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Early lead exposure and childhood adiposity in Mexico city.
Liu, Y, Peterson, KE, Montgomery, K, Sánchez, BN, Zhang, Z, Afeiche, MC, Cantonwine, DE, Ettinger, AS, Cantoral, A, Schnaas, L, et al
International journal of hygiene and environmental health. 2019;(6):965-970
Abstract
BACKGROUND Prenatal and early childhood lead exposures have been associated with reduced weight in infants and young children, while studies that have examined such associations in children during peripubescence are rare. OBJECTIVES We investigated the associations of prenatal and early-life exposure to lead with indices of adiposity in peripubertal children living in Mexico City. METHODS Maternal bone lead (as a proxy for cumulative fetal exposure) was assessed at 1 month postpartum. Blood samples were obtained from children annually from 1 to 4 years. Multivariable linear regression models were used to examine the association between each lead biomarker and BMI z-score, waist circumference, sum of skinfolds and body fat percentage in 248 children aged 8-16 years. RESULTS After adjusting for covariates, maternal patella lead was associated with lower child BMI z-score (β = -0.02, 95% CI: 0.03, -0.01, p = 0.004), waist circumference (β = -0.12 cm, 95% CI: 0.22, -0.03, p = 0.01), sum of skinfolds (β = -0.29 mm, 95% CI: 0.50, -0.08, p = 0.007) and body fat percentage (β = -0.09%, 95% CI: 0.17, -0.01, p = 0.03). No significant associations were detected from the postnatal exposure period. CONCLUSIONS We observed a significant and inverse association of prenatal lead exposure with body composition in Mexican children, suggesting the potential role of early lead exposure in the fetal programming of child growth. Further research on the biological mechanisms underlying these associations is needed.
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Effect of Residential Lead-Hazard Interventions on Childhood Blood Lead Concentrations and Neurobehavioral Outcomes: A Randomized Clinical Trial.
Braun, JM, Hornung, R, Chen, A, Dietrich, KN, Jacobs, DE, Jones, R, Khoury, JC, Liddy-Hicks, S, Morgan, S, Vanderbeek, SB, et al
JAMA pediatrics. 2018;(10):934-942
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IMPORTANCE Childhood lead exposure is associated with neurobehavioral deficits. The effect of a residential lead hazard intervention on blood lead concentrations and neurobehavioral development remains unknown. OBJECTIVE To determine whether a comprehensive residential lead-exposure reduction intervention completed during pregnancy could decrease residential dust lead loadings, prevent elevated blood lead concentrations, and improve childhood neurobehavioral outcomes. DESIGN, SETTING, AND PARTICIPANTS This longitudinal, community-based randomized clinical trial of pregnant women and their children, the Health Outcomes and Measures of the Environment (HOME) Study, was conducted between March 1, 2003, and January 31, 2006. Pregnant women attending 1 of 9 prenatal care clinics affiliated with 3 hospitals in the Cincinnati, Ohio, metropolitan area were recruited. Of the 1263 eligible women, 468 (37.0%) agreed to participate and 355 women (75.8%) were randomized in this intention-to-treat analysis. Participants were randomly assigned to receive 1 of 2 interventions designed to reduce residential lead or injury hazards. Follow-up on children took place at 1, 2, 3, 4, 5, and 8 years of age. Data analysis was performed from September 2, 2017, to May 6, 2018. MAIN OUTCOMES AND MEASURES Residential dust lead loadings were measured at baseline and when children were 1 and 2 years of age. At 1, 2, 3, 4, 5, and 8 years of age, the children's blood lead concentrations as well as behavior, cognition, and executive functions were assessed. RESULTS Of the 355 women randomized, 174 (49.0%) were assigned to the intervention group (mean [SD] age at delivery, 30.1 (5.5) years; 119 [68.3%] self-identified as non-Hispanic white) and 181 (50.9%) to the control group (mean [SD] age at delivery, 29.2 [5.7] years; 123 [67.9%] self-identified as non-Hispanic white). The intervention reduced the dust lead loadings for the floor (24%; 95% CI, -43% to 1%), windowsill (40%; 95% CI, -60% to -11%), and window trough (47%; 95% CI, -68% to -10%) surfaces. The intervention did not statistically significantly reduce childhood blood lead concentrations (-6%; 95% CI, -17% to 6%; P = .29). Neurobehavioral test scores were not statistically different between children in the intervention group than those in the control group except for a reduction in anxiety scores in the intervention group (β = -1.6; 95% CI, -3.2 to -0.1; P = .04). CONCLUSIONS AND RELEVANCE Residential lead exposures, as well as blood lead concentrations in non-Hispanic black children, were reduced through a comprehensive lead-hazard intervention without elevating the lead body burden. However, this decrease did not result in substantive neurobehavioral improvements in children. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00129324.
