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Iron: 197 Research Abstracts

1_ 1991 Jun;58(3):30616.

[Relationship between iron nutrition and nutriment intakes in the menstruating and menopausal women]

[Article in Japanese]

Satoh K.

Medical examinations related to iron nutrition (hemoglobin concentration, serum ferritin concentration and transferrin saturation) and measurements of daily nutriment intakes based on three day dietary records were carried out for 440 female subjects from adolescence to menopause, and the relationships between both parameters were compared. The subjects could be reasonably divided into 3 age groups of menstruating I (1729 years), II (3053 years) women and menopausal (4869 years) women by the oneway analysis of variance. The occurrence of iron deficiency including iron deficient anemia was above 45% both in menstruating I and menstruating II women. In addition, the average amounts of iron intake were 8.7 and 10.2 mg/day in these groups, respectively. These values were below the recommended intake of iron (12 mg/day) for females of these ages in Japan. In menopausal women, the occurrence of iron deficiency decreased to 11.3%, which corresponded to the increase of average iron intake to 11.2 mg/day. Irrespective of age groups, there were almost no significant correlations between the results of medical examinations and the amounts of daily iron intake. Although no improvement in hemoglobin concentration and transferrin saturation was observed in 62 menstruating women, who received 10 mg iron daily as sodium ferrous citrate for 2 months, the average serum ferritin concentrations were significantly increased at 1 and 2 months after the supplement and 2 weeks after they stopped. These therapeutic trials indicate the relationship between iron deficiency and low iron intake in menstruating women. PMID 1880199

2_ 1991 Feb;53(2):5426.

Dietary calcium and iron: effects on blood pressure and hematocrit in young spontaneously hypertensive rats.

Hatton D, Muntzel M, Absalon J, Lashley D, McCarron DA.

Supplemental dietary calcium in spontaneously hypertensive rats (SHRs) aged 2128 d produces a decrease in blood pressure and hematocrit. The simultaneous fall in hematocrit and blood pressure suggests that the changes in blood pressure may be, in part, a consequence of the decrease in hematocrit and reduction in viscosity. To examine this possibility, SHRs aged 21 d were placed on one of four diets varying in iron content. At age 28, the animals showed ironinduced variations in hematocrit (P less than 0.001) but no difference in blood pressure. Subsequent manipulation of the ratio of calcium and iron in the diets of additional groups of animals resulted in variations in hematocrit that were independent of the calciuminduced alterations in blood pressure. We conclude that the effects of calcium on blood pressure are relatively independent of its effects on hematocrit. PMID 1989424

3_ 1991 Jan 6;132(1):356.

[Trichophagia treated successfully by intravenous iron injections]

[Article in Hungarian]

Hadnagy C, Binder P, Grauzer J, Szocs K.

The case of a trichophagic child is presented. Oral and intramuscular iron therapy brought only temporary effect at the age of 3. Seven years later the 10yearold highly intelligent girl ate again hair. She was not anaemic and her serum iron level was not low. Intravenous iron injections applied again ceased immediately the psychic aberration that did not return even after 4 years. The authors are of the opinion that in cases of such psychic anomalies the iron content of the ironrich cerebral ganglia is lower than normal and the disturbance can be ceased by the administration of iron. PMID 1987509

4_ 1990 Dec;30(4):34753.

Effects of training and iron supplementation on iron status of crosscountry skiers.

Pattini A, Schena F.

We have studied the effects of iron treatment on iron deficient crosscountry skiers. Kind and duration of their daily training were also considered. Fortyeight athletes were divided in three balanced groups: Group A received 160 mg ferritinic iron/die, Group B received the same amount of iron and 1 gr of ascorbic acid and Group C was untreated. Blood samples were taken at the start, after two months and four months of supplementation. Hematological and iron status parameters were determined. Average training duration was 80 min a day. Running was the most frequent method of training but also roll and country skiing were commonly used. At the initial sample low serum ferritin values were found in all the three groups (Group A = 23.3 micrograms/l, Group B = 20.9 micrograms/l and Group C = 23.5 micrograms/l). After iron treatment serum ferritin increased in Groups A and B (+67.8% and +63.6% respectively) but was slightly reduced in Group C. Serum iron was unchanged and total iron binding capacity decreased following ferritin increase. Ascorbic acid failed to increase iron absorption in Group B. A significant reduction of haptoglobin (14% and 9% in Group A and B respectively) was also documented. We conclude that crosscountry skiers extensively use running in their training and it may be one of the cause of their poor iron status. Ferritinic iron treatment seems to be effective in replacing iron stores in crosscountry skiers who underwent heavy training. PMID 2079840

5_ 1990 Dec;118(12):13307.

[Irondeficiency anemia in the nursing infant: its elimination with ironfortified milk]

Hertrampf E, Olivares M, Walter T, Pizarro F, Heresi G, Llaguno S, Vega V, Cayazzo M, Chadud P.

We evaluated the effect of ironsupplemented milk on 86 healthy infants who were followed from 3 to 12 months of age. Whole milk was supplemented with 15 mg elementary iron as ferrous sulphate and 100 mg ascorbic acid per 100 g powder. 104 infants received the same milk with no supplement and served as control. All iron nutritional parameters were higher in the supplemented group at 9 and 12 months of treatment (p < 0.01). Irondeficiency anemia was shown in 34% of the control as compared to 0% of the treatment group. The product exhibited excellent tolerance and could therefore be used to eradicate irondeficiency anemia of the infant.

6_ 1990 Nov 25;131(47):25959.

[The incidence of iron deficiency in Hungary among children aged 46 years]

Bernat Sandor I, Szijarto J, Velkey L, Zsiros J, Simon G, Zsigmond G, Kereki E, Kassay L.

The authors found, that the incidence of hypochromic, microcytic anaemia was 4 percent, and more than half of the children were suffered from iron deficiency. The causes are the inadequate daily iron uptake and/or increase iron requirement. It is very important to increase the iron content of the food and/or the prophylactic or therapeutic iron treatment.

7_ 1990 May;63(3):57985.

The effectiveness of various ironsupplementation regimens in improving the Fe status of anaemic rats.

Wright AJ, Southon S.

Less frequent iron supplementation may be equally as beneficial to Fedeficient subjects as routine daily supplementation because of the shortterm suppressive effect of oral dosing with large amounts of Fe on subsequent Fe absorption. In the present study, the possibility that the administration of an Fe supplement every 2nd or 3rd day may be as effective in improving Fe status as a daily supplement was investigated in anaemic rats. Anaemic rats were given a 4 mg Fe supplement every day, on alternate days or every 3rd day, as a single dose with a midday meal or as a multiple dose with a morning, midday and evening meal. A lowFe diet (13 mg/kg) was given at all other times. After 7 d, erythrocyte count, packed cell volume, mean cell volume, haemoglobin concentration and total liver Fe were measured and compared with those of mealfed rats which had not been given any supplemental Fe. Rats which received a supplement every 3rd day, a total supplement of 12 mg, had a similar Fe status to those receiving a daily supplement, a total supplement of 28 mg. Administration of the supplement as a multiple, rather than as a single dose did not improve recovery from the Fe deficiency. It is suggested that less frequent supplementation with a smaller total amount of Fe, should be considered in human subjects. Such a regimen would minimize unpleasant sideeffects of oral Fe therapy, decrease the risk of adverse effects of Fe on the absorption of other essential minerals and substantially cut the cost of supplementation programmes. PMID 2383534

8_ 1990;7(23):17781.

Iron and the risk of cancer.

Stevens RG.

Four epidemiological studies have been performed that are generally consistent with the hypothesis that increased available body iron stores increase the risk of cancer or of general mortality. In a study based on the First National Health and Nutrition Examination Survey in the United States (NHANES), 232 men who developed cancer over a ten year period had a mean transferrin saturation of 33.1% at least 4 years before diagnosis, whereas 3,113 men who did not develop cancer had a transferrin saturation of 30.7% (p = 0.002). The hypothesis is based on two possible biological mechanisms. First, iron can catalyse the production of oxygen radicals and these may be proximate carcinogens. Second, iron may be a limiting nutrient to the growth and replication of a cancer cell. There are at least five areas of potential research related to iron and cancer based on these biological mechanisms: (1) etiology of cancer, (2) etiology of radiationinduced cancer, (3) prognosis after cancer diagnosis, (4) cancer risk resulting from therapy, and (5) interactions with other biochemical factors. An unexpected finding of the human studies done to date has been a highly significant negative association of serum albumin and long term cancer risk. Serum albumin is lower in smokers and older people, however, the negative association persists after controlling for these factors. PMID 2146450

9_ 1989 Dec;65(10):105066; discussion 10858.

Iron and learning potential in childhood.

Lozoff B.

Cognitive function. There is reasonably good evidence that mental and motor developmental test scores are lower among infants with iron deficiency anemia. Although the research on cognitive function in iron deficient older children and adults is sparse and diverse, it suggests that there may be alterations in attentional processes associated with iron deficiency. Iron therapy has not yet been shown effective in completely correcting many of the observed disturbances. Although some aspects of cognitive function seem to change with iron therapy, lower developmental. I.Q., and achievement test scores have still been noted after treatment. The behavioral effects of irondeficiency anemia may be due to changes in neurotransmission. However, the biochemical bases are not yet completely understood. Noncognitive disturbances. A variety of noncognitive alterations during infant developmental testing has also been observed, including failure to respond to test stimuli, short attention span, unhappiness, increased fearfulness, withdrawal from the examiner, and increased body tension. Exploratory analyses suggest that such behavioral abnormalities may account for poor developmental test performance in infants with iron deficiency anemia. These studies indicate the fruitfulness of examining noncognitive aspects of behavior such as affect, attention, and activity, in addition to specific cognitive processes. Activity and work capacity: There has been a steady accumulation of evidence that irondeficiency anemia limits maximal physical performance, submaximal endurance, and spontaneous activity in the adult, resulting in diminished work productivity with attendant economic losses. The relative importance of central and peripheral mechanisms underlying these effects, the extent to which anemia or iron deficiency separate from anemia is responsible, and the counterpart in infants and children remain to be established. This essay has examined recent evidence from research on central nervous system biochemistry and from human studies that iron deficiency adversely affects behavior by impairing cognitive function, producing noncognitive disturbances, and limiting activity and work capacity. The body of research taken as a whole provides increasingly persuasive arguments for intensifying efforts to prevent and treat iron deficiency anemia. PMID 2698245

10_ 1989 Dec;119(12):198491.

Iron and folate utilization in reproducing swine and their progeny.

O'Connor DL, Picciano MF, Roos MA, Easter RA.

The purpose of this investigation was to assess the usefulness of maternal and neonatal swine as animal models for studying iron (Fe) and folate nutrition during reproduction and growth. Sows (n = 18) were fed a purified diet containing 0.6 mg folate/kg diet and either 25 (Fe) or 125 (Fe+) mg iron/kg diet throughout gestation and lactation. Litters were culled to eight on d 2 of lactation and four piglets/litter were given an intramuscular injection of iron dextran (100 mg/kg body wt). Plasma and red blood cell folate concentrations among all sows decreased (greater than 50%) after conception (P less than 0.001). Plasma folate concentration of Fe sows was 47% and 69% of Fe+ sows on d 7 and 21 of lactation, respectively (P less than 0.05). All sows secreted milk that contained low levels of folate (1236 nmol/l) and was devoid of longchain folylpolyglutamates. While mean milk folate concentration significantly decreased after d 1 of lactation among Fe sows, no such decrease was observed in milk from Fe+ sows (P less than 0.05). Liver folate concentration was significantly reduced in piglets nursed by Fe sows and given intramuscular iron dextran. It is concluded that there is an increased dietary requirement for folate and iron during reproduction in swine, and that current recommended amounts of folate (0.6 mg/kg diet) and iron (80 mg/kg diet) may be underestimates of requirements for reproduction. Further, results show that iron nutrition may alter folate utilization in maternal and neonatal swine. PMID 2621491

11_ 1989 Nov;62(3):70717.

The effect of differences in dietary iron intake on 59Fe absorption and duodenal morphology in pregnant rats.

Southon S, Wright AJ, FairweatherTait SJ.

The effect of iron intake on 59Fe absorption throughout pregnancy, and on maternal and fetal Fe status towards the end of pregnancy, was investigated in rats. The influence of pregnancy and dietary Fe on duodenal morphology was also studied. Female rats were fed on a diet containing 17 or 100 mg Fe/kg for 2 weeks before and throughout pregnancy. 59Fe absorption was measured on days 1 or 2, 8 or 9 and 17 or 18 of pregnancy, and maternal and fetal Fe status was determined on days 18 or 19. Pregnancy resulted in a fall in haemoglobin (Hb) concentration. Compared with nonpregnant counterparts, total liver Fe was reduced in the lowFe group, but not in the highFe group, indicating that the fall in Hb in the highFe rats was not associated with an Fedeficient state. 59Fe absorption in rats fed on both diets increased throughout pregnancy, demonstrating that Fe supplementation of the diet, to a level that prevented the development of Fedeficiency, failed to suppress an increase in absorption. Fetal weight appeared to be an important determinant of the efficiency of Fe absorption in late pregnancy. Poor maternal Fe status was accompanied by a reduction in fetal Fe concentration but results also suggested that fetuses were partly protected from maternal Fedeficiency. Pregnancy resulted in increased duodenal circumference and villus dimensions, whilst high dietary Fe reduced duodenal growth in both pregnant and nonpregnant animals. The relevance of this finding is discussed. It was concluded that, in rats, pregnancy per se causes an enhancement in Fe absorption and that the degree of enhancement is in part related to fetal mass. PMID 2605160

12_ 1994 Dec;44(12):2845.

Anaemia in children: Part II. Should primary health care providers prescribe iron supplements by the observation and presence of assumed symptoms?

Thaver IH, Baig L, InamulHaq, Iqbal R.

The dilemma of private practitioners is whether to prescribe or not to prescribe iron supplements on suspicion of anaemia. This cross sectional study was done in an urban squatter settlement with a primary health care centre to assess the significance of symptoms and a history of associated diseases in the diagnosis of anaemia. A total of 321 children were sampled from 1800 children < 5 years of age in a population of 11,000, by systematic random sampling. Mothers were asked about the presence of assumed associated symptoms and diseases which were listlessness, irritability, anaemia, pica, poor weight gain, diarrhoea, acute respiratory infection and malaria in last 3 months. There was significant association between anaemia (Hb < 11 gms%) and irriability (P < .02), anorexia for solid foods (P < .04), pica (P < .001), episode of diarrhoea (P < .001) and poor weight gain (P < .006). There was no significant association between malaria, cold, cough and anaemia. Children with these symptoms complex should receive iron supplements. PMID 7861585

13_ 1994 Dec;86(3):27385.

Ischemia/reperfusion injury is aggravated by an iron supplemented diet and is partly prevented by simultaneous antioxidant supplementation.

van Jaarsveld H, Kuyl JM, Wiid NM.

In humans high levels of storage iron as well as low iron binding capacity are considered risks for ischemic heart disease development. The aim of this study was to determine whether a diet containing iron to a concentration of the recommended upper limit alters the degree of myocardial ischemic/reperfusion injury on rats and whether simultaneous antioxidant supplementation had any effect. Results indicate that the iron supplemented diet increased the degree of oxidative injury while simultaneous antioxidant supplementation prevented much of this increase. The mechanism for this was probably an elevated hydroxyl radical production due to the enlarged transit iron pool. PMID 7712104

14_ 1994 Oct;27(10):234958.

Effect of mild iron overload on liver and kidney lipid peroxidation.

Galleano M, Puntarulo S.

