Hepcidin and Iron Deficiency in Women One Year after Sleeve Gastrectomy: A Prospective Cohort Study.

Iron deficiency with or without anemia, needing continuous iron supplementation, is very common in obese patients, particularly those requiring bariatric surgery. The aim of this study was to address the impact of weight loss on the rescue of iron balance in patients who underwent sleeve gastrectomy (SG), a procedure that preserves the duodenum, the main site of iron absorption. The cohort included 88 obese women; sampling of blood and duodenal biopsies of 35 patients were performed before and one year after SG. An analysis of the 35 patients consisted in evaluating iron homeostasis including hepcidin, markers of erythroid iron deficiency (soluble transferrin receptor (sTfR) and erythrocyte protoporphyrin (PPIX)), expression of duodenal iron transporters (DMT1 and ferroportin) and inflammatory markers. After surgery, sTfR and PPIX were decreased. Serum hepcidin levels were increased despite the significant reduction in inflammation. DMT1 abundance was negatively correlated with higher level of serum hepcidin. Ferroportin abundance was not modified. This study shed a new light in effective iron recovery pathways after SG involving suppression of inflammation, improvement of iron absorption, iron supply and efficiency of erythropoiesis, and finally beneficial control of iron homeostasis by hepcidin. Thus, recommendations for iron supplementation of patients after SG should take into account these new parameters of iron status assessment.

Zinc Protoporphyrin-to-Heme Ratio and Ferritin as Measures of Iron Sufficiency in the Neonatal Intensive Care Unit.

OBJECTIVES: To evaluate ferritin and zinc protoporphyrin-to-heme (ZnPP/H) ratios as biomarkers of iron status in neonates, determine how specific clinical events affected these measures, and assess how iron status changed during hospitalization. STUDY DESIGN: We performed a retrospective study of all infants with paired ferritin and ZnPP/H measurements between October 2014 and May 2016. Concordance of these measurements, effects of sepsis, red blood cell transfusion, erythropoietin treatment, and iron supplementation were assessed. Iron status was measured over time. RESULTS: A total of 228 patients (mean birth weight 1.3 kg, median gestational age 29 weeks) were evaluated. Mean log ZnPP/H values in infants with and without sepsis were not significantly different (4.98 µmol/mol vs 4.97 µmol/mol, adjusted P = .103), whereas log-transformed ferritin values increased significantly during infection (5.23 ng/mL vs 4.04 ng/mL, adjusted P < .001). Ferritin also increased more significantly than ZnPP/H following red blood cell transfusion (ferritin: mean 5.03 ng/mL vs 4.0 ng/mL, P < .001; ZnPP/H: mean 4.85 µmol/mol vs 4.98 µmol/mol, P < .001). The mean iron supplementations at 30, 60, and 90 days were 5.4, 6.9, and 7.4 mg/kg/day, respectively. Ferritin values decreased with advancing postnatal age (adjusted P < .001), with 66% of ferritin values less than 76 ng/mL. Treatment with erythropoietin increased ZnPP/H, but not ferritin levels. CONCLUSIONS: Ferritin is more significantly affected by inflammatory events such as sepsis and transfusion than ZnPP/H, thus, ZnPP/H may be a more reliable marker of iron status in this population. Infants showed worsening iron sufficiency over time despite supplementation above American Academy of Pediatrics guidelines.

[Biological diagnosis of iron deficiency in children]. / Diagnostic biologique de la carence martiale chez l'enfant.