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Effects of wheat-flour biscuits fortified with iron and EDTA, alone and in combination, on blood lead concentration, iron status, and cognition in children: a double-blind randomized controlled trial.
Bouhouch, RR, El-Fadeli, S, Andersson, M, Aboussad, A, Chabaa, L, Zeder, C, Kippler, M, Baumgartner, J, Sedki, A, Zimmermann, MB
The American journal of clinical nutrition. 2016;(5):1318-1326
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BACKGROUND Lead is a common neurotoxicant and its absorption may be increased in iron deficiency (ID). Thus, iron fortification to prevent ID in populations is a promising lead mitigation strategy. Two common fortificants are ferrous sulfate (FeSO4) and ferric sodium EDTA (NaFeEDTA). EDTA can chelate iron and lead. OBJECTIVES Our study objective was to determine the effects of iron and EDTA, alone and in combination, on blood lead (BPb) concentration, iron status, and cognition. DESIGN In this 2 × 2 factorial, double-blind placebo-controlled trial, 457 lead-exposed Moroccan children were stratified by school and grade and randomly assigned to consume biscuits (6 d/wk at school) containing 1) ∼8 mg Fe as FeSO4, 2) ∼8 mg Fe as NaFeEDTA that contained ∼41 mg EDTA, 3) ∼41 mg EDTA as sodium EDTA (Na2EDTA), or 4) placebo for 28 wk. The primary outcome was BPb concentration; secondary outcomes were iron status and cognitive outcomes from subtests of the Kaufman Assessment Battery for Children and the Hopkins Verbal Learning Test. These outcomes were measured at baseline and endpoint. All data were analyzed by intention-to-treat. RESULTS The adjusted geometric mean BPb concentration at baseline was 4.3 μg/dL (95% CI: 4.2, 4.3 μg/dL), and at endpoint these values were 3.3 μg/dL (95% CI: 3.1, 3.5 μg/dL) for FeSO4, 2.9 μg/dL (95% CI: 2.7, 3.0 μg/dL) for NaFeEDTA, 3.3 μg/dL (95% CI: 3.1, 3.5 μg/dL) for EDTA, and 3.7 μg/dL (95% CI: 3.5, 3.9 μg/dL) for placebo. We found an effect of iron (P = 0.009) and EDTA (P = 0.012) for reduced BPb concentrations at endpoint, but no iron × EDTA interaction. Iron fortification improved iron status, but there were no positive effects of iron or EDTA on cognitive test scores. CONCLUSIONS Food fortification with iron and EDTA additively reduces BPb concentrations. Our findings suggest that NaFeEDTA should be the iron fortificant of choice in lead-exposed populations. This trial was registered at clinicaltrials.gov as NCT01573013.
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Effect of N-acetylcysteine administration on the expression and activities of antioxidant enzymes and the malondialdehyde level in the blood of lead-exposed workers.