1. Hepatotoxicity is the most common finding in patients with iron overload since the liver is the major recipient of iron excess, even though the kidney could be a target of iron toxicity. The effect of iron overload was studied in the early stages after irondextran injection in rats, as a model for secondary hemocromatosis. 2. Total hepatic and kidney iron content was markedly elevated over control values 20 h after the iron administration. Plasma GOT, GPT and LDH activities were not affected, suggesting that liver cell permeability was not affected by necrosis. 3. Spontaneous liver chemiluminescence was measured as an indicator of oxidative stress and lipid peroxidation. Light emission was increased fourfold 6 h after iron supplementation. 4. Increases in the generation of thiobarbituric acid reactive substances (TBARS in liver and kidney homogenates were detected after iron administration. 5. The activities of catalase, SOD and glutathione peroxidase were determined. Enzymatic activities declined in liver homogenates by 25, 36 and 32%, respectively, 20 h after iron injection. These activities were not affected in kidney as compared to control values, except for SOD activity that was decreased by 26%. 6. The content of alphatocopherol was decreased by 31% in whole kidney homogenates and by 40% in plasma. 7. Our data indicate that lipid peroxidation occurs after mild iron overload both in liver and kidney. Enzymatic antioxidants are consumed significantly in liver and alphatocopherol content decreases in kidney, suggesting an organspecific antioxidant effect. PMID 7640623

15_ 1994 Oct;125(4):52734.

Comment in: J Pediatr. 1994 Oct;125(4):5778.

Prevention of iron deficiency and psychomotor decline in highrisk infants through use of ironfortified infant formula: a randomized clinical trial.

Moffatt ME, Longstaffe S, Besant J, Dureski C.

OBJECTIVE: To determine the efficacy of ironfortified infant formula in preventing developmental delays and abnormal behavior. DESIGN: Doubleblind, randomized, controlled trial. SETTING: Urban hospital clinic. PARTICIPANTS: A total of 283 healthy, bottlefed infants from very low income families. Children with prematurity, low birth weight, and major anomalies and those who had received more than 2 weeks of evaporatedmilk feedings were excluded. The groups were similar for sociodemographic background variables. Fiftyeight infants (20.5%) dropped out before any outcome data were gathered; 225, 204, 186, and 154 remained at 6, 9, 12, and 15month assessments, respectively. INTERVENTION: Ironfortified formula (12.8 mg iron per liter) versus regular formula (1.1 mg iron per liter). MAIN OUTCOME MEASURES: Iron status was measured on venous blood by determination of hemoglobin, serum iron and ironbinding capacity, serum ferritin, and free erythrocyte protoporphyrin values. The Bayley Scales of Infant Development (mental and psychomotor indexes) and two factors of the Infant Behavior Record (test affect and task orientation) were the outcomes of interest. RESULTS: All measures of iron status were significantly different between groups (p < 0.001). Psychomotor development patterns differed between groups (F3,520, 3.4; p = 0.02) with time. Mean values were similar at 6 months but differed at 9 and 12 months of age (p < 0.001), with a decline of 6.4 points in the regularformula group. By 15 months of age the differences were no longer significant (p = 0.23). Mental development and behavior were not affected. CONCLUSIONS: Ironfortified formula significantly reduced iron deficiency in a highrisk group of infants and prevented a decline in psychomotor development quotients. This effect may be transient, and its longterm significance needs further study.

16_ 1994 Sep;94(9):10239.

Nutritional implications of recombinant human erythropoietin therapy in renal disease.

Sanders HN, Rabb HA, Bittle P, Ramirez G.

The treatment of anemia in patients with renal failure has been dramatically changed with the development of recombinant human erythropoietin (rHuEPO). This review discusses the pathogenesis of the anemia renal failure and the biology of erythropoietin. Causes of poor response to rHuEPO therapy are outlined, and the importance of adequate available iron is highlighted. Parameters used to measure iron adequacy include serum iron levels, transferrin saturation, and ferritin levels. Other nutritional deficiencies, such as folic acid and vitamin B12, can also impair rHuEPO response. Clearly, the advent of rHuEPO treatment for patients with renal failure and anemia has brought another dimension to the care of these patients. Optimal nutrition management is critical for the success of this new agent. PMID 8071484

17_ 1994 Aug;60(2):28692.

Evaluation of effectiveness of ironfolate supplementation and anthelminthic therapy against anemia in pregnancya study in the plantation sector of Sri Lanka.

Atukorala TM, de Silva LD, Dechering WH, Dassenaeike TS, Perera RS.

Intervention measures against anemia available to plantation workers during pregnancy include fortified food supplements (thriposha) and ironfolate supplements containing 60 mg elemental Fe. The effectiveness of these intervention measures was studied in 195 subjects whose iron and nutritional status were assessed at < 24 and > 32 wk of gestation. Taking thriposha conferred no significant benefit on maternal nutritional status, probably because sufficient amounts were not consumed. An increase in the duration of ironfolate supplementation to > 17 wk caused a significant positive change (P < 0.01) in hemoglobin, whereas an increase in the dose frequency had no significant benefit. Anthelminthic therapy in addition to ironfolate supplements caused a significant positive change in hemoglobin (P < 0.001) and serum ferritin (P < 0.005) compared with no supplementation. Thus, anthelminthic therapy significantly increased the beneficial effects of iron supplementation on hemoglobin concentration and iron status. PMID 8030609

18_ 1994 Jun;59(3):1303.

[Antianemia therapy with prophylactic administration of Fe2+ in normal pregnancy and its effect on prepartum hematologic parameters in the mother and neonate]

Roztocil A, Charvatova M, Harastova L, Zahradkova J, Studenik P, Sochorova V, Vajcikova H, Drastichova V, Burnog T, Pilka L.

Eightyfour nonanaemic pregnant women were treated, starting between the 20th24th week of Pregnancy, with Actiferrin Compositum1 capsule per dayfrom the 36th with 2 capsules per day up to childbirth. The group was compared with the results in 57 nonanaemic not treated pregnant women. Haematological parameters were recorded before the onset of treatment, during the first stage of labour and in neonates on the first day after delivery. By means of the nonpaired ttest no significant differences were disclosed between the groups; nevertheless the percentage values of haemoglobin, haematocrit, erythrocytes and serum iron were higher in the treated group, as compared with the nontreated one. Also the ferritin values in neonates of the nontreated group were lower, as compared with the treated group. The paired ttest was highly significant in the Actiferrin treated patients as regards haemoglobin, haematocrit and transferrin values. The results provide evidence that it is indicated to administer as a routine measure Actiferrin Compositum to all pregnant women as prevention of prepartum anaemia of the mother and low ferritin levels in the neonate.

19_ 1994 May;59(5 Suppl):1233S1237S.

Iron status of vegetarians.

Craig WJ.

An appropriately planned wellbalanced vegetarian diet is compatible with an adequate iron status. Although the iron stores of vegetarians may be reduced, the incidence of irondeficiency anemia in vegetarians is not significantly different from that in omnivores. Restrictive vegetarian diets (eg, macrobiotic) are associated with more widespread irondeficiency anemia. Western vegetarians who consume a variety of foods have a better iron status than do those in developing countries who consume a limited diet based on unleavened, unrefined cereals. Whereas phytates, polyphenolics, and other plant constituents found in vegetarian diets inhibit nonhemeiron absorption, vitamin C, citric acid, and other organic acids facilitate nonhemeiron absorption.

PMID 8172127

20_ 1994 Apr;13(2):198202.

Drinking water as an iron carrier to control anemia in preschool children in a daycare center.

DutradeOliveira JE, Ferreira JB, Vasconcellos VP, Marchini JS.

OBJECTIVE: Several foods have been used as iron (Fe) carriers to fight widespread global Fe deficiency and anemia. This paper describes the longitudinal effect of Fefortified drinking water given to a group of Brazilian preschool children. DESIGN: The experimental design included 31 preschool children who attended a daycare institution. Hemoglobin and serum ferritin were the blood parameters used to check the Fe status. Fe++ sulfate (20 mg Fe/L) was added daily to their drinking water container and measurements were obtained before the addition, 4 and 8 months later. RESULTS: The number of Fedeficient children decreased drastically after they started drinking the Feenriched water. Mean hemoglobin values increased from 10.6 to 13.7 g/dL and serum ferritin from 13.7 to 25.6 micrograms/L. There were no problems related to the salt addition or to the children drinking the Feenriched water. CONCLUSION: Feenriched drinking water was shown to be a practical alternative to supply Fe to children attending a daycare institution.

PIP: Iron deficiency affects more than one billion people worldwide, although it is most common among young children and women of childbearing age. Poor iron status has severe nutritional and health consequences. The authors describe the longitudinal effect of ironfortified drinking water given to a group of Brazilian preschool children as a way of combatting iron deficiency and anemia. The statuses of 31 preschool children attending a daycare institution for low socioeconomic families in Ribeirao Preto were followed from November 1990 to October 1991. Iron sulfate was added daily to subjects' drinking water container. Measurements of hemoglobin and serum ferritin levels in the children were taken before the addition and four and eight months later to evaluate iron status. Mean hemoglobin values increased from 10.6 to 13.7 g/dL and serum ferritin from 13.7 to 25.6 ug/L with no problems reported related to the salt addition or to the children drinking the ironenriched water. The number of irondeficient children decreased drastically after they began drinking the ironenriched water. It may therefore be concluded that ironenriched drinking water is a practical alternative to supply iron to children attending a daycare institution. PMID 8006302

21_ 1993 Dec;53(8):78991.

The effect of daily lowdose iron supplements in female blood donors with depleted iron stores: comparison with female nondonors.

BorchIohnsen B, Halvorsen R, Stenberg V, Flesland O, Mowinckel P.

Female blood donors with serum ferritin < or = 20 micrograms l1 and haemoglobin > 120 g l1 participated in an iron supplement study with two different lowdose supplements in a period without donations. Comparable nondonors served as controls. Serum ferritin, haemoglobin and transferrin were determined. Increases in serum ferritin and in haemoglobin, and decrease in transferrin were highly significant (p < 0.01) in both donor groups. In one of the nondonor groups the increase in serum ferritin and decrease in transferrin were highly significant (p < 0.01), while in the other only transferrin changed significantly (p < 0.03). The increases in serum ferritin and haemoglobin over a 5month period were significantly higher among donors (p < 0.001) than among nondonors. We interpret the results to mean that the donors have a more efficient iron absorption. PMID 8140388

22_ 1993 Dec;11(4):2636.

Iron supplementation in pregnancy. General practitioners' compliance with official recommendations.

Eskeland B, Malterud K.

OBJECTIVETo compare general practitioners' routines regarding iron supplementation in pregnancy with national recommendations. DESIGN: Mailed questionnaire to general practitioners. SETTING: A county in western Norway. SUBJECTS: 184 general practitioners. MAIN OUTCOME MEASURES: Descriptive registration of reported routines regarding assessment and supplementation of iron. RESULTS: 11% of general practitioners reported complete adherence to the national programme recommending iron supplements for everyone in the second half of pregnancy and use of sferritin estimation if Hb falls below 11 g/dl. 36% of the doctors prescribed iron supplements routinely irrespective of iron status. 87% reported use of sferritin estimation in antenatal care; usually on indication of low Hb, almost 20% as a routine screening in all pregnancies. CONCLUSION: General practitioners' compliance with national recommendations for iron supplementation in pregnancy is very low and probably reveals a need both for a review of the national recommendations and for an approach to increase compliance with given standards. PMID 8146510

23_ 1993 Dec;40(34):1917.

Influence of living conditions on the incidence of anemia and effects of health guidance and diet supplementation on recovery from anemia of women in fishing villages.

Fujii M, Miyoshi T, Iuchi A, Goto H, Ishimoto H.

Studies were made on the relationship between the incidence of anemia and living conditions of women in fishing villages in Tokushima prefecture, and also on the effects of health guidance and supplementation of the diet with iron enriched food on recovery from anemia. With regard to economic conditions, Hb values were found to be higher in women who spent more money on food and who had much leisure time compared with working hours. With regard to diet, Hb values were higher in women with higher intakes of animal protein and vitamin C. Intake of vitamin C was significantly higher in a group with hemoglobin value of over 12.0 g/dl than in a group with hemoglobin value of under 12.0 g/dl. The cumulative recovery rate from anemia of women receiving health guidance was 61.5% and the cumulative recovery rate from anemia of women receiving Tsukudani (a preparation of small dried sardines) enriched with iron for 60 to 105 days (30 to 75 mg iron per day: average 59.3 mg per day) was 53.3%. But the recovery rate of serum iron was lower than those of Hb and Ht, being about 40% on the average. PMID 8184416

24_ 1993 Nov 27;342(8883):13258.

Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia.

Suharno D, West CE, Muhilal, Karyadi D, Hautvast JG.

Nutritional anaemia, thought to be caused by iron deficiency, affects 5070% of pregnant women in the developing world. The influence of vitamin A and iron supplementation was studied in anaemic pregnant women in West Java, in a randomised, doublemasked, placebocontrolled field trial. 251 women aged 1735 years, parity 04, gestation 1624 weeks, and haemoglobin between 80 and 109 g/L were randomly allocated to four groups: vitamin A (2.4 mg retinol) and placebo iron tablets; iron (60 mg elemental iron) and placebo vitamin A; vitamin A and iron; or both placebos, all daily for 8 weeks. Maximum haemoglobin was achieved with both vitamin A and iron supplementation (12.78 g/L, 95% Cl 10.86 to 14.70), with onethird of the response attributable to vitamin A (3.68 g/L, 2.03 to 5.33) and twothirds to iron (7.71 g/L, 5.97 to 9.45). After supplementation, the proportion of women who became nonanaemic was 35% in the vitaminAsupplemented group, 68% in the ironsupplemented group, 97% in the group supplemented with both, and 16% in the placebo group. Improvement in vitamin A status may contribute to the control of anaemic pregnant women.

25_ 1993 Nov;58(5):6226.

Evaluation of a gastric delivery system for iron supplementation in pregnancy.

Simmons WK, Cook JD, Bingham KC, Thomas M, Jackson J, Jackson M, Ahluwalia N, Kahn SG, Patterson AW.

The present investigation was undertaken to assess the efficacy of oral iron supplementation during pregnancy by using a gastric delivery system (GDS). Three hundred seventysix pregnant women between 16 and 35 y of age and 14 and 22 wk gestation were selected if mild anemia was present (hemoglobin concentration 80110 g/L). The participants were randomly assigned to one of three study groups given no iron, two FeSO4 tablets (100 mg Fe) daily, or one GDS capsule (50 mg Fe) daily. Blood was obtained initially and after 6 and 12 wk for measurement of red blood cell and iron indexes, including serum transferrin receptor. There was a significant and comparable improvement in hematologic and ironstatus measurements in the two groups of women given iron whereas iron deficiency evolved in women given no iron supplement. We conclude that by eliminating gastrointestinal side effects and reducing the administration frequency of an iron supplement to once daily, a GDS offers significant advantages for iron supplementation of pregnant women. PMID 8237866

26_ 1993 NovDec;111(6):43944.

Effect of oral iron therapy on physical growth.

Morais MB, Ferrari AA, Fisberg M.

In order to evaluate the effects of iron therapy on weight and height, we studied 65 children with a mean age of 32 months who were assigned to oral iron therapy with 45 mg/kg/day of elemental iron as ferrous sulfate or ferric hydroxide polymaltose for 8 weeks. The medicine was distributed to the patients and its consumption was checked fortnightly. Statistically significant increases in hemoglobin, serum iron and transferrin levels and in transferrin saturation and ferritin levels were observed. The weightforage and weightforheight Zscores were determined using the ANTHRO computer software (CDC/WHO) which, based on birth and examination dates, permits age estimates with centesimal accuracy for the months using the National Center for Health Statistics (NCHS) standards. Mean Zscores before and after iron therapy demonstrated a significant increase in weightforage (Z = 0.53 after, P < 0.01) and weightforheight (Z = 0.19 before and 0.08 after, P < 0.01) indices, but not in the heightforage index (Z = 0.46 before and Z = 0.46 after iron therapy). A significant decrease in the number of children with inadequate weightforage (< 90%)) and weightforheight (< 90%) indices was observed after iron therapy in patients aged less than 60 months. In conclusion, oral iron therapy for a period of 8 weeks led to a significant weight gain. PMID 8052789

27_ 1993 Sep;58(3):33942.

Decreased rate of stunting among anemic Indonesian preschool children through iron supplementation.

Angeles IT, Schultink WJ, Matulessi P, Gross R, Sastroamidjojo S.

