Effects of iron supplementation to iron depleted and iron replete pregnant Danish women: Defining criteria for identification of women who can manage without supplements: A randomized, placebo-controlled study.

OBJECTIVE: To define criteria based on iron status parameters for the identification of healthy women who do need/do not need iron supplementation during normal pregnancy. METHODS: Randomized, double-blind, placebo-controlled study of 113 women (62 iron-, 51 placebo treated) and their newborns. Iron dose was 66 mg elemental iron as ferrous fumarate daily from 14-18 weeks gestation to delivery. Hemoglobin (Hb), serum (S)-ferritin, S-transferrin saturation percentage, and S-erythropoietin were measured during gestation, prepartum, one week and 8 weeks postpartum. The women were divided in groups according to S-ferritin levels at inclusion:<30,≥30,≥40,≥50 and≥60µg/L. Iron deficiency (ID) was defined as S-ferritin < 15µg/L; iron deficiency anemia (IDA) as S-ferritin < 15µg/L and Hb < 110 g/L. RESULTS: Placebo treated women with S-ferritin levels < 30µg/L at inclusion had a much higher incidence of ID/IDA than placebo treated women with S-ferritin levels≥30,≥40,≥50, and≥60µg/L. S-ferritin levels≥40µg/L were associated with a very low risk of ID/IDA and none of the women with levels≥50 and≥60µg/L displayed ID/IDA. CONCLUSIONS: Women having S-ferritin < 30µg/L in early pregnancy, have a high risk of ID/IDA and should be recommended ferrous iron supplements in appropriate doses. With increasing iron reserves, i.e., increasing S-ferritin, the need for iron supplements diminishes, and placebo treated women having S-ferritin ≥40µg/L seldom develop IDA. Women with S-ferritin levels≥50 and≥60µg/L or higher, have adequate iron reserves and do not need routine iron prophylaxis in pregnancy. The results support the arguments for an individual iron supplementation guided by iron status, to avoid unwanted side effects of unnecessary iron intake.

Iron supplementation in pregnant Danish women revisited: Effects on prepartum and postpartum iron deficiency, anemia, serum erythropoietin; including iron status, erythropoietin and anthropometrics in newborns. A randomized, placebo-controlled study.

OBJECTIVE: To assess effects of iron supplementation, 66 mg elemental iron daily as ferrous fumarate, on iron status markers during normal pregnancies. METHODS: Randomized, double-blind, placebo-controlled study of 119 women (62 iron-, 57 placebo -treated) and their newborns. Hemoglobin (Hb), serum (S)-ferritin, S-transferrin saturation percentage (TSAT) and S-erythropoietin (S-EPO) were measured at 14-18, 24-27 weeks of gestation, prepartum, 1 and 8 weeks postpartum. RESULT: From 24-27 weeks gestation to 8 weeks postpartum, the iron group had higher Hb, S-ferritin and TSAT than the placebo group; prepartum, 11% had iron deficiency (ID) and 0% iron deficiency anemia (IDA) in the iron group, vs 60% and 18% in the placebo group; 8 weeks postpartum 1.6% in the iron group had ID and 1.6% IDA vs 14% and 7% in the placebo group. S-EPO levels in the iron group were lower than in the placebo group (p < 0.001). Mothers prepartum S-EPO values were correlated to newborns cord S-EPO values (p < 0.001). Newborns to iron treated mothers had higher cord S-ferritin levels than those to placebo treated mothers (p = 0.02). Newborn girls had higher cord S-ferritin levels than boys (p < 0.01). There was no impact of iron supplementation on the length of gestation, placental weight, or newborns birth weight. Birth weight was correlated only with mothers' body weight, length of gestation and placental weight. CONCLUSION: Iron supplementation had a "positive" impact on iron status and Hb both during pregnancy and postpartum, with a low frequency of ID/IDA and also a "positive" influence on newborns iron status.

Induction of specific brain oscillations may restore neural circuits and be used for the treatment of Alzheimer's disease.

Brain oscillations underlie the function of our brains, dictating how we both think and react to the world around us. The synchronous activity of neurons generates these rhythms, which allow different parts of the brain to communicate and orchestrate responses to internal and external stimuli. Perturbations of cognitive rhythms and the underlying oscillator neurons that synchronize different parts of the brain contribute to the pathophysiology of diseases including Alzheimer's disease, (AD), Parkinson's disease (PD), epilepsy and other diseases of rhythm that have been studied extensively by Gyorgy Buzsaki. In this review, we discuss how neurologists manipulate brain oscillations with neuromodulation to treat diseases and how this can be leveraged to improve cognition and pathology underlying AD. While multiple modalities of neuromodulation are currently clinically indicated for some disorders, nothing is yet approved for improving memory in AD. Recent investigations into novel methods of neuromodulation show potential for improving cognition in memory disorders. Here, we demonstrate that neuronal stimulation using audiovisual sensory stimulation that generated 40-HZ gamma waves reduced AD-specific pathology and improved performance in behavioural tests in mouse models of AD, making this new mode of neuromodulation a promising new avenue for developing a new therapeutic intervention for the treatment of dementia.

