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Manning ER, Duan Q, Brokamp C. Incorporating Parcel-Based Housing Conditions to Increase the Precision of Identifying Children With Elevated Blood Lead. JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE 2025; 31:621-630. [PMID: 39837309 DOI: 10.1097/phh.0000000000002109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
CONTEXT Area-level predictive models are commonly used to screen children for blood lead levels (BLLs) greater than the Center for Disease Control and Prevention (CDC) blood lead reference value (BLRV) of 3.5 µg/dL. OBJECTIVES To increase screening accuracy and precision by creating a parcel-level model incorporating housing characteristics to predict parcels where children are at high risk. DESIGN Residential addresses associated with child blood lead tests were linked to neighborhood- and parcel-level characteristics and proximity to lead sources. Regression forests were fit using different predictor combinations and compared using cross-validated accuracy and decile-based agreement across all residential parcels. SETTING Hamilton County, Ohio, United States. PARTICIPANTS Children less than 6 years of age with blood lead tests between January 2020 and April 2023. MAIN OUTCOME MEASURE Cross-validated model accuracy and decile-based agreement across residential parcels. RESULTS 27,782 tests were matched to a residential parcel. Regression forests using Parcel + Source (70.8% AUC) and Neighborhood + Parcel + Source predictors (70.3% AUC) had the highest cross-validated accuracy for predicting BLLs >3.5 µg/dL. Parcel-level predictions revealed heterogeneity of risk across parcels within the same tract. CONCLUSIONS Parcel characteristics improved the accuracy of predicting locations of children with BLLs >3.5 µg/dL and can help identify children at high risk living in low-risk areas. A parcel-level identification of housing-based lead hazards could guide and support action to prevent pediatric lead exposure.
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Affiliation(s)
- Erika Rasnick Manning
- Author Affiliations: Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center (Mrs Manning, Dr Duan, and Dr Brokamp); and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio (Dr Brokamp)
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Barg G, Menéndez JA, Friedl JA, Hoyos S, Queirolo EI, Mañay N, Ghazal D, Kordas K. Lead exposure, peripheral neurotransmitter levels and cognitive control: A neurobehavioral study in children from Montevideo, Uruguay. Neurotoxicology 2025; 108:159-168. [PMID: 40189059 DOI: 10.1016/j.neuro.2025.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 03/18/2025] [Accepted: 03/31/2025] [Indexed: 04/12/2025]
Abstract
INTRODUCTION Lead exposure has been linked to significant brain disruptions. However, research on the neural correlates of blood lead level (BLL) and cognitive control remains limited. To address this gap, we investigated event-related potentials (ERPs) during an inhibition task, in conjunction with measurements of serum neurotransmitter availability. METHOD 38 children (58 % girls) aged 9-13 years were evaluated using a go/no-go task. Total hits, commission and omission errors were registered. During the task, ERPs were recorded using a 59-channel array. BLL was measured using atomic absorption via flame or graphite furnace ionization techniques. In an exploratory approach, serum level of neurochemical factors such as BDNF, dopamine, serotonin, and GABA in serum were assessed using enzyme-linked immunosorbent assays. RESULTS Median BLL was 1.00 µg/dL (IQR = 0.7, 1.7). In generalized linear regression models with Poisson distribution, BLL was associated with a 23 % higher commission errors (IRR [95 % CI] = 1.23 [1.14, 1.34]) and 16 % (1.16 [1.08, 1.22]) total omission errors after adjustment for age, sex, maternal education and hemoglobin level. Two ERPs linked to conflict monitoring (N2) and response inhibition (P3) showed positive, although non-significant, modulation by BLL. Regarding the neurotransmitters, dopamine was correlated with BLL particularly when measured concurrently (Spearman's rho = 0.51, p < 0.005) CONCLUSIONS: BLL are associated with deficits in the inhibition of prepotent responses during pre-adolescence. Such failures can hinder academic and social development and increase risky behaviors. This study is the first to examine peripheral neurotransmitter levels and brain activity associated with cognitive control in Pb-exposed children.
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Affiliation(s)
- Gabriel Barg
- Department of Neurosciences and Learning, Universidad Católica del Uruguay, Montevideo, Uruguay.
| | - Juan Andrés Menéndez
- Department of Neurosciences and Learning, Universidad Católica del Uruguay, Montevideo, Uruguay
| | - Juan Andrés Friedl
- Department of Neurosciences and Learning, Universidad Católica del Uruguay, Montevideo, Uruguay
| | - Sandra Hoyos
- Department of Neurosciences and Learning, Universidad Católica del Uruguay, Montevideo, Uruguay
| | - Elena I Queirolo
- Department of Neurosciences and Learning, Universidad Católica del Uruguay, Montevideo, Uruguay
| | - Nelly Mañay
- Faculty of Chemistry, University of the Republic of Uruguay (UDELAR), Montevideo, Uruguay
| | - Diala Ghazal
- Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, Buffalo, NY, USA
| | - Katarzyna Kordas
- Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA
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Gu Q, Liu J, Zhang X, Huang A, Yu X, Wu K, Huang Y. Association between heavy metals exposure and risk of attention deficit hyperactivity disorder (ADHD) in children: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry 2025; 34:921-941. [PMID: 39126497 DOI: 10.1007/s00787-024-02546-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024]
Abstract
Heavy metals can negatively affect children's neurodevelopment, yet the relationship between heavy metals exposure and attention deficit hyperactivity disorder (ADHD) in children remains unclear. We aimed to examine associations between exposure to five common heavy metals (lead, arsenic, mercury, cadmium, and manganese) with neurodevelopmental toxicity and the risk of ADHD in children. Online databases of PubMed, Web of Science, and Embase were searched before February 29, 2024. A total of 31 studies involving 25,258 children were included in the final analysis. Our findings revealed that lead exposure was positively associated with ADHD risk in children (OR = 1.95, 95% CI: 1.57-2.41) overall, while the associations varied among different WHO regions, with the strongest in the Americas. Sensitivity analyses revealed significant associations between arsenic (OR = 1.53, 95% CI: 1.01-2.32) and manganese (OR = 1.79, 95% CI: 1.28-2.49) exposure and ADHD risk after omitting one study. Arsenic exposure was positively associated with ADHD risk in studies conducted in the Americas and adjusted for environmental smoke exposure. Positive associations between manganese exposure and ADHD risk were also found in several subgroup analyses. No significant associations were found for mercury and cadmium exposure. Dose-response meta-analysis suggested that children with higher blood lead levels exhibited a higher probability of ADHD diagnosis. Lead exposure consistently increases the risk of ADHD in children, while arsenic and manganese exposure may be associated with ADHD under different occasions. More research is required to understand heavy metals' impact on ADHD across varying exposure levels, particularly in less contaminated regions.
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Affiliation(s)
- Qianfei Gu
- School of Public Health, Shantou University, Shantou, Guangdong Province, China
- Mental Health Center of Shantou University, Shantou, Guangdong Province, China
| | - Jiayu Liu
- Mental Health Center of Shantou University, Shantou, Guangdong Province, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong Province, China
| | - Xuanzhi Zhang
- Mental Health Center of Shantou University, Shantou, Guangdong Province, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong Province, China
| | - Anyan Huang
- Shantou Maternity & Child Healthcare Hospital, Shantou, Guangdong Province, China
| | - Xinle Yu
- Mental Health Center of Shantou University, Shantou, Guangdong Province, China
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong Province, China
| | - Kusheng Wu
- Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong Province, China.
| | - Yanhong Huang
- Mental Health Center of Shantou University, Shantou, Guangdong Province, China.
- Shantou University Medical College-Faculty of Medicine of University of Manitoba Joint Laboratory of Biological Psychiatry, Shantou, Guangdong Province, China.
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Chen Y, Sun L, Shi H, Mao G, Zhao T, Feng W, Yang L, Wu X. Protective Effect of Protocatechuic Acid on Oxidative Damage and Cognitive Impairment in Pb-Induced Rats. Biol Trace Elem Res 2024; 202:5556-5571. [PMID: 38374329 DOI: 10.1007/s12011-024-04095-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 02/03/2024] [Indexed: 02/21/2024]
Abstract
Protocatechuic acid (PCA), a class of water-soluble phenolic acid abundant in the human diet, has been shown to be of great nutritional interest and to have medicinal value. However, the protective effects against lead (Pb)-induced body injury have not been elucidated. In this study, we explored the protective effect of PCA on Pb-induced oxidative damage and cognitive impairment in rats. The results showed that PCA could reduce the Pb content in rat bodies (blood, bone, brain, liver, and kidney) after Pb exposure. Moreover, PCA may inhibit Pb-induced oxidative damage by increasing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreasing the level of malondialdehyde (MDA) in the brain, liver, and kidney. In addition, PCA may alleviate Pb-induced learning and memory impairment by upregulating neurotransmitter levels; maintaining the normal function of N-methyl-D-aspartate receptors (NMDARs); and promoting Ca2+ influx, thus activating signaling molecules, related protein kinases, and transcription factors in the cAMP-PKA-CREB pathway. In general, PCA could reduce oxidative stress and ameliorate the learning and memory deficits in Pb-treated rats, indicating that PCA may be an effective preventive agent and treatment or plumbism.
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Affiliation(s)
- Yao Chen
- School of the Environment and Safety, School of Emergency Management, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China
- Institute of Environmental Health and Ecological Security, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China
| | - Lu Sun
- School of the Environment and Safety, School of Emergency Management, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China
| | - Hengyu Shi
- School of the Environment and Safety, School of Emergency Management, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China
| | - Guanghua Mao
- School of the Environment and Safety, School of Emergency Management, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China
| | - Ting Zhao
- School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China
| | - Weiwei Feng
- School of the Environment and Safety, School of Emergency Management, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China
- Institute of Environmental Health and Ecological Security, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China
| | - Liuqing Yang
- School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China.
| | - Xiangyang Wu
- School of the Environment and Safety, School of Emergency Management, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China.
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Pennington AF, Smith MR, Chuke SO, Cornwell CR, Allwood PB, Courtney JG. Effects of Blood Lead Levels <10 µg/dL in School-Age Children and Adolescents: A Scoping Review. Pediatrics 2024; 154:e2024067808F. [PMID: 39352036 PMCID: PMC11610497 DOI: 10.1542/peds.2024-067808f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/20/2024] [Indexed: 10/03/2024] Open
Abstract
CONTEXT Lead exposures among school-age children are a major public health issue. Although the harmful effects of lead exposure during the first years of life are well known, there is not as much understanding of the effects of low levels of lead exposure during later childhood. OBJECTIVES To review the effects of blood lead levels (BLLs) <10 µg/dL in school-age children and adolescents. DATA SOURCES We searched Medline, Embase, Global health, CINAHL, Scopus, and Environmental Science Collection databases between January 1, 2000, and May 11, 2023. STUDY SELECTION We included peer-reviewed English-language articles that presented data on the effects of BLLs <10 µg/dL in individuals ages 5 through 18 years. DATA EXTRACTION Data on country, population, analytic design, sample size, age, BLLs, outcomes, covariates, and results were extracted. RESULTS Overall, 115 of 3180 screened articles met the inclusion criteria. The reported mean or median BLL was <5 µg/dL in 98 articles (85%). Of the included articles, 89 (77%) presented some evidence of an association between BLLs <10 µg/dL during school age and detrimental outcomes in a wide range of categories. The strongest evidence of an association was for the outcomes of intelligence quotient and attention-deficit/hyperactivity disorder diagnoses or behaviors. LIMITATIONS Few articles controlled for BLLs at age <5 years, limiting conclusions about the relation between later BLLs and outcomes. CONCLUSIONS BLLs <10 µg/dL in school-age children and adolescents may be associated with negative outcomes. This review highlights areas that could benefit from additional investigation.
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Affiliation(s)
- Audrey F. Pennington
- Lead Poisoning Prevention and Surveillance Branch, Division of Environmental Health Science and Practice, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA USA
| | - Madison R. Smith
- Lead Poisoning Prevention and Surveillance Branch, Division of Environmental Health Science and Practice, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA USA
| | - Stella O. Chuke
- Lead Poisoning Prevention and Surveillance Branch, Division of Environmental Health Science and Practice, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA USA
| | - Cheryl R. Cornwell
- Lead Poisoning Prevention and Surveillance Branch, Division of Environmental Health Science and Practice, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA USA
| | - Paul B. Allwood
- Lead Poisoning Prevention and Surveillance Branch, Division of Environmental Health Science and Practice, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA USA
| | - Joseph G. Courtney
- Lead Poisoning Prevention and Surveillance Branch, Division of Environmental Health Science and Practice, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA USA
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Liu SH, Chen Y, Bellinger D, de Water E, Horton M, Téllez-Rojo MM, Wright R. Pre-natal and early life lead exposure and childhood inhibitory control: an item response theory approach to improve measurement precision of inhibitory control. Environ Health 2024; 23:71. [PMID: 39232724 PMCID: PMC11375946 DOI: 10.1186/s12940-023-01015-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 08/30/2023] [Indexed: 09/06/2024]
Abstract
BACKGROUND Neurodevelopmental performance tasks are often separately analyzed, even when they tap into a similar construct. This may yield mixed findings for associations of an exposure-neurobehavioral outcome. We develop an item response theory (IRT) approach to integrate multiple task variables together to improve measurement precision of the underlying construct. We apply this approach to create an integrative measure of childhood inhibitory control, and study impacts of pre/post-natal lead exposure. METHODS Using data from a prospective cohort based in Mexico (N = 533), we created an inhibitory control scale that integrates accuracy and reaction time information from four inhibitory control tasks (Go/NoGo Letter, Go/NoGo Neutral, Go/NoGo Happy, Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test, Condition 3). Using a generalized partial credit item response theory model, we estimated an inhibitory control index for each participant. We then assessed adjusted associations between umbilical cord blood and 4-year lead and childhood inhibitory control. We developed a resampling approach to incorporate error estimates from the inhibitory control variable to confirm the consistency of the lead-inhibitory control associations. We modeled time-varying associations of lead with each inhibitory control measure separately. RESULTS Participants had a median age of 9 years; 51.4% were males. Umbilical cord blood [-0.06 (95% CI: -0.11, -0.01)] and 4-year lead [-0.07 (95% CI: -0.12, -0.02)] were associated with inhibitory control index at 8-10 years. A resampling approach confirmed that 4-year lead was consistently associated with childhood inhibitory control index. Umbilical cord blood and 4-year lead were each associated with 3 out of 8 measures in separate models. CONCLUSION This is the first application of IRT in environmental epidemiology to create a latent variable for inhibitory control that integrates accuracy and reaction time information from multiple, related tasks. This framework can be applied to other correlated neurobehavioral assessments or other phenotype data.
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Affiliation(s)
- Shelley H Liu
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Yitong Chen
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - David Bellinger
- Department of Neurology, Boston Children's Hospital, Boston, MA, USA
| | | | - Megan Horton
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Martha M Téllez-Rojo
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Robert Wright
- Center for Nutrition and Health Research, National Institute of Public Health, Cuernavaca, Morelos, Mexico
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Farmani R, Mehrpour O, Kooshki A, Nakhaee S. Exploring the link between toxic metal exposure and ADHD: a systematic review of pb and hg. J Neurodev Disord 2024; 16:44. [PMID: 39090571 PMCID: PMC11292919 DOI: 10.1186/s11689-024-09555-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 07/02/2024] [Indexed: 08/04/2024] Open
Abstract
INTRODUCTION Attention-Deficit/Hyperactivity Disorder (ADHD) is a recognized neurodevelopmental disorder with a complex, multifactorial origin. Lead (Pb) and mercury (Hg) are highly toxic substances that can potentially impair brain development and have been implicated in the development of ADHD. This systematic review aims to analyze the epidemiological literature regarding the association between Pb and Hg exposure and the diagnosis of ADHD. METHODS From November 1983 to June 2, 2023, a comprehensive search was conducted in multiple databases and search engines, including PubMed, Web of Science, Scopus, and Google Scholar. Observational studies (case-control, cohort, and cross-sectional) measuring Pb and Hg levels in various biological samples (blood, hair, urine, nail, saliva, teeth, and bone) of children with ADHD or their parents and their association with ADHD symptoms were included. RESULTS Out of 2059 studies, 87 met the inclusion criteria and were included in this systematic review. Approximately two-thirds of the 74 studies investigating Pb levels in different biological samples reported associations with at least one subtype of ADHD. However, most studies examining Hg levels in various biological samples found no significant association with any ADHD subtype, although there were variations in exposure periods and diagnostic criteria. CONCLUSION The evidence gathered from the included studies supports an association between Pb exposure and the diagnosis of ADHD, while no significant association was found with Hg exposure. Importantly, even low levels of Pb were found to elevate the risk of ADHD. Further research is needed to explore the comprehensive range of risk factors for ADHD in children, considering its significance as a neurodevelopmental disorder.
