Correlations Between Iron Status Markers During Normal Pregnancy in Women with and without Iron Supplementation

The aim was to evaluate relationships between iron status markers (haemoglobin, erythrocyte indices, serum iron, serum transferrin, serum transferrin saturation, serum ferritin) in normal pregnancy. Iron status markers were measured at 4-week-intervals during pregnancy and postpartum in 120 healthy women; 62 had daily treatment with tablets containing 66 mg ferrous iron, 58 were treated with placebo. Placebo-treated: Ferritin displayed positive correlations with transferrin saturation during 2nd and 3rd trimester. There were positive correlations between ferritin, erythrocyte MCV and MCH during 2nd and 3rd trimester and postpartum. Prior to delivery and postpartum, ferritin demonstrated positive correlations with haemoglobin. Transferrin saturation showed positive correlations with MCV, MCH and MCHC during 2nd and 3rd trimester and postpartum. Transferrin saturation displayed positive correlations with haemoglobin prior to delivery and postpartum. Iron-treated: In general, there were no correlations between iron status markers. Positive correlations appeared postpartum between ferritin, transferrin saturation and MCHC but not with haemoglobin. Transferrin saturation showed a positive correlation with MCH postpartum, but not with haemoglobin. Conclusion: The patterns of relationships in placebo-treated women were consistent with iron deficient erythropoiesis.     

Serum Ferritin is a Reliable, Non-invasive Test for Iron Status in Pregnancy: Comparison of Ferritin with Other Iron Status Markers in a Longitudinal Study on Healthy Pregnant Women; Erythropoiesis

Background and Aims: To assess the true positive and false positive rates of the iron status markers (serum iron, serum transferrin, transferrin saturation, haemoglobin, haematocrit, mean corpuscular volume (MCV), mean cell haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), erythrocyte count) in the diagnosis of depleted iron stores (iron depletion) during normal pregnancy and postpartum. Methods: Among 120 pregnant women, 58 were randomised to placebo-treatment and 62 to iron-treatment (66 mg ferrous iron daily from 14 weeks of gestation). Iron status markers were measured every 4th week during pregnancy and 8 weeks postpartum. Iron depletion was defined by a serum ferritin concentration < 16 &mgr;g/L. The 5th percentiles for the other iron status markers in the group of iron-treated women were used as cut-off values. Calculations were made in the 2nd and 3rd trimester, praepartum and postpartum. Results: In general, the true positive rates of other iron status markers in the diagnosis of iron depletion (serum ferritin < 16 &mgr;g/L) were low ranging from 0% to 52% during pregnancy and from 9% to 64% postpartum. Transferrin saturation and MCH displayed the highest true positive rates. The false positive rates ranged from 0% to 13% during pregnancy and from 4% to 17% postpartum. Haemoglobin and MCH displayed the highest false positive rates. Conclusions: The sensitivities of the other iron status markers were too low and the false positive rates too high to be of clinical value in the diagnosis of iron depletion. Despite physiologic variations due to haemodilution, the serum ferritin concentration is currently the most reliable non-invasive marker of iron status in pregnancy and postpartum.     

Serum Iron and Transferrin Saturation in Women with Special Reference to Women with Low Transferrin Saturation

Serum iron and total iron binding capacity (TIBC) were determined in a population sample of 1462 women in age strata between 38 and 60. Serum iron and TIBC values were similar in the various ages studied but with a slight trend towards higher serum iron and lower TIBC values in the upper ages. Transferrin saturation was used to divide the material arbitrarily into women with and without iron deficiency. The dividing point chosen was 16%. The women thus defined as iron deficient had lower mean haemoglobin values than women in the total population sample and were more often anaemic. They had also lower MCV, MCH and MCHC indices than women in the total population sample. Of these indices, MCH seemed to discriminate the state of iron deficiency better than MCV and MCHC. Except for an increased mean menstrual blood loss no obvious cause of iron deficiency could be found in these women with low transferrin saturation.     

Serum iron and transferrin saturation in women with special reference to women with low transferrin saturation. The population study of women in G?teborg 1968-1969

Serum iron and total iron binding capacity (TIBC) were determined in a population sample of 1462 women in age strata between 38 and 60. Serum iron and TIBC values were similar in the various ages studied but with a slight trend towards higher serum iron and lower TIBC values in the upper ages. Transferrin saturation was used to divide the material arbitarily into women with and without iron deficiency. The dividing point chosen was 16%. The women thus defined as iron deficient had lower mean haemoglobin values than women in the total population sample and were more often anaemic. They had also lower MCV, MCH and MCHC indices than women in the total population sample. Of these indices, MCH seemed to discriminate the state of iron deficiency better than MCV and MCHC. Except for an increased mean menstrual blood loss no obvious cause of iron deficiency could be found in these women with low transferrin saturation.     

