ascorbic-acid and Bronchopulmonary-Dysplasia

Ascorbic acid (AA), a plasma antioxidant, is maintained at high levels in premature fetal blood and declines rapidly postpartum. The sudden reduction in blood AA levels secondary to premature delivery may increase the risk of oxidant injury, that is, bronchopulmonary dysplasia and intraventricular hemorrhage. There is concern that administration of AA to premature infants, in an effort to increase antioxidant capacity, may cause hemolysis. We felt that the benefits of early AA administration and prevention of the immediate postnatal drop in blood AA levels, might outweigh the risks of erthrocyte damage. Fifty one high-risk premature infants were randomized to receive either normal saline or 100 mg/kg of AA, daily for the first week of life. Double-blind comparisons were made of hemoglobin, hematocrit, erythrocyte morphology, bilirubin, number of blood transfusions and days of phototherapy, renal function tests, the incidence of infection, bronchopulmonary dysplasia, and intraventricular hemorrhage during the first month of life. The administration of AA prevented the immediate postnatal drop in AA and was not associated with evidence of increased hemolysis. No significant differences in renal function, rate of infection, bronchopulmonary dysplasia, or intraventricular hemorrhage were seen between the two groups. This study suggests that AA administration to the premature infant is safe and supports the designing and performance of larger clinical studies of the antioxidant properties of AA.

Topics: Antioxidants; Ascorbic Acid; Bilirubin; Blood Transfusion; Bronchopulmonary Dysplasia; Cerebral Hemorrhage; Cohort Studies; Double-Blind Method; Erythrocytes; Hematocrit; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infections; Kidney; Phototherapy; Reference Values; Safety

Ascorbylperoxide (AscOOH) is a hydrogen peroxide-dependent by-product of ascorbic acid that contaminates parenteral nutrition. In a guinea pig model, it caused oxidized redox potential, increased apoptosis, and decreased alveolarization. AscOOH detoxification is carried out by glutathione peroxidase (GPX). We hypothesize that extremely preterm infants have limited capacity for AscOOH detoxification. Our objective was to determine if there is an association between an early level of urinary AscOOH and later development of bronchopulmonary dysplasia (BPD) or death.. This prospective cohort study included 51 infants at <29 weeks of gestation. Baseline clinical characteristics and clinical outcomes data were collected. Urine samples were collected on days 3, 5, and 7 of life for urinary AscOOH. Blood samples on day 7 were collected for total plasma glutathione, GPX, and glutathione reductase. χ. Urinary AscOOH increased over time ( P = .001) and was higher in infants who later developed BPD or died ( P = .037). Compared with adults and full-term infants, total plasma glutathione concentration was low (median, 1.02 µmol/L; 25th-75th percentiles, 0.49-1.76 µmol/L), whereas GPX and glutathione reductase activities were sufficient (3.98 ± 1.25 and 0.36 ± 0.01 nmol/min/mg of protein, respectively).. Extremely preterm infants have low glutathione levels, which limit their capacity to detoxify AscOOH. Higher first-week urinary AscOOH levels are associated with an increased incidence of BPD or death.

Topics: Ascorbic Acid; Bronchopulmonary Dysplasia; Female; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Humans; Incidence; Infant; Infant Mortality; Infant, Extremely Premature; Infant, Newborn; Male; Parenteral Nutrition; Peroxides; Prospective Studies

Bronchopulmonary dysplasia (BPD) is a frequent complication of premature newborns, particularly very low birth-weight babies (<1500 g). Undoubtedly multiple mechanisms contribute to the adverse outcomes associated with BPD but oxidative stress is one causative factor. In this issue of Free Radical Biology and Medicine, Lavoie et al. describe the increased peroxide generation when the multivitamin solution used for nutritional support, total parenteral nutrition (TPN), is exposed to ambient light. Because the premature newborn has limited antioxidant capacity, this increased oxidative burden from the TPN becomes increasingly significant. Infusion of this light-exposed solution in a newborn guinea pig decreased lung tissue vitamin C but not vitamin E. When the multivitamin and lipid solutions were mixed and then exposed to light, alveolarization of the developing lung was decreased. This study by Lavoie et al. highlights simple measures that can potentially decrease the oxidant burden delivered to this vulnerable population and improve alveolarization.

Topics: Animals; Antioxidants; Ascorbic Acid; Bronchopulmonary Dysplasia; Guinea Pigs; Humans; Infant, Newborn; Infant, Premature; Light; Oxidants; Parenteral Nutrition, Total; Pulmonary Alveoli; Vitamin E

To determine the relation between lipid peroxidation and the antioxidants ascorbate, urate, and glutathione in epithelial lining fluid in ventilated premature babies, and to relate the biochemical findings to clinical outcome.. A cohort study conducted between January 1999 and June 2001.. A NHS neonatal intensive care unit.. An opportunity sample of 43 ventilated babies of less than 32 weeks gestation.. The duration of supplementary oxygen according to the definition of bronchopulmonary dysplasia (BPD; oxygen dependency at 36 weeks gestational age).. Epithelial lining fluid was sampled by bronchoalveolar lavage. Ascorbate, urate, glutathione, and malondialdehyde (a marker of lipid peroxidation) were measured.. Babies who developed BPD had significantly lower initial glutathione concentrations (mean (SEM) 1.89 (0.62) v 10.76 (2.79) microM; p = 0.043) and higher malondialdehyde concentrations (mean (SEM) 1.3 (0.31) v 0.345 (0.09) microM; p < 0.05) in the epithelial lining fluid than those who were not oxygen dependent. These variables were poor predictors of the development of BPD. Gestational age, endotracheal infection, and septicaemia had good predictive power. The level of oxidative damage was associated with the presence of endotracheal infection/septicaemia rather than inspired oxygen concentration.. Endotracheal infection, septicaemia, and gestational age, rather than antioxidant concentrations, are the most powerful predictors of the development of BPD.

