ascorbic-acid and Infant--Premature--Diseases

This article explains the mechanisms underlying choices of pharmacotherapy for hypoxic-ischemic insults of both preterm and term babies. Some preclinical data are strong enough that clinical trials are now underway. Challenges remain in deciding the best combination therapies for each age and insult.

Topics: Acetylcysteine; Allopurinol; Antioxidants; Ascorbic Acid; Biopterins; Erythropoietin; Excitatory Amino Acid Antagonists; Free Radical Scavengers; Fructose; Humans; Hypoxia-Ischemia, Brain; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Melatonin; Memantine; Neuroprotective Agents; Nitric Oxide Synthase Type III; Resveratrol; Stilbenes; Topiramate; Vitamin E; Xenon

The human infant is born with low body stores of vitamin E. Thus, the infant requires an adequate intake of vitamin E soon after birth. If adequate sources of tocopherol are not provided, a clearly defined deficiency state characterized by hemolytic anemia and, after a period of years, spinocerebellar degeneration results. However, the benefit of pharmacologic doses of vitamin E given as prophylaxis against diseases believed to be related to oxygen toxicity (bronchopulmonary dysplasia, retinopathy of prematurity, and periventricular-intraventricular hemorrhage) is not clear. Possible benefits must be balanced against the potential for serious toxicity. Few data are available on the pharmacokinetics of tocopherols in infants, particularly with respect to esterified forms of tocopherol, and little is known about the toxicity associated with parenteral administration of the vitamin.

Topics: Ascorbic Acid; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature, Diseases

Topics: Animals; Ascorbic Acid; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Lactation; Male; Nutritional Requirements; Pregnancy; Sex Factors; Species Specificity; Vitamin E; Vitamin E Deficiency; Vitamins

Topics: Amino Acid Metabolism, Inborn Errors; Animals; Ascorbic Acid; Cystathionine; Diagnosis, Differential; Histidine; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Male; Metabolic Diseases; Methionine; Milk Proteins; Phenylalanine; Rats; Testicular Diseases; Time Factors; Tyrosine

Topics: Anemia, Hypochromic; Ascorbic Acid; Avitaminosis; Birth Weight; Female; Folic Acid; Humans; Infant, Newborn; Infant, Premature, Diseases; Iron; Pregnancy; Time Factors; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Amino Acid Metabolism, Inborn Errors; Animals; Ascorbic Acid; Guinea Pigs; Humans; Infant, Newborn; Infant, Premature, Diseases; Liver; Mixed Function Oxygenases; Phenylalanine; Rats; Tyrosine; Tyrosine Transaminase

Topics: Abetalipoproteinemia; Adult; Anemia; Anemia, Macrocytic; Animals; Ascorbic Acid; Bone Marrow; Deficiency Diseases; Dietary Fats; DNA Replication; Erythropoiesis; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Iron; Kwashiorkor; RNA; Salmonidae; Selenium; Swine; Vitamin B 12; Vitamin E; Vitamin E Deficiency

To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB).. A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity.. Of 9,867 women, 10.4% (. Adverse maternal and neonatal outcomes were significantly more likely with IPTB than with SPTB.

Topics: Adolescent; Adult; Ascorbic Acid; Birth Weight; Delivery, Obstetric; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Small for Gestational Age; Intensive Care Units, Neonatal; Logistic Models; Male; Multivariate Analysis; Parity; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth; Respiratory Distress Syndrome, Newborn; Retrospective Studies; United States; Vitamin E; Young Adult