Measurement of serum ferritin (SF) is currently the laboratory test recommended for diagnosing iron deficiency. In the absence of an associated disease, a low SF value is an early and highly specific indicator of iron deficiency. The WHO criteria proposed to define depleted storage iron are 12µg/L for children under 5 years and 15µg/L for those over 5 years. A higher threshold of 30µg/L is used in the presence of infection or inflammation. Iron deficiency anemia, with typical low mean corpuscular volume and mean corpuscular hemoglobin, is only present at the end stage of iron deficiency. Other diagnostic tests for iron deficiency including iron parameters (low serum iron, increased total iron-binding capacity, low transferrin saturation) and erythrocyte traits (low mean corpuscular volume, increased zinc protoporphyrin) provide little additional diagnostic value over SF. In children, serum soluble transferrin receptor (sTfR) has been reported to be a sensitive indicator of iron deficiency and is relatively unaffected by inflammation. On the other hand, sTfR is directly related to extent of erythroid activity and not commonly used in clinical practice. In population surveys, approaches based on combinations of markers have been explored to improve the specificity and sensitivity of diagnostic. In addition to Hb value determination, a combination of parameters (among transferrin saturation, zinc protoporphyrin, mean corpuscular volume or serum ferritin) was generally used to assess iron deficiency. More recently sTfR/ ferritin index were evaluated, sTfR in conjunction with SF allowing to better distinguishing iron deficiency from inflammatory anemia. Also, hepcidin measurements appeared an interesting marker for diagnosing iron deficiency and identifying individuals in need of iron supplementation in populations where inflammatory or infectious diseases are frequently encountered. Reticulocyte Hb content (CHr) determination is an early parameter of iron deficiency erythropoiesis. CHr can be measured with several automated hematology analyzers and so, used for individual's iron status assessment. In addition to Hb concentration determination, individual's iron status is commonly assessed in the pediatric clinical practice by the SF measurement accompanied by the determination of C-reactive protein for detection of a simultaneous acute infection and/or inflammation.

Zinc protoporphyrin/heme ratio as parameter of iron status in moderately preterm infants: natural course and associations in the first 4 months.

OBJECTIVE: To determine the natural course of zinc protoporphyrin/heme ratio (ZnPP/H) and its role in the detection of iron deficiency (ID) and iron-deficiency anemia (IDA) in the first 4 months of life in moderately preterm infants. STUDY DESIGN: ZnPP/H was measured at 1 week, 6 weeks and 4 months postnatal age in a prospective cohort of 161 Dutch infants born at a gestational age of 32+0 to 36+6 weeks who did not receive an erythrocyte transfusion or iron supplementation. RESULTS: ZnPP/H levels decreased in the first 6 weeks and increased thereafter. At 4 months postnatal age, ZnPP/H was higher in the 11 (8.5%) infants with IDA (mean (s.d.): 260.8 (16.1)) but not in the 27 (21.3%) infants with ID (mean (s.d.): 177.0 (15.1)) compared with normal infants (mean (s.d.): 157.3 (12.5)). CONCLUSION: In moderately preterm infants, ZnPP/H can be of additional value to detect infants at risk for IDA due to iron-deficient erythropoiesis at 4 months of age.

Impact of small-quantity lipid-based nutrient supplement on hemoglobin, iron status and biomarkers of inflammation in pregnant Ghanaian women.