Effects of iron supplementation on growth and hematological status of Indonesian anemic preschool children with low weightforage were investigated. A treatment group (n = 39) received daily supplements of 30 mg Fe and 20 mg vitamin C, whereas a control group (n = 37) received 20 mg vitamin C only for a period of 2 mo. Supplement allocation was double blind. At the start and finish of the study, body weight, height, food intake, and hemoglobin and serum ferritin concentrations were determined. Only the treatment group showed a significant increase in all hematological values (P < 0.001). Height and weight of all children increased (P < 0.01). Increases in height and heightforage Z score in the treatment group were larger (P = 0.001) than the increase in the control group. The positive effect of iron supplementation on linear growth was not caused by increased food intake, but seems to be influenced by decreased morbidity. Iron supplementation may be a relatively inexpensive way to help decrease the high prevalence of stunting. PMID 8237843

28_ 1993 Aug 20;113(19):24145.

[Do we need new guidelines on iron supplementation during pregnancy?]

BorchIohnsen B, Halvorsen R, Andrew M, Matheson I, Rytter E, Forde R, Toverud EL.

Studies have shown that the present official Norwegian recommendations on iron supplementation during pregnancy are not followed. A meeting was arranged in February 1993 to discuss the need to change the recommendations. The article describes the conclusions of the panel. It was proposed that the iron status of the pregnant woman, determined as serum ferritin concentration, should be measured early (before the 15th week of gestation) and iron supplement should be given as selective prophylaxis based on the serum ferritin level. The Directorate of Public Health has been asked to issue new recommendations. PMID 8378906

29_ 1993 Aug;27(4):26670.

[Iron supplementation effects on zinc bioavailability in a regional diet of northeastern Brazil]

Pedrosa LF, Cozzolino SM.

The effects of supplementation with iron on the zinc bioavailability of the regional diet of northeastern Brazil (RDN), were investigated. One assay with Wistar rats, feed on RDN and control diets was carried out. The RDN diets contained 16 mg Zn/kg and levels of 35 mg, 70 mg and 140 mg Fe/kg, respectively. The control diets were prepared according to the standards of the Committee on Laboratory Animal Diets, with levels of protein, iron and zinc identical to those of RDN diets. Index of apparent absorption and zinc retained in the femur of the animals were the parameters utilized to measure zinc bioavailability. The results demonstrated that the supplementation with iron decreased the zinc bioavailability, and the effects were seen to affect diet quality and the Fe:Zn ratio. This fact must be taken into consideration in practices such as the fortying of foodstuffs and the administration of vitaminmineral supplements to populations with nutritional deficiencies. PMID 8209158

30_ 1993 Aug;40(6):45665.

Treadmill exercise of calves with different iron supply, husbandry, and work load.

Piguet M, Bruckmaier RM, Blum JW.

Experiments were designed to study physiological responses of male veal calves to treadmill exercise, dependent on iron intake (20, 35, and 50 mg of iron/kg of milk powder, respectively). Calves were fattened from 75 to 180 kg BW and were either restrained or could freely move on straw litter. The ADG and feed utilization as well as haemoglobin and the plasma iron concentration were positively influenced by iron intake (P < or = 0.05). At the end of the fattening period, calves walked on a treadmill at 0.8, 1.1, or 1.3 m/s for 15 min. Resting values of all cardiorespiratory parameters were similar in all groups. During exercise, heart rate, respiratory rate, respiratory minute volume, and oxygen consumption increased and after 3 min reached steadystate values, which depended on work load. The except was respiratory rate (which reached a maximum already at the lowest speed) and oxygen extraction rate (which remained at basal level during exercise, but in part decreased after walking). In calves fed the least amount of iron, hence with the lowest haemoglobin concentrations, oxygen consumption was lower than in other groups. In addition, cortisol concentrations increased most markedly during exercise in calves fed the least amount of iron. PMID 8237180

31_ 1993 Jul;69(1 Spec No):1923.

Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity.

Bechensteen AG, Haga P, Halvorsen S, Whitelaw A, Liestol K, Lindemann R, Grogaard J, Hellebostad M, Saugstad OD, Gronn M, et al.

The effectiveness of recombinant human erythropoietin (rHuEpo) in raising haemoglobin concentrations in very low birthweight infants was examined in a randomised multicentre study. Twenty nine 'healthy' appropriate for gestational age infants with birth weights 9001400 g entered the study at 3 weeks of age. All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age. Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l. Fourteen infants were randomised to receive 100 U/kg rHuEpo subcutaneously three times a week from week 3 to week 7; 15 infants served as controls. After one week reticulocyte and haemoglobin concentrations were significantly higher in the rHuEpo treated group and the haemoglobin values remained significantly higher throughout rHuEpo treatment and at the concentrations observed in full term infants. No adverse effects were associated with the treatment. In stable very low birthweight infants with optimal iron and protein intakes, moderate dose rHuEpo can produce significant gains in red cell production that may be clinically useful. PMID 8346946

32_ 1993 JulSep;39(3):M57880.

Erythropoietin with oral iron in peritoneal and hemodialysis patients. A comparison in an inner city population.

Raja R, Bloom E, Goldstein M, Johnson R.

Studies on the comparative efficacy of erythropoietin (rHuEPO) in chronic hemodialysis (HD) and peritoneal dialysis (PD) patients are scarce. The authors compared the use of rHuEPO in 74 stable patients on hemodialysis with 24 on chronic peritoneal dialysis. All patients were on oral iron supplements. In PD patients, hematocrits were 23.1 and 30.1%, rHuEPO dose 80.9 and 89.0 U/kg/wk, whereas in HD patients, hematocrits were 21.2 and 27.5 and rHuEPO dose was 140.2 and 165.0 U/kg/wk at initiation and 6 months, respectively. Serum iron and transferrin saturations were unchanged in peritoneal, but decreased in hemodialysis patients on rHuEPO therapy. These findings suggest that rHuEPO is more effective in peritoneal dialysis patients than in hemodialysis patients receiving oral iron. The improved efficacy of rHuEPO in peritoneal dialysis may be due to decreased blood loss, subcutaneous administration, or better removal of inhibitors of erythropoiesis. Peritoneal dialysis may be more cost effective and desirable than hemodialysis for rHuEPO dependent or resistant patients. PMID 8268603

33_ 1993 Jul;57(3):20911.

Influence of low dietary iron and iron overload on urethaninduced lung tumors in mice.

Omara FO, Blakley BR.

Weanling male CD1 mice were fed low iron (7 ppm), control (120 ppm) and iron loaded diets (3000 or 5000 ppm) for 19 weeks. After seven weeks, the mice received 1.5 mg urethan/g ip, and tumor development was evaluated 12 weeks later. The low iron diet increased the incidence of lung adenomas by 86%. The iron loaded diets did not influence adenoma development. Tumor size was unaffected by iron status (p = 0.297). These results indicate that low iron body status promotes tumor development and are inconsistent with the hypothesis that excess iron promotes cancer growth and that low iron protects against tumor growth. PMID 8358683

34_ 1993 Jul;44(1):2934.

Iron status and growth of rats fed different dietary iron sources.

Kapoor R, Mehta U.

The present study was carried out to investigate the availability of iron from spirulina, whole wheat, whole egg and standard ferrous sulphate in terms of haemoglobin formation, serum and tissue iron levels. Male albino Wistar rats were first depleted of iron by giving lowiron diet (9 ppm) and bleeding 12 ml blood at weekly intervals for a period of 21 days. The anaemic rats were repleted with iron sources at a level of 35 ppm for 21 days. Rats receiving whole egg gained significantly (p < 0.01) higher weight than the rest of the three groups. The increase in haemoglobin was significantly higher with ferrous sulphate than with whole wheat (p < 0.05), spirulina and whole egg (p < 0.01). Feeding of ferrous sulphate, whole egg and spirulina produced significantly higher tissue iron levels than feeding of whole wheat. Thus, availability of iron from spirulina and whole egg were found to be comparable to that of the standard. PMID 8332584

35_ 1993 May;91(5):97682.

Effectiveness of ironfortified infant cereal in prevention of iron deficiency anemia.

Walter T, Dallman PR, Pizarro F, Velozo L, Pena G, Bartholmey SJ, Hertrampf E, Olivares M, Letelier A, Arredondo M.

BACKGROUND. Iron deficiency continues to be a common problem among infants throughout the world. Ironfortified formula is effective in preventing iron deficiency but the benefit of ironfortified cereal is controversial. METHODS. We compared ironfortified rice cereal to unfortified rice cereal in infants who were exclusively breastfed for more than 4 months and to ironfortified formula in infants who were weaned to formula before 4 months of age. The design was double blind in respect to the presence or absence of fortification iron in the cereal or formula and included 515 infants who were followed on the protocol from 4 to 15 months of age. Rice cereal was fortified with 55 mg of electrolytic iron per 100 g of dry cereal and infant formula with 12 mg of ferrous sulfate per 100 g of dry powder, levels approximating those in use in the United States. Measures of iron status were obtained at 8, 12, and 15 months. Infants with hemoglobin levels of < 105 g/L were excluded from the study and treated. RESULTS. Consumption of cereal reached plateaus at means of about 30 g/d after 6 months of age in the formulafed groups and 26 g/d after 8 months in the breastfed groups; these amounts are higher than the 19g/d mean intake by the 73% of infants who consume such cereal in the United States. Among infants weaned to formula before 4 months, the cumulative percentages of infants excluded for anemia by 15 months were 8%, 24%, and 4%, respectively, in the fortified cereal, unfortified cereal and formula, and fortified formula groups (P < .01 unfortified vs either fortified group; the difference between the two fortified groups was not significant). In infants breastfed for more than 4 months, the corresponding values were 13% and 27%, respectively, in the fortified and unfortified cereal groups (P < .05). Mean hemoglobin level and other iron status measures were in accord with these findings. CONCLUSION. Ironfortified infant rice cereal can contribute substantially to preventing iron deficiency anemia. PMID 8474819

36_ 1993 Apr;18(2):24964.

Improvements in cognitive performance for schoolchildren in Zaire, Africa, following an iron supplement and treatment for intestinal parasites.

Boivin MJ, Giordani B.

Tested 47 firstyear primary school children at a mission school in rural Zaire for cognitive ability with the Kaufman Assessment Battery for Children (KABC) adopted to the language of Kituba. Within a day of this test, each child was evaluated for blood hemoglobin (Hgb) level and the presence of intestinal parasites. Half of the children received an iron supplement (20 mg Fe) for 30 days and those children positive for the intestinal parasites of ankylostome or ascaris were randomly selected to receive either a vermifuge treatment or placebo. All of the children were again evaluated medically and cognitively 4 weeks after the initiation of treatment. Using discriminant analysis, performance on the Mental Processing Composite of the KABC 1 month after treatment in combination with increases in blood Hgb resulted in the successful classification of 74% in terms whether a child had received both iron supplement and vermifuge treatment (p = .007). With respect to our home evaluation for each child, factors related to the nutritional and economic wellbeing of the home environment proved a reliable marker for Simultaneous Processing ability. However, the present findings also suggest that over the shortterm, changes in blood Hgb that accompany both vermifuge and iron supplement treatment together can improve certain aspects of cognitive ability, perhaps by means of heightened attentional capacity. PMID 8492277

37_ 1993 Feb;72(2):938.

Low dose iron supplementation does not cover the need for iron during pregnancy.

Thomsen JK, PrienLarsen JC, Devantier A, FoghAndersen N.

OBJECTIVETo determine: 1) if 18 mg iron daily is sufficient to cover the iron need during normal pregnancy, and 2) if women, who will not need iron supplementation during pregnancy, can be identified by early screening. DESIGNIn a prospective study the women were randomized to receive either 18 or 100 mg iron daily from the 16th week until delivery. Investigations were performed in the 16th, 30th, and 38th week. SUBJECTSHealthy nulliparae (n = 43) experiencing a normal singleton pregnancy. Only women with a normal hemoglobin concentration and intact iron stores (SFerritin > 15 micrograms/1) in the 16th week were included. VARIABLESThese measurements were done consecutively: 1) the total hemoglobin mass (with carbon monoxide). 2) SFerritin, 3) STransferrin, 4) SIron, 5) red cell indices (hemoglobin concentration, hematocrit, MCV, MCHC). RESULTSChanges in red cell indices and STransferrin were equal in the two groups. There was no significant difference in SFerritin in the 16th week. In the 30th week 3 women (14%) in the 100 mg group and 11 (52%) in the 18 mg group had empty iron stores (p < 0.05). The numbers were 1 (5%) and 15 (72%) in the 38th week (p < 0.0001). The increment in total hemoglobin mass was equal in the two groups from the 16th to the 30th week (13% in the 100 mg group and 12% in the 18 mg group). From the 30th to the 38th week the increment in total hemoglobin mass was largest in the 100 mg group (8.1% versus 2.7%, p < 0.05). CONCLUSIONDespite a normal hemoglobin concentration and intact iron stores in the 16th week, an iron supplementation of 18 mg daily is not sufficient to cover the iron need in many pregnant women in the 3rd trimester. PMID 8383415

38_ 1993 Feb;57(2):1904.

Effect of bovinehemoglobinfortified cookies on iron status of schoolchildren: a nationwide program in Chile.

Walter T, Hertrampf E, Pizarro F, Olivares M, Llaguno S, Letelier A, Vega V, Stekel A.

The Chilean School Lunch program, which serves one million children nationwide, was supplied with three 10g cookies fortified with 6% bovine hemoglobin concentrate, designed to provide 1 mg bioavailable iron per day. A survey of 1000 children was performed after 3 y. Significant differences in hemoglobin concentrations were found in the children from the fortified vs the nonfortified province (P < 0.01). Low serum ferritin values were also significantly more prevalent in the nonfortified group. The effect was evident despite the very low prevalence of anemia in both the fortified and the unfortified school groups. Hemeironfortified cookies are a feasible and effective way to improve the iron status of schoolage children. In regions of high prevalence of irondeficiency anemia, the effect of a hemefortified cookie program should be even more important. PMID 8424387

39_ 1993 Feb;152(2):1204.

The immune response in irondeficient young children: effect of iron supplementation on cellmediated immunity.

Thibault H, Galan P, Selz F, Preziosi P, Olivier C, Badoual J, Hercberg S.

The effects of iron deficiency on immunity remain controversial. This study was designed to assess the impact of iron supplementation on the immune status, in 81 children aged 6 months3 years, at high risk for iron deficiency, using a longitudinal double blind randomised and placebocontrolled study. Lymphocytes of irondeficient children produced less interleukin2 in vitro. Iron supplementation for 2 months increased mean corpuscular volume, serum ferritin and serum transferrin, but had no effect on the parameters of Tcell mediated immunity. The lower interleukin2 levels in irondeficient suggest that cellmediated immunity may be impaired in iron deficiency. PMID 8444218

40_ 1993 Feb;30(2):195200.

Growth performance in anemia and following iron supplementation.

Bhatia D, Seshadri S.

The growth status of anemic (n = 117, Hb 710 g/dl) and normal (n = 53, H > or = 11 g/dl) children 35 years of age living under similar environmental and socioeconomic conditions was evaluated. The dietary intake was assessed on a random subsample of the anemic and normal children. The anemic children had a poorer growth status than normal children as indicated by their significantly (p < 0.001) lower body weight, height and weight for age and significantly (p < 0.001) larger number in Grades II and III malnutrition. Iron supplementation (40 mg elemental iron/day) for six months produced a significant (p < 0.001) increase in Hb levels of both groups (1.6 g/dl in the anemic and 0.8 g/dl in the nonanemic) compared to their respective controls who received sugar placebos. The growth performance of the anemic children supplemented with iron was superior to that of anemic placebo treated children as indicated by a better weight gain and a significantly higher weight for height (p < 0.05). Weight for age was a good differentiator of the anemic from normal while weight for height was a good indicator of the impact of iron supplements on growth. PMID 8375881

41_ 1992 Oct;35(1):111.

Significance of iron bioavailability for iron recommendations.

van Dokkum W.

Recently, recommended dietary allowances (RDA) have been formulated by the Dutch Nutrition Council for minerals and trace elements, including iron (Fe). For some population groups in the Netherlands, it is questionable whether they easily meet the Fe recommendation. An increase in Fe intake is not always possible, but "manipulation" of Fe bioavailability ultimately may result in better Fe utilization. Various factors are known to affect Fe bioavailability. Generally, much attention is paid to dietrelated factors, such as inhibitors and enhancers of Fe availability for absorption. Factors such as pH, oxidation potential, structure of food, and time of digestion often are overlooked. Of the dietrelated factors, heme Fe and ascorbic acid have a strong positive effect on Fe availability for absorption, whereas oxalate and polyphenols seem to be strong inhibitors of Fe availability. Because of the many interactions that may occur simultaneously, the net effect of the various combined factors in a meal is not equal to the sum of the individual factors. PMID 1384622

42_ 1992 Oct;42(4):3138.

