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As part of an ongoing study on the influence of intravenous glucose and fat on nitrogen metabolism we evaluated the relationship between the source of infused energy and plasma amino acid levels. Thirty-two studies were performed in 16... more
As part of an ongoing study on the influence of intravenous glucose and fat on nitrogen metabolism we evaluated the relationship between the source of infused energy and plasma amino acid levels. Thirty-two studies were performed in 16 appropriate-for-gestational-age newborn infants (birth weight, 2150 +/- 115 g; means +/- SEM). In a crossover design each patient received two 6-d periods of isocaloric and isonitrogenous infusions, differing only by the source of calories (high or low fat intakes). For an energy intake of 80 kcal.kg-1.d-1 (335 kJ.kg-1.d-1) there was a significant hypoaminoacidemia (2338 +/- 185 vs 2937 +/- 196 mumol/L, high fat vs low fat) under the high-glucose intake. These data suggest that above an energy intake of 60 kcal.kg-1.d-1 (251 kJ.kg-1.d-1) there is a threshold at which changes in plasma amino acid levels are triggered by variations in the source of infused energy. Careful examination of all variables, including energy sources, is essential when aminograms are compared.
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Research Interests: Obstetrics, Pediatrics, Medicine, Birth Weight, Humans, and 15 moreFemale, Male, Risk factors, Clinical Sciences, Retrospective Studies, Risk Factors, Gestational Age, Asphyxia neonatorum, Apgar Score, Severity of Illness Index, cholestasis, Fetal Distress, Asphyxia, Neonatal Cholestasis, and Respiration Artificial
Research Interests: Medicine, Energy Metabolism, Erythropoietin, Humans, Hemodynamics, and 15 moreHeart rate, Heart, Infant, Anemia, Hemoglobin, Energy Expenditure, Myocardium, Blood Transfusion, Bronchopulmonary Dysplasia, Continuous Wave, Cardiac output, Indirect calorimetry, Erythrocyte transfusion, Doppler echocardiography, and Infant Premature
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Objective: The co-administration of parenteral multivitamins (MVP) with lipid emulsion (LIP) is recommend to prevent lipid peroxidation and enhance antioxidant vitamin bioavailability. The biological effects of this modality have not been... more
Objective: The co-administration of parenteral multivitamins (MVP) with lipid emulsion (LIP) is recommend to prevent lipid peroxidation and enhance antioxidant vitamin bioavailability. The biological effects of this modality have not been studied in neonates. The aim was to test the hypothesis that this total parenteral nutrition (TPN) modality offers a better protection against oxidant stress. Methods: Three groups of preterm infants were randomly assigned to receive: C = amino acids (AA) + MVP exposed to light: MVP + AA, lipids provided separately (n = 10); LE = LIP + MVP exposed to light: MVP administered with lipids, amino acids provided separately (n = 10); LP = LIP + MVP protected from light (n = 10). Blood was sampled on day 7 to measure the redox ratio of glutathione GSSG/(GSSG + GSH) and plasma levels (μM/l) of vitamins A and E. Data (mean ± SEM) were compared by analysis of variance for babies on low (⩽0.25) versus high (>0.25) FiO2. Results: Clinical characteristics and nutrient intakes were similar between groups. In infants receiving C, the redox ratio was more oxidised (p Conclusions: LE protects against the oxidant stress associated with O2 supplementation. This is not explained by the availability of antioxidant vitamins A and E. These data support a trial to evaluate in premature infants the impact of TPN modality on long-term outcomes.
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Parenteral administration of iron is a matter of controversy because it is feared that it could contribute to oxidative reactions. The aim of this study was to verify if irondextran participates in the redox reactions occurring in total... more
Parenteral administration of iron is a matter of controversy because it is feared that it could contribute to oxidative reactions. The aim of this study was to verify if irondextran participates in the redox reactions occurring in total parenteral nutrition (TPN) solutions. Irondextran was compared with different forms of iron in the interaction with peroxides. Hydroperoxide levels were measured by a colorimetric technique in TPN solutions, in presence of varying sources (FeCl2, FeSO4, irondextran, iron sorbitol) and concentrations (0-0.8 mM) of iron. The consumption and inhibition of peroxide generation were tested by analyzing the effect of iron on different sources of peroxides (H2O2, tert-butyl and cumen hydroperoxide). The free radicals produced under conditions of a Fenton-like reaction were measured by the oxidation of scopoletin. And the proportion of Fe3+ freed by both bound-iron sources was counted by measuring the masking effect on the thiol function of cysteine. Free-iron admixture to parenteral nutrition induces the formation of free radicals, whereas sources of bound-iron inhibit the generation of peroxides in parenteral nutrition without implying a Fenton-like reaction. For patients requiring iron supplementation, bound-iron should be added during the preparation of TPN solutions, because it protects against the spontaneous generation of peroxides.
