Synergistic effects of iron deficiency and lead exposure on blood lead levels in children

Background  

Lead poisoning is a well recognized environmental health problem in children. Independent association of iron deficiency and lead exposure with elevated blood lead level (BLL) has been reported. Whether iron deficiency in combination with chronic lead exposure increases BLL and susceptibility to its harmful effects in children needs to be elucidated.     

Interaction of iron deficiency and lead and the hematologic findings in children with severe lead poisoning

Microcytic anemia, long considered an effect of lead poisoning, may in fact result from coexisting iron deficiency. In this study, how RBC size, hemoglobin, and zinc protoporphyrin vary as a function of iron status in a group of children with high lead levels was examined. Charts of all children (N = 51) admitted to Cook County Hospital for treatment of lead poisoning in 1981 to 1983 were reviewed for data on age, blood lead level, hemoglobin concentration, MCV, transferrin saturation and zinc protoporphyrin level. The mean lead level was 86 micrograms/dL and the range was 63 to 190 micrograms/dL. Children with transferrin saturation values less than 7% had a mean MCV of 56 microL, hemoglobin of 8.9 g/dL, and zinc protoporphyrin of 693 micrograms/dL; for those with saturations of 7% to 16%, the values were 61 microL, 10.1 g/dL, and 581 micrograms/dL, respectively; the children with saturations greater than 16% had normal mean MCVs and hemoglobin concentrations (74 microL and 11.4 g/dL) and a mean zinc protoporphyrin value of 240 micrograms/dL (P less than .0005). Multiple linear regression was used to correct for effect of age, and transferrin saturation remained the most important predictor of MCV, hemoglobin, and zinc protoporphyrin levels; the addition of lead did not improve the models. Results of this study suggest that iron deficiency is strongly associated with some of the observed toxicities of lead. Also, lead poisoning can exist without producing microcytosis or anemia, and zinc protoporphyrin concentration may not be a sensitive indicator of lead level in the absence of iron deficiency.     

No difference in iron status between children with low and moderate lead exposure.

We compared the iron status between children 11 to 33 months old with confirmed blood lead levels of 20 to 44 microg/dL and demographically similar children with blood lead levels of <10 microg/dL. There were no differences. Laboratory investigation or empirical treatment for iron deficiency is not justified on the basis of moderately elevated blood lead levels alone.     

Combined iron deficiency and lead poisoning in children. Effect on FEP levels

Concern for the concomitant occurrence of iron deficiency and elevated blood lead in children is raised by animal studies documenting increased gastrointestinal lead absorption in the presence of iron deficiency. An elevation in free erythrocyte protoporphyrin (FEP) above 35 mg/dl is seen with both iron deficiency and lead toxicity. To determine whether the degree of elevation in FEP is useful in predicting which children with elevated blood lead levels have concomitant iron deficiency, 109 children suspected of having an elevated lead burden were studied. A complete blood count, reticulocyte count, FEP, lead, and ferritin were measured on each child. The effect of the independent variables, lead and iron status, both alone and in combination, on the dependent variable, FEP, was analyzed through a linear regression model. Lead status alone accounted for 42 percent of the explained variance in FEP, and the lead-iron interaction increased the explained variance by only an additional 1 percent. Screening for iron deficiency in children with elevated blood lead should continue to be based on dietary and socioeconomic risk factors and not on degree of elevation in FEP.     

Malabsorption of iron in children with iron deficiency.

Inability to absorb oral iron is believed to be an extremely rare cause of therapeutic failure in the treatment of iron deficiency anemia. Six patients who had failed to respond to oral iron therapy were studied by a simple oral absorption test and contrasted with 25 patients with untreated iron deficiency anemia and 10 normal subjects. All six of the patients who were therapeutic failures demonstrated impaired iron absorption in the absence of other clinical evidence of gastrointestinal disease. In the 25 newly diagnosed patients with iron deficiency. 24 demonstrated elevated iron absorptions while 10 ironreplete normal subjects had minimal elevations in their serum iron values following the administration of the test dose of 1 mg of elemental iron per kilogram. When the therapeutic failures were treated with parenteral iron, all had a therapeutic response. In addition, after treatment the impaired absorption of iron improved transiently. All children who absorbed iron readily responded to oral iron therapy.     

