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.

Sociocultural determinants of alcohol and cannabis use and misuse among Nunavimmiut.

OBJECTIVE: Stemming from historical traumas and changes in the Inuit way of life, substance use and its intertwined problems are a major cause of concern for Nunavimmiut. This study's objective is to investigate sociocultural determinants of substance use and misuse to inform culturally appropriate public health programs. METHODS: The 2017 Qanuilirpitaa? survey was conducted among a sample intended to be representative of Nunavimmiut aged 16 and over (total n = 1326). Sociocultural factors included cultural identity, land-based activities, involvement in community activities, social support, and family and community cohesion. The frequency of binge drinking (5 or more drinks on one occasion), cannabis use, and problematic substance use (CAGE and DAST-10) were documented. Data were analyzed using weighted multivariate logistic regressions. Inuit partners were involved from the planning of analyses to the co-interpretation of results. RESULTS: Nearly a third of Nunavimmiut aged 16 and over reported binge drinking at least once a week (29.3%), and 68.6% of drinkers were at risk of potential drinking problems. Forty-five percent (45%) reported using cannabis at least once a week, and 30% of drug users were at risk of potential drug abuse problems. Volunteering and participation in community activities were associated with lower odds of cannabis use, as was frequently going on the land with weekly binge drinking, potential drinking problems, and weekly cannabis use. Social support and community cohesion were associated with higher odds of weekly binge drinking, as was cultural identity (centrality scale) with potential drinking problems. CONCLUSION: Key determinants of substance use relevant to Inuit culture were identified. Results are in line with our Inuit partners' experience in their communities and are coherent with current land-based interventions implemented in Nunavik. A thorough understanding of substance use contexts and related stressors should guide the content and implementation of substance use programs in Nunavik.

RéSUMé: OBJECTIF: Suite aux traumas historiques et changements au mode de vie, l'usage de substance et les problèmes associés sont une source d'inquiétude majeure pour les Nunavimmiut. L'objectif de cette étude est d'investiguer les déterminants socioculturels de l'usage de substances pour adapter les programmes de santé publique à la culture Inuit. MéTHODES: L'enquête Qanuilirpitaa? 2017 repose sur un échantillon sélectionné pour être représentatif des Nunavimmiut (16 ans et plus; n = 1 326). Les déterminants socioculturels incluent : identité culturelle, activités sur le territoire, activités communautaires, support social, cohésion familiale et communautaire. La fréquence de consommation excessive d'alcool (5 consommations ou plus), l'usage du cannabis et l'usage problématique (CAGE et DAST-10) ont été documentés. Données analysées par régression multiple pondérée. Nos partenaires Inuit ont été impliqués de la planification des analyses à la co-interprétation des résultats. RéSULTATS: Près du tiers des Nunavimmiut de 16 ans et plus ont rapporté une consommation hebdomadaire excessive d'alcool (29,3 %) et 68,6 % de ceux consommant de l'alcool étaient potentiellement à risque de consommation problématique. Quarante-cinq pourcent (45 %) ont rapporté consommer du cannabis au moins une fois par semaine et 30 % des consommateurs de drogue étaient à risque de consommation potentiellement problématique. Le bénévolat et la participation aux activités communautaires étaient associés à une cote plus faible d'usage de cannabis, tout comme la pratique fréquente d'activités sur le territoire avec la consommation hebdomadaire excessive d'alcool, d'usage potentiellement problématique d'alcool et d'usage hebdomadaire de cannabis. Le support social et la cohésion communautaire étaient associés à une cote plus élevée de consommation excessive hebdomadaire d'alcool, tout comme l'identité culturelle (centralité) avec l'usage potentiellement problématique d'alcool. CONCLUSION: Des déterminants clés de l'usage de substance spécifiques aux Inuit ont été identifiés. Les résultats concordent avec le vécu de nos partenaires dans leurs communautés et le cadre théorique d'interventions déjà implémentées impliquant des activités sur le territoire et de guérison. Les contextes de consommation et les stresseurs associés devraient guider l'élaboration des programmes au Nunavik.

Profiles of childhood adversities in Inuit from Nunavik: description and associations with indicators of socioeconomic characteristics, support, and community involvement.

