Nutritional iron deficiency is the most common cause of anemia in India. The nearest correlation of iron deficiency anemia (IDA) can be made with Pandu Roga in Ayurveda. As the IDA is a very common prevalent disease in the society and the side effects of oral allopathic iron preparations are very common, therefore to get a better alternative, an Ayurvedic herbomineral medicine, the Trikatrayadi Lauha, was subjected to a clinical trial in children suffering from IDA.
Evaluation of safety and efficacy of the compound Trikatrayadi Lauha suspension in children with IDA.
Settings and Design:
Randomized, double-blind placebo-controlled clinical study.
Materials and Methods:
The study was conducted on 123 children of IDA for a period of 10 weeks. Clinical features and hematological parameters were documented before, during and after treatment.
Statistical Analysis Used:
Observations of the study were analyzed and findings were evaluated by using statistical methods (Student′s t test)
The present study shows that the trial drug Trikatrayadi Lauha suspension is effective to improve clinical features and hematological parameters significantly. The medicine is effective to increase the hemoglobin level 1.94 g/dL (8.52 -10.46 g/dL, P < 0.001) in 5 weeks and 3.33g/dL (8.52 -11.85g/dL, P < 0.001) in 10 weeks. No adverse effect of the trial drug was observed during the study.
The results suggest that Trikatrayadi Lauha is significantly effective in the management of IDA in children.
Anemia; hemoglobin; iron deficiency; Pandu Roga; serum ferritin
A number of preparations are available in Ayurved for treatment of anemia and iron deficiency. This study was designed to evaluate efficacy of some of them. Six most commonly used Ayurvedic iron containing preparations (Navayasa Curna, Punarnavadi Mandura, Dhatri Lauha, Pradarantaka Lauha, Sarva-Juara-Hara Lauha and Vrihat Yakrdari Lauha) were given in a dose of 250 mg b.d. for 30 days to six groups of iron deficient anemic patients; each group consisting of 20 patients. A control group was given Allopathic preparation—Irex-12, (containing—ferrous fumarate, vitamin C, folic acid and vitamin B12); 1 capsule daily for 30 days for comparison. All hematological and iron parameters were determined before and after completion of treatment. The results showed that there was statistically significant rise (p<0.001) in all of them—Hb, PCV, TRBC, MCV, MCH, MCHC and plasma iron, percent saturation and plasma ferritin. Total iron binding capacity decreased significantly (p<0.001). The response of most of Ayurvedic preparations was better than Allopathic preparation and there was no side effect as observed with iron salts The Hb regeneration rate was 0.10 g/dl/day for Allopathic preparation; while it was above this value for all Ayurvedic preparations exceptPradarantaka Lauha which was least effective.Sarva-Juara-Hara Lauha was the drug of choice as Hb regeneration with it was highest 0.16 g/dl/day. Upon analysis of Ayurvedic drugs, these results were found to be consistent and correlated with iron content of the preparation.
Ayurvedic preparations; Iron deficiency; Anemia; Hematological parameters; Iron parameters
Iron is one among the major metals present in the earth's crust and is essential for sound sustenance of human body. Its deficiency leads to various health ailments. Contemporary medicine advises iron supplements in iron deficiency anemia. Ayurvedic classics also quote significant information about administration of iron. Lauha Kalpas are the unique compound herbo-mineral formulations where iron (Lauha) is used as a major ingredient. Relevant literature (Bhaishajya Ratnavali, Charaka Samhita, Rasendra Sara Samgraha etc.) reviewed to gather information about Lauha Kalpas. Critical analysis of these Lauha Kalpas reveals that ancient seers administered iron in a better acceptable form. Unlike popular understanding these are not only Khalviya preparations; but Churna (powders), Avaleha (confectionaries), Rasakriya (solidified decoctions), and Putapaka (incinerated) form of preparations are also found. Apart from solid dosage forms, semisolid dosage forms mentioned in classics are very much useful. Unfortunately most of the formulations are not found in the market. Hence Pharmaceutical firms may bring these unique dosage forms in to the market to supply the healthcare needs of the community. It is interesting that iron preparations are used in Ayurveda in different medical conditions apart from anemia (Pandu). This leaves a scope for further researches on different dosage forms of iron and their indications.
