https://orcid.org/0000-0002-5276-8877
Figures
Abstract
Objective
Arsenic exposure is a significant public health concern, particularly for its impact on children’s cognitive development. Arsenic, a prevalent environmental toxin, is known to disrupt various biological pathways, leading to cognitive deficits and neurodevelopmental issues. Understanding the long-term effects and mechanisms underlying arsenic-induced cognitive impairments is crucial for devising effective interventions.
Methods
This systematic review included observational and experimental studies focusing on children under 18 years exposed to arsenic through drinking water, food, or other environmental sources. Studies were selected through comprehensive database searches, encompassing articles that measured cognitive outcomes via standardized tests. The synthesis was primarily narrative, given the heterogeneity in study designs, exposure levels, and outcomes.
Results
The review analysed findings from 24 studies, showing a consistent inverse relationship between arsenic exposure and cognitive performance in children. Higher arsenic levels were associated with lower IQ scores, slower processing speeds, and impaired memory and language skills. These cognitive deficits were evident across diverse geographical regions and persisted even after adjusting for sociodemographic factors. The studies highlighted the potential for both immediate and long-term cognitive effects, underscoring the importance of early-life exposure.
Conclusions
Arsenic exposure has the potential to impair cognitive development in children. Nonetheless, quantitative meta-analysis is necessary to deduce any conclusions related to its impact. Public health efforts must prioritize reducing arsenic exposure through improved water quality and community-awareness programs. Future research should focus on longitudinal studies to better understand the dose-response relationship and the effectiveness of intervention strategies.
Citation: Tian Y, Hou Q, Zhang M, Gao E, Wu Y (2025) Exposure to arsenic and cognitive impairment in children: A systematic review. PLoS ONE 20(2): e0319104. https://doi.org/10.1371/journal.pone.0319104
Editor: Antonio Peña-Fernández, University of Alcala Faculty of Medicine and Health Sciences: Universidad de Alcala Facultad de Medicina y Ciencias de la Salud, SPAIN
Received: August 20, 2024; Accepted: January 28, 2025; Published: February 26, 2025
Copyright: © 2025 Tian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting information files.
Funding: Hunan Province Natural Science Foundation of China (2022JJ30426).
Competing interests: The authors have declared that no competing interests exist.
Introduction
Arsenic exposure is a significant global health concern, affecting millions of people worldwide [1]. One of the primary routes of exposure is through drinking water and food, particularly in regions where the contamination of groundwater and agricultural products is prevalent [2]. The toxic effects of arsenic have been widely studied, particularly concerning carcinogenic risks, cardiovascular issues, and neurotoxic impacts [3–5]. However, much of this research has centred on adult populations, leaving a critical gap in our understanding of the long-term effects of arsenic exposure on children [3–5].
Recent years have seen growing recognition of the unique vulnerabilities of children to environmental toxins. The developmental processes that occur from conception through adolescence are incredibly sensitive to chemical disruptions, and arsenic exposure during these periods can have lasting and potentially irreversible effects. In particular, there is mounting evidence suggesting that early-life exposure to arsenic can impair neurodevelopment, leading to cognitive deficits, learning disabilities, and other neurobehavioral issues [6–8].
One of the key ways in which arsenic can impact neurodevelopment is through its influence on cellular processes and brain structure [3,9]. Arsenic is known to interfere with various metabolic pathways, including those involved in neurotransmitter production and signalling [3,9]. This interference can disrupt the delicate balance required for healthy brain function, leading to deficits in cognitive performance. For example, arsenic exposure has been shown to reduce the activity of acetylcholinesterase, an enzyme critical for breaking down the neurotransmitter acetylcholine. This disruption can impair synaptic transmission, affecting learning and memory functions [3,9].
Beyond its immediate neurotoxic effects, arsenic can also induce oxidative stress and inflammation in the brain, further compounding its impact on neurodevelopment. Oxidative stress, characterized by an imbalance between free radicals and antioxidants in the body, can damage neurons and other brain cells [10]. Inflammatory responses can exacerbate this damage, leading to cellular apoptosis and potentially contributing to neurodegenerative conditions [9,10]. These mechanisms underscore the multifaceted nature of arsenic’s impact on cognitive development, highlighting the need for comprehensive research into its long-term effects on children’s cognitive health.
The evidence linking arsenic exposure to cognitive impairment in children comes from a variety of sources, including epidemiological studies, clinical research, and animal models [6–8]. Research from various other regions has explored the relationship between arsenic exposure and cognitive outcomes in children [6–8,11,12]. These studies have yielded mixed results, with some showing clear associations between higher arsenic levels and cognitive deficits, while others have found no significant effects [6–8,11,12]. This inconsistency may be due to differences in study design, sample size, exposure levels, or genetic and environmental factors that modulate susceptibility to arsenic’s neurotoxic effects. Nevertheless, the collective evidence points toward a concerning trend that warrants further investigation.
The implications of arsenic-induced cognitive impairment extend beyond individual health outcomes, with broader societal consequences. Cognitive deficits in childhood can hinder educational attainment, limit future employment opportunities, and contribute to socioeconomic disparities. Furthermore, the impacts of arsenic exposure on cognitive function may persist into adulthood, increasing the risk of neurodegenerative conditions such as Alzheimer’s disease or Parkinson’s disease.
In light of these concerns, there is an urgent need to examine the existing literature on arsenic exposure and cognitive impairment in children comprehensively. This study aims to address this need, synthesizing available evidence to provide a clearer understanding of the relationship between arsenic exposure and cognitive development.
Methods
Types of Studies: Our review encompasses any form of observational studies (case-control, cohort, cross-sectional) and experimental trials that investigate the impact of arsenic exposure on cognitive outcomes in children. We include full-text articles and exclude publications available solely as abstracts or unpublished data.