OBJECTIVES: Distress and associated health problems reported by Nunavik Inuit emanate from heterogeneous roots, including adverse childhood experiences. This study aims to (1) identify distinct childhood adversity profiles and (2) examine associations between these profiles and sex, socioeconomic characteristics, social support, and community involvement among Nunavimmiut. METHODS: In a sample of 1109 adult Nunavimmiut, sex, socioeconomic characteristics, support, community involvement, residential school attendance, and 10 forms of adverse childhood experiences (ACEs) were documented using questionnaires. Latent class analyses and weighted comparisons were performed for three subgroups: 18-49 years; 50 years and above with experience of residential school; and 50 years and above without experience of residential school. The analysis design, the manuscript drafts, and the key findings were discussed and co-interpreted with the collaboration of community representatives, taking into consideration Inuit culture and needs. RESULTS: A total of 77.6% of Nunavimmiut reported having experienced at least one form of childhood adversity. Three ACE profiles were identified among the 18-49-year-olds: low ACEs (43.0%), household stressors (30.7%), and multiple ACEs (26.3%). Two profiles characterized ACEs experienced among the 50-year-olds and over with and without history of residential schooling: low ACEs (80.1% and 77.2%, respectively) and multiple ACEs (19.9% and 22.8%, respectively). Among the group of 18-49-year-olds, as compared to the low ACE profile, the profile with household stressors included proportionally more women (odds ratio [OR] = 1.5) and was associated with lower involvement in volunteering and community activities (mean score reduced by 0.29 standard deviation [SD]) and lower family cohesion (SD = - 0.11), while the multiple ACE profile was related to a lower rate of employment (OR = 0.62), lower family cohesion (SD = - 0.28), and lower satisfaction with ability to practice traditional activities (SD = - 0.26). CONCLUSION: Childhood adversities among Nunavimmiut do not occur in isolation and experiencing multiple forms of childhood adversities predicts lower socioeconomic status, support, and community involvement in adulthood. Implications for the planning of health and community services in Nunavik are discussed.

RéSUMé: OBJECTIFS: La détresse et les problèmes de santé associés rapportés par les Inuits du Nunavik émanent de racines hétérogènes, notamment des expériences négatives durant l'enfance. Cette étude vise à : 1) identifier des profils distincts d'adversités vécues durant l'enfance; et 2) examiner les associations entre ces profils et le sexe, les caractéristiques socioéconomiques, le soutien social et l'engagement communautaire des Nunavimmiut. MéTHODES: Dans un échantillon de 1 109 adultes Nunavimmiut, le sexe, les caractéristiques socioéconomiques, le soutien, l'engagement communautaire, la fréquentation des pensionnats et 10 formes d'expériences négatives durant l'enfance (ENE) ont été documentés à l'aide de questionnaires. Des analyses de classes latentes et des comparaisons pondérées ont été réalisées pour trois sous-groupes : 18­49 ans; 50 ans et plus avec et sans expérience de pensionnat. Le plan d'analyses, les ébauches de manuscrit et les principaux résultats ont été discutés et co-interprétés avec la collaboration de représentants des communautés, en tenant compte de la culture et des besoins inuits. RéSULTATS: Un total de 77,6 % des Nunavimmiut ont déclaré avoir vécu au moins une forme d'adversité durant l'enfance. Trois profils d'ENE ont été identifiés chez les 18­49 ans : ENE faibles (43,0 %), facteurs de stress domestiques (30,7 %) et ENE multiples (26,3 %). Deux profils caractérisaient les ENE vécus chez les 50 ans et plus avec et sans antécédents de pensionnat : faibles ENE (80,1 % et 77,2 %, respectivement) et ENE multiples (19,9 % et 22,8 %, respectivement). Parmi le groupe des 18­49 ans, par rapport au profil des ENE faibles, le profil avec facteurs de stress domestiques incluait proportionnellement plus de femmes (rapport de cotes [RC] = 1,5) et était associé à une plus faible implication dans le bénévolat et les activités communautaires (score moyen réduit de 0,29 écart-type [ET]) et une cohésion familiale plus faible (ET = -0,11), tandis que le profil d'ENE multiples était lié à un taux d'emploi plus faible (RC = 0,62), à une cohésion familiale plus faible (ET = -0,28) et à une plus faible satisfaction à l'égard de la capacité à pratiquer des activités traditionnelles (ET = -0,26). CONCLUSION: Les adversités vécues en enfance par les Nunavimmiut ne surviennent pas de manière isolée et le fait de vivre de multiples formes d'ENE prédit un statut socio-économique, un soutien et une implication communautaire inférieurs à l'âge adulte. Les implications pour la planification des services de santé et communautaires au Nunavik sont discutées.