Thrombocytopenia in children with severe iron deficiency

PURPOSE: Thrombocytopenia has been reported in some children with severe iron deficiency anemia, but the validity of the association and the mechanism of the thrombocytopenia are not well established. Six children with severe iron deficiency and thrombocytopenia are described, and the literature is reviewed. PATIENTS AND METHODS: Clinical, hematologic, and morphologic data were collected and analyzed for six patients referred for evaluation of severe microcytic anemia and thrombocytopenia. RESULTS: The children ranged in age from 14 months to 17 years (median age 27 months) and were otherwise healthy. The iron deficiency was nutritional in four patients younger than 3 years of age and resulted from menstrual blood loss in two teenage girls. The mean initial hemoglobin was 2.5 g/dL (range 1.6-4.7) and the mean initial platelet count was 64 x 109/L (range 11-102). Bone marrow examinations were performed in three patients and showed increased numbers of megakaryocytes. After treatment with therapeutic doses of oral iron, all the patients showed rapid increases in their platelet counts. CONCLUSIONS: These observations validate and extend previous reports of an association between severe iron deficiency and thrombocytopenia. The increased numbers of megakaryocytes and the extremely rapid increase in platelet counts after initiation of iron therapy suggest an essential role for iron in a late stage of thrombopoiesis.     

Reversal of iron deficiency anemia-induced peripheral neuropathy by iron treatment in children with iron deficiency anemia

The effects of iron deficiency anemia (IDA) on nerve conduction and efficiency of iron therapy were investigated by peripheral nerve-electrophysiological measurements. Eighteen children (10 boys, eight girls; mean age 31 +/- 1.3 months) with IDA and 12 healthy children (six boys, six girls; mean age 29 +/- 1.3 months) were enrolled into the study. Nerve conduction velocity was measured in the median and posterior tibial nerve. After nerve conduction values were determined in the patients and controls, 6 mg/kg/24 h ferrous sulphate was given orally to the patients for 3 months and nerve conduction velocity tests were performed again. Median/motor and sensory nerve conduction velocity and tibial/motor nerve distal-amplitute values of children with IDA were lower than for the control group (p < 0.05, p < 0.01 and p < 0.001 respectively). With iron supplementation these values increased to the normal levels and even higher than control levels for some parameters. In correlation studies between whole blood parameters and nerve conduction velocity results, there was a correlation between median/sensory nerve conduction velocity values and serum iron levels. Additionally there was a correlation between some nerve conduction velocity values and age. In conclusion, the evidence from this preliminary study suggests that peripheral neuropathy may develop in children with IDA. Peripheral neuropathy symptoms in these patients may be improved by iron therapy.     

Salivary iron status in children with iron deficiency and iron overload.

Forty anaemic (iron deficiency anaemia-27, thalassemia major-8, and aplastic anaemia-5) and 10 non-anaemic children (serving as controls) aged from 8 months to 10 years were selected for the study. The salivary iron was significantly higher in iron deficient and iron overload conditions compared to controls. The mean salivary:serum iron ratio was same in control and iron overload cases, while it was twice as high in iron deficient anaemic children. The correlation between salivary iron and serum iron was significant (r = 0.7392, P less than 0.001) in these cases. The iron deficient anaemic children with hypoalbuminaemia had significantly reduced serum and salivary protein (P less than 0.001), but iron concentrations in serum and saliva remained unaltered. The salivary protein level had significant correlations with serum albumin and serum protein (P less than 0.001). Thus, the iron in saliva is maintained at a higher level and more so in iron deficiency anaemia; it correlates well with serum iron (r = 0.6853, P less than 0.001) in iron deficient anaemic children also and is not affected by co-existing hypoproteinaemic situation.     