Bioavailability of iron from spinach (Spanicia oleracea) cultivated in soil fortified with graded levels of iron.

Reddy NS, Malewar VG.

In vitro availability of iron along with ascorbic acid, oxalic acid and phosphorus contents of two varieties of spinach (Pusa Jyoti and Allgreen) cultivated in soil with different levels of added iron was determined. Addition of graded levels of iron to soil markedly increased the total iron and phosphorus contents and significantly decreased the bioavailability of iron, ascorbic acid and oxalic acid contents of spinach. Ascorbic acid and oxalic acid contents markedly exerted a positive influence while phosphorus exerted a negative influence on the bioavailability of iron. PMID 1438075

43_ 1992 Winter;51(2):146.

Recurrent aphthous stomatitis: the efficacy of replacement therapy in patients with underlying hematinic deficiencies.

Porter S, Flint S, Scully C, Keith O.

A group of thirtyfour patients with recurrent aphthous stomatitis (RAS) and single hematinic deficiencies were given replacement therapy after any reason for the deficiency had been sought and excluded. The response of the RAS was assessed in an open trial. The aphthae in 70% of patients subjectively improved with hematinic replacement therapy, a benefit exceeding the defined placebo response in recurrent aphthous stomatitis. PMID 1463310

44_ 1997 SepOct;91(5):55761.

Management of severe malarial anaemia in Gambian children.

Bojang KA, Palmer A, Boele van Hensbroek M, Banya WA, Greenwood BM.

The optimum management of children with severe malarial anaemia is still uncertain. Hence, we have undertaken a study to determine whether iron treatment is as effective at restoring haemoglobin levels one month after presentation as blood transfusion without iron treatment in children with moderately severe malarial anaemia. Two hundred and eightyseven children with a packed cell volume (PCV) < 15% and malaria infection were recruited into the study; 173 children were assigned to receive blood transfusion because they had a PCV < 12% and/or signs of respiratory distress and the remaining 114 children were allocated at random to receive either blood transfusion (58) or treatment with oral iron (56) for 28 d. Twentyfour children died, 23 in the most severely anaemic group. Fifteen children (65%) died before transfusion was given and most deaths occurred within the first 4 h of admission. One child died in the iron treatment group and 10 subsequently required transfusion. Among the severely anaemic children, those with respiratory distress were at greater risk of death than those without respiratory distress. After 28 d, haematological restoration was significantly better in children who had received iron than in those treated by blood transfusion (P = 0.02). Children who received malaria chemoprophylaxis after discharge from hospital had fewer episodes of malaria and subsequent admissions to a hospital or health centre than those who did not. Children with severe anaemia and clinical signs of respiratory distress must be identified quickly and transfused as soon as possible. However, for less severely anaemic children who are clinically stable, iron therapy offers an alternative to transfusion provided such children can be kept under surveillance and transfused subsequently should this become necessary. PMID 9463667

45_ 1997 Aug;98(2):2924.

The effect of intravenous iron on the reticulocyte response to recombinant human erythropoietin.

Major A, MathezLoic F, Rohling R, Gautschi K, Brugnara C.

We studied the effect of intravenous (i.v.) administration of 200 mg of iron sucrose following an i.v. bolus injection of recombinant human erythropoietin (rHuEPO; 300 U/kg body weight) in seven subjects and compared it with seven subjects treated with rHuEPO alone. Reticulocytes, serum erythropoietin (EPO) and ferritin levels were studied at baseline and daily for the following 8 d. Use of i.v. iron abolished the marked reduction in serum ferritin observed with rHuEPO administration. Although the total number of reticulocytes was not affected by i.v. iron administration, the reticulocyte Hb content and retHb (a measure in g/l of the Hb contained in all reticulocytes) were increased in the i.v. iron/rHuEPO group compared with the group who received rHuEPO alone. Therefore i.v. iron significantly potentiates the haemopoietic response to rHuEPO in normal subjects.

PMID 9266922

46_ 1997 Jul;86(7):6839.

Followon formula in the prevention of iron deficiency: a multicentre study.

Gill DG, Vincent S, Segal DS.

Sixmonthold infants were recruited at 21 centres in the UK and Ireland and randomly assigned to receive matching ironfortified (12.3 mg/l iron) or nonfortified (1.4 mg/l iron) formula for 9 months. Infants already receiving cow's milk continued this feed. Haematological indices and iron status were evaluated at age 6 months, 910 months and 15 months. Four hundred and six infants entered and 302 completed the study. There were no differences between the groups for increases in weight, head circumference or length. Significant differences between the groups were observed at 15 months for haemoglobin, serum ferritin, serum iron and total iron binding capacity. Haemoglobin levels were < 110 g/l in 33% of infants fed cow's milk compared with 13% and 11% in those receiving nonironfortified and ironfortified formula respectively. The corresponding figures for serum ferritin < 10 microg/l were 43%, 22% and 6%. Followon formula provides an acceptable vehicle for preventing iron deficiency in this vulnerable group. PMID 9240873

47_ 1997 Jul;66(1):17783.

Weekly micronutrient supplementation to build iron stores in female Indonesian adolescents.

AngelesAgdeppa I, Schultink W, Sastroamidjojo S, Gross R, Karyadi D.

Different supplementation schemes to build iron stores in female Indonesian adolescents were investigated. Subjects were 273 highschool girls allocated randomly to four treatment groups. During a 3mo period one group received 60 mg Fe, 750 micrograms retinol, 250 micrograms folic acid, and 60 mg vitamin C per day; a second group received 60 mg Fe, 6000 micrograms retinol, 500 mg folic acid, and 60 mg vitamin C once a week; a third group received 120 mg Fe and the same amount of the other three micronutrients as the second group once a week; and a fourth group received only placebos. All subjects were dewormed and supplement allocation was double blind. Blood samples were collected at baseline, after 2 and 3 mo of supplementation, and 6 mo after the last supplement. After 2 mo of supplementation, groups supplemented weekly and daily showed similar significant improvements (P < 0.001) in hemoglobin and retinol concentrations, and supplementation for 3 instead of 2 mo did not significantly increase these two indicators. After 3 mo, the increase in ferritin was approximately equal to 27 micrograms/L in the daily and 1415 micrograms/L in the weekly groups (P < 0.001), the latter having a final concentration of 4245 micrograms/L. At 6 mo postsupplementation there were no significant differences among daily and weekly groups, but the ferritin concentration was still approximately equal to 1012micrograms/L higher (P < 0.001) than in the placebo group. The group supplemented weekly with 60 mg Fe complained less about side effects than the other supplemented groups (P < 0.05). Weekly supplementation with 60 mg Fe and 6000 micrograms retinol for 3 mo was optimal for improving the iron status of the adolescents for approximately equal to 9 mo. PMID 9209187

48_ 1997 Jun;51(6):3816.

Weekly iron supplementation is as effective as 5 day per week iron supplementation in Bolivian school children living at high altitude.

Berger J, Aguayo VM, Tellez W, Lujan C, Traissac P, San Miguel JL.

OBJECTIVE: To compare the efficacy of a daily and a weekly iron supplementation on the hematological status of anemic children living at high altitude. DESIGN: Double blind iron supplementation trial including a placebo control group. SETTING: A socioeconomically disadvantaged district of La Paz, Bolivia (altitude of 4000 m). SUBJECTS: Anemic (hemoglobin concentration < or = 144 g/L), 3.38.3 y old children of both sexes. INTERVENTION: Children received a placebo (n = 57) or a dose of 34 mg of elemental iron per kg body weight (FeSO4 tablets) 1 d per week (n = 58) or 5 d per week (n = 58) for 16 weeks. RESULTS: Hemoglobin and zinc erythrocyte protoporphyrin concentrations improved significantly in supplemented groups but not in the placebo group. Changes in hemoglobin during the study were not significantly different between supplemented groups (weekly group: 15.2 6.9 g/L and daily group: 18.6 11.1 g/L) but were different from the placebo group (0.5 7.1 g/L, P < 0.001). At the end of the supplementation period, the hemoglobin distribution was Gaussian, and similar in both supplemented groups. Adjusting for the initial hemoglobin concentration, final hemoglobin and its changes were similar in both supplemented groups. CONCLUSION: Weekly iron supplementation is as efficacious as daily iron supplementation in improving iron status and correcting moderate iron deficiency anemia in Bolivian school children living at high altitude. SPONSORSHIP: Program supported in part by ORSTROM, the French Ministry of Foreign Affairs and the National Secretary's Office of Health, Bolivia. PMID 9192196

49_ 1997 Jun;11(2):99104.

Liver and colon oxidant status in growing rats fed increasing levels of dietary iron.

Rimbach G, Markant A, Most E, Pallauf J.

A study with four groups, each with 9 individuallyhoused, male albino rats (clinical average weight = 65 g), was undertaken to examine the effect of increasing dietary iron levels on the oxidant status in liver and colon of growing rats. The basal maize/soya diet contained 70 mg iron per kg and was supplemented with 200 (group II), 500 (group III) and 2000 (group IV) mg Fe/kg from iron (II) fumarate. LiverFe was closely correlated (r = 0.997) with dietary Fe intake. Feeding diets supplemented with 500 and 2000 mg Fe/kg over 28 days resulted in significantly elevated TBARS in liver homogenates. Vitamin E in the liver was about 20% lower in group IV compared to the controls. Liver SOD, G6PDH and CAT activities were not influenced by dietary iron, whereas liver GSHPx was decreased in groups III and IV. TBARS in the colon mucosa significantly increased only at a dietary iron supply of 2000 mg per kg. Ironenriched diets caused a moderate dosedependent enhancement in the concentration of methane sulfinic acid in feces samples, which was formed by the reaction of hydroxyl radicals and dimethyl sulfoxide. Liver was more sensitive than the colon mucosa to ironinduced lipid peroxidation. Compared with the recommended iron requirements of growing rats very high dietary iron levels were necessary to induce oxidative stress. PMID 9285890

50_ 1997 Jun;55(6):24756.

Definition and prevalence of anemia in Bolivian women of childbearing age living at high altitudes: the effect of ironfolate supplementation.

Berger J, Aguayo VM, San Miguel JL, Lujan C, Tellez W, Traissac P.

This paper discusses the effect that high altitudes have on iron metabolism and summarizes the results of an ironfolate supplementation trial. The two main objectives of the trial were to determine hemoglobin cutoff values for the diagnosis of anemia in Bolivian women of childbearing age living at high altitudes, and to estimate the prevalence of anemia in this population. The study showed that nutritional anemia is an important public health problem in such populations and that many methods of assessing it lead to an underestimation of prevalence. The cutoff values defined through this study, one of the few iron supplementation trials conducted at high altitudes, confirm the need to establish revised hemoglobin values for the diagnosis of anemia in populations living at high altitudes. PMID 9279061

51_ 1997 Mar;99(3):E2.

Risk of diarrhea related to iron content of infant formula: lack of evidence to support the use of lowiron formula as a supplement for breastfed infants.

Scariati PD, GrummerStrawn LM, Fein SB, Yip R.

BACKGROUND: Concern has been raised by infant feeding experts that supplementing breastfed infants with ironfortified formula rather than lowiron formula may have an undesirable impact on their gastrointestinal flora. Thus far, there have been no clinical studies to address this issue directly. We compared the reported frequency of diarrhea for breastfed infants given ironfortified formula with those fed lowiron formula. METHODS: Mothers participating in a mail panel provided feeding and diarrhea information on their infants at 2, 3, 4, 5, 6, 7, 9, and 12 months (n = 1743). Infants were grouped into five feeding categories: (1) breast milk only, (2) breast milk and lowiron formula, (3) breast milk and ironfortified formula, (4) lowiron formula only, and (5) ironfortified formula only. We calculated the number of diarrheal episodes per week for each feeding category and used rate ratios to estimate the relative impact of lowiron and ironfortified formulas. RESULTS: Among infants who received both breast milk and formula, the rate ratio for ironfortified formula versus lowiron formula was 1.06 (confidence interval, 0.84 to 1.34), indicating that the type of formula a breastfed infant receives does not significantly affect the frequency of diarrhea. CONCLUSIONS: We found no evidence to support the hypothesis that breastfed infants given ironfortified formula are at greater risk of having diarrhea. This, in addition to the fact that ironfortified formula has played a major role in preventing childhood iron deficiency anemia, supports the current recommendation that any formula given to infants be fortified with iron. PMID 9099767

52_ 1997 Feb;42(2):99103.

Supplementing iron intravenously in pregnancy. A way to avoid blood transfusions.

Hallak M, Sharon AS, Diukman R, Auslender R, Abramovici H.

OBJECTIVE: To determine the safety and efficacy of maternal intravenous iron administration to avoid blood transfusion in patients who cannot use oral preparations. METHODS: Patients with persistent irondeficiency anemia who had one of the following indications were included in this study: severe side effects from oral preparations, lack of improvement despite oral iron intake or history of gastrointestinal operations. The total iron amount needed to regenerate iron stores was calculated according to hemoglobin and the patients' weight. Hemoglobin, hematocrit, mean corpuscular volume, serum iron, transferrin and ferritin were evaluated at the start and conclusion of therapy as well as two weeks afterward. RESULTS: Twentysix patients were included in the study; four of them delivered during the therapy course. One patient developed mild signs of allergy (urticaria) after the test dose and was excluded from the study. The remaining 21 pregnant patients (mean gestational age 28 weeks) completed the therapy course and received a mean of 1,000 mg of elemental iron. The hemoglobin was increased from 8.4 1.0 to 10.1 0.6 g/dL at the start and end of therapy, respectively (P < .01) and continued to rise to 10.9 0.6 g/dL two weeks later (P < .01). The serum iron was increased from 3.9 2.0 mumol/L at the start of therapy to 15.5 7.2 at the end (P < .01). The transferrin was decreased from 47.0 7.8 to 41.4 5.3 to 37.1 11.8 mumol/L at the start of, end of and two weeks after therapy, respectively (P < .01). Ferritin levels were increased from 2.9 2.7 ng/mL at the start to 122.8 87.1 at the end of therapy (P < .01) and decreased to 109.4 90.7 ng/mL two weeks after treatment (not significant). Only mild and transient side effects were occasionally reported. CONCLUSION: Intravenous iron administration during pregnancy is an effective method of regenerating hemoglobin and iron stores. It should be considered for patients with severe irondeficiency anemia who cannot use oral preparations. PMID 9058345

53_ 1997;31(3):2448.

Influence of iron alone or with fluoride on caries development in desalivated and intact rats.

Miguel JC, Bowen WH, Pearson SK.

Sugar is used as a vehicle for iron fortification in communities where anemia is prevalent. The purpose of the present study was to investigate the relationship between caries experience and iron concentration in sugar fed to rats subjected to a severe cariogenic challenge. Desalivated and intact animals were assigned to 4 different diet subgroups, 3 receiving iron sucrose (350, 175 and 88 ppm Fe) and a control group. The influence of iron sugar combined with 10 ppm F in drinking water was explored in an additional study. Iron reduces the incidence of smoothsurface carries in desalivated rats at concentrations as low as 88 ppm Fe. In addition, a combination of iron and fluoride reduced the incidence of dental caries in our rats. PMID 9165198

54_ 1997 Jan;48(1):419.

Response to an iron fortification programme in relation to vitamin A status in 612yearold school children.

van Stuijvenberg ME, Kruger M, Badenhorst CJ, Mansvelt EP, Laubscher JA.

Plasma retinol and indices of iron status were measured in 148 school children (612 years) receiving a soup fortified with iron and vitamin C for a period of 15 weeks. The most significant change in serum iron (P = 0.0005) and transferrin saturation (P = 0.0002) was seen in subjects with plasma retinol > or = 40 micrograms/dl, while subjects with plasma retinol < 20 micrograms/dl showed no response. Serum ferritin improved most in the retinol categories < 40 micrograms/dl, suggesting that the absorption of iron was not impaired by marginal vitamin A status, but that it was rather the mobilisation of iron from stores that was affected. Changes in vitamin A status correlated positively and significantly with changes in serum iron (r = 0.37; P = 0.0001) transferrin saturation (r = 0.27; P = 0.004) and haemoglobin (r = 0.21; P = 0.03), but negatively with serum ferritin (r = 0.28; P = 0.003). The presence of marginal vitamin A deficiency in a community may limit the effectiveness of an iron intervention programme and vitamin A status should therefore also be considered when such programmes are planned. PMID 9093548

55_ 1997;28 Suppl 2:6974.

