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Understanding the iron status in pregnant women in Europe provides a foundation for considering the role of iron screening and supplementation. However, available reports and studies have used different approaches that challenge the devising of overall summaries. Moreover, data on pregnant women are limited, and thus, data on women of reproductive age provide useful background information including baseline iron stores in pregnant women. This review considered data that are available from >15 European countries including national surveys and relevant clinical studies. In European women of reproductive age, median or geometric mean serum ferritin (SF) concentrations were estimated at 26-38 μg/L. Approximately 40-55% of this population had small or depleted iron stores (i.e., SF concentration ≤30 μg/L), and 45-60% of this population had apparently replete iron stores. The prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was 10-32% and 2-5%, respectively, depending on the cutoffs used. Approximately 20-35% of European women of reproductive age had sufficient iron stores (SF concentration >70 μg/L) to complete a pregnancy without supplementary iron. During pregnancy, European women in controlled supplementation trials who were not receiving iron supplements displayed increasing prevalences of ID and IDA during pregnancy, which peaked in the middle to late third trimester. Available evidence has suggested that, in gestational weeks 32-39, the median or geometric mean SF concentrations were 6-21 μg/L, and prevalences of ID and IDA were 28-85% and 21-35%, respectively. Women who were taking iron supplements had higher iron status and lower prevalences of ID and IDA, which were dependent on the dose of iron and compliance. The data suggest that, in Europe, the iron status of reproductive-aged women varies by region and worsens in pregnancy without iron supplementation., (© 2017 American Society for Nutrition.)

Project: Meta-analysis of previous studies evaluating associations between content of elements sulphur (S), chlorine (Cl), potassium (K), iron (Fe), copper (Cu), zinc (Zn) and bromine (Br) in normal and cirrhotic autopsy liver tissue samples., Procedure: Normal liver samples from 45 Greenlandic Inuit, median age 60 years and from 71 Danes, median age 61 years. Cirrhotic liver samples from 27 Danes, median age 71 years. Element content was measured using X-ray fluorescence spectrometry., Statistics: Dual hierarchical clustering analysis, creating a dual dendrogram, one clustering element contents according to calculated similarities, one clustering elements according to correlation coefficients between the element contents, both using Euclidian distance and Ward Procedure., Results: One dendrogram separated subjects in 7 clusters showing no differences in ethnicity, gender or age. The analysis discriminated between elements in normal and cirrhotic livers. The other dendrogram clustered elements in four clusters: sulphur and chlorine; copper and bromine; potassium and zinc; iron. There were significant correlations between the elements in normal liver samples: S was associated with Cl, K, Br and Zn; Cl with S and Br; K with S, Br and Zn; Cu with Br. Zn with S and K. Br with S, Cl, K and Cu. Fe did not show significant associations with any other element., Conclusions: In contrast to simple statistical methods, which analyses content of elements separately one by one, dual hierarchical clustering analysis incorporates all elements at the same time and can be used to examine the linkage and interplay between multiple elements in tissue samples., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Iron is essential for normal foetal development. Iron deficiency anaemia in pregnancy is a risk factor for preterm delivery and low birth weight in the newborn. Iron supplementation during gestation increases plasma ferritin and haemoglobin and reduces the prevalence of iron deficiency anaemia. As from June 2008, The Danish National Board of Health had been advocating general iron prophylaxis in pregnancy with 40 mg ferrous iron from the 10th gestation week to delivery. However, the authors suggest that individual prophylaxis according to plasma ferritin should be preferred to general prophylaxis.

This study analysed the influence of extrinsic factors on the phenotypic expression of HFE gene variants in ethnic Danish men. A cohort of 6,020 men aged 30-53 years was screened for HFE C282Y, H63D and S65C variants. Serum iron, serum transferrin, transferrin saturation, and serum ferritin were analysed in 1,452 men and 1,294 men completed a questionnaire on factors, which could influence iron balance. The C282Y allele was present in 5.6%, H63D in 12.8% and S65C in 1.8% of the men. In the entire series, 3% had elevated iron status markers (transferrin saturation > or =50%, ferritin > or =300 microg/L). Self-reported liver disease had an elevating effect and peptic ulcer a lowering effect on iron status markers. Age increased the fraction of men with elevated ferritin from 8.3% at 32-38 years to 16.2% at 46-53 years of age (p = 0.002). Blood donation had a lowering effect on iron status markers (p = 0.0001). Alcohol consumption elevated serum iron and serum ferritin (p = 0.001). Meat consumption had an elevating effect (p = 0.02) and milk consumption a lowering effect (p = 0.03) on serum ferritin. There was no influence of vitamin-mineral tablets on iron status markers. In adjusted logistic regression analysis, the HFE genotype had the highest impact on iron status markers; high alcohol consumption was significantly associated with elevated transferrin saturation. High age and high alcohol consumption were significantly associated with elevated ferritin and high egg consumption and blood donation was significantly associated with normal ferritin levels. In conclusion, the expressivity of HFE variant phenotypes in Danish men was enhanced by alcohol and meat consumption and decreased by milk and egg consumption and blood donation.

Background: Single-meal and short-term studies have shown an enhancing effect of meat on iron absorption, but there are few interventions of longer duration comprising measurements of biomarkers of iron status., Aims of the Study: To assess the impact of a meat-based and a vegetable-based diet on iron status of women of childbearing age., Methods: For 20 weeks, 57 women aged 19-39 years with low iron stores (serum ferritin < or =30 microg/l and haemoglobin > or =120 g/l) consumed either a meat-based or a vegetable-based diet. Haemoglobin and serum ferritin concentrations were measured at baseline, after 10 and 20 weeks. Information about dietary intake before and during intervention, meat/fish intake, menstruation and contraceptive methods were recorded., Results: The women who consumed the meat-based diet had a significantly (P < 0.001) higher intake of meat/fish, 152 (147-168) g/day (median (Q1-Q3)) compared to the women consuming the vegetable-based diet 31 (24-36) g/day, while the total iron intake was similar in the two groups (mean +/- SE) 11.0 +/- 0.5 and 12.3 +/- 0.3/day mg/day, respectively. Serum ferritin remained unchanged in women on the meat-based diet (n = 29)(before intervention (median (Q1-Q3)): 16.3 (12.7-25.3) microg/l and after intervention: 16.5 (10.3-25.3) microg/l, but declined from 17.3 (10.9-23.7) to 11.2 (8.8-14.6) mug/l (P < 0.001) in women on the vegetable-based diet (n = 28)., Conclusion: Our results emphasize the importance of the delicate balance between dietary iron content and iron bioavailability for the maintenance of blood indicators of iron stores in women with initially low iron status.

Iron is mandatory for normal fetal development, including the brain. Iron deficiency may have deleterious effects for intelligence and behavioral development. It is important to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. Iron deficiency anemia during pregnancy is a risk factor for preterm delivery and low birth weight. In the Western countries there is no consensus on iron prophylaxis to pregnant women. An adequate iron balance during pregnancy implies body iron reserves of >or=500 mg at conception. The physiologic iron requirements in the second half of gestation cannot be fulfilled solely through dietary iron. Iron supplements during gestation consistently increase serum ferritin and hemoglobin and reduce the prevalence of iron deficiency anemia. Iron has a negative influence on absorption of other divalent metals and increases oxidative stress in pregnancy, for which reason minimum effective iron dose should be advised. From a physiologic point of view, individual iron prophylaxis according to serum ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are (1) ferritin>70 microg/l: no iron supplements; (2) ferritin 30-70 microg/l: 40 mg ferrous iron daily; and (3) ferritin<30 microg/l: 80-100 mg ferrous iron daily. In controlled studies, there are no documented side effects of iron supplements below 100 mg/day. Iron supplements should be taken at bedtime or between meals to ensure optimum absorption.