Ayurveda; Bhasma; Hematinics; Iron; Lauha Kalpa; pharmaceutics; Rasaushadhi
Procedures for preparation of Lauha Bhasma are described in ancient texts of Ayurveda. These procedures also begin with different source material for iron such as Teekshna Lauha and Kanta Lauha etc. In the present study, we have selected different source materials viz. magnetite iron ore for Kanta Lauha and pure (Armco grade) iron turnings for Teekshna Lauha. The standard procedures of preparation of Lauha Bhasma are carried out in identical conditions for these two raw materials. The final product from the Puta are characterized by using X-ray diffraction and X-ray fluorescence spectroscopy to understanding the crystallographic form or forms of iron oxides and their composition at the end of each Puta. The iron content at the end of repeated Putas (18 for Kanta Lauha and 20 for Teekshna Lauha) have shown a decrease in case of Teekshna Lauha since the starting material is pure iron while it showed only marginal decreases in the case of Kanta Lauha because the Fe3O4 of magnetite is undergoing oxidation to Fe2O3. The trace elements remain within the Bhasma in the form of various oxides of Si, Al, Ca, etc.
Lauha Bhasma; X-ray diffraction; X-ray fluorescence
Lauha Bhasma, an ayurvedic drug, is widely used in iron deficiency anaemia, this ancient drug is claimed to be better absorbed gastrointestinally, and is also claimed to be devoid of the usual side effects associated with administration of the allopathic iron preparations, Physical and chemical methods of standardization required for any quality preparation, is not found in the ayurvedic and the modern literatures for Lauha Bhasma. Thus an approach has been made to standardize Lauha Bhasma. For the purpose of analysis, samples of all the three commonly available variants of Lauha Bhasma were considered. Qualitative analysis indicates the presence of iron both in the ferric and the ferrous forms, A simple spectrophotometric method has been used for simultaneous determination of ferric ferrous and the total iron content in a single aliquot.
The present study was conducted to investigate the oxidant–antioxidant status in iron deficient pregnant anemic women. One hundred thirty pregnant women with iron deficiency anemia (IDA) were divided into three groups, namely mild (50), moderate (50) and severe (30) anemic along with pregnant healthy women as controls (50). The complete blood count, plasma lipid peroxidation products, enzymatic and non-enzymatic antioxidants were measured according to respective protocols. The levels of complete blood count, iron, ferritin along with antioxidant enzymes namely catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione were significantly reduced in all IDA groups. However, the level of oxidized glutathione, lipid peroxides, protein carbonyls, conjugated dienes were found significantly increased in all anemic patients. Antioxidant vitamins, namely C, E and A were also found significantly decreased in IDA patients. On the basis of our results, it may be concluded that IDA tends to increase the pro-oxidant components, which may result in various complications including peroxidation of vital body molecules resulting in increased risk for pregnant women as well as fetus.
Iron deficiency anemia; Oxidants; Antioxidants; Pregnancy
Iron deficiency (ID) during early development impairs myelination and basal ganglia function in animal models.
To examine the effects of iron deficiency anemia (IDA) and iron deficiency (ID) without anemia on infant motor skills that are likely related to myelination and basal ganglia function.
Full-term inner-city African-American 9- to 10-month-old infants who were free of acute or chronic health problems with iron status indicators ranging from IDA to iron sufficiency (n = 106). Criteria for final iron status classification were met by 77 of these infants: 28 IDA, 28 non-anemic iron-deficient (NA ID), and 21 iron-sufficient (IS).
Gross motor developmental milestones, Peabody Developmental Motor Scale, Infant Neurological International Battery (INFANIB), motor quality factor of the Bayley Behavioral Rating Scale, and a sequential/bi-manual coordination toy retrieval task. General linear model analyses tested for linear effects of iron status group and thresholds for effects.
There were linear effects of iron status on developmental milestones, Peabody gross motor (suggestive trend), INFANIB standing item, motor quality, and toy retrieval. The threshold for effects was ID with or without anemia for developmental milestones, INFANIB standing item, and motor quality and IDA for toy retrieval.
Using a comprehensive and sensitive assessment of motor development, this study found poorer motor function in ID infants with and without anemia. Poorer motor function among non-anemic ID infants is particularly concerning, since ID without anemia is not detected by common screening procedures and is more widespread than IDA.
Iron deficiency is still considered the most common nutritional deficiency worldwide and the most significant negative consequence of iron deficiency is iron deficiency anemia (IDA). This study elucidates if IDA among healthy women of child bearing age could be predicted by various iron parameters, using serum ferritin as a gold standard.
