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Iron: 197 Research Abstracts

101_ 1999 Jan;69(1):806.

Effect of daily and weekly micronutrient supplementation on micronutrient deficiencies and growth in young Vietnamese children.

Thu BD, Schultink W, Dillon D, Gross R, Leswara ND, Khoi HH.

BACKGROUND: Micronutrient deficiencies remain common in preschool children in developing countries. Interventions focus on single micronutrients and often lack effectiveness. Weekly instead of daily supplementation may improve effectiveness. OBJECTIVE: The efficacy of weekly and daily supplementation in reducing anemia prevalence and in improving the zinc, vitamin A, and growth status of 624moold Vietnamese children was investigated. DESIGN: In this doubleblind, placebocontrolled trial, the daily group (n = 55) received 8 mg elemental Fe (as iron sulfate), 5 mg elemental Zn (as zinc sulfate), 333 microg retinol, and 20 mg vitamin C 5 d/wk for 3 mo. The weekly group (n = 54) received 20 mg Fe, 17 mg Zn, 1700 microg retinol, and 20 mg vitamin C once a week. A third group (n = 54) received a placebo only. Venous blood samples were collected at the start and end of the supplementation period and anthropometric measurements were taken at the start and 3 mo after the end of supplementation. RESULTS: At baseline, 45.6% of subjects had hemoglobin concentrations < 110 g/L, 36.3% had zinc concentrations < 10.71 micromol/L, and 45.6% had retinol concentrations <0.70 micromol/L. Hemoglobin, retinol, and zinc concentrations of both the weekly and daily groups increased similarly compared with the placebo group (P < 0.001). There was no significant difference in growth between the supplemented groups and the placebo group. However, the heightforage of subjects stunted at baseline increased with z scores of 0.48 (P < 0.001) and 0.37 (P < 0.001) for the daily and weekly groups, respectively. CONCLUSIONS: Weekly and daily supplementation improved hemoglobin, zinc, and retinol concentrations similarly. Neither intervention affected growth of the overall population, but growth of children stunted at baseline was improved through both types of supplementation. PMID 9925127

102_ 1999;107(6):35660.

Incidence of sideropenia and effects of iron repletion treatment in women with subclinical hypothyroidism.

Duntas LH, Papanastasiou L, Mantzou E, Koutras DA.

Sideropenia affects ca. 20% of the world population, and iron dependent anemia is the most frequent type of anemia worldwide. The aim of the study was to investigate the incidence of sideropenia and dependent anemia in patients with subtle changes of the thyroid function, such as subclinical hypothyroidism (SH). 57 women with SH and 61 euthyroid controls (CG) were studied. Serum concentrations of T4, T3, TSH, antiTPO, antiTg, ferrum (Fe), ferritin (Frt) total iron binding capacity (TIBC) and blood count were determined. In SH 17 patients (29.8%) presented low Fe levels (<50 microg/dl). 9 (15.7%) also had decreased Frt, confirming iron deficiency, whereas 8 patients presented additionally diminished hematocrit and hemoglobin levels, suggesting manifested sideropenic anemia. In CG, 10 persons (16%) had sideropenia, 6 (9.8%) had low Fe and Frt and only 3 (4.9%) had blood count alterations suggesting manifested sideropenic anemia. In SH, antiTPO were positive in 39 patients (68%), whereas, in CG only 2 (3.2%) were positive. 8 patients with SH and manifested sideropenic anemia were treated with ironproteinsuccinylate (IPSL), (80 mg Fe /day, for three months), a new iron compound. The repletion treatment safely led to the clinical and laboratory correction of sideropenia and showed a good tolerability. Furthermore, iron treatment provoked a minor increase of T4 and a mild decline of TSH, but the levels were not significant. These results suggest that sideropenia is a common finding in patients with slightly decreased thyroid activity, and that determination of Frt should be routinely advised. Finally, in the assessment of sideropenia and dependent anemia, evaluation of the thyroid function must be taken into account. PMID 10543412

103_ 1999 Jan;129(1):11721.

Iron is well absorbed by healthy adults after ingestion of double fortified (iron and dextrancoated iodine) table salt and urinary iodine excretion is unaffected.

Sattarzadeh M, Zlotkin SH.

Severe deficiencies of iron (Fe) and iodine (I) affect more than one third of the world's population. A table salt, fortified with I and Fe, would be useful in areas in which anemia and goiter coexist. However, interactions between the two minerals have prevented their simultaneous use as fortificants. A method has been developed to coat I with dextran such that after spraying onto table salt, Fe and I do not interact. Our objective was to determine the absorption of Fe and the urinary excretion of I from table salt when provided in meals designed to significantly inhibit or enhance Fe absorption. Subjects (n = 16) ingested Feenhancing and Feinhibiting meals containing 5 g of table salt with 0.39 micromol dextrancoated I as potassium iodide and 1 mg of Fe (ferrous fumarate labeled with 59Fe) per gram of salt. Subjects also received a reference dose of 3 mg of ferrous fumarate labeled with 59Fe to "correct" for interindividual variation in iron absorption at a later date. Measured by wholebody counting, Feabsorption from the Feenhancing meal (36.2 +/ 12.0%, corrected; 13.5 +/ 13.8% uncorrected) was significantly higher than that from the Fe inhibiting meal (7.4 +/ 11.3%, corrected; 4.0 +/ 8.4%, uncorrected) (P < 0.0001). Urinary excretion of iodine at baseline and postingestion were not significantly different (0.89 +/ 0.5 vs. 1.06 +/ 0.39 micromol/L, P < 0.47) and were within the normal range. We conclude that Fe was well absorbed but influenced by the composition of the meal and that urinary excretion of iodine was maintained in the normal range with dextrancoated iodine. PMID 9915886

104_ 1999 Jan;57(1):2531.

Iron and folate fortification in the Americas to prevent and control micronutrient malnutrition: an analysis.

DarntonHill I, Mora JO, Weinstein H, Wilbur S, Nalubola PR.

Although there has been a remarkable decline in the proportion of malnourished children in Latin America, micronutrient deficiencies, especially iron deficiency anemia, remain significant public health problems. A substantial reduction in the prevalence of iron deficiency anemia is an important goal for the end of the decade. Interest in fortifying wheat flour and drymilled maize flour is thus growing, and significant experience in the fortification of flours with iron and the B vitamins, including folate, is emerging. It is necessary to ensure that fortification levels and standards, legislation, and quality assurance and control measures are in place nationally and harmonized regionally. PMID 10047703

105_ 1998 Nov;7(11):100712.

Lipid peroxyl radicals from oxidized oils and hemeiron: implication of a highfat diet in colon carcinogenesis.

Sawa T, Akaike T, Kida K, Fukushima Y, Takagi K, Maeda H.

A diet high in fat and iron is known as a risk factor in cancer epidemiology. However, the details of the molecular mechanism remains to be elucidated. We examined the possible implication of lipid peroxyl radicals generated from fatty acids and hemeiron in DNA damage, and hence in the possibility of colon cancer. F344 female rats were given NnitrosoNmethylurea six times during a 2 week period and then fed diets containing different amounts of safflower oil and hemoglobin (rich in iron) for 36 weeks; the occurrence of colon cancer was determined by H&E staining. In this animal model, simultaneous feeding of a fat diet and hemeiron produced a significant increase (P < 0.05) in the incidence of colon cancer compared with a diet without hemoglobin. Electron paramagnetic resonance and chemiluminescence studies revealed that oxidized refined vegetable oils, particularly safflower oil, readily generated lipid peroxyl radicals in the presence of various heme compounds, and the peroxyl radicals did effectively cleave DNA. Unpurified native vegetable oils contain a high amount of peroxyl radical scavengers, whereas conventional refining processes seem to reduce the levels of many valuable antiperoxyl radical compounds abundant in plant seeds. In conclusion, lipid peroxides and heme components generate peroxyl radical species that exert DNAcleaving activity. A plausible explanation is that lipid peroxyl radicals thus generated, which originated from routine dietary components such as fat and red meat, may contribute, at least in part, to the high incidence of colon cancer. PMID 9829709

106_ 1998 Sep;49(5):3839.

The role of prophylactic iron supplementation in pregnancy.

Singh K, Fong YF, Arulkumaran S.

The prevalence, causes and role of iron prophylaxis in pregnant women was studied. All women delivered at the National University Hospital, Singapore in 1993 had their haemoglobin estimated. If it was less than 11 g/dl, blood was taken for serum iron, ferritin, transferrin, red cell zinc protoporphyrin, serum folate, vitamin B12 and thalassemia screen to establish cause of anaemia. Data was also collected with regards to their antenatal progress and iron prophylaxis. Logistic regression, Chisquare test, Fischer's exact test and MantelHaenszel tests were also used to assess the relationships between categorical variables. The prevalence of anaemia at first antenatal visit was 20.6% while the prevalence of anaemia at delivery was 15.3%. The commonest cause of the anaemia in pregnancy was due to iron deficiency (81.3%). In the nonanaemic group, 90.7% were on prophylactic iron supplements compared to 50.6% in the anaemic group (P < 0.001). Of the 752 women found to be anaemic at booking, 591 received prophylactic iron supplements while 161 women did not. A total of 166 (28.1%) of those with iron supplements were anaemic at delivery, whereas 140 (87.0%) of those who did not receive prophylactic iron remained anaemic at delivery (P < 0.001). Of the 2516 nonanaemic women who received prophylactic iron, 118 (4.7%) developed anaemia at delivery while 133 (34.1%) out of the 390 women who did not receive prophylactic iron were anaemic at delivery (P < 0.001). Multivariate logistic regression analysis revealed the odds of anaemia for a woman not on iron therapy was about 11 times that of her counterpart on prophylactic iron therapy (95% CI 8.76 to 14.13). A 55% reduction in odds of anaemia was estimated per 1 gm% increase in haemoglobin at booking. Prophylactic antenatal iron supplements not only prevent a fall but also improved haemoglobin levels during pregnancy. Those who were not on any iron supplements were 11 times more likely to develop anaemia in the present pregnancy. PMID 10367008

107_ 1998 Sep;27(157):4004.

[Effect of biscuits fortified with haem iron on the intellectual status of preschool children]

SalinasPielago JE, VegaDienstmaier JM, RojasOblitas M.

INTRODUCTION: In undeveloped countries such as Peru there is a high prevalence of ferropenic anemia. In addition, iron deficiency produces cognitive alterations that could be corrected by iron treatment. OBJECTIVE: To evaluate the effect of administration of heme ironfortified cookies on the intellectual status of preschool children. PATIENTS AND METHODS: Using the Goodenough Harris Test (GHT) and Wechsler Preschool and Primary Scale of Intelligence (WPPSI) we studied the intellectual status of 53 children who received heme iron fortified cookies for 68 weeks and 55 controls without fortification, in 2 occasions (before and after intervention). RESULTS: We observed a significantly higher improvement in children who received iron respect to controls for GHT score (p < 0.001), WPPSI score (p < 0.05), WPPSI attentionconcentration subscale (p < 0.01) and WPPSI pure attention subscale (p < 0.05). CONCLUSION: Administration of heme ironfortified cookies may improve the intellectual performance of lowincome preschool children.

108_ 1998 Jul;79(1):F448.

Iron supplementation enhances response to high doses of recombinant human erythropoietin in preterm infants.

Carnielli VP, Da Riol R, Montini G.

AIMS: To determine whether iron supplementation would enhance erythropoiesis in preterm infants treated with high doses of human recombinant erythropoietin (rHuEPO). METHODS: Sixty three preterm infants were randomly allocated at birth to one of three groups to receive: rHuEPO alone, 1200 IU/kg/week (EPO); or rHuEPO and iron, 1200 IU/kg/week of rHuEPO plus 20 mg/kg/week of intravenous iron (EPO + iron); or to serve as controls. All three groups received blood transfusions according to uniform guidelines. RESULTS: Infants in the EPO + iron group needed fewer transfusions than controlsmean (95% CI) 1.0 (0.28 1.18) vs 2.9 (1.843.88) and received lower volumes of bloodmean (95% CI) 16.7 (4.928.6) vs 44.4 (29.059.7) ml/kg. The EPO group also needed lower volumes of blood than the controlsmean (95% CI) 20.1 (6.234.2) vs 44.4 (29.0 59.7) ml/kg, but the same number of transfusions, 1.3 (0.542.06) vs 2.9 (1.84 3.88). Reticulocyte and haematocrit values from postnatal weeks 5 to 8 were higher in the EPO + iron than in the EPO group, and both groups had higher values than the controls. Mean (SEM) plasma ferritin was lower in the EPO group65 (55) micrograms/l than in the EPO + iron group 780 (182) micrograms/l, and 561 (228) micrograms/l in the control infants. CONCLUSIONS: Early administration of high doses of rHuEPO with iron supplements significantly reduced the need for blood transfusion. Intravenous iron (20 mg/kg/week in conjunction with rHuEPO yielded a higher reticulocyte count and haematocrit concentration after the forth week of life than rHuEPO alone. Infants treated with rHuEPO alone showed signs of reduced iron stores. PMID 9797624

109_ 1998 Jul;133(7):7404.

Prophylactic iron supplementation after RouxenY gastric bypass: a prospective, doubleblind, randomized study.

Brolin RE, Gorman JH, Gorman RC, Petschenik AJ, Bradley LB, Kenler HA, Cody RP.

OBJECTIVE: To determine whether prophylactic oral iron supplements (320 mg twice daily) would protect women from iron deficiency and anemia after Rouxen Y gastric bypass. DESIGN: Prospective, doubleblind, randomized study in which 29 patients received oral iron and 27 patients received a placebo beginning 1 month after RouxenY gastric bypass. SETTING: Tertiary care medical center. PATIENTS AND INTERVENTIONS: Complete blood cell count and serum levels of iron, total iron binding capacity, ferritin, vitamin B12, and folate were determined preoperatively and at 6month intervals postoperatively in 56 menstruating women who had RouxenY gastric bypass. MAIN OUTCOME MEASURE: Incidence of iron deficiency and other hematological abnormalities in each treatment group. RESULTS: Hemoglobin, hematocrit, and vitamin B12 levels were significantly decreased compared with preoperative values in both groups. Conversely, folate levels increased significantly over time in both groups. Oral iron consistently prevented development of iron deficiency in the iron group. Ferritin levels did not change significantly in the iron group. However, in placebotreated patients, ferritin levels 2 years postoperatively were significantly decreased compared with preoperative levels. There was no difference in the incidence of anemia between the 2 groups. However, the incidence of microcytosis was substantially greater (P=.07) in placebotreated than irontreated patients. CONCLUSIONS: Prophylactic oral iron supplements successfully prevented iron deficiency in menstruating women after RouxenY gastric bypass but did not consistently protect these women from developing anemia. On the basis of these results we now routinely recommend prophylactic iron supplements to menstruating women who have RouxenY gastric bypass. PMID 9688002

110_ 1998 Jul;14(7):93741.

The synergistic effects of vitamin E and selenium in ironoverloaded mouse hearts.

Bartfay WJ, Hou D, Brittenham GM, Bartfay E, Sole MJ, Lehotay D, Liu PP.

OBJECTIVES: To determine whether supplementation with vitamin E and selenium can improve myocardial antioxidant defenses in ironoverloaded mouse hearts. INTERVENTIONS: Ironoverload state was created in B6D2F1 mice (n = 20) by daily injection of iron dextran (5 mg intraperitoneally/mouse) for four weeks. The mice were also simultaneously randomly assigned to receive vitamin E (alphatocopherol acetate, 40 mg intraperitoneally, n = 5), selenium (sodium selenite, 1 part/million orally, n = 5), both (vitamin E + selenium, n = 5) or irononly treatment (n = 5). The hearts were harvested for determination of selenium concentration and glutathione peroxidase activity. In a subsequent study, 15 B6D2F1 mice were randomly assigned to receive daily injections of iron (n = 5) or iron and combined antioxidant treatment (vitamin E + selenium, n = 5), or to serve as controls (n = 5) for four weeks. The hearts were harvested for determination of total iron concentrations. MAIN RESULTS: Significantly greater concentrations of heart selenium and glutathione peroxidase activity were observed in groups supplemented with both agents, as opposed to irononly treated or single supplemented mice. Significantly lower concentrations of iron were found in controls and in those receiving combined iron and antioxidant treatment (vitamin E + selenium) than in irononly treated mice. CONCLUSIONS: Vitamin E and selenium function synergistically in the myocardium to provide important antioxidant defenses in ironoverload states, including increased concentrations of selenium, increased glutathione peroxidase activity and decreased concentrations of iron. PMID 9706279

111_ 1998 Jul;84(4):31922.

[Intravenous iron in the treatment of postoperative anemia in surgery of the spine in infants and adolescents]

Berniere J, Dehullu JP, Gall O, Murat I.

PURPOSE OF THE STUDY: Spinal fusion surgery often leeds to massive bleeding responsible for anemia in the postoperative period. The aim of this study was to compare the effect of IV iron III hydroxide sucrose complex (Venofer) versus oral iron fumarate administration in postoperative anemia. The efficacy of both treatments was evaluated by comparing hemoglobin level in the postoperative period. METHODS: Two groups of sixteen patients, scheduled for anterior and/or posterior spinal fusion, were compared. Group 1, historical, was treated by supplementation of 10 mg/kg/day oral iron fumarate. Administration was started when hemoglobin level fell below 9 g/100 ml. Group 2 was treated by intravenous iron sucrose complex using same criteria as in group 1 for starting administration. The dosage of iron was individually adapted according to a target hemoglobin level of 13 g/100 ml and to the actual lowest hemoglobin level measured. The total iron deficit was calculated with the following formula: total iron deficit (mg) = 0.24 x body weight (kg) x (target Hbactual Hb)(g/l). The patients were supplemented by 3 mg/kg/day until the calculated iron deficit was compensated. RESULTS: Both groups were identical regarding age and lowest hemoglobin level reached in the postoperative period. Hemoglobin increased by 0.25 g/day in group 1, and by 0.36 g/day in group 2. In others words, the beneficial effect of IV iron versus oral iron administration was as high as 45 per cent (p = 0.003). CONCLUSION: Intravenous iron therapy as ferric sucrose complex is a new and more effective form of iron therapy than oral iron therapy to restore postoperative hemoglobin after spinal surgery in children. PMID 9775031

112_ 1998 Jun;39(6):42731.