Objective: To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy., Methods: A randomized, double-blind intention-to-treat study comprising 427 healthy pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n = 105), 40 mg (n = 108), 60 mg (n = 106), and 80 mg (n = 108) from 18 weeks of gestation. Iron status markers [hemoglobin (Hb), serum ferritin, and serum soluble transferrin receptor (sTfR)] were measured at 18 weeks (inclusion), 32 weeks, and 39 weeks of gestation and 8 weeks postpartum. Side effects of iron supplements were recorded. Iron deficiency was defined as serum ferritin <13 microg/l and iron deficiency anemia as serum ferritin <13 microg/l and Hb <5th percentile in iron replete pregnant women., Results: There were no significant differences between variables in the four groups at inclusion. At 32 and 39 weeks of gestation, group 20 mg had significantly lower median serum ferritin (13 and 16 microg/l) than group 40 mg (17 and 21 microg/l), group 60 mg (18 and 23 microg/l), and group 80 mg (21 and 24 microg/l) (p < 0.0001). At 32 and 39 weeks of gestation, group 20 mg had a significantly higher prevalence of iron deficiency (50 and 29%) than group 40 mg (26 and 11%), group 60 mg (17 and 10%), and group 80 mg (13 and 9%) (p < 0.001). The prevalence of iron deficiency anemia at 39 weeks of gestation was significantly higher in group 20 mg (10%) than in group 40 mg (4.5%), group 60 mg (0%), and group 80 mg (1.5%) (p = 0.02). At 32 weeks of gestation, mean Hb in group 20 mg was lower than in group 80 mg (p = 0.06). There were no significant differences in iron status (ferritin, sTfR, and Hb) between group 40, 60, and 80 mg. Postpartum, group 20 mg had significantly lower median serum ferritin than group 40, 60, and 80 mg (p < 0.01). The prevalence of postpartum iron deficiency anemia was low and similar in the four groups. The frequency of gastrointestinal symptoms was not significantly different in the four iron supplement groups and thus not related to the iron dose., Conclusion: In Danish women, a supplement of 40 mg ferrous iron/day from 18 weeks of gestation appears adequate to prevent iron deficiency in 90% of the women and iron deficiency anemia in at least 95% of the women during pregnancy and postpartum.

In Denmark, the intake of dietary iron has decreased since 1987, when the mandatory iron fortification of flour (30 mg carbonyl iron/kg) was stopped. Since there have been no studies of iron status in elderly Danes after the abolishment of iron fortification, there is a need to assess actual iron status in the elderly population. The objective was to evaluate iron status and the relationship with food composition and dietary and supplemental iron intake in an elderly population in Copenhagen County. Participants in this health examination survey were 358 subjects (171 men, 187 women) 80 years of age from a 1914 cohort study. Blood samples included serum ferritin and hemoglobin (Hb). A dietary survey was performed in 232 subjects (120 men, 112 women) using a dietary history method. Median serum ferritin was 100 microg/l in men and 78 microg/l in women ( p<0.001). Ferritin concentrations <16 microg/l (i.e., depleted iron stores) were found in three men (2%) and in ten women (5%). Median Hb was 140 g/l in men and 131 g/l in women ( p<0.001). Three subjects (0.84%) had iron deficiency anemia (i.e., ferritin <13 microg/l and Hb <5th percentile for iron-replete subjects (121 g/l in men, 114 g/l in women). Ferritin concentrations >300 microg/l (i.e., iron overload) were found in 15 (9%) men and in 5 (3%) women. Median dietary iron intake was higher in men (8.7 mg/day) than in women (7.3 mg/day) ( p<0.001). Serum ferritin was positively correlated to dietary intake of iron, meat, and alcohol and to body mass index in men. Serum ferritin displayed a negative correlation to the consumption of tea. The use of vitamin-mineral supplements containing iron had no influence on iron status. Dietary intake of iron and/or the bioavailability of dietary iron were adequate to maintain a favorable iron status in 80-year-old subjects displaying a low prevalence of iron deficiency and a moderate prevalence of iron overload.

Objective: To evaluate iron status in indigenous Greenlanders and its relationship to gender, age and intake of traditional Greenlandic foods., Methods: Serum ferritin, serum transferrin saturation and haemoglobin were evaluated in a population survey in 1993-1994 comprising 224 Greenlandic individuals (109 men) aged 19-82 yr. The participants were residents in the capital Nuuk (n=73) with a predominantly Western style of living, the town Ilulissat (n=60) with a mixture of Western and Greenlandic style of living, and the small town Uummannaq (n=91) with a predominantly Greenlandic style of living. Consumption of traditional foods was assessed by questionnaire., Results: Intake of traditional foods was more prevalent among elderly than among young individuals and more frequent in Uummannaq than in Ilulissat and Nuuk. Ferritin levels were higher in men than in women (p<0.0001). Median ferritin levels were lowest in Nuuk (men, 92 microg/L; women, 40 microg/L), higher in Ilulissat (men, 104 microg/L; women, 69 microg/L) and in Uummannaq (men, 118 microg/L; women, 46 microg/L) (p<0.001). The prevalence of iron load (ferritin >200 microg/L) was lowest in Nuuk (men: 13.8%, women: 2.3%) intermediate in Ilulissat (men, 11.1%; women, 9.1%) and highest in Uummannaq (men, 32.1%; women, 21.1%). The prevalence of iron depletion (ferritin <16 microg/L) was high in Nuuk (men, 0%; women, 20.5%), and lower in Ilulissat (men, 3.7%; women, 6.1%) and in Uummannaq (men, 0%; women, 10.5%). The prevalence of iron deficiency anaemia (ferritin <13 microg/L and Hb <5th percentile for iron-replete men and women) was 0.92% in men and 0.87% in women. Correlations between age and ferritin were lowest in Nuuk (men, r(s)=0.26, p=0.2; women, r(s)=0.50, p=0.001) intermediary in Ilulissat (men, r(s)=0.37, p=0.06; women, r(s)=0.73, p<0.0001) and highest in Uummannaq (men, r(s)=0.59, p<0.0001; women, rs=0.74, p<0.0001). Intake of traditional foods was correlated with ferritin in men (r(s)=0.29, p=0.01) and women (r(s)=0.40, p<0.0001)., Conclusion: The observed differences in estimated body iron stores in Greenlanders from the three residential areas can be explained by differences in the dietary intake of haem iron.

The purpose of this study was to measure the content of iron (Fe) in liver tissue samples from urbanized Greenlandic Inuit using X-ray fluorescence spectrometry, and compare the results with those obtained in liver tissue samples from urbanized Danes. Normal liver tissue samples were obtained at autopsy from 50 Greenlandic Inuit (27 men, 23 women) with a median age of 61 years (range 23-83) and from 72 Danes (42 men, 30 women) with a median age of 62 years (range 15-87). In the entire series, there was no significant difference between liver iron in Inuit compared with Danes. Likewise, there was no significant gender difference concerning liver iron content, either in Inuit or in Danes. The median iron content (with 5-95 percentile) in Inuit was 17.23 mmol/kg dry liver (5.80-91.80) and in Danes 16.51 mmol/kg dry liver (7.83-39.05). However, when stratified according to age, a trend was revealed showing that Inuit men and women < or = 50 years had a lower liver iron content than Danes (p = 0.05 and p = 0.08) whereas Inuit men and women > 50 years had a higher liver iron content than Danes (p = 0.18 and p = 0.02). There was a significant correlation between liver iron content and age in both Inuit men (rs = 0.49, p = 0.01) and in women (rs = 0.64, p = 0.003), but not in Danes. In Inuit, the median hepatic iron index (liver iron content divided by age) was 0.33 in men and 0.32 in women. The median estimated iron content in the whole liver was 6.54 mmol (365 mg) in Inuit men and 5.41 mmol (302 mg) in Inuit women (p = 0.6). There was no correlation between hepatic iron index and age. In Danes, the median hepatic iron index was 0.46 in men and 0.29 in women (p = 0.01). There was a significant inverse correlation between hepatic iron index and age in the two genders and in the entire series (rs = -0.71, p = 0.0001). The results indicate that young and middle-aged urbanized Inuit have slightly smaller iron stores than urbanized Danes, whereas elderly Inuit have higher iron stores than Danes. In Danes, iron stores plateau at 30 to 40 years of age in men and some years after the menopause in women. In Inuit, iron stores continue to increase in old age, probably to due a lifelong dietary intake of haem iron.

