Screening For Iron Deficiency Research Articles

Screening for Iron Deficiency

Screening for Iron Deficiency

Screening for iron deficiency.

1. Ann Chen Wu, MD* 2. Leann Lesperance, MD, PhD* 3. Henry Bernstein, DO*† 1. *Pediatric Health Associates, Hunnewell Ground Children’s Hospital 2. †Associate Professor of Pediatrics, Harvard Medical School, Boston, MA After completing this article, readers should be able to: 1. Determine the most common cause of iron deficiency in the United States. 2. Describe the pathogenesis of iron deficiency. 3. List populations at high risk for iron deficiency. 4. Outline the common signs and symptoms of iron deficiency. 5. Specify the American Academy of Pediatrics recommendations for screening for iron deficiency. In the March and April issues of Pediatrics in Review, we published a two-part article on managing anemia in a pediatric office practice. This article expands on the various tests for iron deficiency, including some relatively new ones. These articles should be read as complementary.—RJH Iron deficiency is the most common nutritional deficiency in the world, responsible for a staggering amount of ill health, lost productivity, and premature death. Although its prevalence in the United States has declined since the late 1960s, iron deficiency with or without anemia still is seen frequently in infants, toddlers, adolescent females, and women of childbearing age. In fact, iron deficiency anemia remains the most common hematologic disease of infants and children. Anemia is defined as a low hemoglobin (Hgb) concentration or red blood cell (RBC) mass compared with age-specific norms. Anemia may be caused by decreased RBC production, increased RBC destruction, or blood loss. Based on the size of the RBC, hematologists categorize anemia as macrocytic, normocytic, or microcytic. Iron is found in different compartments within the body. Total body iron (measured by ferritin), transport iron (measured by transferrin saturation), serum iron, and other hematologic and biochemical markers are used to describe the degrees of iron deficiency. Iron depletion refers to the earliest stage of diminishing iron stores in the setting of insufficient iron supply. Iron deficiency (without anemia) develops as these iron stores are depleted further and begin to impair Hgb synthesis. Finally, iron deficiency anemia results …

Cord serum ferritin levels, fetal iron status, and neurodevelopmental outcomes: Correlations and confounding variables

Cord serum ferritin levels, fetal iron status, and neurodevelopmental outcomes: Correlations and confounding variables

Hyporesponsiveness to Anemia Therapy—What are we Doing Wrong?

Most patients receiving anemia therapy respond well, with a significant rise in hemoglobin concentration. However, approximately 5%-10% of patients fail to show a satisfactory response despite high doses of erythropoietin. The definition of hyporesponsiveness to anemia therapy is somewhat arbitrary, but it is generally regarded as a failure to achieve a hemoglobin concentration of 10-11 g/dL despite a dose of erythropoietin in excess of 200 U/kg weekly. The condition has many causes, the most important ones being iron deficiency, infection or inflammation, and underdialysis. Investigating a patient's poor response to erythropoietin should begin with a check for compliance, followed by screening for iron deficiency. If doubt exists about the presence of iron deficiency, then a trial of intravenous iron may be given. A reticulocyte count may be helpful. A significantly elevated count suggests the presence of blood loss or hemolysis. The level of C-reactive protein (CRP) may be useful as an indicator of underlying inflammation, and underdialysis may be corrected by increasing the dialysis prescription. If other, minor causes of hyporesponsiveness to erythropoietin have been excluded, then a bone marrow biopsy should be performed. Some patients may require higher doses of erythropoietin, and it is not unreasonable to increase the dose to 10,000 U thrice weekly. Some causes of hyporesponsiveness to erythropoietin, such as iron deficiency and underdialysis, are easily corrected; but others, such as primary bone marrow disorders and hemoglobinopathies, are not possible to overcome.