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Affiliation(s)
- Reyhane Farmani
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Omid Mehrpour
- Michigan Poison & Drug Information Center, Wayne State University School of Medicine, Detroit, MI, USA
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran
| | - Alireza Kooshki
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Samaneh Nakhaee
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran.
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Yan H, Zhai B, Feng R, Wang P, Yang F, Zhou Y. Distribution of blood lead and cadmium levels in healthy children aged 0 to 18 years and analysis of related influencing factors in Henan, China: data findings from 2017 to 2022. Ital J Pediatr 2024; 50:43. [PMID: 38454525 PMCID: PMC10918998 DOI: 10.1186/s13052-024-01614-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 02/24/2024] [Indexed: 03/09/2024] Open
Abstract
BACKGROUND There is still a lack of data on blood lead levels (BLLs) and blood lead levels (BLLs) in healthy children of all ages from 0 to 18 years in China. This study was performed to analyze the BLLs and BCLs in healthy children aged 0-18 years from 2017 to 2022 in urban and rural areas of Henan Province, Central China, as well as their relationships with socio-demographic variables and certain relevant exposure factors. To provide a basis for evaluating public health policy development and exposure risk management. METHODS This was an observational study containing data from 17 prefecture-level cities in Henan, China. Blood Pb and Cd levels were determined using a triple quadrupole inductively coupled plasma mass spectrometer equipped with an autosampler. We first calculated the concentrations of Pb and Cd elements in participants of different genders, ages and years, and then created visual graphs depicting the distribution of each element in terms of gender, age and year (2017-2022). The rates between different groups were compared using the Chi-square test or Fisher exact test (if applicable). The means were compared by one-way ANOVA, medians were compared with the Kruskal-Wallis rank-sum test. Generalized linear models (GLM) were performed to estimate the effects of various factors on blood Pb and Cd concentrations in children. RESULTS We recruited a total of 25,920 children (16,142 boys and 9,778 girls) aged 0.01 to 18.00 years (2.58 (1.00,6.25)). The median of BLLs was 23.48µg/L, around 9.39% of studied children had elevated BLLs. The median of BCLs was 0.66µg/L, around 1.84% of studied children had elevated BCLs. The median blood Pb concentration was higher in boys (23.90µg/L) than in girls (22.75µg/L) (P<0.001). The median blood Pb concentration was highest in the 3-7 years group (24.51µg/L) and the median blood Cd concentration was highest in the 1-3 years group (0.66µg/L) among all age groups. Both BLLs and BCLs were substantially higher in children in 2020-2022 compared to 2017-2019. Rural children had lower BLLs and higher BCLs. The results of the generalized linear model showed that children in households using Oil, coal, pellet or other wood as a fuel for heating, children with higher frequency of exposure to tobacco smoke and beverage intake had significantly increased chances of elevated BLLs and BCLs. CONCLUSIONS Pb and Cd exposure of children in this area is relatively low, but associated risk factors continue to exist in vulnerable populations. This study is the first big data analysis of Pb and Cd in children in Henan, China, and provides baseline information for future research.
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Affiliation(s)
- Hui Yan
- Henan Provincial Clinical Research Center for Pediatric Diseases, Henan Key Laboratory of Pediatric Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China
- Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China
| | - Bo Zhai
- Henan Provincial Clinical Research Center for Pediatric Diseases, Henan Key Laboratory of Pediatric Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China
- Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China
| | - Ruiling Feng
- Henan Provincial Clinical Research Center for Pediatric Diseases, Henan Key Laboratory of Pediatric Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China
- Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China
| | - Penggao Wang
- Henan Provincial Clinical Research Center for Pediatric Diseases, Henan Key Laboratory of Pediatric Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China
- Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China
| | - Fang Yang
- Henan Provincial Clinical Research Center for Pediatric Diseases, Henan Key Laboratory of Pediatric Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.
- Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.
| | - Yang Zhou
- Henan Provincial Clinical Research Center for Pediatric Diseases, Henan Key Laboratory of Pediatric Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.
- Department of Cardiothoracic Surgery, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.
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Schildroth S, Kordas K, White RF, Friedman A, Placidi D, Smith D, Lucchini RG, Wright RO, Horton M, Claus Henn B. An Industry-Relevant Metal Mixture, Iron Status, and Reported Attention-Related Behaviors in Italian Adolescents. ENVIRONMENTAL HEALTH PERSPECTIVES 2024; 132:27008. [PMID: 38363634 PMCID: PMC10871126 DOI: 10.1289/ehp12988] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 12/01/2023] [Accepted: 01/17/2024] [Indexed: 02/17/2024]
Abstract
BACKGROUND Exposure to environmental metals has been consistently associated with attention and behavioral deficits in children, and these associations may be modified by coexposure to other metals or iron (Fe) status. However, few studies have investigated Fe status as a modifier of a metal mixture, particularly with respect to attention-related behaviors. METHODS We used cross-sectional data from the Public Health Impact of Metals Exposure study, which included 707 adolescents (10-14 years of age) from Brescia, Italy. Manganese, chromium, and copper were quantified in hair samples, and lead was quantified in whole blood, using inductively coupled plasma mass spectrometry. Concentrations of Fe status markers (ferritin, hemoglobin, transferrin) were measured using immunoassays or luminescence assays. Attention-related behaviors were assessed using the Conners Rating Scales Self-Report Scale-Long Form, Parent Rating Scales Revised-Short Form, and Teacher Rating Scales Revised-Short Form. We employed Bayesian kernel machine regression to examine associations of the metal mixture with these outcomes and evaluate Fe status as a modifier. RESULTS Higher concentrations of the metals and ferritin were jointly associated with worse self-reported attention-related behaviors: metals and ferritin set to their 90th percentiles were associated with 3.0% [β = 0.03 ; 95% credible interval (CrI): - 0.01 , 0.06], 4.1% (β = 0.04 ; 95% CrI: 0.00, 0.08), and 4.1% (β = 0.04 ; 95% CrI: 0.00, 0.08) higher T -scores for self-reported attention deficit/hyperactivity disorder (ADHD) index, inattention, and hyperactivity, respectively, compared with when metals and ferritin were set to their 50th percentiles. These associations were driven by hair manganese, which exhibited nonlinear associations with all self-reported scales. There was no evidence that Fe status modified the neurotoxicity of the metal mixture. The metal mixture was not materially associated with any parent-reported or teacher-reported scale. CONCLUSIONS The overall metal mixture, driven by manganese, was adversely associated with self-reported attention-related behavior. These findings suggest that exposure to multiple environmental metals impacts adolescent neurodevelopment, which has significant public health implications. https://doi.org/10.1289/EHP12988.
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Affiliation(s)
- Samantha Schildroth
- Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA
| | - Katarzyna Kordas
- Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, USA
| | - Roberta F. White
- Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA
- Department of Neurology, Boston University, Boston, Massachusetts, USA
| | - Alexa Friedman
- Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA
| | - Donatella Placidi
- Department of Occupational Health, University of Brescia, Brescia, Italy
| | - Donald Smith
- Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA
| | - Roberto G. Lucchini
- Department of Occupational Health, University of Brescia, Brescia, Italy
- Department of Environmental Health Sciences, Florida International University, Miami, Florida, USA
| | - Robert O. Wright
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Megan Horton
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Birgit Claus Henn
- Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA
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10
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Sabzevari F, Ahmadipour M, Nezamabadipour N, Jahanara A. Assessment of Blood Lead Levels in Mothers Addicted to Opium and Their Neonates in Kerman: A Cross-sectional Study. ADDICTION & HEALTH 2024; 16:6-10. [PMID: 38651026 PMCID: PMC11032620 DOI: 10.34172/ahj.2024.1439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 03/11/2023] [Indexed: 04/25/2024]
Abstract
Background High blood lead levels (BLLs) in pregnant women are associated with poor outcome in neonates. One of the newest non-occupational sources of lead contamination is opium consumption. Accordingly, this study aimed to assess BLLs in mothers addicted to opium and their neonates in Kerman. Methods This cross-sectional was conducted in Afzalipour hospital in Kerman, from February 2019 to February 2020. The BLLs were measured in 100 opium-addicted and non-addicted mothers and their newborns, and the lead levels higher than 5 μg/dL were considered contamination. Then, the demographic and anthropometric data were compared. Findings Based on the results of the present study, the BLLs of opium-addicted mothers (33.40±9.22 μg/dL vs 3.2±1.5 μg/dL) and their neonates (13.46±4.86 vs 1.1±0.9) were significantly higher (P=0.001) than those of non-addicts. Moreover, the average birth weight of the newborns in the addicted group was significantly lower than in the non-addicted group (2572.8±77.49 vs 2946±46.87) (P=0.001). Besides, there was a significant relationship between the average birth weight and the BLL of the mother and baby, and the average weight of the babies was significantly lower at higher levels of lead. However, no correlation was observed regarding the average height and head circumference of the neonates (P>0.05). Conclusion It seems that the serum level of lead in neonates of opium-addicted mothers contaminated with lead is significantly higher than that of non-addicts, but their anthropometric characteristics at birth were not different from those of the nonaddicted group.
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Affiliation(s)
- Fatemeh Sabzevari
- Department of Pediatrics, Afzalipoor Hospital, Kerman University of Medical Sciences, Kerman, Iran
| | - Maryam Ahmadipour
- Department of Pediatrics, Afzalipoor Hospital, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Abbas Jahanara
- Department of Pediatrics, Bam University of Medical Sciences, Bam, Iran
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11
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Bjørklund G, Tippairote T, Hangan T, Chirumbolo S, Peana M. Early-Life Lead Exposure: Risks and Neurotoxic Consequences. Curr Med Chem 2024; 31:1620-1633. [PMID: 37031386 DOI: 10.2174/0929867330666230409135310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 02/10/2023] [Accepted: 02/16/2023] [Indexed: 04/10/2023]
Abstract
BACKGROUND Lead (Pb) does not have any biological function in a human, and it is likely no safe level of Pb in the human body. The Pb exposure impacts are a global concern for their potential neurotoxic consequences. Despite decreasing both the environmental Pb levels and the average blood Pb levels in the survey populations, the lifetime redistribution from the tissues-stored Pb still poses neurotoxic risks from the low-level exposure in later life. The growing fetus and children hold their innate high-susceptible to these Pb-induced neurodevelopmental and neurobehavioral effects. OBJECTIVE This article aims to evaluate cumulative studies and insights on the topic of Pb neurotoxicology while assessing the emerging trends in the field. RESULTS The Pb-induced neurochemical and neuro-immunological mechanisms are likely responsible for the high-level Pb exposure with the neurodevelopmental and neurobehavioral impacts at the initial stages. Early-life Pb exposure can still produce neurodegenerative consequences in later life due to the altered epigenetic imprints and the ongoing endogenous Pb exposure. Several mechanisms contribute to the Pb-induced neurotoxic impacts, including the direct neurochemical effects, the induction of oxidative stress and inflammation through immunologic activations, and epigenetic alterations. Furthermore, the individual nutritional status, such as macro-, micro-, or antioxidant nutrients, can significantly influence the neurotoxic impacts even at low-level exposure to Pb. CONCLUSION The prevention of early-life Pb exposure is, therefore, the critical determinant for alleviating various Pb-induced neurotoxic impacts across the different age groups.
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Affiliation(s)
- Geir Bjørklund
- Council for Nutritional and Environmental Medicine (CONEM), Toften 24, Mo i Rana, 8610, Norway
| | - Torsak Tippairote
- Department of Nutritional and Environmental Medicine, HP Medical Center, Bangkok 10540, Thailand
| | - Tony Hangan
- Faculty of Medicine, Ovidius University of Constanta, Constanta, 900470, Romania
| | - Salvatore Chirumbolo
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, 37134, Italy
- CONEM Scientific Secretary, Strada Le Grazie 9, 37134, Verona, Italy
| | - Massimiliano Peana
- Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Via Vienna 2, Sassari, 07100, Italy
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12
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Huang CC, Pan SC, Chin WS, Hsu JF, Guo YL. Urinary heavy metals and attention-deficit/hyperactivity symptoms of preschool children: a mixed-exposure analysis. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 268:115714. [PMID: 37992648 DOI: 10.1016/j.ecoenv.2023.115714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 11/15/2023] [Accepted: 11/17/2023] [Indexed: 11/24/2023]
Abstract
The neurotoxic effects of certain heavy metals are well established, but only a few studies have investigated the joint effect of concurrent exposure to multiple ones. The study aims to evaluate the association between mixed exposure to neurotoxic metals and the psychosocial behavior of preschool children. Using a stratified sampling strategy, we recruited participants from 105 kindergartens in 41 townships of Taiwan and excluded those with blood lead levels ≥ 3.5 µg/L. The first-morning void urines were collected and analyzed for cadmium, manganese, arsenic, chromium, lead, and nickel concentrations using inductively coupled plasma mass spectrometry. We applied the parentally reported Strengths and Difficulties Questionnaire (SDQ) and Swanson, Nolan, and Pelham IV (SNAP-IV) scales to evaluate the psychosocial behaviors. Multiple linear regressions were utilized to evaluate the associations between each heavy metal and the outcomes, while the mixed effect of concurrent exposure was estimated by using a Quantile g-computation approach. A total of 977 preschool children were included in the study, and the mean (SD) age was 5.7 (0.7) years old. In single pollutant models, we observed adverse effects of urinary manganese, nickel, arsenic, and lead on the specific subsets of SDQ. Furthermore, the combined effect of six heavy metals significantly affected the hyperactivity/inattention symptoms (beta = 0.46, 95% CI: 0.13-0.78, with all metals increased by one quartile), and chromium and lead were the two major contributors. Similar detrimental effects of urinary cadmium and lead were also observed in the SNAP-IV subsets, although the joint effect analysis was not significant. The study provided evidence that concurrent exposure to multiple heavy metals may exert increased risks of hyperactivity/inattention in children compared to single pollutant exposure. Further studies are needed to verify our findings regarding mixed exposure to multiple neurotoxic metals.
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Affiliation(s)
- Ching-Chun Huang
- Environmental and Occupational Medicine, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan; Environmental and Occupational Medicine, National Taiwan University Hospital Hsin-Chu Branch, HsinChu, Taiwan
| | - Shih-Chun Pan
- National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan
| | - Wei-Shan Chin
- School of Nursing, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan
| | - Jing-Fang Hsu
- National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan
| | - Yue Leon Guo
- Environmental and Occupational Medicine, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan; National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health, Taipei 10005, Taiwan.