Daily and weekly iron supplementation and physical growth of school age Indonesian children.

Soemantri AG, Hapsari DE, Susanto JC, Rohadi W, Tamam M, Irawan PW, Sugianto A.

OBJECTIVE: To investigate the effect of 3 months iron supplementation on physical growth among anemic school children given daily and weekly and to know the response based on hemoglobin level. SUBJECT: One hundred fortyfour children were measured for height, weight and hemoglobin level. Ninety seven children were anemic (67.36%) with Hb level < 12 g/dl and forty seven children were non anemic. anemic children were divided into 2 subgroups and randomly assigned to either daily and weekly Fe treatment for 12 weeks. The non anemic group were treated with weekly iron supplementation, which was accepted by the parents. OUTCOME MEASURES: Children's height, weight, and hemoglobin of T1 and T2 food recall method was used to know calorie, protein, vitamin C and iron intake in both daily and weekly subgroups. Three days food recall was performed in the second and third months by a nutritionist. RESULT: After iron supplementation, the hemoglobin level in both group increased significantly. The average change of hemoglobin between the 2 groups gave no significant difference. W/A and H/A after iron supplementation showed significantly increased in both groups. The average change of W/A and H/A between the 2 groups gave no significant difference. CONCLUSION: Daily and weekly iron supplementation showed no significant difference in increasing of hemoglobin level and physical growth. Further research must be done with appropriate sample size and well design. PMID 9561637

56_ 1996 Dec;19(12):9259.

The iron hypothesisdoes iron cause atherosclerosis?

Meyers DG.

Women experience only 3050% of the coronary heart disease (CHD) incidence and mortality of agematched men. Since oxidation of lowdensity lipoprotein (LDL) cholesterol is important in atherosclerosis, and oxidation is catalyzed by iron, it has been hypothesized that the lower iron stores of women reduce their risk of CHD through lessened lipid peroxide. The biochemistry of oxidation is well described in the literature and involves iron as a catalyst in the formation of powerful free radicals which subsequently modify LDL cholesterol. Chelating iron with desferrioxamine stops oxidation. Iron is present in atherosclerotic gruel and this gruel stimulates lipid peroxidation. Serum deficient in iron has minimal oxidative capacity which increases with iron repletion. At least seven epidemiologic studies have found a positive association between CHD and various indicators of body iron. Conversely 18 epidemiologic studies have found a negative or no association. While biochemically appealing, the iron hypothesis remains unproven. PMID 8957595

57_ 1996 Nov;54(11 Pt 1):34854.

Strategies for the prevention of iron deficiency: iron in infant formulas and baby foods.

Ziegler EE, Fomon SJ.

Iron deficiency is the most prevalent nutrition deficiency among infants and young children in industrialized as well as developing countries. It is a condition that is preventable through appropriate dietary measures. The infant born at term is endowed with a sizable amount of iron, which allows the infant to be fed a nearly ironfree diet (e.g., breast milk) for 46 months without becoming overtly iron deficient. This has led some to conclude that depletion of iron stores in healthy infants is a normal and, hence, innocuous process that usually gives way to gradual repletion of iron stores as dietary diversification leads to greater iron intakes. Preservation of maternal iron stores at the expense of infant iron stores may have offered survival advantages to the human species during evolution. But there is no evidence that depletion of iron stores can offer advantages to infants in industrialized or developing countries. On the contrary, there is ample documentation of shortterm as well as longterm adverse effects from iron deficiency. Prudence therefore dictates that a high priority be assigned to the prevention of iron depletion and deficiency among infants and young children worldwide. PMID 9110563

58_ 1996 Oct;15(5):4348. Asymptomatic giardiasis does not affect iron absorption in children with iron deficiency anemia.

De Morais MB, Suzuki HU, Corral JN, Machado NL, Neto UF.

OBJECTIVE: Malabsorption of iron has been reported in children with symptomatic giardiasis. The aim of this study was to evaluate intestinal absorption of iron in children with asymptomatic giardiasis and iron deficiency anemia. SUBJECTS: Based upon results of blood hemoglobin and stool examination, two groups were established: asymptomatic giardiasis and anemia, and anemia without intestinal parasitosis (control group). Patients were aged 16 years. There was no difference in age, weight, height, or iron nutritional status between the asymptomatic giardiasis and control groups on admission to the study. MEASURES: Intestinal absorption of iron was evaluated using the iron tolerance test and the hemoglobin response to iron therapy. The serum iron tolerance test was based on the increment of iron level 2 hours after administering an iron load of 1 mg/kg of elemental iron in the form of ferrous sulfate, in comparison to the fasting iron level. Hemoglobin response to oral iron therapy was determined by the increment of hemoglobin on day 30 of therapy with ferrous sulfate (5 mg/kg/day of elemental iron). RESULTS: There was no statistical difference between the asymptomatic giardiasis and control groups with reference to the iron tolerance test (159.1 73.1 micrograms/dl and 154.5 76.5 micrograms/dl, respectively) and to the hemoglobin response to iron therapy (1.5 0.7 g/dl and 1.8 1.1 g/dl, respectively). The presence or absence of trophozoites of Giardia lamblia on duodenal aspirate did not affect intestinal absorption of iron. CONCLUSION: Asymptomatic giardiasis did not affect the intestinal absorption of iron and the hemoglobin response to oral iron therapy in irondeficient anemic children.

59_ 1996 Sep;9(23):3417.

The effectiveness of weekly iron supplementation regimen in improving the iron status of Chinese children and pregnant women.

Liu XN, Liu PY.

It is evident that intermittent iron supplementation is better than daily supplementation in two aspects: iron absorption is more efficient and has insignificant side effects in contrast to the daily dose. The significantly higher daily iron loss observed in the daily iron supplemented groups rats also suggests alterations in total body iron metabolism. Based on serum ferritin distribution patterns, intermittent iron supplementation avoids temporary iron overload with daily iron supplemented. We conclude that weekly iron supplementation scheme is safer and easier to administer. This feasible strategy for the control of iron deficient anemia in pregnant women and children would be an effective ironsupplementation program (Baily et al., 1993).

PIP: Most governmental programs to control widespread iron deficiency in the developing world involve providing daily supplements of iron to all children and pregnant women. This approach has generally poor results due in part to doserelated undesirable gastrointestinal side effects and the lack of effective absorption and retention of iron consumed on a daily basis. However, recent evidence indicates that iron is absorbed significantly better when consumed only at intervals coinciding with gut mucosal renewals. That approach also prevents constant high iron concentrations in the gut which may cause undesirable side effects. Much lower iron doses administered intermittently are as effective in correcting iron nutrition and safer than daily doses in iron deficient anemic rats. 246 healthy 36 year olds and 405 pregnant women were enrolled in two studies to determine whether intermittent iron supplementation in humans is more efficient than daily iron administration. Weekly iron supplementation proved to be better than daily supplementation, producing more efficient iron absorption with fewer side effects. Serum ferritin distribution patterns indicate that intermittent iron supplementation avoids the iron overload which results from daily iron supplemented.

60_ 1996 Sep;129(3):3829.

Irondeficiency anemia and infant development: effects of extended oral iron therapy.

Lozoff B, Wolf AW, Jimenez E.

OBJECTIVE: To determine whether extended oral iron therapy corrects lower developmental test scores in infants with irondeficiency anemia. STUDY DESIGN: Doubleblind, controlled trial in Costa Rica involving 32 12 to 23monthold infants with irondeficiency anemia and 54 nonanemic control subjects. Anemic infants were treated with orally administered iron for 6 months; half the nonanemic children were treated with iron and half with placebo. Developmental test scores and hematologic status were evaluated before treatment, after 3 months, and after 6 months. RESULTS: Irondeficient anemic infants received lower mental test scores than nonanemic infants at all three time points (p < 0.05 pretreatment and at 3 months, p = 0.07 at 6 months). There were no significant differences in motor test scores. More of the anemic infants were rated as unusually tearful and unhappy. Anemic infants came from families with lower maternal education and less support for child development and were less likely to be breast fed, were weaned earlier, and consumed more cow milk. CONCLUSIONS: Lower mental test scores persisted in infants with irondeficiency anemia despite extended oral iron therapy and an excellent hematologic response. Irondeficiency anemia may serve as a marker for a variety of nutritional and family disadvantages that may adversely affect infant development. PMID 8804327

61_ 1996 Aug;129(2):25863.

A comparison of oral and intravenous iron supplementation in preterm infants receiving recombinant erythropoietin.

Meyer MP, Haworth C, Meyer JH, Commerford A.

OBJECTIVE: To determine whether intravenously administered iron supplements would improve the hematologic response to recombinant erythropoietin in stable preterm infants. METHODS: Fortytwo preterm infants (<33 weeks' gestation, birth weight < 1500 gm, hematocrit <38%) were treated with recombinant human erythropoietin (Eprex), 600 U/kg per week, and randomly assigned to receive either an oral preparation of ferrous lactate (elemental iron, 12 mg/kg per day) or an intravenous preparation of iron sucrose (6 mg/kg per week). RESULTS: Hematocrits, reticulocyte counts, and transfusions were similar in the oral group (OG) and the intravenous group (IVG). However, markedly higher serum ferritin concentrations were noted in the IVG (p <0.001), and by completion of the study the arithmetic mean values were 265 127 microg/L versus 137 65 microg/L in the IVG and the OG, respectively. The numbers of hypochromic erythrocytes increased in both groups during the study but were significantly higher in the OG (p = 0.04). Mean daily weight gain in the IVG (27 6.4 gm/day) was greater than in the OG (22.9 4.78 gm/day; p = 0.04). CONCLUSIONS: High doses of both orally administered iron and intravenously administered iron sucrose appear to supply sufficient iron for erythropoiesis in stable infants. Storage iron may become depleted after oral supplementation. The intravenous preparation appears to be safe and maintains serum ferritin concentrations, and it may be indicated for patients with low ferritin levels and for those not established on enteral feedings. PMID 8765624

62_ 1996 Jun;63(6):88490. Effects of weekly iron supplementation on pregnant Indonesian women are similar to those of daily supplementation.

Ridwan E, Schultink W, Dillon D, Gross R.

The effect of daily rather than weekly iron supplementation was compared in women who were 824 wk pregnant. One group (n = 68) received 60 mg Fe/d, the second group (n = 71) received 120 mg Fe/wk, given at once. Supplementation lasted 11.3 wk on average, depending on gestational date at entry, and was not supervised. Hemoglobin increased in both groups (P < 0.001); serum ferritin did not change significantly. There was no significant difference between groups for changes in hemoglobin and serum ferritin. In a subgroup of women with a hemoglobin concentration < 110 g/L at baseline (n = 45 daily; n = 54 weekly) no significant withingroup changes occurred in serum ferritin, but the change in the daily group was 4.1 micrograms/L higher than in the weekly group (P = 0.049). Compliance, as indicated by two positive stool tests, was approximately equal to 54.3% in the daily group and 62.2% in the weekly group. We conclude that for the complete sample of subjects, the treatment effect of daily compared with weekly supplementation was similar under conditions resembling a normal antenatal care program.

63_ 1996 Mar;54(3):7384.

Iron and heart disease: the epidemiologic data.

Sempos CT, Looker AC, Gillum RF.

There has developed a general theory of chronic and degenerative disease causationthe Oxidative Stress Theory. This theory states that the production of tissuedamaging free radicals is an essential component in the pathogenesis of chronic diseases and that iron may help to catalyze the reactions producing free radicals. As a result, it has been suggested that the risk of coronary heart disease increases with increasing body iron stores. In support of that hypothesis, a prospective epidemiologic study of heart disease in Finnish men found that the risk of heart attack increased with increasing levels of serum ferritin. However, the vast majority of the epidemiologic data, including results from prospective, crosssectional, and casecontrol and autopsy studies, published since that initial study have failed to support the original hypothesis that high body iron stores increase the risk of coronary heart disease. PMID 8935217

64_ 1996 Feb;126(2):46775.

Dietary iron supplementation does not aggravate experimental malaria in young rats.

Cardoso MA, Ferreira MU, Ribeiro GS, Penteado MD, Andrade Junior HF.

The hypotheses that irondeficient hosts are less susceptible to severe malaria and that iron supplementation aggravates infection have been supported by some clinical and experimental evidence. In the present study, the course of Plasmodium berghei infection was monitored in an experimental model of dietary iron deficiency and iron supplementation. Weanling Wistar rats were fed purified diets with different iron concentrations: 20 mg/kg (Group D, n = 24), 50 mg/kg (Group N, n = 24) and 100 mg/kg (Group S, n = 12). After 15 d, rats from Group D were anemic (mean hemoglobin 81 g/l). The next day, 12 rats from Group D (thereafter Group DS) and 12 rats from Group N (thereafter Group NS) were transferred to the same ironsupplemented diet as in Group S, whereas the remaining animals (Groups D, N and S) were maintained on the original diets for further 14 d. At that time, 9 rats from each group were inoculated intraperitoneally with 10(6) erythrocytic parasites (P. berghei ANKA strain), whereas 3 rats from each group remained as noninfected controls. All animals were killed 14 d after inoculation, when significantly lower levels of hemoglobin, serum iron and percent transferrin saturation were found in infected animals from Group D compared with all other groups. However, the time course of parasitemias was similar in all groups. These data indicate that the development of P. berghei was neither suppressed by iron deficiency nor enhanced by iron supplementation in this model. Furthermore, iron repletion during infection did produce a noticeable improvement of hematological variables in previously irondeficient animals. PMID 8632220

65_ 1996 Jan;6(1):303.

Relationship between blood lead and dietary iron intake in preschool children. A crosssectional study.

Hammad TA, Sexton M, Langenberg P.

The relationship between dietary iron intake and blood lead levels in urban preschool children was investigated in a crosssectional study of 299 children from 9 months to 5 years old. Mothers of children attending the University of Maryland Pediatric Ambulatory Clinic volunteered for the children and themselves to join the study. The data collected included nutritional status, socioeconomic status, medical history, and potential sources of lead exposure. Blood samples from all participants were evaluated for levels of blood lead, serum iron (ferritin), free erythrocyte protoporphyrin, calcium, and hematocrit. The average blood lead level (standard deviation) in the studied population was 11.4 (7.3) micrograms/dL. With multiple linear and logistic regression analyses to adjust for covariates, a negative association (P = 0.03) between blood lead and dietary iron intake was found. This finding is consistent with similar results from experimental studies. It is concluded that there is evidence that higher dietary iron intake is associated with lower blood lead among urban preschool children in the studied population. PMID 8680621

66_ 1996;66(1):6670.

The contribution of dietary iron to iron status in a group of elderly subjects.

Roebothan BV, Chandra RK.

Although it is widely accepted that body iron stores of elderly individuals are largely adequate, recent findings from our laboratory suggest that as many as 9% of a "healthy" sample showed signs of an inadequate body store of this nutrient. In an attempt to see if iron consumption may be a contributing factor, we compared dietary intakes of total iron, heme iron, nonheme iron, ascorbic acid, calcium, dietary fibre, tea and coffee between 19 healthy seniors with inadequate iron stores and 108 healthy seniors with good iron status. The daily consumption of total iron was significantly higher in those with good iron stores. Thus, dietary iron is an important contributor to iron status in old age. PMID 8698549

67_ 1995 Dec;2(12):120918.

[Iron and pregnancy]

Beaufrere B, Bresson JL, Briend A, Farriaux JP, Ghisolfi J, Navarro J, Rey J, Ricour C, Rieu D, Vidailhet M.

