Gina Muckle

Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants

A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and endocrine alterations were observed in experimental animals, following in utero and lactational exposure to PCBs, PCDDs and PCDFs. The lowest observable adverse effect levels (LOAELs) for developmental neurobehavioral and reproduction endpoints, based on body burden of TCDD-toxic equivalents (TEQs) in animals, are within the range of current background human body burdens. Relatively subtle adverse effects on neurobehavioral development and thyroid hormone alterations have also been observed in infants and children exposed to background levels. Exclusive use of the toxic equivalency factor (TEF) approach may underestimate the risk of neurodevelopmental effects, because both Ah receptor dependent and independent mechanisms may be involved in these effects. The use of marker congeners and/or bioassays based on Ah receptor mediated mechanisms are rapid, low cost pre-screening alternatives for expensive and time consuming gas chromatographic-mass spectrometric analysis.

Environmental contaminants and human health in the Canadian Arctic.

The third Canadian Arctic Human Health Assessment conducted under the Canadian Northern Contaminants Program (NCP), in association with the circumpolar Arctic Monitoring and Assessment Programme (AMAP), addresses concerns about possible adverse health effects in individuals exposed to environmental contaminants through a diet containing country foods. The objectives here are to: 1) provide data on changes in human contaminant concentrations and exposure among Canadian Arctic peoples; 2) identify new contaminants of concern; 3) discuss possible health effects; 4) outline risk communication about contaminants in country food; and 5) identify knowledge gaps for future contaminant research and monitoring. The nutritional and cultural benefits of country foods are substantial; however, some dietary studies suggest declines in the amount of country foods being consumed. Significant declines were found for most contaminants in maternal blood over the last 10 years within all three Arctic regions studied. Inuit continue to have the highest levels of almost all persistent organic pollutants (POPs) and metals among the ethnic groups studied. A greater proportion of people in the East exceed Health Canadas guidelines for PCBs and mercury, although the proportion of mothers exceeding these guidelines has decreased since the previous assessment. Further monitoring and research are required to assess trends and health effects of emerging contaminants. Infant development studies have shown possible subtle effects of prenatal exposure to heavy metals and some POPs on immune system function and neurodevelopment. New data suggest important beneficial effects on brain development for Inuit infants from some country food nutrients. The most successful risk communication processes balance the risks and benefits of a diet of country food through input from a variety of regional experts and the community, to incorporate the many socio-cultural and economic factors to arrive at a risk management decision that will be the most beneficial in Arctic communities.

Beneficial Effects of a Polyunsaturated Fatty Acid on Infant Development: Evidence from the Inuit of Arctic Quebec

OBJECTIVES To examine the relation of cord plasma docosahexaenoic acid (DHA) concentration to gestation length, birth size, growth, and infant visual acuity, cognitive, and motor development and the effects on growth and development associated with DHA intake from breast-feeding. STUDY DESIGN DHA, other polyunsaturated fatty acids, and 3 environmental contaminants (polychlorinated biphenyls, mercury, and lead) were assessed in cord plasma and maternal plasma and milk in 109 Inuit infants in Arctic Quebec. Multiple regression was used to examine the relation of cord DHA and DHA from breast-feeding on growth and development at 6 and 11 months, after controlling for contaminant exposure and other potential confounders. RESULTS Higher cord DHA concentration was associated with longer gestation, better visual acuity and novelty preference on the Fagan Test at 6 months, and better Bayley Scale mental and psychomotor performance at 11 months. By contrast, DHA from breast-feeding was not related to any indicator of cognitive or motor development in this full-term sample. CONCLUSIONS The association of higher cord DHA concentration with more optimal visual, cognitive, and motor development is consistent with the need for substantial increases in this critically important fatty acid during the third trimester spurt of synaptogenesis in brain and photoreceptor development.

Prenatal exposure to polychlorinated biphenyls: a neuropsychologic analysis.

Objectives A large body of literature documents the effects of prenatal exposure to polychlorinated biphenyls (PCBs) on cognitive development of children. Despite this fact, no integrative synthesis has been published yet to identify the cognitive functions that are particularly affected. Our aim is to review this literature in an attempt to identify the cognitive profile associated with prenatal PCB exposure. Data sources Studies were identified by searching the PubMed database for articles published before June 2008. We reviewed data from nine prospective longitudinal birth cohorts for different aspects of cognition. Data extraction Associations between indicators of prenatal PCB exposure and performance on cognitive tasks reported in the selected studies are summarized and classified as general cognitive abilities, verbal or visual–spatial skills, memory, attention, and executive functions. Data synthesis The most consistent effects observed across studies are impaired executive functioning related to increased prenatal PCB exposure. Negative effects on processing speed, verbal abilities, and visual recognition memory are also reported by most studies. Converging results from different cohort studies in which exposure arises from different sources make it unlikely that co-exposure with another associated contaminant is responsible for the observed effects. Conclusion Prenatal PCB exposure appears to be related to a relatively specific cognitive profile of impairments. Failure to assess functions that are specifically impaired may explain the absence of effects found in some studies. Our findings have implications in the selection of cognitive assessment methods in future studies.

