Co-administration of parenteral multivitamins (MVP) with lipid emulsions (LIP) prevents lipid peroxidation in light exposed TPN, which may reduce oxygen-induced inflammation. However, this modality is associated with a 5-fold increase in hydroxynonenal, an oxidation product also known to stimulate inflammation. Hypothesis: Mixing intravenous multivitamins with lipids modulates the inflammatory effect of oxidants. Objective: To compare the systemic cytokine response to different modalities of TPN administration. Methods: Preterm infants were randomized to receive, from birth, TPN administered using 3 different modalities providing the same nutrient intake: AA = MVP+amino acid/dextrose solution exposed to ambient light + lipids provided separately (controls) (n=8); LE = MVP administered with LIP exposed to light with amino acid/dextrose provided separately (n=10); LP = MVP administered with LIP protected from light + amino acid/dextrose provided separately (n=8). Upon reaching full TPN infants were sampled (day 7 to 10 of life) for markers: of inflammation (IL-6 and IL-8, pg/mL) in plasma; of oxidant stress (redox potential of glutathione E, mV) in whole blood; and of protein oxidation (D-Tyrosine DiT, ?g/g creat) in urine. Data (mean+SEM) from the 3 regimens were compared by logistic regression and ANOVA, in infants exposed to low (<0.25) vs high (>=0.25) FiO2. Results: Patients (birth weight 754+32 g; gest. age 26.0+0.1 wk; low FiO2 0.22+0.01 and high FiO2 0.32+0.02) in all 3 groups had similar clinical characteristics. DiT did not correlate with cytokines or FiO2. Cytokine levels correlated positively (p<0.001) with FiO2 (IL-6: r= 0.53; IL-8; r= 0.56) and E (IL-6: r= 0.75; IL-8: r= 0.75). A similar interaction was found between FiO2 and TPN modality for IL-6, E and DiT in the AA group, while these markers remained unaffected by oxygen in the LE and LP groups. Conclusion: Delivering light-exposed lipids separate from aminoacids and multivitamins may enhance the detrimental pro-inflammatory effect of oxygen. In view of the potential effects of both, oxidation and inflammation on clinical outcomes, the modality of TPN delivery could be used to prevent potentially harmful inflammatory effects of oxygen.