Infants, young children, and childbearing aged women are particularly exposed to iron deficiency. Pregnancy further increases iron requirements. Nevertheless the consequences of anemia and/or iron deficiency on pregnancy outcome, development of the foetus and postnatal iron status of the infant, remain to be determined. There is a 3fold increase of premature deliveries in iron deficient anemic pregnant women whose anemia is discovered in early pregnancy: however this increased risk of premature delivery is not observed when iron deficiency anemia is discovered in late pregnancy. Iron supplementation during pregnancy improves the maternal hematological parameters but it is still unclear whether it also improves the maternal health and the pre and postnatal development of the child. Based on our actual knowledge, iron supplementation during pregnancy is to be recommended in risk groups only (ie mainly adolescents, low income women, women with multiple pregnancies), using ferrous iron at a dosage of 30 mg per day. PMID 8548003

68_ 1995 NovDec;89(6):6726.

Iron, but not folic acid, combined with effective antimalarial therapy promotes haematological recovery in African children after acute falciparum malaria.

van Hensbroek MB, MorrisJones S, Meisner S, Jaffar S, Bayo L, Dackour R, Phillips C, Greenwood BM.

Whether children with malarial anaemia should receive supplementation with iron or folic acid is uncertain. Therefore, the effects of supplementary treatment with iron or folic acid, given together with chloroquine or pyrimethaminesulfadoxine (Fansidar), has been assessed in 600 Gambian children with uncomplicated falciparum malaria. After one month, haematological recovery was significantly better in the group treated with Fansidar than in the chloroquinetreated group (difference in mean haemoglobin level = 0.54 g/dL, P = 0.01). Children who received iron had a significantly better response than those given placebo (differences in mean haemoglobin level after one month and at dry season followup = 0.70 g/dL, P = 0.006, and 0.81 g/dL, P = 0.001, respectively). Iron supplementation was not associated with increased prevalence of malaria. Supplementation with folic acid did not improve the haematological response but, among children who received Fansidar, the treatment failure rate was significantly higher among those given folic acid than among those given placebo. Thus, supplementation with iron, but not folic acid, improves haematological recovery without increasing susceptibility to malaria. PMID 8594693

69_ 1995 Oct;62(4):7859.

Zinc absorption in infants fed ironfortified weaning food.

FairweatherTait SJ, Wharf SG, Fox TE.

The effect of fortification iron (reduced iron) on zinc absorption from a commercial vegetablebased weaning food was assessed in 11 9moold infants. Each infant was fed a test meal of unfortified or ironfortified product, labeled extrinsically with 1 mg 67Zn or 70Zn (as citrate), and the next day was fed the second product labeled with the other isotope. A complete fecal collection was carried out for 34 d, and the amount of unabsorbed isotope measured by thermalionization quadrupole mass spectrometry. Apparent zinc absorption (isotope intake minus fecal excretion, expressed as the % of dose administered) was 31.1 8.3% (x SD) from the ironfortified food and 28.6%28.6 10.5% from the unfortified food. These values were not significantly different, thus iron fortification of the weaning food did not reduce zinc absorption. PMID 7572710

70_ 1995 Sep;238(3):22330.

Body iron stores, dietary iron intake and coronary heart disease mortality.

Reunanen A, Takkunen H, Knekt P, Seppanen R, Aromaa A.

OBJECTIVES. To assess whether increased body iron stores and dietary iron intake are associated with an increased risk of coronary heart disease mortality. DESIGN. A prospective population study with a mean mortality followup time of 14 years. SETTING. Participants attending a health screening examination carried out in several localities in Finland. SUBJECTS. All 6086 men and 6102 women aged from 45 to 64 years at the baseline examination without known heart disease, who had had serum iron and total iron binding capacity (TIBC) assessed. In a random fifth of these people, dietary iron intake was assessed by a dietary history. INTERVENTIONS. The study was observational without any interventions. MAIN OUTCOME MEASURES. Mortality from coronary heart disease. RESULTS. Altogether, 739 of the men and 245 of the women died from coronary heart disease. No relationship between TIBC and coronary mortality was observed in the men; in the women, an inverse although not significant association was found. Transferrin saturation was inversely but not significantly associated with coronary mortality in men; in women, the relationship was Uformed with a higher mortality at both the lower and higher ends of the distribution. Adjustment for other risk factors did not alter the results. No association was found with dietary iron intake and coronary mortality. CONCLUSIONS. The results do not corroborate earlier findings that excess body iron stores and increased iron intake are associated with an elevated risk of coronary heart disease. PMID 7673851

71_ 1995 Aug;29(4):3017.

[The effect of the use of milk fortified with iron and vitamin C on hemoglobin levels and nutritional status of children under 2]

Torres MA, Sato K, Lobo NF, de Souza Queiroz S.

The impact of the use of fortified powdered whole milk (9 mg of iron and 65 mg of vitamin C/100 g of milk) on the hemoglobin levels of children under 2 years of age was evaluated, over a period of 6 months, in 107 children enrolled in municipal Day Care Centers (DCC) and in 228 seen at a Basic Health Care Unit (BHCU). Before the beginning of the intervention, 66.4% of the children in the DCC and 72.8% of those seen at the BHCU had hemoglobin levels under 11.0 g/dl. After 6 months of fortified milk intake, these percentages fell to 20.6% and 18.0% respectively. The average hemoglobin before the intervention was 10.3 g/dl in the DCC and 10.5 in the BHCU. After 6 months these increased to 11.6 g/dl in the populations studied. Concerning the nutritional condition, evaluated according to Gomez's criteria, 57% of the DCC children presented an improvement, 41.1% showed changes and only 1.9% became worse. In the BHCU, 11.4% presented better condition, 70.6% remained the same and 18% worsened, which demonstrated differences in response regarding improvement of nutritional condition, when fortified milk was used in closed and open environments. The authors conclude that the utilization of enriched foods is an excellent alternative in the treatment of iron deficiency in populations of children under 2 years of age.

PIP: The impact of the use of fortified powdered whole milk (9 mg of iron and 65 mg of vitamin C per 100 g of milk) on the hemoglobin levels of children under 2 years of age was evaluated, over a period of 6 months, in 107 children enrolled in municipal day care centers (DCC) and in 228 seen at a Basic Health Care Unit (BHCU). Before the beginning of the intervention, 66.4% of the children in the DCC and 72.8% of those seen at the BHCU had hemoglobin levels under 11.0 g/dl. After 6 months of fortified milk intake, these percentages fell to 20.6% and 18.0%, respectively. The average hemoglobin level before the intervention was 10.3 g/dl in the DCC and 10.5 g/dl in the BHCU. After 6 months these increased to 11.6 g/dl in the populations studied. Concerning the nutritional condition, evaluated according to Gomez's criteria, 57% of the DCC children showed improvement, 41.1% showed no change, and only 1.9% grew worse. In the BHCU, 11.4% showed improvement, 70.6% remained the same, and 18% worsened, which demonstrated differences in response regarding improvement of nutritional condition when fortified milk was used in closed and open environments. The authors conclude that the utilization of enriched foods is an excellent alternative in the treatment of iron deficiency in populations of children under 2 years of age. (author's)

72_ 1995 Jul;62(1):11720.

Efficacy of weekly compared with daily iron supplementation.

Cook JD, Reddy MB.

A reduction in the frequency of iron supplement administration to once or twice weekly is being widely examined in developing countries on the assumption that the side effects of oral iron will decrease and that the reduction in administered iron will be offset by a lesser inhibition in absorption from iron taken on the previous day. We examined this premise by measuring iron absorption from 50 mg radiolabeled ferrous sulfate in 23 female volunteer subjects divided into two groups. In the first group, a labeled ferrous sulfate supplement was given with water, and in the second group it was given with a ricebased meal. In both groups, absorption was measured in a randomized fashion twice in each subject, once with daily and once with weekly supplementation. Those tested for daily supplementation were given an iron supplement daily for 6 d before testing whereas those tested for weekly supplementation were given no iron for 6 d before testing. When the labeled iron supplement was given with water only, absorption averaged 8.5% with daily and 9.8% with weekly administration compared with 2.3% and 2.6%, respectively, when given with food. The 13% lower absorption observed with daily administration in both groups was not statistically significant (P > 0.20). These results indicate that there is no significant absorptive advantage in giving iron less often than once daily.

73_ 1995 Jul;86(1):6571.

GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas: a randomized controlled trial. Leuprolide Acetate Study Group.

Stovall TG, MuneyyirciDelale O, Summitt RL Jr, Scialli AR.

OBJECTIVE: To determine the effectiveness of leuprolide acetate depot plus iron compared with iron alone in the preoperative treatment of anemia due to prolonged or excessive bleeding associated with uterine leiomyomas. METHODS: This was a phase III, stratified, randomized, doubleblind, placebocontrolled, parallelgroup, 12week multicenter study. Enrolled patients had hemoglobin levels of 10.2 g/dL or less and/or hematocrit values of 30% or less. Patients were entered into one of two strata based on their prestudy hematocrit level: stratum A, hematocrit less than or equal to 28%, and stratum B, hematocrit greater than 28%. Patients within each stratum were randomized to one of three treatment arms: leuprolide acetate depot 7.5 mg, leuprolide acetate depot 3.75 mg, or placebo. All patients received iron orally. Response was defined as a hemoglobin level of 12 g/dL or more and a hematocrit value of 36% or greater. RESULTS: Three hundred nine patients were entered into the study, of whom 265 were evaluated. Using our response criteria, a significantly greater number of patients in both leuprolide acetate groups (combined strata) responded to therapy than did those in the placebo group: 74% in each leuprolide acetate group versus 46% in the placebo group (P < .001). Gonadotropinreleasing hormone agonisttreated patients had a significant reduction in uterine and myoma volume when compared with the placebo group (P < .01). Hot flashes and vaginitis were reported significantly more often (P < .001) in the leuprolide acetatetreated groups than in the placebo group. CONCLUSION: Both dosages of GnRH agonist plus iron were more effective than iron alone in treating the anemia of patients with uterine leiomyomas, in reducing uterinemyoma volume, and in alleviating bleeding and other leiomyomarelated symptoms. PMID 7784025

74_ 1995 Apr;41(12):117.

The effect of iron deficiency and mental stimulation on Indonesian children's cognitive performance and development.

Soewondo S.

Three studies conducted in Indonesia will be described. Soewondo (12) investigated the relation of iron deficiency and cognitive function and impact of iron supplementation on verbal intelligence, attention and concept learning among iron deficient children without anemia and iron deficient anemic children. Half of 176 children, aged 36 years, received elemental Fe for 8 weeks and the other half received placebo. There were significant changes from pre to post intervention evaluations in ferritin, transferrin saturation, free erythrocyte protoporphyrin, and hemoglobin in the iron deficient anemic children. Pre and post treatment psychological test data showed that iron deficiency anemia produced alterations in cognitive processes related to visual attention and concept acquisition. These alterations can be reversed with iron treatment. Idjradinata (4) assessed the impact of iron supplementation on iron deficient infant's mental and psychomotor development. Hundred twenty six subjects aged 12 to 18 month were randomly assigned to either iron treatment or placebo intervention. After 4 months of iron supplementation, the hemoglobin, ferritin and transferrin saturation changed significantly in the iron deficient infants. A developmental delay was observed in the iron deficient anemic infants before intervention and the conditions were reversed after 4 months of iron treatment. Soemiarti (8) examined the effectiveness of a training course given to mothers of children aged 12 to 24 month on the rearing environment and consequently to the child's development. The subjects were 69 mothers of 2035 years old. The training lasted for 21 days by giving mothers training using the program "Ibu Maju Anak Bermutu". The rearing environment improved, also the child's mental and psychomotor development. PMID 7490909

75_ 1995 Feb;74(2):4125.

Iron requirement of chicks fed a semipurified diet based on casein and soy protein concentrate.

Aoyagi S, Baker DH.

An Fe depletion and repletion study was conducted to determine the Fe requirement of chicks fed a caseindextrose diet containing soy protein concentrate. Weight gain, hematocrit, hemoglobin, and serum total Fe showed marked increases when graded levels (0, 5, 10, 20, 30, 40, and 50 mg/kg) of Fe from analytical grade FeSO4.7H2O were added to an Fedeficient basal diet containing 46.5 mg Fe/kg. Subjecting the hemoglobin data to brokenline analysis indicated that the Fe requirement was 38.5 mg/kg of supplemental Fe (i.e., total dietary Fe of 85 mg/kg). Heart hypertrophy was observed in Fedeficient chicks, but Fe supplementation (more than 20 mg/kg) alleviated the problem. PMID 7724467

76_ 1995;31(4):4559.

Iron nutrition and iron status changes in Italian infants in the last decade.

Salvioli GP, Faldella G, Alessandroni R, Lanari M, Di Turi RP.

Two groups of 915 month old Italian infants were studied, at a 9 years' interval, to evaluate and compare feeding practices and their effect on iron status. Nutritional iron supply has increased in the last decade, due to a larger use of breast milk and ironfortified infant formulas. In 1983, 21.6% of infants were breastfed for 5 months or more, compared with 50.6% in 1992. In 1983, 73.3% of infants were fed on fresh cow's milk by the age of 6 months, compared with 7.6% in 1992. Consequently, iron status is markedly improved. In 1983, 5% of the examined infants were anemic and 20.7% showed iron deficiency without anemia, compared with 1.3% and 10.3% respectively in 1992. Our study supports the following recommendations: after 5 months of age exclusively breastfed infants should receive an additional 1 mg/kg/die iron supplement and iron fortified formulas should be used instead of fresh cow's milk during the first year of life. PMID 8851702

77_ 1995 Jan;52(1):5967.

The effect of iron fortification on the fatty acid composition of plasma and erythrocyte membranes in primary school children with and without iron deficiency.

Smuts CM, Tichelaar HY, van Jaarsveld PJ, Badenhorst CJ, Kruger M, Laubscher R, Mansvelt EP, Benade AJ.

An intervention study was designed to evaluate the fatty acid (FA) status of children aged 611 years before and after iron fortification. Irondeficient (ID) and matched controls without ID (n = 30) were selected. All children received soup (160 ml) fortified with 20 mg iron and 100 mg vitamin C for 15 weeks on school days. Measurements before and after intervention included dietary intake, haematological and iron status and FA composition of plasma and erythrocyte membranes (EMBs). The prevalence of low plasma ferritin concentration and transferrin saturation decreased in the ID children by 40% and 56%, respectively, with intervention. Plasma FAs reflected dietary FA intake. In comparison with controls, the ID group presented with increased percentage total saturated FAs (SFAs; p = 0.0002) in their EMB phosphatidylcholine (PC) and reduced percentage total polyunsaturated FAs (PUFAs; p = 0.0037) before intervention. Lower total n3 FAs (p = 0.0070), including eicosapentenoic acid (EPA; p = 0.0034), docosapentenoic acid (DPA; p = 0.0048) and docosahexenoic acid (DHA; p = 0.0058), were observed in the ID group. The EMB phosphatidylethanolamine (PEA) of the ID children presented with lower percentages of alphalinolenic acid (ALA; p = 0.0001), EPA (p = 0.0051) and DHA (p = 0.0084) compared to controls before intervention. Iron intervention was associated with an increase (p < 0.05) in the percentage of n3 FAs in the EMBPC and EMBPEA of the ID group to percentages comparable to that in the control group. It appears that iron status can influence FA metabolism of specific n3 FAs in the EMBs of young children. PMID 7708822

78_ 1995 Jan;29(1):347.

[Evaluation of the effects of intermittent iron supplement on irondeficiency anemia in children]

Liu X, Yang W, Song Y.

A threemonth iron supplement trial was conducted in 238 preschool children, who were divided randomly into three groups supplemented with oral administration of iron preparation at the same dose everyday, every other two days, and each week, respectively, to avoid lowabsorption and sideeffects of oral iron preparation and to evaluate its preventive and treatment effects and sideeffects. Results showed individual ironsupplement by once every other two days or each week was efficient as same as by once everyday in improving anemia and increasing serum ferritin level. It can also reduce transient iron overload and gastrointestinal sideeffects caused by daily iron supplement.

79_ 1994 Dec;72(6):899909.

The effects of iron deficiency and iron overload on cellmediated immunity in the mouse.

Omara FO, Blakley BR.

