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This study aimed to assess associations between prenatal and postnatal exposure to lead (Pb), mercury (Hg) and polychlorinated biphenyls (PCBs) and gray matter volume of key regions of the brain reward circuit, namely the caudate nucleus, putamen, nucleus accumbens (nAcc), the amygdala, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC). Structural magnetic resonance imaging (MRI) was conducted in 77 Inuit adolescents (mean age = 18.39) from Nunavik, Canada, who also completed the Brief Sensation Seeking Scale (BSSS-4) and Sensation Seeking - 2 (SS-2), two self-report questionnaires evaluating the tendency toward sensation seeking, which is a proxy of reward-related behaviors. Exposures to Pb, Hg and PCBs were measured in cord blood at birth, in blood samples at 11 years old and at time of testing (18 years old). Multivariate linear regressions were corrected for multiple comparisons and adjusted for potential confounders, such as participants' sociodemographic characteristics and nutrient fish intake. Results showed that higher cord blood Pb levels predicted smaller gray matter volume in the bilateral nAcc, caudate nucleus, amygdala and OFC as well as in left ACC. A moderating effect of sex was identified, indicating that the Pb-related reduction in volume in the nAcc and caudate nucleus was more pronounced in female. Higher blood Hg levels at age 11 predicted smaller right amygdala independently of sex. No significant associations were found between blood PCBs levels at all three times of exposure. This study provides scientific support for the detrimental effects of prenatal Pb and childhood Hg blood concentrations on gray matter volume in key reward-related brain structures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Exposure to environmental contaminants is an important public health concern for the Inuit population of northern Québec, who have been exposed to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb). During the last 25 years, the Nunavik Child Development Study (NCDS) birth cohort has reported adverse associations between these exposures and brain function outcomes. In the current study, we aimed to determine whether contaminant exposure is associated with alterations of the corpus callosum (CC), which plays an important role in various cognitive, motor and sensory function processes. Magnetic resonance imaging (MRI) was administered to 89 NCDS participants (mean age ± SD = 18.4 ± 1.2). Diffusion-weighted imaging was assessed to characterize the microstructure of the CC white matter in 7 structurally and functionally distinct regions of interest (ROIs) using a tractography-based segmentation approach. The following metrics were computed: fiber tract density, fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). Multiple linear regression models adjusted for sex, age, current alcohol/drug use and fish nutrients (omega-3 fatty acids and selenium) were conducted to assess the association between diffusion-weighted imaging metrics and Hg, PCB 153 and Pb concentrations obtained at birth in the cord blood and postnatally (mean values from blood samples at 11 and 18 years of age). Exposures were not associated with fiber tract density. Nor were significant associations found with cord and postnatal blood Pb concentrations for FA. However, pre- and postnatal Hg and PCB concentrations were significantly associated with higher FA of several regions of the CC, namely anterior midbody, posterior midbody, isthmus, and splenium, with the most pronounced effects observed in the splenium. FA results were mainly associated with lower RD. This study shows that exposure to Hg and PCB 153 alters the posterior microstructure of the CC, providing neuroimaging evidence of how developmental exposure to environmental chemicals can impair brain function and behavior in late adolescence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Inuit communities in Northern Quebec (Canada) are exposed to environmental contaminants, particularly to mercury, lead and polychlorinated biphenyls (PCBs). Previous studies reported adverse associations between these neurotoxicants and memory performance. Here we aimed to determine the associations of pre- and postnatal exposures to mercury, lead and PCB-153 on spatial navigation memory in 212 Inuit adolescents (mean age = 18.5 years) using a computer task which requires learning the location of a hidden platform based on allocentric spatial representation. Contaminant concentrations were measured in cord blood at birth and blood samples at 11 years of age and at time of testing. Multivariate regression models showed that adolescent mercury and prenatal PCB-153 exposures were associated with poorer spatial learning, whereas current exposure to PCB-153 was associated with altered spatial memory retrieval at the probe test trial. These findings suggest that contaminants might be linked to different aspects of spatial navigation processing at different stages., (© 2022 Wiley Periodicals LLC.)

