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A collaborative study of nutritional anemia in third trimester pregnancy was performed in seven Latin American countries. Laboratory measurements included hemoglobin level, mean corpuscular hemoglobin concentration (MCHC), serum iron and iron-binding capacity, serum folate, vitamin B12 and albumin. Iron deficiency (transferrin saturation below 15%) was found in 48% of pregnant women, as compared with 21% of nonpregnant females and 3% of male controls of comparable age. The prevalence of folate deficiency (serum folate below 3 ng/ml.) was 10%, 10% and 9% in these three groups, respectively. Vitamin B12 deficiency (serum level below 80 pg/ml.) was found in 15% of pregnant women, but in less than 1% of both control groups. Anemia, as defined by current WHO criteria, was found in 38.5% of pregnant women, 17.3% of nonpregnant women and 3.9% of men. Analysis of the frequency distribution for hemoglobin levels, based on a Gaussian distribution in normal subjects, suggested that a large portion of subjects considered anemic by WHO criteria were normal and that the true incidence of anemia in pregnant and nonpregnant females was 22 and 12% respectively. Correlation analysis indicated that iron deficiency was of major importance as a cause of anemia, while folate lack was contributory only in pregnancy; no relationship could be demonstrated between vitamin B12 deficiency and anemia.

1. Our data indicate that the effectiveness of whole liver in the treatment of nutritional anemia in rats induced by a milk diet is directly proportional to its available iron and copper content. The other constituents in liver are not needed for maximum hemoglobin regeneration on a diet of milk, iron, copper, and manganese. 2. Commercial preparations of liver products with iron or iron and copper vary greatly in their hemoglobin-regenerating efficiency in rats with nutritional anemia. The variation is correlated directly with the iron and copper content of the preparation. When the copper-iron ratio was too wide hemoglobin regeneration was checked, although the iron supply was sufficient for optimum regeneration.

A study of dietary intakes of calories, protein, fat, carbohydrate and iron, along with determinations of hemogram, serum iron, iron binding capacity, transferrin, transferrin saturation and plasma proteins, was done on 26 Day Care children and 15 non-Day Care controls, aged 7 to 32 months, all registered in a Children and Youth health care program. Significant differences favoring the Day Care children were limited to HGB and HCT in the older children, and HGB, HCT, MCV, MCH, transferrin, and iron binding capacity in the younger children. Daily intakes calculated from nutritional history obtained from the parent or observed in the Day Care unit showed average iron intake low in all children. As a result of these findings, it is suggested that children under two years of age be afforded preference over older children when spaces are available in Day Care Centers, and that the dietary intakes of these children be examined carefully to ensure that they are receiving optimal nutrients.

Summary A disease of cattle locally known as “neck ail,” of long standing in certain localities of southeastern Massachusetts, has been described and shown to be identical with nutritional anemia of cattle occurring in various widely scattered portions of the world and known by various names. The disease is characterized by emaciation, loss of appetite, and a diminution in the red blood cells and in the hemoglobin content of the blood of affected animals. It is caused by an insufficient amount of iron in the native forage which in turn is due to a very low content of iron in the soils on which the forage is grown. As with cases reported by other investigators, spectacular recovery has followed the administration of iron compounds to the affected animals. Addition of an iron compound (iron ammonium citrate) to soils from farms where the disease had occurred, resulted in a uniform large increase in the percentage of iron in grasses grown on these soils. This suggests an alternative method for prevention of the disease.

1. (1) Eleven patients with anaemias of pregnancy were studied over a period of 4 months. Six with megaloblastic, one with normocytic, and one with microcytic anaemia were given a high protein dietary supplement, but no haematological response was observed. 2. (2) A study of eight patients with tropical macrocytic anaemia of pregnancy and bone marrows containing “transitional megaloblasts” leads to the proposition that two factors are present in the aetiology of this anaemia as found in the Gambia: 1. i. a haemolytic factor, which ceases directly on delivery and, in the production of which past malarial infection can be suspected of playing a part. 2. ii. a failure of utilization of haemopoietic substances in pregnancy which lasts for at least a week after delivery. The findings are thought to provide evidence that, in the Gambia, dietary deficiency of haemopoietic substances, or direct competition for them between foetus and mother, are not major factors in the production of this anaemia.

