Vitamin E and Linoleic Acid in the Feeding of Premature Infants

Abstract
1) Premature infants fed a vitamin E- free milk mixture, with or without inclusion of 5% of calories or fat in the form of linoleic acid, develop no apparent clinical evidence of tocopherol deficiency within a period as long as 195 days. a) Characteristic changes in serum vitamin E level and hydrogen peroxide hemolysis occur, but increased urinary excretion of creatine or alpha-amino nitrogen was not observed. b) The typical course of “anemia of prematurity” was observed; increase in absolute hemoglobin mass commenced at about 50 days and was progressive. c) In one infant, after 5 months, serial bone marrow studies revealed an occasional double-nucleated erythroid precursor, but there was no increase in numer with continued depletion. d) Supplementation with vitamin E at 40 days was associated with mild-to-moderate reticulocytosis but not with increase in hemoglobin concentration within a period of 6–10 weeks. e) Supplementation with vitamin E at 70 days in one infant, depleted of vitamin E butt not linoleic acid, resulted in a modest reticulocytosis but not in a rise in hemoglobin. The course of hematologic change was identical to that observed in his twin who had received both tocopherol and linoleic acid from the first week of life. f) Supplementation with vitamin E led to prompt increase in serum vitamin E levels, which was less marked in those infants whose regimen initially included 5% calories as linoleic acid. g) Repletion with linoleic acid at about 55–60 days, following initial repletion with vitamin E at about 40 days, was not associated with increased reticulocytosis or increase in hemoglobin concentration. h) In two infants who received linoleic acid but no vitamin E, the urinary creatine-to-creatinine ratio reached levels of 0.6 and 0.98, which dropped promptly after administration of tocopherol. 2) Premature infants fed a fat-free milk mixture containing 10–25 mg vitamin E daily from the beginning, with or without inclusion of 5% of calories as fat in the form of linoleic acid, likewise exhibited no alteration in typical spontaneous reticulocytosis at 5–7 weeks and followed a course of “anemia of prematurity” for as long as 95 days. a) Vitamin E levels tended to rise slowly, not exceeding 0.5 mg/100 ml until after day 20. This is more notable in infants who received linoleic acid from the beginning and in whom the highest levels achieved were definitely lower than in those infants who had not received linoleic acid from the beginning. b) In identical twins supplemented with tocopherol from the beginning, administration of unsaturated fat at 58 days had no perceptible effect on reticulocytosis or hemoglobin concentration. c) In one of twins given both tocopherol and linoleic acid from the beginning, spontaneous reticulocytosis and typical anemia of prematurity were not prevented, and the hematologic course was identical to that of the other twin who had received only linoleic acid from the beginning. 3) Infants fed a proprietary prepared milk developed adequate levels of serum vitamin E in F but exhibited a definite, moderate reticulocytosis following supplementation with tocopherol at about 40 days. There was no associated increase in hemoglobin concentration. 4) Thus, the inclusion of vitamin E or linoleic acid, or both, from the beginning did not prevent the reticulocytosis observed at 5–7 weeks or the characteristic anemia of prematurity. Nor did supplementation with either or both of these substances at 40–70 days ameliorate the anemia. Likewise, exclusion of either or both from the beginning did not prevent increase in absolute hemoglobin mass which characteristically commences at about 50 days of life. 5) Decrease in 51Cr half-time survival was frequently observed in infants depleted of vitamin E or linoleic acid, but this determination did not appear to be a consistent indicator of tocopherol or linoleic acid deficiency. In certain instances, definite increase in T½ resulted from supplementation with either of these substances, but in no instance did associated increase in hemoglobin concentration occur. Mean initial T½ was normal in fat-free and tocopherol-free groups but low in two of three infants receiving both vitamin E and linoleic acid from birth. This technique would appear to have limited utility in identification of a deficiency state or evaluation of pathogenetic factors. Erythrocyte survival is probably an artifactual, in vitro phenomenon similar to H202 hemolysis but not well correlated with it in incidence nor causally related to it. 6) Results of this study indicate that anemia of prematurity is not basically related to vitamin E deficiency or linoleic acid deficiency, or both, for at least 6 months. Identification of clinical evidence of biochemically demonstrable signs of vitamin E deficiency remains extremely elusive in premature infants under 6 months.

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