[Detection and treatment of iron deficiency anaemia coexisting with inflammation prevalent in aged individuals]

Saito H, Kawamura Y.

As the author found that serum ferritin is decreased below 12 ng/ml in iron deficiency anemia (IDA) even then it is coexisting with anaemia other than IDA, an attempt was made to detect and treat IDA coexisting with anaemia other than IDA. When surveyed in a general hospital admitting 222 patients, anaemias were detected in 95 out of 190 patients aged above 60:82 inflammation anaemia, 9 IDA including 6 cases with inflammation and 4 other anaemias. According to the above results, aged patients above 60 with IDA only and IDA coexisting with inflammation were treated by injecting iron intravenously. By the treatment, haemoglobin (Hb) was increased from 9.0 to 13.8 g/dl and the ratio of Hb increase was 0.59 in 4 patients with IDA only, and Hb was increased from 7.7 to 11.5 g/dl and the ratio of Hb increase was 0.63 in 18 patients with IDA coexisting with inflammation. After the treatment, general disease states were improved in many cases. Thus, the treatment of aged patients with IDA coexisting with inflammation seems to be comparably effective as for IDA only. PMID 9695670

113_ 1998 May;67(5):8737.

Influence of ascorbic acid on iron absorption from an ironfortified, chocolateflavored milk drink in Jamaican children.

Davidsson L, Walczyk T, Morris A, Hurrell RF.

The influence of ascorbic acid on iron absorption from an ironfortified, chocolateflavored milk drink (6.3 mg total Fe per serving) was evaluated with a stableisotope technique in 20 67yold Jamaican children. Each child received two test meals labeled with 5.6 mg 57Fe and 3.0 mg 58Fe as ferrous sulfate on 2 consecutive days. Three different doses of ascorbic acid (0, 25, and 50 mg per 25g serving) were evaluated in two separate studies by using a crossover design. Iron isotope ratios were measured by negative thermal ionization mass spectrometry. In the first study, iron absorption was significantly greater (P < 0.0001) after the addition of 25 mg ascorbic acid: geometric mean iron absorption was 1.6% (range: 0.94.2%) and 5.1% (2.217.3%) for the test meals containing 0 and 25 mg ascorbic acid, respectively. In the second study, a significant difference (P < 0.05) in iron absorption was observed when the ascorbic acid content was increased from 25 to 50 mg: geometric mean iron absorption was 5.4% (range: 2.710.8%) compared with 7.7% (range: 4.7 16.5%), respectively. The chocolate drink contained relatively high amounts of polyphenolic compounds, phytic acid, and calcium, all wellknown inhibitors of iron absorption. The low iron absorption without added ascorbic acid shows that chocolate milk is a poor vehicle for iron fortification unless sufficient amounts of an ironabsorption enhancer are added. Regular consumption of ironfortified chocolate milk drinks containing added ascorbic acid could have a positive effect on iron nutrition in population groups vulnerable to iron deficiency. PMID 9583844

114_ 1998 MayJun;13(3):11420.

[Iron supplementation during pregnancy. Standards and alternatives]

Ortega RM, Quintas ME, Andres P, LopezSobaler AM.

The requirements of iron during gestation are very high and it is difficult to meet them, especially in women who go into a pregnancy with an exhausted storage of the mineral. In industrialized societies there is controversy regarding the usefulness or lack of supplementation. In some cases one recommends a routine iron supplementation during the second half of the pregnancy, in order to improve the situation of all women. Another tendency, keeping in mind the increased capacity for absorption seen during the gestation, is the selective supplementation of iron only after assessing the situation of the pregnant woman. A third alternative that may be useful in the future is that of monitoring the iron status (during the pregnancy and during the entire fertile period of the entire female population), increasing the consumption of foods that are rich in iron (meat, fish, fortified cereals), improving the bioavailability of the ingested iron (drinking orange juice with the meal or eating meat), and using weekly supplements of iron rather than daily supplements, as the former type of supplementation has an effect that is similar to that seen with a daily supplementation, and lacks many of the side effects of this (noncompliance with the standard, gastrointestinal trouble, decreased absorption of other nutrients).

115_ 1998 Apr 3;47(RR3):129.

Recommendations to prevent and control iron deficiency in the United States. Centers for Disease Control and Prevention.

[No authors listed]

Iron deficiency is the most common known form of nutritional deficiency. Its prevalence is highest among young children and women of childbearing age (particularly pregnant women). In children, iron deficiency causes developmental delays and behavioral disturbances, and in pregnant women, it increases the risk for a preterm delivery and delivering a lowbirthweight baby. In the past three decades, increased iron intake among infants has resulted in a decline in childhood irondeficiency anemia in the United States. As a consequence, the use of screening tests for anemia has become a less efficient means of detecting iron deficiency in some populations. For women of childbearing age, iron deficiency has remained prevalent. To address the changing epidemiology of iron deficiency in the United States, CDC staff in consultation with experts developed new recommendations for use by primary healthcare providers to prevent, detect, and treat iron deficiency. These recommendations update the 1989 "CDC Criteria for Anemia in Children and ChildbearingAged Women" (MMWR 1989;38(22):4004) and are the first comprehensive CDC recommendations to prevent and control iron deficiency. CDC emphasizes sound iron nutrition for infants and young children, screening for anemia among women of childbearing age, and the importance of lowdose iron supplementation for pregnant women. PMID 9563847

116_ 1998 Apr;60(4):2529.

The estimation of efficacy of oral iron supplementation during treatment with epoetin beta (recombinant human erythropoietin) in patients undergoing cardiac surgery.

Sowade O, Messinger D, Franke W, Sowade B, Scigalla P, Warnke H.

We estimated the efficacy of oral iron therapy during treatment with rhEPO in patients undergoing cardiac surgery who were contraindicated for autologous blood donation. Seventysix patients were enrolled in this doubleblind, placebocontrolled trial and assigned to the 2 treatment groups (5x500 U/kg body weight rhEPO or placebo intravenously over 14 d before surgery). During the treatment period all patients received 300 mg Fe2+ (iron glycine sulfate) orally per day. rhEPO therapy produced significant increases in hemoglobin concentration (Hb), reticulocyte count, hematocrit (Hct) and the hypochromic red blood cells (HRBC), and a decrease in transferrin saturation (41%) compared to the placebo group before surgery. However, the preoperative increase in HRBC was independent of the baseline ferritin and even correlated positively with the preoperative increase in Hct (r=0.47, p<0.01). In rhEPO patients there were inverse correlations between baseline serum iron and the preoperative increases in Hb (r=0.39, p<0.05), Hct (r=0.50, p<0.01) and HRBC (r=0.53, p<0.001). With this treatment regimen the HRBC appear to reflect the degree of erythropoietic stimulation rather than functional iron deficiency. The preoperative increases in reticulocytes, HRBC and Hb/Hct in patients with ferritin <100 mg/l or transferrin saturation <16% showed no significant difference compared to their complementary groups. The preoperative decrease in storage iron and the inverse correlation between the baseline ferritin and the preoperative change in ferritin (r=0.94, p<0.0001) in the rhEPO group indicate that the iron requirement for hemoglobin synthesis is probably covered by the breakdown of stored iron and an increase in the rate of absorption of orally administered Fe2+. Intravenous rhEPO treatment with 5x500 U/kg body weight in combination with 300 mg oral Fe2+/d given over 14 d before surgery is a suitable regimen to increase Hb by about 1.61 g/dl and Hct by 0.06.

117_ 1997 Dec;12(12):83942.

Doserelated effects of dietary iron supplementation in producing hepatic iron overload in rats.

Plummer JL, MacKinnon M, Cmielewski PL, Williams P, Ahern MJ, Ilsley AH, de la M Hall P.

The influence of varying the level of supplemental dietary iron on the development of hepatic iron overload was examined in rats. Two days after giving birth, Porton rats were fed a diet supplemented with 0, 0.5, 1 or 2% carbonyl iron, to institute dietary iron supplementation to the young via breast milk. After weaning, the offspring continued to receive the assigned diet until 32 weeks of age. Liver biopsies were taken from some rats at 8, 16 and 24 weeks of age and from all rats at 32 weeks of age, for assessment of iron overload. For both male and female rats, hepatic iron content was increased in a dose related manner by feeding supplemented diet. Hepatic iron content of male rats tended to reach a plateau after 8, 16 weeks of supplementation, while that of female rats continued to rise throughout the experimental period, such that the hepatic iron content of female rats was 2.8fold that of similarly treated males at 32 weeks of age. Iron supplementation was associated with only moderate retardation of growth. By choosing an appropriate level of iron supplementation, good (grade IIIIV) hepatic iron loading can be achieved with minimal adverse effects on the animals' overall health. PMID 9504895

118_ 1997 Nov;66(5):117882.

Effect of iron supplementation on the iron status of pregnant women: consequences for newborns.

Preziosi P, Prual A, Galan P, Daouda H, Boureima H, Hercberg S.

We studied the effect of iron supplementation on the iron status of mothers and on biochemical iron status and clinical and anthropometric measures in their infants. The subjects were 197 pregnant women selected at 28 wk +/ 21 d of gestation at a motherandchild health center in Niamey, Niger. Ninety nine women received 100 mg elemental Fe/d throughout the remainder of their pregnancies and 98 received placebo. The prevalence of anemia and iron deficiency decreased markedly during the last trimester of pregnancy in the ironsupplemented group but remained constant in the placebo group. Three months after delivery, the prevalence of anemia was significantly higher in the placebo group. At delivery, there were no differences between the two groups in cord blood iron variables. Three months after delivery, serum ferritin concentrations were significantly higher in infants of women in the ironsupplemented group. Mean length and Apgar scores were significantly higher in infants with mothers in the iron group than in those with mothers in the placebo group.

119_ 1997 Nov;51 Suppl 4:S1624.

The challenge of improving iron nutrition: limitations and potentials of major intervention approaches.

Yip R.

Various approaches to improving iron status are discussed. Success in controlling iron deficiency worldwide will require the exploration and demonstration of all possible options. The approaches, which are not mutually exclusive, include iron supplementation, nutrition education, reducing intestinal parasites (particularly hookworm), expanding fortification of processed foods, and developing crops that are more iron bioavailable. Coordination with existing health and nutrition programs can enhance progress toward better overall nutrition. For example, in the development of food fortification or of crops with higher nutritional value, the combination of multiple micronutrients can be considered. Within the primary health care system, iron supplementation and deworming can be coordinated with other health care activities. The ultimate success in control of iron deficiency will depend on how well the various intervention approaches can be integrated within the current framework of public health, food processing, and agriculture development. PMID 9598788

120_ 1997 Nov;51 Suppl 3:S518.

Iron intake and iron status among adults in the Netherlands.

Brussaard JH, Brants HA, Bouman M, Lowik MR.

OBJECTIVE: To assess the adequacy of iron intake and status, the prevalence of marginal iron status, the physiological and lifestyle factors influencing iron status and the role of dietary factors affecting the bioavailability of iron among Dutch adults. DESIGN: Food consumption was measured with 3 d diet records. Iron status and prevalence of iron deficiency and iron accumulation were evaluated using different criteria. Physical, biochemical and lifestyle characteristics were determined and relationships with iron status were evaluated by bi and multivariate regression analysis. SUBJECTS: A sample of 444 adults, aged 2079 y stratified for sex and 10 y age classes, with an overrepresentation of people with a low habitual intake of vitamin B6. RESULTS: Average iron intake was higher than the recommended daily allowance for the Netherlands in all sexage groups except women aged 2049, in which group average iron intake was 23% below the recommendation. Early iron deficiency, as reflected in low ferritin levels, was not found among men aged 2049, but was observed in 5% of women aged 5079, 11% of men aged 5079, and 16% of women aged 2049. Iron deficiency anaemia as reflected in low haemoglobin levels was found in 05% of the agesex groups. Among men and women, 16% and 13% of variance in haemoglobin level, respectively, could be explained by physiological and dietary factors. For ferritin, the proportions were 36% and 34%, respectively. Iron status was correlated negatively with the vegetable fraction of the diet, and positively with factors from the animal fraction (haem iron, animal protein, meat). Further, haemoglobin was positively correlated with body weight among men, and with both age and use of oral contraceptives among women. Both among men and women, blood donorship in the six months prior to the study was negatively associated with serum ferritin levels. CONCLUSIONS: Women aged 2049 are the adult sexage group with the greatest risk of developing (an early stage of) iron depletion. The most important dietary factors influencing the iron status are the type of iron (haem/nonhaem) and factors affecting the bioavailability of iron. PMID 9598769

121_ 1997 Nov;51 Suppl 4:S257.

Technological approaches to combatting iron deficiency.

Gibson RS.

Iron deficiency is widespread among young children and women of reproductive age, especially in less industrialized countries. It is partly induced by plantbased diets containing low levels of poorly bioavailable iron. The most effective technological approaches to combat iron deficiency in less industrialized countries include supplementation targeted to high risk groups combined with a national program of food fortification and dietary strategies designed to maximize the bioavailability of both the fortificant and the intrinsic food iron. Prerequisites for effective supplementation include an efficient and consistent supply, delivery, and consumption of a highly bioavailable iron supplement. Fortification relies less heavily on compliance and an organized health service but must be regulated by government to eliminate competition with unfortified products. To be effective, a combination of an iron fortificant and food vehicle must be selected which is safe, acceptable to and consumed by the target population, does not adversely effect the organoleptic qualities and shelflife of the food vehicle, and provides iron in a stable, highly bioavailable form. Bioavailability of both the fortificant and the intrinsic food iron can be improved by adding enhancing factors, removing inhibitors such as phytate by enzymatic and nonenzymatic hydrolysis, and using 'protected' fortification compounds. PMID 9598789

122_ 1997 Nov;131(5):6615.

The effect of erythropoietin on the transfusion requirements of preterm infants weighing 750 grams or less: a randomized, doubleblind, placebo controlled study.

Ohls RK, Harcum J, Schibler KR, Christensen RD.

BACKGROUND: Clinical trials of erythropoietin (EPO) administration to preterm infants have not focused on infants weighing 750 gm or less, the population most likely to receive multiple transfusions because of large phlebotomy losses. It is unknown whether preterm infants weighing 750 gm or less will respond to EPO by accelerating erythropoiesis, or whether EPO administered to this population will decrease blood transfusions. METHODS: We randomly assigned 28 extremely low birth weight preterm infants (mean +/ SEM: 24.7 +/ 0.3 weeks' gestation, 662 +/ 14 gm birth weight), in the first 72 hours of life, to receive either EPO (200 U/kg/day) or placebo for 14 days and administered transfusions only according to protocol over a 21day study period. All infants received 1 mg/kg/day iron dextran in their total parenteral nutrition solution during the 14day treatment period. RESULTS: During the 21day study period, a lower number and volume of transfusions were received by the EPO recipients (4.7 +/ 0.7 transfusions per patient and 70 +/ 11 ml/kg per patient) than by the placebo recipients (7.5 +/ 1.1 transfusions per patient and 112 +/ 17 ml/kg per patient; p < 0.05, EPO vs placebo), whereas hematocrits remained similar in the two groups. Reticulocyte counts were similar in both groups on day 1 but were greater in the EPO recipients on day 14 (EPO day 1, 351 +/ 53; EPO day 14, 359 +/ 40 x 10(3)/microl; placebo day 1, 334 +/ 64; placebo day 14, 120 +/ 10 x 10(3)/microl; p < 0.01, EPO vs placebo). Serum ferritin concentrations were similar in both groups at the beginning of the study but were greater in the placebo recipients by day 14 (EPO, 262 +/ 44 microg/L; placebo, 593 +/ 92 microg/L; p < 0.01). No adverse effects of EPO or iron were noted. CONCLUSION: The combination of EPO and parenteral iron stimulates erythropoiesis in preterm infants weighing 750 gm or less and results in fewer transfusions during their first 3 weeks of life.

123_ 1997 Oct 6;159(41):605762.

[Iron requirements and iron balance during pregnancy. Is iron supplementation needed for pregnant women?]

Milman N, Bergholt T, Eriksen L, Ahring K, Graudal NA.

Among fertile, nonpregnant, Danish women, 33% have absent or reduced iron stores; 22% have serum ferritin values above 70 micrograms/l, i.e., iron reserves of more than 530 mg, corresponding to the net iron losses during a normal pregnancy. During pregnancy, the demands for absorbed iron increase from 0.8 to 7.5 mg/day. Controlled studies show that irontreated pregnant women have higher serum ferritin levels, i.e., larger iron stores, and higher haemoglobin levels than placebotreated women. A supplement of 66 mg ferrous iron daily from the beginning of the 2nd trimester prevents iron deficiency anaemia. In Denmark, general iron prophylaxis with 6070 mg ferrous iron daily from 20 weeks of gestation is recommended by the health authorities.

124_ 1997 Oct;76(9):8228.

Iron supplementation in pregnancy: is less enough? A randomized, placebo controlled trial of low dose iron supplementation with and without heme iron.

Eskeland B, Malterud K, Ulvik RJ, Hunskaar S.

BACKGROUND: The purpose of the present study was to evaluate the efficacy of low dose iron supplementation with and without a heme component, prescribed for women in the second half of pregnancy. METHOD: A randomized, double blind, placebo controlled trial. Thirtyone women received a daily dose of 27 mg elemental iron in a product containing both heme iron and nonheme iron (Hemofer), 30 women received the same dose as pure nonheme iron with vitamin C (Collets jern med vitamin C), and 29 women received placebo. A double dummy technique was used to mask tablets. The women were tested for red cell indices and iron status markers (sferritin, siron, Total Iron Binding Capacity and erythrocyte protoporphyrin) throughout pregnancy and 8 and 24 weeks postpartum. The results were analyzed according to the 'intention to treat' principle. RESULTS: The hematological effects were equal in the two treatment groups. 25% of the supplemented women fell below 110 g/l in Hb vs 52% in the placebo group (p < 0.05); none fell below 100 g/l in the supplemented groups, 14% in the placebo group. Iron status was significantly better for all measured parameters in the heme iron group compared to placebo at the end of pregnancy. Differences between the other groups were only shown for some parameters, probably due to the small sample size. In the heme iron group there were fewer women with empty iron stores postpartum than at the start of pregnancy (from 14% to 8%), in the nonheme iron group there was a significant increase (from 3% to 27%), and in the placebo group the percentage of women with empty iron stores was more than doubled (from 21% to 52%). CONCLUSIONS: A daily dose of 27 mg elemental iron, containing a heme component, given in the second half of pregnancy, prevents depletion of iron stores after birth in most women. An equivalent dose of pure inorganic iron seems less effective, but the sample size in this study was too small to demonstrate significant differences between the two treatment groups. PMID 9351406

125_ 2002 Jun;56(6):57981.