Population: Children aged less than 18 years exposed to arsenic through drinking water, food, or other environmental sources.
Exposures: Measurement of arsenic exposure through either.
Biological markers: Including urinary or blood arsenic levels, or other biomarkers indicating recent or cumulative exposure.
Environmental assessments: Including water or soil arsenic levels or dietary arsenic intake.
Outcomes of interest
Cognitive Function: in terms of IQ scores (full-scale, verbal, and performance) or scores from cognitive and neurobehavioral tests (e.g., processing speed, memory recall, and problem-solving skills).
Search strategy
A comprehensive digital search strategy was implemented to identify relevant studies from various medical and scientific databases, including Medline, Scopus, Google Scholar, Cochrane library. A variety of key search terms were used in different combinations to refine the search, including “Arsenic Exposure,” “Cognitive Development,” “Neurobehavioral Outcomes,” “Arsenic Toxicity,” “Children’s Health,” and “Developmental Disorders.” This extensive search spanned from the inception of each database’s records to April 2024, without language restrictions to capture a wide range of international research findings.
Study selection procedure
The study selection process was executed with meticulous precision by two independent reviewers. Initially, each reviewer conducted their own search, and then they jointly reviewed titles and abstracts to identify articles that might meet the inclusion criteria. The full texts of these preliminarily chosen studies were then carefully scrutinized by both reviewers, working independently, to verify their relevance against the predefined criteria. If disagreements arose, the reviewers sought to reach an agreement through discussion. In cases where consensus could not be achieved, a third reviewer was consulted.
Data collection
Structured data extraction was employed under the supervision of the lead researcher. The information gathered included: study title, publication details, descriptions of study design, information about study population, research setting, sample size, baseline characteristics, and cognitive outcomes measured. We also extracted inclusion and exclusion criteria for participants, descriptions of exposure groups based on different levels of arsenic exposure (e.g., low, moderate, or high), duration of follow-up, and final outcomes such as cognitive test scores (IQ, memory, processing speed).
We ensured that all relevant data were extracted systematically using a predefined extraction form. In cases where key data points were not explicitly reported, efforts were made to interpret and include relevant findings based on available information in the studies. However, no studies were excluded from the review solely due to missing data, as our objective was to provide a comprehensive narrative synthesis. As no meta-analysis was conducted, missing data did not directly impact the analysis. Instead, any uncertainties or data gaps were clearly noted and considered in the interpretation of results.
Risk of bias assessment
All the included studies were observational studies and hence, Newcastle-Ottawa Scale (NOS) was utilized for bias risk assessment [13]. We used the Newcastle-Ottawa Scale (NOS) to assess the risk of bias for the included studies. The NOS evaluates three broad perspectives: (1) Selection of the study groups, (2) Comparability of the groups, and (3) Outcome assessment. Selection criteria included aspects like the representativeness of the sample and ascertainment of exposure. Comparability was assessed based on control for key confounding factors, while outcome assessment focused on the robustness and adequacy of follow-up procedures. Each study is awarded a maximum of nine stars across these domains, with higher scores indicating better quality. Specifically, studies were classified as follows: scores of 7–9 were considered low risk of bias, scores of 4–6 were deemed moderate risk of bias, and scores of 0–3 indicated a high risk of bias.
Data synthesis
Given the significant heterogeneity in participant profiles, exposure levels, and outcome measurements across the included studies, a narrative synthesis was employed in place of a meta-analysis. This approach enables a comprehensive qualitative evaluation of the findings, highlighting key relationships between arsenic exposure and cognitive impairment in children.
The narrative synthesis process was structured as follows:
Categorization of studies
Studies were first categorized based on participant demographics, exposure levels, and the nature of the cognitive outcomes measured. This initial categorization allowed for a nuanced understanding of the different study contexts, laying the groundwork for a comparative analysis. This has been reported in Table 1.
Examination of key findings
Studies were examined for key findings, including associations between arsenic exposure levels and specific cognitive outcomes, such as IQ scores. These findings were then synthesized to identify consistent patterns and trends.
Integration of evidence
The synthesized findings were integrated into a comprehensive narrative, highlighting the overarching relationships between arsenic exposure and cognitive impairment in children. This narrative also considered potential confounding variables.
Conclusions and recommendations
Finally, the narrative synthesis provided a conclusion summarizing the key findings and offering recommendations for both future research and policy interventions to address the cognitive risks associated with arsenic exposure in children. This is provided in the discussion section.
Results
Search results
The flowchart in Fig 1 outlines the process of identifying and selecting studies for a systematic review on arsenic exposure and cognitive outcomes. From an initial pool of 1,481 records found across multiple databases, 298 duplicates were removed and 1,109 records were excluded after screening. Overall, 74 studies were extracted for secondary screening out of which 50 were excluded (S1 Table). Ultimately, 24 studies met the eligibility criteria and were included in the review [6–8,11,12,14–32].
Characteristics of the included studies
The 24 studies were conducted in various countries, including Bangladesh, India, Pakistan, Mexico, China, Uruguay, Brazil, Colombia, and Chile. Bangladesh featured prominently with several studies addressing the issue. The majority were cross-sectional studies, with a few cohort studies mixed in. The risk of bias was assessed as Low for seven studies and High for eight studies, while rest of the 9 studies were marked as Moderate, indicating variability in the quality of evidence. The studies varied widely in sample size, from as few as 40 participants to as many as 7,710. Children’s ages generally ranged from early childhood to late adolescence. Arsenic concentrations and exposure were reported differently across studies, with some using urine arsenic levels, others using water arsenic levels, and various methods to determine arsenic exposure. (Tables 1 and 2).