Screening for Iron Deficiency by Dietary History in a High-Risk Population

To the Editor. We appreciate the soundness and validity of the article by Bogen et al1 and their interest in including a dietary survey in the context of well-child care. We submit the following comments to further stimulate research and discussion into the complex matter of nutritional assessment.Our study,2 largely quoted in this article, was based on a retrospective review of patient records. The data of interest came from a brief nutritional questionnaire that was part of a broader systematic review of health and psychosocial issues incorporated into all of the health supervision visits of the lead author (M.B.). Bogen's article, in contrast, was constructed as a prospective study in which the dietary data were obtained by a research assistant from patients recruited solely for the purpose of the study. Thus, there were significant differences in the nature of the sample and in the manner in which the data were collected.The outcomes of the 2 studies diverge most markedly in the proportion of parents who responded positively to the screening questionnaire. This difference would account for the marked difference in specificity (15% vs our 79%), as many more truly noniron-deficient patients screened positive in Bogen's study.Nutritional histories are known to be highly unreliable,3–6 possibly because nutrition and nurture are closely related and emotionally loaded. The dramatic difference in specificity may be attributed to the manner and context of the interview. It is also possible that a research format created a self-selection bias weighed towards high-reporting parents in Bogen's study.Many practices make routine use of standard history-taking questionnaires on various routine as well as sensitive issues. Additional research, comparing history-taking methodology, and better defining screening questions may be worthwhile to answer the following question: How do clinical interviews by primary care physicians compare with written questionnaires obtained by research assistants outside of the physician-patient relationship?We support the recommendation that pediatric primary care should emphasize nutritional history and promote consumption of food items rich in readily-bioavailable iron sources as well as in other micronutrients. This is simply good, common-sense practice. More clinical practice-based research is needed to determine whether structured history-taking can reduce the need for universal hematologic screening for iron deficiency.In Reply. We would like to thank Drs Boutry and Needlman for their comments, in particular for raising the issue of the possible differences between interviews conducted by physicians with their patients, interviews conducted by research assistants, and patient- completed surveys. For our study, we selected the survey format because we had hoped that a standard questionnaire could be used in either doctors' offices or WIC clinics to identify high-risk children in need of blood testing for iron-deficiency anemia. There are both limitations and advantages to the use of surveys as opposed to interviews in the primary care setting, and these vary by the nature of the questions. We are unaware of any published studies evaluating the difference between these methods for health screening.The difference in specificity for the two studies could be attributable to selection bias, as suggested. Another possible explanation is that we did not exclude children with recent infection, premature birth, failure-to-thrive, and elevated lead, as was done in the Boutry and Needlman study. In addition, 25% of our sample had not received WIC in the past 12 months. In an attempt to mimic the broad use of the questionnaire in the community, we approached all children whom the primary care physician was going to screen for anemia at the well child visit.We agree that there is a need for future work in the area of office-based structured assessment of nutritional risk and promotion of healthy diets for children.

Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States.

Iron deficiency anemia in infants can cause developmental problems. However, the relationship between iron status and cognitive achievement in older children is less clear. To investigate the relationship between iron deficiency and cognitive test scores among a nationally representative sample of school-aged children and adolescents. The National Health and Nutrition Examination Survey III 1988-1994 provides cross-sectional data for children 6 to 16 years old and contains measures of iron status including transferrin saturation, free erythrocyte protoporphyrin, and serum ferritin. Children were considered iron-deficient if any 2 of these values were abnormal for age and gender, and standard hemoglobin values were used to detect anemia. Scores from standardized tests were compared for children with normal iron status, iron deficiency without anemia, and iron deficiency with anemia. Logistic regression was used to estimate the association of iron status and below average test scores, controlling for confounding factors. Among the 5398 children in the sample, 3% were iron-deficient. The prevalence of iron deficiency was highest among adolescent girls (8.7%). Average math scores were lower for children with iron deficiency with and without anemia, compared with children with normal iron status (86.4 and 87.4 vs 93.7). By logistic regression, children with iron deficiency had greater than twice the risk of scoring below average in math than did children with normal iron status (odds ratio: 2.3; 95% confidence interval: 1.1-4.4). This elevated risk was present even for iron-deficient children without anemia (odds ratio: 2.4; 95% confidence interval: 1.1-5.2). We demonstrated lower standardized math scores among iron-deficient school-aged children and adolescents, including those with iron deficiency without anemia. Screening for iron deficiency without anemia may be warranted for children at risk.