Kasperczyk, S, Dobrakowski, M, Kasperczyk, A, Machnik, G, Birkner, E
Environmental toxicology and pharmacology. 2014;(2):638-47
Abstract
We investigated whether treatment with N-acetylcysteine (NAC) reduces oxidative stress intensity and restores the expression and activities of superoxide dismutase (Sod1, SOD), catalase (Cat, CAT) and glutathione peroxidase (Gpx1, GPx) in lead-exposed workers. The exposed population was divided randomly into two groups. Workers in the first group (reference group, n=49) were not administered any drugs, while workers in the second group (n=122) were treated with NAC at three doses for 12 weeks (200 mg, 400 mg, 800 mg/day). NAC administered orally to lead-exposed workers normalized antioxidant enzyme activities in blood cells. Oxidative stress intensity measured as malondialdehyde (MDA) levels in serum, leukocytes and erythrocytes significantly decreased after NAC administration. NAC may be an alternative therapy for chronic lead intoxication.
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Blood lead concentration is not altered by high-dose vitamin D supplementation in children and young adults with HIV.
Groleau, V, Herold, RA, Schall, JI, Wagner, JL, Dougherty, KA, Zemel, BS, Rutstein, RM, Stallings, VA
Journal of pediatric gastroenterology and nutrition. 2013;(3):316-9
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OBJECTIVES Optimal vitamin D status is known to have beneficial health effects and vitamin D supplements are commonly used. It has been suggested that vitamin D supplementation may increase blood lead in children and adults with previous lead exposure. The objective was to determine the safety regarding lead toxicity during 12 weeks of high-dose vitamin D3 supplementation in children and young adults with human immunodeficiency virus (HIV). METHODS Subjects with HIV (8-24 years) were randomized to vitamin D3 supplementation of 4000 or 7000 IU/day and followed at 6 and 12 weeks for changes in serum 25-hydroxy vitamin D (25D) and whole-blood lead concentration. This was a secondary analysis of a larger study of vitamin D3 supplementation in children and adolescents with HIV. RESULTS In 44 subjects (75% African American), the baseline mean ± standard deviation serum 25D was 48.3±18.6 nmol/L. Fifty percent of subjects had baseline serum 25D <50.0 nmol/L. Serum 25D increased significantly with D3 supplementation during the 12 weeks. No subject had a whole-blood lead >5.0 μg/dL at baseline or during subsequent visits. Whole-blood lead and 25D were not correlated at baseline, and were negatively correlated after 12 weeks of supplementation (P=0.014). Whole-blood lead did not differ between those receiving 4000 and 7000 IU of vitamin D3. CONCLUSIONS High-dose vitamin D3 supplementation and the concomitant increased serum 25D did not result in increased whole-blood lead concentration in this sample of children and young adults living in a northeastern urban city.
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Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations.
Spector, JT, Navas-Acien, A, Fadrowski, J, Guallar, E, Jaar, B, Weaver, VM
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011;(9):2786-92
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BACKGROUND Low-level lead exposure is widespread and has been implicated as a chronic kidney disease (CKD) risk factor. However, studies evaluating associations of lead dose with newer, potentially more accurate, estimates of kidney function, in participants with a wide range of glomerular filtration rates (GFRs), are scarce. METHODS We compared associations of blood lead and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and cystatin C single variable, multivariable and combined creatinine/cystatin C equations in 3941 adults who participated in the 1999-2002 National Health and Nutrition Examination Survey cystatin C subsample. RESULTS Geometric mean blood lead was 1.7 μg/dL. After multivariable adjustment, differences [95% confidence interval (CI)] in mean eGFR for a doubling of blood lead were -1.9 (-3.2, -0.7), -1.7 (-3.0, -0.5) and -1.4 (-2.3, -0.5) mL/min/1.73 m(2), using the cystatin C single variable, multivariable and combined creatinine/cystatin C equations, respectively, reflecting lower eGFR with increased blood lead. The corresponding differences (95% CI) were -0.9 (-1.9, 0.02) and -0.9 (-1.8, 0.01) using the creatinine-based MDRD and CKD-EPI equations, respectively. In participants aged ≥60 years, differences in mean eGFR ranged from -3.0 to -4.5 mL/min/1.73 m(2), and odds of reduced eGFR (<60 mL/min/1.73 m(2)) were increased for all estimates of GFR. CONCLUSIONS These results support the inclusion of cystatin C-based eGFR in future lead research and provide additional evidence for environmental lead exposure as a CKD risk factor.