Background/aims: Given that their traditional lifestyle and diet still relies on fish and other marine species for sustenance, the Inuit are highly exposed to polychlorinated biphenyls (PCBs) and PCBs are increasingly linked to obesity. However, evidence is not consistent regarding which periods of exposure are most relevant. In this study, we examine whether in utero, childhood, and adolescent exposure to PCBs are related to physical growth at adolescence., Method: Inuit adolescents from Canada (N=212) enrolled in a prospective longitudinal cohort study since birth were assessed for height, weight, body mass index (BMI), fat mass index (FMI) and fat free mass index (FFMI) at 18 years of age. PCB 153 concentrations were quantified in blood samples obtained at birth (umbilical cord), 11, and 18 years of age. Maternal anthropometrics were measured and those for the newborns collected from medical records. Data on biological mothers and participants' sociodemographic characteristics and food security were collected using interviews. Multiple linear regression analyses were used to test associations between PCB 153 concentrations and adolescent anthropometric measures., Results: Cord PCB 153 was not related to height or FFMI at adolescence. By contrast, analyses showed that cord PCB 153 was related to higher BMI, FMI and marginally to weight in girls but not boys. Child PCB 153 was not related to height, weight or FFMI in adolescence. Child PCB 153 was related to lower BMI and FMI at adolescence in both sexes, particularly among those considered overweight or obese during childhood. Adolescent PCB 153 was not associated with any outcome., Conclusion: This study suggests that prenatal exposure to PCBs may have a long-term effect on growth in early adulthood among girls and identifies the peri-pubertal period as another window of sensitivity for the action of PCBs. Our findings also suggest that exposure to PCBs and body size be documented in multiple time periods from infancy to adulthood., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study aimed to examine the relation between anxiety among the at-risk population of Inuit adolescents and diverse developmental risk factors including exposure to environmental chemicals, a subject of concern in Nunavik. Anxiety was assessed in 89 Inuit participants (mean age = 18.4 years; range = 16.2-21.9) with the Screen for Child Anxiety Related Emotional Disorders (SCARED) and the State-Trait Anxiety Inventory (STAI). Potential risk factors for anxiety were documented at birth, 11 years of age and 18 years of age, including blood levels of chemicals (mercury, lead, PCBs) and nutrients, as well as age, sex, estimated IQ, drug and alcohol use, bullying, exposure to domestic violence, food insecurity, crowding and socio-economic status. Results showed that participants scored high on both measures of anxiety, particularly the SCARED, for which the mean score was above the clinical threshold. Multiple regression results show that significant risk predictors obtained from the SCARED scores were female sex (β = 0.32), higher current blood mercury concentration (β = 0.26), food insecurity (β = 0.26) and bullying experiences in the last year (β = 0.21). The significant predictors for the STAI trait anxiety were food insecurity (β = 0.25) and lower estimated IQ (β = -0.31), whereas food insecurity (β = 0.21), lower blood levels of vitamin E (β = -0.25) and higher cord blood mercury concentrations (β = 0.25) were found for STAI situational anxiety. Further regression analyses suggested that the adolescent-related variables were the most important risk factors. Our findings show that Inuit adolescents are at risk for anxiety via multiple contributing factors, particularly current exposure to mercury, food insecurity and female sex., Competing Interests: Declaration of competing interest None, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Motor deficits have frequently been reported in methylmercury (MeHg) poisoning in adults. However, whether exposure to neurotoxic contaminants from environmental sources early in life is associated with neuromotor impairments has received relatively little attention. This study examines the relation of developmental exposure to MeHg, polychlorinated biphenyls (PCBs), and lead to motor function in school-age Inuit children exposed through their traditional diet., Methods: In a prospective study in Nunavik, children (mean age=11.3years) were assessed on a battery of fine motor tasks, namely the Stanford-Binet Copying subtest (N=262), the Santa Ana Form Board, and the Finger Tapping Test (N=215). The relation of mercury (Hg; as an index of MeHg exposure), PCB congener 153 (PCB153), and lead concentrations in cord and current blood samples to task performance was examined using linear regression analyses., Results: After adjustment for potential confounders and control for the other contaminants, higher current PCB concentrations were associated with poorer Santa Ana Form Board and Finger Tapping performance. Results were virtually identical when PCB153 was replaced by other PCB congeners. Higher current Hg levels were independently associated with poorer Finger Tapping performance., Conclusions: This is the first prospective longitudinal study in children to provide evidence of neuromotor impairments associated with postnatal exposure to seafood contaminants from environmental sources. Fine motor speed appears particularly sensitive to the effects of postnatal PCB exposure, which is unusually high in this population. Results with postnatal MeHg are concordant with previous cross-sectional studies with children and adults., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Although prenatal methylmercury exposure has been linked to poorer intellectual function in several studies, data from two major prospective, longitudinal studies yielded contradictory results. Associations with cognitive deficits were reported in a Faroe Islands cohort, but few were found in a study in the Seychelles Islands. It has been suggested that co-exposure to another contaminant, polychlorinated biphenyls (PCBs), may be responsible for the positive findings in the former study and that co-exposure to nutrients in methylmercury-contaminated fish may have obscured and/or protected against adverse effects in the latter., Objectives: We aimed to determine the degree to which co-exposure to PCBs may account for the adverse effects of methylmercury and the degree to which co-exposure to docosahexaenoic acid (DHA) may obscure these effects in a sample of Inuit children in Arctic Québec., Methods: IQ was estimated in 282 school-age children from whom umbilical cord blood samples had been obtained and analyzed for mercury and other environmental exposures., Results: Prenatal mercury exposure was related to poorer estimated IQ after adjustment for potential confounding variables. The entry of DHA into the model significantly strengthened the association with mercury, supporting the hypothesis that beneficial effects from DHA intake can obscure adverse effects of mercury exposure. Children with cord mercury ≥ 7.5 μg/L were four times as likely to have an IQ score < 80, the clinical cut-off for borderline intellectual disability. Co-exposure to PCBs did not alter the association of mercury with IQ., Conclusions: To our knowledge, this is the first study to document an association of prenatal mercury exposure with poorer performance on a school-age assessment of IQ, a measure whose relevance for occupational success in adulthood is well established. This association was seen at levels in the range within which many U.S. children of Asian-American background are exposed.

