effect, a syngerism between clofibrate and vitamin E may explain the coagulapathy. Animals treated with clofibrate, however, tend to have low serum levels of vitamin E arguing against a synergistic effect. It i s also possible t h a t an interaction between warfarin and vitamin E occurs. Warfarin is partially metabolized by oxidative enzymes in the liver; vitamin E, being an antioxidant, could interfere with the degradation of warfarin. However, this also does not appear to be the case since plasma warfarin levels remained virtually unchanged during the test period. Thus, this data and current knowledge of these drugs does not support the thesis that the vitamin E toxicity was drug induced, but rather that there is a direct interference of vitamin E with vitamin K activity. This suggestion is supported, in part, by the observation that vitamin K-deficient animals treated with vitamin E have further depression of vitamin K-dependent factor levels. In view of the interesting observations of these investigators and the fact that the recommended intake of vitamin E is greatly exceeded in many situations, the possibility

of adverse responses to excess vitamin E cannot be disregarded. 0

1. The Pharmacological Basis of Therapeutics. L. S. Goodman and A. Gilman, Editors, fourth edition, pp. 1694-1697. The Macmillan Co., New York, 1970 2. G. M. Berneske, A. R. Butson, E. N. Gauld and D. Levy: Clinical Trail of High Dosage Vitamin E in Human Muscular Dystrophy. Canad. Med. Assn. J. 82: 4 18-421, 1960 3. S. J. Mellette and L. A. Leone: Influence of Age, Sex, Strain of R a t and Fat Soluble Vitamins on Hemorrhagic Syndromes in Rats Fed Irradiated Beef. Fed. Proc. 19: 10451049, 1960 4. B. E. March, E. Wong, L. Seier, J. Sim and J. Biely: Hypervitaminosis E in the Chick. J. Nutrition 103: 37 1-377, 1973 5. H. A. Dymsza and J. Park: Excess Dietary Vitamin E in Rats. Fed. Proc. 34: 912, 1975 6. P. M. Farell and J. W. Willison: Megavitamin E Supplementation in Man. Fed. Proc. 34: 912, 1975 7. J. J. Corrigan, Jr. and F. I. Marcus: Coagulopathy Associated with Vitamin E Ingestion. J. Am. Med. Assn. 230: 1300-1301, 1974

ORAL FEEDING VERSUS TOTAL PARENTERAL NUTRITION IN LOW BIRTHWEIGHT INFANTS There was no significant difference in neonatal mortality and morbidity between in fanis receiving total parenteral nutrition (TPN) and controls who were fed "humanized"milk by continuous nasogastric drip. Key Words: total parenteral nutrition, low birth weight infants

The provision of adequate nutrition is a major problem in the management of newborns of low birthweight. Animal studies suggest that neonatal malnutrition can cause permanent retardation of brain development. It i s even more imperative to provide adequate nutrition t o the small birthweight infant who has a reduced store of nutrients. Cornblath e t al.' found that intravenous sugar and amino acid solutions did not result in significant weight gain in such infants, possibly because calorie in270 NUTRITION REVIEWS I VOL 33,NO. 9 I SEPTEMBER1975

take was limited by the amount of water which could be infused. Higgs e t al.3 postulate that if increased amounts of energy could be given parenterally the improved utilization of amino acids and positive nitrogen balance would result in better weight gain.2 Wilmore and Dudrick4 successfully treated infants by total parenteral ad m i n istration of protein hydrosylate, electrolytes, hypertonic glucose and vitamins using an indwelling venous catheter (TPN). Recently TPN was compared with continuous nasogastric drip (oral) in the treat-

ment of low birthweight infants.' A 10 percent invert sugar solution was begun two hours after birth, first by scalp vein infusion and thereafter a t 6-12 hours by umbilical catheter. After 24 hours oral or parenteral nutrition was commenced. Two groups of 43 infants were randomly selected to receive either oral feeding or TPN. The oral group was fed full-strength "humanized" milk. The milk infused the first three days was supplemented intervenously with 10 percent sugar. Intakes of 166 kcal and 3.2 g protein per kilogram of body weight per day were reached by the fifth day. The TPN group received no oral feeding for ten days, but received parenteral fluids (casein hydrolysate, fat emulsion and dextrose) by continuous umbilical arterial infusion. By the fourth day, maximum intakes of 136 kcal per kilogram of body weight and 3.2 g protein were reached. The entire system, except the arterial catheter, was changed daily until day 10 a t which time oral full-strength "humanized" milk feeding was initiated. Both groups received routine oral milk and nursery care for the next 14 to 28 days. The mortality rate for both treatments was high with pneumonia, septicemia, apnea and enteritis being the most common form of morbidity. In the oral group mortality was 14 percent, while in the TPN group mortality was 20 percent. The added risk of infection from the indwelling catheter with TPN5 apparently was not a problem with the short period of parenteral nutrition used in this study. Though results of biochemical analysis of serum and urine were not included, serum sodium potassium chloride, calcium phosphate, blood urea, serum osmolarity, total protein, albumin, globulin and SGOT were all reported to be within normal limits. Serum cholesterol and plasma amino acid levels were significantly increased during TPN and returned to normal when discontinued. Ghadmi e t al.' also reported high levels of amino acids and particularly of methionine, but no harmful effects of

abnormally high levels of amino acids or unbalanced amino acid ratios caused by administration of protein hydrosylates have been proven.6 The authors found no significant difference in weight gain between the two groups. Unfortunately, a strict comparison is not possible since the infants were not given comparable diets. The diet of the oral group contained more calories, carbohydrate, fat and ash than that of the TPN group. The fact that the TPN caused the same weight gain although it provided fewer calories may indicate more efficient food utilization with TPN. Although there is an urgent need for making TPN benefits available to low birthweight infants, ideal parenteral solutions may not be available. Nutritional needs may be significantly different when food is given parenterally instead of orally; and the possible detrimental effects of the altered blood amino acid pattern and elevated lipid and cholesterol levels resulting from administering such solutions as used in this study should be determined. 0

1. M. Cornblath, A. E. Forbes, R. S. Pildes and J. Greenaard: A Controlled Study of Effect of Early Fluid Administration on Survival of Low Birth Weight Infants. J. Pediat. 69: 911-912, 1966 2. M. E. Shils: Guidelines for Total Parenteral Nutrition. J. Am. Med. Assn. 220: 1721-1729, 1972 3. S. C. Higgs, A. F. Malan and H. De V. Heese: A Comparison of Oral Feeding and Total Parenteral Nutrition in Infants of Very Low Birthweight. S. Afr. Med. J. 48: 2169-2173, 1974 4. D. W. Wilmore and S. J. Dudrick: Growth and Development of an Infant Receiving all Nutrients Exclusively by Vein. J. Am. Med. Assn. 203: 860-864,1968 5. D. W. Wilmore and S. J. Dudrick: Safe LongTerm Venous Catheterization. Arch, Surg. 8: 256-258,1969 6. H. Ghadimi, F. Abaci, S. Kurnar and M. Rathi: Biochemical Aspects of Intravenous Alimentation. Pediarrics 48: 955-965, 1971

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