Between January and June 2009 at primary care clinics of a teaching hospital in Saudi Arabia, 112 anemic (Hemoglobin = 120 g/l) subjects participated in the study. Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), serum ferritin, and hemoglobin electrophoresis were obtained from all participants. Receiver operator characteristic (ROC) curves were used to assess the accuracy of various iron parameters.
With respect to the serum ferritin, the best predictive cut-off value of MCV, MCH and RDW at the most optimal were 76 fl (ROC curve=0.768), 24 Pg (ROC curve=0.72) and 16.1% (ROC curve=0.711), respectively. MCHC was not significant in predicting the iron deficiency in these patients.
IDA can be predicted among women of child bearing age using complete blood count test. MCV, MCH and RDW are the iron parameters of complete blood count test, which is a cost effective, easily accessible and could be useful tool in areas with limited resources and a high prevalence of the disease.
Iron deficiency anemia; Women; Ferritin; MCV; MCH; RDW
A rare case of acute ischemic stroke in a young patient with iron deficiency anemia (IDA) is reported. IDA has been suggested to have an association with stroke, but few cases have proven it thus far. Three physiological mechanisms explaining IDA to ischemic stroke include a hypercoagulable state secondary to IDA, thrombocytosis secondary to IDA, and anemic hypoxia induced by IDA. Our paper shows an example of a hypoxia-induced stroke secondary to IDA in a young woman with menorrhagia. Thrombus formation was ruled out as the Magnetic Resonance Angiogram (MRA) showed no evidence. As all other known causes for stroke were ruled out, the patient's IDA is a reasonable cause for her stroke. Iron deficiency decreases the amount of hemoglobin, which consequently decreases the amount of oxygen in the blood resulting in low-oxygen delivery to the brain. This causes hypoxic conditions in the brain, leading to death of brain tissue. Thus, we suggest a possible relationship between IDA and ischemic stroke in young adults. Considering IDA as one of the risk factors for ischemic stroke and treating with timely transfusions would be an important step one can take to prevent stroke.
The gastrointestinal (GI) tract is a common site of bleeding that may lead to iron deficiency anemia (IDA). Treatment of IDA depends on severity and acuity of patients’ signs and symptoms. While red blood cell transfusions may be required in hemodynamically unstable patients, transfusions should be avoided in chronically anemic patients due to their potential side effects and cost. Iron studies need to be performed after episodes of GI bleeding and stores need to be replenished before anemia develops. Oral iron preparations are efficacious but poorly tolerated due to non-absorbed iron-mediated GI side effects. However, oral iron dose may be reduced with no effect on its efficacy while decreasing side effects and patient discontinuation rates. Parenteral iron therapy replenishes iron stores quicker and is better tolerated than oral therapy. Serious hypersensitive reactions are very rare with new intravenous preparations. While data on worsening of inflammatory bowel disease (IBD) activity by oral iron therapy are not conclusive, parenteral iron therapy still seems to be advantageous in the treatment of IDA in patients with IBD, because oral iron may not be sufficient to overcome the chronic blood loss and GI side effects of oral iron which may mimic IBD exacerbation. Finally, we believe the choice of oral vs parenteral iron therapy in patients with IBD should primarily depend on acuity and severity of patients’ signs and symptoms.
Anemia; Inflammatory bowel disease; Intravenous iron; Iron deficiency; Oral iron
Iron-deficiency anemia (IDA) continues to be the most common single nutrient deficiency in the world. Infants are at particular risk due to rapid growth and limited dietary sources of iron. An estimated 20–25% of the world’s infants have IDA, with at least as many having iron deficiency without anemia. High prevalence is found primarily in developing countries, but also among poor, minority, and immigrant groups in developed ones. Infants with IDA test lower in mental and motor development assessments and show affective differences. After iron therapy, follow-up studies point to long-lasting differences in several domains. Neurofunctional studies showed slower neural transmission in the auditory system despite 1 year of iron therapy in IDA infants; they still had slower transmission in both the auditory and visual systems at preschool age. Different motor activity patterning in all sleep-waking states and several differences in sleep states organization were reported. Persistant sleep and neurofunctional effects could contribute to reduced potential for optimal behavioral and cognitive outcomes in children with a history of IDA.
iron deficiency anemia; sleep; neurofunctions; infancy; childhood
Iron deficiency has been described as the world most common nutritional deficiency and the commonest cause of nutritional anemia in infancy and childhood. The deleterious behavioral and cognitive deficit associated with iron-deficiency anemia could be irreversible. Therefore, the latter should be prevented by early detection of iron deficiency in the non-anemic groups.
