Effect of Two Different Lipid Emulsions on Oxygen Radical Disease and Oxidant Status in VLBW Infants

Presenter: S. Unal (e-mail: [e-mail])

Introduction: Oxidative stress is the unbalance between oxidant generating and antioxidant systems which can lead to tissue damage by free radical formation. Antioxidant enzymes and compounds were generated against free radicals; however, preterms are vulnerable to damages by free radicals as they have limited antioxidant defense systems. It was being thought to be the part of pathogenesis of important morbidities in preterms; so-called oxygen radical disease in neonatology; chronic lung disease (CLD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA). So far, no antioxidant strategies were concluded to decrease radical related neonatal diseases regarded to oxidative stress. This emphasizes the necessity to perform approaches which will change the balance in favor of antioxidants in NICU. Lipid emulsions are the important part of total parenteral nutrition (TPN) which is the major medication for every very low-birth-weight (VLBW) infant. Recently, lipid emulsions containing omega-3 fatty acids were presented to reduce lipid peroxidation compared with olive-oil based emulsions and ROP incidence compared with soy-oil based emulsions. In this study we aimed to compare the occurrence of oxygen radical diseases and the balance of oxidative stress in VLBW infants who received either SMOFlipid (soy oil, middle chain fatty acid, olive oil, fish oil) or ClinOleic (olive oil, soy oil).

Materials and Methods: This prospective-observational study was performed between January 1, 2015 and December 31, 2015 in Etlik Zubeyde Hanim Women’s Health Training Hospital, a level III NICU in Turkey. Inborn VLBW infants whose gestational age were 25 to 32 weeks were included. Infants with major congenital anomalies, hemolytic disease of newborn, and intrauterine hypoxia were excluded. Infants received SMOFlipid (20%; Fresenius Kabi, Pymble, Australia) from January to May and ClinOleic (20%; Baxter, S.A. Belgium) from June to December. TPN was initiated in the first 24 hours of life (amino acid solution 2 g/kg; Primene; Baxter, S.A. Belgium), either of lipid solutions 1 g/kg and glucose and advanced to amino acid–lipid dose of 4.3 g/kg in the third day. Trace elements and water–lipid soluble vitamins were added after 7th day of TPN. Enteral feeding was started as 20 mL/kg within the first 48 hours if infants’ own mothers’ milk was available and on 72th hour if preterm formula was the initial nutrition. Enteral feedings were advanced 20 to 30 mL/kg/day while TPN volume was decreased proportionally, maintaining a 40% of nonprotein calories from lipid emulsion. TPN was discontinued when 80% of total daily feeding volumes were obtained from enteral feeding, thereafter breastmilk was fortified. Oxidative stress was evaluated in three (basal: 7th–21st days) blood samples by total antioxidant capacity (TAC-mmol Trolox equiv/L) and total oxidant status (TOS-mmol H2O2/L) of Erel’s method, then oxidative stress index (OSI (TOS/TACx100)) was calculated. Infants were not included as available for this evaluation if either basal serum was unavailable (missing/inadequate) or the infant was fed with formula, had sepsis, or was on inotrope treatment. Demographic data, clinical characteristics, and total intake of lipid and milk were recorded. Primary outcomes were the TAC, TOS and OSI levels, development of CLD, ROP (≥ stage 2) and secondary outcomes were late onset sepsis (LOS), LOS mortality, NEC (≥ grade 2), cholestasis in infants who received either SMOFlipid or ClinOleic. Statistical analyses were performed with SPSS 15.0. Analyses between groups were performed using chi-square test and Mann–Whitney U-test where appropriate. A p-value of less than 0.05 was considered statistically significant. Friedman test was conducted to test whether there was a significant change in TAC, TOS, and OSI for each group. Wilcoxon test using Bonferroni correction was performed to adjust for multiple comparisons (a p-value of less than 0.017).

Results: During the study period, 261 eligible infants were admitted to NICU and 227 infants (SMOFlipid; 93 and ClinOleic;134) were included in the study. Gestational age (weeks: SMOFlipid; 29 ± 2.0, ClinOleic; 29 ± 2.2), birth weight (grams: SMOFlipid; 1,166 ± 243 g, ClinOleic; 1,154 ± 253 g), and other demographic data were similar in both groups. Incidences of morbidities were found to be similar among SMOFlipid and ClinOleic groups as follows respectively; CLD (4.7 vs. 6.7%; 0.546), ROP (9.4 vs. 11.7%; 0.607), NEC (3.4 vs. 0.8; 0.311), PDA (18.5 vs. 18.7%; 0.973), LOS (14.4% vs 21.4%; 0.193), mortality due to sepsis (30.8 vs. 32.1%; 1.000), cholestasis (1.2 vs. 1.6%, 1.000). Mortality did not differ between groups (7.5 vs. 11.2%; 0.358).The TAC and TOS were studied in 88 (SMOFlipid:39, ClinOleic:49) infants. Basal levels of TAC and TOS, and OSI were similar two groups. When compared with baseline, the TAC and TOS levels on 7th day decreased significantly in ClinOleic group whereas the change was not significantly different in SMOFlipid group. The TAC, TOS, and OSI levels on 21st day were found to be decreased when compared with baseline in both groups, and similar between groups (Fig. 1).

Conclusion: In our study, we demonstrated that occurrence of oxygen radical disease and oxidative status did not differ in VLBW infants who received either SMOFlipid or ClinOleic. Related to these parameters, both lipid emulsions can be used conveniently in VLBW infants.

Keywords: total parenteral nutrition, lipid, oxidative stress, preterm