Background: Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children., Methods: We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children (n=290) were evaluated at birth and at 8-14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood., Results: Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and shows a tendency of a smaller head circumference during childhood., Interpretation: Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduced growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Polychlorinated biphenyls (PCBs), methylmercury (MeHg), and lead (Pb) are environmental contaminants known for their adverse effects on cognitive development., Objectives: In this study we examined the effects of prenatal exposure to PCBs, MeHg, and Pb on cognitive development in a sample of Inuit infants from Arctic Québec., Methods: Mothers were recruited at local prenatal clinics. PCBs, mercury (Hg), Pb, and two seafood nutrients-docosahexaenoic acid (DHA) and selenium (Se)-were measured in umbilical cord blood. Infants (n = 94) were assessed at 6.5 and 11 months of age on the Fagan Test of Infant Intelligence (FTII), A-not-B test, and Bayley Scales of Infant Development-2nd Edition (BSID-II)., Results: Multiple regression analyses revealed that higher prenatal PCB exposure was associated with decreased FTII novelty preference, indicating impaired visual recognition memory. Prenatal Hg was associated with poorer performance on A-not-B, which depends on working memory and is believed to be a precursor of executive function. Prenatal Pb was related to longer FTII fixation durations, indicating slower speed of information processing., Conclusions: PCBs, MeHg, and Pb each showed specific and distinct patterns of adverse associations with the outcomes measured during infancy. By contrast, none of these exposures was associated with performance on the BSID-II, a global developmental measure. The more focused, narrow band measures of cognitive function that appeared to be sensitive to these exposures also provide early indications of long-term impairment in specific domains that would otherwise not likely be evident until school age., Citation: Boucher O, Muckle G, Jacobson JL, Carter RC, Kaplan-Estrin M, Ayotte P, Dewailly É, Jacobson SW. 2014. Domain-specific effects of prenatal exposure to PCBs, mercury, and lead on infant cognition: results from the Environmental Contaminants and Child Development Study in Nunavik. Environ Health Perspect 122:310-316; http://dx.doi.org/10.1289/ehp.1206323.

