Influence of shielding TPN from photooxidation on the number of early blood transfusions in ELBW premature neonates.

OBJECTIVES: The smallest premature neonates often receive blood transfusions early in life. Nonrestrictive transfusion policies are linked to deleterious outcomes. Exposure of total parenteral nutrition (TPN) to ambient light generates oxidation products associated with haemolysis in vitro. Shielding TPN from light limits oxidation. Our hypothesis was protecting TPN from light decreases haemolysis and therefore the need for early blood transfusions. METHODS: Comparison of haemolysis between animals fed enterally and those receiving TPN, and exploratory case-control retrospective analysis of transfusion counts in premature infants receiving light-exposed or light-protected TPN. The statistical analysis was analysis of variance and longitudinal binomial regression model adjusting for potential covariables of transfusion counts. RESULTS: In animals, TPN is associated with higher (P<0.05) haemolysis compared with enteral feeds; photoprotection induces lower peroxide load with no effect on the level of haemolysis. In premature infants, light-exposed (n=76) or light-protected (n=57) populations exhibited similar clinical characteristics. Initial haematocrit, gestational age, and index of disease severity had a significant effect on the number of transfusions. When adjusting for these covariables, photoprotection was no longer significant. CONCLUSIONS: Even though peroxides are associated in vitro with haemolysis, shielding TPN from light to reduce infused peroxides does not significantly decrease the need for early transfusions in premature infants.

Neonatal exposure to oxidants induces later in life a metabolic response associated to a phenotype of energy deficiency in an animal model of total parenteral nutrition.

Failure to protect total parenteral nutrition (TPN) from ambient light exacerbates the generation of peroxides, which affects blood glucose and plasma triacylglyceride (TG) in neonates. Based on the concept that the origin of adult diseases can be traced back to perinatal life, it was hypothesized that neonatal exposure to peroxides may affect energy availability later in life. Three-day-old guinea pigs, fitted with a jugular catheter, were fed regular chow (sham) +/- i.v. 350 microM H2O2 (sham + H2O2) or nourished with light-protected TPN [TPN(-)L, 209 +/- 9 microM peroxides] or light-exposed TPN [TPN(+)L, 365 +/- 15 microM peroxides]. After 4 d, infusions were stopped and animals fed chow. Spontaneous ambulatory movements, fasting blood glucose, glucose tolerance, TG, hepatic activities of glucokinase, phosphofructokinase (key enzymes of glycolysis), and acetyl-CoA carboxylase (key enzymes of lipogenesis) were determined at 12-14 wk and compared by ANOVA (p < 0.05). Relative to sham, the animals from sham + H2O2, TPN(-)L and TPN(+)L groups had lower plasma TG explained for 36% by low phosphofructokinase activity; they had lower glucose tolerance, lower body weight, and lower physical activity. In conclusion, neonatal exposure to oxidant molecules such as peroxides has important consequences later in life on lipid and glucose metabolism leading to a phenotype of energy deficiency.

Inflammatory response in preterm infants is induced early in life by oxygen and modulated by total parenteral nutrition.

The i.v. lipid emulsion (LIP) is a source of oxidants, which may stimulate inflammation. Coadministration of parenteral multivitamins (MVP) with LIP prevents lipid peroxidation in light-exposed total parenteral nutrition (TPN). We hypothesized that this modality of TPN administration affects systemic inflammation, which may be modulated by exposure to oxygen. Premature infants were allocated to three TPN regimens: control regimen - MVP coadministered with amino acid/dextrose exposed to ambient light, LIP provided separately (n = 9) - LIP+MVP light exposed (LE): MVP coadministered with light-exposed LIP (n = 9) - LIP+MVP light protected (LP): MVP coadministered with light-protected LIP (n = 8). In LE and LP, amino acid/dextrose was provided separately. On reaching full TPN, infants were sampled for IL-6 and IL-8 in plasma and the redox potential of glutathione in whole blood (E, mV). Data were compared (ANOVA) in infants exposed to low (<0.25) versus high (> or =0.25) FiO2. Patients (mean +/- SD: birth weight 797 +/- 172 g; GA 26 +/- 1 wk) had similar clinical characteristics in TPN groups. Cytokine levels correlated positively (p < 0.01) with FiO2 and E. High FiO2 stimulated an increase (p < 0.01) in cytokines in control regimen, whereas these markers remained unaffected by oxygen in the LE and LP groups. The choice of a TPN admixture may have important consequences on the systemic inflammatory response triggered by an oxidant stress.

