Routine Iron Supplementation Research Articles

Iron homoeostasis in rheumatic disease

Iron is critical in nearly all cell functions and the ability of a cell, tissue and organism to procure this metal is obligatory for survival. Iron is necessary for normal immune function, and relative iron deficiency is associated with mild immunosuppression. Concentrations of this metal in excess of those required for function can present both an oxidative stress and elevate risks for infection. As a result, the human has evolved to have a complex mechanism of regulating iron and limiting its availability. This homoeostasis can be disrupted. Autoimmune diseases and gout often present with abnormal iron homoeostasis, thus supporting a participation of the metal in these injuries. We review the role of iron in normal immune function and discuss both clinical evidence of altered iron homoeostasis in autoimmune diseases and gout as well as possible implications of both depletion and supplementation of this metal in this patient population. We conclude that altered iron homoeostasis may represent a purposeful response to inflammation that could have theoretical anti-inflammatory benefits. We encourage physicians to avoid routine iron supplementation in those without depleted iron stores.

Effect of education and pill count on hemoglobin status during prenatal care in Nepalese women: A randomized controlled trial

To determine the effect of an education program and/or pill count on the change in hemoglobin levels and the prevalence of anemia in pregnant women. A randomized, factorial design controlled trial was conducted at the Tribhuvan University Teaching Hospital, Nepal. A total of 320 eligible pregnant women receiving prenatal care were randomized into four groups (control, education, pill count and education with pill count) by block randomization with allocation concealment. All recruited women received conventional routine prenatal care with a daily dose of 60 mg iron supplementation. In addition, the education group received an education program. Pill counting was done for the pill count group at their routine prenatal visits. The education with pill count group received both the education program plus pill counting. Baseline hemoglobin at the recruitment phase and follow-up hemoglobin after three months of recruitment were measured. Changes in hemoglobin levels and anemia prevalence were analyzed and compared between groups. The education only and education with pill count groups had significantly higher hemoglobin changes (0.23 and 0.26 g/dL, respectively) than the control group (P < 0.01). Anemia was reduced by 59% in the education group and by 65% in the education with pill count group, compared to the control group (P < 0.05). Pill count alone significantly improved neither the hemoglobin level nor anemia prevalence compared to the control group. An education program along with routine iron supplementation can improve hemoglobin levels and reduce anemia prevalence in pregnant women. Pill count as a measure of compliance has no additional effect on improving hemoglobin status.

Iron Deficiency during Pregnancy: Blessing or Curse?

Iron deficiency is the most common micronutrient deficiency and the most common cause of anemia among pregnant women worldwide [1]. Pregnancy may require as much as 1000 mg of elemental iron to meet the demands for maternal red blood cell expansion and fetal erythropoiesis and to account for blood lost at delivery [2]. As part of its standards for maternal and neonatal care, the World Health Organization recommends routine iron supplementation of 60 mg daily for pregnant women living in areas where malnutrition is prevalent [3]. The rationale underlying this policy is the observed association of anemia with adverse pregnancy outcomes. Specifically, anemia has been linked with low birth weight, preterm birth, decreased infant iron stores, and consequent impaired cognition and growth of the child [4-7] . For the mother, severe anemia may increase the risks of cardiac failure or death from peripartum hemorrhage [7, 8]. In a recent review of 40 trials involving > 12,000 women, routine daily iron supplementation increased hemoglobin levels by -7.5 g/dL and was associated with a decreased risk for anemia at term (relative risk, 0.56; 95% con-

Effects of routine oral iron supplementation with or without folic acid during pregnancy: an updated systematic review