Iron status in Danes 1994. II: Prevalence of iron deficiency and iron overload in 1319 Danish women aged 40-70 years. Influence of blood donation, alcohol intake and iron supplementation.

Iron status, i.e. serum ferritin and haemoglobin (Hb) levels, was assessed in a population survey in 1994 (Dan-Monica 10) comprising 1319 Caucasian Danish women in age cohorts of 40, 50, 60 and 70 years. In the entire series, ferritin levels increased significantly from 40 years to 60 years of age. The prevalence of small iron stores (ferritin 16-32 microg/l), depleted iron stores (ferritin < 16 microg/l) and of iron deficiency anaemia (ferritin < 13 microg/l and Hb < 121 g/l) decreased steadily with age. Blood donors (n = 109) had lower ferritin levels than non-donors (P<0.0001). Ferritin levels in donors were inversely correlated with the cumulated number of lifetime phlebotomies (r(s) = -0.25, P<0.01). Ferritin levels in non-donors (n = 1208) were low in 40-year-old women (median 40 microg/l) and increased to a median of 95 microg/l in 60- and 70-year-old women (P<0.0001). In non-donors 40 years of age, the prevalence of small iron stores was 40.4%, the prevalence of depleted iron stores 10.8% and the prevalence of iron deficiency anaemia 2.16%. The prevalence of iron overload (ferritin >300 microg/l) was 1.54%. Ferritin levels in 60- and 70-year-old non-donors were correlated with the body mass index (r(s) =0.11, P=0.01). Ferritin levels in 50- to 60-year-old non-donors were correlated with alcohol intake (r(s)=0.23, P<0.0001). In the entire series, 37.5% of non-donors took supplemental ferrous iron (median 14 mg iron per day). Iron supplements had a significant positive influence on iron status in 40-year-old premenopausal non-donors but no effect in postmenopausal women or in donors. Non-donors (n = 170) treated with acetylsalicylic acid had lower ferritin levels (median 55 microg/l) than non-treated (n = 1038; median 75 microg/l) (P<0.0001). Compared with the Dan-Monica 1 iron status survey in 1984, the prevalence of iron deficiency and iron deficiency anaemia was unchanged, whereas the prevalence of iron overload displayed a slight increase. The 1987 abolition of the mandatory iron fortification of flour apparently had no negative effect on iron status.

Hemoglobin and erythrocyte indices during normal pregnancy and postpartum in 206 women with and without iron supplementation.

BACKGROUND: The aim was to define reference values for hemoglobin, hematocrit and erythrocyte indices, i.e. erythrocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), in normal pregnancy and after a normal delivery in non-iron-supplemented and iron supplemented women. METHODS: Two hundred and six healthy Danish women included at 9-18 weeks of gestation were allocated to treatment with placebo tablets (n=107) or tablets containing 66 mg iron (n=99). Blood samples were obtained at inclusion, every fourth week during gestation, and 8 weeks postpartum. RESULTS: All hematologic indices were significantly lower in placebo-treated than in iron-treated women. In placebo-treated women, the 5th percentile for hemoglobin was 110 g/L in the 1st trimester; in the 2nd trimester it was 105 g/L in the first and the second, and 103 g/L in the last third; in the 3rd trimester, it was 102 g/L in the first, 100 g/L in the second, and 101 g/L in the last third; postpartum it was 113 g/L. In iron-treated women, the 5th percentile for hemoglobin was 111 g/L in the 1st trimester; in the 2nd trimester it was 109 g/L in the first, 106 g/L in the second, and 103 g/L in the last third; in the 3rd trimester, it was 105 g/L in the first and second, and 110 g/L in the last third; postpartum it was 123 g/L. CONCLUSIONS: Hematologic reference values should be derived from iron replete women. We suggest that the lowest critical hemoglobin value in iron-treated pregnant women should be 110 g/l (6.8 mmol/L) in the 1st trimester, and 105 g/L (6.5 mmol/L) in the 2nd and 3rd trimester.

Iron status and iron balance during pregnancy. A critical reappraisal of iron supplementation.

