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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 (RDEHP), 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 (β=0.78; 95% CI: 0.00, 1.55) and MEP (β=0.92; 95% CI: -0.11, 1.96) concentrations were associated with worse total SRS scores, whereas MnBP and RDEHP were associated with worse Social Awareness (β=0.25; 95% CI: 0.01, 0.50) and Social Communication (β=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 푝=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. [ABSTRACT FROM AUTHOR]

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 푇-scores with a doubling in phthalate concentrations in 510 children with complete data. RESULTS: Mean total SRS 푇-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 푇-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 푇-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 (<400 µg/d) (bMBP = 1:3; 95% CI: 0.4, 2.3; n = 59) compared with those who had adequate folic acid supplementation (=400 µg/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. [ABSTRACT FROM AUTHOR]

Background: Many pregnant women are consuming diets of poor overall quality. Although many studies have linked poor prenatal diet quality to an increased risk of specific diseases in offspring, it is not known if exposure to poor prenatal diet affects core neurophysiological regulatory systems in offspring known to lie upstream of multiple diseases.Objective: We aimed to examine the association between prenatal diet quality and autonomic nervous system (ANS) function in infants at 6 mo of age.Methods: Data from 400 women (aged >18 y, with uncomplicated pregnancies) and their infants participating in the Maternal-Infant Research on Environmental Chemicals-Infant Development cohort were used to investigate links between prenatal diet quality and infant ANS function at 6 mo of age. Prenatal diet quality was assessed using the Healthy Eating Index (2010), calculated from a validated FFQ completed by women during the first trimester. Infant ANS function was measured using 2 assessments of heart rate variability (HRV) including root mean square of successive differences (RMSSD) and SD of N-N intervals (SDNN). Associations were analyzed before and after adjustment for socioeconomic status, maternal depression symptoms, maternal cardiometabolic dysfunction, breastfeeding, and prenatal smoking.Results: Poorer prenatal diet quality was associated with lower infant HRV assessed using RMSSD (B: 0.07; 95% CI: 0.01, 0.13; R2 = 0.013) and SDNN (B: 0.18; 95% CI: 0.02, 0.35; R2 = 0.011). These associations remained significant after adjustment for confounding variables [RMSSD: B: 0.09; 95% CI: 0.003, 0.18; squared semipartial correlation (sp2) = 0.14 and SDNN B: 0.24; 95% CI: 0.0, 0.49; sp2 = 0.13].Conclusions: In a large cohort study, poorer prenatal diet quality was associated with lower offspring HRV, a marker of decreased capacity of the ANS to respond adaptively to challenge. Therefore, poor prenatal diet may play a significant role in the programming of multiple organ systems and could increase general susceptibility to disease in offspring. [ABSTRACT FROM AUTHOR]

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 (mean±SD; milligrams per liter) were almost two times higher for pregnant women living in fluoridated regions (0.87±0.50) compared with nonfluoridated regions (0.46±0.34; p<0.001). 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 (ICC range=0.37-0.40). The municipal water fluoride level was positively associated with creatinine-adjusted MUF (B=0.52, 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 (r=0.31-0.32 but not green tea (r=0.04-0.06). Urinary creatinine and SG correction methods were highly correlated (r=0.91) 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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal bisphenol A (BPA) exposure has been associated with adverse neurodevelopment in epidemiological studies. However, prior studies had limited statistical power to examine sex-specific effects, and few examined child cognition. OBJECTIVES: We estimated the association between prenatal BPA exposure and child neurobehavior at 3 y of age in a prospective cohort of 812 mothers and their children. METHODS: We measured BPA concentration in urine samples collected at ∼12 wk gestation among women enrolled in a 10-city Canadian cohort study. At approximately 3 y of age, we assessed children's cognitive abilities with the Wechsler Primary and Preschool Scale of Intelligence™-III (WPPSI-III) and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's behavior using the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale™-2 (SRS-2). We estimated covariate-adjusted differences in neurobehavioral outcomes with a doubling in BPA concentration and sex-specific associations. RESULTS: BPA was not associated with WPPSI-III scores; child sex did not modify these associations. The association between BPA and BRIEF-P scores was modified by child sex (BPA×sex p-values≤0.03). For example, a doubling of BPA concentration was associated with 1-point (95% CI: 0.3, 1.7) poorer working memory in boys and 0.5-point (95% CI: -1.1, 0.1) better scores in girls. BPA was not associated with most BASC-2 scales; however, it was associated with more internalizing and somatizing behaviors in boys, but not in girls (BPA×sexp-values≤0.08). A doubling of BPA concentration was associated with poorer SRS-2 scores [β=0.3 ( 95% CI: 0, 0.7)]; this association was not modified by sex. CONCLUSION: Prenatal urinary BPA concentration was associated with some aspects of child behavior in this cohort, and some associations were stronger among boys. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