Vitamin A is systemically bioavailable after intratracheal administration with surfactant in an animal model of newborn respiratory distress.

Chronic lung disease (CLD) is a major cause of long-term morbidity in extremely LBW infants with respiratory distress syndrome. Parenteral vitamin A administration decreases the risk of CLD. We tested the hypothesis that intratracheal vitamin A administration with surfactant is systemically bioavailable without interfering with the functional properties of exogenous surfactant. Newborn piglets were ventilated with 100% FiO2 and sequential saline lavage induced respiratory distress syndrome. During lung injury induction, ventilator changes were allowed, but none were made following treatment allocation. Animals were assigned by chance in a blinded control trial to three groups: I=control; II=surfactant; III=surfactant+vitamin A. Hemodynamics, lung mechanics, and blood gases were measured following instrumentation, pre- and posttreatment for 4 h, at which time the liver was sampled for retinol determination. All parameters improved in animals receiving surfactant. A significant interaction existed between time and group for PaO2 and alveolar-arterial oxygen difference (A-aDO2). Hepatic levels of retinol were higher (p<0.001) in animals receiving retinyl acetate. Intratracheal administration of surfactant+vitamin A did not alter the beneficial effects of surfactant on lung compliance and gas exchange. Intratracheal Vitamin A was associated with rapid hepatic uptake. Further studies are warranted.

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

OBJECTIVE: To determine whether photo-protecting total parenteral nutrition in preterm infants influences arterial blood pressure differently according to gender. Blood pressure is influenced by complex mechanisms of vasomodulation. Oxidants are mediators and effectors in such reactions. Shielding total parenteral nutrition from light contributes to decrease the generation of peroxides. Girls may be better protected against an oxidant load than boys. We questioned whether shielding total parenteral nutrition may have cardiovascular effects that are influenced by gender. DESIGN: A post hoc subgroup analysis of the effect of shielding parenteral nutrition from light. SETTING: Neonatal intensive care unit. SUBJECTS: Preterm infants <1000 g with indwelling arterial catheters who received light exposed (n = 20) or light protected (n = 20) parenteral nutrition. INTERVENTIONS: Invasive monitoring, total parenteral nutrition. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure was recorded hourly and compared between light exposed and light protected over the first week of life; timed average maximum velocity (m/s) was measured in the superior mesenteric artery by Doppler; presence of ductus arteriosus was documented by cardiac ultrasound. Data were analyzed by analysis of variance. No differences were noted between light exposed and light protected in clinical determinants that may influence blood pressure. There was an interaction (p < .01) between gender and total parenteral nutrition on blood pressure. In girls (n = 17), systolic and diastolic blood pressures were higher (p < .01) and heart rate lower (p < .01) during light exposed. There was no effect on BP observed in boys (n = 23). The linear correlation between timed average maximum velocity and systolic blood pressure was positive (p < .05). There was no echocardographic difference in hemodynamic variables between boys (n = 21) and girls (n = 9) who had a patent ductus. CONCLUSION: Failure to shield total parenteral nutrition from light results in higher blood pressure in a selected population of critically ill female infants. This information adds to our understanding of the multiple determinants involved in optimizing arterial blood pressure in a critical care environment.

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

There is strong evidence that oxidant molecules from various sources contaminate solutions of parenteral nutrition following interactions between the mixture of nutrients and some of the environmental conditions encountered in clinical practice. The continuous infusion of these organic and nonorganic peroxides provided us with a unique opportunity to study in cells, in vascular and animal models, the mechanisms involved in the deleterious reactions of oxidation in premature infants. Potential clinical impacts of peroxides infused with TPN include: a redox imbalance, vasoactive responses, thrombosis of intravenous catheters, TPN-related hepatobiliary complications, bronchopulmonary dysplasia and mortality. This is a narrative review of published data.

Influence of lung oxidant and antioxidant status on alveolarization: role of light-exposed total parenteral nutrition.

