Trial Of Iron Supplementation Research Articles

Iron supplementation in pregnancy.

Anaemia in pregnancy is a major health problem in many developing countries where nutritional deficiency, malaria and other parasitic infections contribute to increased maternal and perinatal mortality and morbidity. The objective of this review was to assess the effects of iron supplementation on haematological and biochemical parameters, and on pregnancy outcome. The Cochrane Pregnancy and Childbirth Group trials register was searched. Study authors were also contacted. Acceptably controlled trials of iron supplementation for pregnant women. Eligibility and trial quality were assessed by one reviewer. Study authors were contacted for additional information. Twenty trials were included. Iron supplementation raised or maintained the serum ferritin above 10 milligrams per litre. It resulted in a substantial reduction of women with a haemoglobin level below 10 or 10.5 grams in late pregnancy. Iron supplementation, however, had no detectable effect on any substantive measures of either maternal or fetal outcome. One trial, with the largest number of participants of selective versus routine supplementation, showed an increased likelihood of caesarean section and post-partum blood transfusion, but a lower perinatal mortality rate (up to 7 days after birth). Iron supplementation appears to prevent low haemoglobin at birth or at six weeks post-partum. There is very little information on pregnancy outcomes for either mother or baby. There are few data derived from communities where iron deficiency is common and anaemia is a serious health problem.

Erythropoiesis in Patients Stimulated with Erythropoietin: The Relevance of Storage Iron

The clinical importance of iron-restricted erythropoiesis in erythropoietin (EPO)-stimulated patients is controversial. We therefore reviewed 70 patients randomized into clinical trials of aggressive autologous donation and oral iron supplementation, with or without recombinant human EPO therapy. Nineteen (27%) iron-depleted patients produced 5.4+/-2.8 ml RBC/kg compared to 4.8+/-2.3 ml RBC/kg (nonsignificant) in iron-replete patients due to endogenous EPO (placebo group) stimulation. EPO-treated iron-depleted patients produced 20% less RBC than iron-replete patients (8.23+/-3.3 vs. 10. 2+/-4.0, p = 0.066). RBC volume expansion correlated with initial storage iron only in iron-replete patients who received EPO therapy. Initial storage iron status is a marginally important limitation to EPO-mediated erythropoiesis in the setting of oral iron supplementation. Strategies to maintain plasma transferrin saturation with intravenous iron therapy may be desirable to improve the erythropoietic response to EPO in this setting.

Erythropoiesis in Patients Stimulated with Erythropoietin: The Relevance of Storage Iron

Background and Objectives: The clinical importance of iron-restricted erythropoiesis in erythropoietin (EPO)-stimulated patients is controversial. Materials and Methods: We therefore reviewed 70 patients randomized into clinical trials of aggressive autologous donation and oral iron supplementation, with or without recombinant human EPO therapy. Results: Nineteen (27%) iron-depleted patients produced 5.4±2.8 ml RBC/kg compared to 4.8±2.3 ml RBC/kg (nonsignificant) in iron-replete patients due to endogenous EPO (placebo group) stimulation. EPO-treated iron-depleted patients produced 20% less RBC than iron-replete patients (8.23±3.3 vs. 10.2±4.0, p = 0.066). RBC volume expansion correlated with initial storage iron only in iron-replete patients who received EPO therapy. Conclusion: Initial storage iron status is a marginally important limitation to EPO-mediated erythropoiesis in the setting of oral iron supplementation. Strategies to maintain plasma transferrin saturation with intravenous iron therapy may be desirable to improve the erythropoietic response to EPO in this setting.

Iron and folate supplementation in pregnancy.

Anaemia in pregnancy is a major health problem in many developing countries where nutritional deficiency, malaria and other parasitic infections contribute to increased maternal and perinatal mortality and morbidity. The objective of this review was to assess the effects of routine iron and folate supplementation on haematological and biochemical parameters and on pregnancy outcome. The Cochrane Pregnancy and Childbirth Group trials register was searched. Study authors were also contacted. Acceptably controlled trials of routine iron and folate supplementation for pregnant women. Eligibility and trial quality were assessed by one reviewer. Study authors were contacted for additional information. Eight trials involving 5449 women were included. Routine supplementation with iron or folate raised or maintained the serum iron and ferritin levels and serum and red cell folate levels. Supplementation resulted in a substantial reduction of women with a haemoglobin level below 10 or 10.5 grams in late pregnancy. Routine supplementation with iron and folate had no detectable effect on any substantive measures of either maternal or fetal outcome. Routine supplementation with iron and folate appears to prevent low haemoglobin at delivery. There is very little information on other outcomes for either mother or baby. There are few data derived from communities where iron and folate deficiency is common and anaemia is a serious health problem.

High prevalence of anemia after cardiac transplantation in children.

Chronic anemia is common in adults after successful cardiac transplantation. However, the prevalence of anemia in children after cardiac transplantation is uncertain. The purpose of this study was to investigate the prevalence and causes of chronic anemia in well children after cardiac transplantation and in particular to define the role, if any, of iron deficiency, which is important and relatively common in normal children. Twenty children (ages 7 months to 16 years) who were well 4 months to 6 years after cardiac transplantation were studied. Fourteen children (70%) were anemic and enrolled in a prospective trial of iron supplementation. In the majority of children, serum iron and erythropoietin levels were low, although serum ferritin and zinc protoporphyrin levels tended to be normal or high. Only one child demonstrated a definite response to iron supplementation, although the hemoglobin level remained low. Anemia is highly prevalent in this population, and, despite the presence of low serum iron and transferrin saturation, anemia is not usually due to iron deficiency. Although the diagnosis of iron deficiency in this group is difficult and must not be missed, inappropriate therapy should be avoided. In the majority of children, there appears to be an anemia of chronic disease which may be secondary to chronic inflammation or an effect of cyclosporine on erythropoietin production.

Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants

Malaria and anaemia, especially that due to iron deficiency, are two leading causes of morbidity worldwide. Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas. We undertook a randomised comparison of different strategies for control of anaemia and malaria in infants, including an assessment of the effect of iron supplementation on malaria susceptibility. 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October, 1995, were randomly assigned to group DI, receiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3.125 mg pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus weekly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP. supplementation was given from 8 to 24 weeks of age, and the weekly chemoprophylaxis from 8 to 48 weeks. The frequency of severe anaemia (packed-cell volume < 25%) and malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys. The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron (0.62 vs 0.87 cases per person-year; protective efficacy 28.8% [95% CI 6.3-45.8). Iron supplementation had no effect on the frequency of malaria (0.87 vs 1.00 cases per person-year; protective efficacy 12.8% [-12.8 to 32.5]). The groups that received malaria prophylaxis had lower frequencies of both severe anaemia (0.45 vs 1.04 episodes per person-year; protective efficacy 57.3% [43.0-67.9]) and malaria (0.53 vs 1.34 episodes per person-year; protective efficacy 60.5% [48.2-69.9]) than the groups that did not receive prophylaxis. After the end of the intervention period, children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups (relative risks 2.2 [1.3-3.7] and 1.8 [1.3-2.6]). Malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity. Iron supplementation was effective in preventing severe anaemia without increasing susceptibility to malaria. Our findings support iron supplementation of infants to prevent iron-deficiency anaemia, even in malaria-endemic areas.

The effects of iron supplementation during pregnancy, given by traditional birth attendants, on the prevalence of anaemia and malaria

A randomized, double-blind, placebo-controlled community-based trial of oral iron supplementation (200 mg ferrous sulphate daily) administered to multigravid pregnant women by traditional birth attendants (TBAs) was carried out in a rural area of The Gambia. Iron supplementation led to a significant reduction in the prevalence of anaemia and of iron deficiency. Iron supplementation was not accompanied by increased susceptibility to malaria infection; there was no difference in the prevalence and severity of peripheral blood or placental malaria infection between the 2 groups of women. The birth weight of children born to women who received iron prophylaxis was increased by an average of 56 g. It is concluded that oral iron prophylaxis can be successfully delivered through TBAs integrated into a primary health care programme. This simple intervention can produce significant beneficiai effects on the health of the mother without inducing increased susceptibility to malaria and has the potential for reducing perinatal mortality by increasing birth weight.

Iron Supplementation Improves Appetite and Growth in Anemic Kenyan Primary School Children

A randomized, double-blind, placebo-controlled iron supplementation trial was conducted in Kenya to examine the effect of iron supplements on appetite and growth in 87 primary school children. Sustained-release ferrous sulfate (150 mg) or placebo tablets were provided daily at school for 14 wk. Prior to tablet administration, baseline anthropometry, iron nutritional status (hemoglobin and serum ferritin), parasitic infections and clinical indicators of morbidity were measured. A baseline appetite test was conducted twice on each child by quantitatively measuring the ad libitum consumption of a midmorning snack. In addition, each child was asked for a subjective assessment of his or her appetite. Follow-up exams and appetite tests were identical to those at baseline. Findings indicated that provision of iron supplements resulted in improved growth and improved appetite (in terms of both energy intake of the snack and child report of appetite) as compared with children receiving the placebo. The increased energy intake from the snack was 10% of the daily estimated energy intake for children of this same age group living elsewhere in Kenya. Further research into the underlying physiological mechanisms may shed light on the relationship between iron nutritional status and appetite.

Authors' Correction

To the Editor.— In the article, "Randomized, Placebo-Controlled Trial of Iron Supplementation in Infants with Low Hemoglobin Levels Fed Iron-Fortified Formula" by Irigoyen et al (Pediatrics 1991;88:320-326), an error was made on Table 1 (p323) regarding the proportion of children fed milk-based and soy-based formulas. The corrected data follow: [See table in the PDF file] Although this error only relates to the dietary background informarion and does not affect the trial or its results, we would appreciate going on record as having the data corrected.

Randomized, Placebo-Controlled Trial of Iron Supplementation in Infants With Low Hemoglobin Levels Fed Iron-Fortified Formula

In spite of the declining prevalence of iron-deficiency anemia, a large proportion of low-income infants have "low-normal" (11-11.5 g/dL) and "low" (less than 11 g/dL) hemoglobin (Hgb) values. Because most of these infants are fed iron-fortified formulas, it was of interest whether additional iron supplementation would enhance Hgb values. A cohort of 334 healthy, inner-city, minority, 6-month-old infants, fed iron-fortified formulas, with Hgb values ranging from 9 to 11.5 g/dL, participated in a double-blind, randomized, placebo-controlled trial of supplemental iron at 0, 3, and 6 mg/kg per day for 3 months. Hemoglobin values increased significantly with age, regardless of assignment to placebo or supplemental iron (means for the entire cohort: 6 months 10.9 g/dL, 8 months 11.2, 10 months 11.3, and 12 months 11.4). The proportion of "responders" (Hgb level increased greater than or equal to 1 g/dL) was 34% and did not differ significantly by placebo or iron dose. There were no significant differences in mean corpuscular volume or levels of erythrocyte porphyrins or serum ferritin between treatment groups. The implications of this clinical trial are twofold: (1) screening healthy infants fed iron-fortified formula at the age of 6 months is not justified, regardless of socioeconomic status; (2) the clinical practice of routinely treating low-income, "low-Hgb" infants with iron supplementation, without regard to dietary considerations, is unwarranted.

Evaluation of iron-deficiency anemia by an iron supplementation trial in children living at a 2800-m altitude

Hemoglobin, hematocrit, serum iron and total iron-binding capacity were measured in 38 apparently healthy children living in Quito (2:800 meters in altitude). One child was considered anemic according to the WHO reference adjusted to altitude (hemoglobin < 12.3 g/dl) and 10 had transferrin saturation of < 15%. Thirty children received orally 2 mg/kg per day of elemental iron for 3 mth. A significant increase in hemoglobin level, serum iron-concentration, and transferrin saturation, and a significant decrease in total iron-binding capacity were observed. Nine children increased their hemoglobin concentration by > 1 g/100 ml and could be considered as true anemies. At the end of the supplementation, only one child had a transferrin saturation coefficient of < 15%. WHO references for hemoglobin adjusted to altitude seem to underestimate the prevalence of anemia for populations living at high altitudes.

Effect of iron supplementation to women with iron deficiency.

ABSTRACTThe response to iron therapy in 38‐year‐old women was studied in an iron supplementation trial. Women with no or only traces of reticuloendothelial iron in bone marrow samples received in a double‐blind fashion tablets containing 37 mg ferrous iron or placebo three times daily. The women in the iron supplementation group increased significantly more their haemoglobin concentration and packed cell volume than the women in the placebo group. The average increase in haemoglobin concentration was 7.5 g/l. Approximately 75 % of the women in the iron supplementation group increased their haemoglobin concentration in spite of the fact that only 20 % had pretreat‐ment concentrations below 120 g/l. We found no differences in change of haemoglobin concentration, packed cell volume, serum iron concentration, total iron binding capacity or transferrin saturation between subjects with no reticuloendothelial iron and women with only traces of reticuloendothelial iron. We considered it impossible to define “responders” to iron therapy in an acceptable way by means of the iron supplementation test described in this paper.

Prevalences of anemia and iron deficiency anemia in Black and White women in the United States estimated by two methods.

Prevalences of anemia were estimated by two methods for 742 Black and 3,074 White nonpregnant women of childbearing age drawn from a large probability sample of the United States civilian noninstitutionalized population (NHANES I). One method defines the prevalence of anemia as the proportion of women with hemoglobin levels below a 12 g/dl "cut-off". The second method defines the prevalence of anemia as the proportion of women whose hemoglobin values are shifted downwards relative to a distribution of hemoglobin values of non-anemic women. Estimates produced by both methods suggest a higher prevalence of anemia in Black than in White women. Estimates produced by the "cut-off" method, however, are higher than those from the "distribution" method for both racial groups, probably because the "cut-off" method results in large overestimates in populations where anemia prevalence is low. The "distribution" method is further used to estimate the contribution of iron deficiency to anemia. Essentially all anemia in White women and a high proportion of anemia in Black women is associated with iron deficiency in the US civilian noninstitutionalized population. Iron supplementation trials are needed in order to define the magnitude of the problem accurately and plan appropriate public health programs.