Background: Several studies have reported negative associations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and mercury (Hg) with duration of gestation and fetal growth in fish eating populations. Docosahexaenoic acid (DHA) from fish, seafood and marine mammal intake has been reported to be positively related with pregnancy duration and fetal growth. So far, it remains unclear, however, if the associations of environmental contaminants (ECs) with growth are direct or mediated through their relation with the duration of gestation and the degree to which DHA intake during pregnancy attenuates the negative association of ECs with fetal growth., Objectives: To investigate direct and indirect associations of in utero exposure to ECs with fetal growth and pregnancy duration while taking into account the possible positive effects of DHA., Methods: Pregnant Inuit women (N=248) from Arctic Quebec were recruited and cord blood samples were analyzed for PCBs, HCB, Hg and DHA. Anthropometric measurements were assessed at birth. Path models were used to evaluate direct and indirect associations., Results: Cord concentrations of PCB 153, HCB and Hg were significantly associated with shorter duration of pregnancy (β varying from -0.17 to -0.20, p<0.05). Path models indicated that the associations of PCBs, HCB and Hg with reduced fetal growth (β varying from -0.09 to -0.13, p<0.05) were mediated through their relations with shorter gestation duration. Cord DHA was indirectly related to greater growth parameters (β varying from 0.17 to 0.20, p<0.05) through its positive association with gestation duration., Conclusion: Prenatal exposure to ECs was associated with reduced gestation duration, which is a recognized determinant of fetal growth. DHA intake during pregnancy appeared to have independent positive association with fetal growth by prolonging gestation. Whether these associations are causal remains to be elucidated., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Prenatal exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs) has been associated with impaired performance on attention tasks in previous studies, but the extent to which these cognitive deficits translate into behavioral problems in the classroom and attention deficit/hyperactivity disorder (ADHD) remains unknown. By contrast, lead (Pb) exposure in childhood has been associated with ADHD and disruptive behaviors in several studies., Objectives: In this study we examined the relation of developmental exposure to MeHg, PCBs, and Pb to behavioral problems at school age in Inuit children exposed through their traditional diet., Methods: In a prospective longitudinal study conducted in the Canadian Arctic, exposure to contaminants was measured at birth and at school age. An assessment of child behavior (n = 279; mean age = 11.3 years) was obtained from the child's classroom teacher on the Teacher Report Form (TRF) from the Child Behavior Checklist, and the Disruptive Behavior Disorders Rating Scale (DBD)., Results: Cord blood mercury concentrations were associated with higher TRF symptom scores for attention problems and DBD scores consistent with ADHD. Current blood Pb concentrations were associated with higher TRF symptom scores for externalizing problems and with symptoms of ADHD (hyperactive-impulsive type) based on the DBD., Conclusions: To our knowledge, this study is the first to identify an association between prenatal MeHg and ADHD symptomatology in childhood and the first to replicate previously reported associations between low-level childhood Pb exposure and ADHD in a population exposed to Pb primarily from dietary sources.

Background: Lead (Pb) and polychlorinated biphenyls (PCBs) are neurotoxic contaminants that have been related to impairment in response inhibition., Objectives: In this study we examined the neurophysiological correlates of the response inhibition deficits associated with these exposures, using event-related potentials (ERPs) in a sample of school-age Inuit children from Arctic Québec exposed through their traditional diet., Methods: In a prospective longitudinal study, we assessed 196 children (mean age, 11.3 years) on a visual go/no-go response inhibition paradigm. Pb, PCB, and mercury (Hg) concentrations were analyzed in cord and current blood samples. Hierarchical multiple regression analyses were conducted to examine the associations of contaminant levels to go/no-go performance (mean reaction time, percent correct go, percent correct no-go) and five ERPs [N2, P3, error-related negativity, error positivity (Pe), and correct response positivity (Pc)] after control for confounding variables., Results: Current blood Pb concentrations were associated with higher rates of false alarms and with decreased P3 amplitudes to go and no-go trials. Current plasma PCB-153 concentrations were associated with slower reaction times and with reduced amplitudes of the Pe and Pc response-related potentials. Hg concentrations were not related to any outcome on this task but showed significant interactions with other contaminants on certain outcomes., Conclusions: These results suggest that Pb exposure during childhood impairs the child's ability to allocate the cognitive resources needed to correctly inhibit a prepotent response, resulting in increased impulsivity. By contrast, postnatal PCB exposure appears to affect processes associated with error monitoring, an aspect of behavioral regulation required to adequately adapt to the changing demands of the environment, which results in reduced task efficiency.

Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are seafood contaminants known for their adverse effects on neurodevelopment. This study examines the relation of developmental exposure to these contaminants to information processing assessed with event-related potentials (ERPs) in school-aged Inuit children from Nunavik (Arctic Québec). In a prospective longitudinal study on child development, exposure to contaminants was measured at birth and 11 years of age. An auditory oddball protocol was administered at 11 years to measure ERP components N1 and P3b. Multiple regression analyses were performed to examine the associations of levels of the contaminants to auditory oddball performance (mean reaction time, omission errors and false alarms) and ERP parameters (latency and amplitude) after control for potential confounding variables. A total of 118 children provided useable ERP data. Prenatal MeHg exposure was associated with slower reaction times and fewer false alarms during the oddball task. Analyses of the ERP parameters revealed that prenatal MeHg exposure was related to greater amplitude and delayed latency of the N1 wave in the target condition but not to the P3b component. MeHg effects on the N1 were stronger after control for seafood nutrients. Prenatal PCB exposure was not related to any endpoint for sample as a whole but was associated with a decrease in P3b amplitude in the subgroup of children who had been breast-fed for less than 3 months. Body burdens of MeHg and PCBs at 11 years were not related to any of the behavioural or ERP measures. These data suggest that prenatal MeHg exposure alters attentional mechanisms modulating early processing of sensory information. By contrast, prenatal PCB exposure appears to affect information processing at later stages, when the information is being consciously evaluated. These effects seem to be mitigated in children who are breast-fed for a more extended period., ((c) 2010 Elsevier Inc. All rights reserved.)