Nutritional deficiencies and blunted erythropoietin response as causes of the Amemia of critical illness

The purpose of this article was to determine the prevalence of iron, vitamin B12, and folate deficiency and to evaluate the erythropoietin (EPO) response to anemia in a cohort of long-term intensive care unit (ICU) patients. All patients admitted to three academic medical center multidisciplinary ICUs were screened for eligibility into a randomized trial of EPO for the treatment of ICU anemia. On their second or third ICU day, patients enrolled in this trial had EPO levels drawn and were screened for iron, B12, and folate deficiency. Weekly EPO levels were obtained throughout patients' ICU stay. A total of 184 patients were screened for iron, B12, and folate deficiency. Sixteen patients (9%) were iron deficient by study criteria, 4 (2%) were B12 deficient, and 4 (2%) were folate deficient. Mean hemoglobin and reticulocyte percents of the remaining 160 patients were 10.3 +/- 1.2 g/dL and 1.66 +/- 1.09%, respectively. In most patients, serum iron and total iron binding capacity levels were very low, whereas ferritin levels were very high. Mean and median day 2 EPO levels were 35.2 +/- 35.6 mIU/mL and 22.7 mIU/mL, respectively (normal = 4.2-27.8). Serial EPO levels in most persistently anemic patients remained within the normal range. In this cohort, screening for iron, B12, and folate deficiency identified potentially correctable abnormalities in more than 13% of patients and should be considered in those who are anticipated to have long ICU stays. Even at an early point of critical illness, most patients had iron studies consistent with anemia of chronic disease (ACD), as well as a blunted EPO response that may contribute to this ACD-like anemia of critical illness.

World Health Organization Hemoglobin Cut-Off Points for the Detection of Anemia Are Valid for an Indonesian Population

The study was designed to determine whether population-specific hemoglobin cut-off values for detection of iron deficiency are needed for Indonesia by comparing the hemoglobin distribution of healthy young Indonesians with that of an American population. This was a cross-sectional study in 203 males and 170 females recruited through a convenience sampling procedure. Hemoglobin, iron biochemistry tests and key infection indicators that can influence iron metabolism were analyzed. The hemoglobin distributions, based on individuals without evidence of clear iron deficiency and infectious process, were compared with the National Health and Nutrition Survey (NHANES) II population of the United States. Twenty percent of the Indonesian females had iron deficiency, but no male subjects were iron deficient. The mean hemoglobin of Indonesian males was similar to the American reference population at 152 g/L with comparable hemoglobin distribution. The mean hemoglobin of the Indonesian females was 2 g/L lower than that of the American reference population, which may be the result of incomplete exclusion of subjects with milder form of iron deficiency. When the WHO cutoff (Hb < 120 g/L) was applied to female subjects, the sensitivity of 34.2% and specificity of 89.4% were more comparable to the test performance for white American women, in contrast to those of the lower cut-off. On the basis of the finding of hemoglobin distribution of men and the test performance of anemia (Hb < 120 g/L) for detecting iron deficiency for women, it is concluded that there is no need to develop different cut-off points for anemia as a tool for iron-deficiency screening in this population.

Anaemia and iron deficiency screening in adolescence: a pilot study of iron stores and haemoglobin response to iron treatment in a population of 14—15‐year‐olds in Norway

Screening for haemoglobin (Hb) and s‐ferritin, in 176 of all 189 (93%) pupils at 8th grade (14—15‐years‐old) in one Norwegian community was performed in order to map the prevalence of anaemia and depleted iron stores. In order to determine the clinical significance of the findings, a questionnaire aimed at detecting symptoms or risk factors for iron deficiency was completed by all participants, and a 3 mo therapeutic trial with iron was offered to subjects with s‐ferritin values below 15 p.g/l. Four percent of girls and 8% of boys were anaemic according to WHO cut‐off levels. S‐ferritin &lt; 15 p.g/l was found in 25% of girls and 30% of boys. Forty‐four of 48 pupils with s‐ferritin &lt; 15 p.g/l completed the therapeutic trial. Only three pupils had a clinically significant increase in Hb, representing less than 2% of the population. The questionnaire gave no clues that could identify subjects with depleted iron stores. To increase Hb in one 14—15‐y‐old with depleted iron stores, 59 (95% CHI: 20—285) had to be screened and 16 (6—76) had to be given iron treatment. This pilot study suggests that functional iron deficiency is rare in Norwegian adolescents despite a high frequency of low iron stores. A double blind, placebo controlled study covering the entire span of pubescence is needed to confirm these results. □Adolescence, anaemia, iron deficiency, ferritin, haemoglobin, screening, therapeutic trial