BACKGROUND: Iron supplementation in pregnancy is a controversial issue. The aim of this review was to summarize the results of relevant papers on this subject. METHODS: Placebo-controlled studies on iron treatment in pregnancy were identified from the Cochrane database. RESULTS: Among fertile women, 20% have iron reserves of >500 mg, which is the required minimum during pregnancy; 40% have iron stores of 100-500 mg, and 40% have virtually no iron stores. The demand for absorbed iron increases from 0.8 mg/day in early pregnancy to 7.5 mg/day in late pregnancy. Dietary iron intake in fertile women is median 9 mg/day, i.e. the majority of women have an intake below the estimated allowance of 12 18 mg/day. Iron absorption increases in pregnancy, but not enough to prevent iron deficiency anemia in 20%, of women not taking supplementary iron. Iron-treated pregnant women have greater iron reserves, higher hemoglobin levels, and a lower prevalence of iron deficiency anemia than placebo-treated women both in pregnancy as well as postpartum. Furthermore, children born to iron-treated mothers have higher serum ferritin levels than those born to placebo-treated mothers. An iron supplement of 65 mg/day from 20 weeks of gestation is adequate to prevent iron deficiency anemia. CONCLUSIONS: In order to avoid iron deficiency in pregnancy, prophylactic iron supplement should be considered. Iron supplements may be administered on a general or selective basis. The selective approach implies screening with serum ferritin in early pregnancy, in order to identify women who can manage without prophylactic iron.

Iron status in Danes updated 1994. I: prevalence of iron deficiency and iron overload in 1332 men aged 40-70 years. Influence Of blood donation, alcohol intake, and iron supplementation.

Iron status, S-ferritin, and hemoglobin (Hb) were assessed in a population survey in 1994 (DAN-MONICA 10) comprising 1332 Caucasian Danish men equally distributed in age cohorts of 40, 50, 60 and 70 years. Blood donors (n=186) had lower S-ferritin, median 76 microg/l, than nondonors, median 169 microg/l (p<0.0001). S-ferritin in donors was inversely correlated with the number of phlebotomies (r(s)=-0.57, p<0.0001). S-ferritin in nondonors (n=1146) was similar in men 40-60 years of age, median 176 microg/l, and subsequently decreased at 70 years of age to a median of 146 microg/l (p=0.01). In the entire series, the prevalence of small iron stores (S-ferritin 16-32 microg/l) was 2.7%, that of depleted iron stores (S-ferritin <16 microg/l) 0.45%, and that of iron deficiency anemia (S-ferritin <13 microg/l and Hb <129 g/l) 0.15%. Among nondonors, the prevalence of iron overload (S-ferritin >300 microg/l) was 20%. S-ferritin in nondonors correlated with body mass index (r(s)=0.19, p=0.0001) and with alcohol intake (r(s)=0.26, p=0.0001). In the entire series, 28% of the subjects took supplemental iron (median 14 mg ferrous iron daily). Iron supplements had no influence on iron status. Nondonors (n=170) treated with acetylsalicylic acid had lower S-ferritin, median 136 microg/l, than nontreated, median 169 microg/l (p<0.001) and those treated with H(2)-receptor antagonists (n=30) had lower S-ferritin, median 142 microg/l, than nontreated, median 171 microg/l (p<0.04). Compared with the DAN-MONICA 1 iron status survey of Danish men in 1984, the prevalences of iron depletion and iron deficiency anemia are unchanged whereas the prevalence of iron overload has increased significantly. In Denmark, iron fortification of flour was abolished in 1987. This apparently had no negative effect on iron status in men.

Consequences of removing iron fortification of flour on iron status among Danish adults: some longitudinal observations between 1987 and 1994.

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.

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

UNLABELLED: 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.

Iron status in 268 Danish women aged 18-30 years: influence of menstruation, contraceptive method, and iron supplementation.

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.