Narrative synthesis findings
Cognitive Deficits and IQ Scores: Multiple studies have revealed a strong inverse association between arsenic exposure and children’s cognitive function. These studies show that children exposed to higher levels of arsenic have lower IQ scores, with the relationship persisting even after adjusting for sociodemographic factors.
Cognitive decline across various studies.
Wasserman et al. (2004) [31]: This study, conducted in Bangladesh, examined 201 children aged 10 years who had varying levels of arsenic exposure from drinking water. It found a significant inverse association between arsenic exposure and Full-Scale IQ, Performance IQ, and Verbal IQ scores, with the effect persisting after adjusting for sociodemographic covariates and other potential confounders. The study also noted a dose-response relationship, with children exposed to water arsenic levels exceeding 50 µg/L showing markedly lower Performance and Full-Scale IQ scores than those exposed to lower levels.
Wang et al. (2007) [11]: This study, conducted in Shanxi Province, China, examined 720 children aged 8–12 years and found a significant decline in IQ scores across groups with different arsenic exposures. The mean IQ scores decreased from 105 for the control group to 95 for the high-arsenic group, with the difference being statistically significant. The study also highlighted the need for remediation efforts to address arsenic exposure in the region.
Rocha-Amador et al. (2007) [19]: This study, conducted in Mexico, examined the relationship between arsenic exposure and cognitive function in 132 children aged 6–10 years across three rural communities with varying arsenic levels in drinking water. It found a significant inverse association between arsenic in drinking water and Full-Scale, Verbal, and Performance IQ scores, suggesting that arsenic exposure may contribute to cognitive impairment.
Saxena et al. (2022) [25]: This study examined the impact of arsenic exposure on children’s cognitive development in Bihar, India. The study found negative associations for spatial working memory and both arsenic and manganese levels.
Zhou et al. (2020) [30]: Conducted in China, this study examined the relationship between arsenic and other metals exposure and cognitive development in children. The study found that children exposed to higher arsenic levels did not show significantly difference in terms of full IQ, verbal IQ or performance IQ.
Vaidya et al. (2023) [26]: This recent study explored the cognitive effects of arsenic exposure in Nepalese children. The study found a negative association of arsenic exposure with executive function, brain structure, and functional connectivity, using sparse-partial least squares analysis. The study also underscored the importance of early interventions to reduce arsenic exposure, particularly in vulnerable populations.
Ossa et al. (2023) [27]: This study investigated the relationship between arsenic exposure and cognitive development in Colombian children. It found that children exposed to higher arsenic levels had lower cognitive test scores, particularly in language acquisition and problem-solving skills. The study also emphasized the importance of addressing arsenic contamination to protect children’s cognitive health.
Calderon et al. (2001) [22]: This study, conducted in Mexico, explored the neurodevelopmental effects of arsenic exposure on children aged 6–10 years living near a lead smelter. This study showed that the environmental exposure to arsenic influencing CNS function including verbal comprehension, long-term memory, and attention. This suggests that arsenic exposure, particularly from contaminated drinking water, can adversely affect specific cognitive domains.
Manju et al. (2017) [21]: This study examined the relationship between arsenic exposure and cognitive development in Indian children. Exposure to arsenic in drinking water was associated with neurotoxic effects and significantly lower mean IQ grades in children. The study also noted a dose-response relationship, with children exposed to higher arsenic levels showing greater cognitive impairments.
Desai et al. (2018) [7]: This study explored the impact of arsenic exposure on cognitive development in Pakistani children. The study found that there was no independent association between urinary total arsenic and general cognitive abilities.
Vahter et al. (2020) [29]: This study, conducted in Bangladesh, examined the relationship between arsenic exposure and neurodevelopmental outcomes in children. The study found that confirmed lower full developmental raw scores in higher arsenic quintiles, affecting verbal comprehension and perceptual reasoning. The study also noted the importance of controlling for confounding factors, such as socioeconomic status, to fully understand the relationship between arsenic exposure and cognitive impairment.
Ghosh et al. (2017) [20]: This study, conducted in Bangladesh, investigated the impact of arsenic exposure on cognitive development in children aged 8–12 years. The study found a significant negative association between arsenic exposure, as measured by drinking water levels, and IQ scores, with higher arsenic levels correlating with lower full-scale, verbal, and performance IQ scores as determined by Raven’s Progressive Matrices.
Khan et al. (2012) [24]: This study examined the relationship between arsenic exposure and cognitive development in Pakistani children. neither water arsenic (WAs) nor urinary arsenic (UAs) was significantly related to mathematics achievement score and language test score.
Hamadani et al. (2011) [18]: This study investigated the relationship between prenatal arsenic exposure and cognitive development in Bangladeshi children. Early life exposure to arsenic, especially at age 5, was associated with lower verbal and full scale IQ scores, specifically in girls. The study also highlighted the need for early interventions to reduce arsenic exposure, particularly during pregnancy.
Asadullah et al. (2011) [28]: This study examined the relationship between arsenic exposure and neurodevelopmental outcomes in Bangladeshi children. The study found a significant inverse association between exposure to arsenic-poisoned tubewells and lower scores in secondary and primary mathematics. The study also emphasized the importance of policy interventions to address arsenic exposure in contaminated regions.
von Ehrenstein et al. (2007) [16]: This study explored the relationship between arsenic exposure and cognitive development in Bangladeshi children. The study found a significant negative correlation showing that increasing tertiles of urinary arsenic were associated with reductions in certain test scores, with the strongest effects on vocabulary. The study also highlighted the potential for cumulative effects, noting that children with prolonged arsenic exposure experienced greater cognitive impairment.
Rosado et al. (2007) [14]: This study investigated the impact of arsenic exposure on cognitive development in Mexican children. The study found significant inverse relationship between urinary arsenic and visual-spatial abilities, affecting different cognitive tests like the Peabody Picture Vocabulary Test. The study also emphasized the importance of addressing arsenic contamination in vulnerable regions to protect children’s cognitive health.