The Inuit population of Nunavik (Canada) is exposed to immunotoxic organochlorines (OCs) mainly through the consumption of fish and marine mammal fat. We investigated the effect of perinatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) on the incidence of acute infections in Inuit infants. We reviewed the medical charts of a cohort of 199 Inuit infants during the first 12 months of life and evaluated the incidence rates of upper and lower respiratory tract infections (URTI and LRTIs, respectively), otitis media, and gastrointestinal (GI) infections. Maternal plasma during delivery and infant plasma at 7 months of age were sampled and assayed for PCBs and DDE. Compared to rates for infants in the first quartile of exposure to PCBs (least exposed), adjusted rate ratios for infants in higher quartiles ranged between 1.09 and 1.32 for URTIs, 0.99 and 1.39 for otitis, 1.52 and 1.89 for GI infections, and 1.16 and 1.68 for LRTIs during the first 6 months of follow-up. For all infections combined, the rate ratios ranged from 1.17 to 1.27. The effect size was similar for DDE exposure but was lower for the full 12-month follow-up. Globally, most rate ratios were > 1.0, but few were statistically significant (p < 0.05). No association was found when postnatal exposure was considered. These results show a possible association between prenatal exposure to OCs and acute infections early in life in this Inuit population.

Objective: To examine the relation of prenatal polychlorinated biphenyl (PCB) exposure to child performance on neuropsychological tests of attention and information processing. Study design In this prospective, longitudinal study, assessment of prenatal PCB exposure was based on umbilical cord serum and maternal serum and milk concentrations. The children were tested in their homes at age 11 years. Multiple regression was used to examine the relation of this exposure to performance on 15 neuropsychological tests after controlling for a broad range of potential confounding variables., Results: Adverse effects were seen primarily in children who had not been breast fed. Among these children, prenatal PCB exposure was associated with greater impulsivity, poorer concentration, and poorer verbal, pictorial, and auditory working memory. There was no evidence of visual-spatial deficit or increased hyperactivity., Conclusions: These findings are consistent with earlier reports of greater vulnerability to prenatal PCB exposure in children who were not breast fed. It is not clear whether the protection offered by breast-feeding is caused by nutrients in breast milk or better quality of intellectual stimulation often provided by breast-feeding mothers.

Polychlorinated biphenyls (PCBs) are food-chain contaminants that have been shown to induce adverse developmental effects in humans. In the course of an epidemiologic study established to investigate neurodevelopmental deficits induced by environmental PCB exposure in the Inuit population of northern Québec (Nunavik, Canada), we compared three biomarkers of prenatal exposure and models to predict PCB plasma concentration at 6 months postpartum. Concentrations of 14 PCB congeners were measured by high-resolution gas chromatography with electron capture detection in lipids extracted from maternal plasma, cord plasma, breast milk (collected at approximately 1 month postpartum), and 6-month-old infant plasma samples. Similar congener profiles were observed in all biologic samples, and PCB-153, the most abundant and persistent PCB congener, was strongly correlated with other frequently detected PCB congeners in all biologic media. When expressed on a lipid basis, maternal plasma, cord plasma, and milk concentrations of this congener were strongly intercorrelated, indicating that PCB concentration in any of these biologic media is a good indicator of prenatal exposure to PCBs. A multivariate model that included maternal PCB-153 plasma lipid concentration, breast-feeding duration, and the sum of two skin-fold thicknesses (an index of infant body fat mass) explained 72% of PCB-153 plasma concentration variance at 6 months postpartum (p < 0.001). By contrast, based on the product of breast-feeding duration times the concentration of PCBs in plasma lipids, which was used as an index of postnatal PCB exposure in several studies, only 36% of infant plasma concentration was explained.

Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies overlapped substantially, (b)) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and (c)) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Québec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies.