Iron status markers during pregnancy No relationship between levels at the beginning of the second trimester,prior to delivery and post partum

Abstract. Objective . To evaluate whether levels of iron status markers (haemoglobin, serum transferrin saturation, serum ferritin) in pregnant women, measured in the beginning of the second trimester, could be used to predict levels later in pregnancy, pre partum and post partum. Design . Randomized, double-blind, placebo-controlled parallel study. Setting . The Birth Clinic at the Department of Obstetrics, Herning Hospital, Herning, Denmark. Subjects . One hundred and twenty healthy pregnant women between 14 and 18 weeks of gestation. Interventions . Sixty-three women were allocated to treatment with tablets containing 66 mg ferrous iron (as fumarate) daily, and 57 women to treatment with placebo. Main outcome measures . Haemoglobin, serum transferrin saturation, and serum ferritin were measured every 4th week during gestation, prior to delivery, and 1 and 8 weeks post partum. Results . Correlation matrices during pregnancy and post partum were calculated for each iron status marker separately in iron-treated 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 8 weeks or less prior to delivery, and no correlations to values post partum. Serum ferritin values at inclusion could not be used to predict values later in pregnancy or post partum. Conclusion . Haemoglobin, transferrin saturation and serum ferritin values measured in the beginning of the second trimester appear to be unsuitable as guidelines for an individual iron prophylaxis in pregnant women.     

Microcytosis, Anisocytosis and the Red Cell Indices in Iron Deficiency

S ummary . Red cell volume distribution curves have been used to measure micro-cytosis and anisocytosis in normal subjects, blood donors and patients with iron deficiency anaemia. These measurements were more sensitive than the conventional red cell indices for detecting blood donors with a low transferrin saturation. Three stages are suggested as iron deficiency progressively interferes with haemopoietic function. Anisocytosis and an increased percentage of microcytic cells are the first haematological abnormalities to occur and at this stage haemoglobin concentration is usually normal and transferrin saturation less than 32%. At the second stage the MCV and MCH decline, haemoglobin concentration is generally sub-normal, though not below 9 g/dl, and transferrin saturation is usually below 16%. The final stage of iron deficiency is associated with a low MCHC, a haemoglobin concentration below 9 g/dl and a transferrin saturation of less than 16%.     

Iron status of pregnant Filipino women as measured by serum ferritin.

Iron status of pregnant women at different stages of pregnancy was evaluated by comparing values for hemoglobin (Hb), red cell indices, serum iron (SI), transferrin saturation (TS) and serum ferritin (SF) values with those of a group of non-pregnant women of comparable age and socio-economic status. Mean SF values on the second and third trimesters (9.3 +/- 2.60 ng/ml and 7.1 +/- 2.19 ng/ml) were significantly lower compared to that in the first trimester (22.6 +/- 2.20 ng/ml). These levels were also lower than that found in the non-pregnant controls. The trend was the same for TS. Hemoglobin levels of the pregnant subjects were significantly lower than those of the non-pregnant women. Prevalence of iron deficiency based on SF < 12.0 ng/ml and TS < 16.0% was highest at term and lowest during the first trimester indicating a decrease in iron stores as pregnancy progressed. Sensitivity for each of the iron parameters was computed, and it was found that for the diagnosis of iron deficiency in pregnant women, SF has a greater sensitivity than TS, SI, MCV and MCH.     

Serum transferrin receptor levels in patients undergoing evaluation of iron stores: correlation with other parameters and observed versus predicted results

Serum transferrin receptor (sTfR) concentrations were measured in specimens from 77 patients undergoing serum ferritin determination, and the results correlated with serum ferritin, serum iron, serum total iron-binding capacity (TIBC) saturation, erythrocyte mean corpuscular volume (MCV), and mean corpuscular haemoglobin (MCH). All parameters exhibited the expected inverse correlation with sTfR; this correlation was statistically significant for all parameters except serum iron concentration. The frequency with which iron deficiency (defined as absence of stainable marrow iron) is observed in patients with particular ferritin values in this centre was determined and used to estimate the expected number of iron deficient patients in the present study. In no setting were significantly fewer sTfR levels > 3.05 μg/ml observed than expected. However, significantly greater than expected numbers of elevated sTfR values were observed in patients with serum ferritin > 220 μg/l (P = 0.002). The results suggest that the sTfR level is probably not useful as a single test for identification of iron deficiency in unselected patients.     