Abbas et al. (2012) [6]: This study examined the relationship between arsenic exposure and neurodevelopmental outcomes in Pakistani children. The study found a significant inverse association between arsenic levels and intellectual functioning. The study also emphasized the need for remediation efforts to reduce arsenic exposure in contaminated regions.
Nahar et al. (2014) [12]: This study investigated the relationship between prenatal arsenic exposure and cognitive development in Bangladeshi children. The study found a significant inverse association with high arsenic concentration significantly lowering the mean IQ percentile, but the IQ in high arsenic groups did not differ significantly from medium groups. This highlights the potential for high arsenic exposure to contribute to cognitive deficits.
Roy et al. (2011) [15]: This study examined the impact of arsenic exposure on cognitive development in Bangladeshi children aged 8–12 years. The study found those in the second quartile of urinary arsenic had higher scores on oppositional behaviour ratings. The study also noted that arsenic exposure’s neurotoxic effects may contribute to deficits across multiple domains.
Wasserman et al. (2007) [32]: This study, conducted in Bangladesh, expanded upon earlier findings by exploring the relationship between arsenic exposure and intellectual function in 301 6-year-old children. It found a significant inverse association between arsenic levels in drinking water and cognitive test scores, particularly in areas such as performance IQ and processing speed. After controlling for various sociodemographic factors and water manganese levels, arsenic exposure remained negatively correlated with cognitive function, suggesting arsenic’s neurotoxic effects on children’s intellectual development.
Wasserman et al. (2014) [8]: This study investigated the long-term effects of arsenic exposure on cognitive development in Bangladeshi children, particularly those aged 10 years. The study found a significant inverse association between arsenic exposure and cognitive test scores across multiple domains, including full-scale IQ, verbal IQ, and performance IQ. These findings highlight arsenic’s enduring impact on cognitive development, emphasizing the need for early interventions to reduce arsenic exposure from drinking water.
Burgos et al. (2017) [17]: This study explored the impact of environmental arsenic exposure on cognitive development in Chilean children aged 6–15 years. The study found a significant inverse association between arsenic exposure and IQ scores, particularly in children from neighborhoods near waste disposal sites containing heavy metals. The study also found that children born after remediation efforts had significantly higher cognitive test scores than those born before, indicating the potential for mitigation measures to reduce arsenic’s neurotoxic effects.
Wang et al. (2022) [23]: This study examined the impact of arsenic exposure on cognitive development in Chinese children. The study has reported a significant association with prenatal low-level arsenic exposure negatively affected the girls’ performance intelligence quotient (PIQ) and verbal intelligence quotient (VIQ).
Findings based on the Exposure Matrices: Wasserman et al. (2004) primarily investigated arsenic exposure through drinking water, urine, and blood matrices. The study reported a significant inverse association between cognitive decline and arsenic levels in drinking water. Associations with arsenic levels in urine and blood were less pronounced, suggesting that water arsenic levels, likely reflecting direct and prolonged exposure, were the most robust predictors of cognitive outcomes. This highlights the differential significance of exposure matrices in interpreting the cognitive impacts of arsenic exposure.
Similarly, Wang et al. (2007) observed stronger associations between arsenic concentrations in drinking water and reduced IQ scores compared to urinary arsenic. These findings align with the hypothesis that drinking water serves as a primary exposure source, potentially leading to higher systemic absorption compared to other exposure matrices.
In contrast, Nahar et al. (2014) found that urinary arsenic concentrations were more predictive of cognitive deficits than water arsenic levels, indicating that urine, as a biomarker of recent arsenic exposure, may provide insights into the body’s acute response to arsenic exposure. Such findings underscore the importance of understanding the temporal and source-specific variations in arsenic exposure when interpreting its effects on cognitive development. Across the reviewed studies, it is evident that the choice of exposure matrix—be it drinking water, urine, or blood—has implications for the observed associations and their interpretation.
Subdomain-specific deficits
Processing speed.
Arsenic exposure has been consistently associated with deficits in processing speed, a crucial component of cognitive function. Studies from various regions [15–18,20,23,29], including Bangladesh, China, and Mexico, have demonstrated an inverse relationship between arsenic exposure and processing speed scores in children. These findings suggest that arsenic may impair various aspects of neurodevelopment, leading to slower information processing and reaction times. Furthermore, these deficits persist even after adjusting for various confounding factors, indicating arsenic’s direct impact on cognitive function. The dose-response relationship observed in several studies further emphasizes that higher arsenic exposure correlates with more significant impairments in processing speed.
Language and communication.
Beyond overall IQ scores, arsenic exposure has also been linked to deficits in language acquisition and communication skills. Research indicates that children exposed to higher arsenic levels show lower verbal IQ scores and perform worse on language-related tests, affecting their ability to comprehend and produce language effectively [6,7,11,12,14–16,28,30,32]. This relationship is particularly concerning, as language acquisition and communication skills are foundational to cognitive development and learning. The compounded effect of these deficits can contribute to broader cognitive impairments, highlighting arsenic’s multifaceted neurotoxic impact.
Neurodevelopmental tests.
Children exposed to arsenic-contaminated water have shown deficits across various cognitive domains, including processing speed, verbal IQ, and performance IQ. Research indicates that these deficits are pervasive, with higher arsenic exposure correlating with lower cognitive test scores across the board [7,12,21–24,30–32]. The dose-response relationship observed in many studies underscores the significance of arsenic’s impact, with higher exposure levels leading to more substantial cognitive impairments. These findings highlight the need for comprehensive interventions to address arsenic contamination and protect children’s neurodevelopmental health.
Dose-response relationship.
