Using latent class analysis to operationalize a wholistic assessment of Inuit health and well-being.

Many indigenous cultures conceptualize health wholistically, whereby physical, mental, spiritual and relational dimensions of health are interconnected. Yet, quantitative approaches to studying Indigenous health remain anchored in western perspectives, that separate the dimensions of health. This paper aims to operationalize a wholistic indicator of health based on the IQI model of Inuit health. Variables from the 2017 Nunavik Health Survey (N = 1196) were selected based on their representativeness of IQI model. Exploratory Latent Class Analysis (LCA) was used to identify wholistic health profiles. Once participants assigned to their health profile, sociodemographic characteristics were compared across profiles, and multinomial regression models were used to examine the relationship between community-level social determinants of health and the profiles. The LCA revealed three health profiles, labelled as "excellent", "good" and "fair" based on the distribution of answers to the indicators. Nunavimmiut in "excellent" and "good" health were more likely to: rate their health positively; be over 30 years old; be in a relationship; and have participated or volunteered in community events. Nunavimmiut in "fair" health tended to report lower levels of community cohesion, family relationships, and emotional support. Intergrating culturally relevant models of health can support improved health status assessments and identify opportunities for health promotion.

Maternal Folate Status and the Relation between Gestational Arsenic Exposure and Child Health Outcomes.

Gestational arsenic exposure adversely impacts child health. Folate-mediated 1-carbon metabolism facilitates urinary excretion of arsenic and may prevent arsenic-related adverse health outcomes. We investigated the potential for maternal folate status to modify associations between gestational arsenic exposure and child health. We used data from 364 mother-child pairs in the MIREC study, a prospective pan-Canadian cohort. During pregnancy, we measured first trimester urinary arsenic concentrations, plasma folate biomarkers, and folic acid supplementation intake. At age 3 years, we evaluated twelve neurodevelopmental and anthropometric features. Using latent profile analysis and multinomial regression, we developed phenotypic profiles of child health, estimated covariate-adjusted associations between arsenic and these phenotypic profiles, and evaluated whether folate status modified these associations. We identified three phenotypic profiles of neurodevelopment and three of anthropometry, ranging from less to more optimal child health. Gestational arsenic was associated with decreased odds of optimal neurodevelopment. Maternal folate status did not modify associations of arsenic with neurodevelopmental phenotypic profiles, but gestational arsenic was associated with increased odds of excess adiposity among those who exceed recommendations for folic acid (>1000 µg/day). However, arsenic exposure was low and folate status was high. Gestational arsenic exposure may adversely impact child neurodevelopment and anthropometry, and maternal folate status may not modify these associations; however, future work should examine these associations in more arsenic-exposed or lower folate-status populations.

Impact of chronic exposure to legacy environmental contaminants on the corpus callosum microstructure: A diffusion MRI study of Inuit adolescents.

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.

Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children.

BACKGROUND: The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3- to 4-y-old Canadian children. We also investigated potential effect modification by sex and folic acid supplementation. METHODS: We enrolled 2,001 women>18 years of age during the first trimester of pregnancy between 2008 and 2011 from 10 cities in Canada. At 3-4 years of age, 610 children underwent neuropsychological assessments including the Social Responsiveness Scale-II (SRS-2) as a measure of autistic traits and social impairment. We measured 11 phthalate metabolites in maternal first trimester urine samples and assessed folic acid supplementation from reported intakes. We estimated covariate-adjusted differences in SRS-2 T-scores with a doubling in phthalate concentrations in 510 children with complete data. RESULTS: Mean total SRS T-score was 45.3 (SD=6.1). Children with higher gestational exposure to mono-n-butyl (MBP) and mono-3-carboxypropyl (MCPP) concentrations exhibited significantly higher total SRS T-scores, indicating greater overall social impairment, as well as higher scores on subdomains, indicating deficits in social cognition, social communication, social motivation, and restricted interests/repetitive behaviors. A doubling in MBP or MCPP concentrations was associated with 0.6 (95% CI: 0.1, 1.0) and 0.5 (95% CI: 0.1, 0.8) higher total SRS T-scores. Associations were consistently and significantly stronger in boys (ßMBP=1.0; 95% CI: 0.4, 1.6; n=252) compared with girls (ßMBP=0.1; 95% CI: -0.6, 0.7; n=258) and among children who had lower prenatal folic acid supplementation (<400µg/d) (ßMBP=1.3; 95% CI: 0.4, 2.3; n=59) compared with those who had adequate folic acid supplementation (≥400µg/d) (ßMBP=0.4; 95% CI: -0.1, 0.8; n=451). CONCLUSIONS: Higher gestational concentrations of some phthalate metabolites were associated with higher scores of autistic traits as measured by the SRS-2 in boys, but not girls; these small size effects were mitigated by first trimester-of-pregnancy folic acid supplementation. https://doi.org/10.1289/EHP5621.