Background: Health authorities recommend that populations consume a diet providing sufficient iron, and in order to prevent iron deficiency, a number of countries have fortified certain foods with iron. In Denmark, flour was fortified with iron from 1954 until 1987, at which time the mandatory fortification was stopped. This study examines the effect of iron fortification on iron status by comparing the intake of iron with serum ferritin over time and in relation to the removal of flour fortification., Methods: In a cohort of 238 Danish men and women, at baseline ages 35-65 years, dietary intake and serum ferritin were measured, first in 1987/1988 and again in 1993/1994., Results: In 1987/1988 the fortification may have supplied up to 25% of total iron intake, and without this enrichment some 35% of the men and 73% of the women may have had iron intakes lower than 10 mg/day. Assuming that no flour was enriched, iron intake was constant during the 6-year study period. Despite this, after flour fortification was stopped in 1987, serum ferritin increased among both men and postmenopausal women., Conclusions: Considering that mandatory iron fortification of flour affects the entire population, including subjects who are at risk for chronic diseases because of too-high iron stores, the decision to stop the mandatory fortification in Denmark seems to have been well-founded., (Copyright 1999 American Health Foundation and Academic Press.)

The aim of the present study was to evaluate the influence of menstruation, method of contraception, and iron supplementation on iron status in young Danish women, and to assess whether iron deficiency could be predicted from the pattern of menstruation. Iron status was examined by measuring serum (S-) ferritin and hemoglobin (Hb) in 268 randomly selected, healthy, menstruating, nonpregnant Danish women aged 18-30 years. Iron deficiency (S-ferritin <16 microg/l) was observed in 9.7%, of the women, iron deficiency anemia (S-ferritin < 13 microg/l and Hb < 121 g/l) in 2.2%. Iron supplementation, predominantly as vitamin-mineral tablets containing 14-20 mg of ferrous iron was used by 35.1%. The median serum ferritin was similar in non-iron users and in iron users, whereas the prevalence of iron deficiency was 12.6% in nonusers vs. 4.3% in users, the prevalence of iron deficiency anemia 3.4% in nonusers vs. 0%, in users (p=0.17) In non-iron-supplemented women, S-ferritin levels were inversely correlated with the duration of menstrual bleeding (rs= -0.25, p<0.001) and with the women's assessment of the intensity of menstrual bleeding (r(s)= -0.27, p<0.001), whereas no such correlations were found in iron-supplemented women. The results demonstrate that even moderate daily doses of ferrous iron can influence iron status in women with small iron stores. Women using hormonal contraceptives had menstrual bleeding of significantly shorter duration than those using intrauterine devices (IUD) or other methods. There was a high prevalence of small and absent body iron stores in young women, suggesting that preventive measures should be focused on those women whose menstruation lasts 5 days or longer, who have menstrual bleeding of strong intensity, who use an IUD without gestagen, and who are blood donors.

Objective: To examine the association between food intake and serum ferritin over time., Design: Two hundred and thirty-eight individuals, at baseline aged 35, 45, 55 and 65 y, had their food intake assessed by a short food frequency questionnaire and a diet history interview, and serum ferritin measured, first in 1987/88, and again in 1993/94., Setting: The County of Copenhagen, Denmark., Results: Apart from intake frequencies of alcoholic beverages dietary items were poor predictors of serum ferritin. Besides food intake serum ferritin was associated with blood donation in men, and with menopausal status in women., Conclusions: For this middle-aged population, information on alcohol intake and blood loss may be used to rank individuals in relation to iron status, whereas information on intake frequency of dietary items may not.

Among fertile, nonpregnant, Danish women, 33% have absent or reduced iron stores; 22% have serum ferritin values above 70 micrograms/l, i.e., iron reserves of more than 530 mg, corresponding to the net iron losses during a normal pregnancy. During pregnancy, the demands for absorbed iron increase from 0.8 to 7.5 mg/day. Controlled studies show that iron-treated pregnant women have higher serum ferritin levels, i.e., larger iron stores, and higher haemoglobin levels than placebo-treated women. A supplement of 66 mg ferrous iron daily from the beginning of the 2nd trimester prevents iron deficiency anaemia. In Denmark, general iron prophylaxis with 60-70 mg ferrous iron daily from 20 weeks of gestation is recommended by the health authorities.

Serum erythropoietin (EPO) and its relationship to hemoglobin (Hb), iron status markers and iron supplementation during normal pregnancy was assessed in a longitudinal, placebo-controlled study on 118 women, 61 took daily tablets containing 66 mg ferrous iron from the second trimester until delivery and 57 took placebo. Blood samples were obtained at 4-week intervals until delivery as well as post-partum. In the placebo-treated women, median serum EPO rose from 22.5 U/l at inclusion to 35.0 U/l at delivery (P = 0.0001). In the iron-treated women, median serum EPO rose from 23.9 to 29.9 U/l (P = 0.0001). Serum EPO showed a steeper increase in the placebo-treated women than in the iron-treated women (P < 0.05). After delivery, serum EPO became normal in both groups (P = 0.0001). Median Hb was lower in placebo-treated (iron depleted) than in iron-treated (iron repleted) women (P < 0.05). In the placebo-treated women there was a negative correlation and in the iron-treated women a positive correlation between serum EPO and Hb. In the placebo-treated women, inverse correlations existed between serum EPO and serum transferrin saturation and serum ferritin, reflecting the consequences of iron deficiency, whereas the iron-treated women displayed no correlation. A physiological, nonhypoxia-induced increase in EPO production accounts for the basic expansion of the red cell mass during pregnancy. In placebo-treated women, iron deficient erythropoiesis constitutes an additional hypoxic stimulus, which induces a further increase in serum EPO.

Iron status was assessed by serum ferritin and haemoglobin in a population survey comprising 634 randomly selected urban Danes (312 males, 322 females) 14-23 yr old. At all ages, males had significantly higher serum ferritin and haemoglobin values than females. Males: median serum ferritin displayed a steady increase with age from 33 to 109 micrograms/l (rs = 0.53, p < 0.0001). The prevalence of absent mobilizable body iron stores (serum ferritin < 13 micrograms/l) was 3.5% at 16-17 yr of age, gradually declining to 0% at 22-23 yr. None of the males had iron deficiency anaemia (serum ferritin < 13 micrograms/l and haemoglobin < 129 g/l). Females: median ferritin values displayed a slight increase with age from 28 to 39 micrograms/l (rs = 0.19, p < 0.001). The prevalence of absent iron stores was 12.5% at 16-17 yr of age, declining to 6.6% at 22-23 yr. The prevalence of iron deficiency anaemia (serum ferritin < 13 micrograms/l and haemoglobin < 121 g/l) was 4.7% at 16-17 yr of age, declining to 1.3% at 22-23 yr of age. Compared with surveys in other parts of Scandinavia, young Danes had slightly higher serum ferritin levels, and a lower prevalence of iron deficiency.

Several studies have failed to demonstrate an association between Fe status and intake of dietary Fe. However, in the long term, it seems logical to presume that body Fe reserves are, fundamentally, dependent on the intake of bioavailable dietary Fe. This discrepancy may depend on several factors: (1) interindividual variation in biological availability of dietary Fe (differences in intestinal absorption), (2) interactions between dietary Fe and absorption enhancers and inhibitors, (3) variations in physiological (menstruation, childbirth) or unphysiological (blood donation) Fe losses, (4) the failure to adjust dietary intake data for Fe supplements, (5) uncertain food composition data (discrepancies between calculated and chemically measured Fe content in the diet), and (6) diet reporting error (reported intake of dietary Fe may deviate considerably from the true intake). The present study examined associations between dietary intake of Fe (assessed by diet history interview) and Fe status (assessed by ferritin status) among 167 Danish women aged 35-65 years, who were not blood donors, by taking into account diet reporting error (assessed from p-amino benzoic acid-validated urinary N), physiological blood losses (menstruation, childbirth, abortions), and Fe supplementation. Our results indicate that the lack of a general association between Fe status and dietary Fe intake may, in part, be caused by selective diet reporting error.

