Abraham Stekel

Effect of mild iron deficiency on infant mentaldevelopment scores

To evaluate the effects of short-term iron therapy on developmental test scores of infants with varying stages of iron deficiency, 37 infants, all 15 months of age, were tested with the Bayley Scales of Infant Development before and 11 days after beginning a trial of orally administered iron therapy. They were separated into three groups according to iron status: 12 controls, with normal iron nutrition; 11 with mild anemia, i.e., hemoglobin less than 11.0 gm/dl but greater than 8.5 gm/dl; and 15 with iron deficiency without anemia, i.e., Hgb greater than or equal to 11.0 gm/dl but at least one abnormal biochemical measure of iron nutrition (transferrin saturation, free erythrocyte protoporphyrin, or serum ferritin). The Mental Development Index was significantly lower in the anemic infants before treatment, as compared with that of normal controls. Improvement with iron therapy was also significant in those with anemia and in nonanemic patients with two or more biochemical indicators of iron deficiency. The rise in Mental Development Index was associated with improvement in attention span and cooperativeness. These findings suggest that mild iron deficiency has an effect on infant behavior that is rapidly reversible with iron therapy.

Effect of supplementation with an iron-fortified milk on incidence of diarrhea and respiratory infection in urban-resident infants.

To address the hypothesis that increased infectious morbidity is associated with iron supplementation, 783 randomly selected infants were provided with a powdered full fat cows milk (non-fortified group) and 872 with a powdered acidified full fat cows milk fortified with 15 mg of iron as ferrous sulfate (fortified group). All infants were followed from birth to 15 months of age with a monthly home visit by a nurse who recorded morbidity occurring during the previous 30 days. At 9 months of age, 15% of infants in each cohort were receiving breast milk only; data for these infants were segregated to make the third group. Episodes (mean +/- SD) of diarrhea/infant/year were 1.06 +/- 1.29, 1.14 +/- 1.37, and 0.82 +/- 1.04 for the fortified, non-fortified and breast-fed groups, respectively; the fortified and non-fortified bottle-fed groups had a very similar incidence of respiratory illness; 2.66 +/- 2.07 and 2.74 +/- 2.24 episodes/infant/year, respectively. The incidence of respiratory illness for both bottle-fed groups was significantly higher than that for the breast-fed group (2.22 +/- 1.84 respiratory episodes/infant/year). We conclude that for the infants the tested form of iron fortified milk, which is sufficient to lower iron deficiency anemia, does not result in an increased incidence of diarrhea or respiratory illness.

Prevention of iron deficiency by milk fortification. The Chilean experience.

Olivares, M., Walter, T., Hertrampf, E., Pizarro, F. and Stekel, A. (Hematology Unit, Institue of Nutrition and Food Technology, University of Chile, Santiago, Chile). Prevention of iron deficiency by milk fortification. The Chilean experience.

Effect of an iron fortified milk on morbidity in infancy. A field trial

Abstract The effect of an iron fortified milk on gastrointestinal and respiratory illness was evaluated in a prospective longitudinal field trial in which infants were provided beginning at 3 and continuing through 15 months of age with, either iron fortified 15 mg Fe/l (n=53) or non fortified (n=47) milk. Gastrointestinal and respiratory symptoms and signs were recorded daily. The mean incidence of diarrhea was 1.1 and 1.2 episodes per year per child in the fortified and non fortified groups, respectively. The figures per child/year for respiratory infections were 3.9 and 3.9 respectively. The results demonstrate that iron fortification at doses sufficient to significantly eradicate iron deficiency anemia is not associated with an increased incidence of gastrointestinal and respiratory illness.

Hematologic studies of severe undernutrition of infancy. I. The anemia of prolonged caloric deprivation in the pig.