Screening for Hemochromatosis and Iron Deficiency in Employees and Primary Care Patients in Western Germany

Many physicians still believe that iron overload (hemochromatosis) is an uncommon disorder. To estimate the frequency of iron overload and iron deficiency in a group of employees and a group of outpatients. Prospective screening study. Western Germany. 3012 asymptomatic employees and 3027 outpatients of nine practitioners. Serum ferritin levels and transferrin saturation were measured. Participants with repeatedly abnormal results had thorough clinical evaluations to identify the cause of iron deficiency or overload. Gross iron overload (elevated transferrin saturation and ferritin levels) was proven by liver biopsy and phlebotomy treatment in 28 participants (0.4% of female outpatients, 0.7% of male outpatients, 0.2% of female employees, and 0.4% of male employees) and in six siblings of these participants. Of the 34 participants with iron overload, 30 were precirrhotic. Because 60% of an unselected group of employees with elevated transferrin saturation but normal ferritin levels were assumed to have early hemochromatosis, the prevalence of hemochromatosis was estimated to be 1.8% among patients (1.9% in women and 1.6% in men) and 1.0% among employees (1.1% in women and 1.0% in men). Iron deficiency was found in 6.8% of female patients, 2.4% of male patients, 6.0% of female employees, and 0.5% of male employees. Iron deficiency was more common in women, and iron overload was more common in men. Among male employees, iron overload was almost as common as iron deficiency.

The usefulness of zinc protoporphyrin as iron deficiency screening tool for Saudi children

Blood samples from 240 Saudi children aged 1 day-72 months old were analysed for zinc protoporphyrin (ZPP), lead (Pb) and hematological parameters. Elevated blood zinc protoporphyrin concentrations ( >3.3 mug/g Hb) were found in 50.8%. These children had a mean blood ZPP concentration of 6.857 4.925 mug/g (3.35-43.7 mug/g). Blood lead levels >10 mug/dl were found in 8 children in the range of 10.45-61.08 mug/dl. On the other hand, Hb less than 11 g/dl were found in 51.6%. The correlation coefficient between the concentration of ZPP and the hematological parameters and age were tested. Significant negative correlation were found between ZPP concentrations and Hb, HCT, RBC and age. We conclude that the use of hematofluorometer to measure ZPP proved to be an effective and inexpensive screening tool for iron deficiency in children especially in communities where the prevalence of iron deficiency is high.

Use of Diet History in the Screening of Iron Deficiency

To determine the relationship between diet history and microcytic anemia, a proxy for iron deficiency, and the utility of a brief dietary history in screening for microcytic anemia. Cross-sectional study based on review of clinical records. Urban academic primary care clinic. A total of 305 healthy, African-American inner-city children, presenting for well child care at 15 to 60 months of age. Children with recent minor illness or medicinal iron intake, hemoglobinopathies, chronic illnesses, failure to thrive, or elevated lead levels were excluded. A brief dietary history was taken in the course of primary care visits. Dietary deficiency was defined as: (1) less than five servings each of meat, grains, vegetables, and fruit per week; (2) more than 16 oz of milk per day; or (3) daily intake of fatty snacks, sweets, or more than 16 oz of soft drink. Hematologic indices were obtained. The prevalence of microcytic anemia (hemoglobin, < 11 g/dL; mean corpuscular volume, < 73 fL) was 8% (24 of 305). The prevalence of low hemoglobin ( < 11 g/dL) with or without microcytosis was 12% (38 of 305). Dietary deficiency was associated with microcytic anemia (chi 2 = 26.8). As a screening test for microcytic anemia, dietary deficiency had a sensitivity of 71% (17 of 24), specificity of 79% (222 of 281), and negative predictive value of 97% (222 of 229). Microcytic anemia was associated with a deficient diet among low-income African-American children. A brief dietary history correctly identified children at low risk for microcytic anemia 97% of the time.