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13
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Ibarluzea J, Subiza-Pérez M, Arregi A, Molinuevo A, Arranz-Freijo E, Sánchez-de Miguel M, Jiménez A, Andiarena A, Santa-Marina L, Lertxundi A. Association of maternal prenatal urinary fluoride levels with ADHD symptoms in childhood. ENVIRONMENTAL RESEARCH 2023; 235:116705. [PMID: 37479215 DOI: 10.1016/j.envres.2023.116705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 06/17/2023] [Accepted: 07/18/2023] [Indexed: 07/23/2023]
Abstract
BACKGROUND Health concerns about the potential impact of exposure to fluoride via drinking water (DW) on neuropsychological development include behavioral outcomes such as ADHD. OBJECTIVE We aimed to examine the association between prenatal maternal urinary fluoride and symptoms associated with attention-deficit/hyperactivity disorder (ADHD) at the age of 8 and 11 years. METHOD Data from 255 to 236 mother-child pairs from the "Infancia y Medio Ambiente" (INMA) birth cohort (Gipuzkoa; Spain) with maternal urinary F adjusted for creatinine (MUFcr) during pregnancy (first and third trimester) and child assessments of ADHD-like symptoms reported by Conners' Rating Scales-Revised at age of 8 and 11 years was available. Clinical approach was also used: cut off criteria (T > 66). Multiple linear regression models were fitted when outcomes were analyzed as continuous, and logistic regression models when the outcomes were analyzed with a categorical clinical approach. Covariates related to maternal characteristics, birth outcomes, childhood, quality of family context and biomarkers of neuro-toxicants were used. RESULTS No association was found between MUFcr levels during pregnancy and cognitive problems-inattention, hyperactivity or ADHD index score of symptoms at 8 or 11 years. When results were analyzed from the perspective of a clinical approach, at the age of 11 years, there were significant inverse association between MUFcr and being categorized as a cognitive problems-inattention case. ORs were also indicative of a lower risk, although not significant, for ADHD index at age 11. Sensitivity analyses, taking into consideration quality of family context or the levels of other toxicants during pregnancy showed similar results. CONCLUSIONS Higher levels of MUFcr in pregnant women were associated with a lower risk of cognitive problems-inattention at 11 years. These findings are inconsistent with those from previous studies and indicate the need for other population-based studies to confirm or overturn these results.
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Affiliation(s)
- Jesús Ibarluzea
- Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, 20013, San Sebastián, Spain; Faculty of Psychology of the University of the Basque Country (UPV-EHU), 20018, San Sebastian, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain
| | - Mikel Subiza-Pérez
- Faculty of Psychology of the University of the Basque Country (UPV-EHU), 20018, San Sebastian, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain; Bradford Institute for Health Research, Temple Bank House, Bradford Royal Infirmary, BD9 6RJ, Bradford, United Kingdom
| | - Ane Arregi
- Faculty of Psychology of the University of the Basque Country (UPV-EHU), 20018, San Sebastian, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain.
| | - Amaia Molinuevo
- Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain
| | - Enrique Arranz-Freijo
- Faculty of Psychology of the University of the Basque Country (UPV-EHU), 20018, San Sebastian, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain
| | - Manuel Sánchez-de Miguel
- Faculty of Psychology of the University of the Basque Country (UPV-EHU), 20018, San Sebastian, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain
| | - Ana Jiménez
- Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, 20013, San Sebastián, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain
| | - Ainara Andiarena
- Faculty of Psychology of the University of the Basque Country (UPV-EHU), 20018, San Sebastian, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain
| | - Loreto Santa-Marina
- Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, 20013, San Sebastián, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain
| | - Aitana Lertxundi
- Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain; Biodonostia Health Research Institute, Environmental Epidemiology and Child Development Group, 20014, San Sebastian, Spain; Faculty of Medicine and Nursery of the University of the Basque Country (UPV/EHU), 48940, Leioa, Spain
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14
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Dong J, Li X. Lead pollution-related health of children in China: Disparity, challenge, and policy. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 882:163383. [PMID: 37068684 DOI: 10.1016/j.scitotenv.2023.163383] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 03/22/2023] [Accepted: 04/04/2023] [Indexed: 06/01/2023]
Abstract
Lead (Pb) is a neurotoxic metal, and no level of lead exposure is safe for children. China has still experienced problems on child lead poisoning even though the Chinese government has phased out leaded gasoline since 2000. The underlying problem affecting the lead pollution-related health of children in China remains to be comprehensively investigated. It is found that although the significant decline of BLLs, as the Geometric Mean (GM), from 91.40 μg/LGM in 2001 to 37.52 μg/LGM in 2018 is observed, the average BLLs of children are still above 50 μg/L or more [average 59.70 (60.50-65.02, 95 % CI) μg/LGM] after phasing out leaded gasoline since 2000 in China. Lead exposure causes 29.67 MID per 1000 children with a loss of 98.23 (59.40-146.21, 95 % CI) DALYs per 1000 in China, which is greater than the levels reported from the Western Pacific Region and other low- and middle-income countries. A significant correlation is observed between the number of child crimes (NoCCs) and the outcomes of long-term lead exposure for children in China. Although the disparities in BLLs in China are strongly influenced by unequal distributions of potential multi-lead related sources (soil lead, PM2.5 lead, dust lead), unbalance development of local industrialization and economies, as well as incorrect health care for younger children, the notable emissions from coal combustion (CC) and non-ferrous metals (NMS) exploitation dominate the crucial sources of low-level lead exposure to children after phasing out leaded gasoline in China currently. Faced with the unequal and disparate distribution of BLLs in China, the big bottleneck is to decrease the BLLs exertions of 36-45 μg/L in the next few decades. The Chinese government needs to make more efforts on developing more strict guidelines, implementing more policy strategies on prevention and management of blood Pb poisoning, and monitoring the nationwide changes in children's BLLs continuously.
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Affiliation(s)
- Jie Dong
- Department of Environmental Science, School of Geography and Tourism, Shaanxi Normal University, Xi'an, Shaanxi 710062, PR China; International Joint Research Centre of Shaanxi Province for Pollutant Exposure and Eco-environmental Health, Xi'an, Shaanxi 710062, PR China
| | - Xiaoping Li
- Department of Environmental Science, School of Geography and Tourism, Shaanxi Normal University, Xi'an, Shaanxi 710062, PR China; International Joint Research Centre of Shaanxi Province for Pollutant Exposure and Eco-environmental Health, Xi'an, Shaanxi 710062, PR China; Environmental Research Group, School of Public Health, Imperial College London, 80 Wood Lane, London W12 0BZ, UK.
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15
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Su P, Zhang J, Wu J, Chen H, Luo W, Hu M. TREM2 expression on the microglia resolved lead exposure-induced neuroinflammation by promoting anti-inflammatory activities. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 260:115058. [PMID: 37245276 DOI: 10.1016/j.ecoenv.2023.115058] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 05/18/2023] [Accepted: 05/21/2023] [Indexed: 05/30/2023]
Abstract
Neurotoxicity caused by environmental lead (Pb) pollution is a worldwide public health concern, and developing a therapeutic strategy against Pb-induced neurotoxicity is an important area in the current research. Our prior research has demonstrated the significant involvement of microglia-mediated inflammatory responses in the manifestation of Pb-induced neurotoxicity. Additionally, the suppression of proinflammatory mediator activity significantly mitigated the toxic effects associated with Pb exposure. Recent studies have highlighted the critical role of the triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of neurodegenerative disorders. TREM2 exerted protective effects on inflammation, but whether TREM2 is involved in Pb-induced neuroinflammation is poorly understood. In the present study, cell culture experiments and animal models were designed to investigate the role of TREM2 in Pb's neuroinflammation. We examined the impact of pro- and anti-inflammatory cytokines involved in Pb-induced neuroinflammation. Flow cytometry and microscopy techniques were applied to detect microglia phagocytosis and migration ability. Our results showed that Pb treatment significantly downregulated TREM2 expression and altered the localization of TREM2 expression in microglia. The protein expression of TREM2 was restored, and the inflammatory responses provoked by Pb exposure were ameliorated upon the overexpression of TREM2. Furthermore, the phagocytosis and migratory capabilities of microglia, which were impaired due to Pb exposure, were alleviated by TREM2 overexpression. Our in vitro findings were corroborated in vivo, demonstrating that TREM2 regulates the anti-inflammatory functions of microglia, thereby mitigating Pb-induced neuroinflammation. Our results provide insights into the detailed mechanism by which TREM2 alleviates Pb-induced neuroinflammation and suggest that activating the anti-inflammatory functions of TREM2 may represent a potential therapeutic strategy against environmental Pb-induced neurotoxicity.
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Affiliation(s)
- Peng Su
- Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, No.169, Changle West Road, Xi'an 710032, China.
| | - Jianbin Zhang
- Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, No.169, Changle West Road, Xi'an 710032, China
| | - Jinxia Wu
- Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, No.169, Changle West Road, Xi'an 710032, China
| | - Honggang Chen
- Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, No.169, Changle West Road, Xi'an 710032, China
| | - Wenjing Luo
- Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, No.169, Changle West Road, Xi'an 710032, China
| | - Min Hu
- College of Urban and Environmental Sciences, Northwest University, No. 1 Xuefu Ave., Guodu Education and Hi-Tech Industries Zone, Xi'an 710075, China.
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16
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Fiore G, Veneri F, Di Lorenzo R, Generali L, Vinceti M, Filippini T. Fluoride Exposure and ADHD: A Systematic Review of Epidemiological Studies. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59040797. [PMID: 37109754 PMCID: PMC10143272 DOI: 10.3390/medicina59040797] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/12/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023]
Abstract
Background and objectives: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder characterized by two dimensions: inattentiveness and hyperactivity/impulsivity. ADHD may be the result of complex interactions between genetic, biological and environmental factors possibly including fluoride exposure. Materials and methods: A literature search was performed on 31 March 2023 in the following databases: PubMed, Embase and Web of Science. We defined the following inclusion criteria according to the PECOS statement: a healthy child and adolescent population (P), fluoride exposure of any type (E), comparison with low or null exposure (C), ADHD spectrum disorder (O), and ecological, cross-sectional, case-control and cohort studies (S). Results: We found eight eligible records corresponding to seven different studies investigating the effect of fluoride exposure on children and adolescents. One study had a cohort design and one a case-control one, while five were cross-sectional. Only three studies applied validated questionnaires for the purpose of ADHD diagnosis. As regards exposure assessment, levels of fluoride in urine and tap water were, respectively used in three and two studies, while two used both. Three studies reported a positive association with ADHD risk, all assessing exposure through fluoride levels. By using urinary fluoride, conversely, a positive correlation with inattention, internalizing symptoms, cognitive and psychosomatic problems was found in three studies, but no relation was found in the other one. Conclusions: The present review suggests that early exposure to fluoride may have neurotoxic effects on neurodevelopment affecting behavioral, cognitive and psychosomatic symptoms related to ADHD diagnosis. However, due to the heterogeneity of the studies included, current evidence does not allow to conclusively confirm that fluoride exposure is specifically linked to ADHD development.
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Affiliation(s)
- Gianluca Fiore
- Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
| | - Federica Veneri
- Unit of Dentistry & Oral-Maxillo-Facial Surgery, Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance (CHIMOMO), University of Modena and Reggio Emilia, 41124 Modena, Italy
- PhD Program in Clinical and Experimental Medicine, Department of Biomedical, Metabolic and Neural Sciences-University of Modena and Reggio Emilia, 41125 Modena, Italy
| | - Rosaria Di Lorenzo
- Service of Psychiatric Diagnosis and Care (SPDC), Department of Mental Health and Drug Abuse, AUSL Modena, 41124 Modena, Italy
| | - Luigi Generali
- Unit of Dentistry & Oral-Maxillo-Facial Surgery, Department of Surgery, Medicine, Dentistry and Morphological Sciences with Transplant Surgery, Oncology and Regenerative Medicine Relevance (CHIMOMO), University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Marco Vinceti
- Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
- Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA
| | - Tommaso Filippini
- Environmental, Genetic and Nutritional Epidemiology Research Center (CREAGEN), Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
- School of Public Health, University of California Berkeley, Berkeley, CA 94704, USA
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17
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Dufault RJ, Crider RA, Deth RC, Schnoll R, Gilbert SG, Lukiw WJ, Hitt AL. Higher rates of autism and attention deficit/hyperactivity disorder in American children: Are food quality issues impacting epigenetic inheritance? World J Clin Pediatr 2023; 12:25-37. [PMID: 37034430 PMCID: PMC10075020 DOI: 10.5409/wjcp.v12.i2.25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 12/25/2022] [Accepted: 01/09/2023] [Indexed: 03/06/2023] Open
Abstract
In the United States, schools offer special education services to children who are diagnosed with a learning or neurodevelopmental disorder and have difficulty meeting their learning goals. Pediatricians may play a key role in helping children access special education services. The number of children ages 6-21 in the United States receiving special education services increased 10.4% from 2006 to 2021. Children receiving special education services under the autism category increased 242% during the same period. The demand for special education services for children under the developmental delay and other health impaired categories increased by 184% and 83% respectively. Although student enrollment in American schools has remained stable since 2006, the percentage distribution of children receiving special education services nearly tripled for the autism category and quadrupled for the developmental delay category by 2021. Allowable heavy metal residues remain persistent in the American food supply due to food ingredient manufacturing processes. Numerous clinical trial data indicate heavy metal exposures and poor diet are the primary epigenetic factors responsible for the autism and attention deficit hyperactivity disorder epidemics. Dietary heavy metal exposures, especially inorganic mercury and lead may impact gene behavior across generations. In 2021, the United States Congress found heavy metal residues problematic in the American food supply but took no legislative action. Mandatory health warning labels on select foods may be the only way to reduce dietary heavy metal exposures and improve child learning across generations.
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Affiliation(s)
- Renee J Dufault
- Department of Research, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
- College of Graduate Health Studies, A.T. Still University, Kirksville, MO 63501, United States
| | - Raquel A Crider
- Department of Research, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
| | - Richard C Deth
- Department of Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL 33314, United States
| | - Roseanne Schnoll
- Department of Research, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
- Department of Health and Nutrition Sciences, Brooklyn College of CUNY, Brooklyn, NY 11210, United States
| | - Steven G Gilbert
- Department of Research, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
- Department of Research, Institute of Neurotoxicology and Neurological Disorders, Seattle, WA 98105, United States
| | - Walter J Lukiw
- LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States
| | - Amanda L Hitt
- Food Integrity Campaign, Government Accountability Project, Columbia, WA 20006, United States
- Department of Legal, Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
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18
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Butt MS, Javed K, Tariq U. Co-supplementation of Zinc and Calcium Suppresses Bio-absorption of Lead in Sprague Dawley Rats. Biol Trace Elem Res 2023; 201:1317-1326. [PMID: 35399139 DOI: 10.1007/s12011-022-03233-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 04/04/2022] [Indexed: 02/07/2023]
Abstract
Lead (Pb) is a widespread environmental toxicant and its toxicity causes huge health impacts. The present study was conducted to examine the protective role of zinc (Zn) and calcium (Ca) supplements against bio-absorption of Pb in blood and organs including the liver and kidney. Hence, Sprague Dawley rats were divided in to five groups. G1 served as negative control and was provided with standard diet, G2 as positive control receiving standard diet + PbAc (20 mg/kg BW), G3 was provided with standard diet + PbAc (20 mg/kg BW) + ZnSO4 (20 mg/kg BW), G4 with standard diet + PbAc (20 mg/kg BW) + CaCO3 (7.5 g/kg BW) whereas G5 was fed on standard diet + PbAc (20 mg/kg BW) + ZnSO4 (20 mg/kg BW) + CaCO3 (7.5 g/kg BW). The salts were provided as solution, dissolved in 0.5 mL distilled water via orogastric tube. After 35 days, the overnight fasted rats were decapitated, and blood and organs were collected for analysis of levels of metals and liver and kidney function tests. The results depicted significant decrease in Pb concentration in blood and organs while increase in Zn and Ca absorption was observed as a result of Zn and Ca supplementation with Zn being better than Ca alone, specially however, combined effect of these supplements was more profound in improving liver and kidney stress biomarkers and maintained the normal architecture of renal and hepatic parenchyma. It was concluded that Zn and Ca co-supplementation hinder Pb absorption in blood, the liver, and kidney thus suggesting that their intake may protect from Pb toxicity.
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Affiliation(s)
- Masood Sadiq Butt
- Faculty of Food, Nutrition and Home Sciences, National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
| | - Komal Javed
- Faculty of Food, Nutrition and Home Sciences, National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
- Department of Human Nutrition and Dietetics, Riphah International University, Faisalabad, 38000, Pakistan
| | - Urwa Tariq
- Faculty of Food, Nutrition and Home Sciences, National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan.
- Department of Human Nutrition and Dietetics, Riphah International University, Faisalabad, 38000, Pakistan.
