Plasma and urine riboflavin and pyridoxine concentrations in enterally fed very-low-birth-weight neonates.

Preterm infant formulas (PIFs) for very-low-birth-weight (VLBW) infants (birth weight, < 1,500 g) are augmented to provide daily riboflavin and pyridoxine at levels up to five-fold greater than in term infant formula and 18-fold greater than in human milk. We evaluated plasma riboflavin and pyridoxine concentrations in VLBW infants who received PIF during their first postnatal month. Eighty-eight plasma and 124 urine samples were collected for riboflavin- and pyridoxine-concentration measurements from 57 clinically healthy VLBW infants weekly during their first postnatal month. Concentrations were measured using high-performance liquid chromatography. At the time of the sample, patients were receiving > or = 80% of their total calories via enteral feedings. Plasma riboflavin concentrations rose from 45.3 +/- 7.3 ng/ml at baseline (mean +/- SEM) to 173.5 +/- 20.3 ng/ml by 1 week of age and remained at 177.3-199.7 ng/ml during the following three weekly measurements; values were up to 14-fold above baseline concentration. Urine riboflavin concentration increased from 534 +/- 137 ng/ml at baseline to 3,521 +/- 423 ng/ml by 1 week of age and remained at 4,451-5,216 ng/ml during the next 3 weeks. In a similar pattern, baseline plasma (69.4 +/- 10.4 ng/ml) and urine (145 +/- 30 ng/ml) pyridoxine concentrations were significantly increased by 1 week postnatal age; they remained at 163-248 ng/ml (plasma) and 1,573-2,394 ng/ml (urine) through the first postnatal month. Plasma and urine riboflavin and pyridoxine concentrations in enterally fed VLBW infants increased from baseline concentrations by 1 week of postnatal age and remained elevated for the first postnatal month. High daily intake and immature renal development are probable contributing causes of the elevated plasma riboflavin and pyridoxine concentrations. We suggest that lower daily enteral administration of riboflavin and pyridoxine should maintain adequate blood concentrations and minimize potential toxicity.

Retinol (vitamin A) and riboflavin (vitamin B2) administration and metabolism in very low birth weight infants.

The combination of marginal hepatic retinol stores at delivery and the reduction of daily retinol dose due to complications with the delivery system places the VLBW infant receiving parenteral nutrition at high risk for retinol deficiency during the first month of life. This has serious health implications because retinol is essential during this period for normal growth and repair of the pulmonary tissue in VLBW infants. Enterally fed VLBW infants, on the other hand, receive relatively higher doses of retinol from vitamin-supplemented premature infant formula and fortified breast milk. Equally serious is the problem of monitoring vitamin A status in infants receiving supplemental doses of vitamin A. It seems clear that while plasma vitamin A levels are the most easily available method of monitoring vitamin A status, further studies are necessary to determine if these levels correlate with hepatic content. This is of particular concern since liver disease is common in VLBW infants and vitamin A hepatotoxicity has been described in a cohort of 41 patients receiving therapeutic doses of the vitamin. While further research of daily enteral and parenteral retinol requirements of VLBW infants should continue, formulation of a specific VLBW parenteral vitamin supplement should also be developed.

Preliminary assessment of very low calorie diets by conventional and signal-averaged electrocardiography.

Fatalities accompanying the use of very low calorie diets have been attributed to cardiac arrhythmias, which may have been associated with myocardial catabolism and hypokalemia. Delayed activation of damaged regions of myocardium may result in low amplitude potentials late in the QRS complex which have been associated with sustained ventricular tachycardia. We used the techniques of routine electrocardiography, signal averaging of the surface electrocardiogram and ambulatory electrocardiographic (Holter) monitoring to evaluate a group of 11 obese men (116 +/- 14 kg) who consumed a potassium-supplemented 660 kcal/day (2763 kJ/day) milk-based liquid diet for 95 +/- 14 days. Electrocardiographic measurements were made before beginning the diet, during the final week on the diet, and after refeeding. Corrected QT interval, QRS voltage and duration, absence of signal-averaged late potentials and ventricular ectopy during 24 h Holter monitoring during the diet and refeeding did not differ from baseline determinations at any point in the obese subjects. In this study, which involved only 11 subjects, neither standard electrocardiographic techniques nor a newer signal-averaging technique revealed any electrocardiographic changes from the diet. A very large population would have to be studied to evaluate the usefulness of these techniques in predicting myocardial damage serious enough to cause arrhythmias. Until such studies are available, the safety of such diets remains unknown.

Vitamin E levels in premature infants during and after intravenous multivitamin supplementation.