The influence of Fe status on cellmediated immunity was studied in weanling mice fed on Fedeficient (7 mg Fe/kg), Fesufficient (120 mg Fe/kg) and highFe (3000 or 5000 mg Fe/kg) diets for 7 weeks. The contact sensitivity (CS) response to dinitrofluorobenzene (DNFB), the in vivo delayedtype hypersensitivity (DTH) response to sheep erythrocytes (SRBC) and the ability of primed spleen cells to transfer DTH response to naive normal mice were suppressed in mice consuming the Fedeficient diet. HighFe diets (3000 or 5000 mg Fe/kg) selectively suppressed the CS response to DNFB, but the DTH response to SRBC or the transfer of DTH response by primed spleen cells to naive normal mice remained normal. Spleen cell functions associated with the expression of class II major histocompatibility (MHC) surface antigens, concanavalin Ainduced interleukin2 (IL2) secretion or the antigenpresenting cell (APC) ability to stimulate antigendependent proliferation of an SRBCspecific helper Tlymphocyte clone were not altered by Fe status. However, consistent with the suppressed DTH response in the Fedeficient mice was the suppressed concanavalin Ainduced Tlymphocyte blastogenesis and the interferongamma (INFgamma) production by spleen cells from mice fed on the Fedeficient diet. Spleen cells from mice fed on excess levels of Fe in the diet secreted less INFgamma than the control mice, although Tlymphocyte proliferation remained unaffected. Suppression of the cellular immune response associated with Fe deficiency may be related in part to impaired Tlymphocyte proliferation and INFgamma secretion rather than to deficits in IL2 secretion or APC function. PMID 7827010

80_ 2000 Mar;142(3):21723.

Iron supplementation in goitrous, irondeficient children improves their response to oral iodized oil.

Zimmermann M, Adou P, Torresani T, Zeder C, Hurrell R.

OBJECTIVE: In developing countries, many children are at high risk for both goiter and irondeficiency anemia. Because iron deficiency may impair thyroid metabolism, the aim of this study was to determine if iron supplementation improves the response to oral iodine in goitrous, irondeficient anemic children. DESIGN: A trial of oral iodized oil followed by oral iron supplementation in an area of endemic goiter in the western Ivory Coast. METHODS: Goitrous, iodinedeficient children (aged 612 years; n=109) were divided into two groups: Group 1 consisted of goitrous children who were not anemic; Group 2 consisted of goitrous children who were irondeficient anemic. Both groups were given 200mg oral iodine as iodized oil. Thyroid gland volume using ultrasound, urinary iodine concentration (UI), serum thyroxine (T(4)) and whole blood TSH were measured at baseline, and at 1, 5, 10, 15 and 30 weeks post intervention. Beginning at 30 weeks, the anemic group was given 60mg oral iron as ferrous sulfate four times/week for 12 weeks. At 50 and 65 weeks after oral iodine (8 and 23 weeks after completing iron supplementation), UI, TSH, T(4) and thyroid volume were remeasured. RESULTS: The prevalence of goiter at 30 weeks after oral iodine in Groups 1 and 2 was 12% and 64% respectively. Mean percent change in thyroid volume compared with baseline at 30 weeks in Groups 1 and 2 was 45.1% and 21.8% respectively (P<0.001 between groups). After iron supplementation in Group 2, there was a further decrease in mean thyroid volume from baseline in the anemic children (34.8% and 38.4% at 50 and 65 weeks) and goiter prevalence fell to 31% and 20% at 50 and 65 weeks. CONCLUSION: Iron supplementation may improve the efficacy of oral iodized oil in goitrous children with irondeficiency anemia. PMID 10700714

81_ 2000 Mar;88(3):110311.

Iron supplementation improves endurance after training in irondepleted, nonanemic women.

Hinton PS, Giordano C, Brownlie T, Haas JD.

Our objective was to investigate the effects of iron depletion on adaptation to aerobic exercise, assessed by time to complete a 15km cycle ergometer test. Fortytwo irondepleted (serum ferritin <16 microg/l), nonanemic (Hb >12 g/dl) women (1833 yr old) received 100 mg of ferrous sulfate (S) or placebo (P) per day for 6 wk in a randomized, doubleblind trial. Subjects trained for 30 min/day, 5 days/wk at 7585% of maximum heart rate for the final 4 wk of the study. There were no group differences in baseline iron status or in 15 km time. Iron supplementation increased serum ferritin and decreased transferrin receptors in the S compared with the P group. The S and P groups decreased 15km time and respiratory exchange ratio and increased work rate during the 15km time trial after training. The decrease in 15km time was greater in the S than in the P group (P = 0.04) and could be partially attributed to increases in serum ferritin and Hb. These results indicate that iron deficiency without anemia impairs favorable adaptation to aerobic exercise. PMID 10710409

82_ 2000 Mar;105(3):E38.

Clinical safety of ironfortified formulas.

Singhal A, Morley R, Abbott R, FairweatherTait S, Stephenson T, Lucas A.

BACKGROUND: Ironfortified formulas are recommended throughout infancy and are frequently used beyond, yet safety aspects have been inadequately studied. Iron could theoretically increase prooxidant stress, with potential adverse effects, including infection risk, and some clinicians suspect that ironfortified formulas induce gastrointestinal disturbance. OBJECTIVE: A planned component of a large intervention trial has been to test the hypothesis that infants receiving ironfortified formula do not have a higher incidence of infections (primary outcome) or gastrointestinal problems (secondary outcome) than infants on low ironformulas or cow's milk. Methods. Children (n = 493) 9 months old receiving cow's milk were recruited in 3 UK centers and randomized to: 1) cow's milk as before, 2) formula containing.9 mg/L of iron, or 3) an otherwise identical formula but containing 12 mg/L of iron. Children were followed at 3 monthly intervals and the episodes of infections, diarrhea and constipation, and general morbidity to 18 months old were recorded. Hematologic indices of iron status were determined at 18 months old. RESULTS: Serum ferritin concentrations were increased in infants receiving ironfortified formula but there were no intergroup differences in incidence of infection, gastrointestinal problems, or in general morbidity or weight gain. CONCLUSIONS: We were unable to identify adverse health effects in older infants and toddlers consuming a high ironcontaining formula (12 mg/L) even when used in populations with a low incidence of iron deficiency. PMID 10699140

83_ 2000 Mar 1;97(5):2815.

Effect of iron therapy on the whole blood platelet aggregation in infants with iron deficiency anemia.

Kurekci AE, Atay AA, Sarici SU, Zeybek C, Koseoglu V, Ozcan O.

This study was performed to investigate the platelet aggregation alterations in whole blood samples of infants with iron deficiency anemia. Platelet aggregation induced by various concentrations of adenosine diphosphate (ADP) and collagen was studied with impedance aggregometry in 25 patients before and after oral iron therapy and in 12 children of the control group. The posttreatment mean maximum aggregation values were significantly higher (p<0.01) and the posttreatment mean aggregation times were significantly lower (p<0.01) in the study group at all concentrations of ADP and collagen. The aggregation time and maximum aggregation values revealed no significant difference except for the maximum aggregation value at 5 microM ADP (p<0.05) between the study group after therapy and the control group. The differences between the pretreatment and posttreatment mean platelet counts and mean platelet volume values in the study group were statistically significant (p<0.01), whereas those values in the study group after therapy and in the control group were not significantly different. We conclude that iron deficiency anemia in infants, even without clinically meaningful platelet abnormality, may cause dysfunction of the ex vivo whole blood platelet aggregation, and can be reversed by iron therapy. Further studies should be carried out at the enzymatic level to determine whether this platelet aggregation dysfunction in iron deficiency anemia is due to a deficiency in the activation of ironcontaining enzymes. PMID 10709903

84_ 2000 Feb;130(2S Suppl):448S451S.

The potential impact of iron supplementation during adolescence on iron status in pregnancy.

Lynch SR.

Iron deficiency anemia (IDA) during pregnancy is associated with significant morbidity for mothers and infants. Over 50% of pregnant women in developing countries suffer from IDA. It is also prevalent among adolescent girls because the growth spurt and onset of menstruation increase iron requirements. Women who conceive during or shortly after adolescence are likely to enter pregnancy with low or absent iron stores or IDA. Iron supplementation during adolescence is one of the new strategies advocated to improve iron balance in pregnancy. However, iron requirements are highest in the second and third trimesters and the model described here indicates that iron balance at this stage depends more on adequate intakes of bioavailable iron than on the size of the iron stores at conception. Furthermore, although supplementation will correct anemia and increase iron stores in girls, the positive effect on iron status will be temporary if their diets do not contain adequate bioavailable iron. Although iron status in early pregnancy may be improved if the period of supplementation continues up to the time of conception, supplementation before pregnancy should be viewed as an additional strategy to supplementation during the second and third trimesters. PMID 10721925

85_ 2000 Feb;130(2S Suppl):452S455S.

Supplementation with iron and folic acid enhances growth in adolescent Indian girls.

Kanani SJ, Poojara RH.

The prevalence of anemia is high in adolescent girls in India, with over 70% anemic. Ironfolic acid (IFA) supplements have been shown to enhance adolescent growth elsewhere in the world. To confirm these results in India, a study was conducted in urban areas of Vadodora, India to investigate the effect of IFA supplements on hemoglobin, hunger and growth in adolescent girls 1018 y of age. Results show that there was a high demand for IFA supplements and >90% of the girls consumed 85 out of 90 tablets provided. There was an increment of 17.3 g/L hemoglobin in the group of girls receiving IFA supplements, whereas hemoglobin decreased slightly in girls in the control group. Girls and parents reported that girls increased their food intake. A significant weight gain of 0.83 kg was seen in the intervention group, whereas girls in the control group showed little weight gain. The growth increment was greater in the 10 to 14yold age group than in the 15 to 18yold group, as expected, due to rapid growth during the adolescent spurt. IFA supplementation is recommended for growth promotion among adolescents who are underweight. PMID 10721926

86_ 2000 Feb;130(2S Suppl):456S458S.

Reaching young Indonesian women through marriage registries: an innovative approach for anemia control.

Jus'at I, Achadi EL, Galloway R, Dyanto A, Zazri A, Supratikto G, Zizic L, Elder L.

In an effort to build iron stores before pregnancy and reduce the high prevalence of anemia in Indonesia, the Ministry of Health/Indonesia and the MotherCare project implemented an anemia control program for newly wed women. As part of an existing program to counsel couples about marriage and require them to obtain tetanus toxoid immunization before obtaining a marriage certificate, women also were counseled to buy and take 3060 ironfolate (IFA) tablets. Women (n = 344) were enrolled from one of three participating districts in South Kalimantan, Indonesia. At first monitoring, at least 30 d after baseline, 261 women were tested for hemoglobin and asked about their IFA tablet consumption and knowledge of information, education, and communications (IEC) materials promoted through the program. Results showed that there was a decrease in the prevalence of anemia from 23.8 to 14.0% over the course of the program, 98% of women had taken at least some IFA tablets and 56% had taken >30 tablets. PMID 10721927

87_ 2000;78(1):97107.

Costeffectiveness of iron supplementation and malaria chemoprophylaxis in the prevention of anaemia and malaria among Tanzanian infants.

Alonzo Gonzalez M, Menendez C, Font F, Kahigwa E, Kimario J, Mshinda H, Tanner M, BoschCapblanch X, Alonso PL.

Prerequisites for effective interventions against severe anaemia and malaria among infants are economic evaluations to aid the setting of priorities and the making of health policy. In the present study we analysed the cost and effectiveness of three control strategies hypothetically delivered through the Expanded Programme on Immunization (EPI). For the prevention of severe anaemia and from the perspective of the health provider, the costeffectiveness ratios were, respectively, US$ 8, US$ 9, and US$ 21 per disabilityadjusted life year (DALY) for malaria chemoprophylaxis with Deltaprim (a combination of 3.125 mg pyrimethamine and 25 mg dapsone) + iron, Deltaprim alone, or iron supplementation alone. For malaria prevention, Deltaprim + iron cost US$ 9.7 per DALY and Deltaprim alone cost US$ 10.2 per DALY. From a sociocultural perspective the costeffectiveness ratios ranged from US$ 9 to US$ 26 for severe anaemia prevention and from US$ 11 to US$ 12 for the prevention of clinical malaria. These ratios were highly costeffective, as defined by the World Bank's proposed threshold of less than US$ 25 per DALY for comparative assessments. Furthermore, all the preventive interventions were less costly than the current malaria and anaemia control strategies that rely on clinical case management. This economic analysis supports the inclusion of both malaria chemoprophylaxis and iron supplementation delivered through EPI as part of the control strategies for these major killers of infants in parts of subSaharan Africa. PMID 10686744

88_ 2000 Jan;54(1):2935.

Effect of daily iron supplementation on iron status, cellmediated immunity, and incidence of infections in 636 month old Togolese children.

Berger J, Dyck JL, Galan P, Aplogan A, Schneider D, Traissac P, Hercberg S.

OBJECTIVE: To assess the impact of a daily oral iron supplementation on hematological status, cellmediated immunity and susceptibility to infections in children living in an environment where iron deficiency, malaria and other infections are frequent. DESIGN: Randomized, doubleblind iron supplementation including a placebo group. SETTING: A village in Togo, West Africa. SUBJECTS: Of the 229 636monthold children of both sexes recruited, 197 with hemoglobin concentration >/=80 g/l were included and 163 completed the study. INTERVENTION: Children received daily a placebo (n=79) or a dose of 23 mg of elemental iron per kg of body weight (n=84) for 3 months. Hematological, nutritional and immune status were assessed at the beginning and at the end of the supplementation period, and 6 months later. Morbidity was recorded throughout the study. RESULTS: Iron supplementation had a significant and positive effect on iron status of children and no impact on the incidence of infections, especially malaria. Its probable effect on immune status was masked by interference of infections and their treatment, which contributed to improve hematological and immune status in both groups. CONCLUSION: According to the negative consequences of anemia and iron deficiency on global child development, control of iron deficiency by oral iron supplementation in young children has to be conducted, associated with prophylaxis and treatment of malaria and repeated deworming. SPONSORSHIP: Program supported by IRD. European Journal of Clinical Nutrition (2000) 54, 2935 PMID 10694769

89_ 1999 Nov;129(11):201320.

Longterm weekly iron supplementation improves and sustains nonpregnant women's iron status as well or better than currently recommended shortterm daily supplementation.

Viteri FE, Ali F, Tujague J.

This 7mo doubleblind study compared the efficacy of two iron supplementation schemes in improving iron nutrition among 116 healthy fertileage women. They were randomly distributed in three groups, receiving: Group 1, iron + folate (60 mg and 250 microg, respectively) daily for 3 mo (currently recommended scheme), and folate (250 microg) weekly the subsequent 4 mo. Group 2, folate daily, and 60 mg iron only once weekly for 3 mo, and then weekly iron + folate for 4 mo. Group 3, folate daily for 3 mo and then weekly for 4 mo. At baseline, 16% had depleted stores (plasma ferritin <15 microg/L) and 16% had hemoglobin levels <125 g/L. Eight percent had hemoglobin levels <120 g/L. In Group 1 hemoglobin and ferritin increased at 3 mo but returned to near basal conditions after 4 mo of weekly folate. In Group 2, hemoglobin and ferritin increased progressively throughout the 7 mo but mostly after 3 mo. Group 3 did not change. Side effects were highest with daily iron. Weekly iron supplementation over 7 mo (30 doses) improved and sustained iron nutrition at least as effectively and was better tolerated than 90 daily iron supplements consumed during 3 mo. PMID 10539778

90_ 1999 Oct;34(4 Suppl 2):S406.

Beneficial effects of adopting an aggressive intravenous iron policy in a hemodialysis unit.

Macdougall IC, Chandler G, Elston O, Harchowal J.

Iron deficiency is the most common cause of a suboptimal response to epoetin therapy, and the treatment of choice is intravenous (IV) iron. It is also increasingly recognized that IV iron can enhance the response to epoetin, even in ironreplete patients. The aim of the present study was to examine the effects of adopting an aggressive IV iron policy in all patients attending a singlecenter hemodialysis unit. The protocol was simple and practical, and involved administering a weekly IV bolus of 100 mg iron sucrose to all patients with a serum ferritin level of 150 to 1,000 microg/L. Only patients with a serum ferritin level greater than 1,000 microg/L were excluded; patients with a serum ferritin level below 150 microg/L were given a more aggressive IV dosing regimen to get into range for the standard protocol. Among 116 patients included in the study, the mean serum ferritin level increased from 214 microg/L in November 1997 to 564 microg/L in November 1998 (P < 0.0001). Mean hemoglobin increased modestly from 9.6 g/dL to 10.7 g/dL over the same period, but there was a dramatic reduction in mean epoetin dose from 13,277 U/wk to 8,976 U/wk (P < 0.0005), resulting in cost savings of approximately pound 228,000 ($366,000), or pound 152 ($244) per patient per month. No adverse reactions to IV iron were seen among a total of 4,564 injections, and there was no obvious increase in the incidence of infection. This simple, practical IV iron dosing policy resulted in dramatic savings in epoetin dosage and cost with no significant adverse effects. PMID 10516375

91_ 1999 Sep;81(3):2612.