Several studies demonstrate a clear dose-response relationship between arsenic exposure levels and cognitive outcomes in children [6,7,11,12,14,15,17,20,22–24,28–32]. This relationship indicates that higher arsenic levels correlate with more significant declines in intellectual function. The consistent observation of this dose-response relationship across diverse studies and regions highlights arsenic’s detrimental impact on cognitive development. The dose-response relationship also suggests that prolonged or higher levels of arsenic exposure can exacerbate cognitive deficits, including IQ scores and neurodevelopmental test results. This underscores the importance of addressing arsenic exposure early on to prevent significant cognitive impairment.
The review identified that dose-response relationships varied depending on the exposure levels, matrices, and health outcomes assessed. For example, Wasserman et al. (2004) reported a significant dose-response relationship between arsenic concentrations in drinking water (ranging from 10 µg/L to 150 µg/L) and declines in IQ scores among children, with stronger effects at higher exposure levels. In contrast, studies such as Nahar et al. (2014) highlighted dose-response relationships based on urinary arsenic concentrations, where levels above 50 µg/g creatinine were associated with a higher prevalence of cognitive deficits. Similarly, Wang et al. (2007) found a consistent dose-response pattern for arsenic concentrations in drinking water, with neurocognitive impairment increasing at exposure levels exceeding 100 µg/L.
The consistency of dose-response findings was influenced by the matrices used for exposure assessment. Drinking water arsenic concentrations demonstrated more robust and consistent dose-response relationships, likely due to their reflection of long-term cumulative exposure. Urinary arsenic levels, representing more recent exposure, showed variability across studies due to differences in temporal exposure and individual metabolism. This underscores the importance of considering the exposure matrix in interpreting dose-response relationships.
Neurotoxicity mechanisms.
Arsenic’s neurotoxic effects are linked to its disruption of multiple metabolic pathways. One key mechanism involves interfering with neurotransmitter production and signalling, which is essential for healthy brain function. This disruption can lead to impairments in various cognitive domains, including processing speed, language acquisition, and problem-solving skills. Additionally, arsenic exposure can induce oxidative stress and inflammation in the brain, leading to cellular damage. This damage can further contribute to cognitive deficits and neurodevelopmental impairment, emphasizing arsenic’s multifaceted impact on children’s cognitive health [6–8,11,12,14–32].
Longitudinal impacts
Long-term effects.
While most studies included in this review are cross-sectional, they collectively hint at the potential long-term cognitive impacts of arsenic exposure. For instance, Hamadani et al. (2011) [18] examined cognitive function in children exposed to arsenic in utero and found that even early-life exposure could contribute to cognitive deficits later in life. This suggests that arsenic’s neurotoxic effects may persist over time, potentially leading to cumulative cognitive deficits. The longitudinal impacts of arsenic exposure underscore the importance of interventions to reduce exposure early on, particularly in vulnerable populations.
Cumulative exposure.
Several studies suggest that the cognitive deficits associated with arsenic exposure may be cumulative in nature, with children exposed to higher levels for longer periods experiencing more significant impairment [15–17,21,23,24,28,30]. This cumulative effect is particularly concerning, as it suggests that prolonged arsenic exposure can lead to lasting and potentially irreversible cognitive decline. The dose-response relationship observed in many studies reinforces this notion, with higher arsenic levels correlating with more substantial declines in IQ scores and other cognitive test results. This cumulative effect underscores the need for interventions to reduce arsenic exposure early in life to prevent long-term cognitive decline and protect children’s cognitive health.
Regional and cultural differences
International consistency.
Studies from various regions, including Bangladesh, China, and Mexico, consistently show an inverse relationship between arsenic exposure and cognitive function, despite differing cultural and regional contexts [15–18,20,23,29]. This consistency across diverse populations strengthens the argument for arsenic’s neurotoxic effects on children’s cognitive development, highlighting its global impact. The consistent findings across various regions also suggest that arsenic’s neurotoxic effects are not confined to specific cultural or environmental factors, reinforcing the need for global remediation efforts to address arsenic contamination.
Socioeconomic factors.
Several studies account for socioeconomic factors, such as parental education and household income, highlighting that arsenic exposure remains a significant predictor of cognitive deficits even when these factors are controlled [6,7,11,12,14,16,20,22,24–26,30–32]. This indicates that the neurotoxic effects of arsenic are independent of socioeconomic status, emphasizing the need for interventions to reduce arsenic exposure across diverse populations. The consistent association between arsenic exposure and cognitive decline, even after accounting for socioeconomic factors, underscores the direct impact of arsenic on neurodevelopmental health.
Confounding factors.
Many studies included in this review have considered various confounding factors that could influence cognitive development in children, including socioeconomic status, parental education, and co-exposure to other toxins [11,14,16,20,22,23,25,28,30–32]. The findings reveal that while these factors do play a role in cognitive outcomes, arsenic exposure remains a significant predictor of cognitive impairment, even after controlling for these variables. For example, parental education and household income can influence children’s access to educational resources and their overall learning environment, yet studies show that arsenic exposure independently correlates with cognitive deficits. This underscores arsenic’s direct neurotoxic impact on children’s cognitive development.
Discussion
The systematic review on the neurodevelopmental impact of arsenic exposure on children reveals a complex interplay between environmental factors and cognitive development, elucidating significant public health concerns. The pervasive nature of arsenic exposure, particularly in vulnerable regions, underscores an urgent need for targeted interventions and policy reforms.
Arsenic’s neurotoxicity, as evidenced in the included studies, manifests in several key areas of cognitive function, including processing speed, language acquisition, and problem-solving abilities [23–30]. These cognitive domains are crucial for the overall developmental trajectory of a child, affecting educational outcomes and future socioeconomic status. The findings consistently show that arsenic exposure correlates with lower IQ scores and impaired cognitive function, even after adjusting for confounding factors such as socioeconomic status and parental education [11,12,19–31].