The purpose of this study was to evaluate the distribution of haemosiderin iron in various regions of the liver (central, intermediary and peripheral hepatocytes, Kupffer cells, portal macrophages and bile duct epithelial cells) in 174 patients with different hepatic diseases (alcoholic cirrhosis (n = 49), alcoholic steatosis (n = 60), non-alcoholic cirrhosis (n = 16), acute hepatitis (n = 20), clinically overt untreated hereditary haemochromatosis (n = 3), miscellaneous disorders (n = 26)), and in 13 subjects with a normal liver biopsy. Furthermore, the relationship between liver haemosiderin iron, biochemical iron status markers and biochemical liver tests was investigated. In haemochromatosis iron was consistently present in all examined regions of the liver, and in 43% of patients with alcoholic liver disease haemosiderin was present in at least one region of the liver lobule. In 65% of patients with acute hepatitis, haemosiderin was present in macrophages and Kupffer cells. In other hepatic diseases and in normal livers, haemosiderin was rarely seen. Regression analyses showed a correlation between iron status markers in most patients, except in those with high serum aspartate aminotransferase levels. In conclusion, haemosiderin iron is distributed in a typical pattern in haemochromatosis, alcoholic liver disease and acute hepatitis. Both histochemical liver iron and serum ferritin are of value as indirect markers of liver iron stores in patients with moderate hepatocellular damage.

Iron status and body iron reserves were examined in a broad spectrum of the Danish population, and sex- and age-related changes determined. Serum ferritin concentration was employed as an indicator of mobilizable body iron stores. The relationship between serum ferritin and histochemical assessment of stainable bone marrow haemosiderin iron was examined in healthy individuals, defining threshold values for serum ferritin indicating exhausted, small, normal, ample, and increased iron stores. The populations examined comprised 7241 randomly selected normal individuals with an age distribution ranging from newborn to 85 years old. The influence of factors having a significant impact on iron balance, e.g., menstruation, pregnancy, parity, and blood donation, was analysed separately. Newborns had high cord serum ferritin levels, which were to a certain extent dependent on the mother's iron status. Newborns of mothers taking iron supplementation during pregnancy had higher cord serum ferritin than newborns of mothers taking a placebo. In children, the serum ferritin level was relatively constant from 3 years of age until adolescence, where the prevalence of exhausted iron stores was 13% in boys and 18% in girls. In postadolescent men, there was a gradual increase in serum ferritin levels until 30 years of age. Subsequently, serum ferritin remained relatively constant until old age. Among 30- to 70-year-old men, 9.4% had ample iron stores. The prevalence of depleted iron stores was 1.4%, and of iron deficiency anaemia 0.24%. In women, serum ferritin levels remained low from adolescence until the menopause. Among 30- to 50-year-old premenopausal women, the prevalence of ample iron stores was 0.49%, whereas 18% had exhausted iron reserves and 2.6% had iron deficiency anaemia. After menopause, serum ferritin gradually rose and approached male levels. Among 60- to 70-year-old postmenopausal women, 3.0% had ample iron stores, 2.3% had depleted stores and none had iron deficiency anaemia. In fertile women, the choice of contraception had a significant influence on the iron loss at menstruation. Hormonal contraception reduced iron loss, whereas the use of intrauterine devices increased iron loss. These effects were reflected in the serum ferritin levels of menstruating women. In a placebo-controlled study of iron supplementation during pregnancy, serum ferritin levels displayed a characteristic fall both in placebo- and iron-treated women. Among placebo-treated pregnant women at term, 19% had depleted iron reserves and 12% had iron deficiency anaemia, and among iron-treated women, 3% had depleted iron stores and none had iron deficiency anaemia. In non-pregnant women, there was a significant inverse relationship between parity and serum ferritin. Blood donation had a marked influence on the serum ferritin level in the adult population. Among Danes, 20-60 years of age, 27% of men, 15% of premenopausal and 10% of postmenopausal women were blood donors. In all three groups, the prevalence of depleted iron depots was higher in donors than in non-donors. Among premenopausal female blood donors, 31.7% had depleted iron reserves and 3.3% iron deficiency anaemia. In general, Danish men and postmenopausal women had a satisfactory iron status. Adolescent Danish girls and premenopausal women had a high prevalence of iron deficiency, which should be taken into consideration when establishing guidelines and recommendations for nutritional iron intake in this section of the population.

The aim of this randomized, double blind, placebo controlled parallel study was to evaluate whether iron status markers in pregnant women, measured early in the second trimester, could be used to predict levels later in pregnancy, and post partum. One hundred and twenty healthy pregnant women between 14 and 18 weeks of gestation were included. Sixty-three women were allocated to treatment with tablets containing 66 mg ferrous iron (as fumarate) daily, and 57 women to treatment with placebo. Haemoglobin, serum transferrin saturation, and serum ferritin were measured every fourth week during gestation, prior to delivery, one week and eight weeks post partum. Correlation matrices during pregnancy and post partum were calculated for each iron status marker, both in iron and placebo treated women. Haemoglobin, transferrin saturation and serum ferritin values at inclusion displayed steadily declining correlation coefficients with values obtained later in pregnancy. There were no clinically relevant correlations to values obtained eight weeks or less prior to delivery, or post partum. Serum ferritin values at inclusion could not be used to predict values later in pregnancy or post partum. Haemoglobin, transferrin saturation and serum ferritin values measured in the beginning of the second trimester appear unsuitable as guidelines for an individual iron prophylaxis during the remaining period of pregnancy.

In a cohort of term infants (n=91), followed from birth to 12 months, iron intake was examined by 24-h food records, and iron status by blood samples (haemoglobin (Hb)), mean corpuscular volume (MCV), serum values for iron, ferritin and transferrin, and erythrocyte protoporphyrin) at 2, 6 and 9 months. At 9 months of age, 5% had anaemia (Hb<105 g/l), but none had developed iron deficiency according to strict definitions used in this study (serum ferritin < 13 micrograms/l and transferrin saturation < 10%). Infants with high serum ferritin, serum transferrin and erythrocyte protoporphyrin values at one blood sampling also had high values at the following sample (tracking, r=0.45-0.80), suggesting that iron stores at delivery are an important determinant of iron stores during late infancy. Factors related to changes in serum ferritin were investigated by multiple linear regression. From 2 to 6 months, serum ferritin was negatively associated with knee-heel growth velocity (p=0.006) and positively with intake of infant formula (p=0.04). From 6 to 9 months it was negatively associated with intake of bread (p=0.001), and there was a trend for a positive association with intake of meat (p=0.07) and fish (p=0.08) and for a negative association with intake of cow's milk (p=0.07). In conclusion, those with a high growth velocity and a dietary pattern with a high intake of bread and a low intake of meat and fish had lower ferritin values and thereby an increased risk of depleting their iron stores later during infancy.

The purpose of this pedigree study, comprising 29 families with hereditary haemochromatosis (HH), was to evaluate the relationship between the genotype (G), based on HLA typing, and the phenotype, based on measurement of iron status markers (serum transferrin saturation and serum ferritin). Due to tight linkage between the HH locus and the HLA-A locus, 172 relatives of the 29 unrelated probands could be assigned into three groups: G0 who were considered to be normal (n = 53), G1 who were considered to be heterozygotes (n = 105), and G2 who were considered to be homozygotes (n = 14), according to whether they had no, one or two HLA haplotypes in common with the proband. A high serum transferrin saturation (> 60%) was present in 8/14 = 57.1% of the homozygotes, in 11/105 = 10.5% of the heterozygotes, and in 0/53 = 0% of the normals. Of the homozygotes, 8/14 = 57.1% had preclinical disease, 4/14 = 28.6% had clinically overt iron overload, while 2/14 = 14.3% had normal iron status markers. None of the heterozygotes had clinical evidence of iron overload. Analysis of HLA alleles and iron status markers suggested that 11/105 = 10.5% subjects initially classified as heterozygotes (G1) according to HLA typing should be reclassified as homozygotes because of abnormal iron status markers, explained by either: homozygous x heterozygous (n = 7) or heterozygous x heterozygous (n = 2) matings, HLA recombination (n = 1) or strongly abnormal iron status markers (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Iron status, including serum (S-) ferritin and hemoglobin (Hb) was assessed in a population survey of 469 old subjects (70 years of age; 254 men, 215 women); 7.9% of the participants had abnormal laboratory tests indicating diseases which might be connected with inappropriately high S-ferritin levels. Men had a median S-ferritin of 114 micrograms/L, 5-95 percentile 28-373 micrograms/L; 2.4% had values < 15 micrograms/L (i.e., depleted iron stores), 3.5% values from 15-30 micrograms/L (i.e., small iron stores), and 94.1% values > 30 micrograms/L (e.g., replete iron stores); 74.4% had values from 61-300 micrograms/L, and 8.7% values > 300 micrograms/L. Median Hb was 142 g/L (8.8 mmol/L), 5-95 percentile 124-158 g/L (7.7-9.8 mmol/L); Hb values < 129 g/L (8.0 mmol/L) were observed in 7.5%. Iron deficiency anemia (i.e., S-ferritin < 15 micrograms/L and Hb < 129 g/L) was seen in 0.39% of the men. Women had lower S-ferritin than men (p < 0.0001), median 81 micrograms/L, 5-95 percentile 20-273 micrograms/L; 3.3% had values < 15 micrograms/L, 9.3% values from 15-30 micrograms/L, and 87.4% values > 30 micrograms/L; 63.2% had values from 61-300 micrograms/L, and 3.7% values > 300 micrograms/L. Hb was lower in women than in men (p < 0.0001), median 132 g/L (8.2 mmol/L), 5-95 percentile 118-145 g/L (7.3-9.0 mmol/L); Hb values < 121 g/L (7.5 mmol/L) were seen in 6.5%. None of the women had iron deficiency anemia (i.e., S-ferritin < 15 micrograms/L and Hb < 121 g/L).

In a randomized, double-blind, placebo controlled study of the effect of iron supplementation during pregnancy, iron status (hemoglobin (Hb), serum (S-)transferrin saturation, S-ferritin) and S-erythropoietin (EPO) were assessed in 120 healthy pregnant women at 14-16 weeks of gestation, and just before delivery; 63 women were treated with 66 mg iron daily, and 57 with placebo. There were no differences in baseline values in the two groups. At term, the iron treated group had significantly higher Hb, transferrin saturation, S-ferritin (median 22 micrograms/l vs. 14 micrograms/l, (p < 0.0001) and lower S-EPO compared to the placebo treated group. In the iron group, 30.2% had exhausted iron stores (i.e. S-ferritin < 20 micrograms/l), 6.3% latent iron deficiency (S-ferritin < 20 micrograms/l and transferrin saturation < 15%), and no patients had iron deficiency anemia (S-ferritin < 20 micrograms/l and transferrin saturation < 15% and HB < 110 g/l). In the placebo group, 93.0% had exhausted iron stores, 54.4% latent iron deficiency, and 17.5% iron deficiency anemia; S-EPO was inversely correlated to iron status markers: Hb, rs = -0.51, p < 0.001; transferrin saturation, rs = -0.65, p < 0.0001; S-ferritin, rs = -0.31, p < 0.01, suggesting that the elevation in S-EPO was secondary to iron deficient erythropoiesis. Newborns to iron treated mothers had higher cord S-ferritin, median 155 micrograms/l, than newborns to placebo treated mothers, median 118 micrograms/l (p < 0.02); there were no differences in birth weight, transferrin saturation, or S-EPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Histochemical and chemical liver iron and iron status markers (serum (S-) ferritin, transferrin saturation) were determined in 109 patients with various types of liver disease (71 alcoholic, 38 non-alcoholic disease) and 8 normal subjects. In the series as a whole there was a significant correlation between histochemical hepatocyte iron and chemical iron (rho = 0.48, p = 0.0001). Of the iron status markers, only S-ferritin showed clinically significant correlations with histochemical liver iron (rho = 0.54, p = 0.0001) and chemical liver iron (r = 0.45, p = 0.0001) (log vs. log values). The highest correlation was found between S-ferritin and the product of chemical iron x ASAT (r = 0.61, p = 0.0001) (log vs. log values). None of the normal livers had stainable hepatocyte iron; median chemical iron content was 15 mumol/g dry weight (range 8-25). The entire group of alcoholics had a median liver iron content of 21 mumol/g; all patients had a hepatic iron index (hepatic iron/age) of under 1.4. In alcoholic liver disease, median chemical liver iron content was 15 mumol/g (range 3-36) in 35 subjects with grade 0 hepatocyte iron; 24 mumol/g (range 6-90) in 25 subjects with grade 1 + 2 hepatocyte iron; 30 mumol/g (range 14-74) in 11 subjects with grade 3 + 4 hepatocyte iron. Among subjects with alcoholic liver disease and normal liver iron (< 26 mumol/g), 39% had stainable hepatocyte iron vs. 70% in subjects with increased liver iron (> or = 26 mumol/g). The corresponding figures in subjects with non-alcoholic liver disease were 13% and 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Iron status was assessed by measuring serum ferritin and haemoglobin in a population survey in Copenhagen County, comprising 1359 nonpregnant women in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal. Premenopausal women had lower serum ferritin (median 37 micrograms/l) than postmenopausal women (median 71 micrograms/l), p < 0.0001. Of premenopausal women, 17.7% had ferritin < 15 micrograms/l (depleted iron stores), and 23.1% had ferritin levels of 15-30 micrograms/l (small iron stores). Corresponding figures in postmenopausal women were 3.3% and 10.3%. Iron deficiency anaemia (ferritin < 15 micrograms/l and haemoglobin < 121 g/l) was observed in 2.6% of pre- and 0.36% of postmenopausal women. After menstruations had ceased, there was a steep rise in ferritin levels, being most pronounced during the first 7 postmenopausal years. Pre- and postmenopausal multipara had lower ferritin than nulli- and unipara (p < 0.04), indicating that pregnancy and childbirth had a long lasting reducing influence on iron stores. The use of oral hormonal contraceptives had a marked increasing effect on iron stores, being correlated to the number of years the women had been taking the pill.

Bone marrow hemosiderin iron was assessed in 48 patients with alcoholic, and in 34 patients with nonalcoholic liver disease (53 men, 29 women, median age 55 years, range 18-84) and correlated to serum (S)-iron status markers (iron, transferrin, ferritin), as well as to histochemical hepatocyte iron and chemical liver iron content. In a control group of 53 healthy subjects (23 men, 30 women, median age 28 years, range 18-90) marrow hemosiderin iron and iron status markers were evaluated as well. Among liver patients, the marrow iron grade was higher in men than in women (p = 0.03). Correlations were found between marrow iron and histochemical liver iron (rho = 0.38, p = 0.0001) as well as chemical liver iron (rho = 0.33, p = 0.01). Marrow iron was correlated to S-ferritin (rho = 0.53, p = 0.0001), mean red cell volume (rho = 0.34, p = 0.003), and S-transferrin (rho = -0.24, p = 0.02). Alcoholics had a higher marrow iron grade than nonalcoholics (p = 0.001) and controls (p = 0.0001). Among controls, the marrow iron grade was likewise higher in men than in women (p = 0.01). Correlations were found between marrow iron and ferritin (rho = 0.64, p = 0.0001), transferrin saturation (rho = 0.56, p = 0.001), transferrin (rho = 0.53, p = 0.001), S-iron (rho = 0.37, p = 0.01), and hemoglobin in women (rho = 0.38, p = 0.05). The results indicate that alcoholics either have increased marrow hemosiderin iron stores, or display a redistribution of iron in reticuloendothelial cells from soluble ferritin-bound iron to insoluble hemosiderin iron. Among patients with absent marrow hemosiderin iron, 81% had absent hepatocyte hemosiderin iron as well. Among patients with absent hepatocyte hemosiderin iron, 23% had absent and 77% normal or increased marrow hemosiderin iron. Therefore, in patients with iron depletion, assessment of marrow hemosiderin iron yields more relevant information of iron status than assessment of hepatocyte hemosiderin iron.