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19
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Chen X, Cao S, Wen D, Zhang Y, Wang B, Duan X. Domestic dogs as sentinels of children lead exposure: Multi-pathway identification and source apportionment based on isotope technique. CHEMOSPHERE 2023; 316:137787. [PMID: 36623594 DOI: 10.1016/j.chemosphere.2023.137787] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 12/06/2022] [Accepted: 01/06/2023] [Indexed: 06/17/2023]
Abstract
Environmental lead exposure poses risks to children' health, thus exposure sources and pathways identification remain important concern and research scope. Due to sharing the same environment, domestic animals, especially dogs, have been used as useful sentinels to identify human lead exposure. However, more evidence is needed on whether domestic dogs could be used to identify the lead exposure pathways and sources of children. Thus, this study investigated the dietary habits, behaviors, and household environment of children and dogs in a typical coal-fired area in China. The lead levels and lead isotope ratios (Acronym: LIRs, expressed as 208Pb/206Pb and 207Pb/206Pb) in dogs' and children's blood, as well as in environmental media (food, PM2.5, indoor/outdoor dust, drinking water and soil) were measured to explore the predominant lead pollution sources and exposure pathways of children. The results showed that the LIRs of children's blood (208Pb/206Pb = 2.0703 ± 0.0076, 207Pb/206Pb = 0.8501 ± 0.0052) were similar to those of dogs' blood (208Pb/206Pb = 2.0696 ± 0.0085, 207Pb/206Pb = 0.8499 ± 0.0052), as well as similar to the LIRs of environmental media, i.e. children's food (208Pb/206Pb = 2.0731 ± 0.0057, 207Pb/206Pb = 0.8491 ± 0.0036) and coal (208Pb/206Pb = 2.0683 ± 0.017, 207Pb/206Pb = 0.8515 ± 0.01). Children and dogs had similar lead exposure pathways, but the contributions of each exposure pathway were different, i.e., 83.1% vs. 76.9% for children and dogs via food ingestion, 1.4% vs. 5.6% via particulate matter exposure, and 15.5% vs. 17.5% via household dust exposure, respectively. The contribution of food via ingestion to lead exposure remains dominant, and coal combustion is a main lead exposure source for children and domestic dogs.
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Affiliation(s)
- Xing Chen
- School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - SuZhen Cao
- School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Dongsen Wen
- School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Yaqun Zhang
- Gansu Academy of Eco-environmental Sciences, Lanzhou, 730000, China
| | - Beibei Wang
- School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Xiaoli Duan
- School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing, 100083, China.
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20
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Wang T, Guan RL, Zou YF, Zheng G, Shen XF, Cao ZP, Yang RH, Liu MC, Du KJ, Li XH, Aschner M, Zhao MG, Chen JY, Luo WJ. MiR-130/SNAP-25 axis regulate presynaptic alteration in anterior cingulate cortex involved in lead induced attention deficits. JOURNAL OF HAZARDOUS MATERIALS 2023; 443:130249. [PMID: 36332276 DOI: 10.1016/j.jhazmat.2022.130249] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 10/18/2022] [Accepted: 10/21/2022] [Indexed: 06/16/2023]
Abstract
Brain volume decrease in the anterior cingulate cortex (ACC) after lead (Pb) exposure has been linked to persistent impairment of attention behavior. However, the precise structural change and molecular mechanism for the Pb-induced ACC alteration and its contribution to inattention have yet to be fully characterized. The present study determined the role of miRNA regulated synaptic structural and functional impairment in the ACC and its relationship to attention deficit disorder in Pb exposed mice. Results showed that Pb exposure induced presynaptic impairment and structural alterations in the ACC. Furthermore, we screened for critical miRNA targets responsible for the synaptic alteration. We found that miR-130, which regulates presynaptic vesicle releasing protein SNAP-25, was responsible for the presynaptic impairment in the ACC and attention deficits in mice. Blocking miR-130 function reversed the Pb-induced decrease in the expression of its presynaptic target SNAP-25, leading to the redistribution of presynaptic vesicles, as well as improved presynaptic function and attention in Pb exposed mice. We report, for the first time, that miR-130 regulating SNAP-25 mediates Pb-induced presynaptic structural and functional impairment in the ACC along with attention deficit disorder in mice.
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Affiliation(s)
- Tao Wang
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
| | - Rui-Li Guan
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China
| | - Yun-Feng Zou
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning 530021, China
| | - Gang Zheng
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China
| | - Xue-Feng Shen
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China
| | - Zi-Peng Cao
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China
| | - Rui-Hua Yang
- Department of Nutrition & Food Hygiene and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China
| | - Ming-Chao Liu
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China
| | - Ke-Jun Du
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China
| | - Xue-Hang Li
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Ming-Gao Zhao
- Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China.
| | - Jing Yuan Chen
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
| | - Wen-Jing Luo
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
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21
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Bernardina Dalla MD, Ayala CO, Cristina de Abreu Quintela Castro F, Neto FK, Zanirati G, Cañon-Montañez W, Mattiello R. Environmental pollution and attention deficit hyperactivity disorder: A meta-analysis of cohort studies. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2022; 315:120351. [PMID: 36216185 DOI: 10.1016/j.envpol.2022.120351] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/12/2022] [Accepted: 10/01/2022] [Indexed: 06/16/2023]
Abstract
There is already knowledge of the extensive risk factors for attention deficit hyperactivity disorder (ADHD) and recent studies suggest that environmental pollution may contribute to an increase in the incidence of the disorder. The aim of our study was to perform a systematic review and meta-analysis of the risk of ADHD in people younger than 18 years old after exposure to environmental pollution. We searched the MEDLINE, Embase, SciELO, CINAHL, LILACS, Cochrane Central, and Web of Science databases and investigated the grey literature from inception until May 31, 2021. All cohort studies that provided data on exposure to environmental pollutants and ADHD in children and adolescents aged from zero to 18 years old were included. Two reviewers independently selected the studies and applied the quality criteria. If there was a divergence, a third reviewer contributed to the final decision. For the meta-analysis, risk ratios and their confidence intervals were calculated with the MetaXL 5.3 program, using the random effects model. In total, 21 articles were included in this systematic review, and 18 studies met the criteria for the meta-analysis, involving 134,619 participants. The meta-analysis suggested that children exposed to higher levels of heavy metal (RR: 2.41, 95% CI: 1.49-3.90), with low heterogeneity (I2 = 39%), and lead (RR: 2.37, 95% CI: 1.28-4.40), with moderate heterogeneity (I2 = 54%), are at greater risk of developing ADHD than those exposed to lower levels. This meta-analysis suggests that children exposed to higher levels of lead and heavy metal pollution are at greater risk of developing ADHD than those exposed to lower levels.
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Affiliation(s)
- Marcello Dalla Bernardina Dalla
- Cassiano Antônio de Moraes University Hospital, Universidade Federal do Espírito Santo (HUCAM/UFES), Vitória, Brazil; Capixaba Institute for Teaching Research and Innovation of the State Health Department of Espirito Santo (ICEPI-SESA), Vitória, Brazil
| | - Camila Ospina Ayala
- Medical School, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | | | - Felipe Kalil Neto
- Medical School, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Gabriele Zanirati
- Medical School, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Brain Institute of Rio Grande do Sul (InsCer), Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
| | | | - Rita Mattiello
- Medical School, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Social Medicine, Universidade Federal de Rio Grande do Sul, Porto Alegre, RS, Brazil.
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22
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Ahmad WA, Nirel R, Golan R, Jolles M, Kloog I, Rotem R, Negev M, Koren G, Levine H. Mother-level random effect in the association between PM 2.5 and fetal growth: A population-based pregnancy cohort. ENVIRONMENTAL RESEARCH 2022; 210:112974. [PMID: 35192805 DOI: 10.1016/j.envres.2022.112974] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 02/02/2022] [Accepted: 02/16/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND A growing body of literature reports associations between exposure to particulate matter with diameter ≤2.5 μm (PM2.5) during pregnancy and birth outcomes. However, findings are inconsistent across studies. OBJECTIVES To assess the association between PM2.5 and birth outcomes of fetal growth in a cohort with high prevalence of siblings by multilevel models accounting for geographical- and mother-level correlations. METHODS In Israel, we used Maccabi Healthcare Services data to establish a population-based cohort of 381,265 singleton births reaching 24-42 weeks' gestation and birth weight of 500-5000 g (2004-2015). Daily PM2.5 predictions from a satellite-based spatiotemporal model were linked to the date of birth and maternal residence. We generated mean PM2.5 values for the entire pregnancy and for exposure periods during pregnancy. Associations between exposure and birth outcomes were modeled by using multilevel logistic regression with random effects for maternal locality of residence, administrative census area (ACA) and mother. RESULTS In fully adjusted models with a mother-level random intercept only, a 10-μg/m3 increase in PM2.5 over the entire pregnancy was positively associated with term low birth weight (TLBW) (Odds ratio, OR = 1.25, 95% confidence interval, CI: 1.09,1.43) and small for gestational age (SGA) (OR = 1.15, 95% CI: 1.06,1.26). Locality- and ACA-level effects accounted for <0.4% of the variance while mother-level effects explained ∼50% of the variability. Associations varied by exposure period, infants' sex, birth order, and maternal pre-pregnancy BMI. CONCLUSIONS Consideration of mother-level variability in a region with high fertility rates provides new insights on the strength of associations between PM2.5 and birth outcomes.
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Affiliation(s)
| | - Ronit Nirel
- Hebrew University of Jerusalem, Jerusalem, Israel
| | - Rachel Golan
- Ben-Gurion University of the Negev, Beer Sheva, Israel
| | | | - Itai Kloog
- Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Ran Rotem
- Harvard T.H. Chan School of Public Health, Boston, MA, USA; Institute of Research and Innovation, Maccabitech, Tel-Aviv, Israel
| | | | - Gideon Koren
- Institute of Research and Innovation, Maccabitech, Tel-Aviv, Israel; Tel Aviv University, Tel-Aviv, Israel
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23
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Yang C, Kang B, Cao Z, Zhang J, Zhao F, Wang D, Su P, Chen J. Early-Life Pb Exposure Might Exert Synapse-Toxic Effects Via Inhibiting Synapse-Associated Membrane Protein 2 (VAMP2) Mediated by Upregulation of miR-34b. J Alzheimers Dis 2022; 87:619-633. [DOI: 10.3233/jad-215638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: Early-life Pb exposure can cause behavioral and cognitive problems and induce symptoms of hyperactivity, impulsivity, and inattention in children. Studies showed that blood lead levels were highly correlated with neuropsychiatric disorders, and effects of neurotoxicity might persist and affect the incidence of neurodegenerative diseases, for example Alzheimer’s disease (AD). Objective: To explore possible mechanisms of developmental Pb-induced neuropsychiatric dysfunctions. Methods: Children were divided into low blood lead level (BLL) group (0–50.00μg/L) and high BLL group (> 50.00μg/L) and blood samples were collected. miRNA array was used to testify miRNA expression landscape between two groups. Correlation analysis and real-time PCR were applied to find miRNAs that altered in Pb and neuropsychiatric diseases. Animal models and cell experiments were used to confirm the effect of miRNAs in response to Pb, and siRNA and luciferase experiments were conducted to examine their effect on neural functions. Results: miRNA array data and correlation analysis showed that miR-34b was the most relevant miRNA among Pb neurotoxicity and neuropsychiatric disorders, and synapse-associated membrane protein 2 (VAMP2) was the target gene regulating synapse function. In vivo and in vitro studies showed Pb exposure injured rats’ cognitive abilities and induced upregulation of miR-34b and downregulation of VAMP2, resulting in decreases of hippocampal synaptic vesicles. Blockage of miR-34b mitigated Pb’s effects on VAMP2 in vitro. Conclusion: Early-life Pb exposure might exert synapse-toxic effects via inhibiting VAMP2 mediated by upregulation of miR-34b and shed a light on the underlying relationship between Pb neurotoxicity and developmental neuropsychiatric disorders.
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Affiliation(s)
- Changhao Yang
- Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, China
| | - Beipei Kang
- Department of Clinical Laboratory, Xijing Hospital, Air Force Military Medical University, Xi’an, China
| | - Zipeng Cao
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an, China
| | - Jianbin Zhang
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an, China
| | - Fang Zhao
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an, China
| | - Diya Wang
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an, China
| | - Peng Su
- Department of Occupational & Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an, China
| | - Jingyuan Chen
- Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, China
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24
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Dong C, Liu J, Harvey P, Yan C. Characteristics and sources of Pb exposure via household dust from the urban area of Shanghai, China. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 811:151984. [PMID: 34871683 DOI: 10.1016/j.scitotenv.2021.151984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 11/21/2021] [Accepted: 11/22/2021] [Indexed: 06/13/2023]
Abstract
Household dust has been considered as an important pathway for children's environmental Pb exposure. Shanghai was one of the first cities in China that removed Pb from petrol and has been shown in our previous study to have the lowest childhood blood Pb levels in China. This study therefore examines household dust Pb (PbHD) in Shanghai in order to determine the extent and exposure risks of PbHD. Household vacuum cleaner dust samples (n = 40) were collected and analyzed for total Pb concentration, bio-accessible Pb concentration and Pb isotopic compositions (PbIC). The mean concentration of PbHD was 195 mg/kg, which is between 7 and 10 times the Pb concentration of background soil samples from Shanghai. Among the investigated homes, those living in neighborhoods with lower average estate prices have higher dust Pb exposure risks for children. Bio-accessibility of Pb in household dust ranged between 53 and 91%, with a mean value of 71%. Analysis of PbIC of household dust samples (208Pb/206Pb: 2.1096 ± 0.0054; 207Pb/206Pb: 0.8648 ± 0.0025) are a close match to PbIC of coal combustion and solid waste incineration and fit well with those of outdoor air PbIC and urban surface soil PbIC of Shanghai. The study shows that children living in Shanghai are subject to PbHD exposure, with children living in the homes with lower average price having increased susceptibility to PbHD exposure. The data indicate that PbHD is derived primarily from contemporary coal combustion and solid waste incineration rather than common legacy Pb sources (e.g., Pb petrol and paint). Practices including closing doors and windows on days with poor air quality or high wind and preventing shoe wearing inside homes will aid in minimizing outdoor surface soil and ambient particulate intrusion indoors.
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Affiliation(s)
- Chenyin Dong
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China; State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, PR China.
| | - Junxia Liu
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Paul Harvey
- Environmental Science Solutions, Sydney, Australia; Biami Scientific Pty Ltd, Sydney, Australia
| | - Chonghuai Yan
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China.
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25
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Liu J, Portnoy J, Raine A, Gladieux M, McGarry P, Chen A. Blood lead levels mediate the relationship between social adversity and child externalizing behavior. ENVIRONMENTAL RESEARCH 2022; 204:112396. [PMID: 34801542 PMCID: PMC10117419 DOI: 10.1016/j.envres.2021.112396] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 11/12/2021] [Accepted: 11/13/2021] [Indexed: 06/01/2023]
Abstract
BACKGROUND/AIMS The association between social adversity and externalizing behavioral problems in children is well-documented. What is much less researched are biological mechanisms that may mediate such relationships. This study examines the hypothesis that low blood lead mediates the relationship between social adversity and child externalizing behavior problems. METHODS In this cross-sectional study, participants were 131 children aged 11-12 years (mean = 11.90) from Philadelphia, US. A venous fasting blood sample was taken and analyzed for blood lead levels. A social adversity index was calculated based on 10 total indicators derived from a psychosocial interview of the parent and official neighborhood data, while child behavior outcomes (internalizing and externalizing behavior) were assessed using both parent-report and child self-report. RESULTS The mean blood lead level was 2.20 μg/dL. Both relatively higher blood lead levels and higher social adversity scores were associated with higher levels of parent-reported and child self-reported externalizing behaviors. Additionally, blood lead mediated the relationship between social adversity and child-reported externalizing behavior (Indirect effect: B = 0.03, 95% CI: 0.004, 0.09) and partially mediated the relationship between social adversity and parent-reported externalizing behavior (Indirect Effect: B = 0.03, 95% CI: 0.01, 0.07). CONCLUSION To our knowledge, this study is the first to suggest that blood lead levels play a mediating role in the relationship between externalizing behavior problems and social adversity. Findings have potentially important implications for public health and environmental regulation as well as understanding biological mechanisms that link social inequality with health outcomes, especially in youth from low-income, urban areas.