Screening for iron deficiency: an analysis based on bone‐marrow examinations and serum ferritin determinations in a population sample of women

Efficacy of different methods in screening for iron deficiency was re-examined in a randomly selected sample of 38-year-old women (n = 203) with known iron status based on absence/presence of stainable iron in bone-marrow smears. The study was made in 1968-69. Serum ferritin (SF) was determined in 1978 in frozen sera using the Ramco IRMA and, in 1992, samples were re-analysed using a RIA calibrated with the International Standard 80/602 for SF determination. The effect of storage on SF was calculated from a previously established relationship (courtesy of Dr Mark Worwood, Cardiff) between the results obtained with the Ramco assay and assays calibrated with IS 80/602. The distributions in iron replete and iron deficient women showed less overlap (diagnostic efficiency 91%) for SF than for other haematological parameters. The best discrimination was obtained at SF < 16 micrograms/l (specificity 98%; sensitivity 75%). Absence of iron stores was associated with signs of an iron deficient erythropoiesis, starting already at SF 25-40 micrograms/l. Use of multiple criteria to diagnose iron deficiency falsely reduces prevalence figures for iron deficiency.

Iron status, energy intake, and nutritional status of healthy young Asian children.

The iron status, dietary intake, and protein energy nutritional status of healthy Asian children ranging in age from 4 to 40 months was investigated. The serum ferritin, erythrocyte zinc protoporphyrin, haemoglobin and mean corpuscular haemoglobin concentrations, and mean corpuscular volume were determined in a community study of 138 children. Protein energy nutritional status was estimated by anthropometry and a four or five day weighed dietary inventory was completed by 97 children. Concentrations of the serum ferritin, haemoglobin, and mean corpuscular haemoglobin, and the mean corpuscular volume decreased progressively with increasing age. The mean values for these four indices were significantly lower in toddlers between 21 and 23 months age than in infants less than 6 months old. The mean erythrocyte zinc protoporphyrin was high in the first six months, later falling and rising again to peak in the 21 to 23 month age group. Thirty five per cent of children were iron deficient (serum ferritin concentration less than 10 micrograms/l) and low values for the mean corpuscular volume and mean corpuscular haemoglobin were observed in 33% and 35% respectively and 17% were anaemic (haemoglobin concentration less than 110 g/l). No association was observed between biochemical iron status and the dietary intake of energy or iron. Nor was there an association between protein energy nutritional status and iron status. Screening for iron deficiency in communities at risk is recommended and nutrition education using trained link workers is preferred to prophylactic iron treatment.

Use of the Erythrogram in Screening for Iron Deficiency in Elderly Patients

Use of the Erythrogram in Screening for Iron Deficiency in Elderly Patients

Iron status with different infant feeding regimens: Relevance to screening and prevention of iron deficiency

The objective of this study was to evaluate the benefit of screening for anemia in infants in relation to their previous diet. The iron status of 854 nine-month-old infants on three different feeding regimens and on a regimen including iron dextran injection was determined by analysis of hemoglobin, serum ferritin, and erythrocyte protoporphyrin levels and of serum transferrin saturation. Infants were categorized as having iron deficiency if two or three of the three biochemical test results were abnormal and as having iron deficiency anemia if, in addition, the hemoglobin level was less than 110 gm/L. The prevalence of iron deficiency was highest in infants fed cow milk formula without added iron (37.5%), intermediate in the group fed human milk (26.5%), much lower in those fed cow milk formula with added iron (8.0%), and virtually absent in those injected with iron dextran (1.3%). The corresponding values for iron deficiency anemia were 20.2%, 14.7%, 0.6%, and 0%, respectively. The use of iron supplements is therefore justified in infants fed cow milk formula without added iron, even when there is no biochemical evidence of iron deficiency. The low prevalence of iron deficiency in the group fed iron-fortified formula appears to make it unnecessary to screen routinely for anemia in such infants. These results also support the recommendation that infants who are exclusively fed human milk for 9 months need an additional source of iron after about 6 months of age.