We examined hemoglobin (Hb, g/L), iron status (zinc protoporphyrin, ZPP, µmol/mol heme, and transferrin receptor, TfR, mg/L) and inflammation (C-reactive protein, CRP and alpha-1 glycoprotein, AGP) in pregnant Ghanaian women who participated in a randomized controlled trial. Women (n = 1320) received either 60 mg Fe + 400-µg folic acid (IFA); 18 micronutrients including 20-mg Fe (MMN) or small-quantity lipid-based nutrient supplements (SQ-LNS, 118 kcal/d) with the same micronutrient levels as in MMN, plus four additional minerals (LNS) daily during pregnancy. Intention-to-treat analysis included 349, 354 and 354 women in the IFA, MMN and LNS groups, respectively, with overall baseline mean Hb and anemia (Hb <100) prevalence of 112 and 13.3%, respectively. At 36 gestational weeks, overall Hb was 117, and anemia prevalence was 5.3%. Compared with the IFA group, the LNS and MMN groups had lower mean Hb (120 ± 11 vs. 115 ± 12 and 117 ± 12, respectively; P < 0.001), higher mean ZPP (42 ± 30 vs. 50 ± 29 and 49 ± 30; P = 0.010) and TfR (4.0 ± 1.3 vs. 4.9 ± 1.8 and 4.6 ± 1.7; P < 0.001), and greater prevalence of anemia (2.2% vs. 7.9% and 5.8%; P = 0.019), elevated ZPP (>60) [9.4% vs. 18.6% and 19.2%; P = 0.003] and elevated TfR (>6.0) [9.0% vs. 19.2% and 15.1%; P = 0.004]. CRP and AGP concentrations did not differ among groups. We conclude that among pregnant women in a semi-urban setting in Ghana, supplementation with SQ-LNS or MMN containing 20 mg iron resulted in lower Hb and iron status but had no impact on inflammation, when compared with iron (60 mg) plus folic acid (400 µg). The amount of iron in such supplements that is most effective for improving both maternal Hb/iron status and birth outcomes requires further evaluation. This trial was registered at ClinicalTrials.gov as: NCT00970866.

Delaying Iron Therapy until 28 Days after Antimalarial Treatment Is Associated with Greater Iron Incorporation and Equivalent Hematologic Recovery after 56 Days in Children: A Randomized Controlled Trial.

BACKGROUND: Iron therapy begun concurrently with antimalarial treatment may not be well absorbed because of malaria-induced inflammation. Delaying the start of iron therapy may permit better iron absorption and distribution. OBJECTIVE: We compared erythrocyte iron incorporation in children who started iron supplementation concurrently with antimalarial treatment or 28 d later. We hypothesized that delayed iron supplementation would be associated with greater incorporation and better hematologic recovery. METHODS: We enrolled 100 children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L who presented to Mulago Hospital, Kampala, into a randomized trial of iron therapy. All children were administered antimalarial treatment. Children with zinc protoporphyrin (ZPP) ≥80 µmol/mol heme were randomly assigned to start iron supplementation concurrently with the antimalarial treatment [immediate iron (I) group] or 28 d later [delayed iron (D) group]. All children were administered iron-stable isotope (57)Fe on day 0 and (58)Fe on day 28. We compared the percentage of iron incorporation at the start of supplementation (I group at day 0 compared with D group at day 28, aim 1) and hematologic recovery at day 56 (aim 2). RESULTS: The percentage of iron incorporation (mean ± SE) was greater at day 28 in the D group (16.5% ± 1.7%) than at day 0 in the I group (7.9% ± 0.5%; P < 0.001). On day 56, concentrations of hemoglobin and ZPP and plasma ferritin, soluble transferrin receptor (sTfR), hepcidin, and C-reactive protein did not differ between the groups. On day 28, the hemoglobin (mean ± SD) and plasma iron markers (geometric mean; 95% CI) reflected poorer iron status in the D group than in the I group at this intervening time as follows: hemoglobin (105 ± 15.9 compared with 112 ± 12.4 g/L; P = 0.04), ferritin (39.3 µg/L; 23.5, 65.7 µg/L compared with 79.9 µg/L; 58.3, 110 µg/L; P = 0.02), sTfR (8.9 mg/L; 7.4, 10.7 mg/L compared with 6.7 mg/L; 6.1, 7.5 mg/L; P = 0.01), and hepcidin (13.3 ng/mL; 8.3, 21.2 ng/mL compared with 38.8 ng/mL; 28.3, 53.3 ng/mL; P < 0.001). CONCLUSIONS: Delaying the start of iron improves incorporation but leads to equivalent hematologic recovery at day 56 in Ugandan children with malaria and anemia. These results do not demonstrate a clear, short-term benefit of delaying iron. This trial was registered at clinicaltrials.gov as NCT01754701.

Iron Supplementation Affects Hematologic Biomarker Concentrations and Pregnancy Outcomes among Iron-Deficient Tanzanian Women.