Serum vitamin E levels were measured in 19 infants weighing 1.0 to 1.5 kg, in 16 infants weighing less than 1 kg who received 65% of a vial (4.6 mg of vitamin E) of multivitamins (MVI Pediatric) daily, and in another group of 16 infants weighing less than 1 kg who received 30% of a vial (2.1 mg of vitamin E) daily. Supplementation was started within 12 hours of birth. Serum vitamin E levels were also measured after supplementation was discontinued in infants who had received 65% of a vial daily. Vitamin E sufficiency (levels equal to or greater than 0.5 mg/dL) was attained after 48 hours of supplementation in all infants receiving 65% of a vial daily and after 72 hours of supplementation in all infants receiving 30% of a vial daily. Vitamin E sufficiency was not maintained in all infants receiving 30% of a vial daily. Of the infants weighing less than 1 kg who received 65% of a vial daily, 31% had serum levels greater than 3.5 mg/dL, whereas no infant weighing less than 1 kg who received 30% of a vial daily had a level greater than 3.5 mg/dL (P less than .05). Of the infants weighing less than 1 kg who received 30% of a vial daily, 56% had levels less than 1 mg/dL v 6% of infants less than 1 kg who received 65% of a vial daily (P less than .01). Vitamin E levels decreased after MVI Pediatric supplementation with 65% of a vial was discontinued (P less than .05). After MVI Pediatric was discontinued, some infants became vitamin E insufficient.

Evaluation of a pediatric multiple vitamin preparation for total parenteral nutrition. II. Blood levels of vitamins A, D, and E.

This study represents the first attempt to evaluate the American Medical Association Nutrition Advisory Group (NAG) recommendations for intravenous vitamin A, D, and E dosages for infants and children. Patients studied included 18 preterm infants (group 1) and 26 term infants and children (group 2A) receiving total parenteral nutrition for 2 to 4 weeks and eight infants and children receiving total parenteral nutrition for 3 to 6 months (group 2B). Term gestation infants and children up to 11 years of age all received the same dosages (those that were recommended by the NAG for children weighing more than 10 kg). Preterm infants received 65% of these doses. In group 1, cord blood alpha-tocopherol levels were less than 0.22 mg/dL in seven preterm infants (reference value = 0.29 +/- 0.04), but mean levels increased to 1.65 +/- 0.17 mg/dL after four days of treatment. Eight infants consistently received additional vitamin E orally (80 to 150 mg daily), and their levels increased to 2.18 +/- 0.26 mg/dL by four days of study and to 3.49 +/- 0.57 mg/dL after 3 weeks. Oral supplementation in the preterm infants appeared to be unnecessary because intravenous vitamins alone maintained levels above 1.1 mg/dL. In group 2, alpha-tocopherol levels were maintained within the reference range. Patients receiving lipid emulsions containing substantial quantities of alpha-tocopherol had significantly higher blood levels than patients receiving lipid emulsions containing little alpha-tocopherol (P less than .01). Mean 25-OH vitamin D levels were maintained above or within the reference range in groups 2A and 2B.(ABSTRACT TRUNCATED AT 250 WORDS)

Initial clinical trials of the subrenal capsule assay as a predictor of tumor response to chemotherapy.

Retrospective and prospective clinical trials were performed to determine the usefulness of the 6-day subrenal capsule (SRC) assay for the prediction of response to chemotherapy. Evaluable assays were obtained in 86% of 1000 consecutive specimens obtained from a variety of solid malignancies. Analysis of chemotherapeutic sensitivity in this assay gave reproducible and consistent results. The overall predictive accuracy of the assay in 62 retrospective clinical trials in 55 patients was 85%. Of 37 evaluable patients with chemotherapy refractory cancers treated in a prospective trial with single agent chemotherapy as determined by the assay, 14 (38%) responded. Greater degrees of tumor regression in the assay were associated with a higher probability of clinical response. The SRC assay shows potential value as a rapid predictive test for chemotherapeutic selection on an individual patient basis. However, additional prospective clinical trials are necessary to document its ultimate utility.

Concentrations and total daily output of micronutrients in breast milk of mothers delivering preterm: a longitudinal study.

The number of preterm infants fed their own mother's milk appears to be increasing as a result of information suggesting certain benefits over milk from human milk banks or proprietary formulas. It is also apparent that the nutritional requirements of term and preterm infants differ. Thus, the finding of various deficiencies in small preterm infants indicates that studies which examine the nutrient content of milk from mothers who deliver prematurely are important to aid in suggesting appropriate supplementation. In order to provide appropriate recommendations, nutrient content must be assayed during the period of exclusive milk feedings. Accordingly, the concentrations and total daily output of breast milk zinc and copper, and vitamins A, C, and E, were examined in a group of 13 mothers delivering at or before 32 weeks gestation. Collections of a total 24-h output were obtained every 7 days for the first 7 weeks after delivery. Concentrations of all micronutrients were similar to those reported previously during the first 5 weeks of lactation. Most striking, however, was the progressive decline in total output as well as concentration of zinc. After the first 2 weeks of lactation, levels of copper and vitamins A, C, and E were not affected by the duration of lactation. There was substantial variation between mothers in daily output of all the micronutrients. The low output of these micronutrients suggests that some attempt should be made at monitoring the mineral and vitamin status of small preterm infants fed exclusively human milk for the first 3 months of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal alcohol syndrome: failure of zinc supplementation to reverse the effect of ethanol on placental transport of zinc.

clinical observation and experimental animal models indicate that chronic ethanol ingestion during pregnancy results in a well recognized state in the fetus termed fetal alcohol syndrome. We have recently demonstrated, using an in vivo technique, that placental transport of zinc, an essential element for protein synthesis, is significantly decreased by short-term and long-term ethanol ingestion during pregnancy; moreover, total fetal zinc concentration in the offspring of mothers on chronic ethanol diet was significantly decreased compared to pair-fed controls. These findings indicated that the growth retardation in fetal alcohol syndrome may be due partly to a decrease in the transfer of zinc to the fetus. Our current study was designed to investigate whether the defect in placental transport can be overcome by supplementation of the ethanol diet with either 10 or 40 mg of zinc per liter in isocalorically pair-fed pregnant rats. The results indicate that supplementation of the ethanol diet with zinc did not overcome the defect in placental transport of zinc.