Early-Life Exposure to a Mixture of Phenols and Phthalates in Relation to Child Social Behavior: Applying an Evidence-Based Prioritization to a Cohort with Improved Exposure Assessment.

BACKGROUND: Previous studies aiming at relating exposure to phenols and phthalates with child social behavior characterized exposure using one or a few spot urine samples, resulting in substantial exposure misclassification. Moreover, early infancy exposure was rarely studied. OBJECTIVES: We aimed to examine the associations of phthalates and phenols with child social behavior in a cohort with improved exposure assessment and to a priori identify the chemicals supported by a higher weight of evidence. METHODS: Among 406 mother-child pairs from the French Assessment of Air Pollution exposure during Pregnancy and Effect on Health (SEPAGES) cohort, 25 phenols/phthalate metabolites were measured in within-subject pools of repeated urine samples collected at the second and third pregnancy trimesters (∼21 samples/trimester) and at 2 months and 1-year of age (∼7 samples/period). Social behavior was parent-reported at 3 years of age of the child using the Social Responsiveness Scale (SRS). A structured literature review of the animal and human evidence was performed to prioritize the measured phthalates/phenols based on their likelihood to affect social behavior. Both adjusted linear regression and Bayesian Weighted Quantile Sum (BWQS) regression models were fitted. False discovery rate (FDR) correction was applied only to nonprioritized chemicals. RESULTS: Prioritized compounds included bisphenol A, bisphenol S, triclosan (TCS), diethyl-hexyl phthalate (ΣDEHP), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), and mono-benzyl phthalate (MBzP). With the exception of bisphenols, which showed a mixed pattern of positive and negative associations in pregnant mothers and neonates, few prenatal associations were observed. Most associations were observed with prioritized chemicals measured in 1-y-old infants: Each doubling in urinary TCS (ß=0.78; 95% CI: 0.00, 1.55) and MEP (ß=0.92; 95% CI: -0.11, 1.96) concentrations were associated with worse total SRS scores, whereas MnBP and ΣDEHP were associated with worse Social Awareness (ß=0.25; 95% CI: 0.01, 0.50) and Social Communication (ß=0.43; 95% CI: -0.02, 0.89) scores, respectively. BWQS also suggested worse total SRS [Beta 1=1.38; 95% credible interval (CrI): -0.18, 2.97], Social Awareness (Beta 1=0.37; 95% CrI: 0.06, 0.70), and Social Communication (Beta 1=0.91; 95% CrI: 0.31, 1.53) scores per quartile increase in the mixture of prioritized compounds assessed in 1-y-old infants. The few associations observed with nonprioritized chemicals did not remain after FDR correction, with the exception of benzophenone-3 exposure in 1-y-old infants, which was suggestively associated with worse Social Communication scores (corrected p=0.07). DISCUSSION: The literature search allowed us to adapt our statistical analysis according to the weight of evidence and create a corpus of experimental and epidemiological knowledge to better interpret our findings. Early infancy appears to be a sensitive exposure window that should be further investigated. https://doi.org/10.1289/EHP11798.

Sociocultural factors in relation to mental health within the Inuit population of Nunavik.

OBJECTIVE: Built on the Inuit determinants approach of health, this study aimed to identify sociocultural factors associated with mental health among Inuit of Nunavik to guide programs and services. METHODS: The data were collected through the Qanuilirpitaa? 2017, a survey characterized by the involvement of several Inuit representatives. Depressive symptoms (10-item Center for Epidemiologic Studies-Depression scale, CES-D), lifetime suicide ideation and attempts, and past-year ideation were self-reported mental health indicators. Sociocultural factors represented four thematic domains: social support, community activities, traditional practices, and cultural identity. Analyses tested whether the sociocultural factors were associated with indicators of mental health using weighted multivariate regressions. RESULTS: Among the sociocultural factors considered, family cohesion and weekly hunting/fishing activities were associated with lower depression scores. Community cohesion and lower cultural identity (centrality scale) were associated with a lower likelihood of past-year and lifetime ideation while family cohesion was related to a lower likelihood of lifetime attempts. People with psychological distress (higher CES-D, suicidal ideation or attempts) were more likely to participate in healing and wellness activities. CONCLUSION: Although limited by their cross-sectional character, these analyses, based on the community component of the Qanuilirpitaa?, suggest that strengthening of family and community cohesion, and support of regular hunting and fishing deserve further attention as potential cumulative preventive avenues for Inuit mental health.

