Response to: "What is the meaning of non-linear dose-response relationships between blood lead concentrations and IQ?".
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Dose-Response Relationship, Drug↗
Biomedical subjects
Richard L Canfield
Publications and source records attributed to Richard L Canfield.
The effect of maternal PTSD following in utero trauma exposure on behavior and temperament in the 9-month-old infant.
UNLABELLED: In view of evidence of in utero glucocorticoid programming, and our prior observation of lower cortisol levels in 9-month-old infants of mothers with posttraumatic stress disorder (PTSD) compared to mothers without PTSD, we undertook an examination of the effect of in utero maternal stress, as determined by PTSD symptom severity, and maternal cortisol levels on behavioral outcomes in the infant. METHODS: Ninety-eight pregnant women directly exposed to the World Trade Center (WTC) collapse on 9/11 provided salivary cortisol samples and completed a PTSD symptom questionnaire and a behavior rating scale to measure infant temperament, including distress to limitations, and response to novelty. RESULTS: Mothers who developed PTSD in response to 9/11 had lower morning and evening salivary cortisol levels, compared to mothers who did not develop PTSD. Maternal morning cortisol levels were inversely related to their rating of infant distress and response to novelty (i.e., loud noises, new foods, unfamiliar people). Also, mothers who had PTSD rated their infants as having greater distress to novelty than did mothers without PTSD (t = 2.77, df = 61, P = 0.007). CONCLUSION: Longitudinal studies are needed to determine how the association between maternal PTSD symptoms and cortisol levels and infant temperament reflect genetic and/or epigenetic mechanisms of intergenerational transmission.
Adult↗
Deficits in cognitive function and achievement in Mexican first-graders with low blood lead concentrations.
Elevated blood lead levels in children are associated with lower scores on tests of cognitive functioning. Recent studies have reported inverse relations between lifetime exposure and intellectual functioning at blood lead concentrations below 10 microg/dL, the Centers for Disease Control and Prevention's (CDC) level of concern. We report associations between blood lead and cognitive performance for first-grade Mexican children living near a metal foundry. Using a cross-sectional design, we examined the relation between children's concurrent blood lead concentrations (mean (SD) 11.4 microg/dL (6.1)) and their performance on 14 tests of global or specific cognitive functions. The blood lead-cognition relations were modeled using both linear and nonlinear methods. After adjustment for covariates, a higher blood lead level was associated with poorer cognitive performance on several cognitive tests. Segmented linear regressions revealed significant effects of lead but only for the segments defined by a concurrent blood lead concentration below 10-14 microg/dL. One implication of these findings is that at the age of 7 years, even in the absence of information on lead exposure in infancy and early childhood, a test result with blood lead < 10 microg/dL should not be considered safe. Together with other recent findings, these results add to the empirical base of support available for evaluating the adequacy of current screening guidelines and for motivating efforts at primary prevention of childhood lead exposure.
Child↗
Comments on "Recent developments in low-level lead exposure and intellectual impairment in children".
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Child Development↗
Principles and practices of neurodevelopmental assessment in children: lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research.
Principles and practices of pediatric neurotoxicology are reviewed here with the purpose of guiding the design and execution of the planned National Children's Study. The developing human central nervous system is the target organ most vulnerable to environmental chemicals. An investigation of the effects of environmental exposures on child development is a complex endeavor that requires consideration of numerous critical factors pertinent to a study's concept, design, and execution. These include the timing of neurodevelopmental assessment, matters of biologic plausibility, site, child and population factors, data quality assurance and control, the selection of appropriate domains and measures of neurobehavior, and data safety and monitoring. Here we summarize instruments for the assessment of the neonate, infant, and child that are being employed in the Centers for Children's Environmental Health and Disease Prevention Research, sponsored by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, discuss neural and neurobiologic measures of development, and consider the promises of gene-environment studies. The vulnerability of the human central nervous system to environmental chemicals has been well established, but the contribution these exposures may make to problems such as attention deficit disorder, conduct problems, pervasive developmental disorder, or autism spectrum disorder remain uncertain. Large-scale studies such as the National Children's Study may provide some important clues. The human neurodevelopmental phenotype will be most clearly represented in models that include environmental chemical exposures, the social milieu, and complex human genetic characteristics that we are just beginning to understand.