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Affiliation(s)
- Jianghong Liu
- University of Pennsylvania, School of Nursing 418 Curie Blvd., Claire M. Fagin Hall, Philadelphia, PA, 19104, USA.
| | - Jill Portnoy
- University of Massachusetts Lowell, School of Criminology and Justice Studies, 113 Wilder Street, Lowell, MA, 01854, USA.
| | - Adrian Raine
- University of Pennsylvania, Departments of Criminology, Psychiatry, and Psychology, 3718 Locust Walk, McNeil Building, Philadelphia, PA, 19104, USA.
| | - Margaret Gladieux
- University of Pennsylvania, School of Nursing 418 Curie Blvd., Claire M. Fagin Hall, Philadelphia, PA, 19104, USA.
| | - Presley McGarry
- University of Massachusetts Lowell, School of Criminology and Justice Studies, 113 Wilder Street, Lowell, MA, 01854, USA.
| | - Aimin Chen
- University of Pennsylvania, Department of Biostatistics, Epidemiology and Informatics, 423 Guardian Drive, Blockley Hall, Philadelphia, PA, 19104, USA.
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Tasin FR, Ahmed A, Halder D, Mandal C. On-going consequences of in utero exposure of Pb: An epigenetic perspective. J Appl Toxicol 2022; 42:1553-1569. [PMID: 35023172 DOI: 10.1002/jat.4287] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 12/23/2021] [Accepted: 01/01/2022] [Indexed: 11/08/2022]
Abstract
Epigenetic modifications by toxic heavy metals are one of the intensively investigated fields of modern genomic research. Among a diverse group of heavy metals, lead (Pb) is an extensively distributed toxicant causing an immense number of abnormalities in the developing fetus via a wide variety of epigenetic changes. As a divalent cation, Pb can readily cross the placental membrane and the fetal blood brain barrier leading to far-reaching alterations in DNA methylation patterns, histone protein modifications and micro-RNA expression. Over recent years, several human cohorts and animal model studies have documented hyper- and hypo-methylation of developmental genes along with altered DNA methyl-transferase expression by in utero Pb exposure in a dose-, duration- and sex-dependent manner. Modifications in the expression of specific histone acetyltransferase enzymes along with histone acetylation and methylation levels have been reported in rodent and murine models. Apart from these, down-regulation and up-regulation of certain microRNAs crucial for fetal development have been shown to be associated with in utero Pb exposure in human placenta samples. All these modifications in the developing fetus during the prenatal and perinatal stages reportedly caused severe abnormalities in early or adult age, such as - impaired growth, obesity, autism, diabetes, cardiovascular diseases, risks of cancer development and Alzheimer's disease. In this review, currently available information on Pb-mediated alterations in the fetal epigenome is summarized. Further research on Pb-induced epigenome modification will help to understand the mechanisms in detail and will enable us to formulate safety guidelines for pregnant women and developing children.
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Affiliation(s)
- Fahim Rejanur Tasin
- Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, Bangladesh
| | - Asif Ahmed
- Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, Bangladesh
| | - Debasish Halder
- Rare Disease research center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Chanchal Mandal
- Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, Bangladesh
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27
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Wang A, Duan L, Huang H, Ma J, Zhang Y, Ma Q, Guo Y, Li Z, Cheng X, Zhu J, Zhou G, Ba Y. Association between fluoride exposure and behavioural outcomes of school-age children: a pilot study in China. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2022; 32:232-241. [PMID: 32281876 DOI: 10.1080/09603123.2020.1747601] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 03/20/2020] [Indexed: 06/11/2023]
Abstract
To assess the association between fluoride exposure and children's behavioural outcomes, we recruited 325 resident school-age children (7-13 years old) lived in Tongxu County of Henan Province in China. We measured urinary fluoride (UF) concentrations using the ion-selective electrode method. Children's behavioural outcomes were assessed by Conners' Parent Rating Scale-Revised, including conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, anxiety, and ADHD index. It turned out that each 1.0 mg/L increment in UF concentration corresponded with an elevation in the psychosomatic problem score of 4.01 (95% CI: 2.74, 5.28) and a 97% (OR = 1.97, 95% CI: 1.19, 3.27) increase in the prevalence of psychosomatic problems after adjusting for potential influencing factors. The sensitivity analysis results were consistent with those observed in our preliminary analysis. Our study suggests that fluoride exposure is positively related to the behavioural problem in school-age children, psychosomatic problem in particular.
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Affiliation(s)
- Anqi Wang
- Department of Environment Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
- Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Leizhen Duan
- Department of Medical Services, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Hui Huang
- Department of Environment Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
- Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Jun Ma
- Department of Endemic Disease, Kaifeng Center for Disease Control and Prevention, Kaifeng, Henan, P. R. China
| | - Yawei Zhang
- Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, USA
| | - Qiang Ma
- Teaching and Research Office, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Yao Guo
- Nursing College of Henan University of Chinese Medicine, Zhengzhou, Henan, P. R. China
| | - Zhiyuan Li
- Department of Environment Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
- Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Xuemin Cheng
- Department of Environment Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
- Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Jingyuan Zhu
- Department of Environment Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Guoyu Zhou
- Department of Environment Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
- Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Yue Ba
- Department of Environment Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
- Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, P. R. China
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Nayak S, Sahu S, Patra S, John J. Assessment of Copper and Zinc Levels in Hair and Urine of Children With Attention Deficit Hyperactivity Disorder: A Case-Control Study in Eastern India. Cureus 2021; 13:e20692. [PMID: 35106229 PMCID: PMC8786440 DOI: 10.7759/cureus.20692] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/25/2021] [Indexed: 12/04/2022] Open
Abstract
Background Attention deficit hyperactivity disorder (ADHD) is a neuro-developmental ailment diagnosed with inattention and hyperactivity-impulsivity. It is one of the most prevalent neurodevelopmental disorders and has complex aetiology, both genetic and environmental. There is a perceived decrease in skill acquirement, leading to insufficient income and job opportunities as adults, which drives them towards poor physical and mental outcomes compared to their contemporaries without ADHD. The impact of heavy metals on ADHD is a topic of interest but is much less studied. Copper has been implicated as a pro-oxidant and in the metal accelerated production of free radicals that may affect oxidative stress. Zinc also serves as an antioxidant, and changes in its concentrations may impact the homeostasis of oxidative stress. Methods Twenty-four children diagnosed with ADHD were taken as cases and matched with 24 healthy controls. Hair and urine samples were collected from all the study participants. The samples were collected in sterile containers according to established protocols. Acid digestion of hair samples was done using 65% nitric acid and 30% hydrogen peroxide. Urine samples were extracted by a solution of 0.1% Triton-X-100 and 1% ultrapure nitric acid. The levels of zinc and copper were determined in both samples by inductively coupled plasma optical emission spectrometry (ICP-OES). The copper/zinc ratio (Cu/Zn) was calculated from these values. Mann Whitney U Test and receiver operating characteristic (ROC) analysis were done to estimate statistical significance. Results The median age of the study population was eight years. Overall, 34 male and 14 female subjects participated. There was no significant difference in height, weight and BMI between the cases and controls. Hair zinc levels in the ADHD group (198.49 µg g-1 of hair) was significantly lower than the control group (527.05 µg g-1 of hair). However, hair copper levels were increased significantly in the ADHD children (14.01 µg g-1 of hair) compared to the controls (7.43 µg g-1 of hair). Urine zinc levels were significantly lower in cases than controls (525.7 µg g-1 of spot urine creatinine vs 1374.09 µg g-1 of spot urine creatinine). However, copper levels in urine were higher in the ADHD children (17.01 µg g-1 of spot urine creatinine compared to 7.26 µg g-1 of spot urine creatinine in controls). Both hair and urine copper to zinc ratio was significantly higher in the ADHD group. On ROC analysis, the hair Cu/Zn ratio had an area under the curve (AUC) of 0.920 (p-value <0.001), and the urine Cu/Zn ratio had an AUC of 0.967 (p-value <0.001). When used as a diagnostic classifier for ADHD based on the cut-off value determined by ROC, both hair and urine Cu/Zn ratio had high sensitivity and specificity. Conclusion Low zinc levels in the urine and hair of children and higher levels of copper may impact the aetiology of ADHD in these children. At an early stage, the Cu/Zn ratio in both hair and urine samples may be used as a precise biomarker to identify and monitor such children.
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Liu X, Taylor MP, Aelion CM, Dong C. Novel Application of Machine Learning Algorithms and Model-Agnostic Methods to Identify Factors Influencing Childhood Blood Lead Levels. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2021; 55:13387-13399. [PMID: 34546733 DOI: 10.1021/acs.est.1c01097] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
Blood lead (Pb) poisoning remains a global concern, particularly for children in their early developmental years. Broken Hill is Australia's oldest operating silver-zinc-lead mine. In this study, we utilized recent advances in machine learning to assess multiple algorithms and identify the most optimal model for predicting childhood blood Pb levels (BLL) using Broken Hill children's (<5 years of age) data (n = 23,749) from 1991 to 2015, combined with demographic, socio-economic, and environmental influencing factors. We applied model-agnostic methods to interpret the most optimal model, investigating different environmental and human factors influencing childhood BLL. Algorithm assessment showed that stacked ensemble, a method for automatically and optimally combining multiple prediction algorithms, enhanced predictive performance by 1.1% with respect to mean absolute error (p < 0.01) and 2.6% for root-mean-squared error (p < 0.01) compared to the best performing constituent algorithm (random forest). By interpreting the model, the following information was acquired: children had higher BLL if they resided within 1.0 km to the central mine area or 1.37 km to the railroad; year of testing had the greatest interactive strength with all other factors; BLL increased faster in Aboriginal than in non-Aboriginal children at 9-10 and 12-18 months of age. This "stacked ensemble + model-agnostic interpretation" framework achieved both prediction accuracy and model interpretability, identifying previously unconnected variables associated with elevated childhood BLL, offering a marked advantage over previous works. Thus, this approach has a clear value and potential for application to other environmental health issues.
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Affiliation(s)
- Xiaochi Liu
- School of Information Engineering, China University of Geosciences, Beijing 100083, China
- Earth and Environmental Sciences, Faculty of Science and Engineering, Macquarie University, Sydney 2109, New South Wales, Australia
| | - Mark P Taylor
- Earth and Environmental Sciences, Faculty of Science and Engineering, Macquarie University, Sydney 2109, New South Wales, Australia
| | - C Marjorie Aelion
- Department of Environmental Health Sciences, School of Public Health & Health Sciences, University of Massachusetts, Amherst 01003, Massachusetts, United States
| | - Chenyin Dong
- State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, China
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Dufault RJ, Wolle MM, Kingston HMS, Gilbert SG, Murray JA. Connecting inorganic mercury and lead measurements in blood to dietary sources of exposure that may impact child development. World J Methodol 2021; 11:144-159. [PMID: 34322366 PMCID: PMC8299913 DOI: 10.5662/wjm.v11.i4.144] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 05/27/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
Pre-natal and post-natal chemical exposures and co-exposures from a variety of sources including contaminated air, water, soil, and food are common and associated with poorer birth and child health outcomes. Poor diet is a contributing factor in the development of child behavioral disorders. Child behavior and learning can be adversely impacted when gene expression is altered by dietary transcription factors such as zinc insufficiency or deficiency or by exposure to toxic substances permitted in our food supply such as mercury, lead, or organophosphate pesticide residue. Children with autism spectrum disorder and attention deficit hyperactivity disorders exhibit decreased or impaired PON1 gene activity which is needed by the body to metabolize and excrete neurotoxic organophosphate pesticides. In this current review we present an updated macroepigenetic model that explains how dietary inorganic mercury and lead exposures from unhealthy diet may lead to elevated blood mercury and/or lead levels and the development of symptoms associated with the autism and attention deficit-hyperactivity disorders. PON1 gene activity may be suppressed by inadequate dietary calcium, selenium, and fatty acid intake or exposures to lead or mercury. The model may assist clinicians in diagnosing and treating the symptoms associated with these childhood neurodevelopmental disorders. Recommendations for future research are provided based on the updated model and review of recently published literature.
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Affiliation(s)
- Renee J Dufault
- Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
- College of Graduate Health Studies, A.T. Still University, Kirksville, MO 63501, United States
| | - Mesay M Wolle
- Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282, United States
| | - H M Skip Kingston
- Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
- Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282, United States
| | - Steven G Gilbert
- Food Ingredient and Health Research Institute, Naalehu, HI 96772, United States
- Institute of Neurotoxicology and Neurological Disorders, Seattle, WA 98105, United States
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, United States
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Li HB, Ning H, Li SW, Li J, Xue RY, Li MY, Wang MY, Liang JH, Juhasz AL, Ma LQ. An interlaboratory evaluation of the variability in arsenic and lead relative bioavailability when assessed using a mouse bioassay. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2021; 84:593-607. [PMID: 33952142 DOI: 10.1080/15287394.2021.1919947] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Animal bioassays have been developed to estimate oral relative bioavailability (RBA) of metals in soil, dust, or food for accurate health risk assessment. However, the comparability in RBA estimates from different labs remains largely unclear. Using 12 soil and soil-like standard reference materials (SRMs), this study investigated variability in lead (Pb) and arsenic (As) RBA estimates employing a mouse bioassay in 3 labs at Nanjing University, University of Jinan, and Shandong Normal University. Two performances of the bioassay at Nanjing University in 2019 and 2020 showed reproducible Pb and As RBA estimates, but increasing the number of mouse replicates in 2020 produced more precise RBA measurements. Although there were inter-lab variations in diet consumption rate and metal accumulation in mouse liver and kidneys following SRM ingestion due to differences in diet composition, bioassays at 3 labs in 2019 yielded overall similar Pb and As RBA estimates for the 12 SRMs with strong linear correlations between each 2 of the 3 labs for Pb (R2 = 0.95-0.98 and slope = 0.85-1.02) and As RBA outcomes (R2 = 0.46-0.86 and slope = 0.56-0.79). The consistency in RBA estimates was attributed to the relative nature of the final bioavailability outcome, which might overcome the inter-lab variation in diet consumption and metal uptake in mice. These results increased the confidence of use of mouse bioassays in bioavailability studies.
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Affiliation(s)
- Hong-Bo Li
- State Key Laboratory of Pollution Control and Resource Reuse, Jiangsu Key Laboratory of Vehicle Emissions Control, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China
| | - Han Ning
- State Key Laboratory of Pollution Control and Resource Reuse, Jiangsu Key Laboratory of Vehicle Emissions Control, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China
| | - Shi-Wei Li
- School of Water Conservancy and Environment, University of Jinan, Jinan, Shandong, People's Republic of China
| | - Jie Li
- College of Geography and Environment, Shandong Normal University, Jinan, Shandong, People's Republic of China
| | - Rong-Yue Xue
- State Key Laboratory of Pollution Control and Resource Reuse, Jiangsu Key Laboratory of Vehicle Emissions Control, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China
| | - Meng-Ya Li
- State Key Laboratory of Pollution Control and Resource Reuse, Jiangsu Key Laboratory of Vehicle Emissions Control, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China
| | - Meng-Yu Wang
- State Key Laboratory of Pollution Control and Resource Reuse, Jiangsu Key Laboratory of Vehicle Emissions Control, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China
| | - Jia-Hui Liang
- State Key Laboratory of Pollution Control and Resource Reuse, Jiangsu Key Laboratory of Vehicle Emissions Control, School of the Environment, Nanjing University, Nanjing, Jiangsu, People's Republic of China
| | - Albert L Juhasz
- Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia
| | - Lena Q Ma
- Institute of Soil and Water Resources and Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
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Rygiel CA, Dolinoy DC, Bakulski KM, Aung MT, Perng W, Jones TR, Solano-González M, Hu H, Tellez-Rojo MM, Schnaas L, Marcela E, Peterson KE, Goodrich JM. DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes. ENVIRONMENTAL EPIGENETICS 2021; 7:dvab005. [PMID: 34141453 PMCID: PMC8206046 DOI: 10.1093/eep/dvab005] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 03/30/2021] [Accepted: 04/16/2021] [Indexed: 05/08/2023]
Abstract
Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, P < 0.1 was considered significant. DNAm at a locus in CCSER1 (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), P = 0.06] and emotional regulation [3.62 (-0.05, 8.69), P = 0.05]. Cg18515027 (GCNT1) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), P = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), P = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), P = 0.09]. The indirect effect was significant for cg19703494 (TRAPPC6A) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), P = 0.05]. There was also an indirect effect of cg23280166 (VPS11) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), P = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.