[Iron supplementation in a child with severe burns]

Belmonte Torras JA, Tusell Puigbert J, Piera Carreras A, Soler Palacin P, Aulesa Martinez C, Iglesias Berengue J.

Nonintentional burns are still a frequent cause of morbidity in children despite the implementation of preventive campaigns. Children with severe burns (more than 10 % of the body surface) may require iron supplementation, especially in the poststress or recovery phase.We report the case of a 15monthold boy, who suffered polytrauma and burns to 20 % of the body surface. A dermal graft was performed eight days after his admission to the pediatric burns unit, which required transfusion of packed red blood cells. On day 15 hemoglobin value was 9.3 g/dL, the reticulocyte hemoglobin content was reduced to 26.2 pg (normal value: 27.230.3 pg) and the reticulocyte mean corpuscular value was increased to 124 fl (normal value: 101108 fl). These findings were interpreted as a functional iron insufficiency, despite the increased ferritin value (219 ng/mL). We highlight the satisfactory outcome of the different hematologic values, with the development of reticulocyte crisis and normalization of hematological parameters after administration of 0.5 mg/kg/day of ferrous sulfate, plus iron corresponding to the followup milk formula and a regular diet for the child's age. PMID 12042158

126_ 2002 Jun;57(6):45761.

Intravenous iron administration does not significantly increase the risk of bacteremia in chronic hemodialysis patients.

Hoen B, PaulDauphin A, Kessler M.

BACKGROUND: Correction of iron deficiency is critical in chronic hemodialysis patients, and intravenous administration is superior to the oral route in this goal. Recently, concern was raised that intravenous iron administration might promote infection in dialysis patients. METHODS: We reviewed the data from a recent prospective study of 985 patients in which no link between iron therapy and bacteremia had been found. We tested the potential role of the administration route of the iron (intravenous vs. oral), the weekly amount of iron administered and the administration rate on the risk for bacteremia in these patients. RESULTS: were 4fold: in multivariate analysis, neither intravenous iron administration in the whole population nor the weekly amount of iron in the subgroup of i.v. irontreated patients were significant risk factors for bacteremia; iron was not given more frequently intravenously in bacteremic than in nonbacteremic patients; among patients treated with intravenous iron, the frequency and the amount of iron administered were significantly higher in those who developed bacteremia than in those who did not; and in patients receiving i.v. iron, there was an increased risk of bacteremia associated with concurrent administration of erythropoietin, which was not observed in patients receiving iron orally. CONCLUSION: This study failed to demonstrate a significant association between intravenous iron administration and the risk of bacteremia in dialysis patients. However, there might be a slightly increased risk of bacteremia in patients given highfrequency, highdose intravenous iron. PMID 12078950

1279_ 2002 Jun;14(3):3503.

Update on micronutrients: iron and zinc.

Oken E, Duggan C.

The past few years have seen several substantial advances in our understanding of the importance of micronutrients in child health and nutrition. Although historically child nutrition in developing countries has focused on protein and energy sufficiency, more recent efforts have been made to evaluate and eliminate micronutrient deficiencies. Accumulating data have underlined the important longterm health effects that may occur with iron deficiency, and studies continue to confirm the benefits of successful treatment of iron deficiency anemia. Zinc is another micronutrient whose significance to child health is increasingly appreciated. Although breakthroughs in micronutrient research have generally come from populations in developing countries, children in industrialized countries also benefit from increasing knowledge about nutritional requirements and interventions. PMID 12011679

128_ 2002 May;17(5):33740.

Changes of autonomic nervous system function in patients with breathholding spells treated with iron.

Orii KE, Kato Z, Osamu F, Funato M, Kubodera U, Inoue R, Shimozawa N, Kondo N.

To evaluate the autonomic nervous system of patients with breathholding spells after iron treatment, we attempted to determine whether a dysregulation of the autonomic nervous system reflexes exists in children with severe cyanotic breathholding spells. An electrocardiogram for each subject was recorded for 24 hours in the subject's home and parasympathetic activity was investigated by the fast Fourier transform method. Hematologic data and clinical symptoms of all three patients treated with iron improved and attacks of severe breathholding spells disappeared. After iron treatment was started, the heart rate variability increased during sleep. It appears that supplementation of iron is effective in improving the dysregulation of autonomic nervous system reflexes. PMID 12150579

129_ 2002 Apr;75(4):7438.

Treatment of iron deficiency in goitrous children improves the efficacy of iodized salt in Cote d'Ivoire.

Hess SY, Zimmermann MB, Adou P, Torresani T, Hurrell RF.

BACKGROUND: In many developing countries, children are at high risk of both goiter and iron deficiency anemia. Iron deficiency adversely affects thyroid metabolism and may reduce the efficacy of iodine prophylaxis in areas of endemic goiter. OBJECTIVE: The aim of this study was to determine whether iron supplementation in goitrous, irondeficient children would improve their response to iodized salt. DESIGN: We conducted a randomized, doubleblind, placebocontrolled trial in 514yold children in Cote d'Ivoire. Goitrous, irondeficient children (n = 166) consuming iodized salt (1030 mg I/kg salt at the household level) were supplemented with either iron (60 mg Fe/d, 4 d/wk for 16 wk) or placebo. At 0, 1, 6, 12, and 20 wk, we measured hemoglobin, serum ferritin, serum transferrin receptor, wholeblood zinc protoporphyrin, thyrotropin, thyroxine, urinary iodine, and thyroid gland volume (by ultrasonography). RESULTS: Hemoglobin and iron status at 20 wk were significantly better after iron treatment than after placebo (P < 0.05). At 20 wk, the mean reduction in thyroid size in the irontreated group was nearly twice that in the placebo group (x +/ SD percentage change in thyroid volume from baseline: 22.8 +/ 10.7% compared with 12.7 +/ 10.1%; P < 0.01). At 20 wk, goiter prevalence was 43% in the irontreated group compared with 62% in the placebo group (P < 0.02). There were no significant differences between groups in wholeblood thyrotropin or serum thyroxine at baseline or during the intervention. CONCLUSIONS: Iron supplementation improves the efficacy of iodized salt in goitrous children with iron deficiency. A high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodine prophylaxis. PMID 11916762

130_ 2002 Apr;39(4):33946.

Impact of daily versus weekly hematinic supplementation on anemia in pregnant women.

Gomber S, Agarwal KN, Mahajan C, Agarwal N.

OBJECTIVE: To compare the effectivity of weekly versus daily iron therapy in reducing maternal anemia and to evaluate the association of maternal hemoglobin and fetal growth. DESIGN: Prospective. SETTING: Tertiary care teaching hospital in an urban metropolis. METHOD: 40 pregnant women received daily and 40 pregnant women received weekly oral therapy (335 mg of ferrous sulphate and 500 g folic acid) for a period of 14 weeks. The age of each pregnant woman and their baseline anthropometric data (weight, height and body mass index) were estimated. Hemoglobin and hematocrit estimations were carried out during follow period at 4 wks, 8 wks and 14 weeks. Serum ferritin values as a marker of iron status were also calculated in both the groups initially, at 14 weeks and at the time of delivery. Fetal anthropometric indices of 137 full term neonates delivered to mothers included in either of the supplementation groups or admitted to the hospital were also studied in relation to maternal hemoglobin concentration. RESULTS: Forty subjects each were initially randomized into groups I and II. The age of pregnant women along with their baseline anthropometric data were similar in both groups. A total of 29 pregnant women in group I and 27 pregnant women in group II could be regularly followed up. The increase in hemoglobin and hematocrit values were similar in daily and weekly supplemented mothers. An intention to treat analysis also showed similar results. The ferritin values were similar at the start of supplementation and after 14 wks of weekly or daily iron therapy. Birth weight, crown heel length, head circumference of the neonate and placental weight increased significantly with rise in maternal hemoglobin levels. CONCLUSION: Weekly iron supplementation is an effective mode of treating anemia among pregnant women and maternal anemia during pregnancy is adversely associated with fetal growth. PMID 11976463

131_ 2002 Mar;81(3):1547. Epub 2002 Feb 09.

Parenteral iron supplementation for the treatment of iron deficiency anemia in children.

Surico G, Muggeo P, Muggeo V, Lucarelli A, Martucci T, Daniele M, Rigillo N.

Irondeficiency anemia impairs growth and intellectual development in children, which can be reversed only by early diagnosis and iron supplementation. Oral supplementation can efficiently replace stores, but in many cases parenteral iron is needed. Unfortunately some adverse reactions have limited its use in children. We compared the efficacy and safety of intramuscular and intravenous administration in 33 evaluable children with severe iron deficiency and/or irondeficiency anemia who failed to respond to oral iron supplementation. Nineteen children received intravenous infusion and 14 intramuscular injections. All children showed recovery from irondeficiency anemia, with statistically similar improvement in hemoglobin levels. The duration of treatment was longer in those receiving intramuscular injection. Parenteral iron therapy for the treatment of irondeficiency anemia is a rapid, easy, and definitive solution to a longtroubling situation. We suggest the use of parenteral iron, in particular intravenous iron, in children who do not recover from severe irondeficiency anemia after oral therapy. We should consider the physical and neuropsychological sequelae of longlasting iron deficiency in children and the fact that oral supplementation is less likely to replace iron stores. PMID 11904741

132_ 2002 Mar;23(1):5764.

Iron and energy supplementation improves the physical work capacity of female college students.

Mann SK, Kaur S, Bains K.

A nutritionally controlled study was conducted on two groups of 15 female college students aged 16 to 20 years, selected from Punjab Agricultural University, Ludhiana, Punjab, India. The girls were either anemic (hemoglobin 7.7 g/dl) but energy adequate (AEA), or anemic (hemoglobin 7.4 g/dl) and energy deficient (AED). The AEA group was given iron supplementation (60 mg iron/day) for 6 to 9 months along with 100 mg of ascorbic acid, and the AED group was given iron as well as energy supplementation for 3 months. There was a significant (p < .01) increase in weight, body mass index, midupperarm circumference, and body fat in the AED group after ironenergy supplementation. Hemoglobin, serum iron, transferrin saturation, total ironbinding capacity, and unsaturated ironbinding capacity were below normal in both groups; however, after iron and ironenergy supplementation, there was a significant (p < .01) increase, and these indices were in the normal range. There was a significant (p < .01) increase in exercise time and maximum work load tolerance after iron and ironenergy supplementation. Combined energy and iron deficiency had a greater adverse effect on physical work capacity than energy or iron deficiency alone. PMID 11975370

133_ 2002 Feb;43(1):169.

Superoxide dismutase and glutathione peroxidase in erythrocytes of patients with iron deficiency anemia: effects of different treatment modalities.

Isler M, Delibas N, Guclu M, Gultekin F, Sutcu R, Bahceci M, Kosar A.

AIM: To test whether the activities of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) can be affected by oral iron (OI) treatment, parenteral iron (PI) treatment, and parenteral iron treatment with vitamin E supplementation (PIE) in iron deficiency anemia. METHODS: Twentyeight patients with iron deficiency anemia and 18 healthy controls were included in the study. Anemic patients were systematically allocated into 3 treatment groups. The first group (n=8) received OI, the second group (n=10) PI, and the third group (n=10) PIE. SOD and GSHPx activities were determined using commercial kits. RESULTS: Before the treatment, SOD activity was significantly lower in anemic patients than in the control group (KruskalWallis test, p<0.05). After the treatment, SOD activity significantly increased in all three patient groups and reached the values found in the control group (Wicoxon signedrank test, p=0.017 for OI, p=0.047 for PI, and p=0.037 for PIE group). Before the treatment, GSHPx activities in anemic patients were similar to that of control group (KruskalWallis test, p>0.05). Although there was no significant decrease in GSHPx activity after OI treatment, both PI and PIE treatments significantly decreased GSHPx activity (Wilcoxon signedranks test, p=0.007 for PI and p=0.005 for PIE). PIE was more effective than PI treatment in maintaining GSHPX activity. CONCLUSION: Oral iron treatment improved the iron deficiency anemia and recovered antioxidant defense system by increasing SOD activity and maintaining GSHPx activity at normal level. When parenteral iron treatment is inevitable, vitamin E supplementation together with PI treatment may be effective in partially restoring the antioxidant status in this type of anemia. PMID 11828552

134_ 2002 JanFeb;15(1):14.

[Developmental delay in children with iron deficiency anemia. Can this be reversed by iron therapy?]

Antunes H, Goncalves S, TeixeiraPinto A, CostaPereira A.

OBJECTIVE: To compare development of 17 children aged 12 months with iron deficiency anaemia (IDA) and 18 controls without IDA after a 3months followup period and iron therapy in the IDA group. SUBJECTS AND METHODS: Development of all children was evaluated using the Griffith's Scale. Data was collected on parent's social class and education, breastfeeding, number of siblings and clinical nutritional status. RESULTS: At 12 months children with IDA had significantly lower development scoresmean (sd)than those without IDA: 112(5) vs. 121(7). At 15 months, after iron therapy, there were no significant differences between cases and controls. NonIDA children showed significantly lower development scores at 15 months when compared with 12 months (121 vs 115). CONCLUSIONS: The study shows that iron therapy can revert some of the adverse effects in the development of children with IDA and therefore both IDA prevention and treatment can be justified.

135_ 2002;11(1):3641.

Will iron supplementation given during menstruation improve iron status better than weekly supplementation?

Februhartanty J, Dillon D, Khusun H.

To investigate the efficacy of two different iron supplements administered either on a weekly basis or during menstruation, a 16week community experimental study was carried out among postmenarcheal female adolescent students in Kupang, East Nusa Tenggara, Indonesia. Forty eight students received a placebo tablet weekly, 48 other students got an iron tablet weekly and 41 students took an iron tablet for four consecutive days during their menstruation cycle. All subjects were given deworming tablets before supplementation. Haemoglobin, serum ferritin, height, weight, midupper arm circumference and dietary intake were assessed before and after intervention. The supplementation contributed to a significant improvement in the iron status of the intervention groups compared to the placebo group (P < 0.05). In the menstruation group, the haemoglobin concentrations of the anaemic subjects improved significantly (P < 0.05) while for the nonanaemic subjects, serum ferritin concentrations also increased significantly (P < 0.05). In the weekly group for anaemic and nonanaemic subjects, there was a significant increase in both haemoglobin and serum ferritin concentrations (P < 0.05). This study revealed that weekly supplementation of iron tablets continued for 16 weeks contributed a higher improvement to haemoglobin concentration, compared with supplementing iron tablets for four consecutive days during menstruation for four menstrual cycles. This suggests that weekly iron supplementation is preferable. PMID 11890637

136_ 2002;17 Suppl 5:569.

Adjunctive therapy in anaemia management.

Horl WH.

Iron supplementation is essential for adequate response to recombinant human erythropoietin (rHuEPO) or darbepoetin alfa. Oral iron therapy is often ineffective as the quantity of iron absorbed after oral intake may be insufficient to keep pace with the demands of rHuEPOstimulated erythropoiesis in patients with endstage renal disease (ESRD). Currently available i.v. iron preparations include dextran, iron gluconate, and iron sucrose. As rare, but serious, adverse reactions to i.v. iron dextran have been reported, alternative preparations may be preferred. Careful monitoring of iron parameters is required to avoid the effects of overtreatment. Renal anaemia and iron therapy are associated with oxidative stress, leading to a shortening of the lifespan of red blood cells (RBC) and resistance to rHuEPO. rHuEPO therapy may also enhance oxidative stress on RBC. Oxidative stress can be attenuated or prevented by supplementation with vitamin E or melatonin. Vitamin E therapy has also been shown to have a rHuEPOsparing effect. Disturbances of carnitine metabolism may contribute to the development of renal anaemia in ESRD patients. Oral or i.v. Lcarnitine therapy results in an increase in haematocrit and a significant decrease in rHuEPO requirement in HD patients. As yet, there is no general recommendation for Lcarnitine supplementation for ESRD patients with renal anaemia. PMID 12091609

137_ 2001 Dec 15;323(7326):138993.

Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study.

Stoltzfus RJ, Kvalsvig JD, Chwaya HM, Montresor A, Albonico M, Tielsch JM, Savioli L, Pollitt E.

OBJECTIVE: To measure the effects of iron supplementation and anthelmintic treatment on iron status, anaemia, growth, morbidity, and development of children aged 659 months. DESIGN: Double blind, placebo controlled randomised factorial trial of iron supplementation and anthelmintic treatment. SETTING: Community in Pemba Island, Zanzibar. PARTICIPANTS: 614 preschool children aged 659 months. MAIN OUTCOME MEASURES: Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups. RESULTS: Before intervention, anaemia was prevalent and severe, and geohelminth infections were prevalent and lightPlasmodium falciparum infection was nearly universal. Iron supplementation significantly improved iron status, but not haemoglobin status. Iron supplementation improved language development by 0.8 (95% confidence interval 0.2 to 1.4) points on the 20 point scale. Iron supplementation also improved motor development, but this effect was modified by baseline haemoglobin concentrations (P=0.015 for interaction term) and was apparent only in children with baseline haemoglobin concentrations <90 g/l. In children with a baseline haemoglobin concentration of 68 g/l (one standard deviation below the mean value), iron treatment increased scores by 1.1 (0.1 to 2.1) points on the 18 point motor scale. Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura, but not by hookworms. Mebendazole increased development scores by 0.4 (0.3 to 1.1) points on the motor scale and 0.3 (0.3 to 0.9) points on the language scale. CONCLUSIONS: Iron supplementation improved motor and language development of preschool children in rural Africa. The effects of iron on motor development were limited to children with more severe anaemia (baseline haemoglobin concentration <90 g/l). Mebendazole had a positive effect on motor and language development, but this was not statistically significant.

138_ 2001 Nov;35(6):3659.

[Effects of supplementing of calcium, iron and zinc on women's health during pregnancy]

An H, Yin S, Xu Q.

OBJECTIVES: To determine the effects of supplementing biscuits fortified with calcium (Ca) and vitamin D (VD), iron (Fe), vitamin C (VC) and zinc (Zn) to pregnant women from the 5th month of gestation until delivery on their health, and to explore a way to improve their Ca, Fe and Zn nutritional status during pregnancy. METHODS: A total of 313 healthy and primary pregnant women were enrolled and divided into five study groups based on their order visiting the hospitals for prenatal care. Each woman of the study groups was given three pieces of biscuit fortified with VD, Ca and VD, Ca, Zn and VD (Ca + Zn + VD), Ca, Fe, VC and VD (Ca + Fe + VD), Ca, Fe, VC, Zn and VD (Ca + Fe + Zn + VD), respectively, from the 15th month of gestation until delivery (24 weeks in total) daily. The fortified levels were 10 micrograms VD, 400 mg Ca from carbonate calcium, 10 mg Zn from lactate zinc, 10 mg Fe from ferrous lactate, and 50 mg VC, respectively. A parturient women was selected from the same hospital as control after one trial subject for each study groups selected. RESULTS: The daily dietary intakes of Ca, Zn and Fe in pregnant women were only 47.7%, 54.7% and 86.7% of the Recommended Dietary Allowances for Chinese. Incidence of anemia for midterm pregnant women was 35.2%, and Fesupplementation could significantly improved their hemoglobin level (P < 0.05). Prevalence of anemia in the groups of Ca + Fe + Zn + VD and Ca + Fe + VD was 35.3% and 40.7%, respectively, before Fe supplementation and reduced to zero and 4.0%, respectively, after Fe supplementation. Whereas, prevalence of anemia in the other groups without Fe supplementation still kept in a relatively high level. In the groups supplemented with Ca, their plasma Ca level increased, especially with the best results in Ca + VD group. Plasma level of Zn declined with length of gestation, which could be improved by Zn supplementation. Serum level of alkaline phosphatase activity increased a little bit with length of gestation. There was no significant difference in radial and ulnar bone mineral density (BMD) between trial groups and controls two months after delivery. Maternal radial and ulnar BMD correlated significantly with their dietary Ca intakes in Ca + VD group. CONCLUSION: The best way to improve maternal nutritional status is supplementation of Ca + Fe + Zn + VitD, based on the Recommended Dietary Allowances for Chinese. PMID 11840760

139_ 2001 Oct;40(10):54954.

Daily multivitamins with iron to prevent anemia in infancy: a randomized clinical trial.

Geltman PL, Meyers AF, Bauchner H.

This study assessed the effectiveness of multivitamins (MV) with iron as prophylaxis against iron deficiency (ID) and anemia in infancy. The study was a doubleblind, randomized trial at 2 urban primary care clinics. Subjects included healthy, fullterm infants enrolled at their 6month wellchild visit. Parents administered MV, either with iron or without iron, by mouth daily for 3 months. At 9 months of age, 28.3% of 310 had either anemia or ID without anemia. Among infants with any adherence, anemia was found in 11.1% of the iron group and 21.7% in the noniron group (RR=0.5, 95% CI=0.31.0). Iron deficiency without anemia was found in 18.5% of the iron group; 14.4% of the noniron group (p=0.46). When administered daily starting at age 6 months, standarddose multivitamins with iron appear to reduce anemia prevalence at 9 months of age. PMID 11681821

140_ 2001 Oct;57(4):4769.

Iron supplementation during human immunodeficiency virus infection: a doubleedged sword?

Clark TD, Semba RD.

Although iron supplementation is considered beneficial for groups at risk for anemia, concern has been raised that it could be harmful during human immunodeficiency virus (HIV) infection. Studies suggest: (1) faster HIV disease progression in thalassemia major patients receiving inadequate doses of ironchelating drug; (2) higher mortality among patients receiving iron supplementation with dapsone compared with aerosolized pentamidine for prophylaxis against Pneumocytis carinii pneumonia; (3) higher iron stores and mortality among patients with haptoglobin Hp 22 phenotype; and (4) shorter survival among patients with high bone marrow iron deposition. These studies largely involved men in developed countries. Among HIVinfected pregnant women in Africa with a high prevalence of iron deficiency, no relationship was found between indicators of iron status and HIV disease severity. The available data do not contraindicate the current practice of iron supplementation in developing countries where there is a high prevalence of both HIV infection and iron deficiency. Copyright 2001 Harcourt Publishers Ltd. PMID 11601873

1413_ 2001 Oct;16(10):77983.

Maintenance intravenous iron therapy in pediatric hemodialysis patients.

Morgan HE, Gautam M, Geary DF.

Iron supplementation is required for optimal response to erythropoietin (EPO) in hemodialysis patients. This is due to blood lost in the dialysis tubing after dialysis and the increased demand for iron by EPO therapy. Maintenance intravenous (IV) iron was administered according to a standardized protocol to pediatric patients on hemodialysis in our institution. The effect of this protocol on EPO dose, iron indices, anemia, and medication costs was evaluated. Data on two groups of patients were retrieved from the health records. Group 1 (n=14) consisted of patients treated in the 18 months prior to the protocol. These patients received oral iron supplements and occasional IV iron. Group 2 (n=5) consisted of all patients treated with the IV iron protocol. There was no difference in clinical characteristics and mean values for monthly hemoglobin, serum iron, ferritin, and transferrin saturation between groups. The dose of EPO was significantly reduced in group 2 compared with group 1 (193.9 +/ 121.4 vs. 73.9 +/ 39.0 units/kg per week, P<0.05). Medication costs were reduced by 26% in group 2. No significant adverse events were seen. Maintenance IV iron reduced the dose of EPO required to maintain blood hemoglobin levels. Our results also suggest that maintenance IV iron is a moreeconomic method of iron supplementation for pediatric hemodialysis patients. PMID 11605781

142_ 2001 Sep;51(3):2259.

[Utilization of different iron concentrations on pregnant adolescents also supplemented with zinc and folate] Nogueira NN, Marreiro DN, Parente JV, Cozzolino SM.

The pregnant teenager is considered at nutritional risk specially due to the fact that most of them still growing and developing. Therefore the demands of pregnancy compete with those of growth causing an extra need for her and the fetus (1). Iron, zinc and folate are essential nutrients that are frequently low on the teenagers diet. Besides that there is not much specific information available about these nutrient recommendations and their interaction among each other. The data available is limited and demands more investigation. This study was conducted at a Public Maternity Hospital located at Teresina, Piauf, Brazil. The main objective of this study was to investigate the effect of different concentrations of iron supplementation (80 and 120 mg of ferrous sulfate) together with folate (250 micrograms) and zinc (5 mg) on the hemoglobin concentration and iron stores (plasma ferritin) of pregnant adolescents. The supplementation was done from the 16th to 20th weeks of gestation until delivery. The data founded proved that either 80 mg or 120 mg of iron supplements had similar effect on the improvement of hemoglobin concentration although results showed no statistical significance. PMID 11795240

1435_ 2001 SepOct;47(5):5115.

Anemia and iron target realization in 1998: clinical management of anemia in 1,639 patients on hemodialysis.

Salahudeen AK, Fleischmann E, Ahmed A, Bower JD.

Anemia management in hemodialysis patients continues to evolve, and recently, greater emphasis has been placed on the wider use of intravenous iron to maintain adequate iron levels. This survey provides scarcely available yet potentially useful information on the clinical treatment of anemia in a large cohort of hemodialysis patients. The erythropoietin and iron administration details and pertinent laboratory measurements from 1,639 patients were analyzed for the month of December, 1998. A standardized protocol had been used in that erythropoietin was begun at a total weekly dose of 150 U/kg IV or 100 U/kg subcutaneously and was then adjusted to maintain a hematocrit (Hct) of 3336%. Iron supplements, oral, IV, or both, were administered to maintain percent transferrin saturation (TSAT) at 2030% and/or a serum ferritin of 100500 ng/ml. No intravenous iron was administered if the ferritin was more than 500 ng/ml. Although 82% of patients were on iron supplementation and, among them, 58% were on IV iron, the percentage of patients with TSAT >20, i.e., bioavailable iron, was only 51%. The serum ferritin was high at 498 +/ 10 ng/ml (mean +/ SEM) and 88% and 10% of patients had serum ferritin >100 and >1,000 ng/ml, respectively, suggestive of sequestration of part of the infused iron. Erythropoietin was administered to 96% of patients, 99.5% by IV route. The latter was consistent with the US dialysis population at large but in variance with DOQI preference for the subcutaneous route. The target Hct range of 3336 was found in 33%, with a mean Hct of 34.0 +/ 0.12. When the data were reanalyzed by excluding patients who had not been receiving erythropoietin and had not been on dialysis for at least 3 months, the percentage of patients achieving the target Hct increased to 37%. Paired analysis of 875 patients present in 1996 and 1998 showed that, although there was a marked increase in the use of IV iron, the improvement in anemia was modest, and there was evidence for increased iron accumulation. In summary, this 1998 survey on the clinical practice of anemia management in a large hemodialysis population indicates that there is a marked increase in needbased IV iron usage that was associated with modest improvement in anemia and evidence for increased iron storage. A maintenance iron dosing protocol with smaller doses of iron, such as 25 mg of iron dextran per hemodialysis, may make bioavailable iron continuously present for erythropoiesis, yet may reduce the chance for iron catalyzed lipid peroxidation and tissue iron deposition. PMID 11575828

144_ 2001 Sep;89(1):1102.

Effect of weekly or successive iron supplementation on erythropoietin doses in patients receiving hemodialysis.

Kato A, Hamada M, Suzuki T, Maruyama T, Maruyama Y, Hishida A.

AIMS: To conduct a 3month prospective study to determine the optimal way for intravenous iron supplementation in hemodialysis (HD) patients with resistance to recombinant human erythropoietin (rHuEPO) therapy due to deficient iron storage. METHODS: Thirtyfive HD patients with iron deficiency were divided into three groups: (1) patients receiving an intravenous infusion of 40 mg of iron during the first ten HD sessions (n = 12); (2) patients receiving 40 mg of iron injected once a week for 10 weeks (n = 12), and (3) patients without any iron supplementation (n = 11). The rHuEPO dosage was adjusted to maintain hemoglobin levels >10.0 g/dl, and the degree of anemia was assessed 3 months later. RESULTS: In group 1, the hemoglobin levels were significantly increased after 4 weeks and remained increased until the end of the study (p < 0.01). In group 2, the hemoglobin levels were gradually increased until the end of the study (p < 0.01). There was no difference in the final hemoglobin values between both groups. The rHuEPO dosage was significantly decreased from 131 +/ 18 to 90 +/ 17 U/kg/week in group 1 (p < 0.01), but could not be changed in group 2 during the observation period despite a similar elevation of the serum ferritin level. In group 3, the rHuEPO doses were rather increased at the end of the study (p < 0.05). CONCLUSION: Aggressive iron supplementation for the short term may be effective to restore rHuEPO hyporesponsiveness in HD patients with functional iron deficiency. Copyright 2001 S. Karger AG, Basel PMID 11528242

145_ 2001 Aug;80(8):6838.

Iron supplementation in pregnancy evidence and controversies.

Haram K, Nilsen ST, Ulvik RJ.

Approximately 20% of women in industrialized countries have iron deficiency in pregnancy. This article focuses on the diagnostic problem of anemia and iron deficiency and discusses different strategies for iron supplementation in pregnancy. Sferritin is commonly used to diagnose empty iron stores and is considered useful early in pregnancy as a diagnostic tool. Mean cellular volume (MCV), sFe and erythrocyte distribution width is too unspecific. Serum transferrin receptor (sTfR) is a relatively novel promising indicator of iron deficiency. Iron demands of the pregnant women are discussed as well as the dietary content of iron. Both beneficial and adverse effects of iron supplementation are outlined. It is not documented that supplementation has any substantial effect on birth weight or various complications in pregnancy. However, supplementation corrects the iron store and biochemical parameters of iron deficiency including hemoglobin concentration (Hb) and maintains the maternal iron stores in the puerperium. Recent literature also suggests that iron supply to the pregnant women may have beneficial effects on the iron content of neonates the first year of life. PMID 11531608

146_ 2001 Jul;90(7):72431.

Ironfortified and unfortified cow's milk: effects on iron intakes and iron status in young children.

Virtanen MA, Svahn CJ, Viinikka LU, Raiha NC, Siimes MA, Axelsson IE.

Iron intakes and iron status were evaluated in 36 young Swedish children given either ironfortified or unfortified cow's milk. All children had good iron status and had received breast milk or ironfortified formulae during infancy. Twenty 1yold children were randomized to a diet with ironfortified milk (7.0 or 14.9 mg Fe l(1) and 16 to a diet with unfortified milk. The iron intakes in the unfortified group at 15 and 18 mo (mean +/ SD 5.19 +/ 2.29 and 5.84 +/ 1.62 mg d(1)) were low in relation to Nordic Nutrition Recommendations, while the intakes in the ironfortified group (10.20 +/ 2.60 and 10.87 +/ 2.79mg d(1)) were normal in relation to recommendations. The gain (increase) from receiving fortified diet during the study period was at most [upper limit for 95% confidence interval (CI)] 2.6 g l(1) in blood haemoglobin, 1.9 fl in mean corpuscular volume, 2.7 micromol in serum iron and 4.5% in transferrin iron saturation, and the gain (decrease) was at most (lower limit for 95% CI) 0.29g l(1) in serum transferrin and 0.9mg l(1) in serum transferrin receptor (TfR). None of these differences was statistically significant. There was an almost significantly higher increase in serum ferritin (1.4 times higher relation of values at the end compared with the beginning, p = 0.06) and a significantly higher (1.2; p = 0.047) decrease in TfR/ log10 ferritin ratio in the fortified group. CONCLUSION: Oneyearold children starting out with good iron status given either ironfortified or unfortified cow's milk from 12 to 18 mo maintain sufficient iron status during this period. However, children fed unfortified cow's milk have an iron intake which is low in relation to recommendations and the quantitative development of their reserve iron in iron stores seems to be weaker than that of the fortified group. The consequences of this require further study. PMID 11519973

147_ 2001 JulAug;37(7):4508.

Differing sensitivity of tumor cells to apoptosis induced by iron deprivation in vitro.

Kovar J, Valenta T, Stybrova H.

We studied the sensitivity of tumor cells to the induction of apoptosis by iron deprivation. Iron deprivation was achieved by the employment of a defined irondeficient culture medium. Mouse 38C13 cells and human Raji cells die within 48 and 96 h of incubation in irondeficient medium, respectively. On the contrary, mouse EL4 cells and human HeLa cells are completely resistant to the induction of death under the same experimental arrangement. Deoxyribonucleic acid fragmentation analysis by agarose gel electrophoresis as well as flow cytometric analysis after propidium iodide staining detected in 38C13 and Raji cells, but not in EL4 and HeLa cells, changes characteristic to apoptosis. The 38C13 cells, sensitive to iron deprivation, also displayed a similar degree of sensitivity to apoptosis induction by thiol deprivation (achieved by 2mercaptoethanol withdrawal from the culture medium) as well as by rotenone (50 nM), hydroxyurea (50 microM), methotrexate (20 nM), and doxorubicin (100 nM). Raji cells shared with 38C13 cells a sensitivity to rotenone, methotrexate, doxorubicin, and, to a certain degree, to hydroxyurea. However, Raji cells were completely resistant to thiol deprivation. EI4 and HeLa cells, resistant to iron deprivation, also displayed a greater degree of resistance to most of the other apoptotic stimuli than did their sensitive counterparts. We conclude that some tumor cells in vitro are sensitive to apoptosis induction by iron deprivation, while other tumor cells are resistant. All the tumors found to be sensitive to iron deprivation in this study (four cell lines) are of hematopoietic origin. The mechanism of resistance to apoptosis induction by iron deprivation differs from the mechanism of resistance to thiol deprivation. PMID 11573821

148_ 2001 Jun;14(3):18590.

The effect of weekly iron supplementation on anaemia and on iron deficiency among female tea pluckers in Bangladesh.

Gilgen D, MascieTaylor CG.

AIM: To investigate the effect of weekly iron supplementation on anaemia and iron deficiency among adult, female tea pluckers. METHOD: A randomized doubleblind intervention trial was conducted in a tea estate in Bangladesh where a total of 280 women received either weekly iron supplementation (200 mg ferrous fumarate and 200 mg folic acid) for 24 weeks or a matching placebo. Capillary blood samples were drawn at baseline and posttrial to determine haemoglobin, haematocrit and ferritin concentration. Mean corpuscular haemoglobin concentration (MCHC) was calculated using the haemoglobin and haematocrit values. RESULTS: The mean haemoglobin concentration in the supplemented group increased by 5.52 g L1 over the study period, on average, while ferritin values decreased by 0.33 microgram L1. The control group showed a decrease in both mean haemoglobin (0.24 g L1) and ferritin (5.32 micrograms L1). Those individuals in the supplemented group with the lowest pretrial haemoglobin and ferritin values experienced the greatest improvements posttrial, whereas nonanaemic individuals showed a decrease in both haemoglobin and ferritin concentrations. A total of 62.2% of women in the supplemented group reported feeling better and more energetic compared to 51.1% in the placebo group; 14.4% of the supplemented group and 22.7% of the control group complained about sideeffects. CONCLUSION: Weekly iron supplementation was logistically simpler and cheaper than daily supplementation but would have to be continued on a longer term basis in order to combat both anaemia and iron deficiency. PMID 11424510

149_ 2001 Jun;47(3):1325.

The effect of iron supplementation on visualevoked potentials in infants with irondeficiency anemia.

Sarici SU, Okutan V, Dundaroz MR, Serdar AM, Akin R, Deda G, Gokcay E.

Flash visualevoked potentials were studied in 20 infants with irondeficiency anemia to determine the effect of iron deficiency on visual function by using visualevoked potentials in this type of anemia. After iron therapy for 12 weeks, visualevoked potentials were retested in these otherwise healthy infants. All infants showed an excellent hematological response to iron therapy. Posttreatment visualevoked potential N2 latencies (negative deflections) decreased significantly compared to the pretreatment values (p < 0.05). These results suggest that irondeficiency anemia causes subclinical visual impairment, and visualevoked potentials may be a useful noninvasive means of detecting subtle effects of nutritional deficiencies and monitoring the nutritional status of infants. PMID 11419674

150_ 2001 May;138(5):67987.

Iron supplementation of breastfed Honduran and Swedish infants from 4 to 9 months of age.

Domellof M, Cohen RJ, Dewey KG, Hernell O, Rivera LL, Lonnerdal B.

OBJECTIVE: The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different populations. Study design: In a randomized, placebocontrolled, masked clinical trial, we assigned term Swedish (n = 101) and Honduran (n = 131) infants to 3 groups at 4 months of age: (1) iron supplements, 1 mg/kg/d, from 4 to 9 months, (2) placebo, 4 to 6 months and iron, 6 to 9 months, and (3) placebo, 4 to 9 months. All infants were breastfed exclusively to 6 months and partially to 9 months. RESULTS: From 4 to 6 months, the effect of iron (group 1 vs 2 + 3) was significant and similar in both populations for hemoglobin, ferritin, and zinc protoporphyrin. From 6 to 9 months, the effect (group 2 vs group 3) was significant and similar at both sites for all iron status variables except hemoglobin, for which there was a significant effect only in Honduras. In Honduras, the prevalence of iron deficiency anemia at 9 months was 29% in the placebo group and 9% in the supplemented groups. In Sweden, iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months (<3%). CONCLUSION: Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breastfed infants. The unexpected hemoglobin response at 4 to 6 months in both populations suggests that regulation of hemoglobin synthesis is immature at this age.

151_ 2001 May;56(5):68790.

Iron, infection and the evolutionary ecology of heart disease.

Summers K.

Levels of iron intake and stored iron have been implicated as risk factors for coronary heart disease. More recently, considerable interest has centered on the role of a variety of infectious pathogens, particulary bacterial pathogens, in the development of artherosclerosis and heart disease. The mechanism whereby elevated iron levels increase the risk of coronary heart disease is not well understood. Here it is proposed that the influence of iron levels on the persistence, pervasiveness and intensity of bacterial infections may play an important role in the development of coronary heart disease. Copyright 2001 Harcourt Publishers Ltd. PMID 11388788

152_ 2001 May;33(5):7416.

Effects of iron repletion on blood volume and performance capacity in young athletes.

Friedmann B, Weller E, Mairbaurl H, Bartsch P.

PURPOSE: The purpose of this study was to find out whether iron repletion leads to an increase in red blood cell volume (RBV) and performance capacity in irondeficient nonanemic athletes. METHODS: 40 young elite athletes (1325 yr) with low serum ferritin (< 20 microg.L1) and normal hemoglobin (males > 13.5 g.dL1, females > 11.7 g.dL1) were randomly assigned to 12wk treatment with either twice a day ferrous iron (equivalent to 2 x 100 mg elemental iron) or with placebo using a double blind method. Before and after treatment, hematological measures and parameters of iron status were determined in venous blood. RBV, blood volume (BV), and plasma volume (PV) were measured by CO rebreathing. For determination of the aerobic and anaerobic capacity (maximal accumulated oxygen deficit, MAOD), the athletes performed an incremental as well as a highly intensive treadmill test. RESULTS: After 12 wk, ferritin levels were within the normal range in the irontreated group (IG) with a significant (P < 0.001) mean increase by 20 microg.L1 opposed to a slight nonsignificant decrease in the placebo group (PG). RBV did not change significantly in either group nor did any of the hematological measures. However, only in IG there were significant increases in VO2max and in O2 consumption in the MAOD test. MAOD and maximal capillary lactate concentration remained unchanged in both treatment groups. CONCLUSIONS: The results indicate that in young elite athletes with low serum ferritin and normal hemoglobin concentration iron supplementation leads to an increase in maximal aerobic performance capacity without an augmentation of RBV. PMID 11323542

153_ 2001 Apr 12;140(7):20913.

[Clinical and economic significance of iron replacement in anemia treated with recombinant human erythropoietin in patients on hemodialysis]

Vankova S, Safarova R, Horackova M, Herink J, Rychlik I, Bahbouh R, Putova I.

BACKGROUND: Anaemia is a common phenomenon encountered in patients on hemodialysis. Although treatment with rHuEPO therapy is effective, it may fail even at high doses. As rHuEPO efficacy depends on the bioavailability of iron, we monitored the effect of consistent iron supplementation on hematocrit levels and rHuEPO dosage. METHODS AND RESULTS: 24 patients of our outpatient dialysis centre were included in this study. The mean age was 59 years. The age group over 60 included 14 patients. The mean duration of dialysis treatment was 23.8 months. The patients were followed for 6 months according to the NKFDOQI (National Kidney Foundation Dialysis Outcomes Quality Initiative) recommendations for the treatment of anaemia. Following values were examined monthly: hematocrit, transferin saturation (TSAT) and ferritin. Iron and rHuEPO dosage was adjusted accordingly. Genetic tests for haemochromatosis were conducted in 4 patients with the highest value of TSAT and ferritin. TSAT increased from a mean of 15.9% to 35.9% (p < 0.001). In 23 patients (96%) TSAT levels were within the recommended range after the treatment. Hematocrit increased from 27.7% to 35.7% (p < 0.001). The recommended value of 33% was achieved in 18 patients (75%). The weekly dose of eHuEPO fell from 3958 IU (International Unit) to 2042 IU (p < 0.001), i.e. 1857 IU of rHuEPO were saved per week, per patient. The average dose of iron administered was 157 mg per week. The average level of ferritin rose from 457 micrograms/k to 1387 micrograms/l (p < 0.001). All results were comparable, even in the group of the senior's selected cases. Genetic testing for haemochromatosis showed mutation H63D in heterozygous state of HFE gene in 2 of 4 patients with the highest value of TSAT and ferritin. Sufficient iron supplementation leads to a significant rise in hematocrit and a concomitant decrease of required rHuEPO doses. TSAT, and not ferritin, is a good marker of iron bioavailability. CONDITIONS: The financial savings due to decreased rHuEPO requirements are 20 times higher than the costs related to iron supplementation, calculated in relation to prices valid for the Czech Republic in 1999. Cause and effect of increased level of ferritin should be carefully studied.

154_ 2001 Apr;37(4):7507.

Melatonin prevents oxidative stress resulting from iron and erythropoietin administration.

Herrera J, Nava M, Romero F, RodriguezIturbe B.

Intravenous iron (Fe) and recombinant human erythropoietin (rHuEPO) are routine treatments in the management of anemia in patients with chronic renal failure. We investigated the oxidative stress acutely induced by these therapies and whether pretreatment with oral melatonin (MEL) would have a beneficial effect. Nine patients (four women) were studied within 1 month of entering a chronic hemodialysis program in the interdialytic period. Plasma malondialdehyde (MDA), red blood cell glutathione (GSH), and catalase (CAT) activity were measured in blood samples obtained before (baseline) and 1, 3, and 24 hours after the administration of Fe (100 mg of Fe saccharate intravenously over 1 hour) or rHuEPO (4,000 U intravenously). One hour before these treatments, patients were administered a single oral dose of MEL (0.3 mg/kg) or placebo. Each patient was studied on four occasions, corresponding to studies performed using either placebo or MEL in association with intravenous Fe and rHuEPO administration. Baseline data showed increased oxidative stress in patients with endstage renal failure. Increments in oxidative stress induced by Fe were more pronounced at the end of the administration: MDA, baseline, 0.74 +/ 0.09 nmol/mL; 1 hour, 1.50 +/ 0.28 nmol/mL (P: < 0.001); GSH, baseline, 2.51 +/ 0.34 nmol/mg of hemoglobin (Hb); 1 hour, 1.66 +/ 0.01 nmol/mg Hb (P: < 0.001); and CAT activity, baseline, 27.0 +/ 5.7 kappa/mg Hb; 1 hour, 23.3 +/ 4.2 kappa/mg Hb (P: < 0.001). rHuEPOinduced increments in oxidative stress were more pronounced (P: < 0.001) at 3 hours (MDA, 1.24 +/ 0.34 nmol/mL; GSH, 1.52 +/ 0.23 nmol/mg Hb; CAT activity, 18.0 +/ 3.1 kappa/mg Hb). MEL administration prevented the changes induced by Fe and rHuEPO and had no adverse side effects. These studies show that intravenous Fe and rHuEPO in doses commonly used to treat anemia in chronic hemodialysis patients acutely generate significant oxidative stress. Oral MEL prevents such oxidative stress and may be of clinical use. PMID 11273875

155_ 2001 Apr;31(2):1516.

Changes in serum lipid concentrations during iron depletion and after iron supplementation.

Choi JW, Kim SK, Pai SH.

To investigate the effects of body iron depletion and iron supplementation on serum lipid concentrations, hematologic indices, iron markers, and serum lipid profiles were measured in 427 girls, age 1419 yr. There were no significant differences in serum lipid concentrations between subjects with moderate iron deficiency anemia (blood Hb < 12.0 g/dL) and healthy controls. However, serum total cholesterol concentration (mean +/ SD, 148 +/ 16 mg/dL) in severely anemic subjects with blood Hb < 8.0 g/dL was significantly lower than in subjects with blood Hb > or = 14.0 g/dL (170 +/ 17 mg/dL) (p < 0.01). Moreover, serum triglyceride concentration in subjects with blood Hb > 14.0 g/dL was 2fold higher than in the severely anemic subjects. Mean values of serum total cholesterol and triglyceride (149 +/ 17 mg/dL and 58 +/ 22 mg/dL) in girls with severe anemia were significantly elevated after iron supplementation (164 +/ 17 mg/dL and 98 +/ 26 mg/dL) (p < 0.01, respectively). In the severely anemic subjects, blood Hb concentration was correlated with serum total cholesterol (r = 0.49, p < 0.01) and triglyceride concentrations (r = 0.51, p < 0.01). These findings indicate that severe iron deficiency anemia in girls is attended by decreased concentrations of serum total cholesterol and triglyceride, and that these reduced serum lipid levels return to normal following iron supplementation. PMID 11337904

156_ 2001 Apr;15(4):1735.

[The effects of iron supplementation on auditory brainstem response with iron deficiency anemia in rats]

Zhou B, Sun A, Wang S, Ma Y, Shen J, Wang Q.

OBJECTIVE: To evaluate the therapeutic methods of sensorineural hearing loss with iron deficiency anemia and their effects. METHOD: Sixtyeight Wistar rats were randomly divided into 3 groups: Group A (iron deficiency group A) 24 rats, group B (iron deficiency group B) 24 rats and group C (control group) 20 rats. Group A and B were fed with iron deficiency diet for 6 weeks. By analyzing ABR and DPOAE, hearing loss was detected in group A and B. Then, group A was given iron supplementation diet and hyperbaric oxygen therapies, and group B was given iron supplementation diet only. RESULT: The auditory thresholds and period latencies (PL) of I waves of ABR and DPOAE amplitude in 2 kHz and 3 kHz within group A and B were significantly different before and after treatment (P < 0.05). But the effects of treatment between these two groups had not significant differences (P > 0.05). CONCLUSION: It suggested that good results can be obtained by early iron supplementation in iron deficiency hearing loss cases. Hyperbaric Oxygen therapy may not be necessary. PMID 12541645

157_ 2001 Mar 23;114(1128):1348.

Dietary iron intakes and biochemical iron status of 1549 year old women in New Zealand: is there a cause for concern?

Ferguson EL, Morison IM, Faed JM, Parnell WR, McKenzie J, Wilson NC, Russell DG.

AIM: To assess dietary iron intakes and biochemical iron status of a nationally representative sample of nonpregnant 1549 year old women (n=1,751) in New Zealand. METHODS: A crosssectional national survey was conducted in 1996/97. Women were selected via a multistage stratified cluster sampling procedure with increased sampling of Maori and Pacific women. Dietary iron intakes were estimated using a 24hour diet recall. Biochemical iron status was assessed on a nonfasting venipuncture blood sample (n=1,047) via haemoglobin, mean cell volume, erythrocyte zinc protoporphyrin, transferrin receptors and serum ferritin. RESULTS: Average daily dietary iron intakes ranged from 9.6 mg/day among Pacific women to 10.5 mg/day among Maori women; 41% of 2049 year olds and 45% of adolescents were at risk of low dietary iron intakes. The estimated percentage of 1549 year old women with iron deficiency anaemia ranged from 1.45.5%, and for iron deficiency without anaemia from 0.712.6% depending on the age group and criteria used. CONCLUSIONS: The overall estimated prevalence of suboptimal biochemical iron status among 1549 year old women in New Zealand ranged from 713%, which compared favourably with premenopausal women living in other western countries. This situation is, however, a public health concern given the potential negative functional consequences associated with even mild iron deficiency. PMID 11346162

158_ 2001 Mar;49(2):17383.

Unanticipated favorable effects of correcting iron deficiency in chronic hemodialysis patients.

Polak VE, Lorch JA, Means RT Jr.

BACKGROUND: Correction of anemia in hemodialysis patients is seldom completely attained, and the response of parameters other than hemoglobin concentration to anemia correction has not been evaluated in detail. METHODS: Laboratory parameters that suggest iron deficiency occurred in 1015% of 206 recombinant human erythropoietin (rhEPO)treated patients. Oral iron was given for 9 months and intravenous iron thereafter on a patientspecific basis when iron deficiency was evident. Eightyseven hemodialysis patients with data for 12 months were followed for another 12 months. A computerized information system enabled data management and analysis. RESULTS: With oral iron, serum ferritin decreased (P < 0.001), indicating further iron depletion. With intravenous iron, hemoglobin increased, evidence of iron deficiency decreased, and less rhEPO was needed. Striking macrocytosis appeared. Serum albumin and serum creatinine/kg body weight (an index of muscle mass) increased, while blood pressure decreased. Data were reanalyzed in four mean corpuscular volume (MCV) quartiles and two ferritin subsets at study onset. Iron deficient erythropoiesis (low MCV, mean corpuscular hemoglobin [MCH], and transferrin saturation) was striking in quartile 1; low ferritin was prevalent in all quartiles. With intravenous iron, hemoglobin increased only in quartile 1, the quartile with the greatest decrease (52%) in rhEPO dose. MCV increased in all quartiles (P < 0.001). Serum albumin increased in all MCV quartiles and both ferritin subsets, but significant creatinine/kg increase and blood pressure decrease occurred only in the lowferritin subset. CONCLUSIONS: Macrocytosis occurred with intravenous iron replacement. The universal MCV increase suggests unrecognized, inadequately treated, folic acid deficiency unmasked by an adequate iron supply. There was also improved well being. Effects were most clearly evident in patients with deficient iron stores. PMID 11288758

159_ 2000 Dec;77(3):20917.

The apparent effect of iron supplementation on serum selenium levels in teenage pregnancy.

Dawson EB, Albers JH, McGanity WJ.

Numerous studies have suggested a significant role of selenium in the prevention of gynecological carcinoma. These were epidemiological and prospective in humans and therapeutic in laboratory animals. However, no studies have been reported regarding the normal serum selenium levels during pregnancy. The maternal total blood volume increases 3050% during the second and third trimesters, resulting in lower measured serum levels for those metabolites, which are not increased significantly during pregnancy. A longitudinal study of the serum selenium levels in teenage pregnancy during the last two trimesters and 3 mo postpartum showed progressive elevation from 49 +/ 7 microg/dL after the 32nd week of pregnancy to 114 +/ 7 microg/dL at term, which was statistically significant (p < or = 0.001). Prenatal supplementation with 18 mg of iron per day prevented this elevation. The results of this study suggest that serum selenium levels in women normally double during pregnancy and this doubling is prevented by the minimal daily supplementation of 18 mg of iron, which may be due to increased absorption of selenium into the erythrocytes and incorporation into the glutathione peroxidase enzyme. PMID 11204463

160_ 2000 Dec;39(6):2639.

Schooladministered weekly iron supplementationeffect on the growth and hemoglobin status of nonanemic Bolivian schoolage children. A randomized placebocontrolled trial.

Aguayo VM.

BACKGROUND: Recent data suggest that daily iron supplementation of ironreplete children could impair their growth. If verified for weekly iron supplementation these results would markedly complicate targeting and implementing schoolbased weekly iron supplementation programs. AIM OF THE STUDY: To ascertain the effect of weekly iron supplementation on the growth and hemoglobin status of nonanemic schoolage children. SUBJECTS AND METHODS: 73 Bolivian nonanemic schoolage children randomly assigned to the treatment group (n = 37; receiving supplements containing FeSO4 during 18 weeks) or the control group (n = 36; receiving a placebo during the same period). Hemoglobin concentration and anthropometric measures were determined for each child at the beginning (T0) and the end (T18) of the study. RESULTS: The treatment group did not show any significant variation in hemoglobin concentration between T0 and T18 (1.6 +/ 10.4 g/L; P = 0.40) whereas the control group showed a significant decrease in hemoglobin concentration (4.6 +/ 10.9 g/L; P = 0.03). Anthropometric changes were not significantly different between the treatment and the control groups for weight, (1.63 +/ 1.11 kg vs 1.88 +/ 0.79 kg; P = 0.30), height (2.35 +/ 0.94 cm vs 2.11 +/ 1.03 cm; P = 0.34) or midupper arm circumference (0.29 +/ 0.57 cm vs 0.22 +/ 0.54 cm; P = 0.64). CONCLUSION: In our study, weekly iron supplementation of nonanemic schoolage children had no negative effect on their growth while having a positive effect in preventing significant decreases in hemoglobin concentration. These results suggest that in regions where iron deficiency anemia (IDA) is prevalent, a simple and costeffective way to control IDA in schoolage children is to give weekly iron supplements to all children at school. PMID 11395986

161_ 2000 Dec;42(6):62530.

Shortterm developmental outcome of iron prophylaxis in infants.

Yalcin SS, Yurdakok K, Acikgoz D, Ozmert E.

Department of Social Pediatrics, Institute of Child Health, Ankara, Turkey.

BACKGROUND: Previous studies on the cognitive effects of iron treatment have focused on anemic or nonanemic irondeficient infants. The effect of iron supplementation on cognitive development among ironsufficient infants has not been studied. The aim of the present study was to examine the effect of iron supplementation on performance in the Bayley Scales of Infant Development (BSID) and anthropometric measurement in 6monthold ironsufficient healthy infants. METHODS: Healthy, ironsufficient infants who were 6 months of age and were attending the Well Baby Clinic were considered for enrollment. Infants were randomly assigned to take ferrous sulfate supplementation (1 mg/kg per day) or no supplementation and were followed for 3 months. Anthropometric measurement, hematologic status and BSID were evaluated on admission and after 3 months. RESULTS: Seven infants in the intervention group and nine in the control group completed the study. No significant differences were observed in anthropometric measurements and complete blood counts between the two groups after the 3 month study period. The mean transferrin saturation (TS) level decreased significantly in the control group during the study period (from 15.3+/2.6 to 7.8+/5.1%; P = 0.0117), but no such reduction was seen in the intervention group. At the end of the study, the TS of the control group was found to be significantly lower than that of the intervention group (7.8+/5.1 vs. 19.9+/7.9%, respectively; P = 0.0033). The BSID scores of infants in both groups were within the normal range on admission and at the end of the study period. CONCLUSIONS: Shortterm iron supplementation did not change developmental test scores despite the hematologic response in ironsufficient healthy infants. The high prevelance of irondeficiency anemia and its relationship with adverse developmental outcome suggests that prevention of irondeficiency anemia with prophylaxis needs to be emphasized, rather than treatment. PMID 11192518

162_ 2000 Nov 24;485(23):1136.

Iron starvation leads to increased expression of Cu/Znsuperoxide dismutase in Aspergillus.

Oberegger H, Zadra I, Schoeser M, Haas H.

Department of Microbiologie, Medical School, University of Innsbruck, FritzPreglStr. 3, A6020 Innsbruck, Austria.

In a search for ironregulated proteins of Aspergillus nidulans and Aspergillus fumigatus a 16kDa protein was identified which is about 5fold upregulated during iron starvation in both species and which can be approximately 500fold enriched by simple onestep chromatography on Amberlite XAD16 resin. Nterminal protein sequence analysis and cloning of the respective A. nidulans cDNA identified this protein as a Cu/Znsuperoxide dismutase (SODA). Northern analysis revealed that upregulation of sodA expression occurs at the level of transcript accumulation. This seems to be a specific low iron response and not a general starvation answer since sodA transcript levels do not respond to carbon or nitrogen starvation. In contrast, copper depletion leads to transcriptional downregulation of sodA. Furthermore, sodA expression was found still to be subject to iron regulation in an A. nidulans mutant lacking SREA, a regulator of iron homeostasis, indicating that sodA expression is regulated by an SREAindependent mechanism. The data presented suggest that SODA plays a protective role under iron deplete conditions. PMID 11094151

163_ 2000 Nov;130(11):26916.

Supplemental vitamin A improves anemia and growth in anemic school children in Tanzania.

Mwanri L, Worsley A, Ryan P, Masika J.

We conducted a randomized controlled trial of the effects of dietary supplements on anemia, weight and height in 136 anemic school children from a low socioeconomic background in Bagamoyo District schools in Tanzania. The aim of the current study was to investigate the impact of dietary supplements on anemia and anthropometric indices of anemic school children. The supplements were vitamin A alone, iron and vitamin A, iron alone or placebo, administered in a doubleblinded design for 3 mo. All supplements were provided with local corn meals. Hemoglobin concentration, body weight and height were measured at baseline and at followup after supplementation. Vitamin A supplementation increased the mean hemoglobin concentration by 13.5 g/L compared with 3.5 g/L for placebo [P < 0.0001, 95% confidence interval (CI) 6.1913.57), the mean body weight by 0.6 kg compared with 0.2 kg for placebo (P < 0.0001, 95% CI 0.190.65) and the mean height by 0.4 cm compared with 0.1 cm for placebo (P = 0.0009, 95% CI 0.080.42). However, the group of children who received combined vitamin A and iron supplementation had the greatest improvements in all indicators compared with placebo (18.5 g/L, P < 0.0001, 95% CI 14.8122.23; 0.7 kg, P < 0. 0001, 95% CI 0.430.88 and 0.4 cm, P < 0.0001, 95% CI 0.220.56 for hemoglobin, weight and height, respectively). It is likely that vitamin A supplementation may have a useful role in combating the problems of vitamin A deficiency and anemia, as well as in improving children's growth, in developing countries. PMID 11053508

164_ 2000 NovDec;20(6):66773.

Is absorption of highdose oral iron sufficient in peritoneal dialysis patients?

Dittrich E, Puttinger H, Schneider B, Horl WH, HaagWeber M, Vychytil A.

OBJECTIVE: Iron supplementation plays a major role in erythropoietintreated endstage renal disease patients. For peritoneal dialysis (PD) patients, oral iron substitution is more convenient than intravenous therapy. However, disturbed iron absorption and adverse effects may be limiting factors for oral treatment. Nevertheless, we compared the response to a highdose and lowdose oral iron absorption test between PD patients and healthy control subjects. PATIENTS AND INTERVENTIONS: In 34 PD patients and 15 healthy control subjects, blood samples were taken at baseline as well as 2, 4, and 8 hours after oral intake of 4 tablets iron sulfate (105 mg elemental iron per tablet). In a subgroup of 6 PD patients and 6 control subjects, the oral iron absorption test was repeated using 1 tablet iron sulfate. RESULTS: There was no significant difference in the increase in serum iron during the test between the two groups. As known for healthy subjects, iron absorption was significantly better in PD patients with absolute iron deficiency compared to those with functional iron deficiency. Ironrepleted PD patients showed the lowest iron absorption, indicating that a high dose of oral iron did not overwhelm the ability of the bowel tract to reject unneeded iron. Increasing the oral iron dose from 1 to 4 tablets was followed by a better response in a small subgroup of PD patients compared to control subjects. Side effects such as nausea and vomiting occurred more frequently during highdose oral iron in control subjects than in PD patients (20% vs 8.8%). CONCLUSION: Highdose oral iron is well absorbed in irondepleted PD patients. This kind of oral iron therapy should be considered in some subgroups of PD patients with iron deficiency, particularly in those patients with poor vascularization of arm veins or intolerance to intravenous iron preparations. PMID 11216557

165_ 2000 Oct;106(4):7006.

Prospective randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams.

Franz AR, Mihatsch WA, Sander S, Kron M, Pohlandt F.

OBJECTIVES: To examine whether early enteral iron supplementation (EI) would improve serum ferritin as a measure of nutritional iron status at 2 months of age and would prevent definite iron deficiency (ID) in infants with a birth weight of <1301 g. METHODS: Infants were randomly assigned to receive enteral iron supplementation of 2 to 6 mg/kg/day as soon as enteral feedings of >100 mL/kg/day were tolerated (EI) or at 61 days of life (late enteral iron supplementation [LI]). Nutritional iron status was assessed: 1) at birth, 2) at 61 days of life, 3) when the infants reached a weight of 1.6 times birth weight, and 4) before blood was transfused at a hematocrit of <.25. ID was defined by any one of the following criteria: ferritin, <12 microg/L; transferrin saturation, <17%; or increase of absolute reticulocyte counts by >50% one week after the onset of enteral iron supplementation. Restrictive red cell transfusion guidelines were followed and all transfusions were documented. Erythropoietin was not administered. The primary outcome variables were: 1) ferritin at 61 days and 2) the number of infants with ID. RESULTS: Ferritin at 61 days was not different between the groups. Infants in the LI group were more often irondeficient (26/65 vs 10/68) and received more blood transfusions after day 14 of life. No adverse effects of EI were noted. CONCLUSIONS: EI is feasible and probably safe in infants with birth weight <1301 g. EI may reduce the incidence of ID and the number of late blood transfusions. ID may occur in very low birth weight infants despite early supplementation with iron and should be considered in the case of progressive anemia.preterm infant, iron supplementation, iron deficiency, blood transfusion. PMID 11015511

166_ 2000 Sep;52(3):14750.

[Pharmacoeconomics in hemodialysis. Role of iron in the treatment with erythropoietin]

Navino C, David P, Cofano MF, Borlandelli S, Verzetti G.

BACKGROUND: Although its efficacy is well known, the high economic cost of erythropoietin (EPO) raises the question of pharmacoeconomics in HD. An optimal Hb level with the lowest dosage of EPO seams to be correlated to the way of administration and an adequate iron supplementation. METHODS: The study evaluates the influence of iron supplementation on the control of EPOrelated expenses. RESULTS: A serum ferritin level higher than 50 pg/ml in hemodialysis patients on chronic EPO therapy turned out to be adequate to keep an optimal Hb level. Our data show that this value, as far as pharmacoeconomic is concerned, is highly underestimated. CONCLUSIONS: A higher i.v. iron supplementation correlates with a significant raise of serum ferritin level and saves on EPOrelated expenses up to 1 million/per patient/per year. PMID 11227366

167_ 2000 SepOct;94(5):4939.

The impact of iron supplementation on reinfection with intestinal helminths and Schistosoma mansoni in western Kenya.

Olsen A, Nawiri J, Friis H.

A randomized, placebocontrolled, doubleblind trial was carried out in 199496 among 231 children and 181 adults in order to determine the effects of iron on reinfection rates and intensities of hookworm, Ascaris lumbricoides, Trichuris trichiura and Schistosoma mansoni. Adults given 60 mg elemental iron twiceweekly for 12 months had significantly lower reinfection rates of A. lumbricoides (16.7% vs 31.9%, P = 0.046), T. trichiura (6.9% vs 20.6%, P = 0.03) and S. mansoni (38.3% vs 61.8%, P = 0.008) compared to adults given placebo. In contrast, adults allocated to iron had a significantly higher reinfection rate of hookworm at the 4month examination (11.1% vs 0%, P = 0.009), but the difference was not significant at 8 and 12month followup examinations. Iron supplementation had no effect on reinfection intensities in adults. Surprisingly, iron supplementation had no effect on either reinfection rates or intensities in children. Multiple logistic regression analyses controlling for baseline infection status confirmed the effect in adults of iron on A. lumbricoides, T. trichiura and S. mansoni reinfection rates. The effect is suggested to be due to reduced risk behaviour, to improved immune function or to unfavourable host gut conditions caused by an increased oxidative stress. In each case, the lack of effect in children remains to be explained. In contrast, iron supplementation apparently was shortlived in favour of hookworm infection, an effect that needs further clarification. The findings suggest that iron supplementation has a role to play in helminth control programmes and that intraluminal factors may contribute to the regulation of some helminth infections. PMID 11132373

168_ 2000 Aug;9(4):497500.

Intravenous versus oral iron supplementation for preoperative stimulation of hemoglobin synthesis using recombinant human erythropoietin.

Rohling RG, Zimmermann AP, Breymann C.

To compare two modalities of iron supplementation for the preoperative stimulation of erythropoiesis using recombinant human erythropoietin (rhEPO), 12 adults in normal hemoglobin and iron status due for elective surgery were randomized to rhEPO 200 U/kg body weight subcutaneously twice weekly combined with either iron sucrose 200 mg intravenously twice weekly or iron sulfate 160 mg/day orally, for 3 weeks preoperatively. Efficacy was measured by the increases over baseline in hemoglobin, reticulocyte count, and ferritin determined 3 days before surgery; preoperative reticulocyte count and ferritin were significantly higher with intravenous iron, whereas the only significant intragroup increases in hemoglobin between time points also occurred in this group. Intravenous iron significantly boosts the hematopoietic response to rhEPO and prevents iatrogenic iron depletion in otherwise healthy candidates for elective surgery. PMID 10982248

169_ 2000 Jul;70(4):1727.

Effect of daily and intermittent iron supplementation on iron status of high school girls.

Kianfar H, Kimiagar M, Ghaffarpour M.

This experimental study was designed to investigate the effects of daily versus intermittent iron supplementation on iron status of high school girls in Zahedan and Rasht cities in 19961997. The subjects were selected randomly from among students of grades 13 of four high schools in each city. Anemia was determined by measuring hematological indices. 260 anemic and a similar number of nonanemic subjects of 4 high schools were selected and allocated randomly to 4 treatment groups. During a 3month period, the test groups were given 150 mg ferrous sulfate tablets (50 mg Fe). Subjects in group 1 received a daily dose, groups 2 & 3 received twice or once weekly doses respectively. The control group received no iron supplement. For these subjects, in addition to hematological indices biochemical iron indices were measured in the beginning and at the end of the study. The increases in hemoglobin concentration in anemic subjects were not significantly different among supplemented groups but were different from the control group (p < 0.00001). Among anemic subjects, changes in serum ferritin levels in 3 supplemented groups were significantly different from the control group. Serum ferritin in Group 1 was also increased to a greater extent than groups 2 and 3 (P < 0.00001). It is concluded that over the study period a weekly iron dose was as effective as a daily dose in treating anemia but the daily dose was more effective in improving iron stores than a weekly dose in the short run. PMID 10989766

170_ 2000 Jun;71(6):148594.

Lack of hemoglobin response to iron supplementation in anemic mexican preschoolers with multiple micronutrient deficiencies.

Allen LH, Rosado JL, Casterline JE, Lopez P, Munoz E, Garcia OP, Martinez H.

BACKGROUND: In developing countries, incomplete resolution of anemia with iron supplementation is often attributed to poor compliance or inadequate duration of supplementation, but it could result from deficiencies of other micronutrients. OBJECTIVE: Our objective was to assess children's hematologic response to supervised, longterm iron supplementation and the relation of this response to other micronutrient deficiencies, anthropometry, morbidity, and usual dietary intake. DESIGN: Rural Mexican children aged 1836 mo (n = 219) were supplemented for 12 mo with either 20 mg Fe, 20 mg Zn, both iron and zinc, or placebo. Children were categorized as ironunsupplemented (IUS; n = 109) or iron supplemented (IS; n = 108). Hemoglobin, hematocrit, mean corpuscular volume, mean cell hemoglobin, plasma concentrations of micronutrients that can affect hematopoiesis, anthropometry, and diet were assessed at 0, 6, and 12 mo; morbidity was assessed biweekly. RESULTS: At baseline, 70% of children had low hemoglobin (</=115 g/L), 60% had low hematocrit, 48% were ferritin deficient, 10% had deficient and 33% had low plasma vitamin B12 concentrations, 29% had deficient vitamin A concentrations, and 70% had deficient vitamin E concentrations. Iron supplementation increased ferritin from 11 +/ 14 microg/L at baseline to 31 +/ 18 microg/L after 6 mo (P < 0.001) and 41 +/ 17 microg/L after 12 mo. However, anemia persisted in 30% and 31% of supplemented children at 6 and 12 mo, respectively, and was not significantly different between the IUS and IS groups at 12 mo. Initial plasma vitamin B12, heightforage, and dietary quality predicted the hematopoietic response to iron. CONCLUSION: Lack of hemoglobin response to iron was associated with indicators of chronic undernutrition and multiple micronutrient deficiencies. PMID 10837289

171_ 2000 Jun;35(7):173744.

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

Silverberg DS, Wexler D, Blum M, Keren G, Sheps D, Leibovitch E, Brosh D, Laniado S, Schwartz D, Yachnin T, Shapira I, Gavish D, Baruch R, Koifman B, Kaplan C, Steinbruch S, Iaina A.

OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/ 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization. PMID 10841219

172_ 2000 May;70(3):11925.

Risk of iron overload among middleaged women.

Kato I, Dnistrian AM, Schwartz M, Toniolo P, Koenig K, Shore RE, ZeleniuchJacquotte A, Akhmedkhanov A, Riboli E.

Iron overload, expressed as increased body iron stores, has been recognized as a potential hazard because it promotes the generation of oxygen radicals. We analyzed factors associated with serum ferritin levels (an indicator of body iron stores) among middleaged women with a high prevalence of nutrient supplement use. Serum ferritin concentrations were determined on automated immunoassay for 487 healthy women with the mean age of 57 years who participated in the New York University Women's Health Study. The mean serum ferritin concentration in postmenopausal women was more than twice that in premenopausal women. Serum ferritin concentrations progressively increased with advancing age, but adjustment for menopausal status considerably weakened this association. Among nondietary factors, nonwhite ethnicity, obesity and cigarette smoking were positively associated with serum ferritin concentrations. After adjustment for these factors and for menopausal status, serum ferritin levels were positively associated with meat intake and multivitamin use and inversely associated with breakfast cereal consumption. However, none of these lifestyle factors positively associated with serum ferritin levels had a significant impact on serum ferritin levels above 100 ng/ml (approximately equal to median concentration). Our results suggest that iron overload seems unlikely among middle aged women through their diet and nutritional supplements. PMID 10883405

173_ 2003 Jul;78(1):14553.

Efficacy and tolerability of lowdose iron supplements during pregnancy: a randomized controlled trial.

Makrides M, Crowther CA, Gibson RA, Gibson RS, Skeaff CM.

BACKGROUND: Iron deficiency anemia (IDA) is common in pregnant women, but previous trials aimed at preventing IDA used highdose iron supplements that are known to cause gastrointestinal side effects. OBJECTIVE: The objective was to assess the effect on maternal IDA and iron deficiency (ID, without anemia) of supplementing pregnant women with a low dosage (20 mg/d) of iron. Effects on iron status were assessed at the time of delivery and at 6 mo postpartum. Gastrointestinal side effects were assessed at 24 and 36 wk of gestation. DESIGN: This was a randomized, doubleblind, placebocontrolled trial of a 20mg daily iron supplement (ferrous sulfate) given from 20 wk of gestation until delivery. RESULTS: A total of 430 women were enrolled, and 386 (89.7%) completed the followup to 6 mo postpartum. At delivery, fewer women from the ironsupplemented group than from the placebo group had IDA [6/198, or 3%, compared with 20/185, or 11%; relative risk (RR): 0.28; 95% CI: 0.12, 0.68; P < 0.005], and fewer women from the ironsupplemented group had ID (65/186, or 35%, compared with 102/176, or 58%; RR: 0.60; 95% CI: 0.48, 0.76; P < 0.001). There was no significant difference in gastrointestinal side effects between groups. At 6 mo postpartum, fewer women from the ironsupplemented group had ID (31/190, or 16%, compared with 51/177, or 29%; RR: 0.57; 95% CI: 0.38, 0.84; P < 0.005). The rate of IDA between the groups did not differ significantly at 6 mo postpartum. CONCLUSION: Supplementing the diet of women with 20 mg Fe/d from week 20 of pregnancy until delivery is an effective strategy for preventing IDA and ID without side effects. PMID 12816784

174_ 2003 Jun;82(6):53742.

Selective iron supplementation based on serum ferritin values early in pregnancy: are the Norwegian recommendations satisfactory?

Sandstad B, BorchIohnsen B, Andersen GM, DahlJorgensen B, Froysa I, Leslie C, Aas MH, Eig TR, Sandem SO.