The biologic mechanisms proposed for arsenic’s neurotoxic effects include disruption of neurotransmitter signalling, induction of oxidative stress, and promotion of inflammation within the brain [3,9]. These disruptions can lead to neuronal damage and apoptosis, which are likely contributors to the cognitive deficits observed. This mechanistic understanding is crucial as it not only helps in diagnosing the extent of damage but also in guiding therapeutic interventions aimed at mitigating the neurotoxic effects [3,9].
Further exploration into arsenic’s neurotoxic mechanisms reveals its potential to disrupt mitochondrial function, leading to decreased energy production within brain cells. This mitochondrial dysfunction can exacerbate the production of reactive oxygen species, thus amplifying oxidative stress and promoting a cycle of cellular damage and death. Additionally, arsenic interferes with the developmental regulation of gene expression in neural cells, which can alter the normal patterns of brain development and lead to structural and functional abnormalities. These insights into the cellular and molecular effects of arsenic provide a clearer picture of how extensive the damage can be, emphasizing the need for protective measures during critical periods of brain development [3,9].
Examining regional variations in the impact of arsenic exposure also reveals significant cultural considerations that influence both exposure levels and outcomes. Dietary habits, local water sourcing practices, and traditional medicine use can all affect arsenic exposure. For instance, regions with a high dependence on groundwater for drinking and irrigation may experience higher exposure levels, influencing the degree of cognitive impairments observed in these populations [33]. Cultural factors also play a crucial role in the acceptance and success of intervention strategies. Tailoring interventions to fit local customs and practices can enhance their effectiveness, promoting better compliance and more profound health impacts. This calls for culturally sensitive approaches to designing and implementing arsenic mitigation strategies, ensuring they are not only scientifically sound but also socially acceptable.
The variability in methods used for arsenic detection across the included studies contributes significantly to differences in sensitivity, specificity, and detection limits. Among the methods reported, Inductively Coupled Plasma Mass Spectrometry (ICP-MS) offers the highest sensitivity with detection limits as low as 0.0003 ppb, whereas X-Ray Fluorescence (XRF) and Anion Exchange High-Performance Liquid Chromatography (AE-HPLC) have higher limits of detection at approximately 0.7 ppb and 0.2 to 0.8 ppb, respectively. This methodological heterogeneity partly explains the discrepancies observed in arsenic concentration levels reported in different studies, especially in regions where concentrations are close to the detection limits of less sensitive methods. For instance, studies employing ICP-MS reported lower detectable arsenic levels compared to studies using XRF, which could influence risk assessments and mitigation strategies. Furthermore, the choice of method impacts the reliability of arsenic speciation, as methods like AE-HPLC are more suited for distinguishing between arsenite and arsenate compared to ICP-MS, which primarily quantifies total arsenic. These differences underscore the importance of considering detection methods when interpreting and comparing results, as well as when designing future studies to standardize analytical approaches and minimize variability.
The global nature of arsenic exposure and its profound impact on child health necessitates a coordinated response from public health authorities and governments. Interventions need to focus on preventing exposure, especially in high-risk areas, by improving water quality and establishing strict regulations on arsenic levels in consumer products and industrial emissions. The studies highlight the effectiveness of community-based interventions, such as the installation of arsenic-removal systems, which have led to improved cognitive outcomes in children from previously high-exposure areas [34].
Moreover, the evidence suggests that early-life exposure to arsenic could have lasting effects that extend into adulthood, potentially increasing the risk of neurodegenerative diseases. This long-term risk reinforces the need for early and aggressive intervention strategies that not only address immediate exposure but also monitor populations over time for emerging cognitive issues.
The dose-response relationships identified in this review reveal important insights into the health effects of arsenic exposure. The observed associations between arsenic exposure and adverse outcomes, such as cognitive decline, were strongly influenced by the exposure matrices and assessment methods used. Studies measuring arsenic levels in drinking water, such as Wasserman et al. (2004) and Wang et al. (2007), demonstrated more consistent dose-response relationships, particularly at exposure levels exceeding 100 µg/L. This consistency likely stems from drinking water’s role as a primary and cumulative source of arsenic exposure, providing a clearer link to long-term health effects.
In contrast, studies using urinary arsenic levels, such as Nahar et al. (2014), showed dose-response relationships that varied based on recent exposure and individual differences in arsenic metabolism. These variations underscore the temporal nature of urinary arsenic as a biomarker and its potential to capture short-term exposure rather than cumulative effects. Blood arsenic levels, used less frequently, were often intermediate in terms of reflecting both recent and long-term exposure, contributing to inconsistencies in dose-response findings.
The variability in dose-response relationships across studies highlights the critical role of exposure assessment methods and matrices. While drinking water arsenic concentrations provided the most consistent results, urinary and blood arsenic measurements introduced variability due to differences in individual metabolism, exposure timing, and environmental factors. These findings emphasize the need for future studies to standardize exposure assessment methods and consider the matrix’s influence when interpreting dose-response relationships.
The socioeconomic impact of cognitive deficits induced by arsenic exposure cannot be overstated. Children suffering from these deficits are likely to face challenges in academic achievement, resulting in lower educational attainment and reduced job prospects in adulthood [10,18]. This perpetuates a cycle of poverty in communities already vulnerable to environmental toxins. Furthermore, the burden of cognitive deficits extends beyond the individual to the societal level, where increased healthcare costs and lost productivity impose significant economic strains. Addressing these socioeconomic impacts requires integrated strategies that combine health interventions with educational support programs, ensuring that affected children can achieve optimal developmental outcomes despite their exposure to arsenic.
