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This review focuses on the prevention and treatment of anemia in women who have just given childbirth (postpartum anemia). The problem of anemia both prepartum and postpartum is far more prevalent in developing countries than in the Western societies. The conditions for mother and child in the postpartum, nursing, and lactation period should be as favorable as possible. Many young mothers have a troublesome life due to iron deficiency and iron deficiency anemia (IDA) causing a plethora of symptoms including fatigue, physical disability, cognitive problems, and psychiatric disorders. Routine screening for postpartum anemia should be considered as part of the national maternal health programs. Major causes of postpartum anemia are prepartum iron deficiency and IDA in combination with excessive blood losses at delivery. Postpartum anemia should be defined as a hemoglobin level of <110 g/l at 1 week postpartum and <120 g/l at 8 weeks postpartum. Bleeding exceeding normal blood losses of approximately 300 ml may lead to rapid depletion of body iron reserves and may, unless treated, elicit long-standing iron deficiency and IDA in the postpartum period. The prophylaxis of postpartum anemia should begin already in early pregnancy in order to ensure a good iron status prior to delivery. The most reliable way to obtain this goal is to give prophylactic oral ferrous iron supplements 30-50 mg daily from early pregnancy and take obstetric precautions in pregnancies at risk for complications. In the treatment of slight-to-moderate postpartum IDA, the first choice should be oral ferrous iron 100 to 200 mg daily; it is essential to analyze hemoglobin after approximately 2 weeks in order to check whether treatment works. In severe IDA, intravenous ferric iron in doses ranging from 800 to 1,500 mg should be considered as first choice. In a few women with severe anemia and blunted erythropoiesis due to infection and/or inflammation, additional recombinant human erythropoietin may be considered. Blood transfusion should be restricted to women who develop circulatory instability due to postpartum hemorrhage. National health authorities should establish guidelines to combat iron deficiency in pregnancy and postpartum in order to facilitate a prosperous future for both mothers and children in a continuing globalized world.

This review provides a status on the definition, prevalence, causes, and consequences of anemia in women who have given childbirth, i.e., postpartum anemia. The diagnosis of iron deficiency anemia relies on a full blood count including hemoglobin, serum ferritin, and serum soluble transferrin receptor, which appear to be reliable indicators of anemia and iron status 1 week postpartum while serum transferrin saturation is an unreliable indicator several weeks after delivery. It is recommended that postpartum anemia should be defined by hemoglobin <110 g/L at 1 week postpartum and <120 g/L at 8 weeks postpartum. The major causes of postpartum anemia are prepartum anemia combined with acute bleeding anemia due blood losses at delivery. Normal peripartum blood losses are approximately 300 ml, but hemorrhage >500 ml occur in 5-6% of the women. In healthy women after normal delivery, the prevalence of anemia (hemoglobin <110 g/L) 1 week postpartum is 14% in iron-supplemented women and 24% in non-supplemented women. In consecutive series of European women, the prevalence of anemia 48 h after delivery is approximately 50%. In developing countries, the prevalence of postpartum anemia is in the range of 50-80%. Postpartum anemia is associated with an impaired quality of life, reduced cognitive abilities, emotional instability, and depression and constitutes a significant health problem in women of reproductive age.

Anemia is a major global health problem, especially in developing countries. This fundamental health issue still has not been solved and continues to exist affecting the health, quality of life, and working capacity in billions of people all over the world. This paper gives a review on the prevalence and major causes of anemia seen on a global scale. Most cases of anemia are due to iron deficiency, which often work in symphony with folate deficiency and/or vitamin B12 deficiency as well as with infections. More efforts should be dedicated to tackle this massive problem--we have the tools, and we know the ways. Iron fortification of appropriate food items combined with iron supplements in specific population groups has proven to be efficient. Initially, the efforts should be centered on the specific risk groups for iron deficiency anemia, i.e., young children, adolescent females, women of reproductive age, as well as pregnant women and postpartum lactating mothers.