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Affiliation(s)
- Christine A Rygiel
- Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
| | - Dana C Dolinoy
- Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
- Department of Nutritional Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
| | - Kelly M Bakulski
- Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
| | - Max T Aung
- Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, 490 Illinois Street, San Francisco, CA 94143, USA
| | - Wei Perng
- Department of Nutritional Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
- Department of Epidemiology and the Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center Colorado School of Public Health, University of Colorado Denver Anschutz Medical Center, 12474 East 19th Avenue, Aurora, CO 80045, USA
| | - Tamara R Jones
- Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
| | - Maritsa Solano-González
- Center for Nutrition and Health Research, National Institute of Public Health, Universidad No. 655 Colonia Santa María Ahuacatitlán, Cerrada Los Pinos y Caminera C.P. 62100, Cuernavaca, Morelos, México
| | - Howard Hu
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 2001 N. Soto St., Los Angeles, CA 90033, USA
| | - Martha M Tellez-Rojo
- Center for Nutrition and Health Research, National Institute of Public Health, Universidad No. 655 Colonia Santa María Ahuacatitlán, Cerrada Los Pinos y Caminera C.P. 62100, Cuernavaca, Morelos, México
| | - Lourdes Schnaas
- National Institute of Perinatology, Mexico City, Calle Montes Urales 800, Lomas - Virreyes, Lomas de Chapultepec IV Secc, Miguel Hidalgo, 11000 Ciudad de México, CDMX, Mexico
| | - Erika Marcela
- National Institute of Perinatology, Mexico City, Calle Montes Urales 800, Lomas - Virreyes, Lomas de Chapultepec IV Secc, Miguel Hidalgo, 11000 Ciudad de México, CDMX, Mexico
| | - Karen E Peterson
- Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
- Department of Nutritional Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
| | - Jaclyn M Goodrich
- Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
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Wei H, Baktash MB, Zhang R, Wang X, Zhang M, Jiang S, Xia Y, Zhao X, Hu W. Associations of maternal exposure to fine particulate matter constituents during pregnancy with Apgar score and duration of labor: A retrospective study in Guangzhou, China, 2012-2017. CHEMOSPHERE 2021; 273:128442. [PMID: 33082001 DOI: 10.1016/j.chemosphere.2020.128442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 09/16/2020] [Accepted: 09/24/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Limited evidence is available for demonstrating effects of prenatal PM2.5 and its components exposure on Apgar score and duration of labor. OBJECTIVE We sought to investigate the associations between PM2.5 constituents, Apgar score and duration of labor, and evaluated the potential mediating role of duration of labor. METHODS This study included 5396 participants. The V4·CH.02 was applied to assessing exposure to PM2.5 constituents. The associations between PM2.5 constituents Apgar score and duration of labor were examined by multivariate linear regression. Mediation analysis was conducted to estimate the potential mediation effect of duration of labor. RESULTS Trimester-specific exposure to soil dust was significantly associated with 1-min Apgar score (1st trimester: OR: 1.03, 95% CI:0.97, 1.10; 2nd trimester: OR: 1.07, 95% CI: 1.01, 1.14; 3rd trimester: OR: 1.07, 95% CI: 1.01, 1.13), duration of first stage of labor (1st trimester: β: 0.32, 95% CI: 0.07, 0.58; 2nd trimester: β: 0.27, 95% CI: 0.04, 0.51; 3rd trimester: β: 0.37, 95% CI: 0.13, 0.61) and duration of second stage of labor (1st trimester: β: 0.04, 95% CI: -0.00, 0.09; 2nd trimester: β: 0.05, 95% CI: 0.01, 0.10; 3rd trimester: β: 0.05, 95% CI: 0.00, 0.09). The duration of labor mediated the relationship between soil dust and 1-min Apgar score. CONCLUSION This study demonstrated that prenatal exposure to soil dust was significantly associated with the risk of abnormal 1-min Apgar score and extended stage of labor.
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Affiliation(s)
- Hongcheng Wei
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Mohammad Basir Baktash
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Rui Zhang
- Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Xu Wang
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Mingzhi Zhang
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Suzhi Jiang
- Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China
| | - Yankai Xia
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Xiaomiao Zhao
- Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
| | - Weiyue Hu
- State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
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Sahu S, Nayak S, John J. Unmet need to screen for lead toxicity in the prevention of ADHD. J Family Med Prim Care 2021; 10:586-587. [PMID: 34017799 PMCID: PMC8132821 DOI: 10.4103/jfmpc.jfmpc_2065_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 12/02/2020] [Indexed: 11/08/2022] Open
Affiliation(s)
- Suchanda Sahu
- Department of Biochemistry, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Saurav Nayak
- Department of Biochemistry, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Joseph John
- Department of Paediatrics, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
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Rasnick E, Ryan PH, Bailer AJ, Fisher T, Parsons PJ, Yolton K, Newman NC, Lanphear BP, Brokamp C. Identifying sensitive windows of airborne lead exposure associated with behavioral outcomes at age 12. Environ Epidemiol 2021; 5:e144. [PMID: 33870016 PMCID: PMC8043737 DOI: 10.1097/ee9.0000000000000144] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 02/12/2021] [Indexed: 11/25/2022] Open
Abstract
Despite the precipitous decline of airborne lead concentrations following the removal of lead in gasoline, lead is still detectable in ambient air in most urban areas. Few studies, however, have examined the health effects of contemporary airborne lead concentrations in children. METHODS We estimated monthly air lead exposure among 263 children (Cincinnati Childhood Allergy and Air Pollution Study; Cincinnati, OH; 2001-2005) using temporally scaled predictions from a validated land use model and assessed neurobehavioral outcomes at age 12 years using the parent-completed Behavioral Assessment System for Children, 2nd edition. We used distributed lag models to estimate the effect of airborne lead exposure on behavioral outcomes while adjusting for potential confounding by maternal education, community-level deprivation, blood lead concentrations, greenspace, and traffic related air pollution. RESULTS We identified sensitive windows during mid- and late childhood for increased anxiety and atypicality scores, whereas sensitive windows for increased aggression and attention problems were identified immediately following birth. The strongest effect was at age 12, where a 1 ng/m3 increase in airborne lead exposure was associated with a 3.1-point (95% confidence interval: 0.4, 5.7) increase in anxiety scores. No sensitive windows were identified for depression, somatization, conduct problems, hyperactivity, or withdrawal behaviors. CONCLUSIONS We observed associations between exposure to airborne lead concentrations and poor behavioral outcomes at concentrations 10 times lower than the National Ambient Air Quality Standards set by the US Environmental Protection Agency.
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Affiliation(s)
- Erika Rasnick
- Department of Statistics, Miami University, Oxford
- Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center
| | - Patrick H. Ryan
- Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center
- Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
| | | | | | - Patrick J. Parsons
- Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Albany
- Department of Environmental Health Sciences, School of Public Health, University at Albany, Rensselaer, New York
| | - Kimberly Yolton
- Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
- Division of General and Community Pediatrics, Cincinnati Children’s Hospital Medical Center
| | - Nicholas C. Newman
- Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
- Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Albany
- Department of Environmental and Public Health Sciences, University of Cincinnati, Cincinnati, Ohio
| | - Bruce P. Lanphear
- Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
| | - Cole Brokamp
- Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center
- Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
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Cognitive Impairment Induced by Lead Exposure during Lifespan: Mechanisms of Lead Neurotoxicity. TOXICS 2021; 9:toxics9020023. [PMID: 33525464 PMCID: PMC7912619 DOI: 10.3390/toxics9020023] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/19/2021] [Accepted: 01/25/2021] [Indexed: 12/25/2022]
Abstract
Lead (Pb) is considered a strong environmental toxin with human health repercussions. Due to its widespread use and the number of people potentially exposed to different sources of this heavy metal, Pb intoxication is recognized as a public health problem in many countries. Exposure to Pb can occur through ingestion, inhalation, dermal, and transplacental routes. The magnitude of its effects depends on several toxicity conditions: lead speciation, doses, time, and age of exposure, among others. It has been demonstrated that Pb exposure induces stronger effects during early life. The central nervous system is especially vulnerable to Pb toxicity; Pb exposure is linked to cognitive impairment, executive function alterations, abnormal social behavior, and fine motor control perturbations. This review aims to provide a general view of the cognitive consequences associated with Pb exposure during early life as well as during adulthood. Additionally, it describes the neurotoxic mechanisms associated with cognitive impairment induced by Pb, which include neurochemical, molecular, and morphological changes that jointly could have a synergic effect on the cognitive performance.
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Takagi M, Tanaka A, Seyama H, Uematsu A, Kaji M, Yoshinaga J. Source Identification Analysis of Lead in the Blood of Japanese Children by Stable Isotope Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E7784. [PMID: 33114314 PMCID: PMC7660687 DOI: 10.3390/ijerph17217784] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 10/19/2020] [Accepted: 10/20/2020] [Indexed: 11/16/2022]
Abstract
Considering the negative effect of lead (Pb) on children's neurodevelopment, Pb exposure should be minimized to the lowest extent possible, though the blood Pb (BPb) concentrations in Japanese children are among the lowest in the world. To identify the sources of Pb in blood, isotope ratios (IRs: 207Pb/206Pb and 208Pb/206Pb) of Pb (PbIR) in whole blood from eight Japanese children were measured by multi-collector ICP mass spectrometry. Further, samples of house dust, soil, duplicate diet, and tobacco, collected from home environments, were also measured and were compared with PbIR of blood case by case. The relative contribution of Pb in the home environment to BPb were estimated by linear programming (finding an optimal solution which satisfy the combination of IRs and intakes from various sources) when appropriate. Source apportionment for three children could be estimated, and contributions of diet, soil, and house dust were 19-34%, 0-55%, and 20-76%, respectively. PbIR for the remaining five children also suggested that non-dietary sources also contributed to Pb exposure, though quantitative contributions could not be estimated. Non-dietary sources such as soil, house dust, and passive tobacco smoke are also important contributors to Pb exposure for Japanese children based on PbIR results.
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Affiliation(s)
- Mai Takagi
- Department of Environment Systems, University of Tokyo, Chiba 277-8563, Japan;
- National Institute for Environmental Studies, Ibaraki 305-8506, Japan; (A.T.); (H.S.)
| | - Atsushi Tanaka
- National Institute for Environmental Studies, Ibaraki 305-8506, Japan; (A.T.); (H.S.)
| | - Haruhiko Seyama
- National Institute for Environmental Studies, Ibaraki 305-8506, Japan; (A.T.); (H.S.)
| | - Ayumi Uematsu
- Division of Endocrinology and Metabolism, Shizuoka Children’s Hospital, Shizuoka 420-8660, Japan;
| | - Masayuki Kaji
- Shizuoka Public Health Center, Shizuoka 420-0846, Japan;
| | - Jun Yoshinaga
- Department of Environment Systems, University of Tokyo, Chiba 277-8563, Japan;
- Faculty of Life Science, Toyo University, Gunma 374-0193, Japan
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Hawari I, Eskandar MB, Alzeer S. The Role of Lead, Manganese, and Zinc in Autism Spectrum Disorders (ASDs) and Attention-Deficient Hyperactivity Disorder (ADHD): a Case-Control Study on Syrian Children Affected by the Syrian Crisis. Biol Trace Elem Res 2020; 197:107-114. [PMID: 32347445 DOI: 10.1007/s12011-020-02146-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 04/06/2020] [Indexed: 11/29/2022]
Abstract
Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are two developmental disorders that affect children worldwide, and are linked to both genetic and environmental factors. This study aims to investigate the levels of lead, manganese, and zinc in each of ASD, ADHD, and ASD with comorbid ADHD in Syrian children born or grown during the Syrian crisis. Lead and manganese were measured in the whole blood, and zinc was measured in the serum in 31 children with ASD, 29 children with ADHD, and 11 children with ASD with comorbid ADHD (ASD-C) compared with 30 healthy children, their ages ranged between 3 and 12 years. Blood lead levels were higher in the groups of ASD-C (245.42%), ASD (47.57%), and ADHD (14.19%) compared with control. Lead levels were significantly higher in children with ASD in the age of 5 or less compared with control, and they were also higher in the male ASD compared with females (P = 0.001). Blood manganese levels were lower in the groups of ASD-C (10.35%), ADHD (9.95%, P = 0.026), and ASD (9.64%, P = 0.046). However, serum zinc levels were within the reference range in all groups of study. Lead and manganese were positively correlated with each other (P = 0.01). Lead increase and manganese decrease may associate with the incidence of ASD, ADHD, or the co-occurrence of both of them together. Further studies are needed to examine the relationship between metal levels and the co-occurrence of ASD and ADHD together.
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Affiliation(s)
- Israa Hawari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Damascus, 17th April, Mazzeh, Damascus, Syria.
| | - Mohamad Bashar Eskandar
- Department of Pediatrics, Faculty of Medicine, University of Damascus, 17th April, Mazzeh, Damascus, Syria
| | - Samar Alzeer
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Damascus, 17th April, Mazzeh, Damascus, Syria
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Cantoral A, Montoya A, Luna-Villa L, Roldán-Valadez EA, Hernández-Ávila M, Kershenobich D, Perng W, Peterson KE, Hu H, Rivera JA, Téllez-Rojo MM. Overweight and obesity status from the prenatal period to adolescence and its association with non-alcoholic fatty liver disease in young adults: cohort study. BJOG 2020; 127:1200-1209. [PMID: 32145139 DOI: 10.1111/1471-0528.16199] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2020] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To examine the associations of maternal and child overweight status across multiple time-points with liver fat content in the offspring during young adulthood. DESIGN Cohort study. SETTING ELEMENT Cohort in Mexico City. POPULATION Pregnant women with singleton births (n = 97). METHODS We quantified hepatic triglyceride content (liver fat content) by proton magnetic resonance spectroscopy (1H MRS) and conventional T2-weighted MRIs (3T scanner) in 97 young adults from the ELEMENT birth cohort in Mexico City. Historical records of the cohort were used as a source of pregnancy, and childhood and adolescence anthropometric information, overweight and obesity (OWOB) were defined. Adjusted structural equation models were run to identify the association between OWOB in different life stages with liver fat content (log-transformed) in young adulthood. MAIN OUTCOME Maternal OWOB at the time of delivery was directly and indirectly associated with the liver fat content in the offspring at young adulthood. RESULTS Seventeen percent of the participants were classified as having NAFLD. We found a strong association of OWOB between all periods assessed. Maternal OWOB at time of delivery (β = 1.97, 95% CI 1.28-3.05), and OWOB status in the offspring at young adulthood (β = 3.17, 95% CI 2.10-4.77) were directly associated with the liver fat content in the offspring. Also, maternal OWOB was indirectly associated with liver fat content through offspring OWOB status. CONCLUSION We found that maternal OWOB status is related to fatty liver content in the offspring as young adults, even after taking into account OWOB status and lifestyle factors in the offspring. TWEETABLE ABSTRACT There was an association between pre-pregnancy overweight and the development of NAFLD in adult offspring.
