Samuel Gross

Vitamin E-dependent anemia in the premature infant. I. Effects of large doses of medicinal iron

Description of a hemolytic anemia associated with vitamin E deficiency in premature infants prompted study of the relationships of medicinal iron, vitamin E, and hematologic parameters during the early life of such infants. A total of 186 patients categorized according to birth weight and gestational age were placed in study groups: (1) no iron or vitamin E supplement, (2) oral vitamin E supplement, (3) oral iron supplement, and (4) iron and vitamin E supplements. Significantly lower mean hemoglobin and serum vitamin E concentrations, with higher reticulocyte count and hydrogen peroxide fragility, were found during the second month of life in infants with a gestational age less than 36 weeks who were not receiving vitamin E. Hemoglobin values were lowest and reticulocyte counts highest in vitamin E-deficient infants of low gestational age who received supplemental iron. These observations suggest that therapeutic doses of iron increase red cell hemolysis during a period of vitamin E deficiency.

Vitamin E-dependent anemia in the premature infant. II. Relationships between gestational age and absorption of vitamin E**

The association of vitamin E deficiency and hemolytic anemia in small premature infants prompted study of intestinal absorption of vitamin E in infants of various gestational and chronologic ages. A direct relationship was found between the gestational age of the premature infant and his ability to maintain vitamin E sufficiency during the first 3 months of life; infants of lowest gestational age were least able to achieve vitamin E sufficiency, even when receiving a vitamin E supplement. In infants whose gestational age was less than 32 weeks, progressive improvement in the intestinal absorption of the vitamin was seen as the chronologic equivalent of a full-term gestational age was approached. Oral administration of iron is implicated as interfering with the intestinal absorption of vitamin E. Since maintenance of vitamin E sufficiency appears to be nutritionally important in the premature infant, the efficacy of other routes of administration of the vitamin should be explored.

Vitamin E-dependent anemia in the premature infant

Studies on serum tocopherol levels, hematopoietic responses, and erythrocyte phospholipid fractions were carried out in agroup of low-birth-weight (mean, 1,530 gm) premature infants whose diets were supplemented with either water-soluble (TPGS) or fat-soluble (TA) forms of d-alpha tocopheryl (25 IU/day). Significantly higher serum tocopherol levels and early maintenance of higher hemoglobin values were observed in the infants who received the water-soluble tocopheryl preparation. Comparable but less marked differences in these values were identified in similarly paired groups fed lower concentrations of the tocopheryls in combination with iron. The lowest hemoglobin levels were recorded in the infants fed formulas containing TA and iron. Among a selected group of vitamin E-deficient infants, evidence of lipid instability in the erythrocyte membrane was manifested by decreased values of phosphatidyl ethanolamine.

VITAMIN E, RED CELL LIPIDS AND RED CELL STABILITY IN PREMATURITY*

In primates, the induction of vitamin E deficiency results in a dyspoietic hyporegenerative anemia, with an ultimate decrease in red cell survival. Accompanying the deficiency is an elevation of in vitro fragility of erythrocytes to hydrogen peroxide. Abnormal in vitro sensitivity of erythrocytes to hydrogen peroxide has also been described, concomitant with vitamin E deficiency, in a variety of malabsorptive disorders, which however, lack an anemia causally related to the vitamin E deficiency.2 Vitamin E-dependent anemias in the human are clinically and morphologically the result of impaired and abnormal m a t u r a t i ~ n , ~ . ~ and invariably occur as part of a proteintalorie malnutrition syndrome. Recently described in the small, vitamin E-deficient premature infant is an anemia causally related to the deficiency, which is hemolytic in nature and is associated with an abnormally elevated erythrocyte hydrogen peroxide fragility.= Since one certain biological action of vitamin E (tocopherol) is that of an antioxidant at the cellular level,B it is logical to assume that lack of vitamin E may result in accelerated red cell lysis. due to an increase in the rate of erythrocyte membrane lipid peroxidation. Because the premature infant invariably undergoes a rapid growth spurt during the first year of life, with a subsequent outstripping of iron stores, it is common practice to give the infant relatively large amounts of exogenous iron early in life as a means of forestalling the development of the late anemia of prematurity. Valent iron is a known catalyst in the autooxidation of unsaturated fatty acids.*O It is possible that excess iron increases erythrocyte lipid peroxidation at a time when the usual antiperoxidant mechanisms of the red cell are deficient. The present set of experiments was designed, therefore, to identify the relationships between vitamin E-dependent hemolytic anemia, administration of iron, and erythrocyte lipids during the first 4 months of life in the premature infant.

Social and behavioral studies on hemophilicchildren and their families

This paper reports on a long-term psychiatric study of 35 hemophilic children andtheir 22 families. Its purpose was to evaluate the adjustment of the young hemophilic patient to his illness and to his life situation, and the possible relationship between parental attitudes toward hemophilia and the childs personality development and clinical course. The majority of patients and their parents showed a good adaptation to the illness. The mothers, in particular, played an essential role in promoting a healthy personality development. Bleeding episodes without known trauma, often in relation to anticipated events, were observed in many prepubertal boys. Several adolescents showed an improved clinical state following a reversal of behavior from a passive dependent state to an aggressive, at times daring, independence. The study emphasizes the need for continuous, reassuring support given by the pediatrician. The encouragement of healthful interpersonal activity and of reasonably aggressive pursuits is especially important in promoting a good adaptation of the hemophilic child.