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.

The aim of this epidemiologic population survey was to assess the penetrance of the most frequent hemochromatosis (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 by restriction fragment length polymorphism analysis. Subsequently, iron status markers (serum transferrin saturation, serum ferritin) were analyzed in 1,452 men. The C282Y allele was present in 5.6%, H63D in 12.8%, and S65C in 1.8% of the men. We found 23 out of 6,020 (0.38%) C282Y homozygotes, of whom two had been treated with phlebotomy. Among untreated C282Y homozygotes (n = 21) with available iron status markers (transferrin saturation n = 18, ferritin n = 16), 89% had elevated transferrin saturation >or=50%, 94% had elevated ferritin >or=300 microg/L, and 88% had elevation of both iron status markers; seven out of 16 (44%) had ferritin values >800 microg/L. One C282Y homozygote had normal iron status markers possibly due to nonexpressivity. Among C282Y/H63D compound heterozygotes (n = 66), 23% had elevated transferrin saturation, 27% elevated ferritin, and 9% elevation of both iron status markers. Among H63D/H63D homozygotes (n = 74), 15% had elevated transferrin saturation, 19% elevated ferritin, and 5.4% elevation of both iron status markers. Among C282Y/wild type (wt) heterozygotes (n = 255), 9% had elevated transferrin saturation, 9% elevated ferritin, and 1.2% elevation of both iron status markers. Among H63D/wt heterozygotes (n = 600), 8% had elevated transferrin saturation, 12% elevated ferritin, and 2% elevation of both iron status markers. None of the men with the S65C variant displayed elevation of both iron status markers. In conclusion, this study demonstrates a high penetrance of the C282Y variant in Danish men followed by the H63D variant while the S65D variant had no significant impact on iron status markers.

The blood haemoglobin concentration is one of the most frequently used laboratory parameters in clinical practice. There is evidence that haemoglobin levels are influenced by tobacco smoking. The objective of this study was to evaluate the impact of smoking and alcohol consumption on haemoglobin concentrations in apparently healthy subjects living at sea level. A retrospective, epidemiological cohort study was performed in 1984. Participants were 1,503 men and 1,437 non-pregnant women evenly distributed in age cohorts of 30, 40, 50, and 60 years. Information of smoking habits and alcohol consumption were obtained by a questionnaire. Haemoglobin was measured in the fasting state on Coulter-S. Men displayed no difference in mean haemoglobin levels in the four age groups. In women, mean haemoglobin increased gradually with age (p = 0.001). Fifty-nine percent of men and 50% of women were daily smokers. Female smokers displayed a significant positive correlation between number of cigarettes/day and haemoglobin concentrations (r = 0.12, p = 0.002). Heavy smokers (more than ten cigarettes/day) had significantly higher mean haemoglobin (1.4% higher in men, on average 3.5% higher in women) than non-smokers (p < 0.01). Smokers demonstrated a significant correlation between cigarettes/day and drinks/week in men (r = 0.24, p < 0.001) and women (r = 0.16, p < 0.001). Non-smokers displayed a significant positive correlation between drinks/week and haemoglobin concentrations in men (r = 0.14, p = 0.001) and women (r = 0.08, p = 0.05). In non-smokers, alcohol consumption >14 drinks/week and more than seven drinks/week for men and women, respectively, increased mean haemoglobin by 1.3% in men and by average 1.9% in women compared with those consuming < or =14 and less than or equal to seven drinks/week. Smokers displayed similar results. Body mass index per se had no direct influence on haemoglobin levels but had indirect positive influence in men through its correlation with tobacco smoking and alcohol consumption. Tobacco smoking has an increasing effect on haemoglobin concentrations in both genders, which is proportional to the amount of tobacco smoked. The effect appears to be more pronounced in women. Likewise, high alcohol consumption has an increasing effect on haemoglobin in both genders, being most pronounced in women. However, in clinical biochemistry, the relatively small changes in haemoglobin do not justify the use of separate reference ranges in smokers and alcohol consumers.