RéSUMé: OBJECTIF: Basée sur la conception Inuit des déterminants de la santé, cette étude identifie des facteurs socioculturels associés à la santé mentale chez les Inuit du Nunavik afin de guider les programmes et les services de santé. MéTHODE: Les données proviennent de Qanuilirpitaa? 2017, une enquête ayant impliqué plusieurs représentants Inuit. Les symptômes dépressifs (échelle Center for Epidemiologic Studies-Depression, 10 items, CES-D), les idéations suicidaires et les tentatives de suicide à vie, et les idéations au cours des derniers mois furent les indicateurs de santé mentale analysés. Des facteurs socioculturels investigués représentaient, eux, quatre domaines : support social, activités communautaires, pratiques traditionnelles et identité culturelle. Des régressions multivariées pondérées ont testé les associations entre les facteurs socioculturels et la santé mentale. RéSULTATS: Parmi les facteurs socioculturels investigués, la cohésion familiale et une pratique hebdomadaire de chasse/pêche étaient associées au score dépressif inférieur. La cohésion communautaire et une identité culturelle (centralité) plus faible s'associaient à une probabilité moindre d'idéations suicidaires à vie et au cours des 12 derniers mois; la cohésion familiale était associée à une probabilité moindre des tentatives suicidaires à vie. Les personnes rapportant une détresse supérieure (CES-D élevé, idéations ou tentatives) participaient davantage à des activités de guérison/de bien-être. CONCLUSION: Limitées par leur caractère transversal, ces analyses, inspirées du volet communautaire de Qanuilirpitaa?, suggèrent qu'un renforcement de la cohésion familiale et communautaire, ainsi qu'un soutien d'activités de chasse et de pêche régulières méritent davantage d'attention en tant qu'avenues préventives cumulatives potentielles pour la santé mentale des Inuit.

Relocating to a new or pre-existing social housing unit: significant health improvements for Inuit adults in Nunavik and Nunavut.

OBJECTIVES: In 2014-2015, over 400 social housing units were constructed in selected communities in Nunavik and Nunavut, two Inuit regions in northern Canada where housing shortages and poor quality housing are endemic and undermine population health. This paper presents results from a before-and-after study examining the effects of rehousing, i.e., relocating to a newly constructed or pre-existing social housing unit, on psychosocial health and asthma-related symptoms for Inuit adults. METHODS: Baseline data were collected 1-6 months before, and follow-up data 15-18 months after rehousing. Of the 289 participants at baseline, 186 were rehoused. Of the 169 participants eligible at follow-up, 102 completed the study. Self-reported health measures included psychological distress, perceived stress in daily life, perceived control over one's life, and asthma-related symptoms. Data are analyzed using multilevel models for longitudinal data. RESULTS: After adjusting for age, sex, and region of residence, participants reported significantly lower levels of psychological distress and perceived stress in daily life, and improved sense of control over their lives 15 to 18 months after rehousing. Participants were also significantly less likely to report asthma-related symptoms at follow-up. CONCLUSION: Significant positive health impacts are observed for adults who relocated to newly constructed or pre-existing social housing units. Increasing investments to redress the housing situation across Inuit Nunangat is required, not only to improve living conditions but also to improve the health and well-being of the population.

Household overcrowding and psychological distress among Nunavik Inuit adolescents: a longitudinal study.