Routine antenatal iron (Fe) or iron and folic acid (FeFol) supplementation may improve maternal health and pregnancy outcomes. This review assesses the efficacy, effectiveness and safety of routine daily (D) or intermittent (I) supplementation. The Cochrane Pregnancy and Childbirth Group's Trials Register (October 2007) was searched and relevant organizations were contacted for identification of additional trials. All randomized trials evaluating the effect of routine antenatal D or I Fe or FeFol were selected considering their methodological quality. Primary outcomes included maternal and infant clinical and laboratory outcomes.Forty‐nine trials, involving 19147 women, were included. The data suggest improved Hb and Fe nutrition compared to non supplemented women. There are no significant differences between D and I in any specific variables except for higher rate of hemoconcentration during 2–3 trimesters in D than in I, and also higher side‐effects in D, except for vomiting that is more common in I. D Fe and FeFol results in slightly higher maternal Hb at term. Iron deficiency and its anemia at term were slightly less likely to occur in women on D Fe than in non supplemented women. Further studies are needed to assess the effects of pre‐conceptional iron and folate status and antenatal Fe or FeFol doses administered either D or I with emphasis on functional and perinatal outcomes.

Effects of antenatal multiple micronutrient supplementation on children's weight and size at 2 years of age in Nepal: follow-up of a double-blind randomised controlled trial

SummaryBackgroundThe negative effects of low birthweight on the later health of children in developing countries have been well studied. However, undertaking programmes to address this issue can be difficult since there is no simple correlation between increasing birthweight and improving child health. In 2005, we published results of a randomised controlled trial in Nepal, in which 1200 women received either iron and folic acid or a supplement that provided the recommended daily allowance of 15 vitamins and minerals, over the second and third trimesters of pregnancy. Here, we report on 2–3 years' follow-up of children born during the trial.MethodsWe visited children at home and obtained data for the primary outcomes of weight and height, for childhood illnesses, and maternal blood haemoglobin. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN88625934.FindingsBetween December, 2005, and December, 2006, we assessed 917 children (455 controls, 462 intervention) at a mean age of 2·5 years. Mean birthweight had been 77 g (95% CI 24–130) greater in the micronutrient group than in controls. At 2·5 years old, controls weighed a mean of 10·7 kg (SD 1·38), and those in the intervention group 10·9 kg (SD 1·54). Children of women who had taken multiple micronutrient supplements during pregnancy were a mean 204 g (95% CI 27–381) heavier than controls. They also had greater measurements than controls in the circumference of the head (2·4 mm [95% CI 0·6–4·3]), chest (3·2 mm [0·4–6·0]), and mid-upper arm (2·4 mm [1·1–3·7]), and in triceps skinfold thickness (2·0 mm [0·0–0·4]). Systolic blood pressure was slightly lower in the intervention group (2·5 mm Hg [0·5–4·6]).InterpretationIn a poor population, the effects of maternal multiple micronutrient supplementation on the fetus persisted into childhood, with increases in both weight and body size. These increases were small, however, since those exposed to micronutrients had an average of 2% higher weight than controls. The public-health implications of changes in weight and blood pressure need to be clarified through further follow-up.

Critical Review of Strategies to Prevent and Control Iron Deficiency in Children

Iron deficiency is prevalent in infants and young children in developing countries and is associated with adverse developmental outcomes. The routine provision of additional iron by food fortification or the use of iron supplements is generally recommended. The wisdom of this approach in regions where the transmission of Plasmodium falciparum malaria is perennial and intense is now being questioned, because a large trial in Pemba, Tanzania, demonstrated an increased risk of serious morbidity among children under the age of 3 years who were given routine daily iron and folic acid supplements. However, the results of a concurrent substudy suggest that the untoward effects occurred in children who were not iron deficient, and that iron deficiency itself is associated with an increased risk of severe morbidity that can be reduced by iron and folic acid supplementation. There is an urgent need for additional research to confirm these observations, to establish the role, if any, of the concurrent folic acid supplementation, to evaluate the risk of alternative methods for delivering iron that, on theoretical grounds, could be safer, and to establish the programmatic feasibility of targeting iron fortificants or supplements to iron-deficient children. It is evident that a single strategy for ensuring adequate iron nutrition in young children in different parts of the world is no longer likely to be satisfactory. Moreover, integration with other health-related strategies, particularly malaria control programs, will be essential.

Content of antenatal care services in secondary health care facilities in Nigeria: implication for quality of maternal health care

To assess the contents of antenatal care and to relate the findings to the adequacy of maternal health care. Cross-sectional study. Public secondary health-care facilities. Pregnant women. Three hundred and ninety consecutive pregnant women attending 12 selected secondary health facilities were recruited proportionate to the client load recorded for each facility during the year preceding the study. Interviews were conducted using the antenatal care exit interview form of the Safe Motherhood Needs Assessment package. Antenatal care services provided to pregnant women in current pregnancy. Blood pressure measurement, abdominal palpation and detection of foetal heart rate were provided to all participants. Three hundred and eighty-six (99%) were reached with at least one educational message. One hundred and sixty-seven (42.8%) had haemoglobin or packed cell volume estimated, whereas 168 (43.1%) had urine checked for protein, at least once during antenatal visits. Routine iron and folate supplements, and malaria prophylaxis were, respectively, given to 142 (36.4%) and 25 (6.4%). The antenatal care service as provided had reasonable capacity for intervention against pre-eclampsia and some foetal problems, and could contribute to delivery in a health facility and by a health worker. Capacity to address the possible effects of severe anaemia and malaria in pregnancy was lacking. Equipping health-care facilities with capacity to detect anaemia and proteinuria as well as ensuring that iron and folate supplements, and malaria prophylaxis are given to all pregnant women would help to meet national guidelines and improve quality of service.

Routine Iron Supplementation in Pregnancy Has No Effect on Iron Status of Children at Six Months and Four Years of Age

The iron status at 6 months and 4 years of children born to women who were randomly allocated to receive 20 mg of iron daily in the second half of pregnancy did not differ from children of mothers in the control group.

A Randomized Placebo-controlled Trial to Determine the Effect of Iron Supplementation on Pregnancy Outcome in Pregnant Women With Hemoglobin >13.2 g/dL

Recommendations that pregnant women routinely take iron, to increase the mother’s hemoglobin concentration and to provide iron for the fetus and placenta, fail to account for the fact that normal pregnancy is characterized by hemodilution. Thus, an iron-induced increase in hemoglobin (Hb) may represent a pharmacological but not a physiological effect. In addition, iron loss declines during pregnancy because of increased absorption and missed menses. This randomized double-blind, placebo-controlled trial attempted to relate iron supplementation to pregnancy outcomes in 727 pregnant women whose Hb was >13.2 g/dL early in the second trimester of pregnancy. The participants, 17 to 35 years of age, had singleton pregnancies and a body mass index (BMI) of 19.8 to 26 kg/m2, and had no diseases related to polycythemia. The women took either a 150-mg tablet of ferrous sulfate containing 50 mg of elemental iron or a placebo tablet each day throughout pregnancy. The actively treated and control groups did not differ significantly at the outset with respect to age, gestational age, gravidity, BMI, socioeconomic status, or Hb level. No significant differences were found in the rate of premature labor, duration of pregnancy, birth weight, weight gain, perinatal mortality risk, number of cesarean deliveries for obstetrical reasons, or low 10-minute Apgar scores. Hypertensive disorder was more frequent in the case group than in control women, as was the rate of small-for-gestational-age births. Third-trimester Hb levels were higher in women taking a supplement, but not to a clinically significant degree. These findings suggest that routine iron supplementation has no rational basis for nonanemic pregnant women, and may in fact have some adverse effects.

A randomised placebo‐controlled trial to determine the effect of iron supplementation on pregnancy outcome in pregnant women with haemoglobin ≥ 13.2 g/dl

To study the effect of iron supplementation on pregnancy outcome in pregnant women with haemoglobin (Hb) > or = 13.2 g/dl. A randomised, double-blind, placebo-controlled trial. Routine health services. Seven hundred and twenty-seven pregnant women with Hb > or = 13.2 g/dl in the early stage of the second trimester. Each woman took one ferrous sulphate [DOSAGE ERROR CORRECTED] tablet (150 g tablet, containing 50 mg of elemental iron) [DOSAGE ERROR CORRECTED] daily in the case group (n = 370) or placebo in the control group (n = 357) throughout pregnancy. Pregnancy outcome. While there were no significant differences in demographic and obstetric characteristics between the two groups before any intervention, small-for-gestational-age birth rate and the number of women with hypertension disorder increased significantly in the case group in comparison with the control group (57 [15.7%] versus 36 [10.3%], P = 0.035, 10 [2.7%] versus 3 [8%], P = 0.05, respectively). Our finding proves that routine iron supplementation in nonanaemic women is not rational and may be harmful.