This review focuses on the occurrence, prevention and treatment of anaemia during pregnancy in Western societies. Iron deficiency anaemia (IDA) is the most prevalent deficiency disorder and the most frequent form of anaemia in pregnant women. Minor causes of anaemia are folate and vitamin B12 deficiency, haemoglobinopathy and haemolytic anaemia. Anaemia is defined as haemoglobin of <110 g/L in the first and third trimester and <105 g/L in the second trimester. The diagnosis relies on haemoglobin, a full blood count and plasma ferritin, which can be supported by plasma transferrin saturation and serum soluble transferrin receptor. Among fertile, non-pregnant women, approximately 40% have ferritin of or=10 g/L, oral iron therapy has proved effective and should continue. Treatment with intravenous iron is superior to oral iron with respect to the haematological response. Intravenous iron is considered safe in the second and third trimester, while there is little experience in the first trimester. Intravenous iron of 600-1,200 mg should be considered: (1) as second option if oral iron fails to increase haemoglobin within 2 weeks; (2) as first option at profound IDA, i.e. haemoglobin of <90 g/L in any trimester beyond 14 weeks gestation; and (3) as first option for IDA in third trimester. Profound IDA has serious consequences for both woman and foetus and requires prompt intervention with intravenous iron. This is especially important for the safety of women who for various reasons oppose blood transfusions.

The objective was to assess the frequencies of haemochromatosis (HFE) gene mutations or variants C282Y, H63D and S65C in ethnic Danes. This is a prospective epidemiologic population study. A cohort of 6,020 Danish men aged 30-50 years was screened for HFE C282Y (c845G-->A), H63D (c187C-->G) and S65C (c193A-->T) gene variants, assessed on saliva or blood samples by restriction fragment length polymorphism (RFLP) analysis. The C282Y gene variant allele was present in 5.6%, H63D in 12.8% and S65C in 1.8% of the chromosomes. In the entire series, we observed 1.4% H63D/C282Y, 0.1% S65C/C282Y and 0.4% H63D/S65C compound heterozygotes. The C282Y allele frequency in Denmark is of similar order as reported in other Scandinavian countries: Iceland 5.1%, Faeroe Islands 6.6%, Norway 6.8% and Sweden 5.8%. Also, the H63D frequency in Denmark is close to the frequencies in other Scandinavian countries: Iceland 10.9%, Faeroe Islands 15.2%, Norway 11.4% and Sweden 12.1%.

Discovery of genetic variants of the HFE gene has made it possible to screen for hereditary hemochromatosis. However, genetic screening raises ethical, legal, social, and psychological questions, which need to be addressed. To assess the psychological impact on individuals undergoing genetic screening for hereditary hemochromatosis and to determine the effects of providing different levels of information to the participants. Male residents, aged 30-50 years (n = 10,993) were invited to a genetic screening for hereditary hemochromatosis. Carriers of the gene variants H63D, S65C, and C282Y were offered additional biochemical screening using serum ferritin and transferrin saturation. Psychological factors were evaluated through questionnaires before and after genetic and biochemical screening. According to genotype, participants were divided into three groups with different risks profiles for having/developing clinical hemochromatosis (at-risk, uncertain risk, no risk). Before completion of the questionnaires, 929 participants received only genetic information and 366 received both genetic and biochemical information. At-risk participants receiving only genetic information generally displayed negative reactions to the test result, whereas participants receiving both genetic and biochemical information were more satisfied and had fewer negative psychological reactions to the test result. Genetic screening is more readily accepted by subjects when genetic information is supported by biochemical measurements, especially in participants with a risk of clinical disease.