Acute childhood leukemia presenting as aplastic anemia: The response to corticosteroids

Response to corticosteroid therapy is described in 6 children whose initial diagnosis was acquired aplastic anemia, but who eventually developed acute, lymphoblastic leukemia. A short-term course of corticosteroids during the period of aplasia produced an extremely rapid return to apparent hematologic and clinical normality until manifestations of leukemia appeared. The dramatic response in preleukemic patients is in marked contrast to the ineffectiveness of corticosteroids in the treatment of nonleukemic or classic acquired aplatic anemia.

Chronic thrombocytopenia in childhood.

tient. ~8 In the past, as many as 30% of patients with hematemesis or melena have had no documented etiology?, lo The availability of improved instrumentation and experience with pediatric endoscopy should further clarify the etiology of upper gastrointestinal hemorrhage. Mallory-Weiss mucosal lacerations are commonly found in adults. All patients with this syndrome do not present with the classical history, severity or clinical course of the original report in 19297, 10 Although the alcohol debauch was considered the precipitating event of gastroesophageal laceration, other associated factors, including closed chest massage, coughing, hiccuping under anesthesia, and straining with lifting or at stool, have been enumerated. 3, 1o The age of occurrence is unusual in our patients, but the atypical presentation and benign clinical coUrse have been previously reported. 3, ~~ The experience with these patients confirms our conviction that the Mallory-Weiss syndrome d o e s occur in children. With the increasing utilization of endoscopy in pediatric patients, we anticipate that other reports will follow. REFERENCES 1. Mallory GK, and Weiss S: Hemorrhages from lacerations of the cardiac orifice due to vomiting, Am J Med Sci 178:506, 1929. 2. Holmes KD: Mallory-Weiss syndrome: Review of 20 cases and literature review, Ann Surg 164:810, 1966. 3. Weaver DH, Maxwell JG, and Castleton KB: MalloryWeiss syndrome, Am J Surg 118:887, 1969. 4. Clemenz FW, and Dawson RG: Esophageal dyskinesia and the Mallory-Weiss syndrome, Arch Surg 93:614, 1966. 5. Koehler PR: New approaches to the radiological diagnosis of Mallory-Weiss Syndrome, Br J Radiol 42:354, 1969. 6. Gteason WA, Tedesco FJ, Keating JP, and Goldstein PD: Fiberoptic gastrointestinal endoscopy in infants and children, J PEDIATR 85:810, 1974. 7. Tedesco FJ, Goldstein PD, Gleason WA, and Keating JP: Upper gastrointestinal endoscopy in the pediatric patient, Gastroenterology 70:492, 1976. 8. Ament ME, Gans SL, and Christie DL: Experience with esophagogastroduodenoscopy in diagnosis of 79 pediatric patients with hematemesis, melena or chronic abdominal pain, Gastroenterology 68:858, 1975. 9. Brayton D: Gastrointestinal bleeding of unknown origin, Am J Dis Child 107:288, 1964. 10. Watts D, and Admirand WH: Mallory-Weiss syndrome a reappraisal, JAMA 230:1674, 1974.

Exchange transfusion with citrated whole blood for disseminated intravascular coagulation

Disseminated intravascular coagulation in 4 full-term infants and one 4-year-old child was successfully treated with exchange transfusions of stored, 12- to 72 hour old, citrated whole blood. Heparin was not used. The causative, or related, disorders included the respiratory distress syndrome, ABO incompatibility, and streptococcal sepsis. In all patients, except one, an infant with galactosemia and streptococcemia, the clotting factors promptly returned to normal. In the galactosemic infant with streptococcal sepsis, a rebound delay occurred with return to normal of the secondary clotting disorder following correction of the metabolic defect. The mechanism of action is, in part, related to a “clearing” process by the exchange transfusion, which, because of ready availability, should receive priority as the treatment of choice for disseminated intravascular coagulation in the newborn infant and probably in older patients as well.

The relationship between milk protein and iron content on hematologic values in infancy

A study of 144 infants from a homogeneous, low-income group was undertaken in order to determine the effects of various protein and iron contents of prepared cows milk formulas on hematologic values. Altogether, 4 formulas were used in the study: relatively lower protein (15 Gm. per liter) with trace or supplemental amounts of iron, and higher protein (24 Gm. per liter) with trace or supplemental amounts of iron. Complete hematologic data, including bound iron and iron-binding capacities, were obtained from birth through 18 months. Similar pre- and postpartum data were obtained on the mothers. All of the infants received iron-free cereals and consistent dietary regimens. Those infants who were fed the higher protein, trace-iron formulas had the lowest mean hemoglobin and serum iron levels. Conversely, the highest hemoglobin and iron values were observed among the infants fed the lower protein formulas, irrespective of the iron content.

Cyclic parenteral nutrition during bone marrow transplantation in children

Nine children underwent ten bone marrow transplants for malignancies and were supported by parenteral alimentation administered in cyclic fashion 18 hours daily. Children received cyclic parenteral nutrition for an average of 29 days, which provided a caloric intake (mean ± SD) of 55.9 ± 18.1 Kcal/kg/day, and a nitrogen intake of 0.28 ± 0.08 g/kg/day. Nutritional status was assessed using nitrogen balance, creatinine‐height index, and visceral protein concentrations including serum albumin, transferrin, and prealbumin. Minimal transient elevation in tests of liver function were observed without marked derangement in blood glucose, electrolytes, or osmolality. Unlike prealbumin, determinations of nitrogen balance, creatinine‐height index, serum albumin and transferrin concentrations did not parallel changes in clinical status. Cyclic parenteral alimentation is a practical approach to the maintenance of nutrition during intensive antitumor therapy and provides an infusion‐free period for the administration of drugs and blood transfusions without interfering with nutritional support. Prealbumin accurately reflects changes in the patient‐s clinical status at any point and is easily and reliably determined.