BACKGROUND: Iron deficiency is a highly prevalent micronutrient abnormality and the most common cause of anemia globally, worsening the burden of adverse pregnancy and child outcomes. OBJECTIVE: We sought to evaluate the response of hematologic biomarkers to iron supplementation and to examine the predictors of the response to iron supplementation among iron-deficient pregnant women. METHODS: We identified 600 iron-deficient (serum ferritin ≤12 µg/L) pregnant women, aged 18-45 y, presenting to 2 antenatal clinics in Dar es Salaam, Tanzania using rapid ferritin screening tests, and prospectively followed them through delivery and postpartum. All women received 60 mg Fe and 0.25 mg folate daily from enrollment until delivery. Proportions meeting the thresholds representing deficient hematologic status including hemoglobin <110 g/L, ferritin ≤12 µg/L, serum soluble transferrin receptor (sTfR) >4.4 mg/L, zinc protoporphyrin (ZPP) >70 mmol/L, or hepcidin ≤13.3 µg/L at baseline and delivery were assessed. The prospective change in biomarker concentration and the influence of baseline hematologic status on the change in biomarker concentrations were assessed. Regression models were estimated to assess the relation of change in biomarker concentrations and pregnancy outcomes. RESULTS: There was significant improvement in maternal biomarker concentrations between baseline and delivery, with increases in the concentrations of hemoglobin (mean difference: 15.2 g/L; 95% CI: 13.2, 17.2 g/L), serum ferritin (51.6 µg/L; 95% CI: 49.5, 58.8 µg/L), and serum hepcidin (14.0 µg/L; 95% CI: 12.4, 15.6 µg/L) and decreases in sTfR (-1.7 mg/L; 95% CI: -2.0, -1.3 mg/L) and ZPP (-17.8 mmol/L; 95% CI: -32.1, 3.5 mmol/L). The proportions of participants with low hemoglobin, ferritin, and hepcidin were 73%, 93%, and 99%, respectively, at baseline and 34%, 12%, and 46%, respectively, at delivery. The improvements in biomarker concentrations were significantly greater among participants with poor hematologic status at baseline - up to 12.1 g/L and 14.5 µg/L for hemoglobin and ferritin concentrations, respectively. For every 10-g/L increase in hemoglobin concentration, there was a 24% reduced risk of perinatal mortality (RR = 0.76; 95% CI: 0.59, 0.99) and a 23% reduced risk of early infant mortality (RR = 0.77; 95% CI: 0.60, 0.99). The risk of anemia at delivery despite supplementation was predicted by baseline anemia (RR = 2.11; 95% CI: 1.39, 3.18) and improvements in ferritin concentration were more likely to be observed in participants who took iron supplements for up to 90 d (RR = 1.41; 95% CI: 1.13, 1.76). CONCLUSION: Iron supplementation decreases the risk of maternal anemia and increases the likelihood of infant survival among iron-deficient Tanzanian pregnant women. Interventions to promote increased duration and adherence to iron supplements may also provide greater health benefits.

Comparison of iron status 28 d after provision of antimalarial treatment with iron therapy compared with antimalarial treatment alone in Ugandan children with severe malaria.

BACKGROUND: The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation. OBJECTIVES: We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment.. DESIGN: Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations ≥80 µmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron. RESULTS: At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 µmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 µg/L (95% CI: 84.2, 121.0 µg/L) compared with 152.9 µg/L (128.8, 181.6 µg/L), respectively; P ≤ 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P < 0.011]. CONCLUSIONS: Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration. This trial was registered at clinicaltrials.gov as NCT01093989.

Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers.

N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans.

[A neonate with anaemia of prematurity: zinc protoporphyrin identifies iron deficiency anaemia without iron deficiency]. / Een prematuur met anemie: zinkprotoporfyrine identificeert ijzergebreksanemie zonder ijzergebrek.