BACKGROUND: The aims of the present study were to evaluate the recommendations by comparing compliance and adequacy of iron status at 6 weeks postpartum between one group given advice only and one group given advice plus iron supplement. In the latter group the efficacies of two iron preparations of different strengths and types were compared. METHODS: Ninetythree women had been given advice only (Group I) and were enrolled in the project at 6 weeks postpartum. Two hundred and thirtythree women enrolled at their second antenatal visit and were given advice plus iron supplement; those with sferritin <60 microg/L were randomized to a daily dose of 1) 60 mg Fe2+ (Ferromax) or 2) 3.6 mg heme iron plus 24 mg Fe2+ (Hemofer), and started taking the supplement at once if sferritin <20 microg/L or at 20 weeks if 2060 microg/L. In addition to hemoglobin as routine, sferritin was measured in all the women at 6 weeks postpartum. RESULTS: At 6 weeks postpartum median sferritin was 28 and 34 microg/L in Groups I and II, respectively, and a significantly higher mean sferritin (46.5 vs. 37.3 microg/L; p < 0.05) was found in women taking the highest dose. There were no correlations between sferritin in early pregnancy and at 6 weeks postpartum. Peripartum blood loss was the main indicator for iron status at 6 weeks postpartum. CONCLUSION: Iron supplementation based on iron status early in pregnancy, with 60 mg ferrous iron or 27 mg iron containing heme, resulted in adequate iron stores at 6 weeks postpartum among 75% or 70% of the women, respectively. However, 6 weeks were not sufficient to rebuild iron stores in women with large peripartum blood loss. PMID 12780424

175_ 2003 Jun;133(6):1974S1977S.

Iron supplement use among women in the United States: science, policy and practice.

Cogswell ME, KettelKhan L, Ramakrishnan U.

The use of iron supplements is an accepted treatment for nonhereditary anemia. The use of iron supplements as prophylaxis is more controversial. We estimated the proportion of persons who consumed supplements that contain iron among the following groups: nonpregnant, nonlactating adolescents, aged 1418 y (n = 992); women aged 1950 y (n = 5,062); women aged 51 y and older (n = 3,593); pregnant women (n = 295); and lactating women (n = 97) using data from the National Health and Nutrition Examination Survey, 19881994. We found that the proportion (% +/ SE) of U.S. women consuming supplements containing iron in the previous month was 9 +/ 2% among nonpregnant, nonlactating adolescents; 23 +/ 1% among women aged 19 y and older; 72 +/ 4% among pregnant women; and 60 +/ 8% among lactating women. Low income women were less likely to consume supplements containing iron. Minority women were less likely to consume supplements containing iron in all groups except adolescents. Among consumers of supplements that contain iron, the median intake of iron was 11 mg/d among nonpregnant adolescents, approximately 17 mg/d among nonpregnant women, 58 mg/d among pregnant women and 57 mg/d among lactating women. Use of supplements that contain iron was associated with a significantly reduced prevalence of iron deficiency among women 1950 y but not among other groups. Groups at highest risk of iron deficiency (e.g., low income and minority women) are often least likely to consume supplements containing iron, suggesting that supplement use is unrelated to actual need. PMID 12771348

176_ 2003 May 24;326(7399):1124.

Iron supplementation for unexplained fatigue in nonanaemic women: double blind randomised placebo controlled trial.

Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, Bischoff T, de Vevey M, Studer JP, Herzig L, Chapuis C, Tissot J, Pecoud A, Favrat B.

OBJECTIVE: To determine the subjective response to iron therapy in nonanaemic women with unexplained fatigue. DESIGN: Double blind randomised placebo controlled trial. SETTING: Academic primary care centre and eight general practices in western Switzerland. PARTICIPANTS: 144 women aged 18 to 55, assigned to either oral ferrous sulphate (80 mg/day of elemental iron daily; n=75) or placebo (n=69) for four weeks. MAIN OUTCOME MEASURES: Level of fatigue, measured by a 10 point visual analogue scale. RESULTS: 136 (94%) women completed the study. Most had a low serum ferritin concentration; <or= 20 microg/l in 69 (51%) women. Mean age, haemoglobin concentration, serum ferritin concentration, level of fatigue, depression, and anxiety were similar in both groups at baseline. Both groups were also similar for compliance and dropout rates. The level of fatigue after one month decreased by 1.82/6.37 points (29%) in the iron group compared with 0.85/6.46 points (13%) in the placebo group (difference 0.95 points, 95% confidence interval 0.32 to 1.62; P=0.004). Subgroups analysis showed that only women with ferritin concentrations <or= 50 microg/l improved with oral supplementation. CONCLUSION: Nonanaemic women with unexplained fatigue may benefit from iron supplementation. The effect may be restricted to women with low or borderline serum ferritin concentrations. PMID 12763985

177_ 2003 Apr;40(4):296301.

Anemia prophylaxis in adolescent school girls by weekly or daily ironfolate supplementation.

Agarwal KN, Gomber S, Bisht H, Som M.

OBJECTIVE: To examine the benefits of anemia prophylaxis in adolescent school.girls by weekly or daily ironfolate supplementation. DESIGN: Prospective study. SETTING: Government girl schools of northeast Delhi. SUBJECTS: 2088 subjects (with hemoglobin greater than 7.9 g/dL), including 702 on daily and 695 on weekly ironfolate administration; 691 girls served as controls. RESULTS: About 85% girls were iron deficient out of which 49.3% were anemic. Weekly administration took longer time to raise hemoglobin but was effective as well as practical. Plasma ferritin estimation in girls showed rise in level in both the treated groups. CONCLUSION: Weekly administration of ironfolate was a practical and effective strategy for anemia prophylaxis in adolescent school girls. PMID 12736400

178_ 2003 Apr;133(4):107580.

Homefortification with iron and zinc sprinkles or iron sprinkles alone successfully treats anemia in infants and young children.

Zlotkin S, Arthur P, Schauer C, Antwi KY, Yeung G, Piekarz A.

Although iron deficiency is the most common singlenutrient deficiency in infants and children, other deficiencies may develop concurrently, including zinc deficiency. In previous studies, we used homefortification with "Sprinkles," singleserve sachets containing microencapsulated ferrous fumarate added to weaning foods, to successfully treat anemia. This mode of micronutrient delivery is amenable to the delivery of other micronutrients. However, the relative efficacy of multiple micronutrient supplements for the treatment of anemia requires evaluation due to possible nutrient interactions. Thus, we evaluated the relative efficacy of Sprinkles formulated with iron and zinc in anemic infants, compared with Sprinkles formulated with iron alone. We studied 304 anemic infants (mean age 10.3 +/ 2.5 mo; hemoglobin 87.4 +/ 8.4 g/L) in rural Ghana. A combined supplementation group (FeZn) received daily Sprinkles containing 80 mg iron and 10 mg zinc; a comparison group (Fe) received Sprinkles (80 mg iron) without zinc for 2 mo. The rate of recovery from anemia was higher in the Fe group compared with the FeZn group (74.8 vs. 62.9%; P = 0.048). The plasma zinc concentration decreased significantly in both groups (P < 0.05). A significant decline in the height for age Zscore was observed in the FeZn group (P = 0.0011), but there was no change in the Fe group. These results suggest that in a controlled setting, homefortification using micronutrient Sprinkles with iron, or iron and zinc, was very successful in treating anemia; however, this intervention alone was insufficient to improve zinc status or promote catchup growth in this stunted and wasted population. PMID 12672922

179_ 2003 Apr;8(4):3105.

The effect on haemoglobin of the use of iron cooking pots in rural Malawian households in an area with high malaria prevalence: a randomized trial.

Geerligs PP, Brabin B, Mkumbwa A, Broadhead R, Cuevas LE.

BACKGROUND: Innovative lowcost sustainable strategies are required to reduce the high prevalence of irondeficiency anaemia in developing countries. METHODS: We undertook a communitybased randomized controlled intervention trial to assess the effects of cooking in iron or aluminium cooking pots in Malawian households in an area with high malaria prevalence. Analysis was by intention to treat and consistency of use. The primary outcomes were change in haemoglobin and iron status. FINDINGS: The study population comprised 164 participants eating from aluminium cooking pots and 158 from iron cooking pots. The mean haemoglobin change was significantly increased after 6 weeks in adults who consistently ate from an iron cooking pot (+3.6 g/l compared to 3.2 g/l, mean difference between groups 6.8 g/l, 95% CI +0.86, +12.74). In children, no significant haemoglobin change was observed in consistent pot users, although they showed a significant reduction in iron deficiency (iron 8.6 ZP/g and aluminium 10.8 ZP/g, mean difference 2.2 ZP/g, 95% CI +1.08, +3.32). INTERPRETATION: Rural Malawian adults in a high malaria transmission area who consistently consume food prepared in iron cooking pots show a significant rise in haemoglobin after 6 weeks use. Children showed a reduction in iron deficiency, but no significant improvement in haemoglobin, possibly because of their high malaria parasite prevalence. Using iron cooking pots in developing countries could provide an innovative way to prevent iron deficiency and anaemia in malarious areas where regular iron supplementation is problematic. PMID 12667149

180_ 2003 Mar;77(3):7205.

Multiple micronutrient supplementation during pregnancy does not lead to greater infant birth size than does irononly supplementation: a randomized controlled trial in a semirural community in Mexico.

Ramakrishnan U, GonzalezCossio T, Neufeld LM, Rivera J, Martorell R.

BACKGROUND: Little is known about the benefits of prenatal multivitamin and mineral supplements in reducing low birth weight. OBJECTIVE: We conducted a randomized, doubleblind clinical trial in semirural Mexico to compare the effects of multiple micronutrient (MM) supplements with those of iron supplements during pregnancy on birth size. DESIGN: Pregnant women (n = 873) were recruited before 13 wk of gestation and received supplements 6 d/wk at home, as well as routine antenatal care, until delivery. Both supplements contained 60 mg Fe, but the MM group also received 11.5 times the recommended dietary allowances of several micronutrients. RESULTS: At recruitment, the women in the 2 groups were not significantly different in age, parity, economic status, height, or hemoglobin concentration but differed significantly in marital status (4.6% and 2.0% of women in the MM and irononly groups, respectively, were single mothers) and mean (+/ SD) body mass index (in kg/m(2); 24.6 +/ 4.3 and 23.8 +/ 3.9 in the irononly and MM groups, respectively). Losses to followup (25%) and compliance (95%) did not differ significantly between the groups. In intenttotreat analyses (MM group: n = 323; irononly group: n = 322), mean (+/ SD) birth weight (2.981 +/ 0.391 and 2.977 +/ 0.393 kg in the MM and irononly groups, respectively) and birth length (48.61 +/ 1.82 and 48.66 +/ 1.83 cm in the MM and irononly groups, respectively) did not differ significantly between the groups. CONCLUSION: These findings suggest that MM supplementation during pregnancy does not lead to greater infant birth size than does irononly supplementation. PMID 12600867

181_ 2003 Mar;77(3):6517.

Redistribution of vitamin A after iron supplementation in Indonesian infants.

Wieringa FT, Dijkhuizen MA, West CE, Thurnham DI, Muhilal, Van der Meer JW.

BACKGROUND: Deficiencies of iron and vitamin A are prevalent worldwide. Singlemicronutrient supplementation is widely used to combat these deficiencies. However, micronutrient deficiencies often occur concurrently, and there are many interactions between micronutrients. OBJECTIVE: This study investigated interactions among 3 important micronutrientsiron, vitamin A, and zincwhen they are given as supplements. DESIGN: In a randomized, doubleblind, placebocontrolled supplementation trial, 387 Indonesian infants aged 4 mo were supplemented 5 d/wk for 6 mo with 10 mg Fe, 10 mg Zn, 2.4 mg betacarotene, 10 mg each of Fe and Zn, 10 mg Zn + 2.4 mg betacarotene, or placebo. Complete data on micronutrient status, including hemoglobin, ferritin, retinol, zinc, and the modified relative dose response (a measure of liver retinol stores), were available from 256 infants at the end of the study. RESULTS: Ironsupplemented infants had significantly lower plasma retinol concentrations and a significantly higher prevalence of vitamin A deficiency, as defined by a plasma retinol concentration <0.70 micromol/L, than did the nonsupplemented infants. In contrast, the modified relative dose response of the ironsupplemented infants indicated greater liver stores of vitamin A. Iron supplementation improved iron status, and zinc supplementation improved zinc status, but betacarotene supplementation did not significantly improve vitamin A status. CONCLUSIONS: In this study, iron supplementation in infants with marginal vitamin A status led to lower plasma vitamin A concentrations and simultaneously to greater vitamin A liver stores. This implies a redistribution of retinol after iron supplementation, which might induce vitamin A deficiency. Therefore, iron supplementation in infants should be accompanied by measures to improve vitamin A status. PMID 12600856

182_ 2003 Feb;47(1):1720.

A partial supplementation of pasteurized milk with vitamin C, iron and zinc.

Biringen Loker G, Ugur M, Yildiz M.

After supplementation trials, vitamin C, iron and zinc levels were increased by 1789%, 59% and 30%, respectively. Partially supplemented pasteurized milk could be a new alternative with its high nutritive value, good sensory properties and low cost. PMID 12653430

183_ 2003 Feb;51(1 Pt 1):318.

[Iron supplementation associated with malaria prevention among pregnant women in Abidjan]

Carre N, Eono P, Kouakou K, Duponchel JL, Marquis M, Zahui KH.

BACKGROUND: Despite the demonstrated efficacy of iron supplements and malaria prevention, the effectiveness of antenatal care programs for prevention of anaemia (haemoglobin rate<11 g/dL) in pregnant women is low in West Africa. Apart from the issue of availability and despite low cost, the major reason evoked is the lack of motivation of pregnant women and health care professionals. In this study, iron supplements and malaria prophylactics were provided free of charge during pregnancy. The treatment was proposed at the first antenatal visit, with the objective of not interfering with routine practice of birth attendants and women in latter antenatal visits. METHODS: Haemoglobin rates were measured and Plasmodium falciparum tested for among pregnant women in four maternity units in Abidjan. The tests were carried out at inclusion during the first antenatal visit and during immediate postpartum in 631 pregnant women who delivered in one of the four wards. Considering the objective of the study, compliance was assessed for the month prior to delivery. RESULTS: Despite an habitual decrease in iron deficiency at the end of pregnancy, haemoglobin rates in the study population increased from 10.4 g/dL at inclusion to 10.9 g/dL during postpartum. Prevalence of anemia consequently decreased from 62.8% to 49.4% (p<0.01). A similar increase of 0.7 g/dL was observed among women stating a regular (57%) or irregular (36.9%) compliance with the protocol. A decrease of 0.4 g/dL (s.t.: 1.8 g/dL) was observed among women stating a lack of compliance with the protocol (5.6%). The prevalence of anaemia according to compliance was consequently 43.1%, 49.7% and 70.1% (p=0.02). Severe anaemia (<8 g/dL) at inclusion was an independent risk factor for postpartum anaemia although a 2.9 g/dL increase (s.t.: 2.0 g/dL) was observed in the latter (p<0.01). However, the 11 g/dL threshold was not reached. CONCLUSION: It is therefore important to reinforce the availability of treatments to prevent anaemia in pregnant women due to their demonstrated efficiency as a part of routine antenatal activities. PMID 12684579

184_ 2003 Jan;18(1):1416.

The effect of correction of anaemia in diabetics and nondiabetics with severe resistant congestive heart failure and chronic renal failure by subcutaneous erythropoietin and intravenous iron.

Silverberg DS, Wexler D, Blum M, Tchebiner JZ, Sheps D, Keren G, Schwartz D, Baruch R, Yachnin T, Shaked M, Schwartz I, Steinbruch S, Iaina A.

BACKGROUND: A mild anaemia is often found in patients with congestive heart failure (CHF), but its significance is uncertain. In an open uncontrolled study we investigated the effect of correcting this anaemia [haemoglobin (Hb) 9.511.5 g%] with subcutaneous (s.c.) erythropoietin (Epo) and intravenous (i.v.) iron (Fe) in 179 patients, 84 type II diabetics and 95 nondiabetics, with moderate to severe CHF which was resistant to maximally tolerated doses of standard CHF medications. METHODS: Epo, s.c., was given every 13 weeks to achieve and maintain the Hb at 12.5 g%. Fe (Fe sucroseVenofer) was added i.v. as necessary to maintain the Fe stores. Duration of treatment was 11.8 + 8.2 months. RESULTS: With the EpoFe treatment the Hb increased from 10.41 +/ 1.0 to 13.1 +/ 1.3 g% in diabetics and from 10.5 +/ 1.0 to 12.9 +/ 1.2 g% in nondiabetics. Comparing the diabetics and nondiabetics, the New York Heart Association functional class improved by 34.8 and 32.4%, respectively. breathlessness and/or fatigue, as measured by a selfadministered Visual Analogue Scale, improved by 69.7 and 67.4%, and the left ventricular ejection fraction improved by 7.4 and 11.5%, respectively. The number of hospitalizations fell by 96.4 and 95.3%, respectively, compared with the pretreatment period. Although the glomerular filtration rate (GFR) was falling at a rate of approximately 1 ml/min/month before the study in both groups, neither the mean serum creatinine nor the GFR changed significantly during the study period. The mean dose of Epo needed, measured in IU/week/kg body weight, was similar in the two groups. CONCLUSION: The correction of the mild anaemia that was found in diabetics and nondiabetics with resistant CHF and mild to moderate chronic renal failure improved the cardiac function and patient functional status, stabilized the renal function and markedly reduced the need for hospitalization. PMID 12480972

185_ 2003 JanMar;68(1):2933.

[Irondeficiency anemia in children. A old problem not yet resolved]

RamirezMayans JA, OrtizLopez C, GarciaCampos M, CervantesBustamante R, MataRivera N, ZarateMondragon F, MasonCordero T.

Irondeficiency anemia is still a health problem worldwide. Iron supplementation of some foods such as milk formulas and cereals apparently has not been the solution due to bioavailability of iron. In Mexico, there is high prevalence of anemia in children to date, mainly those under 2 years of age and predominantly in the Southern part of the country. Probably the main causes are irondeficiency anemia in pregnant women, recurrent infections, such as gastroenteritis and parasites, and the most important one undoubtedly, deficient iron intake. PMID 12940096

186_ 2002 Dec;147(6):74753.

Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, irondeficient children: a randomized, doubleblind, controlled trial.

Zimmermann MB, Zeder C, Chaouki N, Torresani T, Saad A, Hurrell RF.