Parenteral multivitamins (MVP) are linked to the generation of peroxides, which cause oxidant injury in lungs associated with alveolar remodelling linked to lung disease of prematurity. This study was to investigate the relationship between alveolar development and lung oxidant-antioxidant status as modulated by the mode of administration of multivitamins with total parenteral nutrition (TPN). Four groups of guinea pig pups received parenteral nutrition differing by 1) mode of MVP admixture: with amino acid solution (AA-MVP) or lipid emulsion (LIP-MVP); 2) light exposure: TPN exposed (LE) or shielded from light (LP). After 2 or 4 days of TPN, vitamins C and E, 8-isoprostaneF2alpha and alveolarization index were determined in lungs and GSSG/GSH in lungs and blood. Exposure to light and the mode of MVP admixture did not influence vitamin E and isoprostane levels. Blood glutathione redox potential was more oxidized in LE and LIP-MVP groups after 4-day infusions, whereas lung redox potential was more reduced in LE groups. LP and LIP-MVP had a beneficial effect, with higher number of alveoli. Globally, results indicate that in this model, alveolarization and modifications in lung redox potential are two independent events induced by light exposed TPN.

In preterm neonates, is the risk of developing bronchopulmonary dysplasia influenced by the failure to protect total parenteral nutrition from exposure to ambient light?

Light-exposed total parenteral nutrition (TPN) generates peroxides that contribute to an oxidant load. Shielding TPN from light protects against lung remodelling. In preterm infants, photoprotection of TPN is associated with a 30% reduction in bronchopulmonary dysplasia in a post-hoc analysis. This analysis provides justification for a randomized controlled trial.

Shielding parenteral multivitamins from light increases vitamin A and E concentration in lung of newborn guinea pigs.

BACKGROUND & AIMS: Exposure of parenteral multivitamin preparation (MVP) to light generates peroxides. Light-exposed MVP induces an oxidant stress in lung but not in liver. This discrepancy suggests differences in handling of infused antioxidant vitamins between the two organs. HYPOTHESIS: antioxidant capacity of lung depends on the MVP concentration and light protection of infused solutions. METHODS: Protocol 1: four groups of three-day old guinea pigs received the base solution (5% dextrose + 0.45% NaCl) enriched with 0%, 1%, 2% and 3% MVP. Protocol 2: three further groups received the base solution + 2% MVP either light-exposed or light-protected or light-protected + 300 microM H2O2. After 4 days, lung and liver were sampled for vitamin determinations. Data were analyzed by ANOVA. RESULTS: In lung, vitamins A-C-E reached a plateau with 1% MVP. In liver, vitamin A and E increased according to their concentration in solutions. Light exposure and added-H2O2 were associated with lower vitamin E in lung and liver. Retinol was higher in lung and lower in liver of animals receiving light-protected compared to light-exposed solutions. CONCLUSIONS: Light protection of 1% MVP is a better way to improve the pulmonary oxidant-antioxidant balance than to increase MVP (>1%) in parenteral nutrition.

Variations in metabolic response to TPN are influenced more by sex than by light exposure.

BACKGROUND: Failure to protect total parenteral nutrition (TPN) solutions from ambient light induces the generation of peroxides, which contributes to the oxidation of several amino acids. We hypothesized that photo-protection improves the metabolic response to TPN. AIM: To study the effects of photo-protecting TPN on urinary nitrogen and vitamin C excretion and to evaluate in premature infants the influence of sex. PATIENTS AND METHODS: Premature infants were randomized to receive from birth light-exposed (LE) or light-protected (LP) TPN. Upon reaching full TPN, parenteral nutrient intakes were correlated with normalized urinary nitrogen and vitamin C concentrations. RESULTS: No differences were observed between LE and LP. However, sex-related differences were observed in nitrogen and vitamin C handling. In boys, 50% of the nitrogen loss was explained by parenteral amino acid intake, whereas in girls, no correlation was found. The inverse correlation observed between intake and urinary excretion only in girls suggests a state of greater vitamin C utilization in girls. CONCLUSIONS: These results demonstrate that sex-related differences in nitrogen/protein metabolism reported during enteral nutrition are seen during TPN as well. Sex is an important variable that will need to be taken into account in future studies evaluating the potential clinical effects of photo-protecting TPN.

Shielding Parenteral Nutrition From Light Improves Survival Rate in Premature Infants.