Summary The subject of nutritional anemiain infancy and childhood is reviewed, with emphasis on the etiology, the pathogenesis, and the mechanisms of iron metabolism involved. In twenty infants and children with severe nutritional anemia, satisfactory therapeutic results were obtained when oral iron was administered. Every other patient in this series received large doses of ascrobic acid additionally which improved the response to iron therapy. The observations were critically analyzed and evaluated. The hemoglobin values were restored rapidly to a normal range in all cases. The average daily hemoglobin response in the group treated with oral iron alone was 0.205 Gm. The average daily hemoglobin response in the group treated with oral iron and ascorbic acid amounted to 0.347 Gm. The average length of treatment in the first group was twenty-one days, while the same was achieved after seventeen days of therapy in the second group. It is concluded that the oral administration of iron in nutritional anemia of infancy and childhood is equally efficacious as other types of treatment. Apparently ascorbic acid increases the absorption and to some extent may aid the utilization of orally given iron.

The effect of radiant energy upon the metabolism of small doses of Fe in the nutritional anemia of the rat seems to have been little studied. Foster1 produced anemia in rats by milk feeding and observed the effect of radiant energy in preventing and curing this type of anemia. There was a slight but definite effect in increasing the hemoglobin and the number, size and saturation of the red cells.We have made the following studies upon the effect of radiant energy upon both the prevention and cure of nutritional anemia in the rat.Preventive Studies. Young rats at weaning were fed upon whole milk. Daily doses of pure Fe from 0.05 to 0.30 mg. were given, with and without 3/4 hour ultraviolet irradiation of the rat daily, with the General Electric Sunlight Mazda Lamp, Type S-I, at a distance of 4 feet. This lamp has recently been described by Carter.2 Weekly estimations of hemoglobin and red cell counts were made by the technique described by Beard and Myers.8With milk alone, milk plus irradiation, irradiated...

IT IS a well known fact that many pullets become thin, pale, and develop general or specific diseases after they have been in production for a time. Dukes and Schwarte (1932) found no significant correlation between spring egg production and hemoglobin level of the blood. Cook and Harmon (1933), on the other hand, reported that egg production caused a marked drop in hemoglobin level and that it rose again soon after production stopped. If egg production does cause a drop in hemoglobin level of the blood, it would result in abnormal cell activities and predispose the birds to disease. Some feedstuffs and mineral preparations are being advocated by commercial firms as supplements for laying rations to increase their iron content and thus prevent a possible nutritional anemia. The purpose of this paper is to add to and possibly aid in clarifying the existing data on the influence of egg production . . .

Summary Ferrous sulfate, ferric citrate, ferric chloride and colloidal ferric oxide were found ineffective in preventing anemia in rats when added to an exclusive whole milk diet. The addition of a small amount of copper (0.16 mgm. daily) as copper sulfate was quite effective. The addition of both copper and iron proved highly-effective in preventing nutritional anemia in rats. This confirms the work of Hart, Steenbock, Waddell, and Elvehjem (5). The prevention of nutritional anemia in rats fed an exclusive milk diet through the addition of small amounts of copper and iron suggests a method for determining the total nutritive effect (aside from reproduction) of milk produced under various conditions, without the use of a basal ration.

There is no reliable evidence to show that cancer occurs more often in well nourished persons than in persons with nutritional anemia, or vice versa . Obese persons appear to be as susceptible to cancer as emaciated, anemic persons. In the late stages of cancer, however, there may be anemia or deficiency in the quality and quantity of the blood, but this is apparently a result of the cancerous condition and not the cause of it. Anemia is often caused by deficient diet, but it may also be due to inheritance or to a disturbance in function of the blood-forming organs. The work here reported was planned to determine what influence, if any, a nutritional anemia may have upon the growth of transplantable malignant neoplasms in animals.