Community Water Fluoridation and Urinary Fluoride Concentrations in a National Sample of Pregnant Women in Canada.

BACKGROUND: Fluoride exposures have not been established for pregnant women who live in regions with and without community water fluoridation. OBJECTIVE: Our aim was to measure urinary fluoride levels during pregnancy. We also assessed the contribution of drinking-water and tea consumption habits to maternal urinary fluoride (MUF) concentrations and evaluated the impact of various dilution correction standards, including adjustment for urinary creatinine and specific gravity (SG). METHODS: We measured MUF concentrations in spot samples collected in each trimester of pregnancy from 1,566 pregnant women in the Maternal-Infant Research on Environmental Chemicals cohort. We calculated intraclass correlation coefficients (ICCs) to assess variability in MUF concentrations across pregnancy. We used regression analyses to estimate associations between MUF levels, tea consumption, and water fluoride concentrations as measured by water treatment plants. RESULTS: Creatinine-adjusted MUF values ([Formula: see text]; milligrams per liter) were almost two times higher for pregnant women living in fluoridated regions ([Formula: see text]) compared with nonfluoridated regions ([Formula: see text]; [Formula: see text]). MUF values tended to increase over the course of pregnancy using both unadjusted values and adjusted values. Reproducibility of the unadjusted and adjusted MUF values was modest ([Formula: see text]). The municipal water fluoride level was positively associated with creatinine-adjusted MUF ([Formula: see text], 95% CI: 0.46, 0.57), accounting for 24% of the variance after controlling for covariates. Higher MUF concentrations correlated with numbers of cups of black ([Formula: see text] but not green tea ([Formula: see text]). Urinary creatinine and SG correction methods were highly correlated ([Formula: see text]) and were interchangeable in models examining predictors of MUF. CONCLUSION: Community water fluoridation is a major source of fluoride exposure for pregnant women living in Canada. Urinary dilution correction with creatinine and SG were shown to be interchangeable for our sample of pregnant women. https://doi.org/10.1289/EHP3546.

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-Children's 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.

Prenatal exposure to methylmercury and PCBs affects distinct stages of information processing: an event-related potential study with Inuit children.

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.

The relation of lead neurotoxicity to the event-related potential P3b component in Inuit children from arctic Québec.

The event-related potential (ERP) P3b, a cognitive electrophysiological measure that has been linked to working memory processing in many experimental paradigms, was measured in Inuit children from Nunavik (Arctic Québec, Canada) to assess lead (Pb) neurotoxicity. Visual and auditory oddball paradigms were administered at 5 (N=27) and 11 (N=110) years of age, respectively, to elicit this ERP component. Pearson correlations and multiple regression analyses were performed to examine the associations between Pb levels and P3b parameters (peak latency and amplitude). Greater prenatal Pb exposure was related to a decrease in P3b amplitude at 5 years of age, and early childhood Pb exposure was associated with delayed P3b latency at 5 years. No significant association was observed at 11 years. These results, in line with those from previous neurobehavioral studies, suggest that Pb exposure affects cognitive processing in children even though the Pb levels measured in a large majority of our sample were below the threshold value for public health intervention used by federal agencies. This study strengthens the arguments for reducing sources of Pb exposure in Nunavik and for lowering the blood Pb concentrations considered "acceptable" in governmental policies.