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Effect of calcium supplementation on blood lead levels in pregnancy: a randomized placebo-controlled trial.
Ettinger, AS, Lamadrid-Figueroa, H, Téllez-Rojo, MM, Mercado-García, A, Peterson, KE, Schwartz, J, Hu, H, Hernández-Avila, M
Environmental health perspectives. 2009;(1):26-31
Abstract
BACKGROUND Prenatal lead exposure is associated with deficits in fetal growth and neurodevelopment. Calcium supplementation may attenuate fetal exposure by inhibiting mobilization of maternal bone lead and/or intestinal absorption of ingested lead. OBJECTIVE Our goal was to evaluate the effect of 1,200 mg dietary calcium supplementation on maternal blood lead levels during pregnancy. METHODS In a double-blind, randomized, placebo-controlled trial conducted from 2001 through 2003 in Mexico City, we randomly assigned 670 women in their first trimester of pregnancy to ingest calcium (n = 334) or placebo (n = 336). We followed subjects through pregnancy and evaluated the effect of supplementation on maternal blood lead, using an intent-to-treat analysis by a mixed-effects regression model with random intercept, in 557 participants (83%) who completed follow-up. We then conducted as-treated analyses using similar models stratified by treatment compliance. RESULTS Adjusting for baseline lead level, age, trimester of pregnancy, and dietary energy and calcium intake, calcium was associated with an average 11% reduction (0.4 microg/dL) in blood lead level relative to placebo (p = 0.004). This reduction was more evident in the second trimester (-14%, p < 0.001) than in the third (-8%, p = 0.107) and was strongest in women who were most compliant (those who consumed > or = 75% calcium pills; -24%, p < 0.001), had baseline blood lead > 5 microg/dL (-17%, p < 0.01), or reported use of lead-glazed ceramics and high bone lead (-31%, p < 0.01). CONCLUSION Calcium supplementation was associated with modest reductions in blood lead when administered during pregnancy and may constitute an important secondary prevention effort to reduce circulating maternal lead and, consequently, fetal exposure.
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Long-term outcome of repeated lead chelation therapy in progressive non-diabetic chronic kidney diseases.
Lin-Tan, DT, Lin, JL, Yen, TH, Chen, KH, Huang, YL
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2007;(10):2924-31
Abstract
BACKGROUND Previous research suggest that repeated lead-chelation therapy decelerates progression of renal insufficiency in non-diabetic (non-DM) patients with high-normal body lead burden (BLB). Study findings are limited by relatively short-term follow-up and small sample size. METHODS A total of 116 non-DM patients with chronic kidney diseases (serum creatinine level of 1.5-3.9 mg/dl), high-normal BLB (>60 microg and <600 microg) and no lead exposure history were randomly assigned to a chelation or control group in this 4-year clinical trial. For 3 months, the 58 chelation group patients received initial lead-chelation therapy with calcium disodium EDTA, and the 58 control group patients received placebos. During the ensuing 48 months, repeated chelation therapy was administered weekly to chelation group patients unless, on repeated testing, BLB was <60 microg; the control group patients received weekly placebo infusions for 5 weeks at 6-month intervals. RESULTS Mean change in the glomerular filtration rate (GFR) in the chelation group was -1.8 +/- 8.8 ml/min/1.73 m(2), as compared with -12.7 +/- 8.4 ml/min/1.73 m(2) in the control group (P <0.0001) at study end. Chelation group rates of decline in the GFR was lower than that in the control group, although they had similar decline rates before chelation. At study end, 18 patients, including 15 control group patients, had elevated serum creatinine levels to two times the baseline values. Both Cox and Kaplan-Meier analysis demonstrated repeated chelation therapy was the important determining factor of progression of renal insufficiency. CONCLUSIONS Repeated chelation therapies can, over a four-year period, slow progression of renal insufficiency in non-DM patients with high-normal BLB.