Summary The diagnosis of those anemias of early infancy which occur during the first four to six weeks of life was considered. This embraces the newborn period when adjustment to extrauterine life takes place. During this time profound alterations occur in various systems, including that of hematopoiesis. A satisfactory evaluation of the blood picture may be obscured by these changes as well as by the changes incident to growth and development. The evidence presented in this paper points to the remarkable adaptation and integration of physiologic processes by which sudden and drastic shifts in blood levels are kept in check in the early newborn period. Recent studies reveal, for instance, that the hemoglobin level is usually sustained or shows only a gradual decline during this period. Similarly, the type of nutritional anemia which depends on maternal iron deficiency is of infrequent occurrence during the first days of life. Adjustments in hematopoiesis may take place at varying rates of speed, and protective mechanisms may be upset. To facilitate the interpretation of the blood disorders of this period, normal blood formation and the forces which control hematopoietic equilibrium during fetal life and in the newborn period have been reviewed. In the light of accumulating information, it is possible to relate some of the manifestations of the anemias of this period to deficiencies of one or more hematopoietic factors. Some of the features of erythroblastosis fetalis and of hemorrhagic disease may be explained on this basis. Retarded elaboration of essential hematopoietic principles by the young infant probably contributes to the pathogenesis of a blood disorder. In addition to its other functions, transfusion may serve as an accelerating influence in the production of these elements by newborn infants. Since erythroblastic or Cooley's anemia, familial hemolytic jaundice and hypoplastic anemia may make their initial appearance during the latter part of the newborn period, it is important to look for certain hematologic features by which these conditions may be recognized.

Our knowledge of some of the many aspects of the problem of anemia has been enlarged recently by studies on the milk anemia of the rat. Thus from the work of the Wisconsin investigators the importance of Cu in Hb regeneration is now generally appreciated. Cu therapy, however, does not present any particular difficulty, while Fe deficiencies and Fe therapy still remain important problems in the clinic. For such investigations milk anemia is a convenient experimental approach. Although much work has been done there is still some uncertainty regarding the response of anemic rats to small doses of Fe.1, 2 Certain investigators3, 4 have reported that glutamic acid supplements Fe in nutritional anemia, but this has not been confirmed by others.5The following experiments were carried out with about 300 rats in order to clarify some of the discrepancies in regard to the effect of Fe in anemia and to determine whether glutamic acid could be employed as an effective vehicle for the administration of minerals in sec...

While our studies on milk anemia1, 2 were in progress, evidence appeared in the literature3, 4 which indicated that cobalt stimulated blood regeneration in nutritional anemia, Therefore, experiment...

Nutritional anemia is common and is found particularly among pregnant women in Malaysia as in other developing countries. Over the 1953-1962 period 73048 women were treated in the Maternity Hospital at Kuala Lumpur Malaysia; 2250 or 3.1% of this group had severe anemia. One half 1066 were investigated fully. In the remainder an accurate diagnosis was not made before treatment was instituted and the type of anemia was classified as "unknown." Of those investigated fully normoblastic iron deficiency anemia was found in 676 (64%) and megaloblastic anemia was found in 373 (35%). The megaloblastic anemia was invariably associated with an iron deficiency anemia and the more severe the anemia the higher was the proportion with a megaloblastic crythropoiesis. The mortality of anemic mothers was significantly higher (15.5/1000) than those with no anemia (3.5/1000). The effects of maternal anemia on the fetus were considerable and include the following: the prematurity rate among infants of anemic mothers was 18.1% 3 times that of infants born to nonanemic mothers; the perinatal loss in the anemic mother was 13.1% twice that of the nonanemic mother (6.8%); and the stillbirth rate among infants born to anemic mothers was 91.0/1000 compared with a rate of 15.7/1000 among infants born to nonanemic mothers. The findings indicate the seriousness of severe anemia in pregnancy. Etiological factors are considered since this will be the basis of rational therapy. Iron deficiency anemia may develop for several reasons. There is usually a dietary deficiency of iron and there may also be a lowered absorption from the gut. Also there may be excessive blood loss due to hookworm and menorrhagia and there are the demands of repeated childbearing. Apart from hookworm infestation insufficient dietary intake of iron was the principal cause of anemia among the women in the study with iron deficiency anemia. Among the women with megatoblastic anemia folic acid was the prime deficiency leading to this type of anemia. The anemia was aggravated by increasing malnutrition as demonstrated by diminished serum albumin and globulin concentration. The diagnosis of severe iron deficiency anemia was made by estimation of the hemoglobin concentration supplemented in some cases by serum iron studies. Megaloblastic anemia in pregnancy can only be diagnosed with accuracy by a bone marrow smear. Consideration of the etiology of anemia in Malaysia led to a standard treatment among the pregnant women studies. The treatment approach is reviewed in detail.