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Affiliation(s)
- A Cantoral
- Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - A Montoya
- Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - L Luna-Villa
- Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - E A Roldán-Valadez
- Hospital General de México 'Dr. Eduardo Liceaga', Mexico City, Mexico
- Department of Radiology, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | | | - D Kershenobich
- Instituto Nacional de Ciencias Médicas y Nutrición 'Salvador Zubirán', Mexico City, Mexico
| | - W Perng
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - K E Peterson
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - H Hu
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
- Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA
| | - J A Rivera
- Instituto Nacional de Salud Pública, Cuernavaca, Mexico
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Li Y, Cha C, Lv X, Liu J, He J, Pang Q, Meng L, Kuang H, Fan R. Association between 10 urinary heavy metal exposure and attention deficit hyperactivity disorder for children. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:31233-31242. [PMID: 32483719 DOI: 10.1007/s11356-020-09421-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 05/22/2020] [Indexed: 06/11/2023]
Abstract
Attention deficit hyperactivity disorder (ADHD) is associated with heavy metal exposure during adolescent development. However, the direct clinical evidence is limited. To investigate the possible association between environmental heavy metal exposure and ADHD, a case-control study was conducted with children aged 6-14 years in Guangzhou, China. Results showed that median concentrations of chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), molybdenum (Mo), tin (Sn), barium (Ba), and lead (Pb) in the urine of the case group were significantly higher than those of the control group. Children with ADHD had significantly higher levels of 8-OHdG and MDA compared with those from the control group. In addition, correlations between urinary Co, Ni, Cu, Mo, and Sn were significantly correlated with 8-OHdG and MDA concentrations in urine. After the case and control groups were combined together and the first quartile was used as the reference category, odds ratios (ORs) of ADHD for children increased significantly with the quartile increasing of urinary Co, Cu, and Sn. Our study provides a clinical evidence that Co, Cu, and Sn exposure, particularly Sn exposure, may be an environmental risk of the incurrence of ADHD for children. Furthermore, Co, Ni, Cu, Mo, and Sn exposures were significantly correlated with DNA and lipid damage.
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Affiliation(s)
- Yonghong Li
- Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China
- Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou, 510631, China
| | - Caihui Cha
- Guangzhou Women and Children's Medical Center, Guangzhou, 510120, China
| | - XueJing Lv
- Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou, 510631, China
| | - Jian Liu
- Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou, 510631, China
| | - Jiaying He
- Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou, 510631, China
| | - Qihua Pang
- Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou, 510631, China.
| | - Lingxue Meng
- Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou, 510631, China
| | - Hongxuan Kuang
- Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou, 510631, China
| | - Ruifang Fan
- Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou, 510631, China.
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Dong C, Taylor MP, Gulson B. A 25-year record of childhood blood lead exposure and its relationship to environmental sources. ENVIRONMENTAL RESEARCH 2020; 186:109357. [PMID: 32330765 DOI: 10.1016/j.envres.2020.109357] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 03/05/2020] [Accepted: 03/05/2020] [Indexed: 06/11/2023]
Abstract
Broken Hill, the oldest silver (Ag)-zinc (Zn)-lead (Pb) mining community in Australia, has a legacy and ongoing problem of environmental Pb exposure that was identified as early as 1893. To reduce Pb exposure risks, identifying potential exposure pathways and related factors is a critical first step. This study examined blood lead (PbB) levels of children ≤60 months old (n = 24,106 samples), along with Pb concentrations in corresponding soil (n = 10,160 samples), petri-dish dust (n = 106 houses) and ceiling dust (n = 80 houses) over a 25-year period from 1991 to 2015. Regression analysis was used to examine the relationships between environmental Pb sources and children's blood lead (PbB) outcomes. Analysis of the dataset showed Aboriginal children in Broken Hill had a geometric mean PbB of 7.4 μg/dL (95% CI: 6.7-7.4) being significantly higher (p < 0.01) than non-Aboriginal children (PbB 6.2 μg/dL, 95% CI: 6.2-6.3) for all years between 1991 and 2015. Children at the age of 24-36 months had a higher PbB compared with other age groups. Higher PbB levels were also statistically associated with lower socio-economic status and children living in houses built before 1940 (p < 0.01). Blood Pb was also significantly correlated with both soil Pb and indoor petri-dish dust Pb loadings, confirming that these are important pathways for exposure in Broken Hill. A 100 mg/kg increase in soil Pb was associated with a 0.12 μg/dL increase in childhood PbB. In addition, PbB concentrations increased with indoor petri-dish dust Pb loadings (i.e., 0.08 μg/dL per 100 μg/m2/30 days). The 25-year data show that the risk of exposure at ≥ 10 μg/dL was seemingly unavoidable irrespective of residential address (i.e., children of all ages presenting with a ≥10 μg/dL across the whole city area). In terms of moving forward and mitigating harmful early-life Pb exposures, all children aged 24-36 months should be prioritised for feasible and effective intervention practices. Primary intervention must focus on mitigating contemporary ongoing dust emissions from the mining operations and the associated mine-lease areas along with household soil remediation, to help prevent recontamination of homes. Additional practices of dust cleaning using wet mopping and wiping techniques, vacuuming of carpets and furnishings, ongoing monitoring of children and household dust remain important but short-lived abatement strategies. Overall, the key goal should be to eliminate risk by removing contamination in the wider environment as well as in individual homes.
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Affiliation(s)
- Chenyin Dong
- Department of Earth and Environmental Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia; Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, PR China.
| | - Mark Patrick Taylor
- Department of Earth and Environmental Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia.
| | - Brian Gulson
- Department of Earth and Environmental Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia; CSIRO Land and Water, Lucas Heights, NSW, 2234, Australia
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Kponee-Shovein KZ, Weisskopf MG, Grashow R, Rotem RS, Coull BA, Schnaas L, Hernández-Chávez MDC, Sanchez B, Peterson K, Hu H, Téllez-Rojo MM. Estimating the causal effect of prenatal lead exposure on prepulse inhibition deficits in children and adolescents. Neurotoxicology 2020; 78:116-126. [PMID: 32126243 PMCID: PMC12042602 DOI: 10.1016/j.neuro.2020.02.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 02/27/2020] [Accepted: 02/28/2020] [Indexed: 12/20/2022]
Abstract
During pregnancy, maternal lead from earlier exposures mobilizes and crosses placental barriers, placing the developing fetus at risk for lead exposure and neurodevelopmental deficits. Some neuronal circuits known to be affected in neurodevelopment disorders can be probed with simple physiological behavioral paradigms. One such neural biomarker is Pre-Pulse Inhibition (PPI), an indicator of adequate sensorimotor gating processing. In clinical studies, deficits in PPI have been associated with neurodevelopmental disorders in human subjects. To our knowledge, no studies have examined the use of PPI as a biomarker of toxicant effects on the brain in epidemiological studies. We aimed to estimate the causal effect of prenatal lead exposure, assessed by maternal cortical bone lead concentrations, on PPI in 279 children from Mexico City. in vivo maternal cortical bone lead measurements were taken at four weeks postpartum at the mid-tibia shaft using a K-Shell X-ray fluorescence instrument. PPI recording occurred in an isolated clinical setting and eye blink responses were measured using electromyography. We assessed if the conditions for causal inference held in our study and used the results of our assessment to estimate the causal effect of prenatal lead exposure on PPI using an ordinary least squares regression model, a marginal structural model, and the parametric g-formula. Results were consistent across the three modeling approaches. For the parametric g-formula, a one standard deviation (10.0 μg/g) increase in prenatal lead significantly reduced PPI by approximately 19.0 % (95 % CI: 5.4 %, 34.3 %). This decrease is similar in magnitude to clinical studies on schizophrenia, which have observed PPI impairments in patients with schizophrenia as compared to controls. Our results are consistent with findings from other studies establishing an association between lead exposure and neurodevelopmental disorders in children and suggest that PPI may be useful as an objective biomarker of toxicant effects on the brain.
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Affiliation(s)
- Kalé Z Kponee-Shovein
- Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Marc G Weisskopf
- Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Rachel Grashow
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Ran S Rotem
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Brent A Coull
- Departments of Biostatistics and Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Lourdes Schnaas
- Division of Research in Community Interventions, Instituto Nacional De Perinatología Isidro Espinosa De Los Reyes, Miguel Hidalgo, Mexico
| | - Maria Del Carmen Hernández-Chávez
- Division of Research in Community Interventions, Instituto Nacional De Perinatología Isidro Espinosa De Los Reyes, Miguel Hidalgo, Mexico
| | - Brisa Sanchez
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Karen Peterson
- Departments of Global Public Health and Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Howard Hu
- University of Washington School of Public Health, Seattle, Washington, USA
| | - Martha M Téllez-Rojo
- Center for Nutrition and Health Research, National Institute of Public Health, Mexico
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Fiłon J, Ustymowicz-Farbiszewska J, Krajewska-Kułak E. Analysis of lead, arsenic and calcium content in the hair of children with autism spectrum disorder. BMC Public Health 2020; 20:383. [PMID: 32204706 PMCID: PMC7092413 DOI: 10.1186/s12889-020-08496-w] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 03/10/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Explanation of the pathogenesis and treatment of autism spectrum disorders (ASD) is one of the most significant challenges for scientists today. It is believed that a major pathogenetic factor of this condition is epigenetic changes caused by environmental factors, including toxic metals (cadmium (Cd), lead (Pb), mercury (Hg), aluminium (Al), and arsenic (As)). The nervous system may also be affected by deficiencies of both micro- and macroelements (e.g. calcium (Ca), zinc (Zn)). The aim of the study was to analyze the concentrations of Pb, As, and Ca in the hair of children with ASD and a control group. METHODS The materials for the study comprised hair samples collected from 30 children diagnosed with ASD (case group) and 30 children randomly selected from the general population of Bialystok and surrounding region (control group). Concentrations of Pb, As, and Ca were tested with electron microscopy scanning method. Next, the content of the analyzed elements in the hair was assessed as well as their impact on autism development in the children and the mutual interactions between them. The obtained results were statistically analyzed with Statistica PL 12.5., using the Mann-Whitney U test, and Spearman correlation coefficient. RESULTS Mean Ca level in the hair of the case group was lower than the mean level of this element in the control group. Mean As and Pb concentration in the hair of children with ASD was statistically significantly higher than the mean concentration of this element in the hair of children without neurological disorders. Statistically insignificant weak positive correlations between Ca and As content and negative between Ca and Pb in the hair of children from the case group were noted. Also, statistically significant mean positive correlations between Pb and As were observed. CONCLUSIONS In this small study, according to the observations, children diagnosed with ASD suffer from Ca deficiency and toxic metal overload (As and Pb). These abnormalities may play the main role, as an environmental factor, in the pathogenesis of the analyzed disorder.
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Affiliation(s)
- Joanna Fiłon
- Department of Integrated Medical Care, Medical University of Bialystok, Marii Sklodowskiej-Curie 7A, 15-096 Bialystok, Poland
| | | | - Elżbieta Krajewska-Kułak
- Department of Integrated Medical Care, Medical University of Bialystok, Marii Sklodowskiej-Curie 7A, 15-096 Bialystok, Poland
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Muñoz MP, Rubilar P, Valdés M, Muñoz-Quezada MT, Gómez A, Saavedra M, Iglesias V. Attention deficit hyperactivity disorder and its association with heavy metals in children from northern Chile. Int J Hyg Environ Health 2020; 226:113483. [PMID: 32106053 DOI: 10.1016/j.ijheh.2020.113483] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 12/24/2019] [Accepted: 02/04/2020] [Indexed: 12/09/2022]
Abstract
INTRODUCTION Exposure to lead and arsenic has been associated with child behavior problems. In Arica, a northern city of Chile, the natural presence of arsenic in water has been registered. Also, the city has a history of heavy metals contamination of anthropogenic origin. The purpose of this study was to explore the association between the concentration of blood lead and urinary inorganic arsenic with attention deficit hyperactivity disorder (ADHD) as reported by parents. METHODS Cross-sectional design with data analysis of 2656 children between the ages of 3 and 17 enrolled at the Environmental Health Center of Arica between 2009 and 2015. The diagnosis of ADHD was made based on the parents' response to questions about health history. Multiple logistic regression models were used to adjust for confounding variables. RESULTS The prevalence of ADHD was 6.4%. The means urinary inorganic arsenic and blood lead were 21 μg/L and 1.5 μg/dl, respectively. In the lead model adjusted for sex, age, housing material quality and exposure to secondhand tobacco smoke report; children with blood lead concentrations ≥5 μg/dl were more likely to develop ADHD [Odds Ratio (OR): 2.33 95% confidence intervals (CI) 1.32-4.12)]. Regarding arsenic, the adjusted model revealed a higher chance of developing ADHD in the fifth quintile of exposure (OR = 2.02 IC 95% 1.12-3.61). CONCLUSION The findings of this study suggest that exposure of children to lead and inorganic arsenic was associated with ADHD. This study provides additional evidence to existing literature regarding the potential role of toxic metals such as lead and arsenic in children's behavior. However, our findings should be interpreted with caution due to the limitations of the study.
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Affiliation(s)
- María Pía Muñoz
- Escuela de Salud Pública, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Paola Rubilar
- Escuela de Salud Pública, Facultad de Medicina, Universidad de Chile, Santiago, Chile.; Centro de Epidemiología y Políticas de Salud Pública, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile
| | - Macarena Valdés
- Escuela de Salud Pública, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - María Teresa Muñoz-Quezada
- Centro de Investigación en Neuropsicología y Neurociencias Cognitivas, Facultad de Ciencias de la Salud, Universidad Católica del Maule, Talca, Chile
| | - Andrea Gómez
- Escuela de Salud Pública, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Marta Saavedra
- Departamento de Salud Pública, Secretaria Regional Ministerial de Salud Arica y Parinacota, Arica, Chile
| | - Verónica Iglesias
- Escuela de Salud Pública, Facultad de Medicina, Universidad de Chile, Santiago, Chile..
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Li MM, Gao ZY, Dong CY, Wu MQ, Yan J, Cao J, Ma WJ, Wang J, Gong YL, Xu J, Cai SZ, Chen JY, Xu SQ, Tong S, Tang D, Zhang J, Yan CH. Contemporary blood lead levels of children aged 0-84 months in China: A national cross-sectional study. ENVIRONMENT INTERNATIONAL 2020; 134:105288. [PMID: 31765862 DOI: 10.1016/j.envint.2019.105288] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 10/23/2019] [Accepted: 10/23/2019] [Indexed: 05/25/2023]
Abstract
Despite the global abundance of studies on children's lead (Pb) exposure, the magnitude of Pb exposure among children across China remains unclear, especially for rural areas. In 2000, Pb was removed from petrol, marking a change in the sources of Pb exposure in China. To better understand children's Pb exposure and inform potential approaches to exposure reduction, we conducted a national blood Pb survey of 31,373 children (0-84 months old) from May 2013 to March 2015, using a multi-stage and multi-strata sampling method. Blood lead levels (BLLs) were tested using graphite furnace atomic absorption spectrometry with a detection limit of 1 µg/L. The results show that Chinese children had a contemporary geometric mean (GM) BLL of 26.7 μg/L, with 8.6% of BLLs exceeding 50 µg/L. Boys had higher BLLs (GM 27.2 μg/L) compared to girls (GM: 25.9 μg/L) (p < 0.001). Children at the age of 0-36 months had a lower PbB (GM 25.7 μg/L) level compared with those aged 36-84 months (GM 27.9 μg/L) (p < 0.001). When taking into account sociodemographic factors, a multivariate logistic regression analysis shows that the odds ratios (OR) of having a BLL of 27 µg/dL (i.e., median BLL of this study) or higher were 1.88 (95% CI: 1.76, 2.02) and 1.35 (95% CI: 1.22, 1.49) for homes using coal and biomass fuels, respectively, compared to those using gas or electricity. Meanwhile, children in homes close to roads were more likely to have BLLs exceeding 27 µg/dL (OR: 1.11, 95% CI: 1.03, 1.20). In China, rural children had higher BLLs compared to urban children. As a result of pediatric exposure to Pb, there were approximately 144 million and 36 million IQ points lost for rural children and urban children, respectively, revealing a disparity of Pb exposure between rural and urban areas in China. Cleaner domestic fuels and improved cooking/heating equipment will reduce contemporary Pb exposure in rural areas. In addition, the association between contemporary BLLs and distance away from roads further suggests that resuspension of legacy soil/dust Pb should not be neglected in future remediation programs and household interventions. As a large scale survey, this study provides evidence for revising the reference value of BLL, improving the guideline for clinical and public health management, and implementing interventions to prevent adverse health outcomes associated with low-level Pb exposure in children.