Researchers in the Netherlands have reported that the associations of prenatal polychlorinated biphenyl (PCB) exposure with poorer cognitive performance in childhood are generally stronger and statistically significant only among non-breast-fed children. This paper reports a similar pattern of greater vulnerability among non-breast-fed children in the Michigan cohort of children whose mothers had eaten PCB-contaminated Lake Michigan fish. It is difficult to determine from prospective human longitudinal data whether the apparent decreased vulnerability among breast-fed children is due to nutrients in breast milk that might attenuate the adverse neurochemical effects of this exposure and/or the more optimal intellectual stimulation that was provided by the breast-feeding mothers in these cohorts. The latter interpretation was supported by analyses demonstrating that virtually all of the positive associations between breast-feeding and cognitive outcome can be accounted for statistically by measures of quality of parental intellectual input and that the adverse effects associated with prenatal PCB exposure were also markedly stronger in children raised by less verbally competent mothers, who presumably provided less optimal intellectual stimulation. Because there were no consistent patterns of differential vulnerability for either gender, these data did not support the hypothesis that prenatal PCB exposure may disrupt cognitive development due to the estrogenic or antiestrogenic properties of its congeners and metabolites.

Benchmark dose (BMD) analysis is used to determine levels of exposure to environmental contaminants associated with increased public health risk. In this study we used a benchmark approach to evaluate the risks associated with prenatal exposure to polychlorinated biphenyls (PCBs). We evaluated for intellectual impairment a cohort of children whose prenatal PCB exposure had been assessed from biologic specimens. We calculated BMDs and lower-bound confidence limits (BMDLs) for four end points using four sets of risk criteria. BMDLs were estimated using three different statistical methodologies. The BMDs and BMDLs were remarkably consistent across the four end points for each set of risk criteria, but differed substantially for the different risk criteria. The proportion of the sample considered at risk ranged from 9.8% for the least protective criteria to 74.1% for the most protective. Two methodologies, likelihood ratio and bootstrapping, generated generally similar BMDLs. BMD analysis provides a straightforward, reliable method for evaluating levels of exposure associated with increased public health risk. In the analyses performed in this study, the number of individuals considered at risk depended more on the risk criterion selected than on the outcome assessed.

Polychlorinated biphenyls are a family of synthetic hydrocarbon compounds that were used historically for a broad range of industrial purposes. Although banned in the 1970s, they continue to be ubiquitous in landfills, sediments, and wildlife. Prenatal polychlorinated biphenyl exposure was evaluated in a sample of children born to women who had eaten relatively large quantities of polychlorinated biphenyl-contaminated Lake Michigan fish. This exposure was found to be associated with poorer intellectual function after controlling statistically for a broad range of potential confounding variables. Deficits included poorer recognition memory in infancy, lower scores on a preschool IQ test, and poorer verbal IQ and reading comprehension at 11 years of age. Although breast-fed children were exposed postnatally to elevated levels of polychlorinated biphenyls from maternal milk, the adverse effects associated with prenatal exposure were markedly stronger in the children who were not breast-fed. It is not clear whether the adverse effects were attenuated in the breast-fed children due to certain nutrients in the breast milk or due to better quality of intellectual stimulation provided by the breast-feeding mothers. Virtually no adverse effects were found in relation to postnatal exposure to polychlorinated biphenyls from breast-feeding, indicating that the fetus is particularly vulnerable to this exposure.

In this paper, we respond to the criticisms and concerns raised by D.V. Cicchetti, A.S. Kaufman, & S.S. Sparrow (this issue) in their review of the PCB literature, with particular attention to our own research in Michigan. We agree that multiple comparisons and functional significance are issues that would benefit from more discussion. However, because the effects associated with exposure to environmental contaminants are generally subtle, the risk of Type II error would be unacceptably high if researchers were to adopt the authors' recommendation to use a Bonferroni correction. We describe the hierarchical approach we have used to deal with the issue of multiple comparisons, which emphasizes the need to base interpretation on consistent patterns in the data and on replicated findings. The issue of confounding is one that has received considerable attention in the PCB studies and, given that one can never measure every possible confounder, the range of control variables that have been evaluated is impressive. We disagree with the authors' assertion that only standardized test scores are sufficiently reliable for use in these studies; behavioral teratogens often involve subtle effects, which can be identified most effectively by innovative, narrow-band tests that have not yet been normed. Moreover, longitudinal statistical analysis is not necessarily the method of choice for the issues being addressed in this literature. One important new development that Cicchetti et al. fail to note is the emergence of evidence from both the Michigan and Dutch cohorts indicating that breast-fed children are markedly less vulnerable. It is not yet clear to what degree this protective effect is attributable to nutrients in breast milk or to more optimal intellectual stimulation by nursing mothers, or both. However, the discovery of effect modifiers that can explain individual differences in vulnerability marks an important advance in our growing understanding of the teratogenic effects of exposure to environmental contaminants on child development. © 2004 Wiley Periodicals, Inc. Psychol Schs 41: 625–637, 2004. [ABSTRACT FROM AUTHOR]

Focuses on the environmental exposure to polychlorinated biphenyls (PCB). Features of PCB; Information on a study commissioned by the U.S. Environmental Protection Agency about Lake Michigan sports fishermen who had eaten quantities of fish having accumulated levels of PCB; List of biological indicators of PCB exposure; Effects of PCB exposure during infancy and early childhood.