Iron deficiency anaemia: does it really matter?

Iron deficiency is common in inner city areas in 2-year-olds in the UK and is almost exclusively related to poor feeding practices, with inappropriate carbohydrate-rich food, late weaning, and an excess of unmodified cow's milk containing no available iron. The potential seriousness of iron deficiency is often ignored, but it can lead to a poor neurodevelopmental outcome, poor growth and recurrent infections. It is best managed by advice on weaning onto iron-rich foods and avoidance of large intake of unmodified milk. There is a strong case for screening in poorer areas, and the provision of routine iron supplementation to vulnerable populations in parallel with the currently recommended vitamin supplementation.

Effect of the maternal βE-globin gene on hematologic responses to iron supplementation during pregnancy

Background:It is customary in Southeast Asia to treat pregnant anemic women with iron supplements, but anemia in this region may be complicated by thalassemia and hemoglobinopathies, which lead to an ineffective response.Objective:The aim was to determine whether routine iron supplementation during pregnancy in this area, which has a high prevalence of thalassemia and hemoglobinopathies, is an effective control strategy for iron deficiency anemia.Design:A prospective study was conducted. Seventy-six pregnant women, including 43 who were heterozygous for the hemoglobin E (Hb E) gene, 20 who were heterozygous for Hb E and had α-thalassemia, and 13 who were homozygous Hb E, as well as 77 pregnant women who had no thalassemia gene, participated in this investigation. All pregnant women received a daily dose of 120 mg elemental Fe for an average of 133.5 d. Hematologic variables and serum ferritin concentrations were measured before supplementation and after supplementation at the gestational age of 28–32 wk. Differences in hematologic variables and serum ferritin were assessed.Results:Significant differences in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin responses were found between the nonthalassemia group and the 3 groups with the Hb E gene after adjustment for the following baseline values: age, body mass index, duration of iron supplementation, and ferritin concentration. Significant differences in the improvements in mean corpuscular volume and mean corpuscular hemoglobin values between the 3 groups indicate a poorer response at the cellular level in the pregnant women with the Hb E gene. Further analysis showed a significant difference in the hemoglobin response only for women who were homozygous for Hb E.Conclusion:Iron supplementation during pregnancy is not beneficial for pregnant women who are homozygous for Hb E, but a routine intervention should not cause iron overload, as judged from this short observation period.

Iron status in elite skiers

The iron status of 54 male and 30 female elite skiers (biathlon, alpine and cross-country skiers) was studied during snow training and compared with that of relevant control groups. There was no significant difference between skiers and controls in mean Hb, serum ferritin, total iron-binding capacity, frequency of iron deficiency or anemia. Iron deficiency was found in 4 women (1 of whom was anemic) and 1 man, all in the cross-country group. The urinary iron concentration, investigated 1 day after hard cross-country training in 29 skiers, did not differ from that of a control group. In a separate study, 13 cross-country skiers were followed with repeated tests during a whole year. No change was seen in their iron status. Our results show that the iron status of both endurance and alpine skiers is comparable to that of a normal population and that there is no need for routine iron supplementation.