Neutrophil hypersegmentation in children with iron deficiency anemia

Neutrophil hypersegmentation (NH) is usually associated with vitamin B12 or folic acid deficiency. NH is seen in iron deficiency anemia but there are very few case studies about this. Neutrophil hypersegmentation was evaluated in 94 children with iron deficiency anemia; 23 healthy children comprised the control group with similar ages. NH was found in 76/94 (81%) in the study group and 2/23 (9%) of the control group. The difference was statistically significant (p < .01).     

Policy statement on iron deficiency in pre-school-aged children

AIM: We aimed to develop policy in relation to three areas: (i) the diagnosis of iron deficiency; (ii) maternal-infant issues and the prevention of iron deficiency; and (iii) the treatment of iron deficiency. METHODS: Within each of these topic areas we completed a literature review and developed recommendations to help direct activities of the Royal Australasian College of Physicians, update paediatricians and guide clinical practice. RESULTS: Iron deficiency can be defined using cut-off values for laboratory measures of iron status or, if an intercurrent infection is not present, by demonstrating a response to a therapeutic trial of iron. The appropriate measures of iron status vary depending upon the presence of intercurrent infection. Full-term babies are born with iron stores sufficient to meet their needs to age 4-6 months but premature infants are not. After age 6 months infants are dependent upon dietary iron from complementary foods even with continued breastfeeding. Infants <33 weeks gestation or <1800 g birthweight should receive iron from 4 weeks of age. In most settings recommended treatment of iron deficiency is with oral ferrous sulphate as a single or twice daily dose of between 3 and 6 mg/kg/day. CONCLUSIONS: Iron deficiency is prevalent and an important determinant of child health. Precise and accurate diagnosis remains challenging. Iron supplementation is required for premature and low-birthweight infants. Oral iron salts remain the recommended treatment of choice in most instances.     

儿童铁缺乏症及缺铁性贫血防治进展

铁是人体必需微量元素中含量最多的一种,膳食中可利用铁长期不足,常可导致铁缺乏(iron deficiency)和缺铁性贫血(iron deficiency anemia,IDA)[1].小儿IDA是机体对铁的摄入不足,需要量增加或铁丢失过多造成机体内贮存铁缺乏,导致血红蛋白合成障碍引起的一种贫血[1].     

Effects of iron deficiency versus iron deficiency anemia on brainstem auditory evoked potentials in infancy

There has been little or no evidence of brainstem auditory evoked potentials (BAEPs) among infants with iron deficiency (ID) that is not severe enough to cause anemia. To our knowledge, the effect of ID on auditory functions and/or potentials has not been investigated previously, though it seems reasonable that it should be associated with BAEP measures intermediate between those observed in iron deficiency anemia (IDA) and in iron sufficiency, considering the role of iron in myelin formation and maintenance. We therefore aimed in this study to investigate the effect of ID on BAEPs by comparing three groups of infants with ID, IDA and iron sufficiency (control) both before and after iron treatment (in iron-deficient groups). Three groups of infants (IDA, n = 25; ID, n = 24; Control, n = 44) were compared on the basis of hematological laboratory parameters and BAEP measurements both at entry into and after (12 weeks treatment with oral iron in IDA and ID groups) the study. BAEP measurements recorded at 85 dB both at entry into and after the study were not significantly different among the groups, although a sufficient response to iron treatment was achieved in iron-deficient groups (Group I and Group II). The only positive finding determined in our study was a slight decrease in latencies obtained at the end of the study when compared to the pre-study values in all three groups of the study in accordance with the expected age-dependent developmental changes. Although no negative electrophysiological effect of ID on brainstem auditory functions was found in the present study, further longer term (late childhood or adult) studies are necessary to elucidate the relationships among anemia (maybe other than IDA), ID and auditory functions, and clinical implications of hearing loss (if any) should be questioned.