Abstract: Serum samples from 285 4-year-old Michigan children were evaluated for levels of 11 environmental contaminants. Polychlorinated biohenyls (PCBs) were found in half the samples tested; polybrominated biphenyls (PBBs) in 13-21 percent; dicholorodiphenyl trichloroethane (DDT), in more than 70 percent. Nursing (Mothers' milk) was the principal source of these exposures. Congener specific analysis documented the presence of at least one highly toxic PCB congener, 2,3',4,4',5-pentachlorobiphenyl. The data demonstrate the multigenerational impact of female exposure to persistent organic environmental contaminants. [ABSTRACT FROM AUTHOR]

Presents a study which further investigated adverse neonatal outcomes associated with intrauterine exposure to polychlorinated biphenyls (PCB). Administration of the Fagan's test of visual recognition memory at seven months; Measures of prenatal PCB exposure; Correlation of post-natal exposure from nursing and visual recognition memory.

Discusses a study by Jens Walkowiak and colleagues in this issue which reports an association between prenatal and postnatal exposure to polychlorinated biphenyls (PCB) and childhood cognitive function. Relation of child performance to parental scores on the Home Observation for Measurement of the Environment (HOME); Relation of HOME scores to cognitive outcome, which showed a threshold effect; How a greater sensitivity to damage during the prenatal period seems to render the fetus more vulnerable to small quantities of neurotoxicants.

Cord serum and maternal milk levels of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) were examined in relation to maternal serum levels. Maternal serum levels were significantly higher than cord serum levels for both types of compounds. Placental passage was indicated by significant material to cord serum correlations for both PCBs (r = .42) and PBBs (r = .81). Correlations between material serum and milk levels were similar. Higher PBB correlations were probably due to greater reliability in the measurement of PBB levels in serum and milk. [ABSTRACT FROM AUTHOR]

Background: In utero exposure to polychlorinated biphenyls, a ubiquitous environmental contaminant, has been linked to adverse effects on neurologic and intellectual function in infants and young children. We assessed whether these effects persist through school age and examined their importance in the acquisition of reading and arithmetic skills. Methods: We tested 212 children, recruited as newborns to overrepresent infants born to women who had eaten Lake Michigan fish contaminated with polychlorinated biphenyls. A battery of IQ and achievement tests was administered when the children were 11 years of age. Concentrations of polychlorinated biphenyls in maternal serum and milk at delivery were slightly higher than in the general population. A composite measure of prenatal exposure was derived from concentrations in umbilical-cord serum and maternal serum and milk. Results: Prenatal exposure to polychlorinated biphenyls was associated with lower full-scale and verbal IQ scores after control for potential confounding variables such as socioeconomic status (P = 0.02). The strongest effects related to memory and attention. The most highly exposed children were three times as likely to have low average IQ scores (P<0.001) and twice as likely to be at least two years behind in reading comprehension (P = 0.03). Although larger quantities of polychlorinated biphenyls are transferred by breast-feeding than in utero, there were deficits only in association with transplacental exposure, suggesting that the developing fetal brain is particularly sensitive to these compounds. Conclusions: In utero exposure to polychlorinated biphenyls in concentrations slightly higher than those in the general population can have a long-term impact on intellectual function. (N Engl J Med 1996;335:783-9.) [ABSTRACT FROM AUTHOR]

Presents information about the Polychlorinated biphenyls (PCBs), a synthetic compounds commonly used as insulation in electrical machinery. Effects of PCBs residues in water, soil and fatty tissue of food animals to the nervous system of animals and infants; Effects of PCBs exposure in children's IQ; How PCB affected intellectual capacity when absorbed before birth.

Chronic exposure to methylmercury (MeHg), lead (Pb) and polychlorinated biphenyls (PCBs) has been associated with a range of attention deficits in children, but it is not known whether selective spatial attention is also altered. We modified the classic Posner paradigm, which assesses visuospatial attention, to also assess vigilance and impulsivity. This paradigm is based on the well-documented findings that a target will be detected more quickly if a visual cue indicates beforehand where it will appear, and more slowly if the cue indicates a false spatial location. In our task, visual distractors were introduced, in addition to the classic Posner trials, to assess impulsivity, and a central smiley face, whose eye-movement cued the location of the targets, to measure spatial attention. This task was administered to 27 school-age Inuit children (mean age = 11.2 years) from Nunavik (Arctic Quebec, Canada), in which pre- and postnatal exposures to environmental contaminants had been documented from birth. After controlling for the impact of confounding variables, multivariable regressions revealed that prenatal exposures to PCBs and Pb were significantly associated with greater inattention and impulsivity, respectively, while current exposure to Pb was significantly associated with longer reaction times. Although a significant correlation was observed between cord blood PCB concentration and decreased visuospatial performance, no significant association was found after adjustment for confounders. No effect was found for Hg exposures. These results suggest that our adapted Posner paradigm is sensitive in detecting a range of attention deficits in children exposed to environmental contaminants; implications for future studies are discussed. [ABSTRACT FROM AUTHOR]

Abstract: The Inuit from Nunavik (Northern Québec) are one of the most highly exposed populations to environmental contaminants in North America mainly due to the bioaccumulation of contaminants in fish and marine mammals that constitute an important part of their diet. This follow-up study aimed to assess the impact of exposure to contaminants on visual brain development in school-age Inuit children (mean age=10.9 years). Concentrations of polychlorinated biphenyls (PCBs), mercury (Hg), and lead (Pb) were measured in umbilical cord blood and again in blood samples at the time of testing, reflecting pre- and current exposure, respectively. Pattern-reversal visual evoked potentials (VEPs) were scalp-recorded at the occipital cortex. Visual stimulation consisted of achromatic gratings presented at four visual contrast levels: 95%, 30%, 12% and 4%. The relation between environmental contaminant body burdens and VEPs was examined by regression analysis controlling for confounding variables, including fish nutrients and other toxicants. No significant association was found for PCB exposure after statistical adjustments. Cord blood mercury level was associated with a reduction of the N75 amplitude at the highest contrast level and with a delay of the N75 latency at the 12% contrast level. Prenatal exposure to lead was associated with a delay of the N150 latency at most contrast levels. This study suggests that heavy metal exposure, in particular during the gestational period, can impair the development of visual processing. [Copyright &y& Elsevier]

Exposure to mercury, lead and polychlorinated biphenyls (PCBs) have been associated with emotional dysregulation, but their neuronal correlates have yet to be examined. Inuit from Nunavik (Northern Quebec, Canada) face internalizing problems and are among the most exposed individuals to these environmental contaminants in the world. The aim of this study was to examine the link between pre- and postnatal exposure to these contaminants and brain fear-circuitry in Inuit adolescents. Facial expression stimuli were presented to participants (mean age = 18.3 years) in a magnetic resonance imaging (MRI) scanner. Fear conditioning and extinction tasks included neutral faces as the conditioned threat and safety cues and a fearful face paired with a shrieking scream as the unconditioned stimulus. Functional MRI data were gathered at the conditioning phase (n = 71) and at the extinction phase (n = 62). Mercury, lead and PCB 153 concentrations were measured in blood samples at birth (cord blood) and at the time of the adolescent testing to estimate pre- and postnatal exposure, respectively. For each time point, exposures were categorized in tertiles (low, moderate and high exposed groups). Mixed analyses of variance were conducted for each contaminant of interest controlling for sex, age, socioeconomic status, drug/alcohol use, food insecurity and contaminant co-exposure. Results revealed greater differential activation during the conditioning phase in the right orbitofrontal cortex in participants with moderate and high concentrations of cord blood PCB 153 compared to those in the low exposure group. During the extinction phase, the high prenatal mercury exposed group showed a lower differential activation in the right and left anterior cingulate cortex compared to those in the low-exposed group; whereas there was a higher differential activation in right dorsolateral prefrontal cortex in the high postnatal lead exposed group compared to the moderate- and low-exposed groups. Our study is the first to show alterations in the prefrontal brain areas in fear conditioning and extinction tasks in relation to environmental contaminant exposures. The observed brain correlates may advance our understanding of the emotional problems associated with environmental chemical toxicity. • Exposure to environmental contaminants (mercury, lead and PCB) is associated with emotional dysregulation • Brain fear-circuitry was examined in exposed Inuit adolescents from Nunavik using fMRI • Orbitofrontal cortex activation to discriminative fear learning was affected in association with prenatal PCB exposure • Prenatal exposure to Hg and current Pb exposure were associated with dysfunctions of fear extinction brain responses. [ABSTRACT FROM AUTHOR]