Central Nervous System↗
Low-level environmental lead exposure and children's intellectual function: an international pooled analysis.
Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 microg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 microg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5-10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 microg/dL and declined to 9.4 microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 microg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 microg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were 3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 microg/dL was significantly greater than that observed for those with a maximal blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is associated with intellectual deficits.
Child↗
Impaired neuropsychological functioning in lead-exposed children.
Neuropsychological functions were assessed in 174 children participating in a longitudinal study of low-level lead exposure. At age 5 1/2 years, children were administered the Working Memory and Planning Battery of the Cambridge Neuropsychological Testing Automated Battery. Measures of sociodemographic characteristics of the family, prenatal and perinatal risk, quality of caregiving and crowding in the home, and maternal and child intelligence were used as covariates to test the hypothesis that children with higher lifetime average blood lead concentrations would perform more poorly on tests of working memory, attentional flexibility, and planning and problem solving. The lifetime average blood lead level in this sample was 7.2 micrograms per deciliter (mug/dL; range: 0-20 mug/dL). Children with greater exposure performed more poorly on tests of executive processes. In both bivariate and multivariate analyses, children with higher lifetime average blood lead concentrations showed impaired performance on the tests of spatial working memory, spatial memory span, intradimensional and extradimensional shifts, and an analog of the Tower of London task. Many of the significant associations remained after controlling for children's intelligence test scores, in addition to the other covariates. These findings indicate that the effects of pediatric lead exposure are not restricted to global indexes of general intellectual functioning, and executive processes may be at particular risk of lead-induced neurotoxicity.
Attention↗
Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter.
BACKGROUND: Despite dramatic declines in children's blood lead concentrations and a lowering of the Centers for Disease Control and Prevention's level of concern to 10 microg per deciliter (0.483 micromol per liter), little is known about children's neurobehavioral functioning at lead concentrations below this level. METHODS: We measured blood lead concentrations in 172 children at 6, 12, 18, 24, 36, 48, and 60 months of age and administered the Stanford-Binet Intelligence Scale at the ages of 3 and 5 years. The relation between IQ and blood lead concentration was estimated with the use of linear and nonlinear mixed models, with adjustment for maternal IQ, quality of the home environment, and other potential confounders. RESULTS: The blood lead concentration was inversely and significantly associated with IQ. In the linear model, each increase of 10 microg per deciliter in the lifetime average blood lead concentration was associated with a 4.6-point decrease in IQ (P=0.004), whereas for the subsample of 101 children whose maximal lead concentrations remained below 10 microg per deciliter, the change in IQ associated with a given change in lead concentration was greater. When estimated in a nonlinear model with the full sample, IQ declined by 7.4 points as lifetime average blood lead concentrations increased from 1 to 10 microg per deciliter. CONCLUSIONS: Blood lead concentrations, even those below 10 microg per deciliter, are inversely associated with children's IQ scores at three and five years of age, and associated declines in IQ are greater at these concentrations than at higher concentrations. These findings suggest that more U.S. children may be adversely affected by environmental lead than previously estimated.
Child, Preschool↗
Low-level lead exposure, executive functioning, and learning in early childhood.
The current paper presents evidence relating low-level lead exposure to impaired executive functioning in young children. Using the Shape School task, we assessed focused attention, attention switching, working memory, and the ability to inhibit automatic responses in a cohort of 170 children. Participants performed the Shape School task at both 48 and 54 months of age; the mean blood lead level was 6.49 microg/dl at 48 months. After controlling for a wide range of sociodemographic, prenatal, and perinatal variables, blood lead level was negatively associated with children's focused attention while performing the tasks, efficiency at naming colors, and inhibition of automatic responding. In addition, children with higher blood lead levels completed fewer phases of the task and knew fewer color and shape names. There was no association between blood lead and performance on the most difficult tasks, those requiring attention switching or the combination of inhibition and switching. Children's IQ scores were strongly associated with blood lead and Shape School performance, and when entered as a covariate, only color knowledge and the number of tasks completed remained significant. Results provide only weak support for impaired executive functioning, but the deficits in color knowledge may indicate a primary sensory deficit or difficulty with forming conditional associations, both implicating disruptions in dopamine system function.
Attention↗