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The nitrogen retention and plasma amino acid concentration were determined in eight preterm infants (mean birth weight 970 +/- 130 g; mean gestational age 28 +/- 1 weeks) receiving successively total parenteral nutrition and their own... more
The nitrogen retention and plasma amino acid concentration were determined in eight preterm infants (mean birth weight 970 +/- 130 g; mean gestational age 28 +/- 1 weeks) receiving successively total parenteral nutrition and their own mother's milk. The nitrogen retention during both regimens was comparable to the fetal accretion rate. Plasma amino acid concentrations were lower during the enteral phase of the study than during parenteral nutrition. The metabolic response of small preterm infants is related to the quality of amino acids as well as to the route of intake.
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There is a general willingness to eliminate sulfites from the diet because of adverse reactions. Because little is known about the biological effects of these antioxidants in vivo, we compared clinical and nutritional parameters in... more
There is a general willingness to eliminate sulfites from the diet because of adverse reactions. Because little is known about the biological effects of these antioxidants in vivo, we compared clinical and nutritional parameters in newborn infants receiving two parenteral amino acid solutions containing either 300 mg/dl or no metabisulfite. The primary objective was to verify whether decreasing the sulfur content of parenteral nutrition would diminish the calciuria of newborn infants. In a crossover design, 18 newborn infants received two regimens differing only in their metabisulfite content. Nitrogen and mineral balances; clinical parameters such as mean heart and respiratory rates, body temperature, and transcutaneous PO2 and PCO2 (n = 7); and energy expenditure were similar in both regimens. Withdrawing bisulfites from the diet did not change calciuria, put an extra burden on the infant's metabolic adaptation, or cause short-term clinical repercussions.
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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... more
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.
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To separate the respective influence of the level and source of infused energy on nitrogen metabolism, 32 studies were performed in 16 appropriate-for-gestational-age newborn infants (birth weight 2150 +/- 115 g, means +/- SEM). In a... more
To separate the respective influence of the level and source of infused energy on nitrogen metabolism, 32 studies were performed in 16 appropriate-for-gestational-age newborn infants (birth weight 2150 +/- 115 g, means +/- SEM). In a cross-over design, each patient received two 6-d periods of isocaloric and isonitrogenous (450 mg.kg-1.d-1) infusions, differing only by the source of calories (high or low fat intakes). Half of the patients were studied at 60 kcal.kg-1.d-1, the other half at 80 kcal.kg-1.d-1. Nitrogen balance, urinary 3-methylhistidine excretion, glycemia, and insulin were compared. The results suggest that for an intravenous energy intake ranging from 60 to 80 kcal.kg-1.d-1, glucose and fat provide an equivalent nitrogen sparing effect in the newborn infant. At an energy level covering maintenance requirements, it is the infant's clinical condition rather than the source of energy which affects most the magnitude of amino acids participation in energy metabolism.
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Background. Peroxides have been reported to contaminate lipid emulsions and amino acid solutions used in total parenteral nutrition (TPN). This is particularly disturbing in newborn infants who are prone to several diseases related to... more
Background. Peroxides have been reported to contaminate lipid emulsions and amino acid solutions used in total parenteral nutrition (TPN). This is particularly disturbing in newborn infants who are prone to several diseases related to immature defense mechanisms against oxidative challenges. It is not clear whether the antioxidants in multivitamins help protect parenteral nutrients against the hazards of oxidation. Objective. To evaluate the role of a multivitamin preparation (MVI) on the actual peroxide load received by patients on TPN. Methodology. The generation of peroxides in parenteral nutrition was tested first using test solutions. We compared the relative contribution of commercially available amino acid solutions, a lipid emulsion, and MVI on the level of peroxides in clinically relevant TPN solutions. Second, we measured the level of peroxides actually infused at the bedside. In both circumstances, the effects of time and light exposure were isolated. The level of peroxid...
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Research Interests: Free Radicals, Gene expression, Humans, Animals, Glutathione, and 15 moreLight, Fibrosis, Lung, Hydrogen Peroxide, Guinea Pig, Amino Acid Profile, Bronchopulmonary Dysplasia, Amino Acid Sequence, Base Sequence, Drug Stability, Biochemistry and cell biology, Gene Expression Regulation, drug storage, Guinea pigs, and Collagen type I
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... more
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? To review clinical trials reporting the effect of light-exposed vs light-protected PN to determine whether photoprotection reduces neonatal mortality in preterm infants. Electronic databases, abstracts in relevant journals, and references in manuscripts between 1980 and 2014. Newborn, premature infants, PN, photoprotection, shielding from light, randomization, mortality, death. Consensus for inclusion reached by 2 reviewers; meta-analysis of trials and observational studies reporting mortality at 36 weeks' gestational age or hospital discharge. Four trials meeting selection criteria, which involved a total of 800 newborn premature infants, were included....