Anaemia is a common problem in premature infants and is generally easy to treat with iron supplementation. If the anaemia persists despite appropriate correction of deficiencies, more extensive evaluation is required. We describe a case of a premature male infant with a production-deficient anaemia without metabolic deficiencies, eventually identified as anaemia of prematurity. This type of anaemia is commonly diagnosed but its highly variable and complex aetiology and phenotype are often poorly understood. A probable explanation for the anaemia of prematurity in this case was a transient iron incorporation defect, identifiable by high levels of zinc protoporphyrin.

A multicenter, randomized clinical trial of IV iron supplementation for anemia of traumatic critical illness*.

OBJECTIVE: To evaluate the efficacy of IV iron supplementation of anemic, critically ill trauma patients. DESIGN: Multicenter, randomized, single-blind, placebo-controlled trial. SETTING: Four trauma ICUs. PATIENTS: Anemic (hemoglobin < 12 g/dL) trauma patients enrolled within 72 hours of ICU admission and with an expected ICU length of stay of more than or equal to 5 days. INTERVENTIONS: Randomization to iron sucrose 100 mg IV or placebo thrice weekly for up to 2 weeks. MEASUREMENTS AND MAIN RESULTS: A total of 150 patients were enrolled. Baseline iron markers were consistent with functional iron deficiency: 134 patients (89.3%) were hypoferremic, 51 (34.0%) were hyperferritinemic, and 64 (42.7%) demonstrated iron-deficient erythropoiesis as evidenced by an elevated erythrocyte zinc protoporphyrin concentration. The median baseline transferrin saturation was 8% (range, 2-58%). In the subgroup of patients who received all six doses of study drug (n = 57), the serum ferritin concentration increased significantly for the iron as compared with placebo group on both day 7 (808.0 ng/mL vs 457.0 ng/mL, respectively, p < 0.01) and day 14 (1,046.0 ng/mL vs 551.5 ng/mL, respectively, p < 0.01). There was no significant difference between groups in transferrin saturation, erythrocyte zinc protoporphyrin concentration, hemoglobin concentration, or packed RBC transfusion requirement. There was no significant difference between groups in the risk of infection, length of stay, or mortality. CONCLUSIONS: Iron supplementation increased the serum ferritin concentration significantly, but it had no discernible effect on transferrin saturation, iron-deficient erythropoiesis, hemoglobin concentration, or packed RBC transfusion requirement. Based on these data, routine IV iron supplementation of anemic, critically ill trauma patients cannot be recommended (NCT 01180894).

Iron status biomarkers and C-reactive protein in children aged 19 to 72 months in Chile.

BACKGROUND: The Chilean Ministry of Health has combated iron deficiency through the delivery of fortified milk by the National Complementary Feeding Program (NCFP). OBJECTIVE: To assess iron status and associations between biomarkers of iron status and serum C-reactive protein (CRP) in 218 beneficiaries of the NCFP aged 19 to 72 months in Santiago and Valparaiso, Chile. METHODS: Blood was collected from a cross-sectional representative sample. Iron status (measured by hemoglobin, zinc protoporphyrin, and serum ferritin levels) and inflammation (according to CRP level) were determined. RESULTS: Serum CRP level was positively associated with serum ferritin and zinc protoporphyrin levels (r = 0.16 and r = 0.15; p = .0168 and p = .0290, respectively). Serum ferritin was higher among children with high CRP (> 10 mg/dL) than among those with low CRP (< or = 10 mg/dL) (p = .003). After adjustment for 10, 6, and 5 mg/L CRP, the prevalence of low serum ferritin changed from 56.4% without adjustment to 60.6%, 61.5%, and 42.7%, respectively, and the prevalence of high zinc protoporphyrin changed from 22.9% to 21.6%, 17.4%, and 17.9%, respectively. There were no differences between regions in biomarkers of iron status. There was no association between consumption of fortified milk and the prevalence of abnormal serum ferritin (< 15 microg/L) after adjustment for sex, age, and breastfeeding (OR, 1.00; 95% CI, 0.99 to 1.01; p = .288). After adjustment for 10 mg/L CRP, 5.5% were classified as having iron-deficiency anemia, 42.7% as having iron-deficiency erythropoiesis, 17.9% as having depleted iron stores, and 35.8% as having normal iron status. CONCLUSIONS. CRP level was positively associated with: serum ferritin and zinc protoporphyrin levels. Chilean children aged 19 to 72 months from Santiago and Valparaiso who were beneficiaries of the NCFP had a low prevalence of iron-deficiency anemia, a high prevalence of iron-deficiency erythropoiesis, and a moderate prevalence of depleted iron stores.