OBJECTIVE: In many developing countries, children are at high risk for both goiter and anemia. Iron (Fe) deficiency adversely effects thyroid metabolism and reduces efficacy of iodine prophylaxis in areas of endemic goiter. The study aim was to determine if cofortification of iodized salt with Fe would improve efficacy of the iodine in goitrous children with a high prevalence of anemia. DESIGN AND METHODS: In a 9month, randomized, doubleblind trial, 615 yearold children (n=377) were given iodized salt (25 microg iodine/g salt) or dualfortified salt with iodine (25 microg iodine/g salt) and Fe (1 mg Fe/g salt, as ferrous sulfate microencapsulated with partially hydrogenated vegetable oil). RESULTS: In the dualfortified salt group, hemoglobin and Fe status improved significantly compared with the iodized salt group (P<0.05). At 40 weeks, the mean decrease in thyroid volume measured by ultrasound in the dualfortified salt group (38%) was twice that of the iodized salt group (18%) (P<0.01). Compared with the iodized salt group, serum thyroxine was significantly increased (P<0.05) and the prevalence of hypothyroidism and goiter decreased (P<0.01) in the dualfortified salt group. CONCLUSION: Addition of encapsulated Fe to iodized salt improves the efficacy of iodine in goitrous children with a high prevalence of anemia. PMID 12457449

187_ 2002 Nov 16;325(7373):1142.

Effect of iron supplementation on incidence of infectious illness in children: systematic review.

Gera T, Sachdev HP.

OBJECTIVE: To evaluate the effect of iron supplementation on the incidence of infections in children. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: 28 randomised controlled trials (six unpublished and 22 published) on 7892 children. INTERVENTIONS: Oral or parenteral iron supplementation or fortified formula milk or cereals. OUTCOMES: Incidence of all recorded infectious illnesses, and individual illnesses, including respiratory tract infection, diarrhoea, malaria, other infections, and prevalence of positive smear results for malaria. RESULTS: The pooled estimate (random effects model) of the incidence rate ratio (iron v placebo) was 1.02 (95% confidence interval 0.96 to 1.08, P=0.54; P<0.0001 for heterogeneity). The incidence rate difference (iron minus placebo) for all recorded illnesses was 0.06 episodes/child year (0.06 to 0.18, P=0.34; P<0.0001 for heterogeneity). However, there was an increase in the risk of developing diarrhoea (incidence rate ratio 1.11, 1.01 to 1.23, P=0.04), but this would not have an overall important on public health (incidence rate difference 0.05 episodes/child year, 0.03 to 0.13; P=0.21). The occurrence of other illnesses and positive results on malaria smears (adjusted for positive smears at baseline) were not significantly affected by iron administration. On metaregression, the statistical heterogeneity could not be explained by the variables studied. CONCLUSION: Iron supplementation has no apparent harmful effect on the overall incidence of infectious illnesses in children, though it slightly increases the risk of developing diarrhoea.

188_ 2002 Oct 25;127(43):22512.

[Disease prevention by vitamins and trace elements]

Pfeiffer AF, Einig Ch.

SUMMARY: Vitamins and trace elements are largely provided by a balanced nutrition. In industrialized countries, though, frequent deficiencies occur e.g. in folic acid and vitamin D as well as iodide, iron and calcium. A short review of recommended daily intake is presented.

189_ 2002 Oct;76(4):8137.

Cofortification of ironfortified flour with zinc sulfate, but not zinc oxide, decreases iron absorption in Indonesian children.

Herman S, Griffin IJ, Suwarti S, Ernawati F, Permaesih D, Pambudi D, Abrams SA.

BACKGROUND: Iron deficiency is a major nutritional concern in developing countries, and food fortification is a common strategy to treat it. In Indonesia wheat flour is fortified with 60 mg Fe/kg, but because of increasing concerns about marginal zinc status in atrisk populations, consideration is being given to cofortifying flour with zinc. However, little is known about the effect of zinc fortification of flour on iron bioavailability or about the optimum form of zinc supplementation. OBJECTIVE: We measured iron and zinc bioavailability from wheatflour dumplings containing 25 g flour fortified with 60 mg Fe/kg, either alone or with 60 mg Zn/kg as zinc oxide or as zinc sulfate. DESIGN: Ninety children aged 48 y were recruited and assigned randomly to the 3 groups; 86 completed the study. Iron and zinc absorption were measured with established stableisotope methods. RESULTS: Iron absorption from the flour fortified with iron only was good (15.9 +/ 6.8%), but when corrections were made for hemoglobin concentrations, it was significantly lower from the flour cofortified with zinc sulfate (11.5 +/ 4.9%; P < 0.05) but not from the flour cofortified with zinc oxide (14.0 +/ 8.9%). Zinc absorption was not significantly different between the zinc oxide and zinc sulfate cofortified flours (24.1 +/ 8.2% compared with 23.7 +/ 11.2%; P = 0.87). CONCLUSIONS: Iron and zinc appear to be highly bioavailable from foods made from fortified flour, but zinc sulfate cofortification may have a detrimental effect on iron absorption. PMID 12324295

190_ 2002 Oct;48(5):395400.

Effect of meals with milk on body iron stores and improvement of dietary habit during weight loss in female rhythmic gymnasts.

Kawano Y, Ishizaki S, Sasamoto S, Katoh Y, Kobayashi S.

This study investigated the effect of different timings of milk intake on body iron stores and improvement in the dietary habit of female collegiate rhythmic gymnasts. Subjects took iron tablets at both breakfast and dinner times during a weightloss period. In addition, subjects ingested lowfat milk twice a day either at breakfast or dinner (group I; n = 7), or between meals (group II; n = 6) for 3 mo. Blood was collected four times. Red blood cell count, hemoglobin, serum iron, ferritin and erythropoietin concentrations were measured. Subjects completed a dietary survey for three consecutive days before each blood sampling. The mean body fat in both groups I and II was significantly lower after 3 mo than at the start of the study (p < 0.01). Red blood cell count and hemoglobin of group I were significantly higher as compared to those of group II (p < 0.05). Serum iron concentrations and transferrin saturation values remained unchanged in both groups. Serum ferritin concentrations in group I were significantly higher 3 mo after the start of the study, but this was not observed in group II. Energy and carbohydrate intake in group II, but not in group I, were significantly lower after 3 mo as compared to those after 1 and 2 mo as a result of missing meals. In conclusion, ironsupplemented meals via milk ingestion did not decrease body iron stores and maintained higher body iron stores compared to a diet that included milk intake between meals. Further, milk intake with meals is related to keeping regular meal times and frequency. PMID 12656214

191_ 2002 Oct;5(5):61924.

Acceptability of the use of iron cooking pots to reduce anaemia in developing countries.

Prinsen Geerligs P, Brabin B, Mkumbwa A, Broadhead R, Cuevas LE.

OBJECTIVE: To evaluate acceptability, compliance and attitude towards the use of iron pots compared with aluminium pots, for cooking in a community that traditionally did not use iron pots. DESIGN: Randomised trial. SETTING: Two rural Malawian villages. SUBJECTS: Fiftytwo households received iron pots and 61 aluminium pots. RESULTS: Pot characteristics were assessed by a questionnaire after 3, 6, 11 and 20 weeks of use. Within households using iron pots there was a significant decrease in acceptability score with usage, from an initial value of 13.7 to 11.4 (range 120) Answers to questions concerning cooking characteristics showed that after 3 weeks' use the aluminium pot scored better, whereas after 20 weeks fewer answers differed between the iron and aluminium pot groups. Almost a third of the households planned to continue using iron pots daily after 20 weeks, although they had ready access to their former aluminium pot. The presence of a group of consistent pot users suggests that if households were convinced about daily use, then they were likely to maintain consistent use. Some householders considered that iron pots required less firewood for cooking than aluminium pots. The main problems related to lower acceptability were rusting and pot weight. About 25% of problems with iron pots were unrelated to their cast iron characteristics. Overall 23.4% of the households indicated they would buy an iron pot. CONCLUSIONS: The low acceptability of iron pots for cooking could limit their value as an intervention to control irondeficiency anaemia. Design modifications and better instructions on pot use should improve acceptability. The study highlights the need to assess the acceptability of interventions in order to facilitate their adoption in traditional communities. PMID 12372154

192_ 2002 Sep 21;360(9337):90814.

Intermittent administration of iron and sulfadoxinepyrimethamine to control anaemia in Kenyan children: a randomised controlled trial.

Verhoef H, West CE, Nzyuko SM, de Vogel S, van der Valk R, Wanga MA, Kuijsten A, Veenemans J, Kok FJ.

BACKGROUND: Iron supplementation is recommended for children at high risk of anaemia, but its benefits may not outweigh the associated risk of malaria in areas of seasonal transmission. We investigated the effect on haemoglobin concentrations of intermittent administration of iron supplements and sulfadoxinepyrimethamine in symptomfree children under intense health surveillance. METHODS: In a trial of two by two factorial design, 328 anaemic Kenyan children were randomly assigned either iron or placebo and sulfadoxinepyrimethamine or placebo (82 to each group). Primary outcomes were haemological indicators of iron status and inflammation at the end of the followup, and occurrence of malaria attacks. Morbidity surveillance consisted of medical examinations every 4 weeks, continuous passive case detection, and visits twice a week to community healthworkers. Analyses were by intention to treat. FINDINGS: After 12 weeks, the groups assigned iron plus sulfadoxinepyrimethamine, iron alone, or sulfadoxinepyrimethamine alone had higher haemoglobin concentrations than the group assigned placebo (treatment effect adjusted for prognostic factors at baseline: 11.1 g/L [95% CI 7.5 to 14.7]; 10.7 g/L [7.1 to 14.3]; and 3.1 g/L [0.5 to 6.7]). Administration of iron plus sulfadoxinepyrimethamine also lowered the proportion with anaemia from 100% at baseline to 36% at 12 weeks, and of iron deficiency from 66% at baseline to 8% at 12 weeks. Survival analysis showed no evidence of substantially increased risk of malaria after iron supplementation. INTERPRETATION: Iron supplementation gives substantial health benefits, which may outweigh possible inherent risks caused by malaria. A larger study than ours is needed to assess benefits and risks of intermittent administration of sulfadoxinepyrimethamine in reducing the incidence of malaria attacks in areas of seasonal malaria transmission.

193_ 2002 Sep;78(923):5337.

Investigation and management of iron deficiency anaemia in general practice: a cluster randomised controlled trial of a simple management prompt.

Logan EC, Yates JM, Stewart RM, Fielding K, Kendrick D.

BACKGROUND: Iron deficiency anaemia (IDA) remains the most common cause of anaemia and is frequently secondary to occult gastrointestinal blood loss requiring further investigation. The study was designed to prospectively assess the adequacy of investigation of IDA and to establish whether a simple computerised prompt would increase the completeness of investigation of patients presenting to their general practitioners. PATIENTS AND METHODS: All men aged >20 and women aged >50 newly found to have a probable IDA (n=431) in primary care were randomised according to general practice (n=89) to one of two computer generated prompts, by the haematology laboratories in two large district general hospitals. Data were collected 12 months after the index date. The primary outcome measure was the adequacy of investigation of the cause of anaemia. Multiple logistic regression was used to analyse each binary outcome. RESULTS: Two hundred and three (47%) of 431 patients presenting to their general practitioner with an IDA were adequately managed and 140/357 (39%) of patients who were otherwise fit for investigation had no tests at all. Twenty one (17%) of 125 patients who did have adequate investigation at the time of presentation were found to have colorectal cancer. Only 30% of patients had a confirmed diagnosis within 12 months. The prompt did not affect the level of investigation (odds ratio 0.88, 95% confidence interval (CI) 0.60 to 1.29, p=0.52). The initial prescribing of oral iron was improved (odds ratio 2.19, 95% CI 1.27 to 3.77, p=0.005), but not the documented prescribing of a full therapeutic course or the use of follow up blood counts. CONCLUSIONS: The investigation and management of IDA presenting in general practice remains inadequate and is not improved by a simple management prompt. PMID 12357013

194_ 2002 Aug;130(8):8658.

[Correction of anemia in hemodialysis, effect of intravenous iron without erythropoietin]

Alvo M, Elgueta L, Aragon H, Cotera A.

BACKGROUND: In the last two decades, the use of erythropoietin for the correction of anemia in hemodialysis patients has been recommended. In Chile, only 10% of hemodialysis patients use erythropoietin, therefore, the correction of iron deficiency must be optimized. AIM: To report the effects of intravenous iron without erythropoietin in the management of anemia in hemodialysis patients. MATERIAL AND METHODS: Retrospective analysis of 42 patients that received intravenous ferrous sacharate in doses of 100 mg/week during 5 weeks and 100 mg bimonthly during six months. These patients did not receive erythropoietin. RESULTS: Thirty six patients had iron deficiency. Basal ferritin was 137 +/ 22 micrograms/l and increased to 321 +/ 28 micrograms/l after treatment. Packed red cell volume increased from 24 +/ 2% to 29 +/ 3%. No adverse effects were reported. CONCLUSIONS: Iron deficiency is frequent in hemodialyzed patients. Intraveineous iron is safe and effective in the treatment of iron deficiency in these patients. PMID 12360794

195_ 2002 Aug;55(4):52944.

Women's perceptions of iron deficiency and anemia prevention and control in eight developing countries.

Galloway R, Dusch E, Elder L, Achadi E, Grajeda R, Hurtado E, Favin M, Kanani S, Marsaban J, Meda N, Moore KM, Morison L, Raina N, Rajaratnam J, Rodriquez J, Stephen C.

The World Health Organization estimates that 58% of pregnant women in developing countries are anemic. In spite of the fact that most ministries of health in developing countries have policies to provide pregnant women with iron in a supplement form, maternal anemia prevalence has not declined significantly where largescale programs have been evaluated. During the period 199198, the MotherCare Project and its partners conducted qualitative research to determine the major barriers and facilitators of iron supplementation programs for pregnant women in eight developing countries. Research results were used to develop pilot program strategies and interventions to reduce maternal anemia. Acrossregion results were examined and some differences were found but the similarity in the way women view anemia and react to taking iron tablets was more striking than differences encountered by region, country or ethnic group. While women frequently recognize symptoms of anemia, they do not know the clinical term for anemia. Half of women in all countries consider these symptoms to be a priority health concern that requires action and half do not. Those women who visit prenatal health services are often familiar with iron supplements, but commonly do not know why they are prescribed. Contrary to the belief that women stop taking iron tablets mainly due to negative side effects, only about onethird of women reported that they experienced negative side effects in these studies. During iron supplementation trials in five of the countries, only about onetenth of the women stopped taking the tablets due to side effects. The major barrier to effective supplementation programs is inadequate supply. Additional barriers include inadequate counseling and distribution of iron tablets, difficult access and poor utilization of prenatal health care services, beliefs against consuming medications during pregnancy, and in most countries, fears that taking too much iron may cause too much blood or a big baby, making delivery more difficult. Facilitators include women's recognition of improved physical well being with the alleviation of symptoms of anemia, particularly fatigue, a better appetite, increased appreciation of benefits for the fetus, and subsequent increased demand for prevention and treatment of iron deficiency and anemia. PMID 12188461

196_ 2002 Jul;76(1):15664.

Diet and iron status of nonpregnant women in rural Central Mexico.

Backstrand JR, Allen LH, Black AK, de Mata M, Pelto GH.

BACKGROUND: Few studies have examined the relation of iron status to diet in populations from developing countries with high levels of iron deficiency and diets of poor quality. OBJECTIVE: The objective was to identify nutrients, dietary constituents, and foods that are associated with better iron status in a rural Mexican population. DESIGN: A prospective cohort study was conducted in rural central Mexico. The subjects were 125 nonpregnant women aged 1644 y. During the 12 mo before blood collection, food intakes were assessed repeatedly by a combination of dietary recalls, food weighing, and food diaries [mean (+/SD) days of food intake data: 18.8 +/ 5.9 d]. Hemoglobin, hematocrit, and plasma ferritin were measured at the end of the study. RESULTS: Higher plasma ferritin concentrations were associated with greater intakes of nonheme iron and ascorbic acid after control for age, BMI, breastfeeding, season, and the time since the birth of the last child. Higher ascorbic acid intakes, but not higher intakes of heme and nonheme iron, predicted a lower risk of low hemoglobin and hematocrit values after control for the background variables. Consumption of the alcoholic beverage pulque predicted a lower risk of low ferritin and low hemoglobin values. Seasonal variation in ferritin, hemoglobin, and hematocrit values was observed. CONCLUSION: Better iron status was associated with greater intakes of foods containing nonheme iron and ascorbic acid. PULQUE:a beverage containing iron, ascorbic acid, and alcoholmay influence the iron status of women in rural central Mexico. PMID 12081829

197_ 2002 Jul;76(1):198204.

Iron absorption in breastfed infants: effects of age, iron status, iron supplements, and complementary foods.

Domellof M, Lonnerdal B, Abrams SA, Hernell O.

BACKGROUND: Iron supplements are often recommended for older breastfed infants, but little is known about factors affecting iron absorption from human milk or supplements. OBJECTIVE: We investigated the effects of age, iron status, and iron intake on iron absorption in healthy, term, breastfed infants. DESIGN: Twentyfive infants were randomly assigned to receive either 1) iron supplements (1 mg x kg(1) x d(1)) from 4 to 9 mo of age, 2) placebo from 4 to 6 mo and iron supplements from 6 to 9 mo, or 3) placebo from 4 to 9 mo. Infants were exclusively breastfed to 6 mo and partially breastfed to 9 mo of age. Iron absorption was assessed by giving (58)Fe with mother's milk at 6 and 9 mo. Blood samples were obtained at 4, 6, and 9 mo, and complementary food intake was recorded at 9 mo. RESULTS: At 6 mo, mean (+/SD) fractional iron absorption from human milk was relatively low (16.4 +/ 11.4%), with no significant difference between ironsupplemented and unsupplemented infants. At 9 mo, iron absorption from human milk remained low in ironsupplemented infants (16.9 +/ 9.3%) but was higher (P = 0.01) in unsupplemented infants (36.7 +/ 18.9%). Unexpectedly, iron absorption at 9 mo was not correlated with iron status but was significantly correlated with intake of dietary iron, including supplemental iron. CONCLUSIONS: Changes in the regulation of iron absorption between 6 and 9 mo enhance the infant's ability to adapt to a lowiron diet and provide a mechanism by which some, but not all, infants avoid iron deficiency despite low iron intakes in late infancy. PMID 12081835