Human milk and breast feeding: an update on the state of the art.

PIP: Current approaches to infant feeding have been based on the level of available knowledge of nutritional requirements of full term and low birth weight (LBW) infants and on established cultural traditions in many contemporary societies. This discussion summarizes existing information about infant nutrition and immunobiologic aspects of human milk, which may influence the choice of breast versus bottle feeding of infants in different parts of the world. The average caloric requirement for a normal full term infant from the 2nd day of age through the 1st year of life is estimated to be about 100-110 Kcal/kg/day. Caloric intake of less than 80 Kcal/kg/day is usually insufficient for physiologic needs and intakes over the average requirement may be associated with obesity. The minimum requirement for protien has been estimated to be about 1.8 gm/100 Kcal and protein intake of over 4.5 gm/100 Kcal may result in an increased urea nitrogen retention. The nutritional requirements of premature and LBW infants have not been clearly established, but the nutritional needs of a LBW infant appear to be significantly higher than the requirements of a normal full term infant. The chemical composition of human milk exhibits considerable variation between different individuals and in the same individual at different times of lactation, as well as between samples obtained from mothers of LBW infants and full term infants. Fresh milk contains a wealth of components that provide specific and nonspecific defenses against infectious agents or other macromolecules. The concentrations of protein, whey protein nitrogen, sodium and potassium in cow's milk are 2-3 times higher than in human milk. Only limited information is available about the spectrum of environmental chemical and toxins present in cow's milk. The composition of human milk meets the minimum requirements for protein and calories for a growing full term infant, despite the fact that protein content of pooled human milk is low (0.9 gm/ml). Breastfeeding seems to result in a more balanced solute load because breastfed babies appear to require less water than babies fed on cow's milk. Commercial formula products often require reconstitution and supplementation with certain additives during manufacture or at the time of its feeding to the infant. Careful, but sparse epidemiologic studies conducted recently in several rural and urban settings, demonstrated a striking resistance of breastfed infants to colonization by coliform organisms. In modern times possibly the single most important consideration for the use of breastfeeding is its cost. Infants fed human milk do not grow as rapidly as those fed most commercial formulas, but there is no evidence to suggest that rapid growth is a desirable goal of nutrition for normal neonates. Conclusive evidence of overwhelming nutritional advantages of human nilk and breastfeeding over commercial milk products (which are properly reconstituted under sterile conditions) is not available at this time.^ieng

Relative toxicity and metabolic effects of cholecalciferol and 25-hydroxycholecalciferol in chicks.

The relative toxicity and metabolic effectiveness of cholecalciferol (CC) and 25-hydroxycholecalciferol (25-HCC) in chicks were evaluated by feeding six graded levels of each and observing gross and microscopic pathology as well as several metabolic parameters of calcium metabolism. Renal tubular calcification was observed when CC was fed at the rate of 10.0 mg/kg of diet and when 25-HCC was fed at the rate of 0.1 mg/kg diet. Thus, 100-fold increase in toxicity results when the hydroxylated form of CC is fed. Both microscopic renal lesions and increased renal calcium and inorganic phosphate concentrations occurred in chicks with normal serum calcium concentrations.

Protracted diarrhea and malnutrition in infancy: Changes in intestinal morphology and disaccharidase activities during treatment with total intravenous nutrition or oral elemental diets.

Two therapeutic regimens were compared in 16 infants with protracted diarrhea and malnutrition. Eight patients were treated with total parenteral nutrition given via a central vein (group A); the remaining eight patients received a combination of dilute parenteral nutrients given in a peripheral vein plus continuous enteral feedings of an elemental diet (group B). All patients recovered although two infants in group B were switched to TPN treatment after a poor response to the elemental diet. Intestinal biopsies were performed: (1) before treatment; (2) after 2 to 3 weeks of TPN or elemental diet; and (3) after 2 to 3 weeks of Nutramigen feedings. Before treatment, all patients had atrophic changes in the jejunal epithelium and deficient disaccharidase and trypsin activities. The second biopsy showed morphologic recovery in all patients, incomplete recovery of lactase and trypsin in both treatment groups, and complete recovery of sucrase and maltase activities only in group B patients. The third biopsy showed normal morphology and complete recovery of all enzymes measured. The mean number of hospital days was 46 +/- 4.8 for group A and 34 +/- 1.6 for group B (p less than 0.05) suggesting that patients given enteral feedings early tended to have a more rapid return of intestinal function and of some intestinal enzymes.