To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin (EPO) in very low birth weight (VLBW) infants.. A prospective, controlled, randomized, unmasked trial lasting 21 days was performed in 29 clinically stable VLBW infants <31 weeks' gestation and <1300 g birth weight not treated with red blood cell transfusions during the study period. Mean (+/- standard error of the mean) age at study entry was 23 +/- 2.9 days. After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex (IPC), participants were randomized to receive 18 days of treatment with: 1) oral IPC alone (oral iron group); 2) 300 U of recombinant human EPO (r-HuEPO) kg/day and daily oral IPC (EPO + oral iron group); 3) 2 mg/kg/day of intravenous iron sucrose, r-HuEPO, and oral iron (intravenous iron + EPO group). To assess efficacy of the 3 treatments, serial blood samples were analyzed for hemoglobin (Hb), hematocrit (Hct), reticulocyte count, red blood cell indices and plasma levels of transferrin, transferrin receptor (TfR), ferritin, and iron. Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde (MDA) and o-tyrosine.. At the end of treatment, Hb, Hct, reticulocyte count, and plasma TfR were markedly higher in both of the EPO-treated groups, compared with the oral iron group. At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group, compared with the EPO + oral iron group. During treatment, plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups. By the end of treatment, ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups. Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups, plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sampled at the end of the 2-hour parenteral iron infusion, compared with values observed immediately before and after parenteral iron-dosing.. In stable VLBW infants receiving EPO treatment, parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small, but significant, augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone. However, to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury, we suggest that the parenteral iron dose used should be reduced and/or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity.

Topics: Administration, Oral; Ascorbic Acid; Blood Cell Count; Drug Therapy, Combination; Erythrocyte Indices; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Intravenous; Iron; Malondialdehyde; Prospective Studies; Tyrosine

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

We tested the hypothesis that vitamin C supplementation of premature neonates is associated with hemolysis.. A double-blind, randomized, controlled trial of vitamin C supplementation (50 mg/day) was undertaken in premature neonates (birth weight, 1000 to 1500 gm). Infants were randomly assigned to receive vitamin C (Ce-Vi-Sol) (n = 32) or placebo (n = 24) for 14 days. Twenty-three subjects per group were required to detect a difference of 1 SD in corrected carboxyhemoglobin values (alpha = 0.05, beta = 0.10).. Day 14 vitamin C levels were lower in control subjects than in supplemented neonates (62 +/- 24 vs 125 +/- 62 micromol/L, p = 0.005). There was no difference in corrected blood carboxyhemoglogin concentrations (0.72 +/- 0.44 vs 0.72 +/- 0.23%; p = 0.95), other parameters of hemolysis, weight gain, blood sampled, presumed septic episodes, necrotizing enterocolitis, feeding intolerance, or transfusion. On day 14, bilirubin values were higher in control subjects than in the supplemented group (77 +/- 37 vs 55 +/- 33 micromol/L; p = 0.04). When a distant outlier in the nonsupplemented group was excluded (163 micromol/L), statistical significance was lost (73 +/- 32 vs 55 +/- 33 micromol/L; p = 0.09).. Oral supplementation of premature infants with vitamin C is not associated with evidence of increased erythrocyte destruction, hyperbilirubinemia, or other morbidity.

Topics: Anemia, Hemolytic; Ascorbic Acid; Double-Blind Method; Female; Hemolysis; Humans; Hyperbilirubinemia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male

Little information exists about the plasma target nutritional needs of the >15 million premature infants <37 weeks gestation. Investigating ascorbic acid’s (AscA) role in infant health, our study details the relationship of infant characteristics and maternal health on infant plasma AscA level (pAscA) during postnatal development. Furthermore, we determined pAscA influence during the first week of life (EpAscA) with later infant morbidities. We hypothesize that pAscA is influenced by gestational organ immaturity, as well as maternal factors, with EpAscA associated with greater morbidity risk. We conducted a prospective longitudinal observational study of pAscA, demographics and hospital course detailed in infants ≤34 weeks. Sixty-three subjects were included, with >200 urine and plasma data points analyzed. Maternal smoking, exposure to magnesium sulfate (MgSO4) and advancing gestational and postnatal age were associated with lower pAscA. Non-white infants and those ≤30 weeks that developed bronchopulmonary dysplasia or retinopathy of prematurity had lower pAscA. Prenatal smoking, MgSO4, birth gestational age and race negatively influence pAscA. These results show prenatal and postnatal developmental factors influencing initial pAscA and metabolism, potentially setting the stage for organ health and risk for disease. Assessment of dietary targets may need adjustment in this population.