Breath holding spells in 91 children and response to treatment with iron.

Mocan H, Yildiran A, Orhan F, Erduran E.

To evaluate the prognosis of breath holding spells (BHS) after iron treatment, 91 children (56 boys, 35 girls) aged between 6 months and 40 months (median, 17) were followed prospectively for a median of 45 months (range, 689). In 49 of the children, the frequency of BHS was less than 10 each month, in 22 it was 1030 each month, and in 20 more than 30 each month. The spells were cyanotic in 60 children. All patients were evaluated initially and during follow up for haematological indices. Electroencephalographic and electrocardiographic abnormalities were also recorded. Sixty three patients were found to have iron deficiency anaemia and were treated with iron (6 mg/kg/day) for three months. Other patients were not given any treatment. After three months, there was a significant difference for correction of cyanotic spells between children who had been treated with iron and those who had not (84.1% v 21.4%). During further follow up, febrile convulsions occurred in 10 children (six were on iron treatment initially). It appears that treating iron deficiency anaemia is effective in reducing the frequency of BHS. PMID 10451402

92_ 1999 Jul;81(1):F459.

Iron nutritional status in preterm infants fed formulas fortified with iron.

Griffin IJ, Cooke RJ, Reid MM, McCormick KP, Smith JS.

AIMS: To prospectively evaluate the iron nutritional status of preterm infants fed either a term (0.5 mg/dl iron) or preterm (0.9 mg/dl) formulas fortified with iron after hospital discharge. METHODS: Healthy low birthweight preterm infants were randomly assigned into three groups at the time of hospital discharge. Group A were fed an iron fortified preterm formula (0.9 mg/dl iron) until 6 months corrected age; group B, a fortified term formula (0.5 mg/l iron) until 6 months corrected age group C, the preterm formula between hospital discharge and term, then the term formula until 6 months corrected age. RESULTS: Seventy eight infants were followed up to 6 months corrected age. Iron intake from formula differed significantly between the groups (A, 1.17 mg/kg/day (SD 0.32) > C, 0. 86 mg/kg/day (SD 0.40) = B, 0.81 mg/kg/day (SD 0.23); p < 0.0001). Haemoglobin concentrations were similar to those of iron sufficient preterm infants of the same postnatal age, and term infants of the same postmenstrual age (after 3 months of age). There were no significant differences in haemoglobin concentration (p = 0.391), plasma ferritin (A vs B, p = 0.322), or in the incidence of iron deficiency (A vs B, p = 0.534). CONCLUSIONS: Iron fortified formulas containing between 0.5 and 0.9 mg/dl iron seem to meet the iron nutritional needs of preterm infants after hospital discharge. PMID 10375362

93_ 1999 Jul;13(12):516.

Longterm zinc and iron supplementation in children of short stature: effect of growth and on trace element content in tissues.

Perrone L, Salerno M, Gialanella G, Feng SL, Moro R, Di Lascio R, Boccia E, Di Toro R.

We evaluated the effect of one year of supplementation with iron plus zinc (12 mg/day of Fe+++ and 12.5 mg/day of Zn++), zinc alone (12.5 mg/day of Zn++) and placebo on growth and on the iron, zinc, copper and selenium tissue contents in 30 wellselected children of short stature (16 M and 14 F; 411 years old). Before and after supplementation, we measured the concentrations of iron, transferrin, ferritin, zinc and copper in serum, of zinc in erythrocytes and leukocytes, and of zinc, copper and selenium in hair, as well as glutathione peroxidase activity in erythrocytes. Before supplementation, ferritin and serum, erythrocyte and hair zinc contents were significantly lower than in age matched controls, while the other measured indices were in the normal range. Iron plus zinc supplementation caused an improvement in growth rate in all subjects, i.e., the median Zscore increased from 2.22 +/ 0.45 to 0.64 +/ 0.55; (p < 0.01). In the zincsupplemented group, only the subjects whose ferritin levels were higher than 20 ng/L before supplementation showed a similar improvement of growth rate. Iron plus zinc supplementation could be a reasonable treatment in short, prepubertal children affected by marginal zinc and iron deficiency. PMID 10445218

94_ 1999 Jun;69(6):125763.

Adding zinc to prenatal iron and folate supplements improves maternal and neonatal zinc status in a Peruvian population.

Caulfield LE, Zavaleta N, Figueroa A.

BACKGROUND: Maternal zinc deficiency during pregnancy may be widespread among women in developing countries, but few data are available on whether prenatal zinc supplementation improves maternal and neonatal zinc status. OBJECTIVE: We studied whether maternal zinc supplementation improved the zinc status of mothers and neonates participating in a supplementation trial in a shantytown in Lima, Peru. DESIGN: Beginning at gestation week 1024, 1295 mothers were randomly assigned to receive prenatal supplements containing 60 mg Fe and 250 microg folate, with or without 15 mg Zn. Venous blood and urine samples were collected at enrollment, at gestation week 2830, and at gestation week 3738. At birth, a sample of cord vein blood was collected. We measured serum zinc concentrations in 538 women, urinary zinc concentrations in 521 women, and cord zinc concentrations in 252 neonates. RESULTS: At 2830 and 3738 wk, mothers receiving zinc supplements had higher serum zinc concentrations than mothers who did not receive zinc (8.8 +/ 1.9 compared with 8.4 +/ 1.5 micromol/L and 8.6 +/ 1.5 compared with 8.3 +/ 1.4 micromol/L, respectively). Urinary zinc concentrations were also higher in mothers who received supplemental zinc (P < 0.05). After adjustment for covariates and confounding factors, neonates of mothers receiving zinc supplements had higher cord zinc concentrations than neonates of mothers who did not receive zinc (12.7 +/ 2.3 compared with 12.1 +/ 2.1 micromol/L). Despite supplementation, maternal and neonatal zinc concentrations remained lower than values reported for wellnourished populations. CONCLUSION: Adding zinc to prenatal iron and folate tablets improved maternal and neonatal zinc status, but higher doses of zinc are likely needed to further improve maternal and neonatal zinc status in this population. PMID 10357748

95_ 1999 Mar 13;318(7185):6937.

Erratum in: BMJ 2000 Jul 1;321(7252):23.

Iron supplemented formula milk related to reduction in psychomotor decline in infants from inner city areas: randomised study.

Williams J, Wolff A, Daly A, MacDonald A, Aukett A, Booth IW.

OBJECTIVE: To compare the effect of unmodified cows' milk and iron supplemented formula milk on psychomotor development in infants from inner city areas when used as the main milk source. DESIGN: Double blind, randomised intervention trial. SETTING: Birmingham health centre. SUBJECTS: 100 infants, mean age 7.8 months (range 5.7 to 8.6 months), whose mothers had already elected to use unmodified cows' milk as their infant's milk source. INTERVENTION: Changing to an iron supplemented formula milk from enrolment to 18 months of age, or continuing with unmodified cows' milk. MAIN OUTCOME MEASURES: Developmental assessments using Griffiths scales at enrolment and at 18 and 24 months. RESULTS: 85 participants completed the trial. There were no significant differences in haemoglobin concentration between the two groups at enrolment, but by 18 months of age 33% of the unmodified cows' milk group, but only 2% of the iron supplemented group, were anaemic (P<0.001). The experimental groups had Griffiths general quotient scores that were not significantly different at enrolment, but the scores in both groups declined during the study. By 24 months the decrease in the mean scores in the unmodified cows' milk group was 14.7 whereas the decrease in the mean scores in the iron supplemented group was 9.3 (P<0.02, 95% confidence interval 0.4 to 10.4). Mean subquotient scores were considerably lower in the unmodified cows' milk group at 24 months; significantly so for personal and social scores (P<0.02, 1.2 to 16.8 [corrected]). CONCLUSION: Replacing unmodified cows' milk with an iron supplemented formula milk up to 18 months of age in infants from inner city areas prevents iron deficiency anaemia and reduces the decline in psychomotor development seen in such infants from the second half of the first year.

96_ 1999 Mar;69(3):497503. Effect of iron, iodine, and betacarotenefortified biscuits on the micronutrient status of primary school children: a randomized controlled trial.

van Stuijvenberg ME, Kvalsvig JD, Faber M, Kruger M, Kenoyer DG, Benade AJ.

BACKGROUND: Deficiencies of iron, iodine, and vitamin A are prevalent worldwide and can affect the mental development and learning ability of schoolchildren. OBJECTIVE: The aim of this study was to determine the effect of micronutrientfortified biscuits on the micronutrient status of primary school children. DESIGN: Micronutrient status was assessed in 115 children aged 611 y before and after consumption of biscuits (fortified with iron, iodine, and betacarotene) for 43 wk over a 12mo period and was compared with that in a control group (n = 113) who consumed nonfortified biscuits. Cognitive function, growth, and morbidity were assessed as secondary outcomes. RESULTS: There was a significant betweengroup treatment effect on serum retinol, serum ferritin, serum iron, transferrin saturation, and urinary iodine (P <0.0001) and in hemoglobin and hematocrit (P <0.05). The prevalence of low serum retinol concentrations (<0.70 micromol/L) decreased from 39.1% to 12.2%, of low serum ferritin concentrations (<20 microg/L) from 27.8% to 13.9%, of anemia (hemoglobin <120 g/L) from 29.6% to 15.6%, and of low urinary iodine concentrations (<100 microg/L) from 97.5% to 5.4%. There was a significant betweengroup treatment effect (P <0.05) in cognitive function with the digit span forward task (shortterm memory). Fewer school days were missed in the intervention than in the control group because of respiratory (P = 0.097) and diarrhearelated (P = 0.013) illnesses. The intervention had no effect on anthropometric status [corrected]. CONCLUSIONS: Fortified biscuits resulted in a significant improvement in the micronutrient status of primary school children from a poor rural community and also appeared to have a favorable effect on morbidity and cognitive function [corrected].

97_ 1999 Mar;53(3):18994.

Nutrient intake and iron status of Australian male vegetarians.

Wilson AK, Ball MJ.

OBJECTIVE: The study was designed to investigate the iron intake and status of Australian, male vegetarians aged between 20 and 50 y. DESIGN: Cross sectional comparison of male vegetarians and age/sex matched omnivores. SETTING: Freeliving community subjects. SUBJECTS: 39 ovolactovegetarians, 10 vegans and 25 omnivores were recruited by local advertisement. OUTCOME MEASURES: A 12d semiquantitative dietary record to assess iron and zinc intake. Iron status was assessed by measurement of serum ferritin and haemoglobin concentrations. RESULTS: Mean (s.d.) daily iron intakes of both the ovolactovegetarians (20.4 (7.7) mg/d) and vegans (22.9 (6.2) mg/d), were significantly higher than the omnivores' intake of 15.8 (4.5) mg/d. Ovolactovegetarians and vegans had significantly (P < 0.001 and P < 0.05, respectively) lower serum ferritin concentrations than omnivores: mean (s.d.): 64 (46.9), 65 (49.9) and 121 (72.5) ng/ml, respectively. Significantly more ovolactovegetarians and vegans than omnivores had serum ferritin concentrations below 25 ng/ml and below 12 ng/ml (P < 0.05). A higher proportion of omnivores had concentrations above 200 ng/ml (P < 0.05). The differences in serum ferritin concentrations between the vegetarians and omnivores remained significant even after exclusion of iron supplement users. CONCLUSION: Australian male vegetarians had iron intakes higher than those of omnivores and above recommended levels, but their iron status was significantly lower. PMID 10201799

98_ 1999 Feb;180(2 Pt 1):48390.

Adding zinc to prenatal ironand folate tablets improves fetal neurobehavioral development.

Merialdi M, Caulfield LE, Zavaleta N, Figueroa A, DiPietro JA.

Center for Human Nutrition, Department of International Health, The Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, USA.

OBJECTIVE: Our objective was to examine whether improvement in maternal zinc status during pregnancy is positively associated with fetal neurobehavioral development in a Peruvian population. STUDY DESIGN: We electronically monitored, at 32 and 36 weeks' gestation, 55 fetuses whose mothers were randomly assigned to receive, during pregnancy, a daily supplement containing 60 mg iron and 250 microg folate, with or without 15 mg zinc. Fetal heart rate and movement patterns were quantified in 55 and 34 fetuses, respectively, as indexes of neurobehavioral development. RESULTS: Fetuses of mothers who received zinc supplementation showed fewer episodes of minimal fetal heart rate variability, increased fetal heart rate range, an increased number of accelerations, an increased number of movement bouts, an increased amount of time spent moving, and an increased number of large movements. Differences by supplementation type increased with gestational age and were statistically significant at 36 weeks' gestation (P <.05). CONCLUSION: Improving maternal zinc status through prenatal supplementation may improve fetal neurobehavioral development. PMID 9988823

99_ 1999 Feb;53(2):1026.

Treatment for iron deficiency anaemia with a combined supplementation of iron, vitamin A and zinc in women of Dinajpur, Bangladesh.

Kolsteren P, Rahman SR, Hilderbrand K, Diniz A.

OBJECTIVE: The study was set up to determine to what extent the addition of a supplement of vitamin A alone or in combination with zinc would improve standard iron treatment and correction of iron deficiency anaemia. DESIGN: 216 nonpregnant anaemic women of 1545 years of age with haemoglobin levels < or = 100 g/l were randomly assigned to three treatment groups. One group (A) received iron alone, a second group (B) received iron and vitamin A, and a third group (C) received iron, vitamin A and zinc. Every woman was given one iron capsule per day for 60 days as FeSO4 containing 60 mg of elemental iron. In addition, groups B and C received 200,000 i.u. of vitamin A, given as a supervised dose, on the first day of the treatment after collection of the blood sample. Group C received one zinc tablet per day for 60 days as zinc gluconate containing 15 mg of elemental zinc. SETTING: The northwestern part of Bangladesh in the urban slums of Dinajpur district between February and August 1995. SUBJECTS: To select women with a haemoglobin level of < or = 100 g/l, all the women of four randomly selected municipal slums of the district in the targeted age group (328) were invited to take part in the study. Blood samples were analysed for haemoglobin, serum iron, total iron binding capacity (TIBC), ferritin, retinol and zinc. RESULTS: Out of the 328 women screened, 254 (77.5%) had a haemoglobin level < or = 100 g/l and 322 (98%) < or = 120 g/l. The three treatment schedules significantly increased haemoglobin levels and improved iron parameters, except for serum iron in the group who received iron alone. The group who received iron, vitamin A and zinc responded best with an increase in haemoglobin of 17.9 g/l as compared to the group receiving iron alone (13.4 g/l). Iron and vitamin A treatment gave an intermediate response of 15.9 g/l. However, these differences are only statistically significant only for the group who received iron, vitamin A and zinc and only for the increase in haemoglobin, P = 0.03. CONCLUSION: The results are suggestive that the addition of vitamin A and zinc to the treatment for anaemia can increase haemoglobin levels more than with iron alone. PMID 10099942

100_ 1999 Feb;158(2):14751.

Oral iron is sufficient for erythropoietin treatment of very low birth weight infants.

Kivivuori SM, Virtanen M, Raivio KO, Viinikka L, Siimes MA.

The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO) treated very low birthweight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron (ferrofumarate, 6 mg of iron/kg per day). Another 14 infants received the same erythropoietin dose and intramuscular iron (ferroxypolymaltose, once 12 mg of iron/kg weekly). Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO. After the 3week study period, haemoglobin concentrations and reticulocyte counts were similar in the rHuEPOtreated groups and both were higher than in the group not receiving rHuEPO (P < 0.001). In both rHuEPOtreated groups the transferrin receptor concentration increased from 6.87.2 mg/l to 10.5 11.3 mg/l. CONCLUSION: In erythropoietintreated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron. PMID 10048613