To determine the prevalence of iron deficiency in the non-anemic under-five children and to document its variation among the age classes of these children.
Subjects and Methods:
Under-five children presenting at a tertiary hospital were consecutively enrolled, Serum ferritin levels of the subjects were used to assess the iron status and serum ferrritin level of less than 12 ng/ml was considered as iron deficiency. Data were analyzed using SPSS version 15.0. Chi-square tests were employed as necessary for test of significance in each of the characteristics of the population at P ≤ 0.05.
A total of 178 non anemic under-five children were studied, their mean hematocrit and serum ferrritin values were 35.5 (2.8%) and 54.9 (76.1) ng/ml respectively. Forty-nine (27.5% [49/178]) of the study population was iron deficient and there was no significant difference in the prevalence of iron deficiency among the age classes (P = 0.75).
This study has documented a high prevalence of iron deficiency in non-anemic under-five children presenting at the outpatient department and emergency room of a tertiary health facility in Enugu. All the age classes were relatively affected. A further research into the causes of iron deficiency in this age group is recommended.
Anemia; Deficiency; Ferritin; Iron; Under-five children
Recently, hepcidin expression in adipose tissue has been described and shown to be increased in patients with severe obesity. We tried to assess the effect of obesity on hepcidin serum levels and treatment outcome of iron deficiency anemia in children.
This was a case control study included 70 children with iron deficiency anemia "IDA" (35 obese and 35 non-obese) and 30 healthy non-obese children with comparable age and sex(control group). Parameters of iron status (Serum iron, ferritin, transferrin, total iron binding capacity and transferrin saturation) and serum hepcidin levels were assessed initially and after 3 months of oral iron therapy for IDA.
Compared to the control group, serum hepcidin was significantly lower in non-obese children with IDA(p < 0.01) and significantly higher in obese children with IDA (p < 0.01). Hepcidin increased significantly in non-obese children with IDA after 3 months of iron therapy (P < 0.01). On the other hand, obese children showed non-significant change in hepcidin level after iron therapy (p > 0.05). Although hepcidin showed significant positive correlations with Hb, serum iron and transferrin saturation in non-obese children with IDA, it showed significant negative correlations with Hb, serum iron and transferrin saturation in obese children with IDA (P < 0.05).
Obesity increased hepcidin levels and was associated with diminished response to oral iron therapy in childhood iron deficiency anemia.
Obesity; Hepcidin; Iron deficiency; Children
Iron is an essential mineral for the body, and iron deficiency generally leads to anemia. However, because non-anemic iron deficiency can exist, we performed a comprehensive transcriptome analysis of the liver to define the effects of this condition on the body. Four-week-old male rats were fed a low-iron diet (approximately 3 ppm iron) for 3 days and compared with those fed a normal diet (48 ppm iron) by pair feeding as a control. The rats in the iron-deficient diet group developed a non-anemic iron-deficient state. DNA microarray analysis revealed that during this short time, this state conferred a variety of effects on nutrient metabolism in the liver. In comparison with long-term (17 days) iron-deficiency data from a previous study, some of the changed genes were found to be common to both short- and long-term iron deficiency models, some were specific to the short-term iron deficiency model, and the others were oppositely regulated between the two feeding terms. Taken together, these data suggest that although the blood hemoglobin level itself remains unchanged during non-anemic iron deficiency, a variety of metabolic processes involved in the maintenance of the energy balance are altered.