Topics: Ascorbic Acid; Female; Gestational Age; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Magnesium Sulfate; Pregnancy; Prospective Studies

To reach nutritional standards, human milk has to have 2g/dL of protein. In 2013, Lafeber stated that when human milk is fortified up to 2g/dL, it may increase its osmolality up to 500 mOsm/kg. He also warned that care must be taken when adding a drug or vitamins to human milk.. We studied, for the first time, the impact of adding multivitamins (ADEC) on human fortified milk osmolality.. The osmolality of 36 pasteurized, fortified human milk samples was measured. The amount of milk required as a solvent to maintain osmolality below 500 mOsm/kg was then determined.. The osmolality of 2mL of fortified human milk reached up to 750 mOsm/kg when the multivitamins ADEC was added. The osmolality decreased proportionately as the solution was diluted and if vitamins are added in two half-doses each time. It is only with 20mL of milk that the osmolality lowers to its initial rate of 430 mOsm/kg. The stronger the milk's fortification is, the greater impact it has on the milk's osmolality.. New nutritional recommendations for premature infants are needed. In the meantime, when the fortified milk intake is under 20mL, it is preferable to extend parenteral intakes with fat-soluble vitamins or reduce doses of vitamins in milk. Also, we should use enriched human milk as a fortifier and be cautious with indiscriminate fortification or when adding drugs and electrolyte solutions.

Topics: Ascorbic Acid; Dietary Proteins; Food, Fortified; Guideline Adherence; Humans; Infant, Premature, Diseases; Milk, Human; Osmolar Concentration; Vitamin A; Vitamin D; Vitamin E; Vitamins

Topics: Anemia, Iron-Deficiency; Ascorbic Acid; Auditory Diseases, Central; Auditory Pathways; beta Carotene; Cryptoxanthins; Diet; Female; Folic Acid; Hearing Loss; Humans; Infant, Premature, Diseases; Male; Maternal Nutritional Physiological Phenomena; Neurogenesis; Pregnancy; Pregnancy Complications

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

Allantoin, the oxidation product of uric acid (UA), can be used as an in vivo marker of free radical generation. The aims of the present study were to evaluate the allantoin changes in plasma and bronchoalveolar lavage fluid (BALF) as well as to examine plasma levels of ascorbic acid (AA) and its oxidation product, dehydroascorbic acid (DHAA), in infants with or without chronic lung disease (CLD) during the first week of life. The study population was 20 infants of 24-30 weeks gestation, comprising 10 who subsequently developed CLD and 10 without CLD. In the CLD infants, the plasma allantoin/UA ratio showed a significant increase after day 1 and continued to increase gradually to reach a peak on day 6 (6.5 +/- 4.1% for CLD and 2.1 +/- 0.9% for non-CLD infants). The allantoin/UA ratio in BALF was also higher in CLD infants and the difference reached significance on days 4-6 (41.2 +/- 15.8% for CLD and 11.7 +/- 9.9% for non-CLD infants). In contrast to allantoin, the plasma DHAA/AA ratio did not differ between the 2 groups throughout the study period. Our findings that the allantoin/UA ratios were significantly higher in CLD than non-CLD infants not only in plasma but also in BALF, and that the intergroup differences of this ratio in both plasma and BALF was more prominent in the latter half of the first week of life further confirm our previous speculation that oxygen radicals are involved in the development of neonatal CLD.

Topics: Allantoin; Ascorbic Acid; Biomarkers; Bronchoalveolar Lavage Fluid; Chronic Disease; Cohort Studies; Dehydroascorbic Acid; Female; Free Radicals; Humans; Infant, Newborn; Infant, Premature, Diseases; Lung Diseases; Male; Oxidation-Reduction; Uric Acid

This study was undertaken after the observation in a premature infant of a hemolytic anemia with Heinz bodies that appeared to result from administration of a multivitamin preparation. In vitro incubation of erythrocytes of premature infants with sodium ascorbate (0.1 mg/ml) for 3 hours significantly raised the number of Heinz body-containing cells from 17.6 +/- 5.7% to 27.2 +/- 8.2% (mean +/- SE). Erythrocytes of term infants and those of adults developed Heinz bodies after exposure to higher sodium ascorbate concentrations (1.0 mg/ml). Erythrocytes of adult and newborn guinea pigs were similarly affected by sodium ascorbate. Daily intraperitoneal injections of 500 mg of sodium ascorbate, given for 7 days to four adult guinea pigs, caused significant Heinz body formation. These studies indicate that the erythrocytes of premature infants are uniquely sensitive to the development of Heinz bodies after exposure to sodium ascorbate. The levels required to produce Heinz bodies in vitro are in the range of those found in vivo after routine administration of vitamin C to premature infants. The significance of these observations in the development of hyperbilirubinemia in premature infants and in the safety of vitamin C remains to be determined.