Iron Supplementation for Postoperative Anaemia Following Major Paediatric Orthopaedic Surgery

There is increasing evidence that the anaemia of surgery is not iron deficient and is, therefore, unresponsive to iron supplementation. Oral iron is best avoided postoperatively, particularly in children, due to its dose-dependent side effects. We undertook a national survey of major paediatric orthopaedic surgical units in the UK to investigate the current management of postoperative anaemia with particular reference to iron supplementation. Middle-grade doctors and charge nurses at 23 major paediatric orthopaedic units in the UK were contacted by telephone and a structured questionnaire was used to determine the management of postoperative anaemia in major hip, pelvic and spinal surgery. Only one (4.3%) of the units surveyed had a formally established protocol for the management of postoperative anaemia. Only 10 out of 23 units (43.5%) did not routinely prescribe iron postoperatively. Of the remaining units, 11 commenced iron based on the postoperative haemoglobin level while only 2 used iron supplementation after investigation of serum haematinics for iron deficiency. One unit used erythropoietin in the treatment of postoperative anaemia. Iron supplementation continues to be used in major paediatric orthopaedic surgery in the treatment of postoperative anaemia in the absence of iron deficiency. Given the current available evidence, we call for an end to the practice of routine iron supplementation for postoperative anaemia following major paediatric orthopaedic surgery in the UK.

WITHDRAWN: 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.

Iron in the Brain

After completing this article, readers should be able to: 1. Describe the role of iron in proteins involved in neuronal and glial energy metabolism, myelin production, and monoamine neurotransmitter metabolism. 2. Indicate the neonates who are at risk for iron deficiency. 3. Explain how iron deficiency affects the biochemistry, structure, signaling molecules, and electrophysiology of the hippocampus. 4. Describe the primary causes of iron overload in the neonate. 5. Explain why the preterm infant is at particular risk for iron deficiency. This article is designed to acquaint readers with the role of iron in early brain development. Several important principles that govern the effects of nutrients on the immature brain are discussed, followed by an explanation of the roles of iron during development. Because the developing brain is sensitive to iron overload as well as iron deficiency, both are discussed in the context of human studies and in model systems. The first guiding principle of nutrient-brain interactions during development is the concept of timing, dose, and duration. (1) The positive or negative effects of any nutrient depend on which brain regions or processes are developing at the time that nutrient status is altered and the requirements of those regions for the nutrient during that time of development. Generally, the more rapidly an area is developing, the more vulnerable it is. Dependence on specific nutrients during phases of rapid proliferation or differentiation results in the second principle, a regionalization of brain effects during periods of nutrient deficiency. In the case of iron deficiency, certain brain areas that are dependent on iron for proper development are more vulnerable than areas that are less dependent on iron. Additionally, these same brain areas are likely to be more vulnerable at certain time points than at others. To exert a maximal effect on regional brain development, the timing of iron …

Effects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial

Neonatal mortality is the biggest contributor to global mortality of children younger than 5 years, and low birthweight is a crucial underlying factor. We tested the hypotheses that antenatal multiple micronutrient supplementation would increase infant birthweight and gestational duration. We did a double-blind, randomised controlled trial in Dhanusha district, Nepal. Women attending for antenatal care with singleton pregnancies at up to 20 weeks' gestation were invited to participate. Participants were randomly allocated either routine iron and folic acid supplements (control; n=600) or a multiple micronutrient supplement providing a recommended daily allowance of 15 vitamins and minerals (intervention; n=600). Supplementation began at a minimum of 12 weeks' gestation and continued until delivery. Primary outcome measures were birthweight and gestational duration. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN88625934. Birthweight was available for 523/600 infants in the control group and 529/600 in the intervention group. Mean birthweight was 2733 g (SD 422) in the control group and 2810 g (453) in the intervention group, representing a mean difference of 77 g (95% CI 24-130; p=0.004) and a relative fall in the proportion of low birthweight by 25%. No difference was recorded in the duration of gestation (0.2 weeks [-0.1 to 0.4]; p=0.12), infant length (0.3 cm [-0.1 to 0.6]; p=0.16), or head circumference (0.2 cm [-0.1 to 0.4]; p=0.18). In a poor community in Nepal, consumption of a daily supplement containing a recommended daily allowance of 15 micronutrients in the second and third trimesters of pregnancy was associated with increased birthweight when compared with a standard iron and folic acid preparation. The effects on perinatal morbidity and mortality need further comparisons between studies. Published online March 3, 2005 http://image.thelancet.com/extras/04art11045web.pdf.