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Affiliation(s)
- Min-Ming Li
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China; Children's Health Department, Shanghai Center for Women and Children's Health, Shanghai 200062, PR China
| | - Zhen-Yan Gao
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China; Department of Gynaecology and Obstetrics, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, PR China
| | - Chen-Yin Dong
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Mei-Qin Wu
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Jin Yan
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Jia Cao
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Wen-Juan Ma
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Ju Wang
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Ying-Liang Gong
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Jian Xu
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Shi-Zhong Cai
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Jing-Yuan Chen
- Department of Occupational and Environmental Health and Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, PR China
| | - Shun-Qing Xu
- Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
| | - Shilu Tong
- Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Pudong, Shanghai 200127, PR China; Institute of Environment and Population Health, School of Public Health, Anhui Medical University, Hefei 230032, PR China; School of Public Health and Social Work, Queensland University of Technology, Kelvin Grove, 4056 QLD, Australia
| | - Deliang Tang
- Department of Environmental Health Sciences, Columbia Center for Children's Environmental Health, Mailman School of Public Health, Columbia University, New York, NY, United States
| | - Jun Zhang
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China
| | - Chong-Huai Yan
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China.
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46
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Nilsen FM, Tulve NS. A systematic review and meta-analysis examining the interrelationships between chemical and non-chemical stressors and inherent characteristics in children with ADHD. ENVIRONMENTAL RESEARCH 2020; 180:108884. [PMID: 31706600 PMCID: PMC6937727 DOI: 10.1016/j.envres.2019.108884] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 09/25/2019] [Accepted: 10/29/2019] [Indexed: 05/05/2023]
Abstract
Children may be more vulnerable to the combined interactions of chemical and non-chemical stressors from their built, natural, and social environments when compared to adults. Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed childhood neurodevelopmental disorder and is considered a major public health issue, as 75% of childhood cases persist into adulthood. ADHD is characterized by developmentally inappropriate levels of hyperactivity, impulsivity, and inattention, with the neurotransmitter serotonin regulating these symptoms. Monoamine oxidase A (MAOA) aids in serotonin uptake and is often implicated in behavioral and emotional disorders, including ADHD. When children are exposed to cigarette smoke, bisphenol A (BPA), or organophosphate pesticides, MAOA activity is inhibited. Non-chemical stressors, such as traumatic childhood experiences, and lifestyle factors, complicate the relationship between genotype and exposures to chemical stressors. But the co-occurrence among outcomes between exposures to chemical stressors, non-chemical stressors, and the low activity MAOA genotype suggest that mental illness in children may be influenced by multiple interacting factors. In this systematic review, we examine the existing literature that combines exposures to chemical and non-chemical stressors (specifically childhood trauma), MAOA characteristics, and ADHD diagnosis to investigate the interrelationships present. We observe that chemical (lead [Pb], phthalates/plasticizers, persistent organic pollutants, and cigarette smoke) exposure is significantly related to ADHD in children. We also observed that existing literature examining the interaction between MAOA, exposures to chemical stressors, and traumatic experiences and their effect on ADHD outcomes is sparse. We recommend that future studies investigating childhood ADHD include chemical and non-chemical stressors and inherent characteristics to gain a holistic understanding of childhood mental health outcomes.
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Affiliation(s)
- Frances M Nilsen
- Oak Ridge Institute for Science and Education Post-Doctoral Participant, U.S. EPA, Office of Research and Development, National Exposure Research Laboratory, 109 TW Alexander Dr., Research Triangle Park, NC, USA.
| | - Nicolle S Tulve
- U.S. EPA, Office of Research and Development, National Exposure Research Laboratory, 109 TW Alexander Dr., Research Triangle Park, NC, USA.
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47
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Li HB, Chen XQ, Wang JY, Li MY, Zhao D, Luo XS, Juhasz AL, Ma LQ. Antagonistic Interactions between Arsenic, Lead, and Cadmium in the Mouse Gastrointestinal Tract and Their Influences on Metal Relative Bioavailability in Contaminated Soils. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2019; 53:14264-14272. [PMID: 31731833 DOI: 10.1021/acs.est.9b03656] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Soils are often co-contaminated with As, Pb, and Cd. To what extent ingested metal(loid)s interact with each other in the gastrointestinal tract and influence their RBA (relative bioavailability) is largely unknown. Three soils predominantly contaminated with As (MS, mining/smelting impacted), Pb (WR, wire rope production impacted), and Cd (EP, enamel pottery production impacted) were administered to mice individually or in binary and tertiary combinations with sodium arsenate, Cd chloride, and/or Pb acetate. In binary combinations, ∼10-fold higher Pb addition decreased As-RBA in MS (26.0 ± 6.28% to 17.1 ± 1.08%), while ∼10-fold higher As addition decreased Pb-RBA in WR (61.3 ± 2.41% to 28.8 ± 5.45%). This was possibly due to the formation of insoluble Pb arsenate in mouse intestinal tract, as indicated by the formation of precipitates when As and Pb co-occurred in water or simulated human gastrointestinal fluids. Due to competition for shared absorption transporters, ∼10- and 100-fold higher Pb addition decreased Cd-RBA in EP (95.8 ± 12.9% to 67.8 ± 12.8% and 62.8 ± 8.24%). Tertiary combinations showed that interactions between two metal(loid)s were affected by the presence of the third metal(loid). Our study suggests that As oxyanion could interact with Pb or Cd ions in the mouse gastrointestinal tract, and the interactions vary depending on concentration and solution characteristics.
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Affiliation(s)
- Hong-Bo Li
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment , Nanjing University , Nanjing 210023 , People's Republic of China
| | - Xiao-Qiang Chen
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment , Nanjing University , Nanjing 210023 , People's Republic of China
| | - Jue-Yang Wang
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment , Nanjing University , Nanjing 210023 , People's Republic of China
| | - Meng-Ya Li
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment , Nanjing University , Nanjing 210023 , People's Republic of China
| | - Di Zhao
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment , Nanjing University , Nanjing 210023 , People's Republic of China
| | - Xiao-San Luo
- Jiangsu Key Laboratory of Agricultural Meteorology, International Center for Ecology, Meteorology, and Environment , Nanjing University of Information Science & Technology , Nanjing 210044 , People's Republic of China
| | - Albert L Juhasz
- Future Industries Institute , University of South Australia , Mawson Lakes , South Australia 5095 , Australia
| | - Lena Q Ma
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment , Nanjing University , Nanjing 210023 , People's Republic of China
- Soil and Water Science Department , University of Florida , Gainesville , Florida 32611 , United States
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48
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Perng W, Tamayo-Ortiz M, Tang L, Sánchez BN, Cantoral A, Meeker JD, Dolinoy DC, Roberts EF, Martinez-Mier EA, Lamadrid-Figueroa H, Song PXK, Ettinger AS, Wright R, Arora M, Schnaas L, Watkins DJ, Goodrich JM, Garcia RC, Solano-Gonzalez M, Bautista-Arredondo LF, Mercado-Garcia A, Hu H, Hernandez-Avila M, Tellez-Rojo MM, Peterson KE. Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project. BMJ Open 2019; 9:e030427. [PMID: 31455712 PMCID: PMC6720157 DOI: 10.1136/bmjopen-2019-030427] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 07/23/2019] [Accepted: 07/25/2019] [Indexed: 11/17/2022] Open
Abstract
PURPOSE The Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother-child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes. PARTICIPANTS n=1643 mother-child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico. FINDINGS TO DATE Maternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling. FUTURE PLANS As the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures. TRIAL REGISTRATION NUMBER NCT00558623.
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Affiliation(s)
- Wei Perng
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado, USA
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado, USA
| | - Marcela Tamayo-Ortiz
- National Council of Science and Technology, National Institute of Public Health, Mexico City, Mexico
| | - Lu Tang
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Brisa N Sánchez
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Alejandra Cantoral
- National Council of Science and Technology, National Institute of Public Health, Mexico City, Mexico
| | - John D Meeker
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Dana C Dolinoy
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
- Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, United States
| | - Elizabeth F Roberts
- Department of Anthropology, University of Michigan, Ann Arbor, Michigan, USA
| | - Esperanza Angeles Martinez-Mier
- Department of Cariology, Operative Dentistry and Dental Public Health, Indiana University School of Dentistry, Indianapolis, Indiana, USA
| | | | - Peter X K Song
- Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Adrienne S Ettinger
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Robert Wright
- Department of Environmental Medicine & Public Health, Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA
| | - Manish Arora
- Department of Environmental Medicine & Public Health, Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA
| | - Lourdes Schnaas
- Division of Research in Community Interventions, Instituto Nacional de Perinatologia, Mexico City, Mexico
| | - Deborah J Watkins
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Jaclyn M Goodrich
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Robin C Garcia
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - Maritsa Solano-Gonzalez
- Center for Nutrition and Health Research, National Institute of Public Health, Cuernavaca, Mexico
| | | | - Adriana Mercado-Garcia
- Center for Nutrition and Health Research, National Institute of Public Health, Cuernavaca, Mexico
| | - Howard Hu
- Department of Environmental and Occupational Health, University of Washington School of Public Health, Seattle, Washington, USA
| | - Mauricio Hernandez-Avila
- Dirección de Prestaciones Económicas y Sociales, Mexican Institute of Social Security, Mexico City, Mexico
| | - Martha Maria Tellez-Rojo
- Center for Nutrition and Health Research, National Institute of Public Health, Cuernavaca, Mexico
| | - Karen E Peterson
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
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49
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Wang X, Liu C, Zhang M, Han Y, Aase H, Villanger GD, Myhre O, Donkelaar AV, Martin RV, Baines EA, Chen R, Kan H, Xia Y. Evaluation of Maternal Exposure to PM 2.5 and Its Components on Maternal and Neonatal Thyroid Function and Birth Weight: A Cohort Study. Thyroid 2019; 29:1147-1157. [PMID: 31298631 DOI: 10.1089/thy.2018.0780] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background: Particulate matter (PM) air pollution is an environmental risk to public health. The prevalence of thyroid disease during pregnancy has increased rapidly in recent decades, but the available data on the relationships among air pollution, thyroid function, and birth outcomes in pregnant women, particularly in China, are scarce. We aimed to evaluate the association between maternal exposure to PM2.5 and its components and maternal and neonatal thyroid function and to investigate whether thyroid function acts as a mediator between air pollution and birth weight. Methods: In this prospective birth cohort study, the levels of maternal exposure to PM2.5 and its components during the first trimester were assessed in 433 pregnant women in Nanjing, China, enrolled during 2014-2015. We evaluated the levels of maternal exposure to PM2.5 and its six main constituents-organic matter (OM), black carbon (BC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and soil dust-using the V4.CH.02 product of the Dalhousie University Atmospheric Composition Analysis Group. The maternal serum-free thyroxine (fT4), thyrotropin (TSH), and thyroid peroxidase antibody (TPOAb) levels during the second trimester were measured through electrochemiluminescent microparticle immunoassays. The neonatal TSH levels were detected using an AutoDELFIA Neonatal TSH kit within 72 hours after birth, and the birth weight Z-score of each newborn was estimated. Results: Higher exposure to maternal PM2.5 and some components (BC and NH4+) decreased the maternal fT4 level (p < 0.05), and the birth weight Z-score was decreased (p < 0.05) by higher exposure to maternal PM2.5 and some components (OM, BC, NO3-, and NH4+). A mediation analysis clarified that the maternal fT4 levels explained 15.9%, 18.4%, and 20.9% of the associations of maternal PM2.5, BC, and NH4+ exposure with the birth weight Z-score, respectively (p < 0.05). After additional sensitivity analyses including only nonpreterm participants (n = 418) and non-TPOAb-positive participants (n = 415), the models remained stable. Conclusions: Our results suggest an inverse association between maternal exposure to PM2.5 and its components and the maternal fT4 levels. Maternal fT4 might act as a mediator between exposure to PM2.5 and its components and birth weight.
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Affiliation(s)
- Xu Wang
- 1State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- 2Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Cong Liu
- 3Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of Health, School of Public Health, Fudan University, Shanghai, China
| | - Mingzhi Zhang
- 1State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- 2Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yingying Han
- 1State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- 2Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Heidi Aase
- 4Department of Child Development and Norwegian Institute of Public Health, Oslo, Norway
| | - Gro Dehli Villanger
- 4Department of Child Development and Norwegian Institute of Public Health, Oslo, Norway
| | - Oddvar Myhre
- 5Department of Toxicology and Risk Assessment, Norwegian Institute of Public Health, Oslo, Norway
| | - Aaron van Donkelaar
- 6Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Canada
| | - Randall V Martin
- 6Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Canada
- 7Harvard-Smithsonian Center for Astrophysics, Cambridge, Massachusetts
| | - Erica Anne Baines
- 8Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Renjie Chen
- 3Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of Health, School of Public Health, Fudan University, Shanghai, China
| | - Haidong Kan
- 3Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of Health, School of Public Health, Fudan University, Shanghai, China
| | - Yankai Xia
- 1State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- 2Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
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50
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Liu X, Wei F, Cheng Y, Zhang Y, Jia G, Zhou J, Zhu M, Shan Y, Sun X, Yu L, Merzenich MM, Lurie DI, Zheng Q, Zhou X. Auditory Training Reverses Lead (Pb)-Toxicity-Induced Changes in Sound-Azimuth Selectivity of Cortical Neurons. Cereb Cortex 2019; 29:3294-3304. [PMID: 30137254 DOI: 10.1093/cercor/bhy199] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Revised: 07/20/2018] [Accepted: 07/26/2018] [Indexed: 01/16/2023] Open
Abstract
Lead (Pb) causes significant adverse effects on the developing brain, resulting in cognitive and learning disabilities in children. The process by which lead produces these negative changes is largely unknown. The fact that children with these syndromes also show deficits in central auditory processing, however, indicates a speculative but disturbing relationship between lead-exposure, impaired auditory processing, and behavioral dysfunction. Here we studied in rats the changes in cortical spatial tuning impacted by early lead-exposure and their potential restoration to normal by auditory training. We found animals that were exposed to lead early in life displayed significant behavioral impairments compared with naïve controls while conducting the sound-azimuth discrimination task. Lead-exposure also degraded the sound-azimuth selectivity of neurons in the primary auditory cortex. Subsequent sound-azimuth discrimination training, however, restored to nearly normal the lead-degraded cortical azimuth selectivity. This reversal of cortical spatial fidelity was paralleled by changes in cortical expression of certain excitatory and inhibitory neurotransmitter receptor subunits. These results in a rodent model demonstrate the persisting neurotoxic effects of early lead-exposure on behavioral and cortical neuronal processing of spatial information of sound. They also indicate that attention-demanding auditory training may remediate lead-induced cortical neurological deficits even after these deficits have occurred.
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Affiliation(s)
- Xia Liu
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China
| | - Fanfan Wei
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China
| | - Yuan Cheng
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China.,New York University-East China Normal University Institute of Brain and Cognitive Science, New York University-Shanghai, Shanghai, China
| | - Yifan Zhang
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China.,New York University-East China Normal University Institute of Brain and Cognitive Science, New York University-Shanghai, Shanghai, China
| | - Guoqiang Jia
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China.,New York University-East China Normal University Institute of Brain and Cognitive Science, New York University-Shanghai, Shanghai, China
| | - Jie Zhou
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China.,New York University-East China Normal University Institute of Brain and Cognitive Science, New York University-Shanghai, Shanghai, China
| | - Min Zhu
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China.,New York University-East China Normal University Institute of Brain and Cognitive Science, New York University-Shanghai, Shanghai, China
| | - Ye Shan
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China
| | - Xinde Sun
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China
| | - Liping Yu
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China
| | | | - Diana I Lurie
- Center for Structural and Functional Neuroscience, Center for Environmental Health Sciences, Department of Biomedical & Pharmaceutical Sciences, College of Health Professions and Biomedical Sciences, University of Montana, Missoula, MT, USA
| | - Qingyin Zheng
- Transformative Otology and Neuroscience Center, Binzhou Medical University, Yantai, China
| | - Xiaoming Zhou
- Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, Institute of Cognitive Neuroscience, Collaborative Innovation Center for Brain Science, School of Life Sciences, East China Normal University, Shanghai, China.,New York University-East China Normal University Institute of Brain and Cognitive Science, New York University-Shanghai, Shanghai, China
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