Topics: Adult; Anemia, Hemolytic; Animals; Ascorbic Acid; Erythrocytes; Erythrocytes, Abnormal; Female; Guinea Pigs; Heinz Bodies; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases

The accumulation of ascorbic acid in the brain by active transport establishes a high brain-plasma gradient of the vitamin. An insult to the CNS may result in an efflux of ascorbate into the circulation with a consequent rise of plasma levels. We measured plasma ascorbic acid levels in premature neonates on days 1, 3, and 5 of life, and the infants underwent ultrasonographic examination to detect intracranial hemorrhage. Neonates with intraventricular hemorrhage sustained significantly higher plasma ascorbate levels than their controls. Infants with massive bleeding had higher levels than those with a smaller hemorrhage. These results suggest that an efflux of ascorbic acid into the circulation occurs secondary to intracranial hemorrhage.

Topics: Apgar Score; Ascorbic Acid; Biological Transport, Active; Birth Weight; Cerebral Hemorrhage; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Time Factors; Urea

We have previously shown that substantial losses of fat-soluble (FS) vitamin A from parenteral alimentation solution occur due to adsorption in the intravenous tubing and photodegradation in the bottle. This study assessed the delivery of other vitamins, viz, FS vitamin E and water-soluble (WS) vitamin C, from parenteral alimentation solution. The solution containing 2.0 ml/L of an aqueous multivitamin infusion was infused at a constant rate of 10 ml/h using a standard intravenous administration set. Multiple aliquots of the solution from the bottle and the effluent obtained sequentially in a 24-h period were analyzed for concentrations of vitamins E and C. Both vitamins remained relatively stable in the bottle. A significant amount (12%) of vitamin E was lost in the intravenous tubing. No losses of vitamin C were incurred in the intravenous tubing. The data suggest that delivery of FS vitamin E from parenteral alimentation solutions is less than optimum because of adsorptive losses. Similar losses are not encountered with WS vitamin C.

Topics: Ascorbic Acid; Gastrointestinal Diseases; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Parenteral Nutrition; Parenteral Nutrition, Total; Time Factors; Vitamin E

Topics: Amino Acid Metabolism, Inborn Errors; Ascorbic Acid; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature, Diseases; Male; Tyrosine

Topics: Amino Acid Metabolism, Inborn Errors; Ascorbic Acid; Child Development; Chromatography, Paper; Diet Therapy; Fatigue; Feeding Behavior; Female; Growth Disorders; Humans; Infant, Newborn; Infant, Premature, Diseases; Intelligence; Intelligence Tests; Phenylalanine; Pregnancy; Pregnancy Complications; Tyrosine

Topics: Amino Acid Metabolism, Inborn Errors; Ascorbic Acid; Birth Weight; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Taurine; Tyrosine

Topics: Administration, Oral; Amino Acid Metabolism, Inborn Errors; Amino Acids; Anemia; Ascorbic Acid; Diagnosis, Differential; Hepatitis; Humans; Infant, Newborn; Infant, Premature, Diseases; Jaundice, Neonatal; Male; Rickets; Tyrosine

Topics: Ascorbic Acid; Follow-Up Studies; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Mass Screening; Metabolism, Inborn Errors; Tyrosine

Topics: Ascorbic Acid; Catecholamines; Epinephrine; Humans; Infant, Newborn; Infant, Premature, Diseases; Metabolism, Inborn Errors; Norepinephrine; Nutritional Requirements; Tyrosine; Vanilmandelic Acid

Topics: Anabolic Agents; Ascorbic Acid; Birth Weight; Body Weight; Female; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Pediatric Nursing; Thiamine

Topics: Animals; Ascorbic Acid; Body Weight; Diet Therapy; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature, Diseases; Metabolic Diseases; Milk; Tyrosine

Topics: Amino Acid Metabolism, Inborn Errors; Ascorbic Acid; Birth Weight; Blood; Female; Humans; Hydroxyindoleacetic Acid; Infant, Newborn; Infant, Premature, Diseases; Male; Phenylalanine; Tyrosine; Urine

Topics: Ascorbic Acid; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Rickets