Iron status was assessed by measuring serum (S-) ferritin and hemoglobin (Hb) in a population survey comprising 1359 nonpregnant Danish women, in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal. Median age for menarche was 14 years, for menopause (artificial and natural) 48 years. Premenopausal women had lower S-ferritin (median 37 micrograms/l) than postmenopausal women (median 71 micrograms/l; p less than 0.0001). Of the premenopausal women, 17.7% had S-ferritin less than 15 micrograms/l (i.e., depleted iron stores), and 23.1% S-ferritin of 15-30 micrograms/l (i.e., small iron stores). Corresponding figures in postmenopausal women were 3.3% and 10.3%. Hb values in premenopausal women were mean 137 +/- 10 (SD) g/l (8.5 +/- 0.6 mmol/l) vs. 140 +/- 10 g/l (8.7 +/- 0.6 mmol/l) in postmenopausal women (p less than 0.0001); 4.1% of pre- and 3.3% of postmenopausal women had values less than 121 g/l (7.5 mmol/l). Iron deficiency anemia (i.e., S-ferritin less than 15 micrograms/l and Hb less than 121 g/l) was found in 2.6% of pre- and 0.36% of postmenopausal women. Premenopausal multipara had lower S-ferritin than nulli- and unipara (p less than 0.04). The use of oral contraceptives had a marked influence on iron stores; premenopausal women taking the pill had higher S-ferritin and a lower frequency of depleted iron reserves than nonusers (p less than 0.01). Postmenopausal estrogen treatment had no influence on S-ferritin or Hb.

Iron status, including serum (S-)ferritin and hemoglobin (Hb), was assessed in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years. S-ferritin levels were similar in 30- and 40-year-old women; they displayed a significant increase in 50-year-old women and a further significant increase in 60-year-old women. In the 30- and 40-year-old women, median S-ferritin was 38 micrograms/l, 5-95 percentile 6-135 micrograms/l; 17.2% had values less than 15 micrograms/l (i.e., depleted iron stores), 22.7% values from 15 to 30 micrograms/l (i.e., small iron stores), and 60.1% values greater than 30 micrograms/l (i.e., replete iron stores). In the 50-year-old women, median S-ferritin was 54 micrograms/l, 5-95 percentile 10-164 micrograms/l; 10.3% had values less than 15 micrograms/l, 16.5% values from 15 to 30 micrograms/l, and 73.2% values greater than 30 micrograms/l. For the 60-year-old women, median S-ferritin was 84 micrograms/l, 5-95 percentile 25-249 micrograms/l; 1.6% had values less than 15 micrograms/l, 8.6% values from 15 to 30 micrograms/l, and 89.8% values greater than 30 micrograms/l. Blood donors (n = 180) had lower S-ferritin than nondonors in all age-groups (p less than 0.001). In the entire series, Hb levels were similar in 30- and 40-year-old women, median 137 milligrams (8.5 mmol/l), 5-95 percentile 121-152 milligrams (7.5-9.4 mmol/l), and higher in 50- and 60-year-old women, median 140 milligrams (8.7 mmol/l), 5-95 percentile 123-158 milligrams (7.6-9.8 mmol/l) (p less than 0.0001). Hb values less than 121 milligrams (7.5 mmol/l) were observed in 3.8% of the women. Women with S-ferritin less than 15 micrograms/l (n = 161) had lower Hb, median 134 milligrams (8.3 mmol/l), than those with S-ferritin greater than or equal to 15 micrograms/l, median 139 milligrams (8.6 mmol/l) (p less than 0.001). Iron deficiency anemia (S-ferritin less than 15 micrograms/l and Hb less than 121 milligrams) was seen in 2.3% of 30- and 40-year-old women, and in 1.1% of 50- and 60-year-old women.

Iron status including S-ferritin and haemoglobin (Hb) was assessed in a population survey comprising 1433 Danish males in age cohorts of 30, 40, 50 and 60 years. There was no significant difference in S-ferritin levels between the age groups. In the entire series, median S-ferritin was 126 micrograms 1-1, 5-95% tile 31-378 micrograms 1-1, range 5-3600 micrograms 1-1; 1.2% had values less than 15 micrograms 1-1 (i.e. depleted iron stores), 3.7% values from 15-30 micrograms 1-1 (i.e. small iron stores), and 95.1% values greater than 30 micrograms 1-1 (i.e. replete iron stores); 73.8% had values from 61-300 micrograms 1-1, and 9.5% values greater than 300 micrograms 1-1. Blood donors had lower S-ferritin than non-donors and a higher frequency of depleted iron stores (p less than 0.0001). Hb values showed no age variation; median values was 155 g 1-1 (9.6 mmol 1-1), 5-95% tile 137-171 g 1-1 (8.5-10.6 mmol 1-1). Hb values less than 129 g 1-1 (8.0 mmol 1-1) were observed in 1.7%, and values less than 121 g 1-1 (7.5 mmol 1-1) in 0.8%. Males with S-ferritin less than 15 micrograms 1-1 (n = 17) had lower Hb, median 148 g 1-1 (9.2 mmol 1-1), than those with S-ferritin greater than or equal to 15 micrograms 1-1, median 155 g 1-1 (9.6 mmol 1-1) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A longitudinal study of iron status markers (haemoglobin (Hb), serum (S-) iron, S-transferrin, transferrin saturation, S-ferritin) was performed in 31 chemotherapy treated patients with small cell lung cancer. At discovery, eight patients were anaemic (Hb less than 121 g l-1). Hb, S-iron and transferrin saturation were lower (P less than 0.01), and S-ferritin higher (P less than 0.01) than in healthy subjects. Chemotherapy induced an immediate fall in Hb (P less than 0.003), increase in S-iron (P less than 0.003) and transferrin saturation (P less than 0.001). Later in the disease a fall in S-transferrin (P less than 0.006) and an increase in S-ferritin (P less than 0.02) occurred. Thirty patients died during the 2 years observation. S-ferritin at discovery was correlated to performance status score (r = 0.57, P = 0.01) and to survival (r = -0.63, P less than 0.0002). Patients with S-ferritin less than or equal to 400 micrograms l-1 (n = 13) had longer survival than those with S-ferritin greater than 400 micrograms l-1 (n = 18) (P = 0.004).

Iron status markers, serum iron, serum transferrin, transferrin saturation and serum ferritin were analysed in 162 homozygous patients with clinical haemochromatosis, in 12 homozygous relatives with preclinical haemochromatosis, in 84 heterozygous, and in 9 normal subjects. In the distinction between homozygous patients with clinical haemochromatosis and heterozygotes, transferrin saturation and serum ferritin showed the highest diagnostic efficiencies. A diagnostic efficiency of 0.97 was obtained with a transferrin saturation value of 60%. A discriminatory transferrin saturation value of greater than 50% correctly classified 173 out of the 174 individuals with preclinical + clinical haemochromatosis, whereas a discriminatory value of greater than 60% identified 158 out of the 162 patients with clinical haemochromatosis. All patients with clinical haemochromatosis had transferrin saturation values greater than 50%. 10 heterozygotes had transferrin saturation values greater than 50%, and 3 values greater than 60%. Normal subjects had transferrin saturation values less than 47%. A diagnostic efficiency of 0.99 was obtained using a discriminatory serum ferritin value of 800 micrograms/l. Patients with clinical haemochromatosis had higher ferritin (p less than 0.001) than subjects with preclinical haemochromatosis, who in turn had higher values than heterozygotes (p less than 0.001). Iron status markers in heterozygotes and normal subjects displayed no significant differences.