Many migrants do not speak the official language of their host country. This linguistic gap has been found to be an important contributor to disparities in access to services and health outcomes. This study examined primary care mental health practitioners' experiences with linguistic diversity. 113 practitioners in Montreal completed a self-report survey assessing their experiences working with allophones. About 40 % of practitioners frequently encountered difficulties working in mental health with allophone clients. Few resources were available, and calling on an interpreter was the most common practice. Interpreters were expected to play many roles, which went beyond basic language translation. There is a clear need for training of practitioners on how to work with different types of interpreters. Training should highlight the benefits and limitations of the different roles that interpreters can play in health care delivery and the differences in communication dynamics with each role. [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]

Background: Despite experimental evidence that lactational exposure to persistent organic pollutants (POPs) can impact health, results from epidemiologic studies are inconclusive. Inconsistency across studies may reflect the inability of current methods to estimate children's blood levels during specific periods of susceptibility. Objectives: We developed a toxicokinetic model to simulate blood POP levels in children from two longitudinal birth cohorts and aimed to validate it against blood levels measured at 6, 16, and 45 months of age. Methods: The model consisted of a maternal and a child lipid compartment connected through placental diffusion and breastfeeding. Simulations were carried out based on individual physiologic parameters; duration of breastfeeding; and levels of POPs measured in maternal blood at delivery, cord blood, or breast milk. Model validity was assessed through regression analyses of simulated against measured blood levels. Results: Simulated levels explained between 10% and 83% of measured blood levels depending on the cohort, the compound, the sample used to simulate children's blood levels, and child's age when blood levels were measured. Model accuracy was highest for estimated blood POP levels at 6 months based on maternal or cord blood levels. However, loss in model precision between the 6th and the 45th month was small for most compounds. Conclusions: Our validated toxicokinetic model can be used to estimate children's blood POP levels in early to mid-childhood. Estimates can be used in epidemiologic studies to evaluate the impact of exposure during hypothesized postnatal periods of susceptibility on health. [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]

Alcohol consumption during pregnancy, a known teratogen often associated with drug use and smoking is a well-known public health concern. This study provides prevalence data for alcohol, smoking, and illicit drug use before, during, and after pregnancy among Inuit. Factors associated with alcohol use are also identified. Two hundred and eight Inuit women from Arctic Quebec were interviewed at mid-pregnancy, and at 1 and 11 months postpartum to provide descriptive data on smoking, alcohol, and drug use during pregnancy, and the year before and after pregnancy. Sociodemographic and family characteristics potentially associated with alcohol use were documented. Ninety-two percent of the women reported smoking and 61% reported drinking during pregnancy. Episodes of binging during pregnancy were reported by 62% of the alcohol users, which correspond to 38% of pregnant women. Thirty-six percent of the participants reported using marijuana during pregnancy. Alcohol use and binge drinking during pregnancy were more likely to be reported by women who lived in less crowded houses, had a better knowledge of a second language, drank alcohol more often and in larger amounts prior to pregnancy, and used illicit drugs. Binge drinkers were more likely to be single women and to have had fewer previous pregnancies. Postpartum distress and violence were more likely to be experienced by women who used alcohol during pregnancy. Binge drinking during pregnancy was best predicted by drinking habits before pregnancy, maternal symptoms of depression, the use of illicit drugs during pregnancy, and the number of young children living with the mother. These results confirm that alcohol is a major risk factor to maternal and child health in this population, underscoring the need for culturally relevant and effective prevention programs. [ABSTRACT FROM AUTHOR]