Declining blood lead and zinc protoporphyrin levels in Ecuadorian Andean children.

OBJECTIVES: To investigate current lead (Pb) exposure in children living in Andean Ecuadorian communities. Blood Pb (PbB) and zinc protoporphyrin (ZPP) levels were used respectively as biomarkers of acute and chronic Pb poisoning. The current PbB-ZPP levels were compared with previous pediatric PbB-ZPP levels recorded over years in the study area. DESIGN AND METHODS: Samples of whole blood were collected from 22 Andean children of Quechua and Mestizo backgrounds and measured for PbB concentrations by graphite furnace atomic absorption spectroscopy. ZPP/heme ratio and ZPP whole blood (ZPP WB) levels were measured with a hematofluorometer. RESULTS: The mean PbB level for children in the current study group was 14.5 µg/dL, which was significantly lower than the mean PbB level of 41.1 µg/dL found in the same study area in the 1996-2000 test period, and lower than the 22.2 µg/dL mean level found in the 2003-2007 period. The current mean ZPP/heme ratio was 102.1 µmol/mol, and the mean ZPP WB level was 46.3 µg/dL, both lower than values previously found in children in the study area. CONCLUSION: While the current pediatric PbB-ZPP levels in the study area remain elevated in some children, the overall levels indicate a decline relative to levels observed in the same Pb-contaminated area in the period between 1996 and 2007. The elevated ZPP levels suggest a history of chronic Pb exposure, and potential iron deficiency in some children. The overall reduction in PbB-ZPP levels suggests a positive outcome of a Pb-exposure education and prevention program, and the therapeutic intervention of succimer chelation therapy.

Iron supplementation in premature infants using the zinc protoporphyrin to heme ratio: short- and long-term outcomes.

OBJECTIVE: The objective of this study was to determine the effect of incrementally higher doses of iron on the zinc protoporphyrin to heme ratio (ZnPP/H) and serum ferritin, and developmental outcomes in premature infants at risk for iron deficiency. STUDY DESIGN: Infants eligible for this prospective, randomized blinded trial were between 27 and 30 completed weeks of gestation, older than 1 week of age and tolerating 100 ml kg(-1) per day of enteral feedings. The control group was treated with 2.2 mg kg(-1) per day of ferrous sulfate and the treatment group was treated with 3 to 12 mg kg(-1) per day based on the ZnPP/H. Infants had follow-up with Bayley exams at 6 and 24 months corrected age. Statistical evaluation included Student's t-tests and Fisher's exact test. RESULT: Eighty-one infants were enrolled (40 control, 41 treatment). The average total iron dose for the control group was 2.2 mg kg(-1) per day and for the treatment group was 10.4 mg kg(-1) per day (P<0.05). The ZnPP/H was not different between the two groups. The ferritin at the end of the study was decreased in the control group but remained stable in the treatment group (control initial 202±109 ng ml(-1), final 168±141 ng ml(-1) (P<0.05); treatment initial 187±131 ng ml(-1), final 176±118 ng ml(-1)). At 24 months, infants with psychomotor development index <85 occurred in 25% of the subjects in the control group and in 7% of subjects in the treatment group in a post hoc analysis (odds ratio, 4.2; 95% confidence interval, 0.7 to 43, P=0.07). CONCLUSION: The ZnPP/H may not be a reliable marker of iron status when used in a short period of time during iron supplementation. Infants treated with a lower dose of ferrous sulfate had a decreasing serum ferritin and a trend toward increased motor delays at 24 months.