The general impact of blood donation on iron status has been studied in Danish males. Iron stores were assessed by serum (S-) ferritin and haemoglobin (Hb) in a population survey comprising 1433 males in age cohorts of 30, 40, 50, and 60 years; 389 (27%) were blood donors and 1044 (73%) non-donors. Hb levels were identical in donors and non-donors, mean 155 +/- 11 (SD) g/l (9.6 +/- 0.7 mmol/l); values less than 129 g/l (8.0 mmol/l) were observed in 1.3% of donors vs 1.9% of non-donors. Correlations between S-Ferritin and Hb were slight and without practical clinical relevance: rS = 0.13, p less than 0.01 in donors vs rS = 0.16, p less than 0.0001 in non-donors. Donors had lower S-Ferritin, median 95 micrograms/l, than non-donors, median 136 micrograms/l (p less than 0.0001). S-Ferritin values less than 15 micrograms/l (i.e. depleted iron stores) were seen in 3.3% of donors vs 0.4% of non-donors, and S-Ferritin values of 15-30 micrograms/l (i.e. small iron stores) in 9.8% of donors vs 1.4% of non-donors. Iron-deficiency anaemia (i.e. S-Ferritin less than 15 micrograms/l and Hb less than 129 g/l) was seen in 0.26% of donors vs 0.10% of non-donors; employing the 5th percentile for Hb (137 g/l (8.5 mmol/l] as discriminatory value increased the percentage of iron-deficiency anaemia to 0.51% in donors vs 0.10% in non-donors. Blood donation had a marked influence on iron status in the adult male population. The frequency of phlebotomy should be adjusted according to S-Ferritin as well as Hb levels. If Hb is used as single criterion for donation, only donors with pre-donation values greater than or equal to 135-137 g/l should be allowed phlebotomy. Optimal donation standards should include monitoring of iron status through measurement of S-Ferritin and Hb, combined with individualised postdonation iron supplementation.

The general impact of blood donation on iron status was studied in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal; 180 (13%) were blood donors. Iron stores were assessed by serum (S)-ferritin and hemoglobin (Hb). Hb levels were not significantly different in donors: mean 137 +/- 10 (SD) g/l (8.5 +/- 0.6 mmol/l) compared with nondonors, 139 +/- 11 g/l (8.6 +/- 0.7 mmol/l). Values less than 121 g/l (7.5 mmol/l) were observed in 3.3% of donors vs 3.8% of nondonors. Correlations between S-ferritin and Hb were without practical relevance: rs = 0.29, p less than 0.0001 in donors vs rs = 0.22, p less than 0.0001 in nondonors. Blood donation had a profound influence on iron status, especially in the premenopausal women population. Donors had lower S-ferritin than nondonors in all age-groups and in pre- and postmenopausal groups (p less than 0.001 in all groups). Premenopausal donors had a median S-ferritin of 31 micrograms/l vs 39 micrograms/l in nondonors, postmenopausal donors of 47 micrograms/l vs 72 micrograms/l in nondonors. S-ferritin values less than 15 micrograms/l (i.e., depleted iron stores) were observed in 31.7% of premenopausal donors vs 15.2% of nondonors, and in 7.0% of postmenopausal donors vs 2.9% of nondonors. Iron deficiency anemia (i.e., S-ferritin less than 15 micrograms/l and Hb less than 121 g/l) was seen in 2.8% of donors vs 1.5% of nondonors. Donors using oral contraceptives had higher S-ferritin, median 33 micrograms/l compared with nonusers, 22 micrograms/l, and a lower frequency of depleted iron stores, 29% vs 39%. Ideally, the frequency of phlebotomy should be adjusted according to S-ferritin as well as Hb levels. If Hb is used as single criterion for donation, only donors with predonation values greater than or equal to 124-125 g/l should be allowed to undergo phlebotomy.

Iron status (haemoglobin, S-ferritin, S-iron, S-transferrin, and transferrin saturation) was evaluated in an epidemiological survey comprising a representative sample of 118 (4%) of the 40- to 49-year-old Faroese male population. All had normal haemoglobin, (mean +/- SD 153 +/- 9 g/l; 9.5 +/- 0.6 mmol/l). Median S-ferritin was 151 micrograms/l, 5-95 percentile 46-588 micrograms/l, observed range 33-1166 micrograms/l. None had depleted iron stores (S-ferritin less than or equal to 20 micrograms/l), 2.5% had 'small' iron stores (S-ferritin 21-40 micrograms/l), 80.5% had 'normal' iron stores (S-ferritin 41-300 micrograms/l) and 17% had 'increased' iron stores (S-ferritin greater than 300 micrograms/l). Transferrin saturation values were greater than 16% in all males; high values greater than 50% were found in 9.3%, and the combination of high transferrin saturation and S-ferritin greater than 300 micrograms/l was found in 3.4% of the males. Median P-ascorbic acid was 26 mumol/l, 5-95 percentile 7-67 mumol/l; significantly higher in subjects taking vitamin supplements (n = 35, median 50 mumol/l) than in those not taking supplements (n = 81, median 23 mumol/l) (p less than 0.0001). There was no correlation between P-ascorbic acid and iron status markers. The results indicate a high frequency of ample iron reserves in the Faroese male population.

Iron status, including S-ferritin, S-iron, S-total iron binding capacity (TIBC), TIBC saturation, haemoglobin (Hb) and dietary iron intake, was assessed in a population study comprising 92 healthy 85-year-old subjects (32 males, 60 females). S-iron, S-TIBC, TIBC saturation and S-ferritin values were not significantly different in the two sexes. Males had a geometric mean S-ferritin of 130 micrograms/l, females of 98 micrograms/l. Ferritin levels less than 15 micrograms/l (i.e. depleted iron stores) were found in one female (1.6%); and in one male (3.1%), who in addition had iron deficiency anaemia. None of the females displayed latent iron deficiency (i.e. S-ferritin less than 15 micrograms/l and S-TIBC saturation less than 15%) or iron deficiency anaemia. Arithmetic mean Hb was 145 +/- 13 (SD) g/l (9.0 +/- 0.8 mmol/l) in males and 139 +/- 11 g/l (8.6 +/- 0.7 mmol/l) in females (p less than 0.02). Median nutritional iron intake was 10 mg/day (range 3-17), higher in males (median 12) than in females (median 9) (p less than 0.0001). Iron intake showed significant correlations to S-iron, S-TIBC and TIBC saturation, but not to S-ferritin.

Serum iron, serum transferrin and transferrin saturation were studied in 253 healthy, non-anaemic children 4, 8 and 13 years old, and in 60 healthy, non-anaemic adults having serum ferritin values greater than or equal to 15 micrograms/l. One hundred and ninety-six children had serum ferritin values greater than or equal to 15 micrograms/l (i.e. replete iron stores), 35 had intermediate ferritin values from 10-14 micrograms/l and 22 had ferritin values less than 10 micrograms/l (i.e. depleted iron stores). Iron replete children showed a gradual rise in serum iron and transferrin saturation values with age. Serum iron and transferrin saturation values were lower (P less than 0.001, P less than 0.0001) and transferrin values higher (P less than 0.0001) in iron replete children compared to adults. Iron replete children had a 2.5 centile transferrin saturation value of 5%; 19.9% of these children had saturation values less than 15% and 8.2% had values less than 10%. In iron depleted children a transferrin saturation value less than 7% yielded the highest diagnostic efficiency as regards exhausted iron stores, although with a low predictive value of a positive test. The transferrin saturation is unsuitable as a single diagnostic criterion in the evaluation of iron deficiency in children and should always be combined with other indicators of iron status.