Alterations of visual evoked potentials in preschool Inuit children exposed to methylmercury and polychlorinated biphenyls from a marine diet.

The aim of the present study was to assess the impact of chronic exposure to polychlorinated biphenyls (PCBs) and methylmercury on visual brain processing in Inuit children from Nunavik (Northern Québec, Canada). Concentrations of total mercury in blood and PCB 153 in plasma had been measured at birth and they were again measured at the time of testing in 102 preschool aged children. Relationships between contaminants and pattern-reversal visual evoked potentials (VEPs) were assessed by multivariate regression analyses, taking into account several potential confounding variables. The possible protective effects of selenium and omega-3 polyunsaturated fatty acids against methylmercury and PCB toxicity were also investigated. Results indicate that exposure to methylmercury and PCBs resulting from fish and sea mammal consumption were associated with alterations of VEP responses, especially for the latency of the N75 and of the P100 components. In contrast, the concomitant intake of omega-3 polyunsaturated fatty acids was associated with a shorter latency of the P100. However, no significant interactions between nutrients and contaminants were found, contradicting the notion that these nutrients could afford protection against environmental neurotoxicants. Interestingly, significant associations were found with concentrations of neurotoxicants in blood samples collected at the time of testing, i.e. at the preschool age. Our findings suggest that VEP can be used as a valuable tool to assess the developmental neurotoxicity of environmental contaminants in fish-eating populations.

Neuromotor functions in Inuit preschool children exposed to Pb, PCBs, and Hg.

The aim of this study was to examine the effects of prenatal and postnatal chronic exposure to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb) on the neuromotor development of preschool children. The study population consisted of 110 preschool Inuit children from Nunavik (Canada). Blood Hg, PCBs and Pb concentrations were measured at birth (cord blood) and at the time of testing. Gross motor functions were evaluated and a neurological examination was performed. Fine neuromotor performance was assessed using quantitative measures of postural hand tremor, reaction time, sway oscillations, as well as alternating and pointing movements. Potential covariates were documented including demographic and familial characteristics, other prenatal neurotoxicants (alcohol, tobacco) and nutrients (selenium (Se), Omega-3 polyunsaturated fatty acids (n-3 PUFA)). Hierarchical multivariate regression analyses were performed, controlling for significant covariates. Gross motor development was not linked to prenatal exposures. However, significant associations were observed between blood Pb concentration at testing time and changes in reaction time, sway oscillations, alternating arm movements and action tremor. For some of these outcomes, neuromotor effects of Pb exposure are observed at blood concentrations below 10 microg/dl. Negative effects of PCBs on neuromotor development were not clearly observed, neither were the potential beneficial effects of n-3 PUFA and selenium. Tremor amplitude was related to blood Hg concentrations at testing time, which corroborate an effect already reported among adults.

Gestational age and birth weight in relation to n-3 fatty acids among Inuit (Canada).

Seafood consumption during pregnancy carries both benefits (high n-3 FA intake) and risks (exposure to environmental contaminants) for the developing fetus. We determined the impacts of marine n-3 FA and environmental contaminants on gestational age (GA) of Nunavik women and the anthropometric characteristics of their newborns. FA and contaminant (polychlorinated biphenyls and mercury) concentrations were measured in cord plasma of Nunavik newborns (n = 454) and compared with those of a group of newborns (n = 29) from southern Québec. Data were collected from hospital records and birth certificates. In Nunavik newborns, arachidonic acid (AA) was two times lower (P < 0.0001), whereas DHA concentration, the sigman-3 / sigman-6 ratio, and the percentage of n-3 highly unsaturated FA (HUFA) (of the total HUFA) were three times higher (P < 0.0001) compared with southern Québec newborns. After controlling for confounders, GA and birth weight were higher by 5.4 d [95% confidence interval (CI): 0.7-10.1] and 77 g (95% CI: -64 to 217) in the third tertile of percentage of n-3 HUFA (of the total HUFA) as compared with the first tertile. There was no evidence that contaminants had negative effects on GA or birth weight. In this seafood-eating population, an increase in the proportion of n-3 HUFA (of the total HUFA), measured in umbilical cord plasma phospholipids, was associated with a significantly longer GA.