Increased yet iron-restricted erythropoiesis in postpartum mothers

Iron deficiency in the postpartum period is common and associated with impaired quality of life. Interpretation of ordinary laboratory parameters is considered to be simple in postpartum women, as normalization of pregnancy induced physiological changes is assumed to take place in the early postpartum period. We have studied changes in erythrocyte and iron parameters during the first 11 postpartum months. Erythrocyte parameters and iron markers, serum ferritin, and soluble transferrin receptor (sTfR), and an inflammation marker, neopterin, were investigated in healthy mothers 6 weeks (n = 104), 4 months (n = 100), and 11 months (n = 43) after giving birth to a term infant. Healthy nonpregnant and nonlactating women (n = 61) were included as controls. The hemoglobin level increased throughout the first 11 postpartum months and was significantly higher from 4 months on, compared to control women. At all time points, the mothers had significantly lower mean corpuscular volume (MCV) and higher erythrocyte count and percentage of hypochromic erythrocytes. sTfR levels were significantly higher over the whole serum ferritin distribution during the first 4 postpartum months compared to the controls, indicative of an increased cell production. At 6 weeks, postpartum mothers had higher neopterin levels and this was associated with markers of a low iron status, not including sTfR. Substantial changes in erythrocyte and iron parameters were observed in the postpartum period, consistent with an increased, but iron restricted erythropoiesis. The increased erythropoietic activity was reflected in higher sTfR concentrations. Given the vital role for iron in both mothers and infants, further studies are warranted for establishing proper cut off levels for sTfR as an iron marker in postpartum women.     

Clinical laboratory diagnosis and aging. 3: Evaluation of a study of aging--complete blood and urine status

The results of the determination of hematologic values from 262 men and 242 women, participants of an aging study and half of each group 44.4 +/- 0.9 and 63.0 +/- 0.9 (men) and 44.4 +/- 0.9 and 62.8 +/- 0.8 years old (women), respectively, are compared. In men, one analyte (hemoglobin decreasing) and four indices show significant differences (MCV increasing, MCH decreasing, MCHC decreasing, RDW increasing). In the older group, the iron level and the transferrin saturation are also significantly lower. In women, erythrocytes and the hematocrit are significantly higher in the older group whereas the indices MCH and MCHC are lower and the RDW increases. At the same time, the iron level, transferrin and the transferrin saturation decrease whereas ferritin doubles. The sex differences of the hematologic parameters are more pronounced in the younger participants and especially remarkable in ferritin in both age groups. The results of the semiquantitative analysis of ten urine parameters by reagent strip show differences with respect to sex (e.g., leucocytes and erythrocytes) and age (e.g., specific gravity, pH, nitrite, protein, erythrocytes). The usefulness of the estimation of glucose in urine is discussed in connection with the corresponding serum glucose levels.     

Iron status in women with and without gestational diabetes mellitus

ObjectiveGestational diabetes mellitus (GDM) affects approximately 7% of all pregnancies. Pregnancy, mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress. A transitional metal, especially iron, which is particularly abundant in the placenta, is important in the production of free radicals. Also, studies have shown that free radicals have a role in GDM. As there are little data about iron status in GDM, this study was performed to compare iron status in GDM and control group.Research Design and MethodsIn this case-control study, 34 women with diagnosed GDM were compared with 34 non-GDM women in the control group at 24–28 weeks of pregnancy in terms of iron status, including ferritin, serum iron, total iron-binding capacity (TIBC), hemoglobin (Hb), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH).ResultsIn this study, concentration of serum ferritin, iron, transferrin saturation and hemoglobin, MCV, and MCH was significantly higher in the GDM group and TIBC was significantly lower in this group (P<.05). No significant association was observed with the other variables including familial history of diabetes and GDM.ConclusionOur findings indicate an association between increased iron status and GDM. The role of iron excess from iron supplementation in the pathogenesis of GDM needs to be examined.     

