Elsevier

Free Radical Biology and Medicine

Volume 49, Issue 9, 15 November 2010, Pages 1380-1386
Free Radical Biology and Medicine

Original Contribution
Determinants of oxidant stress in extremely low birth weight premature infants

https://doi.org/10.1016/j.freeradbiomed.2010.07.018Get rights and content

Abstract

Early in life, premature neonates are at risk of oxidant stress. They often require total parenteral nutrition (TPN), which is, however, contaminated with oxidation products. Coadministration of parenteral multivitamins (MVP) with a lipid emulsion (LIP) prevents lipid peroxidation. We hypothesized that LIP + MVP induces a lower oxidant load compared to preparations in which MVP is administered with an amino acid solution (AA + MVP). The aim of this study was to compare markers of oxidant stress in premature neonates receiving LIP + MVP, either exposed to or protected from light, or AA + MVP. Antioxidant vitamins, the redox potential of glutathione, isoprostane, and dityrosine were measured in urine or blood sampled on days 7 and 10 from babies requiring low (< 0.25) vs high (≥ 0.25) fractional inspired O2. Oxygen supplementation induced a more oxidized redox potential and increased dityrosine with AA + MVP only. Adding MVP in the lipid rather than the amino acid moiety of TPN protects against the oxidant stress associated with O2 supplementation. Photoprotection added no benefit. Blood transfusions were found to produce a pronounced oxidant load masking the beneficial effect of LIP + MVP. The impact of these findings relates to a strong association between a more oxidized redox potential and later bronchopulmonary dysplasia, a clinical marker of oxidant stress.

Section snippets

Materials and methods

A prospective study comparing the effects of the mode of TPN delivery on antioxidant status was conducted in premature infants in the neonatal intensive care unit at the Children's and Women's Health Centre of British Columbia from 2006 to 2009. Once the infant reached full TPN, urine and blood were sampled 72 h apart on postnatal day 7 (sample 1, S1) and postnatal day 10 (± 24 h; sample 2, S2). In blood, the redox potential of glutathione and the levels of antioxidant vitamins A and E were

Results

Of the 126 eligible subjects, consent was obtained for 56 and they were distributed by chance to one of the three TPN protocols. Three patients in the AA group and one in the LE group died before sampling because of complications of extreme prematurity. Of the 52 subjects completing the study, 16 received the AA modality, 17 the LE regimen, and 19 the LP modality. The clinical characteristics were similar between the three groups (Table 1); so were the nutrient intakes (intravenous + enteral;

Discussion

We have compared markers of protein oxidation, lipid peroxidation, and overall redox balance in a population at high risk of oxidant stress. We found that oxygen and the TPN modality, to a lesser degree, contributed to the redox status of very premature infants. The later occurs independent of the antioxidant vitamin status. Results in Table 3 confirm that premature infants are subjected to a greater oxidant stress than adult subjects [27], [34], [35], [36]. The biological significance of the

Acknowledgment

This work was supported by the Canadian Institutes of Health Research (MOP 79403).

References (48)

  • R.F. Maier et al.

    Changing practices of red blood cell transfusions in infants with birth weights less than 1000 g

    J. Pediatr.

    (2000)
  • M. Comporti et al.

    Plasma F2-isoprotanes are elevated in newborn infants and inversely correlated to gestational age

    Free Radic. Biol. Med.

    (2004)
  • M. Vento et al.

    Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen

    J. Pediatr.

    (2003)
  • B.B. Warner et al.

    Free radical mediated diseases in pediatrics

    Semin. Perinatol.

    (1992)
  • J.C. Lavoie et al.

    Development of glutathione synthesis and γ-glutamyl transpeptidase activities in tissues from newborn infants

    Free Radic. Biol. Med.

    (1998)
  • L. Knafo et al.

    Association between H2O2-dependent by-products of ascorbic acid and increased hepatic acetylcoenzyme A carboxylase activity

    Clin. Chem.

    (2005)
  • S. Laborie et al.

    Paradoxical role of ascorbic acid and riboflavin in solutions of parenteral nutrition: implication in photoinduced peroxide generation

    Pediatr. Res.

    (1998)
  • J.C. Lavoie et al.

    Interaction between ascorbate and hydrogen peroxides generated by light-exposed riboflavin induces lung remodeling

    J. Pharmacol. Exp. Ther.

    (2004)
  • P. Chessex et al.

    Photooxidation of parenteral multivitamins induce hepatic steatosis in a neonatal animal model of intravenous nutrition

    Pediatr. Res.

    (2002)
  • M.R. Bassiouny et al.

    A randomized controlled trial on parenteral nutrition, oxidative stress, and chronic lung disease in preterm infants

    J. Pediatr. Gastroenterol. Nutr.

    (2009)
  • P. Chessex et al.

    Early life events, sex, and arterial blood pressure in critically ill infants

    Pediatr. Crit. Care

    (2010)
  • K.M. Silvers et al.

    Limiting light-induced lipid peroxidation and vitamin loss in infant parenteral nutrition by adding multivitamin preparations to Intralipid

    Acta Paediatr.

    (2001)
  • J.C. Lavoie et al.

    Effect of co-administration of parenteral multivitamins with the lipid emulsion on lung remodeling in an animal model of TPN

    Pediatr. Pulmonol.

    (2005)
  • P. Lavoie et al.

    Inflammatory response in preterm infants is induced early in life by oxygen and modulated by TPN

    Pediatr. Res.

    (2010)
  • Cited by (53)

    • Parenteral nutrition and oxidant stress in the newborn: A narrative review

      2019, Free Radical Biology and Medicine
      Citation Excerpt :

      Mortality, an all-encompassing outcome is commonly used when comparing populations of premature infants. Four studies with a total of 800 infants [39,49,120,146] were included in this meta-analysis after using the following key words: premature newborns, PN, photo-protection, shielding from light, randomization, mortality or death. Mortality was half in the light-protected group (95% confidence interval, 0.32–0.87).

    • Non-invasive assessment of oxidative stress in preterm infants

      2019, Free Radical Biology and Medicine
      Citation Excerpt :

      Also, levels of these biomarkers were higher in preterm that received parenteral nutrition, as well as in preterm compared to term infants [61,62]. Other biomarkers related to lipid peroxidation that have been determined in urine samples are isoprostanes [63–68], TBARS [69] and MDA [70]. Regarding isoprostanes, their determination is useful for ductus arteriosus ibuprofen treatment monitoring since their levels usually decrease after the treatment [67], as well as in the study of the beneficial effects of human milk since these newborns show lower levels than those fed with preterm formula [63,68].

    • Melatonin treatment in fetal and neonatal diseases

      2018, Pathology Research and Practice
    • Novel angiotensin-converting enzyme inhibitory peptides from caseins and whey proteins of goat milk

      2017, Journal of Advanced Research
      Citation Excerpt :

      In addition, goat milk proteins are more digestible and medically is being recommended for newborn when human milk is lacking [6]. In newborns, milk feeding contributes to protect against oxidative stress and the associated diseases such as cardiovascular disorder [7,8]. Hypertension is recognized as a serious risk factor for cardiovascular disease [9].

    View all citing articles on Scopus
    View full text