Extract: These studies were designed to define alterations in erythropoiesis that resulted from prolonged and controlled caloric deprivation. The caloric deprivation in the animal model chosen simulated that experienced by human infants receiving caloric intakes so restricted that infantile marasmus results.The model chosen was the young piglet receiving a diet that would support normal growth when given in adequate amounts. The intake of this diet was so restricted as to stabilize the weight of the animals at 5.0 to 7.0 kg from one to ten months of age.The studies of erythropoiesis in control piglets revealed a relatively high reticulocyte count associated with rapid growth and expansion of the red cell mass during the early months of life. The hematocrit and the hemoglobin levels increased with age, although there was a slight decrease in the total red cell mass per unit of body weight with increasing age.Iron kinetic studies were performed in normal growing pigs (table V). The mean values for plasma iron turnover (mg Fe/100 ml whole blood/24 h) were 2.07 at one month of age, 1.54 at two months of age, and 1.06 at three months of age. The mean percentage of injected Fe59 that appeared in the circulating erythrocytes seven days after injection was 95 at one month, 82 at two months, and 76 at three months of age. These findings are consistent with the presence of a decreasing rate of erythropoiesis and hemoglobin synthesis accompanying the relative decrease in growth rate with progressive age.Animals maintained on a very restricted caloric intake were found to have immediate alterations in erythropoiesis (table VI). Plasma iron turnover in these animals was 2.26 mg on the second day following dietary restriction and only 1.28 mg when measured four days after dietary restriction. After ten days, the value was reduced to 0.88 mg. A prompt decrease in urinary erythropoietin excretion was detected during this time and persisted throughout the period of observation while the animals were on the restricted diet (fig. 3). The appearance of iron in circulating erythrocytes seven days following the injection of Fe59 was found to be 100% when iron was given two days following dietary restriction. When the isotope was given four days following initiation of the restricted diet, 86.5% appeared in the circulating erythrocytes at seven days. A further decrease to 52% was observed in a study initiated ten days after dietary restriction.The alterations in erythropoiesis demonstrated by iron kinetic studies were also reflected by a decrease in the reticulocyte count and by an increase in the myeloid: erythroid ratio in bone marrow examined serially.The measurement of the Cr51 total erythrocyte mass prior to dietary restriction was 24.8 ml/kg (fig. 8). After thirty days on restricted caloric intake, the mean value was 25.8 ml/kg. Erythropoiesis, although decreased, continued at a rate sufficient to maintain a constant red cell mass during this immediate period of caloric restriction.Prolonged caloric deprivation produced a decline in hemoglobin levels and hematocrit in the experimental pigs (fig. 7). The reticulocyte count fell from the level of 5.6 to 1 % or less during the period of dietary restriction and was maintained at the low level of 1 % throughout the period of observation. Cr51 erythrocyte mass, which was maintained at a constant level during the first thirty days of dietary restriction, showed thereafter a progressive fall throughout the period of undernutrition and paralleled the fall in hematocrit (table VIII) . Levels of protein, folate, and iron in serum were maintained within the normal range throughout the period of caloric deprivation.Studies performed in pigs after five to seven months of dietary restriction found plasma iron turnover to be lower than that observed in the control animals and essentially the same as that observed after ten days of diet restriction. After six months of diet restriction, iron utilization was reduced to a maximum utilization of 3 1 to 64 % (fig. 9).After a period ofseven to eight months of dietary restriction, five animals were offered diet ad libitum. Within three to eight days, a prompt increase in erythropoietin excretion was seen; the reticulocyte count increased and, by six days after ad libitum feedings, had reached levels characteristic of normal, rapidly growing pigs. An increase in plasma iron turnover and per cent utilization of iron was measured ten days after initation of ad libitum feedings, and the myeloid: erythroid ratio reflected an increase in erythroid precursors soon after starting ad libitum feedings.The hematocrit decreased promptly after initiation of the ad libitum diet. The lowest level was reached in five days. The Cr51 total red cell mass had increased during the period of falling hematocrit, and the total plasma volume had also greatly increased at this time. The early fall in hematocrit was thus due to the increase in the plasma volume, rather than to any decrease in the circulating erythrocyte mass.Speculation: The availability of an animal model of prolonged caloric deprivation uncomplicated by infection, parasitism, or blood loss has demonstrated that caloric deprivation per se will result in a modest reduction in hematocrit and hemoglobin concentration that is paralleled by a reduction in the total circulating red cell mass. Such animals fail to demonstrate a deficiency of specific nutrients essential for normal erythropoiesis. The finding by others that caloric deprivation may be associated with a hypometabolic state suggests that anemia accompanying caloric deprivation may not be a primary consequence of inadequate nutrition but, rather, a reflection of an adaptive reduction in hemoglobin concentration in the face of a reduced demand for oxygen transport.

Hematologic studies of severe undernutrition of infancy. II. Erythropoietic response to phlebotomy by calorie-deprived pigs.

Extract: These studies have determined the erythropoietic response of the chronically calorie-deprived pig to the hypoxic stress of phlebotomy. Three animals were maintained on diets sufficiently restricted to prohibit weight gain from twenty-one days to six months of age. The animals were anemic, with hematocrit values of 35%, and were subjected to controlled phlebotomy of one-third the total erythrocyte mass. During a subsequent two-month period, two of the animals were given a caloric diet ad libitum and a seven-fold increase in weight, accompanied by active erythropoiesis and an increase in hematocrit, was observed. Phlebotomy studies were repeated after the period of ad libitum feeding. The erythropoietic response to phlebotomy was evaluated in both the undernourished and the rehabilitated pigs by study of erythropoietin excretion, circulating reticulocyte numbers, iron kinetics, Cr51 total RBG mass, bone marrow morphology, and changes in serum iron concentration.When measured on day 2 preceeding phlebotomy, the calorie-deprived animals had very low concentrations of urinary erythropoietin (0.06 U/24 h) which, following blood loss, promptly increased to a concentration of 2.0 U/24 h. A similar prompt response was seen in the rehabilitated animals (fig. 1). Prior to phlebotomy, plasma iron turnover was < 1.0mg/100 ml whole blood/24 h and promptly increased to 1.5–2.0 mg/100 ml whole blood/24 h by four days after phlebotomy (fig. 2). There was a marked increase in iron utilization for erythrocyte production when measured six days following phlebotomy (fig. 3). A decrease in the myeloid: erythroid ratio of the marrow accompanied these other evidences of increasing erythropoiesis (fig. 4). The degree of response in the calorie-deprived and in the rehabilitated animals was similar. The calorie-deprived animals had a higher reticulocyte response to phlebotomy than the animals fed ad libitum, but reestablished the prephlebotomy hematocrit no more rapidly (figs. 5 and 6). The higher reticulocyte counts in the undernourished pigs was shown to be related to less mature reticulocytes entering the circulation following the bleeding stress, reflecting a greater degree of marrow ‘shift’ (fig. 8).Calculation of total erythrocyte production in response to phlebotomy under conditions of severe caloric deprivation and ad libitum feeding demonstrates that a comparable response occurred under both experimental conditions.Speculation: These studies support the hypothesis that anemia accompanying chronic caloric deprivation in the pig is not caused by a primary lack of essential nutrients, but represents an adaptive response to the decreased metabolic needs of the chronically undernourished organism. It is likely that the moderate anemia sometimes seen in marasmic infants is due to a similar mechanism. If such is the case, therapeutic measures such as blood transfusions and administration of various hematinics directed primarily at altering this adaptive phenomenon would appear contraindicated in the management of the marasmic infant.