Some studies have explored the impact of other contaminants alongside arsenic, particularly fluoride, to understand how multiple environmental toxins interact and affect cognitive development. These studies consistently find that arsenic exposure correlates with cognitive decline, even when accounting for the influence of other toxins [11,12,23,26,30,32]. For instance, research conducted in China and Bangladesh has shown that arsenic exposure’s neurotoxic effects persist across various cognitive domains, including IQ scores, processing speed, and memory recall, despite the presence of other contaminants like fluoride. This highlights the need for comprehensive interventions to address arsenic exposure specifically and reduce its direct impact on children’s cognitive health.
Despite the extensive data linking arsenic exposure to cognitive deficits, there remain significant gaps in our understanding of the dose-response relationship and the potential for recovery following exposure cessation. Future research should aim to define the threshold levels of arsenic exposure that lead to detectable cognitive impairments and to evaluate the effectiveness of various mitigation strategies in reversing these effects.
Additionally, there is a need for longitudinal studies that follow children over longer periods to assess the lasting impacts of early-life exposure and the efficacy of early interventions. Such studies would provide invaluable insights into the critical windows of vulnerability and the potential for neuroplasticity and recovery in the developing brain.
This study has several notable strengths. First, it offers a comprehensive analysis of existing data on the impact of arsenic exposure on cognitive functions, synthesizing a wide range of sources. The use of established risk assessment tools such as the Newcastle-Ottawa Scale ensures a structured evaluation of study quality. Additionally, a rigorous data extraction and analysis protocol enhances the reliability of the results.
However, some limitations should also be acknowledged. The included studies varied significantly in terms of population, dosage, and duration of exposure, leading to considerable heterogeneity in the findings. This variation may limit the generalizability of the results to broader populations. Moreover, most of the included studies were observational, which restricts our ability to establish causality between arsenic exposure and memory impairment. Lastly, despite efforts to gather all relevant studies, potential publication bias cannot be completely ruled out.
Conclusion
The evidence from this systematic review clearly indicates that arsenic exposure is a significant risk factor for cognitive impairment in children, with potential long-term effects that could span a lifetime. The findings call for an immediate and robust response to reduce arsenic exposure in affected regions and to protect future generations from its debilitating effects on brain development and cognitive function. Policymakers, researchers, and public health officials must prioritize this issue, ensuring that children in all regions have the opportunity to achieve their full cognitive potential in a safe and supportive environment.
Supporting information
S1 Table. List of all the extracted studies for secondary screening (N = 74).
https://doi.org/10.1371/journal.pone.0319104.s001
(DOCX)
References
- 1. Bhat A, Ravi K, Tian F, Singh B. Arsenic contamination needs serious attention: an opinion and global scenario. Pollutants. 2024;4(2):196–211.
- 2. Khosravi-Darani K, Rehman Y, Katsoyiannis IA, Kokkinos E, Zouboulis AI. Arsenic exposure via contaminated water and food sources. Water. 2022;14(12):1884.
- 3. Thakur M, Rachamalla M, Niyogi S, Datusalia AK, Flora SJS. Molecular mechanism of arsenic-induced neurotoxicity including neuronal dysfunctions. Int J Mol Sci. 2021;22(18):10077. pmid:34576240
- 4. States JC, Srivastava S, Chen Y, Barchowsky A. Arsenic and cardiovascular disease. Toxicol Sci. 2009;107(2):312–23. pmid:19015167
- 5. Tchounwou PB, Yedjou CG, Udensi UK, Pacurari M, Stevens JJ, Patlolla AK, et al. State of the science review of the health effects of inorganic arsenic: perspectives for future research. Environ Toxicol. 2019;34(2):188–202. pmid:30511785
- 6. Abbas S, Mehmood E, Qureshi A, Ahmad F, Vehra S, Khan A. An assessment of relationship between arsenic in drinking water, health status and intellectual functioning of children in district Kasur. Pak J Nutr. 2012;11.
- 7. Desai G, Barg G, Queirolo EI, Vahter M, Peregalli F, Mañay N, et al. A cross-sectional study of general cognitive abilities among Uruguayan school children with low-level arsenic exposure, potential effect modification by methylation capacity and dietary folate. Environ Res. 2018;164:124–31. pmid:29486343
- 8. Wasserman GA, Liu X, Loiacono NJ, Kline J, Factor-Litvak P, van Geen A, et al. A cross-sectional study of well water arsenic and child IQ in Maine schoolchildren. Environ Health. 2014;13(1):23. pmid:24684736
- 9. Zhang J, Hu T, Wang Y, Zhang X, Zhang H, Lin J, et al. Investigating the neurotoxic impacts of arsenic and the neuroprotective effects of dictyophora polysaccharide using SWATH-MS-based proteomics. Molecules. 2022;27(5):1495. pmid:35268596
- 10. Vázquez Cervantes GI, González Esquivel DF, Ramírez Ortega D, Blanco Ayala T, Ramos Chávez LA, López-López HE, et al. Mechanisms associated with cognitive and behavioral impairment induced by arsenic exposure. Cells. 2023;12(21):2537. pmid:37947615