The aim of the study was to investigate whether the well-known high anemia prevalence in pregnant women from the eastern Mediterranean and Asian regions decreased when the women immigrated to a low-frequency region (Denmark). During 70 months, 1,741 pregnant immigrant women referred from primary care to an obligatory hemoglobinopathy screening were eligible for the study, as their screening was negative. To compare this group with a cohort of 205 pregnant ethnic Danish women, the groups were matched by gestational age, and a total of 406 immigrant women were included. Hemoglobin (Hb) and iron status parameters were examined in the two groups. The prevalence of anemia was higher in the immigrant group (20.0%) compared to the Danish women (4.9%) (P < 0.0001). Blood Hb concentration was 119 +/- 12 g/l (mean +/- SD) in the immigrant group compared to 122 +/- 9 g/l in the Danish group (P = 0.01). Erythrocyte mean corpuscular volume (MCV) was also lower in the immigrant group (87 +/- 7 fl vs 96 +/- 4 fl) (P < 0.0001). A total of 13.1% of the immigrant women had an MCV <80 fl (the lower reference limit) compared to 0.0% in the Danish group, and plasma iron, ferritin, and transferrin saturation values indicated iron deficiency. Conclusively, the pregnant immigrant women had significantly higher prevalence of anemia compared to pregnant women of Danish origin. It indicates the need for an alternative routine screening procedure for this population group, which should also include nutritional counselling.

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.

The review focuses on iron balance during pregnancy and postpartum in the Western affluent societies. Iron status and body iron can be monitored using serum ferritin, haemoglobin, serum soluble transferrin receptors (sTfR) and the sTfR/ferritin ratio. Requirements for absorbed iron increase during pregnancy from 0.8 mg/day in the first trimester to 7.5 mg/day in the third trimester. Average requirement during the entire gestation is approximately 4.4 mg/day. Intestinal iron absorption increases during pregnancy, but women with ample body iron reserves have lower absorption than those with depleted reserves, so increased absorption is, in part, due to progressive iron depletion. Apparently, women do not change dietary habits when they become pregnant. Non-pregnant Scandinavian women have a median dietary iron intake of approximately 9 mg/day, i.e. more than 90% of the women have an intake below the recommended approximately 18 mg/day. Non-pregnant women have a low iron status, 42% have serum ferritin levels 70 microg/l corresponding to body iron of >or=500 mg. The association between high haemoglobin during gestation and a low birth weight of the newborns is caused by inappropriate haemodilution. In placebo-controlled studies on healthy pregnant women, there is no relationship between the women's haemoglobin and birth weight of the newborns and no increased frequency of preeclampsia in women taking iron supplements.

This study aims to evaluate iron prophylaxis in pregnant women from the individual aspect, i.e. according to serum ferritin levels at the beginning of pregnancy, and to assess which dose of iron would be adequate to prevent iron deficiency (ID) and iron deficiency anaemia (IDA) during pregnancy and postpartum. A randomised, double-blind study comprising 301 healthy Danish pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n=74), 40 mg (n=76), 60 mg (n=77) and 80 mg (n=75) from 18 weeks gestation (inclusion) to 8 weeks postpartum. Iron status markers [serum ferritin, serum soluble transferrin receptor (sTfR), haemoglobin] were recorded at 18, 32 and 39 weeks gestation and 8 weeks postpartum. Body iron was calculated using the serum sTfR/serum ferritin ratio. ID was defined by serum ferritin <12 microg/l in pregnancy and <15 microg/l postpartum; IDA as serum ferritin <12 microg/l and haemoglobin <5th percentile in iron-replete pregnant women. Women in the iron supplement groups were stratified according to serum ferritin levels at inclusion; 50.7% had ferritin 70 microg/l. At 32 weeks, women with ferritin 30 microg/l had an ID frequency of: 20-mg group 20.0%, 40 mg 13.9%, 60 mg 5.7%, 80 mg 5.1% (p<0.001). Women with ferritin >70 microg/l had no ID. Postpartum, ID was found in 4.7% in 20-mg group, 2.9% in group 40 mg and 0% in group 60 and 80 mg. IDA: At 32 weeks, women with ferritin 30 microg/l displayed IDA. Body iron at 18 weeks was 10.4 mg/kg, similar in the four iron groups. Later in pregnancy body iron declined significantly, being lower the 20 mg group, and similar in the 40, 60 and 80-mg groups. Postpartum body iron rose to inclusion levels being 9.3 mg/kg in the 20-mg group and 10.5 mg/kg in the 40-, 60- and 80-mg groups. This study gives an estimate of iron dosage in individual iron prophylaxis adjusted to serum ferritin levels in early pregnancy. In the prevention of ID, we suggest 80-100 mg ferrous iron/day to women having ferritin 70 microg/l have no need for iron supplement.

