Cadmium Exposure and Neurodevelopment in US Children
Cadmium Exposure and Neurodevelopment in US Children
Background Low-level environmental cadmium exposure in children may be associated with adverse neurodevelopmental outcomes.
Objective Our aim was to evaluate associations between urinary cadmium concentration and reported learning disability (LD), special education utilization, and attention deficit hyperactivity disorder (ADHD) in U.S. children using National Health and Nutrition Examination Survey (NHANES) data.
Methods We analyzed data from a subset of participants in NHANES (1999–2004) who were 6–15 years of age and had spot urine samples analyzed for cadmium. Outcomes were assessed by parent or proxy-respondent report. We fit multivariable-adjusted logistic regression models to estimate associations between urinary cadmium and the outcomes.
Results When we compared children in the highest quartile of urinary cadmium with those in the lowest quartile, odds ratios adjusted for several potential confounders were 3.21 [95% confidence interval (CI): 1.43, 7.17] for LD, 3.00 (95% CI: 1.12, 8.01) for special education, and 0.67 (95% CI: 0.28, 1.61) for ADHD. There were no significant interactions with sex, but associations with LD and special education were somewhat stronger in males, and the trend in the ADHD analysis was only evident among those with blood lead levels above the median.
Conclusions These findings suggest that children who have higher urinary cadmium concentrations may have increased risk of both LD and special education. Importantly, we observed these associations at exposure levels that were previously considered to be without adverse effects, and these levels are common among U.S. children.
Cadmium is a heavy metal found in the earth's crust that is disseminated in the environment both by natural processes and by human activities such as fossil fuel burning, waste incineration, smelting procedures, and the use of phosphate fertilizers (Agency for Toxic Substances and Disease Registry 2008). Uptake of environmental cadmium in plants and animals results in human exposures via food or tobacco smoke, and occupational exposures can occur as well [European Food Safety Authority (EFSA) 2009]. Cadmium is known to be nephrotoxic (EFSA 2009), but there is also a growing body of evidence suggesting that cadmium exposure may have adverse neurodevelopmental consequences.
Several animal studies have reported effects of cadmium on electrophysiological parameters, markers of neurotransmitter function, and neurobehavioral outcomes (Ali et al. 1986; Desi et al. 1998; Lehotzky et al. 1990; Nagymajtenyi et al. 1997; Nation et al. 1983, 1984, 1989, 1990). Studies in children have reported associations between higher cadmium levels and mental retardation (Jiang et al. 1990; Marlowe et al. 1983), decreased verbal IQ (Thatcher et al. 1982), lower neuropsychological test performance (Bonithon-Kopp et al. 1986; Stellern et al. 1983), learning disability (LD) (Capel et al. 1981; Ely et al. 1981; Pihl and Parkes 1977), poor reading performance (Thatcher et al. 1984b), neurophysiological evoked potential differences (Thatcher et al. 1984a), and behavioral problems in the presence of concurrently elevated lead levels (Marlowe et al. 1985a). In contrast, other human studies have failed to detect significant multivariable-adjusted associations between markers of cadmium exposure and neurodevelopmental outcomes (Cao et al. 2009; Gillberg et al. 1982; Lee et al. 2007; Marlowe et al. 1985b; Moon et al. 1985; Wright et al. 2006). These studies varied in size, quality, and design. In addition, they used several different exposure metrics, evaluated different windows of susceptibility, and differed in their consideration of potentially important confounders. These factors may help explain the inconsistent results, and further research could help resolve some of the discrepancies.
In this study, we analyzed a large representative sample of U.S. children 6–15 years of age from the National Health and Nutrition Examination Survey (NHANES), to determine whether higher levels of urinary cadmium were associated with attention deficit hyperactivity disorder (ADHD), LD, or placement in special education. To our knowledge, this is the largest study to evaluate associations between urinary cadmium and neurodevelopmental outcomes, and the first to do so in a nationally representative sample of U.S. children.