The diagnosis of iron deficiency anemia in sickle cell disease

We determined the prevalence and optimal methods for laboratory diagnosis of iron deficiency anemia in patients with sickle cell disease. Laboratory investigations of 38 nontransfused and 32 transfused patients included transferrin saturation, serum ferritin, mean corpuscular volume (MCV), and free erythrocyte protoporphyrin (FEP). Response to iron supplementation confirmed the diagnosis of iron deficiency anemia in 16% of the nontransfused patients. None of the transfused patients were iron deficient. All iron-deficient patients (mean age 2.4 yr) had a low MCV, serum ferritin less than 25 ng/ml, transferrin saturation less than 15%, and FEP less than 90 micrograms/dl RBC. Following therapy, all parameters improved and the hemoglobin concentration increased greater than 2 g/dl. A serum ferritin below 25 ng/ml was the most reliable screening test for iron deficiency. There were 13% false positive results with transferrin saturation, 3% with MCV, and 62% with FEP. FEP values correlated strongly with reticulocyte counts. The high FEP was in part due to protoporphyrin IX and not completely due to zinc protoporphyrin, which is elevated in iron deficiency. We conclude that iron deficiency anemia is a potential problem in young nontransfused sickle cell patients. Serum ferritin below 25 ng/ml and low MCV are the most useful screening tests.     

Soluble transferrin receptor in Aboriginal children with a high prevalence of iron deficiency and infection

OBJECTIVES: Aboriginal children in tropical Australia have a high prevalence of both iron deficiency and acute infections, making it difficult to differentiate their relative contributions to anaemia. The aims of this study were to compare soluble transferrin receptor with ferritin in iron deficiency anaemia (IDA), and to examine how best to distinguish the effect of iron deficiency from infection on anaemia. METHODS: We conducted a prospective study of 228 admissions to Royal Darwin Hospital in children from 6 to 60 months of age. Transferrin receptor concentrations were measured by a particle-enhanced immunoturbidimetric assay and ferritin by a microparticle enzyme immunoassay. RESULTS: On multiple regression, the best explanatory variables for haemoglobin differences (r2=33.7%, P<0.001) were mean corpuscular volume (MCV), red cell distribution width (RDW) and C-reactive protein (CRP); whereas transferrin receptor and ferritin were not significant (P>0.4). Using > or =2 abnormal indices (MCV, RDW, blood film)+haemoglobin <110 g/l as the reference standard for IDA, transferrin receptor produced a higher area under the curve on receiver operating characteristic curve analysis than ferritin (0.79 vs. 0.64, P<0.001) or the transferrin receptor-ferritin index (0.77). On logistic regression, the effect of acute infection (CRP) on haemoglobin was significant (P<0.001) at cut-offs of 105 and 110 g/l, but not at 100 g/l when only iron deficiency indicators (MCV, RDW, blood film) were significant. CONCLUSIONS: Transferrin receptor does not significantly improve the diagnosis of anaemia (iron deficiency vs. infection) over full blood count and CRP, but in settings with a high burden of infectious diseases and iron deficiency, it is a more reliable adjunctive measure of iron status than ferritin.     

Red cell indices as predictors of iron depletion in blood donors

The objective of this study was to investigate whether red cell indices mean cell volume (MCV) and mean cell haemoglobin (MCH) were lower in frequent blood donors and hence, indirectly, able to predict impending iron depletion. Serum ferritin and/or soluble transferrin receptor levels can be used to evaluate iron status but are not practical for routinely screening blood donors prior to donation. Hb, MCV and MCH were measured on venous blood from 886 blood donors using a Sysmex E-5000. Full details were obtained for all donors of each earlier donation over the previous 3 years. MCV and MCH levels were lowest in donors with the highest frequency of previous blood donation. There was a significant negative correlation between MCV and number of donations in males and females and between MCH and number of donations in females, over the 3 year period 1995-97. Similar trends were observed when only the previous year's donations (1997) were considered with all categories showing significant negative correlations and additionally, Hb levels in females showed negative correlation with number of donations in 1997. In conclusion, increased frequency of blood donations is associated with lower MCV and MCH. These red cell indices, or more sophisticated parameters such as percentage hypochromic cells, should be used to monitor early onset of iron depletion in frequent blood donors.     