About half of Nunavik Inuit live in overcrowded households compared to very few Canadians from the general population. Living in overcrowded households is associated with greater risks of suffering from mental health problems for Canadian adolescents. The present work aims at studying prospectively the hypothesised relationship between household overcrowding at childhood and psychological distress during adolescence among Nunavik Inuit, as well as the hypothesised relationship between these phenomena when they are both measure at adolescence. Recruited as part of the Nunavik Child Development Study, 220 participants were met at 11 years old in average and then when they were 18 years old in average. Household overcrowding was assessed using the people per room ratio. Psychological distress symptoms were operationalised at adolescence using depressive symptoms and suicidal thoughts. The results did not show that childhood household crowding had a long-term effect on psychological distress. An absence of moderation by sex of the association was also found in the present study. Despite those results, household crowding could be a risk factor only when in interaction with other elements related with poverty or housing or could be experienced as a difficulty for adolescents on other aspects than depressive symptoms and suicidal thoughts.

Socio-economic inequalities in blood mercury (Hg) and serum polychlorinated biphenyl (PCB) concentrations among pregnant Inuit women from Nunavik, Canada.

OBJECTIVE: We examined the relationships between socio-economic characteristics and mercury (Hg) and polychlorinated biphenyl (PCB) concentrations among pregnant Inuit women from Nunavik. METHOD: We used biomonitoring data from 208 pregnant Inuit women recruited in the 14 villages of Nunavik between September 2011 and December 2013. Blood samples were collected to monitor levels of blood Hg and serum congener PCB-153 (surrogate of total PCB concentration). Ratio of omega 3/omega 6 polyunsaturated fatty acids, a validated biomarker of marine country food consumption, was also measured in red blood cell membranes to determine maternal dietary profile. Data on socio-economic characteristics (income and education), health-related lifestyles, and reproductive history were collected through questionnaires. Association between socio-economic characteristics and contaminant concentrations was assessed using linear regressions. RESULTS: We observed a significant inverse relationship between education and Hg levels. Lower concentrations of Hg were observed among women who had completed high school compared to women who had not completed high school. However, no association was observed between level of education and concentration of PCBs. CONCLUSION: Socio-economic disparities in maternal exposure to Hg exist in Nunavik. Further research is needed to determine whether environmental health inequalities also exist in other subgroups of the Nunavik population and in other Indigenous communities in Canada.

The Predictive Value of Head Circumference Growth during the First Year of Life on Early Child Traits.

Atypical head circumference (HC) growth has been associated with neurodevelopmental disorders. However, whether it is associated with specific aspects of development in early childhood in the general population is unknown. The objective of this study was to assess the predictive value of HC growth as an early biomarker of behavioral traits. We examined longitudinal associations between HC growth from 0 to 12 months and temperament, cognitive, and motor development at 24 months. A subsample of healthy children (N = 756) was drawn from the 3D (Design, Develop, Discover) cohort study. Early HC growth was modeled with latent growth curve analysis. Greater postnatal HC growth predicted lower temperamental effortful control and lower surgency/extraversion in boys. HC growth did not predict cognitive or fine motor scores, but did predict greater gross motor skills in boys. No significant effect of HC growth was found in girls. This study is the first to demonstrate an association between postnatal HC growth and specific aspects of child development in a healthy population. Results suggest HC growth overshadows brain mechanisms involved in behavioral traits in early infancy. Whether links are maintained throughout development and the mechanisms involved correspond to traits found in atypical populations remains to be studied.

Teen pregnancy in Inuit communities - gaps still needed to be filled.

Teen pregnancy is depicted around the world as an important cause of health disparities both for the child and the mother. Accordingly, much effort has been invested in its prevention and led to its decline in the northern hemisphere since the mid-1990s. Despite that, high rates are still observed in the circumpolar regions. As Inuit communities have granted better understanding of teenage pregnancy a priority for the coming years, this article comprehensively reviews this multidimensional issue. By depicting current prevalence, likely determinants and possible impacts documented among Inuit of Canada, Alaska and Greenland, and contrasting them to common knowledge that has emerged from other populations over the years, great gaps surface. In some regions, the number of pregnancies per number of Inuit women aged between 15 and 19 years has increased since the turn of the millennium, while statistics from others are either absent or difficult to compare. Only few likely determinants of teenage pregnancy such as low education and some household factors have actually been recognized among Inuit populations. Documented impacts of early pregnancy on Inuit women and their children are also limited compared to those from other populations. As a way to better address early pregnancy in the circumpolar context, the defence for additional scientific efforts and the provision of culturally adapted sexual health prevention programmes appear critical.