PIP: The influence of menstruation, method of contraception, and low-dose iron supplementation on iron status was investigated in 268 randomly selected, healthy, nonpregnant women 18-30 years of age from Copenhagen, Denmark. In addition, risk factors for development of iron deficiency in fertile women were identified. Iron deficiency (serum ferritin 16 mcg/l) was present in 9.7% and iron deficiency anemia (serum ferritin 13 mcg/l and hemoglobin 121 g/l) in 2.2%. 94 women (35.1%) took iron supplements, generally as a vitamin-mineral tablet containing 14.20 mg of ferrous iron. Median serum ferritin was the same (39 mcg/l) in users and non-users of iron supplements; however, the prevalence of iron deficiency was 12.6% in non-users compared with 4.3% in users and that of iron deficiency anemia was 3.4% in non-users vs. 0% in users. In non-users of iron supplements, serum ferritin levels were inversely correlated with the duration of menstrual bleeding (p 0.001) and women's assessment of the intensity of their bleeding (p 0.001). No such associations were found in supplement users. Menstrual bleeding in women using hormonal contraception (mean, 4.8 days) was significantly shorter than in those using IUDs (mean, 5.7 days). Median ferritin levels were 40 mcg/l in oral contraceptive users and 38 mcg/l in IUD users. Median serum ferritin levels also were higher in women who were not blood donors than in the 40 women (14.9%) who were regular donors (40 mcg/l and 30 mcg/l, respectively). These findings suggest that preventive measures should focus on women whose menstruation lasts 5 days or more, who have menstrual bleeding of strong intensity, who use an IUD without gestagen, and who are blood donors. These women should be encouraged to consume a diet rich in iron with a high bioavailability and/or to take a daily tablet containing 14-20 mg of ferrous iron.

Pulse oximetry at fibre-optic bronchoscopy in local anaesthesia: indication for postbronchoscopy oxygen supplementation?

The requirement for supplementary oxygen (O2) after fibre-optic bronchoscopy (FOB) was evaluated by means of pulse oximetry in 34 patients (19 men) of median age 62 years (range 28-85) who had had a diagnostic FOB. The patients were allocated at random into two groups, each of 17 persons, which were comparable concerning sex, age and the dose of benzodiazepine (diazepam tablets 10 mg 1 h before FOB and midazolam 2-5 mg i.v. during FOB) used for premedication. Patients in group 1 had lower pulmonary function (FEV1, FVC as a percentage of predicted values) than patients in group 2 (P < 0.02). The oxygen saturation of the haemoglobin (SpO2) in the tip of the index finger was recorded continuously for 30 min after the administration of oral diazepam, during FOB and for 120 min after the FOB procedure. All patients received nasal O2 supplement 21 min-1 during FOB. After FOB, O2 was discontinued in group 1, while group 2 continued to receive O2 21 min-1 for 120 min. The incidence of hypoxaemic episodes (SpO2 < or = 90% for a period of a minimum of > or = 12 s) after oral diazepam, before FOB, was similar in the two groups, 35%. After FOB, the incidence of hypoxaemic episodes was 88% in group 1 and 41% in group 2 (P < 0.01). The cumulated duration of hypoxaemia after FOB was a median of 30 s (range 0-7140) in group 1 and a median of 0 s (0-156) in group 2 (P < 0.0001). Impaired lung function (FEV1 < 75% of predicted value) was a risk factor for hypoxaemia. Postbronchoscopy, O2 supplement should be administered to sedated patients with impaired lung function until the patients have fully recovered.

Serum concentrations of lignocaine and its metabolite monoethylglycinexylidide during fibre-optic bronchoscopy in local anaesthesia.

Fibre-optic bronchoscopy was performed in local anaesthesia using lignocaine. Serum concentrations of lignocaine and its active metabolite monoethylglycinexylidide (MEGX) were measured in 16 patients at regular intervals up to 120 min after administration. Lignocaine was administered as an aerosol in the upper respiratory tract and as a solution in the bronchial tree. The total dose of lignocaine ranged from 243 to 608 mg (2.4-8.0 mg kg-1 body weight). The dose of lignocaine given as an aerosol ranged from 163 to 508 mg (1.6-6.6 mg kg-1) and the dose given as a solution ranged from 60 to 180 mg (0.8-2.5 mg kg-1). The highest median serum lignocaine concentration, 10.5 mumol l-1, was measured 20 min after administration. None of the patients had toxic serum lignocaine levels (> 26 mumol l-1) or adverse effects. The highest median serum MEGX concentration, 1.7 mumol l-1, was measured 120 min after administration. The dose of lignocaine, expressed in mg per kg body weight correlated with serum lignocaine and serum MEGX (rs = 0.47 and rs = 0.39, respectively). Lignocaine is a clinically safe, local anaesthetic agent provided the total dose does not exceed 6-7 mg kg-1 body weight.

Serum erythropoietin during normal pregnancy: relationship to hemoglobin and iron status markers and impact of iron supplementation in a longitudinal, placebo-controlled study on 118 women.

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 requirements and iron balance during pregnancy. Is iron supplementation needed for pregnant women?]. / Jernbehov og jernbalance under svangerskabet. Er det nødvendigt med jerntilskud til gravide?

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.

Cord serum erythropoietin in 90 healthy newborn term infants: relationship to blood gases and iron status markers.