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Research Interests: Radiation Protection, Humans, Female, Animals, Male, and 15 moreRegression Analysis, Light, Infant, Newborn Infant, Analysis of Variance, Retrospective Studies, Blood Transfusion, Gestational Age, Hematocrit, Enteral Nutrition, Case Control Studies, Hemolysis, Peroxides, Medical and Health Sciences, and Guinea pigs
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Research Interests: Radiation Protection, Oxidative Stress, Birth Weight, Prospective studies, Humans, and 12 moreBlood Glucose, Female, Male, Light, Lipid metabolism, Triglycerides, Newborn Infant, Parenteral Nutrition, Prospective Study, Enteral Nutrition, total parenteral nutrition, and Paediatrics and reproductive medicine
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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... more
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
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
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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... more
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.
Research Interests: Free Radicals, Vitamins, Oxidative Stress, Free Radical, Pregnancy, and 21 moreHumans, Female, Blood sampling, Glutathione, Newborn Infant, Oxidative stress and free radical biology and medicine, Amino Acids, Adult, Snap, Hyperbaric Oxygenation, Biological markers, Amino Acid Profile, Blood Transfusion, Bronchopulmonary Dysplasia, Parenteral Nutrition, Premature Birth, MVP, Biochemistry and cell biology, Tpn, Redox State, and Redox Potential
M-mode echocardiographic features suggesting a patent ductus arteriosus are based on two groups of indirect criteria: dilation of the left cardiac cavities and changes of systolic time intervals. The reliability of the first group of... more
M-mode echocardiographic features suggesting a patent ductus arteriosus are based on two groups of indirect criteria: dilation of the left cardiac cavities and changes of systolic time intervals. The reliability of the first group of criteria has been questioned in fluid-limited, mechanically ventilated preterm infants. The sensitivity of the systolic time intervals in the same circumstances is investigated. Twenty-three patients with a large patent ductus arteriosus were selected. Review of their echocardiograms shows that the sensitivity of the various criteria (expressed as percentage of positivity) was as follows: inversion of the ratio of left ventricular preejection period to right ventricular preejection period, 91.3%; left ventricular preejection period to left ventricular ejection time over right ventricular preejection period to right ventricular ejection time less than 1,83%; left atrium dilation, 74%; shortening of left ventricular preejection period, 70%; dilation of left ventricular internal dimensions in diastole, 65%; increase in left atrium/aorta, 52%; and decrease of left ventricular preejection period to left ventricular ejection time, 48%. Three criteria involving time intervals (left ventricular preejection period to right ventricular preejection period, left ventricular preejection period, and left ventricular preejection period to left ventricular ejection time) had 100% specificity. The lowest specificity was found with criteria involving the left atrium (left atrial to aortic root ratio 75% and left atrium 63%). It is concluded that study of systolic time intervals is a reliable means of detecting preterm infants with hemodynamically significant left-to-right shunt through a patent ductus arteriosus even if the infants are mechanically ventilated and fluid restricted.
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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... more
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. A post hoc subgroup analysis of the effect of shielding parenteral nutrition from light. Neonatal intensive care unit. Preterm infants <1000 g with indwelling arterial catheters who received light exposed (n = 20) or light protected (n = 20) parenteral nutrition. Invasive monitoring, total parenteral nutrition. 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. 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.
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Research Interests: Nutrition and Dietetics, Nutrition, Photochemistry, Concentration, Antioxidants, and 16 moreVitamin A, Clinical Nutrition, Liver, Animals, Light, Vitamin E, Lung, Lipid peroxidation, Ascorbic Acid, Analysis of Variance, Guinea Pig, Augmentation, Drug Stability, Parenteral Nutrition, Oxidation-Reduction, and MVP
A comparison has been made of the influence of feeding own mother's milk and formula on the oxidation and accretion of energy and macronutrients in the growing preterm infant of very low birth weight (less than 1,300 g) by using... more
A comparison has been made of the influence of feeding own mother's milk and formula on the oxidation and accretion of energy and macronutrients in the growing preterm infant of very low birth weight (less than 1,300 g) by using the combined techniques of nutrient balance and computerized indirect calorimetry. There were 22 studies in formula-fed infants and 15 studies in premature infants fed own mother's milk. Despite their lower metabolizable energy intake, the infants fed own mother's milk grew in weight, length, and head circumference at a rate approximating those of the formula-fed group. The metabolic rate was significantly lower in the infants fed own mother's milk (56.0 +/- 0.9 v 62.6 +/- 0.8 kcal/kg/d; P less than .001). The protein intake, oxidation, and accretion were similar in the two groups. The infants fed own mother's milk had a significantly lower fat intake (P less than .001), higher fat oxidation (P less than .025) and consequently lower fat accretion (P less than .001) than the formula-fed infants. The proportional fat content of the daily weight gain was lower in the infants fed own mother's milk (16% v 33%; P less than .001) but protein content was similar (13% v 12%). The accretion of energy, fat, and protein correlated with the respective metabolizable intakes in both groups (r = .81 to .98; P less than .001), suggesting that accretion rates and hence composition of weight gain are dependent on levels of energy and macronutrient intake.