Topics: Aging; Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Cohort Studies; Glutathione; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infections; Lipid Peroxidation; Logistic Models; Lung; Malondialdehyde; Oxidative Stress; Oxygen; Prognosis; Respiration, Artificial; Uric Acid

Chronic lung disease of prematurity (CLD) remains a common cause of morbidity and mortality in preterm infants. Oxygen toxicity remains a major risk factor for the development of CLD and as a consequence the antioxidant status of CLD babies is a major focus of interest. In the present study, we determined whether ascorbate, urate, and total glutathione concentrations were decreased in infants who developed CLD when compared to those who did not. From 34 preterm infants, 141 serial bronchoalveolar lavage fluid (BALF) and plasma samples were collected: 12 developed CLD (median gestation 26 weeks, range 23-28 weeks, median birth weight 780 g, range 630-1070 g), 16 developed and recovered from respiratory distress syndrome (RDS) (median gestation 31 weeks, range 26-39 weeks, median birth weight 1820 g, range 840-4160 g), and six were ventilated for non-respiratory reasons, (median gestation 35 weeks, range 32-38 weeks, median birth weight 2180 g, range 1100-2860 g). Following birth, the concentration of BALF ascorbate, urate and glutathione decreased over the 1st week in all three groups. Thereafter, BALF ascorbate increased in RDS and control infants during the 2nd week but this increase was delayed by 2 weeks in the CLD infants. No differences were noted between the RDS and CLD groups for urate and total glutathione in BALF or urate in plasma. BALF protein concentration was similar in all three groups except for a rise at day 7 in the CLD group but this did not reach statistical significance. Conclusion. A delayed increase in bronchoalveolar lavage fluid ascorbate concentration might be associated with an increased risk of developing chronic lung disease of prematurity.

Topics: Analysis of Variance; Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Case-Control Studies; Female; Glutathione; Humans; Infant, Newborn; Infant, Premature; Male; Uric Acid

Many complications of prematurity have been suggested to result from free radical generation and an inadequacy of antioxidative capacity. We measured the plasma total peroxyl radical-trapping capability (TRAP) and concentrations of the main chain-breaking antioxidants contributing to it, i.e. uric acid, ascorbic acid, alpha-tocopherol, protein sulfhydryl groups and bilirubin, in 21 preterm infants with a mean birth weight of 1440 g and gestational age of 30 wk. The infants were divided into two groups according to their short-term outcome; the good outcome group (GOG) (N = 11) with no signs of morbidity and the poor outcome group (POG) (N = 10) with intraventricular haemorrhage and/or bronchopulmonary dysplasia and/or retinopathy. Arterial blood samples were obtained 3 and 10 days postpartum. TRAP was measured with a chemiluminescent method. As a comparison, venous blood samples from 13 adults (aged from 18 to 34) were used. At day 3 the poor outcome group had significantly higher TRAP than the good outcome or control group, mainly because of elevated uric acid concentration. Also the concentration of unidentified antioxidants was significantly lower in GOG. By day 10 the TRAP decreased substantially in both groups. However, from the components of TRAP, both ascorbate and the unidentified fraction decreased more in POG (p = 0.017 and 0.021, respectively). Furthermore in POG on day 10 urate concentration did not significantly differ from day 3 values. In conclusion, in preterm infants high TRAP was associated with high plasma uric acid concentration and a poor short-term prognosis.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Bilirubin; Bronchopulmonary Dysplasia; Case-Control Studies; Female; Free Radical Scavengers; Humans; Infant, Newborn; Infant, Premature; Intracranial Hemorrhages; Male; Prognosis; Retinopathy of Prematurity; Uric Acid; Vitamin E

To evaluate the relative importance of biochemical markers of antioxidant status, gestational age, and parameters of neonatal care in the clinical outcome of premature infants.. A prospective, observational, longitudinal study of the association between these factors was conducted. Blood was collected from an in situ arterial line within two hours of birth and at intervals thereafter, when blood was drawn for routine clinical purposes. Outcome was assessed as death, or survival with or without bronchopulmonary dysplasia (BPD). One hundred and forty four babies of 22 to 39 weeks of gestation, who required intensive care at the Jessop Hospital for Women, between January 1993 and April 1994, were recruited.. Low gestational age at birth was the most important predictor of mortality and the development of BPD. Having corrected for gestational age, low plasma antioxidant activity at birth was an independent risk factor for mortality. Plasma vitamin C at birth was significantly higher in the babies who died compared with those with a good outcome, but this effect was not sustained after correcting for gestational age. Repeated measures of Analysis of Variance revealed a postnatal increase in antioxidant activity, caeruloplasmin, retinol, cholesterol corrected alpha tocopherol, and red blood cell superoxide dismutase (SOD) activity. Vitamin C, on the other hand, declined in all groups after birth. Logistic regression analysis revealed that the greater the number of packed cell transfusions received during intensive care, and the higher the concentration of vitamin C on the second day of life, the greater the risk of developing BPD.. After correcting for the effect of gestational age, low plasma antioxidant activity at birth was an independent risk factor for mortality. Frequent blood cell transfusions over the first week of life are associated with an increased risk of developing BPD. This association may be causal.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Blood Transfusion; Bronchopulmonary Dysplasia; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Intensive Care, Neonatal; Male; Prospective Studies; Regression Analysis; Risk Factors; Survival Rate