Effect of early iron deficiency on reactivity of the rat parietal association cortex

The effect of early iron deficiency on the reactivity of the rat parietal association cortex was studied by determining excitability thresholds, fatigability and extension of the responsive field to direct cortical stimulation. Iron deficiency during the period of rapid brain growth caused a significant increase of cortical chronaxie values as well as increased fatigability of direct cortical responses, indicating a detrimental effect on the axodendritic synapses. Since the parietal association area plays an important role in brain association processes, a dysfunction of this cortical area could be a causal link between early iron deficiency and behavioral or learning deficits.

Nutrición de folato en escolares

RESUMEN En un grupo de escolares de baja conditionsocio—economics, se encontro una prevalencia dedeficiencia de acido folico (folato eritrocitario <140 ng/ml) de un 6.0%. Los niveles de folatoencontrados fueron mas bajos que los obtenidosen un grupo de lactantes.REFERENCIAS 1. Olivares M., Anderson M., Llaguno S. y Stekel A.:Folato serico y eritrocitario en cl lactante. Rev. Chil.Pediatr. 54; 246,1983.2. Waters A.H., Mollin D.L.: Studies on the folic acidactivity of human serum. J. Clin. Path. 14: 355, 1961. 3. Hoffrand A. V., Beverly FA., MolUn D.L.: Methodof assay of red cell folate activity and the value ofthe assay as a test for folate deficiency. J. Clin.Path. 19: 17, 1966.4. Weil A., Mawacher E.: Folic acid and pregnancy: Isthere a real problem? ... Schweiz. Med. Wschr. 107: 1943, 1977. 5. Herbert V.: Aseptic addition methods for lactobaci-llus casei assay for folate activity in human serum.J. Oin. Path. 19: 12, 1966.6. Wagner G.: Folic acid. In: Present knowledge inNutrition. Olson, R.G., Broquist, H.P., Chichester,CO., Darby, W.J., Kolbye Jr., A.C. and Stalvey,R.M. The Nutrition Foundation Inc. Washington,D.C., 1984. p. 322-346.7. Herbert V.: Biochemical and hematological lesionsin folic acid deficiency. Am. J. Clin. Nutr. 20: 562,

Folic acid nutrition in marasmic infants

Abstract To determine the prevalence of low folic acid levels in infants with marasmic malnutrition and to study its response to daily supplements of folic acid, a group of 80 malnourished infants 2 to 22 months of age were studied. In 12.5% of the group, serum folic acid levels were under 3ug/l and in 16.3%, red cell folic acid levels were under 140ug/l. In a sub group of 28 infants we determined the levels of folic acid on admission and discharge from a nutritional recovery center. During their hospital stay (median 117 days with a range of 94 to 130) infants received exclusively cows milk with a daily supplement of 100ug of folic acid. On discharge, a significant increase of serum folic levels to normal values was observed. A similar improvement, but not to the same extent, was appreciated in red cell folates. Inadequate quantity of supplementation or short time of observation could explain the lack of complete correction in the erythrocyte folic concentration.

Age-related changes in laboratory measures of iron nutrition in childhood

Abstract In the diagnosis of iron deficiency, age related variations of laboratory indices must be considered. With the purpose of analyzing these variations 154 children 6 to 9 years of age were studies. We determined hemoglobin, serum iron, total iron binding capacity, transferrin saturation, free erythrocyte protoporphyrin and serum ferritin. In order to exclude subjects possibly iron deficient, we analyzed only those children who complied with the following criteria: Hb≥11.9 and serum ferritin≥15 ug/1. For the estimation of the cut point of Fe/TIBC we required, in addition, FEP≤75 ug/dl RBC and for the calculation of FEP we required a transferrin saturation ≥15%. Results show a median and 95% confidence range for transferrin saturation of 26.7% (10.6–41.8) and for FEP of 64 ug/dl RBC (47–99).