Gastrointestinal iron absorption has been measured by whole body counting in 17 patients with chronic uremia undergoin regular hemodialysis. Absorption was expressed as whole body retention 14 days after oral administration of 10 muCi 59Fe together with a carrier dose of 10 mg Fe2+. The percentage incorporation in the total erythrocyte mass of administered 59Fe (erythrocyte incorporation) and absorbed 59Fe (red cell utilization) was estimated as well. Geometric mean iron absorption was 14.3 +/- 2.0 (S.D.)% and significantly higher than the value obtained in a normal control group (p less than 0.03). Geometric mean erythrocyte incorporation was 11.6 +/- 2.3 (S.D.)% and arithmetic mean red cell utilization was 84.4 +/- 6.0 (S.E.M.)%. Neither of these parameters differed from corresponding values in the control group (p greater than 0.1 and p greater than 0.2, respectively). The correlation between iron absorption and erythrocyte incorporation was highly significant (r=0.94, p less than 0.001). Patients on regular hemodialysis are subjected to considerable iron loss which should be treated by iron supplementation; oral iron administration is recommended in view of the adequate gastrointestinal absorption.

Iron stores were evaluated by serum ferritin determinations in 948 menstruating and 141 non-menstruating female blood donors. Blood donation was associated with a decrease in ferritin. First-time donors (n = 163) had a geometric mean ferritin of 24 micrograms/l and multiple-time donors a value of 19 micrograms/l (p less than 0.01). In the donating population 31.5% had ferritin values less than 15 micrograms/l (i.e. depleted iron stores). Menstruating donors had lower mean serum ferritin than non-menstruating donors (p less than 0.001), and a higher frequency of ferritin values less than 15 micrograms/l (p less than 0.05). There was no relationship between ferritin levels and the number of pregnancies. The frequency of donations was more predictive of ferritin levels than the number of donations. Mean ferritin displayed a moderate fall up to the 2nd donation, and was hereafter relatively constant, whereas an increase in donation frequency was accompanied by a significant decrease in ferritin. Female donors, especially when phlebotomised greater than or equal to 3 times per year, should have their iron status checked at appropriate intervals by measurement of serum ferritin and should be advised regular iron supplementation.

Bone marrow haemosiderin iron was correlated with various laboratory parameters of iron status in order to define a reliable laboratory index of marrow iron stores. Marrow iron, serum iron, plasma transferrin, transferrin saturation, iron absorption, red cell iron incorporation and serum ferritin were measured in 21 non-dialysed, 20 peritoneal dialysed and 34 haemodialysed patients with chronic uraemia. Diagnostic accuracy of the laboratory tests in terms of diagnosing reduced marrow iron stores was expressed as the predictive value of a positive test and a negative test, and efficiency. Diagnostic efficiency of serum iron, plasma transferrin and transferrin saturation was too low to be of value in the individual patient. Iron absorption and red cell incorporation had a higher diagnostic efficiency, but are unpractical for routine use. Serum ferritin displayed a high diagnostic efficiency and appears to be a reliable index of marrow iron stores, suitable for sequential monitoring of iron status in uraemic subjects.

Gastrointestinal iron absorption, by means of whole body counting, has been measured in 15 patients with chronic renal failure, not requiring dialysis. Whole body retention 14 days after oral administration of 10 muCi 59Fe together with a carrier dose of 10 mg Fe2+ was taken as expression of absorption. The percentage incorporation in the total erythrocyte mass of administered 59Fe (erythrocyte incorporation) and absorbed 59Fe (red cell utilization) was estimated as well. Iron absorption was 9.6+/-2.0 (S.D.)% (geometric mean) and erythrocyte incorporation 7.5+/-2.3 (S.D.)% (geometric mean) while red cell utilization averaged 80.3+/-4.8 (S.E.M.)% (arithmetic mean). None of these parameters were significantly different from those obtained in a normal control group (p greater than 0.5, p greater than 0.9 and p greater than 0.2, respectively). The correlation between iron absorption and erythrocyte incorporation was highly significant (r=1.00, p less than 0.001). Iron supplementation is often indicated in the investigated category of patients due to increased blood loss and insufficient iron intake and should be given orally in consideration of the normal gastrointestinal absorption.

The content of iron, copper, zinc and selenium was measured by energy-dispersive X-ray fluorescence (XRF) spectrometry in normal liver tissue obtained at autopsy from 16 females and 12 males 46-87 years old. The precision of the XRF analysis, expressed by the coefficient of variation was: iron, 1.8%; copper, 3.2%; zinc, 1.0%; and selenium, 26.7%. In large liver samples, mean amount-of-substance contents of elements in dry liver tissue were: iron, 16.95 mmol/kg (range 7.90-27.31 mmol/kg); copper, 0.33 mmol/kg (0.08-0.76 mmol/kg); zinc, 5.12 mmol/kg (2.92-9.47 mmol/kg); selenium 0.02 mmol/kg (less than 0.004-0.04 mmol/kg). Furthermore the amounts of iron, copper and zinc were measured in wet-ashed Menghini needle biopsy specimens taken from the centre of 20 large liver samples. There was good agreement between results obtained in biopsy specimens and large samples concerning iron (r = 0.96, P less than 0.001) and zinc (r = 0.97, P less than 0.001), but not concerning copper (r = 0.66, P less than 0.01). XRF analysis appears to be a convenient method for element analysis in liver tissue and for measurement of iron and zinc in needle biopsy specimens.

Twelve patients in maintenance hemodialysis, receiving long-term oral iron therapy, have been treated with i.v. iron dextran, in order to evaluate the effect on the Hb level. Both Hb and hematocrit were unchanged before and after the iron dextran infusion (p greater than 0.5, p greater than 0.7, respectively). Oral iron therapy is usually sufficient to maintain an adequate iron balance in dialysed patients and should be preferred to parenteral iron in view of the better utilization and absence of side-effects. The indication for parenteral iron should be limited to patients with impaired gastrointestinal iron absorption.

Iron status, including hemoglobin, S-ferritin, S-iron, S-transferrin, transferrin saturation and the erythrocyte zinc protoporphyrin/hemoglobin (ZPP:Hb) ratio, was evaluated in 85 healthy iron-supplemented mothers at parturition and in 74 of their term newborn infants. Of the mothers, 17% had a S-ferritin level less than 15 micrograms/l (i.e. depleted iron stores), 9.9% had S-ferritin less than 15 micrograms/l and transferrin saturation less than 15% (i.e. latent iron deficiency), and 2.4% had S-ferritin less than 15 micrograms/l, transferrin saturation less than 15% and Hb less than 120 g/l (i.e. iron deficiency anemia). Newborn infants had higher S-ferritin than mothers: median 128 micrograms/l versus 21 micrograms/l (p less than 0.0001), higher transferrin saturation: 48% vs. 21% (p less than 0.0001), and higher ZPP:Hb ratio: 74 mumol/mol Hb vs. 41 mumol/mol Hb (p less than 0.0001). During the first 5 post-natal days, median S-ferritin rose from 128 to 236 micrograms/l (p less than 0.0001). S-ferritin appeared to be the best single indicator of maternal iron status. Ferritin levels in newborn infants were correlated to levels in mothers (rs = 0.36, p less than 0.01), indicating that fetal iron reserves are dependent on maternal iron stores.

Gastrointestinal iron absorption has been measured by means of whole body counting in 13 patients after renal allotransplantation. Whole body retention 14 days after oral administration of 10 muCi 59Fe together with a carrier dose of 9.9 mg Fe2+ was used as an expression of absorption. The percentage incorporation in the total erythrocyte mass of administered 59Fe (erythrocyte incorporation) and absorbed 59Fe (red cell utilization) was estimated as well. Geometric mean iron absorption was 12.4 +/- 2.5 (S.D.)% and geometric mean erythrocyte incorporation 11.1 +/- 3.0 (S.D.)% while arithmetic mean red cell utilization was 95.6 +/- 8.6 (S.E.M.)%. None of these parameters differed significantly from those obtained in normal subjects (p greater than 0.2, p greater than 0.1, pgreater than 0.3, respectively). Iron absorption and erythrocyte incorporation in renal transplanted patients did not differ significantly from the values measured in non-dialysed and dialysed patients with chronic renal failure (p greather than 0.1). The correlation between iron absorption and erythrocyte incorporation was highly significant (r = 0.96, p less than 0.001).