In this study, we examined the cord serum erythropoietin (EPO) level in newborn infants in relation to venous cord blood gases and iron status markers (cord serum ferritin, cord serum transferrin saturation). The subjects were 90 healthy newborn term infants with a normal birth and 90 healthy women with an uncomplicated pregnancy and delivery. Within 14-18 weeks of gestation, 47 prospective mothers, allocated at random, received tablets containing 66 mg ferrous iron daily, and 43 received a placebo. Serum EPO was measured in women prior to delivery. Serum EPO, serum ferritin and serum transferrin saturation were analyzed in cord blood from the newborn. Blood gases (PO2, PCO2 and standard HCO3, PH) were measured in venous cord blood and Apgar scores were recorded. The cord serum EPO level in the newborn was not significantly affected by the iron supplementation to the mothers. In the entire series, the geometric mean cord serum EPO was 36 U/I, (median 32 U/I, 5-95% 16-150, range 12-380). There was no correlation between cord serum EPO and APgar score, cord blood PO2, PCO2, standard HCO3 and pH. In the newborn of placebo-treated mothers, log cord serum EPO was inversely correlated with log cord serum ferritin (r = -0.54, P < 0.0002) and cord serum transferrin saturation (r = -0.39, P < 0.011), suggesting that iron deficiency may occur in this newborn group.

Relationship between dietary iron intake, corrected for diet reporting error, and serum ferritin in Danish women aged 35-65 years.

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.

Serum ferritin in Danes: studies of iron status from infancy to old age, during blood donation and pregnancy.

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.

A longitudinal study of iron status in healthy Danish infants: effects of early iron status, growth velocity and dietary factors.

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.

[Preclinical hereditary hemochromatosis--is there an indication for preventive screening?]. / Praeklinisk hereditaer haemokromatose--er der behov for profylaktisk screening?

A 54 year-old previously healthy woman was admitted with staphylococcus aureus septicaemia. The patient had been treated with oral iron supplementation for two years due to fatigue. In the evaluation of postinfectious anaemia, serum transferrin saturation and serum ferritin were found persistently elevated with values of 74% and 950 micrograms/1, respectively. Hereditary haemochromatosis was suspected even though there was no history of liver disease or diabetes mellitus in the family. A bone marrow biopsy showed a normal content of haemosiderin iron. The liver biopsy revealed haemosiderosis, mainly located to the periportal hepatocytes, and fibrosis in the portal tracts. The HLA-type was A3, B7, B37. Over a period of ten months, a total of 3.9 g of iron was removed by venesection while S-ferritin declined to 31 micrograms/l. A sister to the proband had an identical HLA type, but normal iron status markers, either indicating heterozygosity or homozygosity with lack of penetrance. In preclinical hereditary haemochromatosis, early diagnosis and treatment is essential in order to prevent organ damage and to improve prognosis. Prophylactic screening is recommended. The identification of one homozygous subject in a Danish year-cohort of 60.000 persons costs approximately 40.000 Danish kroner (7.000 US+).

Iron status in young Danish men and women: a population survey comprising 548 individuals.

Iron status was assessed by measurement of serum (S-) ferritin and hemoglobin (Hb) in 548 randomly selected healthy Danes (264 men, 284 women) with a median age of 25 years (range 16-31). S-ferritin values in men displayed a gradual increase with age, and at all ages, men had higher values than women. Iron deficiency (i.e., S-ferritin < 16 micrograms/l) was observed in 0.8%; none had iron deficiency anemia (i.e., S-ferritin < 16 micrograms/l and Hb < 129 g/l). Daily iron supplementation was used by 15.5%. The frequency of iron deficiency was 0% in supplement users vs 0.9% in nonusers. The frequency of preclinical hereditary hemochromatosis was 0.38%. There was a slight insignificant increase in S-ferritin values of women with age. Iron deficiency was observed in 14.7% of 16- to 19-year-olds, in 9.2% of 20- to 24-year-olds, and in 8.6% of 25- to 31-year-old women (p < 0.01), and iron deficiency anemia (i.e., S-ferritin < 16 micrograms/l and Hb < 121 g/l) in 14.7%, 3.4%, and 3.7%, respectively (p < 0.01). Daily iron supplementation was used by 21.5%. The frequency of iron deficiency in users was 4.9% vs. 10.8% in nonusers, and the frequency of iron deficiency anemia 1.6% in users vs. 5.8% in nonusers. The results indicate a satisfactory iron status in young men. There is a high frequency of iron deficiency in young women, suggesting that preventive measures should be considered in this risk group.