Association between immune activation,changes of iron metabolism and anaemia in patients with HIV infection

Abstract: The pathogenesis of anaemia associated with human immunodeficiency virus infection is still far from being understood. It cannot be explained by direct effects of the virus on the haematopoietic system. Recent data suggest a role for immune activation. In a cross-sectional study we compared blood cell counts, haemoglobin and erythropoietin levels of 63 HIV-seropositive individuals with immune activation markers (interferon-γ, serum and urine neopterin, and β2-microglobulin) and with parameters or iron metabolism (serum iron, transferrin, free iron binding capacity, ferritin). We found significant correlations between the concentrations of haemoglobin and the immune activation markers and erythropoietin concentrations. Additional significant correlations existed between the parameters of iron metabolism and haemoglobin levels, and ferritin correlated inversely with transferrin. In sum, low haemoglobin levels in patients were associated with enhanced cellular immune activation, as seen by increased interferon-γ, neopterin and β2-microglobulin, and with changes of iron metabolism: low haemoglobin was associated with low transferrin and free iron binding capacity and high ferritin levels. Endogenous release of cytokines such as interferon-γ-inhibiting crythropoiesis may be one underlying cause of anaemia in these patients.     

Iron and pregnancy—a delicate balance

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 ~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 ~9 mg/day, i.e. more than 90% of the women have an intake below the recommended ~18 mg/day. Non-pregnant women have a low iron status, 42% have serum ferritin levels ≤30 μg/l, i.e. small or depleted iron reserves and 2–4% have iron deficiency anaemia; only 14–20% have ferritin levels >70 μg/l corresponding to body iron of ≥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.     

Serum transferrin receptors in detection of iron deficiency in pregnancy

 A prospective hospital-based study was conducted to evaluate the efficacy of serum transferrin receptors in the detection of iron deficiency in pregnant women. The iron status of 100 pregnant women with single uncomplicated term pregnancies in the first stage of labor was established using standard laboratory measures. These included complete hemogram, red cell indices, serum iron, percent transferrin saturation, and serum ferritin. In addition, serum transferrin receptor (STFR) was estimated. The results of 81 women with complete laboratory profiles were analyzed. Thirty-five (43.2%) women were anemic (hemoglobin <11 g/dl). Hemoglobin (Hb) showed a significant correlation with MCH, MCHC, serum iron, and percent transferrin saturation, suggesting that the anemia was likely to be due to iron deficiency. The mean STFR level was 18.05±9.9 mg/l in the anemic women and was significantly raised (p<0.001) compared with that of the nonanemic women. STFR correlated significantly with Hb (p<0.001), MCH (p<0.05), MCHC (p<0.01), serum iron (p<0.01), and percent transferrin saturation (p<0.01) and also showed a highly significant correlation with the degree of anemia. Serum ferritin in these women did not correlate with Hb, and only 54.4% of the women had levels <12 ng/ml, which does not reflect the true prevalence of iron deficiency. Serum transferrin receptor estimation is thus a useful measure for detecting iron deficiency in pregnancy. Received: August 26, 1998 / Accepted: March 30, 1999     

Relative iron deficiency in hereditary spherocytosis

Seventy-three patients with hereditary spherocytosis (HS) (58 nonsplenectomized, 15 splenectomized) were studied to evaluate iron status and the adequacy of iron availability for erythropoiesis. Splenectomized patients, who had hemoglobin levels in the normal or upper normal range, had higher levels of serum iron, transferrin saturation, and serum ferritin than normal matched controls and normal zinc protoporphyrin (ZnPP) levels. On the contrary, nonsplenectomized patients presenting with mild to severe anemia had higher red cell ZnPP concentrations than both splenectomized subjects and matched normal controls. ZnPP in nonsplenectomized patients correlated inversely with Hb concentration, mean corpuscular volume (MCV), mean red cell hemoglobin concentration (MCHC), transferrin saturation, and serum iron, and directly with reticulocyte count. At multiple regression analysis only Hb concentration was a significant explanatory variable for high ZnPP. The authors conclude that a number of nonsplenectomized HS patients have relative iron deficiency primarily because of expansion of erythropoiesis caused by anemia.     

Iron status markers in hereditary haemochromatosis: distinction between individuals being homozygous and heterozygous for the haemochromatosis allele

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.     

Iron status and the effect of iron supplementation in Thai male blood donors in northern Thailand

The iron status of voluntary and professional male donor groups was investigated. The study indicated that serum ferritin level was lower significantly in those who donated three times per year compared to the first time donors (p less than 0.05) in voluntary donor group. Similar results were observed among the professional donors. Whereas haemoglobin, haematocrit and transferrin saturation were not altered by donating blood in both groups. It also showed that, in general, the body iron stores of professional donors were lower to those of voluntary donors. Supplementation with iron over a period of three months produced a rise in serum ferritin levels and the percentage prevalence of iron depleted subjects decreased from 23.6% to 6.4%. Haemoglobin, haematocrit and transferrin saturation levels also improved.