Normative Data of Hemoglobin Concentration and Free Erythrocyte Protoporphyrin in a Private Pediatric Practice: A 1990 Update

Free erythrocyte protoporphyrin (FEP) and hemoglobin (Hgb) concentrations were tested in 790 children in a private pediatric office; results were compared to those obtained in 1984. Only 16 children (2%) had abnormal FEPs in 1990 compared to 76 children (9.6%) in the earlier study. The mean FEP in the normal group also decreased significantly in each age group studied. The hemoglobin concentrations were not significantly different in most of the age groups studied. Screening for iron deficiency in our pediatric practice by determining hemoglobin and FEP concentrations had a much lower yield in 1990 than in 1984.

Iron deficiency: definition and diagnosis.

There has been a continuous refinement over the past several decades of methods to detect iron deficiency and assess its magnitude. The optimal combination of measurements differs for clinical and epidemiological assessment. Clinically, the major problem is to distinguish true iron deficiency from other causes of iron-deficient erythropoiesis, such as the anaemia of chronic disease. Epidemiologically, techniques that provide quantified estimates of body iron are preferable. For both purposes, the serum ferritin is the focal point of the laboratory detection of iron deficiency. Serum ferritin measurements provide a reliable index of body iron stores in healthy individuals, a cost-effective method of screening for iron deficiency, and a useful alternative to bone marrow examinations in the evaluation of anaemic patients. Preliminary studies indicate that measurement of the serum transferrin receptor may be the most reliable way to assess deficits in tissue iron supply.

Preventing iron deficiency in preschool children by implementing an educational and screening programme in an inner city practice.

To assess the feasibility and acceptability of screening young children for iron deficiency in a deprived inner city practice and to assess the effects of a programme of dietary education. Prospective study of children in general practice, comparison with historical controls. A deprived inner city practice. 127 Children aged 13-24 months. Findings were compared with those in 110 children of the same age studied previously. All mothers received dietary education antenatally and in the first year after giving birth. Screening for iron deficiency (defined as mean cell volume less than 75 fl and haemoglobin concentration less than 105 g/l) and haemoglobinopathy (when appropriate) was offered for all children attending for immunisation against measles, mumps, and rubella over 12 months; capillary blood samples were taken after immunisation. Uptake of the screening programme expressed as the percentage of all children eligible for immunisation who were screened, and the effectiveness of the dietary education as shown by the prevalence of iron deficiency in the two groups. Altogether, 122 of the 127 (96%) children who attended for immunisation had their haemoglobin concentration and mean cell volume measured; 90% of all children aged 13-24 months in the practice were screened. Dietary education, clinical procedures, and counselling were incorporated successfully into the clinic's work. Ten children (8%) were iron deficient, all of whom responded to iron supplements, and eight had a haemoglobinopathy trait. In the previous study 110 children (70%) had been screened and 28 children (25%) had been iron deficient. The two groups were similar in terms of sex, social class, and ethnic group. Screening young children for iron deficiency, sickle cell disease, and thalassaemia when they attended for immunisation was acceptable and successful in a socially deprived inner city practice. Dietary education may have accounted for some of the reduction in the prevalence of iron deficiency that occurred over the two years.

Prevalence of iron deficiency in Saudi children from birth to 15 months of age

A cross-sectional study was carried out to determine the prevalence of iron deficiency among healthy Saudi children from birth to 15 months of age. The groups studied were: newborns, 3-4 months, 5-6 months, 7-8 months, 9-10 months and 12-15 months of age. The age groups were dictated by the vaccination schedule. Serum ferritin was measured and transferrin saturation calculated in each subject. The lower limits of normal were taken as a transferrin saturation of less than 10% and a serum ferritin of less than 12 micrograms/l. A total of 333 serum samples was adequate for analysis. None of the newborns or the 3-4-month-old infants had evidence of iron deficiency. At 5-6 months only 3.3% of subjects had iron deficiency. In the subsequent older age groups the prevalence of iron deficiency increased significantly with age from 9.3% to 12.7% and reached 14.5% in the oldest age group. Screening for iron deficiency in children attending well-baby clinics and hospitals at ages of 12-15 months is recommended.