Anémies maternelles sévères et issues de grossesse

The aim of this study was to determine the effects of severe antenatal maternal anemia on pregnancy outcome. and methods. A retrospective study comparing 2 groups of pregnant women: 111 (pregnant women) with anemia (Hb < 8 g/dl), 111 non- anemic pregnant women (Hb >10 g/dl). Clinical and biological characteristics for both groups were compared. Data on the newborn babies were collected. In the anemic group: iron deficiency was the most common cause of anemia (92.7%). There was no significant difference between the 2 groups with respect to age or parity. Maternal anemia was found to be significantly associated with more frequent preterm birth (29.2% vs 9.2%) and increased low birth weight (2933 g vs 3159 g). The literature is not conclusive on the influence of anemia in pregnant women. More frequent preterm birth and low birth weight have been reported in the majority of studies considering mild to moderate maternal anemia (in contrast to our study where the mothers had severe anemia). Many studies indicated that routine iron supplementation during pregnancy may have beneficial effects on pregnancy outcome. Severe anemia in pregnancy may have adverse effects for the newborn and should be treated or prevented early in pregnancy.

Bioavailability of iron, zinc, and other trace minerals from vegetarian diets

Iron and zinc are currently the trace minerals of greatest concern when considering the nutritional value of vegetarian diets. With elimination of meat and increased intake of phytate-containing legumes and whole grains, the absorption of both iron and zinc is lower with vegetarian than with nonvegetarian, diets. The health consequences of lower iron and zinc bioavailability are not clear, especially in industrialized countries with abundant, varied food supplies, where nutrition and health research has generally supported recommendations to reduce meat and increase legume and whole-grain consumption. Although it is clear that vegetarians have lower iron stores, adverse health effects from lower iron and zinc absorption have not been demonstrated with varied vegetarian diets in developed countries, and moderately lower iron stores have even been hypothesized to reduce the risk of chronic diseases. Premenopausal women cannot easily achieve recommended iron intakes, as modified for vegetarians, with foods alone; however, the benefit of routine iron supplementation has not been demonstrated. It may be prudent to monitor the hemoglobin of vegetarian children and women of childbearing age. Improved assessment methods are required to determine whether vegetarians are at risk of zinc deficiency. In contrast with iron and zinc, elements such as copper appear to be adequately provided by vegetarian diets. Although the iron and zinc deficiencies commonly associated with plant-based diets in impoverished nations are not associated with vegetarian diets in wealthier countries, these nutrients warrant attention as nutritional assessment methods become more sensitive and plant-based diets receive greater emphasis.

Iron supplementation in pregnancy

Iron deficiency is the most common nutritional disorder in the world. Pregnant women are at especially high risk for iron deficiency and iron deficiency anemia. A considerable proportion of pregnant women in both developing and industrialized countries become anemic during pregnancy. The prevalence of anemia in pregnant women has remained unacceptably high worldwide despite the fact that routine iron supplementation during pregnancy has been almost universally recommended to prevent maternal anemia, especially in developing countries over the past 30 years. The major problem with iron supplementation during pregnancy is compliance. Despite many studies, the relationship between maternal anemia and adverse pregnancy outcome is unclear. However, there is now sufficient evidence that iron supplements increase hemoglobin and serum ferritin levels during pregnancy and also improve the maternal iron status in the puerperium, even in women who enter pregnancy with adequate iron stores. Recent information also suggests an association between maternal iron status in pregnancy and the iron status of infants postpartum. The necessity of routine iron supplementation during pregnancy has been debated in industrialized countries and routine supplementation is not universally practiced in all these countries. In view of existing data, however, routine iron supplementation during pregnancy seems to be a safe strategy to prevent maternal anemia in developing countries, where traditional diets provide inadequate iron and where malaria and other infections causing increased losses are endemic.