Although an extensive literature has documented a broad range of cognitive performance deficits in children with prenatal alcohol exposure, little is known about how the neurophysiological processes underlying these deficits may be affected. Event-related potentials (ERPs), which reflect task-specific changes in brain electrical activity, provide a method for examining multiple constituents of cognitive processing at the neural level. We recorded ERPs in 217 children from Inuit communities in Arctic Quebec (M age = 11.3 years) during 2 different tasks-Go/No-go response inhibition and continuous recognition memory. Children were classified as either alcohol-exposed (ALC) or controls (CON) depending on whether the mother reported binge drinking during pregnancy. Both groups performed comparably in terms of accuracy and reaction time on the tasks, and both tasks elicited the expected effects on ERPs when responses were compared across conditions. However, the ALC group showed slower P2 latencies on Go/No-go, suggesting an altered neurophysiological response associated with initial visual processing of the stimuli. On the memory task, the ALC group showed reduced FN400 amplitude to New items, known as the familiarity effect, and reduced amplitude for the late positive component, possibly reflecting impairment in memory retrieval. These findings show that, even in tasks in which alcohol-exposed children exhibit behavioral performance that is comparable to controls, fetal alcohol exposure is associated with altered neurophysiological processing of response inhibition and recognition memory. The data suggest that fetal alcohol exposure is associated with reduced efficiency in the initial extracting of the meaning of a stimulus, reduced allocation of attention to the task, and poorer conscious, explicit recognition memory processing. [ABSTRACT FROM AUTHOR]

Objective: To compare children's cognitive, motor, and language development at 2 years of age after assisted reproductive technologies (ARTs) relative to natural conception.Methods: The 3D-Study (2010-2012) is a prospective cohort study, which sought to improve the understanding among perinatal events, obstetric outcomes, and child development. A total of 2,366 pregnant women were recruited, of whom 278 conceived with ART: ovarian stimulation, intrauterine sperm insemination, in vitro fertilization, intracytoplasmic sperm injection, or in vitro maturation. Natural conception was defined as the unassisted establishment of pregnancy. Cognitive, motor, and language neurodevelopmental outcomes were compared between ART and natural conception groups at 24 months using the Bayley Scales of Infant and Toddler Development, 3rd edition, and the MacArthur-Bates Communicative Development Inventories. Adjusted linear regression models evaluated the effect of ART on neurodevelopmental outcomes using natural conception as a reference.Results: A total of 175 children in the ART group (62.9%) and 1,345 children in the natural conception group (64.4%) underwent neurodevelopmental assessment at 24 months postpartum. After adjusting for relevant confounders, children born after ART showed no difference in Bayley scales' cognitive scores (B1 [standard error]=-1.60 [0.9], 95% confidence interval [CI] -3.36 to 0.16), composite motor scores (B1 [standard error]=-1.33 [1.0], 95% CI -3.29 to 0.63), or MacArthur-Bates language scores (B1 [standard error]=-0.28 [2.1], 95% CI -4.39 to 3.83). No difference was observed when independent ART techniques were compared nor when comparing in vivo (ovarian stimulation or intrauterine insemination) or in vitro (in vitro fertilization, intracytoplasmic sperm injection, or in vitro maturation) techniques (P>.05).Conclusion: Children born after ART had similar cognitive, motor, and language development as children born after natural conception at 2 years of age. These findings may be useful in the clinical counseling of patients undergoing ART. [ABSTRACT FROM AUTHOR]