Imported occupational lead poisoning: report of four cases.

BACKGROUND: In most industrialized countries, occupational lead poisoning has become increasingly rare, however this metal remains a serious health hazard in the rest of the world. REPORT OF CASES: We observedfour male patients (aged 35 / 54 years) who had suffered recurrent abdominal pain due to recent lead exposure (for 7 to 13 months) in two Chinese battery recycling plants. On their return to Italy, three of them presented normocytic, normochromic anaemia. The diagnosis was confirmed by high lead levels in the blood and urine, decreased erythrocyte delta-aminolevulinic acid dehydratase (ALA-D), raised erythrocyte zinc protoporphyrin (ZP), and elevated urinary excretion of b-aminolevulinic acid (ALA-U) and porphyrins. Chelation with EDTA resulted in increased urinary lead excretion, improvement of the clinical picture, decreased ZP, and progressive normalization of the other lead biomarkers (Pb-B, ALA-D, ALA-U, urinary porphyrins). CONCLUSIONS: Temporary work in developing countries may result in imported lead poisoning. Differential diagnosis of this unusual condition requires careful medical history collection and specific toxicological analysis. Preventive measures for workers going abroad are needed.

Overweight impairs efficacy of iron supplementation in iron-deficient South African children: a randomized controlled intervention.

BACKGROUND: Many countries in the nutrition transition have high rates of iron deficiency (ID) and overweight (OW). ID is more common in OW children; this may be due to adiposity-related inflammation reducing iron absorption. OBJECTIVE: We investigated whether weight status predicts response to oral iron supplementation in ID South African children. DESIGN: A placebo-controlled trial of oral iron supplementation (50 mg, 4 × weeks for 8.5 months) was done in ID 6- to 11-year-old children (n=321); 28% were OW or obese. BMI-for-age z-scores (BAZ), hepcidin (in a sub-sample), hemoglobin, serum ferritin (SF), transferrin receptor (TfR), zinc protoporphyrin (ZnPP) and C-reactive protein (CRP) were measured; body iron was calculated from the SF to TfR ratio. RESULTS: At baseline, BAZ correlated with CRP (r=0.201, P<0.001) and CRP correlated with hepcidin (r=0.384, P<0.001). Normal weight children supplemented with iron had significantly lower TfR concentrations at endpoint than the OW children supplemented with iron and the children receiving placebo. Higher BAZ predicted higher TfR (ß=0.232, P<0.001) and lower body iron (ß=-0.090, P=0.016) at endpoint, and increased the odds ratio (OR) for remaining ID at endpoint in both the iron and placebo groups (iron: OR 2.31, 95% CI: 1.13, 4.73; placebo: OR 1.78, 95% CI: 1.09, 2.91). In the children supplemented with iron, baseline hepcidin and BAZ were significant predictors of endpoint TfR, with a trend towards a hepcidin × BAZ interaction (P=0.058). CONCLUSION: South African children with high BAZ have a two-fold higher risk of remaining ID after iron supplementation. This may be due to their higher hepcidin concentrations reducing iron absorption. Thus, the current surge in OW in rapidly developing countries may undercut efforts to control anemia in vulnerable groups. The trial is registered at clinicaltrials.gov as NCT01092377.

Zinc protoporphyrin-to-heme ratios in high-risk and preterm infants.