BACKGROUND: Intravenous nutrition preparations that are not photoprotected generate oxidants, which are deleterious for cell survival. The question remains: are these observations of clinical relevance in individuals receiving parenteral nutrition (PN), especially in those who exhibit immature antioxidant defenses such as premature infants? OBJECTIVE: To review clinical trials reporting the effect of light-exposed vs light-protected PN to determine whether photoprotection reduces neonatal mortality in preterm infants. DATA SOURCE: Electronic databases, abstracts in relevant journals, and references in manuscripts between 1980 and 2014. SELECTION CRITERIA: Newborn, premature infants, PN, photoprotection, shielding from light, randomization, mortality, death. METHODS: Consensus for inclusion reached by 2 reviewers; meta-analysis of trials and observational studies reporting mortality at 36 weeks' gestational age or hospital discharge. RESULTS: Four trials meeting selection criteria, which involved a total of 800 newborn premature infants, were included. Across trials, gestational age (mean ± SD) ranged from 26 ± 1 to 31 ± 2 weeks, birth weight from 775 ± 161 to 1588 ± 366 g, and mortality from 5%-32%. Mortality in the light-protected group was half of that in the light-exposed group (95% confidence interval, 0.32-0.87) and twice as high in males compared with females (χ2, P = .01). CONCLUSION: Shielding PN from light has vital repercussions that call for action to provide photoprotected delivery systems and infusion sets in premature infants. Further studies should be extended to the increasing number of children and adults receiving long-term home PN to evaluate the effects of light protection on severe complications that impede their quality of life.

Photoprotection of parenteral nutrition enhances advancement of minimal enteral nutrition in preterm infants.

BACKGROUND: Light exposure of TPN generates peroxides which induce vasoconstriction. Mesenteric vasoconstriction may affect feeding tolerance. Since photo-protection of TPN decreases peroxide generation, we hypothesized that shielding TPN from light may improve the establishment of minimal enteral nutrition in preterm infants. METHODS: Infants were randomized to TPN being light exposed (LE) or protected (LP) from birth. Feeding volumes were monitored through 7 days of life in those initiated on minimal enteral nutrition (MEN). Comparisons between LP and LE were performed by ANOVA. RESULTS: Daily increments and cumulative volumes of enteral feeds (mL/kg birth weight/d) during the first week of life were significantly higher in LP (n = 18) than LE (n = 19). CONCLUSION: Photo-protection of parenteral nutrition enhances advancement of MEN in preterm infants. Further research is needed to substantiate these findings and determine whether this confers long-term nutritional advantages.

The mode of delivery of parenteral multivitamins influences nutrient handling in an animal model of total parenteral nutrition.

BACKGROUND: Very low birthweight preterm infants receive early total parenteral nutrition (TPN) to optimize protein balance. Adding multivitamins (MVP) to the lipid emulsion (MVP+LIP) rather than to the amino acid+dextrose moiety of TPN (AA+MVP) limits the effects of light exposure on lipid peroxidation and vitamin loss. AIM: Compare the effects of the mode of delivery of MVP on nutrient handling and indices of oxidant stress. METHODS: Three-day old guinea pig pups were assigned to TPN containing MVP+amino acids+dextrose+heparin and electrolytes, with lipids provided separately (AA+MVP). Solutions were light exposed (LE, n = 8) or light protected (LP, n = 9). In a further group (n = 7), MVP was co-administered with the lipid moiety and light exposed (LIP+MVP). Variables measured in urine (creatinine, nitrogen, vitamin C) and in liver (protein, glutathione, isoprostane, vitamins A, E, C) were compared by ANOVA. RESULTS: Urinary nitrogen and vitamin C were higher (P<0.05) during LE, while hepatic levels of vitamin C were higher (P<0.05) with LIP+MVP. These results were not related to total peroxide levels in TPN or to markers of oxidant stress. CONCLUSION. Co-administration of MVP with lipid or light protected amino acids offers comparable beneficial effects on nitrogen and vitamin C metabolism.

Effect of coadministration of parenteral multivitamins with lipid emulsion on lung remodeling in an animal model of total parenteral nutrition.

Exposure of parenteral multivitamin solutions (MVP) to ambient light generates peroxides and vitamin loss, and induces initiation of fibrosis and a reduced alveolar count in an animal model of total parenteral nutrition (TPN). Adding MVP to the lipid moiety of TPN prevents lipid peroxidation and vitamin loss. The aim of the study was to compare modes of delivery of MVP on lung procollagen mRNA and alveolar counts. Three-day-old guinea pig pups were infused continuously with one of three intravenous solutions: 1) control = dextrose; 2) AA + MVP = MVP given with the dextrose + amino-acid moiety, in a "piggyback" setup with a lipid emulsion mixed close to the infusion site; and 3) LIP + MVP = same as AA + MVP, except that MVP is given with the lipid emulsion. After 4 days, lungs were prepared for alveolar count (intercept technique) and for quantification of the procollagen/beta-actin mRNA ratio (initial step of fibrosis). Data were compared by ANOVA. The procollagen mRNA was lower (P < 0.05) in animals receiving LIP + MVP than those with AA + MVP. But the two modes of admixture of MVP had the same effect on the alveolar counts, which were lower (P < 0.01) than controls. The mode of delivery of TPN affects lung remodeling. Although LIP + MVP protects against the initiation of lung fibrosis, the absence of a beneficial effect on alveolar counts suggests that these features of lung remodeling are not caused by a unique component of TPN. Specific roles of peroxides, components of MVP, and light exposure on lung remodeling need to be explored before LIP + MVP can be recommended as an alternative mode of parenteral vitamin delivery.

Elevated umbilical cord ghrelin concentrations in small for gestational age neonates.

Ghrelin has orexigenic effects. It is present in umbilical cord plasma in full-term neonates, raising the prospect that ghrelin plays a role in fetal and neonatal energy balance. We measured ghrelin in small (SGA), appropriate (AGA), and large (LGA) for gestational age neonates and evaluated whether ghrelin levels are modulated by neonatal insulin and glucose concentrations. Plasma concentrations of ghrelin, insulin, and glucose were measured in cord blood sampled at birth in 123 SGA, AGA, and LGA neonates (gestational age, 24-41 wk) born to mothers with and without diabetes. Ghrelin was detected in samples from all infants. Its concentration was 40% higher in SGA neonates (mean +/- SD, 2436 +/- 657 pg/ml) compared with AGA (1738 +/- 380) and LGA (1723 +/- 269) neonates. There was a positive correlation between ghrelin and gestational age in AGA/LGA (r = 0.23; P < 0.05) and a negative correlation in SGA (r = -0.67; P < 0.005) neonates. Therefore, the difference in ghrelin between SGA and AGA/LGA neonates decreases with advancing gestational age. Birth weight z-score, maternal hypertension, and glucose concentrations were significant determinants of ghrelin concentrations. In conclusion, SGA neonates present with higher umbilical cord ghrelin plasma concentrations than AGA/LGA neonates. Ghrelin may play a physiological role in fetal adaptation to intrauterine malnutrition.

Photoprotection prevents TPN-induced lung procollagen mRNA in newborn guinea pigs.

BACKGROUND: Photo-exposed intravenous multivitamin solutions (MVP) carry a peroxide load. Peroxidation induces gene expression of procollagen. We hypothesized that photo exposure of the MVP solution might promote pulmonary fibrosis. The aim of the study was to assess the potential for MVP to increase procollagen mRNA. METHODS: Three day old guinea pigs were assigned to the following intravenous regimens, either: Control (C): 5% dextrose + 0.45% NaCl; C + 200 or 500 microM H(2)O(2); C + 500 microM H(2)O(2) + 10 microM GSSG; [C + 1% MVP +/- [amino acids + lipids]] +/- photoprotected. After 4 d, levels of pulmonary alpha1(I) procollagen mRNA and glutathione were determined. Results were compared by ANOVA. RESULTS: Photoprotection of MVP or TPN prevents light induction of procollagen mRNA. The effect of MVP + light was associated with a peroxide load coupled with a low glutathione level. This was also observed with the 500 microM H(2)O(2) group. The addition of GSSG prevented the increase of procollagen mRNA caused by H(2)O(2). CONCLUSION: An oxidant stress caused by the infusion of peroxides in an organism with a weak antiperoxide capacity induces the transcription of the gene encoding for procollagen alpha1(I). The results confirm the antiperoxide activity of lung glutathione. Parenteral nutrition could be a clinical condition favoring the initiation of lung fibrosis, especially in premature newborn infants who have low glutathione levels.

Postnatal gender-dependent maturation of cellular cysteine uptake.

BACKGROUND: In view of the functional capacity of glutathione synthesis in premature infants, and because the availability of cysteine is one the rate limiting steps in glutathione synthesis, we hypothesized that the low glutathione levels in premature infants may be due to immaturity of the active cellular uptake of cysteine. OBJECTIVE: To document in cells from newborn infants the effect of maturity and gender on cysteine uptake and consequently on glutathione levels. METHODS: Incorporation of L-[35S] cysteine was measured in leukocytes from cord blood and from tracheal aspirates (TAC) of newborn infants of varying (gestational as well as postnatal) ages and gender. Cysteine uptake was correlated with glutathione in TAC. RESULTS: The maturity of newborn girls positively influences cysteine uptake, which is responsible for 78% of the variation in their glutathione content. However, in newborn boys, gestational and postnatal ages did not influence the cysteine uptake. DISCUSSION: Cysteine uptake appears to be the limiting step explaining the reported gender-related differences in glutathione as well as the low levels of this central antioxidant found in premature infants. The immature cysteine uptake found in cells from premature infants raises questions about the bioavailability of this conditionally essential amino acid in regimens of parenteral nutrition for human neonates.

Multivitamin solutions for enteral supplementation: a source of peroxides.

OBJECTIVE: We investigated whether solutions of enteral vitamin supplementation are involved in the generation of peroxides and whether that contamination is biologically significant. METHODS: Peroxide contents of oral multivitamin preparations were measured over 3 wk after the initial opening of the containers. In selected premature infants (younger than 35 wk gestation), urinary peroxides were measured after initiating oral multivitamin supplementation. RESULTS: Peroxides in multivitamin solutions for enteral use are predominantly organic peroxides because they resist catalase. After the initial opening of the containers, there was a two-fold increase in total peroxides levels (P < 0.05) even in the preparation without riboflavin, a catalyst for the generation of peroxides. Initiation of oral vitamin supplementation was associated with increased (P < 0.05) urine peroxide levels. The high organic peroxide load did not correlate with its urinary excretion, mostly in the form of H(2)O(2). The excretion of H(2)O(2) corresponded to its oral intake from the multivitamin solution. CONCLUSIONS: Compared with parenteral multivitamin solutions, the enteral preparations contained higher organic peroxide levels starting with the initial opening of the bottles. The increased urinary excretion of H(2)O(2) after enteral multivitamin supplementation suggested a systemic diffusion of peroxides or of components of the multivitamin preparation responsible for the generation of peroxides. This oxidant load was not quenched by the immature antioxidant defenses of premature infants.

Determinants of oxidant stress in extremely low birth weight premature infants.

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 O(2). 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 O(2) 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.

Shielding parenteral nutrition from light: does the available evidence support a randomized, controlled trial?

BACKGROUND: Exposure of total parenteral nutrition to ambient light induces the generation of peroxides, creating oxidant stress, which potentially compounds complications of prematurity. Photograph protection of total parenteral nutrition reduces the peroxide load and has been shown to be associated with nutritional and biochemical benefits in animals and humans. It is unclear whether this reduction in peroxides from total parenteral nutrition leads to a reduction in the complications of prematurity, such as bronchopulmonary dysplasia. Our hypothesis was that shielding total parenteral nutrition from ambient light is linked to clinical benefits. OBJECTIVE: The purpose of this work was to determine whether photograph protection of total parenteral nutrition (light protected), as compared with no photoprotection (light exposed), reduces the occurrence of bronchopulmonary dysplasia or death in preterm infants. METHODS: The Canadian Neonatal Network provided data for infants born in 2006 at <28 weeks' gestation admitted to level 3 NICUs in Canada. A retrospective analysis was performed comparing bronchopulmonary dysplasia and death in infants who received light-exposed or light-protected parenteral nutrition. Data were analyzed by using logistic regression models. RESULTS. Thirteen NICUs offered partial light-protected (total parenteral nutrition bag only, intravenous tubing exposed) and 13 offered light-exposed parenteral nutrition; not a single NICU offered complete light-protected parenteral nutrition (total parenteral nutrition bag plus intravenous tubing). The incidence of bronchopulmonary dysplasia or death was 66% with light-protected (n = 428) vs 59% with light-exposed (n = 438) parenteral nutrition. CONCLUSIONS: Partial photograph protection of total parenteral nutrition was not associated with a reduction in bronchopulmonary dysplasia or death as compared with no photograph protection; this relationship is confounded by covariates with strong associations with bronchopulmonary dysplasia. Partial photograph protection of total parenteral nutrition solutions confers no clinical benefit, while consuming valuable resources. A randomized, controlled trial is justified to determine whether there is a true "cause-and-effect" relationship between complete photoprotection of total parenteral nutrition and bronchopulmonary dysplasia or death.