Abstract and Introduction
Abstract
Background Low-level environmental cadmium exposure in children may be associated with adverse neurodevelopmental outcomes.
Objective Our aim was to evaluate associations between urinary cadmium concentration and reported learning disability (LD), special education utilization, and attention deficit hyperactivity disorder (ADHD) in U.S. children using National Health and Nutrition Examination Survey (NHANES) data.
Methods We analyzed data from a subset of participants in NHANES (1999–2004) who were 6–15 years of age and had spot urine samples analyzed for cadmium. Outcomes were assessed by parent or proxy-respondent report. We fit multivariable-adjusted logistic regression models to estimate associations between urinary cadmium and the outcomes.
Results When we compared children in the highest quartile of urinary cadmium with those in the lowest quartile, odds ratios adjusted for several potential confounders were 3.21 [95% confidence interval (CI): 1.43, 7.17] for LD, 3.00 (95% CI: 1.12, 8.01) for special education, and 0.67 (95% CI: 0.28, 1.61) for ADHD. There were no significant interactions with sex, but associations with LD and special education were somewhat stronger in males, and the trend in the ADHD analysis was only evident among those with blood lead levels above the median.
Conclusions These findings suggest that children who have higher urinary cadmium concentrations may have increased risk of both LD and special education. Importantly, we observed these associations at exposure levels that were previously considered to be without adverse effects, and these levels are common among U.S. children.
Introduction
Cadmium is a heavy metal found in the earth's crust that is disseminated in the environment both by natural processes and by human activities such as fossil fuel burning, waste incineration, smelting procedures, and the use of phosphate fertilizers (Agency for Toxic Substances and Disease Registry 2008). Uptake of environmental cadmium in plants and animals results in human exposures via food or tobacco smoke, and occupational exposures can occur as well [European Food Safety Authority (EFSA) 2009]. Cadmium is known to be nephrotoxic (EFSA 2009), but there is also a growing body of evidence suggesting that cadmium exposure may have adverse neurodevelopmental consequences.
Several animal studies have reported effects of cadmium on electrophysiological parameters, markers of neurotransmitter function, and neurobehavioral outcomes (Ali et al. 1986; Desi et al. 1998; Lehotzky et al. 1990; Nagymajtenyi et al. 1997; Nation et al. 1983, 1984, 1989, 1990). Studies in children have reported associations between higher cadmium levels and mental retardation (Jiang et al. 1990; Marlowe et al. 1983), decreased verbal IQ (Thatcher et al. 1982), lower neuropsychological test performance (Bonithon-Kopp et al. 1986; Stellern et al. 1983), learning disability (LD) (Capel et al. 1981; Ely et al. 1981; Pihl and Parkes 1977), poor reading performance (Thatcher et al. 1984b), neurophysiological evoked potential differences (Thatcher et al. 1984a), and behavioral problems in the presence of concurrently elevated lead levels (Marlowe et al. 1985a). In contrast, other human studies have failed to detect significant multivariable-adjusted associations between markers of cadmium exposure and neurodevelopmental outcomes (Cao et al. 2009; Gillberg et al. 1982; Lee et al. 2007; Marlowe et al. 1985b; Moon et al. 1985; Wright et al. 2006). These studies varied in size, quality, and design. In addition, they used several different exposure metrics, evaluated different windows of susceptibility, and differed in their consideration of potentially important confounders. These factors may help explain the inconsistent results, and further research could help resolve some of the discrepancies.
In this study, we analyzed a large representative sample of U.S. children 6–15 years of age from the National Health and Nutrition Examination Survey (NHANES), to determine whether higher levels of urinary cadmium were associated with attention deficit hyperactivity disorder (ADHD), LD, or placement in special education. To our knowledge, this is the largest study to evaluate associations between urinary cadmium and neurodevelopmental outcomes, and the first to do so in a nationally representative sample of U.S. children.
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