- 11. Wang S-X, Wang Z-H, Cheng X-T, Li J, Sang Z-P, Zhang X-D, et al. Arsenic and fluoride exposure in drinking water: children’s IQ and growth in Shanyin county, Shanxi province, China. Environ Health Perspect. 2007;115(4):643–7. pmid:17450237
- 12. Nahar MN, Inaoka T, Fujimura M, Watanabe C, Shimizu H, Tasmin S, et al. Arsenic contamination in groundwater and its effects on adolescent intelligence and social competence in Bangladesh with special reference to daily drinking/cooking water intake. Environ Health Prev Med. 2014;19(2):151–8. pmid:24254803
- 13. Lo CK-L, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol. 2014;14:45. pmid:24690082
- 14. Rosado JL, Ronquillo D, Kordas K, Rojas O, Alatorre J, Lopez P, et al. Arsenic exposure and cognitive performance in Mexican schoolchildren. Environ Health Perspect. 2007;115(9):1371–5. pmid:17805430
- 15. Roy A, Kordas K, Lopez P, Rosado JL, Cebrian ME, Vargas GG, et al. Association between arsenic exposure and behavior among first-graders from Torreón, Mexico. Environ Res. 2011;111(5):670–6. pmid:21439564
- 16. von Ehrenstein OS, Poddar S, Yuan Y, Mazumder DG, Eskenazi B, Basu A, et al. Children’s intellectual function in relation to arsenic exposure. Epidemiology. 2007;18(1):44–51. pmid:17149142
- 17. Burgos S, Tenorio M, Zapata P, Cáceres DD, Klarian J, Alvarez N, et al. Cognitive performance among cohorts of children exposed to a waste disposal site containing heavy metals in Chile. Int J Environ Health Res. 2017;27(2):117–25. pmid:28245674
- 18. Hamadani JD, Tofail F, Nermell B, Gardner R, Shiraji S, Bottai M, et al. Critical windows of exposure for arsenic-associated impairment of cognitive function in pre-school girls and boys: a population-based cohort study. Int J Epidemiol. 2011;40(6):1593–604. pmid:22158669
- 19. Rocha-Amador D, Navarro ME, Carrizales L, Morales R, Calderón J. Decreased intelligence in children and exposure to fluoride and arsenic in drinking water. Cad Saude Publica. 2007;23(Suppl 4):S579–87. pmid:18038039
- 20. Ghosh S, Chakraborty D, Mondal N. Effect of arsenic and manganese exposure on intellectual function of children in arsenic stress area of Purbasthali, Burdwan, West Bengal. Expo Health. 2017;9:1–11.
- 21. Manju R, Hegde AM, Parlees P, Keshan A. environmental arsenic contamination and its effect on intelligence quotient of school children in a Historic Gold Mining Area Hutti, North Karnataka, India: a pilot study. J Neurosci Rural Pract. 2017;8(3):364–7. pmid:28694614
- 22. Calderón J, Navarro ME, Jimenez-Capdeville ME, Santos-Diaz MA, Golden A, Rodriguez-Leyva I, et al. Exposure to arsenic and lead and neuropsychological development in Mexican children. Environ Res. 2001;85(2):69–76. pmid:11161656
- 23. Wang Y, Wang Y, Yan C. Gender differences in trace element exposures with cognitive abilities of school-aged children: a cohort study in Wujiang city, China. Environ Sci Pollut Res Int. 2022;29(43):64807–21. pmid:35474433
- 24. Khan K, Wasserman GA, Liu X, Ahmed E, Parvez F, Slavkovich V, et al. Manganese exposure from drinking water and children’s academic achievement. Neurotoxicology. 2012;33(1):91–7. pmid:22182530
- 25. Saxena R, Gamble M, Wasserman GA, Liu X, Parvez F, Navas-Acien A, et al. Mixed metals exposure and cognitive function in Bangladeshi adolescents. Ecotoxicol Environ Saf. 2022;232:113229. pmid:35131582
- 26. Vaidya N, Holla B, Heron J, Sharma E, Zhang Y, Fernandes G, et al; Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA). Neurocognitive analysis of low-level arsenic exposure and executive function mediated by brain anomalies among children, adolescents, and young adults in India. JAMA Netw Open. 2023;6(5):e2312810. pmid:37171822
- 27. De la Ossa CA, Ramírez-Giraldo AF, Arroyo-Alvis K, Marrugo-Negrete J, Díez S. Neuropsychological effects and cognitive deficits associated with exposure to mercury and arsenic in children and adolescents of the Mojana region, Colombia. Environ Res. 2023;216(Pt 3):114467. pmid:36265603
- 28. Asadullah MN, Chaudhury N. Poisoning the mind: arsenic contamination of drinking water wells and children’s educational achievement in rural Bangladesh. Econ Educ Rev. 2011;30(5):873–88.
- 29. Vahter M, Skröder H, Rahman SM, Levi M, Derakhshani Hamadani J, Kippler M. Prenatal and childhood arsenic exposure through drinking water and food and cognitive abilities at 10 years of age: a prospective cohort study. Environ Int. 2020;139:105723. pmid:32298878
- 30. Zhou T, Guo J, Zhang J, Xiao H, Qi X, Wu C, et al. Sex-specific differences in cognitive abilities associated with childhood cadmium and manganese exposures in school-age children: a prospective cohort study. Biol Trace Elem Res. 2020;193(1):89–99. pmid:30977088
- 31. Wasserman GA, Liu X, Parvez F, Ahsan H, Factor-Litvak P, van Geen A, et al. Water arsenic exposure and children’s intellectual function in Araihazar, Bangladesh. Environ Health Perspect. 2004;112(13):1329–33. pmid:15345348
- 32. Wasserman GA, Liu X, Parvez F, Ahsan H, Factor-Litvak P, Kline J, et al. Water arsenic exposure and intellectual function in 6-year-old children in Araihazar, Bangladesh. Environ Health Perspect. 2007;115(2):285–9. pmid:17384779
- 33. Khan MI, Ahmad MF, Ahmad I, Ashfaq F, Wahab S, Alsayegh AA, et al. Arsenic exposure through dietary intake and associated health hazards in the middle east. Nutrients. 2022;14(10):2136. pmid:35631276
- 34. Zacher T, Endres K, Richards F, Robe LB, Powers M, Yracheta J, et al. Evaluation of a water arsenic filter in a participatory intervention to reduce arsenic exposure in American Indian communities: the strong heart water study. Sci Total Environ. 2023;862:160217. pmid:36410482