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Iron and/or zinc supplementation did not reduce blood lead concentrations in children in a randomized, placebo-controlled trial.
Rosado, JL, López, P, Kordas, K, García-Vargas, G, Ronquillo, D, Alatorre, J, Stoltzfus, RJ
The Journal of nutrition. 2006;(9):2378-83
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There is increasing interest in the interaction of nutritional deficiencies with toxic metals. Iron deficiency and elevated blood lead concentrations (PbB) reportedly occur together, and zinc also plays an important role in lead metabolism. The objective was to evaluate the effect of zinc and/or iron supplementation on PbB of children attending schools in the neighborhood of a smelter complex for 6 mo. We conducted a double-blind, placebo-controlled field trial in 9 elementary schools located within a 3.5-km radius of a metal foundry in Torreón, Mexico. Of the 602 first-graders enrolled, 517 completed supplementation and had initial and final PbBs. Children were given either 30 mg of iron, 30 mg of zinc, both, or a placebo daily for 6 mo. Baseline and final measures included nutritional status and PbB. The overall prevalence of iron and zinc deficiencies was 12.1 and 30.3%, respectively, and 10.3% were anemic. The PbB concentration decreased in all experimental groups (P < 0.05). After controlling for initial PbB, groups administered zinc and/or iron did not have lower PbB concentrations than the placebo group (P < 0.05). In conclusion, iron supplementation of lead-exposed children significantly improved iron status but did not reduce PbBs. Zinc supplementation did not reduce PbBs independently of zinc nutritional status. Neither iron nor zinc can be recommended as the sole treatment for lead-exposed school children.
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Efficacy of iron and/or zinc supplementation on cognitive performance of lead-exposed Mexican schoolchildren: a randomized, placebo-controlled trial.
Rico, JA, Kordas, K, López, P, Rosado, JL, Vargas, GG, Ronquillo, D, Stoltzfus, RJ
Pediatrics. 2006;(3):e518-27
Abstract
OBJECTIVE Lead exposure in children has been associated with both global and specific cognitive deficits. Although chelation therapy is advised for children with blood lead concentrations of >44 microg/dL, treatment options for children with lower blood lead values are limited. Because lead absorption is related to children's nutritional status, micronutrient supplements may be 1 strategy for combating low-level, chronic lead exposure. This study was designed to test the efficacy of iron and zinc supplementation for lowering blood lead concentrations and improving cognitive performance in schoolchildren who live in a lead-contaminated city. METHODS This randomized, double-blind, placebo-controlled field trial was conducted in public elementary schools in Torreón, an industrialized city in northern Mexico. A metal foundry, located close to the city center and within 3.5 km of 9 schools, was the main source of lead exposure. A total of 602 children who were aged 6 to 8 years and regularly attending first grade in the study schools were enrolled. Children were given 30 mg of iron, 30 mg of zinc, both, or a placebo daily for 6 months. A total of 527 completed the treatment, and 515 were available for long-term follow-up, after another 6 months without supplementation. Eleven cognitive tests of memory, attention, visual-spatial abilities, and learning were administered at baseline and each follow-up. RESULTS There were no consistent or lasting differences in cognitive performance among treatment groups. CONCLUSIONS Daily supplementation with iron and/or zinc may be of limited usefulness for improving cognition in lead-exposed schoolchildren. However, these treatments may be effective in settings with higher prevalence of nutritional deficiencies or in younger children.