Effect of prenatal exposure to polychlorinated biphenyls on incidence of acute respiratory infections in preschool Inuit children.

Objective We set out to assess whether environmental prenatal exposure to polychlorinated biphenyls (PCBs) is associated with incidence of acute respiratory infections in preschool Inuit children. Study design We reviewed the medical charts of 343 children from 0 to 5 years of age and evaluated the associations between PCB-153 concentration in umbilical cord plasma and the incidence rates of acute otitis media (AOM) and of upper and lower respiratory tract infections (URTIs and LRTIs, respectively). Results The incidence rates of AOM and LRTIs were positively associated with prenatal exposure to PCBs. Compared with children in the first quartile of exposure (least exposed), children in fourth quartile (most exposed) had rate ratios of 1.25 (p < 0.001) and 1.40 (p < 0.001) for AOM and LRTIs, respectively. There was no association between prenatal PCB exposure and incidence rate of URTIs or hospitalization. Conclusion Prenatal exposure to PCBs could be responsible for a significant portion of respiratory infections in children of this population.

Acute infections and environmental exposure to organochlorines in Inuit infants from Nunavik

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.

Prenatal Methylmercury, Postnatal Lead Exposure, and Evidence of Attention Deficit/Hyperactivity Disorder among Inuit Children in Arctic Québec

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.

Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age

BACKGROUND The beneficial effects of prenatal and early postnatal intakes of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on cognitive development during infancy are well recognized. However, few studies have examined the extent to which these benefits continue to be evident in childhood. OBJECTIVE The aim of this study was to examine the relation of n-3 PUFAs and seafood-contaminant intake with memory function in school-age children from a fish-eating community. DESIGN In a prospective, longitudinal study in Arctic Quebec, we assessed Inuit children (n = 154; mean age: 11.3 y) by using a continuous visual recognition task to measure 2 event-related potential components related to recognition memory processing: the FN400 and the late positive component (LPC). Children were also examined by using 2 well-established neurobehavioral assessments of memory: the Digit span forward from Wechsler Intelligence Scales for Children, 4th edition, and the California Verbal Learning Test-Childrens Version. RESULTS Repeated-measures analyses of variance revealed that children with higher cord plasma concentrations of docosahexaenoic acid (DHA), which is an important n-3 PUFA, had a shorter FN400 latency and a larger LPC amplitude; and higher plasma DHA concentrations at the time of testing were associated with increased FN400 amplitude. Cord DHA-related effects were observed regardless of seafood-contaminant amounts. Multiple regression analyses also showed positive associations between cord DHA concentrations and performance on neurobehavioral assessments of memory. CONCLUSION To our knowledge, this study provides the first neurophysiologic and neurobehavioral evidence of long-term beneficial effects of n-3 PUFA intake in utero on memory function in school-age children.

Thyroid Hormone Levels of Pregnant Inuit Women and Their Infants Exposed to Environmental Contaminants

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.

Cohort Profile: The Maternal-Infant Research on Environmental Chemicals Research Platform

BACKGROUND The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health. METHODS Women were recruited during the first trimester from 10 sites across Canada and were followed through delivery. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, occupation, life style, medical history, environmental exposures and diet. Information on the pregnancy and the infant was abstracted from medical charts. Maternal blood, urine, hair and breast milk, as well as cord blood and infant meconium, were collected and analysed for an extensive list of environmental biomarkers and nutrients. Additional biospecimens were stored in the studys Biobank. The MIREC Research Platform encompasses the main cohort study, the Biobank and follow-up studies. RESULTS Of the 8716 women approached at early prenatal clinics, 5108 were eligible and 2001 agreed to participate (39%). MIREC participants tended to smoke less (5.9% vs. 10.5%), be older (mean 32.2 vs. 29.4 years) and have a higher education (62.3% vs. 35.1% with a university degree) than women giving birth in Canada. CONCLUSIONS The MIREC Study, while smaller in number of participants than several of the international cohort studies, has one of the most comprehensive datasets on prenatal exposure to multiple environmental chemicals. The biomonitoring data and biological specimen bank will make this research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals.