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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. [ABSTRACT FROM AUTHOR]

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. Key words: benchmark dose analysis, dose—response, environmental contaminants, in utero exposure, organochlorine contaminants, polychlorinated biphenyls, risk analysis. Environ Health Perspect 110:393–398 (2002). [Online 8 March 2002] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ∼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 PCB153 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. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to methyl mercury (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. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to methyl mercury (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: An increasing number of studies have shown that several ubiquitous environmental contaminants possess thyroid hormone-disrupting capacities. Prenatal exposure to some of them, such as polychlorinated biphenyls (PCBs), has also been associated with adverse neurodevelopmental effects in infants. OBJECTIVES: In this study we examined the relationship between exposure to potential thyroid hormone-disrupting toxicants and thyroid hormone status in pregnant Inuit women from Nunavik and their infants within the first year of life. METHODS: We measured thyroid hormone parameters [thyroid stimulating hormone (TSH), free thyroxine (fT4), total triiodothyronine (T3), thyroxine-binding globulin (TBG)] and concentrations of several contaminants [PCB-153, hydroxylated metabolites of PCBs (HO-PCBs), pentachlorophenol (PCP) and hexachlorobenzene (HCB)] in maternal plasma at delivery (n = 120), in umbilical cord plasma (n = 95), and in infant plasma at 7 months postpartum (n = 130). RESULTS: In pregnant women, we found a positive association between HO-PCBs and T3 concentrations (β = 0.57, p = 0.02). In umbilical cord blood, PCB-153 concentrations were negatively associated with TBG levels (β = -0.26, p = 0.01). In a subsample analysis, a negative relationship was also found between maternal PCP levels and cord fT4 concentrations in neonates (β = -0.59, p = 0.02). No association was observed between contaminants and thyroid hormones at 7 months of age. CONCLUSION: Overall, there is little evidence that the environmental contaminants analyzed in this study affect thyroid hormone status in Inuit mothers and their infants. The possibility that PCP may decrease thyroxine levels in neonates requires further investigation. [ABSTRACT FROM AUTHOR]

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 (CI) infections. Maternal plasma during delivery and infant plasma at 7 months of age were sampled and assayed for PCBs and DDE. Compared to rates kr infants in the first quartile of exposure to PCBs (least exposed), adjusted rate ratios kr infants in higher quartiles ranged between 1.09 and 1.32 kr URTIs, 0.99 and 1.39 for otitis, 1.52 and 1.89 for CI 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 kr the full 12-month follow-up. Globally, most rate ratios were> 1.0, but few were statistically significant (p c 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. [ABSTRACT FROM AUTHOR]

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 l0 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 Quebec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies. [ABSTRACT FROM AUTHOR]

The Inuit population residing in Nunavik (northern Québec, Canada) relies on species from the marine food web for subsistence and is therefore exposed to high doses of environmental contaminants such as polychlorinated biphenyls and methylmercury and to a lesser extent lead. In view of the neurotoxic properties of these substances following developmental exposure, we initiated a study on infant development in this remote coastal population. Here we report the magnitude of prenatal exposure to these contaminants and to selective nutrients in Inuit mothers and their newborns who were recruited on the Hudson Bay coast. We conducted interviews during the women's pregnancies and at 1 and 11 months postpartum and collected biological samples for mercury, lead, polychlorinated biphenyls (PCBs), and chlorinated pesticides analyses as well as selenium and N-3 polyunsaturated fatty acids (n3-PUFA). Cord blood, maternal blood, and maternal hair mercury concentrations averaged 18.5 µg/L, 10.4 µg/L, and 3.7 µg/g, respectively, and are similar to those found in the Faroe Islands but lower than those documented in the Seychelles Islands and New Zealand cohorts. Concentrations of PCB congener 153 averaged 86.9, 105.3, and 131.6 µg/kg (lipids) in cord plasma, maternal plasma, and maternal milk, respectively; prenatal exposure to PCBs in the Nunavik cohort is similar to that reported in the Dutch but much lower than those in other Arctic cohorts. Levels of n3-PUFA in plasma phospholipids and selenium in blood are relatively high. The relatively low correlations observed between organochlorine and methylmercury concentrations may make it easier to identify the specific developmental deficits attributable to each toxicant. Similarly, the weak correlations noted between environmental contaminants and nutrients will facilitate the documentation of possible protective effects afforded by either n3-PUFA or selenium against neurotoxic contaminants. Key... [ABSTRACT FROM AUTHOR]

The objectives of this study were to to identify maternal characteristics associated with traditional food consumption and to examine food items associated with polychlorinated biphenyls (PCBs) and mercury body burden in pregnant Inuit women from Northern Québec. We interviewed women from three communities at mid-pregnancy and at 1 and 11 months postpartum. We measured PCBs, Hg, and selenium in maternal blood; Hg was also measured in maternal hair. The women reported eating significant amounts of fish, beluga muktuk/fat, seal meat, and seal fat. Although consumption of fish and seal was associated with lower socioeconomic status, consumption of beluga whale was uniform across strata. Fish and seal meat consumption was associated with increased Hg concentrations in hair. Traditional food intake during pregnancy was unrelated to PCB body burden, which is more a function of lifetime consumption. This study corroborated previous findings relating marine mammal and fish consumption to increased Hg and selenium body burden. Despite widespread knowledge regarding the presence of these contaminants in traditional foods, a large proportion of Inuit women increased their consumption of these foods during pregnancy, primarily because of pregnancy-related changes in food preferences and the belief that these foods are beneficial during pregnancy. Key words: Canada, Inuit, methylmercury, polychlorinated biphenyls. Environ Health Perspect 109:957-963 (2001). [Online 12 September 2001] http://ehpnet1.niehs.nih.gov/docs/200l/109p957-963muckle/abstr act.html [ABSTRACT FROM AUTHOR]