The results of this study indicate clearly that iron fortification of an infant formula, offered to premature infants from the newborn period, affords effective prophylaxis against iron deficiency. Acquisition of hemoglobin iron keeps pace with the rapid growth of these infants. Hematologic observations from the tenth week of life are indistinguishable from those of healthy term infants receiving optimal nutritional care. On the other hand, the majority of premature infants who derive iron solely from iron-fortified and iron-containing solid foods, even when these foods are fed from an early age, develop true iron deficiency anemia. This nutritional anemia can be corrected effectively by the addition to the diet of a formula containing 12 mg. of elemental iron per quart.

Summary and Conclusions As a result of feeding pigeon peas Cajan cajan (L) Millsp. to rats on an anemia-producing diet the following conclusions seem justified: 1. Gandules or pigeon peas exhibit curative properties in this type of anemia. 2. Fresh peas show greater regeneration than the ash of equivalent quantities, when both are fed at levels suboptimal for normal hemoglobin regeneration. 3. It is suggested that experiments designed to produce less than maximum regeneration may show differences in the efficiency of various foods and perhaps throw light on the question of the role of inorganic versus organic constituents in hemoglobin formation.

Pure milk fed to young rats produces severe anemia which finally results in death in the majority of cases. In our studies of the pathological changes which take place during the course of nutritional anemia in the albino rat, the findings in the liver and spleen seem to have considerable value in the differential diagnosis of this type of anemia as contrasted with the infectious type caused by Bartonella muris. All our examined animals showed a severe degree of anemia with an erythrocyte count of less than 3 million per c.mm. and a Hb content of less than 4 gm. per 100 cc. Most of the animals died spontaneously, while 5 were killed during the course of the disease. The spontaneous death of the anemic animals was consistently preceded by a rapid loss of weight during the last days of life. The liver and spleen were weighed and fixed with the other organs in Zenker, alcohol and formalin. Slides for microscopic study were stained with hematoxylin-eosin, van Gieson, Mallory, Bielschovsky, Sudan III and Turnb...

Summary Laboratory rats have been fed a diet of raw whole milk supplementedwith 20 per cent of honey. Rats receiving milk to which 16 per cent sucrose was added served as controls. Rats which received a milk-dark honey mixture ad libitum showedan increase in the hemoglobin content of their blood, while the hemoglobin content of rats fed light honey or sucrose supplement in their milk gradually decreased, The gain in weight as well as the food consumption in the first group was also greater. In paired feeding experiments, it was demonstrated that rats receiving a dark honey supplement were able to maintain their hemoglobin at almost the initial level, while the hemoglobin content of rats fed a light honey supplement declined to a level only about 30 per cent of normal, where it remained almost constant. The hemoglobin content of the blood of the control animals receiving a sucrose supplement fell steadily. When the hemoglobin content of the blood of young rats was reduced by a whole milk diet to 6 or 4 Gm. per 100 c.c. level, the addition of 20 per cent dark honey to the milk caused a gradual increase in the hemoglobin, while the addition of 20 per cent light honey permitted a gradual further decline in the hemoglobin until a level of about 3 Gm. per 100 c.c. was reached. It is concluded that the dark honey can play a role in the preventionand cure of nutritional anemia in rats, while light honey is less effective as a source of the blood-forming mineral elements.

During the study of some 1,300 patients in Malaya suffering from nutritional anaemia, 25 presented with signs of a pure iron-deficiency anaemia, including a normoblastic bone marrow picture. On treatment with parenteral iron little improvement of the anaemia took place and the bone marrow was later found to be grossly megaloblastic. An adequate improvement of the anaemia followed subsequent treatment with folic acid. This sequence of events shows that severe iron deficiency may interfere with the development of megaloblastic changes in the bone marrow, changes which would normally be expected in patients with a folic acid deficiency. Not only is the characteristic peripheral blood picture of a megaloblastic anaemia absent, but also the megaloblastic changes in the bone marrow.