The aim of the study was to assess the frequencies of the hereditary hemochromatosis HFE mutations C282Y, H63D, and S65C in the population in the Faroe Islands. The series comprised 200 randomly selected blood donors of Faroese heritage. The frequency of the C282Y, H63D, and S65C mutations on the HFE gene was assessed by genotyping using the polymerase chain reaction (PCR) technique and calculated from direct allele counting. We found no C282Y homozygous subjects; 28 (14.0%) subjects were C282Y heterozygous and four subjects were C282Y/H63D compound heterozygous (2.0%). The C282Y allele frequency was 8.0% (95% CI 5.3-10.7%). The series contained three (1.5%) H63D homozygous subjects and 60 (30.0%) H63D heterozygous subjects. The H63D allele frequency was 17.5% (95% CI 13.8-21.2%). There were four (2.0%) S65C heterozygous subjects. The S65C allele frequency was 1.0% (95% CI 0.3-2.5%). The frequency of the C282Y mutation is high in Faroese blood donors, being close to and not significantly different from the frequencies reported in other Scandinavian countries: Denmark 5.7%, Norway 6.6%, Iceland 5.1%, and Sweden 6.1%. The frequency of the H63D mutation in Faroese subjects is significantly higher than the frequency in Denmark 12.8% (p=0.007), Iceland 10.9% (p=0.003), and Sweden 12.4% (p=0.015), but not from the frequency in Norway 11.2% (p=0.063). The frequency of the S65C mutation in Faroese subjects is not significantly different from the frequencies in Denmark 1.5% and Sweden 1.6%. Screening of larger groups of the Faroese population for HFE mutations especially C282Y should be considered in order to establish the penetrance.

The aim of the study was to assess the frequency of the C282Y and H63D mutations of the hemochromatosis gene (HFE) in ethnic Danes. The series comprised 2501 subjects (1284 men) of Danish heritage who were drawn at random from the Census Registry in age cohorts of 30, 40, 50, and 60 years. The frequency of the C282Y and H63D mutations was assessed on blood samples by genotyping using a polymerase chain reaction (PCR) technique. The HFE genotype distribution was in Hardy-Weinberg equilibrium (p=0.85). C282Y mutation: 9 subjects (0.36%) were homozygous and 265 subjects (10.6%) were heterozygous. H63D mutation: 40 subjects (1.6%) were homozygous and 584 subjects (23.4%) were heterozygous. C282Y/H63D compound heterozygosity was found in 36 subjects (1.4%). The C282Y allele frequency was 5.7% [95% confidence interval (CI) 5.0-6.3%] and the H63D allele frequency was 13.3% (95% CI 12.3-14.2%). In conclusion, the C282Y frequency is relatively high in the Danes, being close to the frequency in other Scandinavian countries, i.e., Iceland 5.1%, the Faroe Islands 6.6%, and Sweden 5.7%, but significantly lower than in Norway 6.6% (p=0.02). Also, the H63D frequency in Danes is close to and not significantly different from the frequency in Iceland 10.9%, Norway 11.2%, and Sweden 12.4%, but significantly lower than in the Faroe Islands 15.4% (p=0.046).

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.