OBJECTIVES: To refine the reference range for the zinc protoporphyrin-to-heme ratio (ZnPP/H) of preterm infants, we assessed the impact of maternal risk factors on ZnPP/H and evaluated the impact of changes in iron supplementation on iron status. STUDY DESIGN: The reference range for neonatal ZnPP/H was refined using prospective data from 31 reference infants ≤ 35 weeks' postmenstrual age (PMA) plus retrospective data from 51 infants <30 weeks' PMA, and 59 infants 30-40 weeks' PMA. Cord blood and first week of life values were compared when both were available. The impact of maternal risk factors was assessed by examining prospectively collected ZnPP/H from 48 high-risk infants. The effect of changing iron supplementation guidelines was evaluated by retrospective chart review of serial ZnPP/H from 194 infants. RESULTS: Cord ZnPP/H was lower at 30-35 weeks' gestation than at 24-26 weeks' gestation (P = .01). Cord ZnPP/H values from insulin-dependent diabetic mothers were elevated compared with reference values. Changing the iron supplementation protocol was not associated with improved ZnPP/H measurements. CONCLUSIONS: Cord blood and postnatal reference ranges for ZnPP/H are defined. Iron balance depends on a complex interaction of prenatal and postnatal factors.

[Acute lead poisoning: a singular case of hemolytic anemia and lead colic]. / Intossicazione acuta da piombo: un caso singolare di anemia emolitica e colica saturnina.

BACKGROUND: Acute lead poisoning due to food intake is exceptional in adults and often associated with mental illness OBJECTIVES: to describe a case report of acute lead intoxication with haemolytic anemia and lead colic. METHODS: A 41-year old male patient was admitted to hospital for abdominal pain and persistent constipation. Abdominal X-ray showed a radiopaque mass in the caecum and progressive anaemia was observed The patient was discharged with a diagnosis of bowel obstruction. Due to persistence of the symptoms he was again hospitalized; abdominal X-ray showed diffuse radiopaque particles in the colon and haemoglobin (hb) had dropped to 8.7 g/dl. Blood levels of lead and zinc protoporphryin were 106.7 microg/dl and 6.6 microg/gHb, respectively. The timely start of chelating therapy led to a rapid return to normal peripheral blood counts and a decline in blood lead levels. RESULTS: Although acute lead poisoning due to intake with food is exceptional in adults and often associated with mental illness, in this case, it was not possible to clarify the route and vehicle of ingestion of the toxic. Lead body burden was shown as a caecal mass, probably as a result of ingesting a single bolus of lead dust which, considering the size and density of the mass, was estimated as weighing several grammes. This acute lead intake induced an acute haemolysis due to enhanced fragility of the erythrocyte membrane. CONCLUSIONS: In the course of acute lead intoxication, the critical organ is not the bone marrow, but rather the red blood cell, leading to haemolysis and anaemia.

The effectiveness of fortified flour on micro-nutrient status in rural female adults in China.

This research was designed to evaluate the effectiveness of fortified flour on micronutrient status in poor rural adult women. A total of 4,700 farmers as the intervention group were supplied with multi-nutrient fortified wheat flour for three years, while 2750 farmers as the control group were supplied with unfortified wheat flour. Wheat flour was fortified with vitamins A, B-1, B-2, niacin, folic acid, iron and zinc in mg/kg at 2, 3.5, 3.5, 35, 1, 20 and 25, respectively. Blood samples were taken at baseline and annually from about 300 volunteer adult females aged 20-60 years in each group. Hemoglobin (Hb), serum retinol, serum iron, free erythrocyte protoporphyrin, serum zinc were measured annually and a dietary survey conducted every 6 months. Average intakes of fortified micronutrients increased to adequate levels with average consumption of fortified flour at 117 g per person per day. Intervention groups showed a significant increase in terms of Hb levels from 24 m to 36 m and anemia rate decreased from 15.1% at baseline to 10.8% at 36 m. Serum iron levels of the intervention group significantly increased from 12 m to 36 m and erythrocyte protoporphyrin decreased from 24 m to 36 m respectively. Serum retinol and serum zinc of intervention group improved significantly from 12 m to 36 m compared with baseline and control group. The results showed that the fortified flour could improve micronutrient status of adult females in poor rural region.