SummaryThe amount of coenzymatically active Vit. B6 was determined in plasma and leukocytes in patients with various diseases. Values for plasma and leukocytes varied widely in all groups examined. A statistically significant decrease of plasma B6 was found only in patients with nutritional anemia and various forms of leukemia. However, the amount of pyridoxal phosphate was very low in individual patients with various other diseases. This may indicate a decreased intake of vitamin in some hospitalized patients or an increased need for it. B6 values in leukocytes were consistently decreased in patients with various forms of leukemia. In contrast, cells from normal bone marrow and from tonsils showed significantly higher amounts of pyridoxal phosphate. The findings are discussed with reference to a specific disturbance in B6 metabolism in some neoplastic conditions.

The concentration of vitamin B12 in blood serum and its excretion in the urine were assayed by the E. coli mutant technic in two patients after total gastrectomy and by use of the more sensitive Euglena gracilis method in four cases of pernicious anemia in relapse and 1 case of well controlled nutritional macrocytic anemia. Following parenteral administration of 100 µg. vitamin B12 intramuscularly to two patients with total gastrectomy, much higher blood levels were observed within the first few hours than those reported by others under similar circumstances in normals. Following oral administration of vitamin B12 together with a potent intrinsic factor concentrate from hog stomach, a rise in blood levels of vitamin B12 was observed in patients with pernicious anemia. The normal serum levels of vitamin B12 could not be maintained, however, for the entire duration of the oral treatment, in spite of the apparent hematologic and clinical remission. The urinary output of vitamin B12 was in all instances less than 0.5 per cent of the total dose of vitamin B12 ingested during the experimental period, in spite of an optimal or suboptimal hematopoietic response obtained. A similar situation existed in patients with total gastrectomy, as well as in the patient with controlled macrocytic nutritional anemia, when vitamin B12 was ingested alone or with intrinsic factor concentrate. The intensity of the obtained hematopoietic response in patients with pernicious anemia indicates the absorption of much larger amounts of vitamin B12 from the intestine than is indicated by the total urinary output of vitamin B12; therefore the anchorage and retention of a large part of vitamin B12 in the storage depots of the body after its absorption from the intestine must occur. A sharp increase in the urinary output of vitamin B12 was observed during or immediately following the hematopoietic response in all patients with pernicious anemia treated orally with vitamin B12 and intrinsic factor concentrate, i.e., coincident with or immediately following the reticulocyte peak in blood. Similar observation was reported by the authors in the previous series of investigations. Of many possible interpretations of this finding, the most plausible appears to be the metabolic release of free vitamin B12 from its complex binding in the body during hyperactivity of the hematopoietic organs and its escape through the kidneys.

I T 15 hoped that Perspectives in Nutrition will review the literature selectively, interpret it moderately and present a spectrum of ideas that will serve as a continual stimulation to nutritional research applied to medical problems.

1. The evidence is submitted from a number of reliable sources that copper is necessary and a specific catalytic agent in haemoglobin formation. 2. The amount of copper present as a contaminant of therapeutic iron is entirely a matter of chance. 3. Copper is present in some foods but in wider variation than iron. In food absorption through processing this source of copper has almost completely been eliminated. 4. In nutritional anemia it is important to be certain of the presence of copper.

Nutritional anemia in childhood is common even in the United States. It is usually due to iron deficiency developing from an inadequate diet, especially an excessive amount of milk. The diagnosis is often easily made. Inadequate intake of iron affects every body system, particularly the gastrointestinal tract. Less common nutritional anemias result from deficiency of folic acid, vitamin B12 or essential amino acids. Treatment is simple and usually quickly effective when proper and specific medication is used.

Summary Six pairs of Holstein male calves were used in a study of the susceptibility of calves to nutritional anemia when fed whole milk exclusively and of the effect of supplementing such a diet with inorganic iron and copper. Physical appearance, growth, determinations of the number of erythrocytes and amount of hemoglobin in the blood, and post-mortem examination showed that the calves on milk alone developed nutritional anemia while those receiving iron and copper in addition to milk did not. Considerable difference in appearance and size of the internal organs was revealed on post-mortem examination. Of particular interest in this connection was the marked difference in size of the testes and spleens, those of the calves receiving the mineral supplements being much larger. The livers of the calves fed iron and copper were found to contain large quantities of these two minerals as compared to the amounts found in the livers of calves fed milk exclusively.