Trajectories of Alcohol Use and Binge Drinking Among Pregnant Inuit Women.

BACKGROUND: This study investigated trajectories of alcohol use and binge drinking among Inuit women starting from a year before pregnancy until a year after delivery, examined transition rates between time periods, and established whether specific factors could be identified as predictors of changes in alcohol behaviors. METHODS: Drinking trajectories and movement among alcohol users and binge drinkers (i.e. non-binging and binging) were explored by Markov modeling across time periods. Two hundred and forty-eight Inuit women from Arctic Quebec were interviewed at mid-pregnancy, and at 1 and 11 months postpartum to obtain descriptive data on alcohol use during the year before pregnancy, the conception period, the pregnancy and the year after delivery. RESULTS: The proportions of drinkers and bingers were 73 and 54% during the year prior to pregnancy and 62 and 33% after delivery. Both alcohol use and binge drinking trajectories demonstrated a significant drop in prevalence between the year before conception to the conception period. We also noted high probabilities of becoming an abstainer or not binging at this time. However, up to 60% of women continued to drink alcohol during pregnancy. Women in couples and not consuming marijuana were more likely to decrease their binge drinking at conception. CONCLUSIONS: This study emphasizes the importance of including the period around conception in the definition of drinking patterns during pregnancy. The importance of considering alcohol consumption in a multidimensional way (personal, familial and social determinants) is also addressed while trying to minimize problems both for the fetus and the mother.

Household crowding and food insecurity among Inuit families with school-aged children in the Canadian Arctic.

OBJECTIVES: We examined the relation of household crowding to food insecurity among Inuit families with school-aged children in Arctic Quebec. METHODS: We analyzed data collected between October 2005 and February 2010 from 292 primary caregiver-child dyads from 14 Inuit communities. We collected information about household conditions, food security, and family socioeconomic characteristics by interviews. We used logistic regression models to examine the association between household crowding and food insecurity. RESULTS: Nearly 62% of Inuit families in the Canadian Arctic resided in more crowded households, placing them at risk for food insecurity. About 27% of the families reported reducing the size of their children's meals because of lack of money. The likelihood of reducing the size of children's meals was greater in crowded households (odds ratio=3.73; 95% confidence interval=1.96, 7.12). After we adjusted for different socioeconomic characteristics, results remained statistically significant. CONCLUSIONS: Interventions operating across different levels (community, regional, national) are needed to ensure food security in the region. Targeting families living in crowded conditions as part of social and public health policies aiming to reduce food insecurity in the Arctic could be beneficial.

A physiologically based pharmacokinetic model for the assessment of infant exposure to persistent organic pollutants in epidemiologic studies.

BACKGROUND: It has been suggested that pre- and postnatal exposure to persistent organic pollutants (POPs) can promote several adverse effects in children, such as altered neurodevelopment. Epidemiologic studies to date have relied on the analysis of biological samples drawn pre- or post-natally for exposure assessment, an approach that might not capture some key events in the toxicokinetics of POPs. OBJECTIVES: We aimed to build a generic physiologically based pharmacokinetic (PBPK) modeling framework for neutral POPs to assess infant toxicokinetic profiles and to validate the model using data on POP levels measured in mothers and infants from a Northern Québec Inuit population. METHODS: The PBPK model developed herein was based upon a previously published model to which an infant submodel was added. Using the model and maternal blood levels at the time of delivery, exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), 2,2',3,4,4',5'-hexachlorobiphenyl (PCB-138), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB-180) in mothers was estimated to subsequently simulate infant blood, breast milk, and cord blood POP concentration. Simulations were then compared with corresponding measured levels through Spearman correlation analyses. RESULTS: Predictions were highly correlated with measured concentrations for PCB-153, PCB-180, PCB-138, HCB, and p,p'-DDE (r = 0.83-0.96). Weaker correlations were observed for p,p'-DDT and beta-HCH for which levels were near the limits of detection. CONCLUSION: This is the first study to validate a PBPK model of POPs in infants on an individual basis. This approach will reduce sampling efforts and enable the use of individualized POP toxicokinetic profiles in the epidemiologic studies of POP adverse effects on child development.

Assessment of pre- and postnatal exposure to polychlorinated biphenyls: lessons from the Inuit Cohort Study.

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.