Despite global goals set by United Nations’ agencies over the past decade for significant reductions in iron deficiency anemia (IDA), it remains a largely unaddressed public health problem affecting more than two billion people, one-third of the world’s population. The negative impact of IDA on health and human potential are greatest in the developing world, where it is estimated that 51% of children younger than four years of age are anemic, mainly due to a diet that is inadequate in bioavailable iron. Studies in both developed and developing countries have consistently shown mental and motor impairments that may not be reversible in children younger than two years of age with IDA. From a public health standpoint there are four possible interventions for the prevention of anemia: dietary diversification to include foods rich in absorbable iron; fortification of staple foods including targeted fortification of complementary foods for infants and young children; the provision of iron supplements; and ‘home-fortification’. In response to a United Nations Children’s Fund (UNICEF) request to develop a new approach to IDA, our research group developed ‘Sprinkles’ for home-fortification of complementary foods. Sprinkles are single-dose sachets (like small packets of sugar) containing micronutrients in powder form (encapsulated iron, zinc, vitamins A, C and D, and folic acid), which are easily sprinkled onto any home-prepared complementary food. Sprinkles were developed to overcome many of the side effects and disadvantages of iron drops. We have demonstrated that Sprinkles are as effective as iron drops in the treatment and prevention of anemia. Sprinkles are easier to use and are, therefore, better accepted than iron drops, which may improve adherence to iron interventions.
Anemia; Fortification; Infants; Iron; Micronutrients; Sprinkles
Introduction. Iron deficiency anemia and thalassemia are the most common causes of microcytic anemia. Powerful statistical computer programming enables sensitive discriminant analyses to aid in the diagnosis. We aimed at investigating the performance of the multiple discriminant analysis (MDA) to the differential diagnosis of microcytic anemia. Methods. The training group was composed of 200 β-thalassemia carriers, 65 α-thalassemia carriers, 170 iron deficiency anemia (IDA), and 45 mixed cases of thalassemia and acute phase response or iron deficiency. A set of potential predictor parameters that could detect differences among groups were selected: Red Blood Cells (RBC), hemoglobin (Hb), mean cell volume (MCV), mean cell hemoglobin (MCH), and RBC distribution width (RDW). The functions obtained with MDA analysis were applied to a set of 628 consecutive patients with microcytic anemia. Results. For classifying patients into two groups (genetic anemia and acquired anemia), only one function was needed; 87.9% β-thalassemia carriers, and 83.3% α-thalassemia carriers, and 72.1% in the mixed group were correctly classified. Conclusion. Linear discriminant functions based on hemogram data can aid in differentiating between IDA and thalassemia, so samples can be efficiently selected for further analysis to confirm the presence of genetic anemia.
This study was conducted to compare quality of mother-infant interactions during feeding in infants with or without iron deficiency anemia (IDA).
Infants and caregivers were screened at their 9- to 10-month-old health maintenance visits at an inner-city clinic in Detroit. Those who were full-term and healthy received a venipuncture blood sample to assess iron status. Of the 77 infants who met final iron status criteria, 68 infants and mothers were videotaped during feeding interaction at the Child Development Research Laboratory. The quality of mother-infant interaction during feeding was scored on the Nursing Child Assessment Feeding Scale (NCAFS). Twenty-five infants with IDA (HB < 110 g/L and at least 2 abnormal iron measures) were compared to 43 non-anemic infants (HB ≥ 110 g/L) using ANOVA and GLM models with covariate control.
Mothers of IDA infants responded with significantly less sensitivity to infant cues and less cognitive and social-emotional growth fostering behavior than mothers of non-anemic infants. The pattern of results was similar for scales of contingent behaviors. The magnitude of the differences in maternal ratings was large (0.8-1.0 SD after covariate adjustment). IDA infants were rated significantly lower on clarity of cues and overall (effect sizes 0.5 SD).
IDA in infancy was associated with less optimal mother-infant interactions during feeding. Future interventions might target feeding interaction and consider effects on infant iron status and developmental/behavioral outcomes among IDA infants, as well as infant feeding practices per se.
Iron-deficiency anemia; mother-infant interaction; NCAFS; feeding
To assess dose-response relations between severity of iron deficiency (ID) and infant social-emotional behavior.
Cohort of 9- to 10-month-old African-American infants (n = 77 with final iron status classification). Infants were provided oral iron for 3 months. Social-emotional outcomes included mother and examiner ratings at 9 and 12 months and quantitative behavioral coding from videotape at 12 months. General linear model analyses tested for linear effects of iron status group (ordered from worst to best – iron-deficient anemic (IDA), non-anemic iron-deficient (NA ID), iron-sufficient (IS)) and determined thresholds for effects.
There were significant (p < .05) linear effects of poorer iron status for shyness (increasing, maternal rating), orientation-engagement and soothability (decreasing, examiner ratings), and the following quantitatively-coded behaviors: positive affect (decreasing) and latencies to engage with the examiner (increasing) and move away from the examiner (decreasing). The threshold for all but one effect was ID with or without anemia vs. IS.
Infant social-emotional behavior appears to be adversely affected by ID with or without anemia. ID without anemia is not detected by common screening procedures and is more widespread than IDA. Infant social-emotional behavior can profoundly influence the caregiving environment, with repercussions for overall development.
The aim of this study was to evaluate sensitivity and specificity for reticulocyte hemoglobin content (CHr) compared to other hematimetric and biochemical iron parameters, in particular, mean corpuscular hemoglobin (MCH), when screening for iron deficiency in elderly anemic patients. Bone marrow staining negative for iron was used as the gold standard criterion for iron deficiency anemia (IDA). Sensitivity and specificity for CHr, soluble transferrin receptor (sTfR), soluble transferrin receptor/log ferritin (TfR-F index), ferritin, MCH, and transferrin saturation were determined. The best cut-off point for CHr was 30.5 pg corresponding to a sensitivity and specificity of 93% and 69% for IDA, respectively. For MCH, a sensitivity of 93% and a specificity of 86%, respectively, correspond to an optimal cut-off of 28.5 pg. Analysis of CHr was not superior to MCH with respect to sensitivity and specificity when screening for IDA in elderly anemic patients.
Iron deficiency remains a very common nutritional problem despite the improvement in nutrition and increased understanding of methods for its prevention. Thus, we try to create a new method for screening iron nutrition through infant nutrition history.
Among the children who visited Inha University Hospital from March 2006 to July 2012, 181 children with iron deficiency anemia (IDA) and 52 children without IDA ranging from 6 to 36 months of age were reviewed in this study. We used the age when they began to wean food, the type of sort weaning foods, the time required for successful weaning, iron content in weaning foods, and the duration of breastfeeding for scoring infant nutrition history based on a questionnaire.
The mean score of the IDA group was 7.8±2.6 points, which was significantly higher than that of the control group (5.6±2.1) (p=0.000). If we set up the cutoff value at 6 points, this screening has 86.8% sensitivity and 36% specificity. In addition, as the IDA score increased, there was a falling trend of hemoglobin.
The IDA score does not have high specificity or high sensitivity. However, this study conveys that those patients who record a high score have low hemoglobin. Therefore, we suggest this score system for screening more IDA patients via nonpainful techniques.
Iron-deficiency anemia; Weaning; Breast feeding; Diet; Nutrition
Iron deficiency is a common cause of anemia. In end-stage renal disease (ESRD), iron deficiency impairs the therapeutic efficacy of recombinant erythropoietin. Oral or parental iron supplements usually are effective in treating iron deficiency anemia (IDA). Some patients, however, respond poorly to iron supplements and are diagnosed as having iron-refractory iron deficiency anemia (IRIDA). The disease represents a medical challenge but its underlying mechanism was unclear. Hepcidin is a central player in iron homeostasis. It down-regulates the iron exporter ferroportin, thereby inhibiting iron absorption, release and recycling. In ESRD, plasma hepcidin levels are elevated, which contributes to iron deficiency in patients. Matriptase-2, a liver transmembrane serine protease, has been found to have a major role in controlling hepcidin gene expression. In mice, defects in the Tmprss6 gene encoding matriptase-2 result in high hepcidin expression and cause severe microcytic anemia. Similarly, mutations in the human TMPRSS6 gene have been identified in patients with IRIDA. Thus, matriptase-2 is critical for iron homeostasis and may play a role in renal disease.
matriptase-2; TMPRSS6; hepcidin; end-stage renal disease; EPO resistance
Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia (IDA) because of its effectiveness and low cost. But unfortunately in many iron deficient conditions, oral iron is a less than the ideal treatment mainly because of adverse events related to the gastrointestinal tract as well as the long course required to treat anemia and replenish body iron stores. The first iron product for intravenous use was high-molecular-weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to prescribe intravenous iron in the treatment of iron deficiency anemia for many years. In 1999 and 2001, two new intravenous iron preparations (ferric gluconate and iron sucrose) were introduced into the market as safer alternatives to iron dextran. Over the last five years, three new intravenous iron dextran-free preparations have been developed and have better safety profiles than the more traditional intravenous compounds, as none require test doses and all these products are promising in respect to a more rapid replacement of body iron stores (15-60 minutes/infusion) as they can be given at higher doses (from 500 mg to more than 1000 mg/infusion). The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, safety profile and toxicity of intravenous iron for the treatment of iron deficiency anemia.
Iron deficiency; Anemia, iron-deficiency; Iron compounds; Infusions, intravenous
An adequate supply of iron is essential for normal development of the fetus and newborn child. Iron deficiency and iron deficiency anemia (IDA) during pregnancy increase the risk of preterm birth and low birth weight. Iron is important for development of the fetal brain and cognitive abilities of the newborn. Children born to iron-deficient mothers will start their lives suffering from iron deficiency or even IDA. Oral iron prophylaxis to pregnant women improves iron status and prevents development of IDA. The Danish National Board of Health has since 1992 recommended prophylactic oral iron supplements to all pregnant women and the currently advocated dose is 40–50 mg ferrous iron taken between meals from 10 weeks gestation to delivery. However, 30–40 mg ferrous iron is probably an adequate dose in most affluent societies. In developed countries, individual iron prophylaxis guided by iron status (serum ferritin) has physiological advantages compared to general iron prophylaxis. In contrast, in most developing countries, general iron prophylaxis is indicated, and higher doses of oral iron, for example, 60 mg ferrous iron or even more should be recommended, according to the present iron status situation in the specific populations of women of fertile age and pregnant women.
Iron-deficiency anemia (IDA) is associated with alterations in infant behavior and development that may not be corrected with iron therapy.
To determine if a home-based intervention to foster child development improves behavior and development of infants with IDA.
Infants with IDA and nonanemic infants aged 6 and 12 months were treated with oral iron and randomly assigned to a year of surveillance or intervention. Infants in the surveillance group were visited weekly, and information on iron intake, feeding, and health were recorded. Infants in the intervention were visited weekly, and the home visits included an hour-long program to foster child development by providing support to the mother-infant relationship. The number of infants enrolled was 128 (66 who received intervention) and 149 (70 intervention) at 6 and 12 months, respectively. Psychologists who were unaware of iron status and intervention assignment assessed infants' cognitive, motor, and social-emotional development (Bayley Scales) at the beginning, midpoint, and end of the year; 116 6-month-olds and 134 12-month-olds had at least 2 assessments. Hierarchical linear modeling was used to analyze change over time.
Infants with IDA, regardless of enrollment age, were rated as less positive in social-emotional behavior at baseline. There were significant interactions between iron status and intervention associated with change in cognitive performance and positive social-emotional behavior. Infants with IDA who received intervention had developmental trajectories comparable to those of nonanemic infants in the intervention and surveillance groups, but these infants did not catch up in social-emotional behavior. Infants with IDA who received surveillance showed less increase in cognitive scores and had declines in positive social-emotional ratings.
Home-based intervention to foster child development improved cognitive and social-emotional scores in infants with IDA, but social-emotional differences remained between infants with IDA and those without IDA.
anemia; iron deficiency; home-visiting; infants; development
Iron sucrose originator (ISORIG) has been used to treat iron deficiency and iron deficiency anemia for decades. Iron sucrose similars (ISSs) have recently entered the market. In this non-clinical study of non-anemic rats, five doses (40 mg iron/kg body weight) of six ISSs marketed in Asian countries, ISORIG or saline solution (control) were administered intravenously over four weeks to compare their toxicologic effects. Vasodilatory effects, impaired renal function and hepatic damage were only observed in the ISS groups. Significantly elevated serum iron and transferrin saturation levels were observed in the ISS groups suggesting a higher release of iron resulting in higher amounts of non-transferrin bound (free) iron compared to ISORIG. This might explain the elevated oxidative stress and increased levels of inflammatory markers and antioxidant enzymes in the liver, heart and kidneys of ISS-treated animals. Physico-chemical analyses showed that the molecular structure of most of the ISSs differed greatly from that of the ISORIG. These differences may be responsible for the organ damage and oxidative stress observed in the ISS groups. Significant differences were also found between different lots of a single ISS product. In contrast, polarographic analyses of three different ISORIG lots were identical, indicating that the molecular structure and thus the manufacturing process for ISORIG is highly consistent. Data from this study suggest that ISSs and ISORIG differ significantly. Therefore, before widespread use of these products it would be prudent to evaluate additional non-clinical and/or clinical data proving the safety, therapeutic equivalence and interchangeability of ISSs with ISORIG.
Anemia; inflammation; iron deficiency; iron sucrose; iron sucrose similar; oxidative stress.