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[Display omitted] • This is the first study to examine associations between prenatal fluoride exposure and disruptions to visual acuity and cardiac autonomic function in infants. • In this Canadian pregnancy cohort, prenatal fluoride exposure was linked to poorer visual acuity. • Prenatal fluoride exposure was linked to lower heart rate variability (root mean square of successive differences) • Results suggest that prenatal fluoride exposure may be associated with poorer central and peripheral markers of nervous system functioning in infant offspring. Prenatal fluoride exposure can have adverse effects on children's development; however, associations with visual and cardiac autonomic nervous system functioning are unknown. We examined associations between prenatal fluoride exposure and visual acuity and heart rate variability (HRV) in 6-month-old infants. We used data from Canadian mother-infant pairs participating in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. We estimated prenatal fluoride exposure using: i) fluoride concentration in drinking water (mg/L), ii) maternal urinary fluoride adjusted for specific gravity (MUF SG ; mg/L) and averaged across pregnancy, and iii) maternal fluoride intake (µg/kg/day) from consumption of water, tea, and coffee, adjusted for maternal body weight (kg). We used multivariable linear regression to examine associations between each measure of fluoride exposure and Teller Acuity Card visual acuity scores (n = 435) and assessed HRV (n = 400) using two measures: root mean square of successive differences (RMSSD) and the standard deviation of N-N intervals (SDNN) measured at 6-months of age. Median (IQR) values for water fluoride, MUF SG , and daily fluoride intake were 0.20 (IQR: 0.13–0.56) mg/L; 0.44 (0.28–0.70) mg/L and 4.82 (2.58–10.83) µg/kg/day, respectively. After adjustment for confounding variables, water fluoride concentration was associated with poorer infant visual acuity (B = - 1.51; 95 % CI: −2.14,-0.88) and HRV as indicated by lower RMSSD (B = -1.60; 95 % CI: −2.74,-0.46) but not SDNN. Maternal fluoride intake was also associated with poorer visual acuity (B = -0.82; 95 % CI: −1.35,-0.29) and lower RMSSD (B = -1.22; 95 % CI: −2.15,-0.30). No significant associations were observed between MUF SG and visual acuity or HRV. Fluoride in drinking water was associated with reduced visual acuity and alterations in cardiac autonomic function in infancy, adding to the growing body of evidence suggesting fluoride's developmental neurotoxicity. [ABSTRACT FROM AUTHOR]

• Prenatal PBDE exposure can interfere with children's neurodevelopment. • PBDE blood concentrations in Canada are less than half those in the U.S.A. • We measured PBDEs in maternal blood and assessed IQ for 592 3-year-old children. • Prenatal PBDE exposure was related to lower IQ scores, but only among boys. • It suggests sex-specific neurotoxicity at the low PDBE levels in Canada. Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with adverse neurodevelopmental outcomes in children, but evidence remains mixed regarding sex differences in this association. To examine the prospective association between prenatal PBDE exposure and cognitive ability in young children, as well as potential sex differences. The study was conducted in a multi-site Canadian pregnancy cohort recruited in 2008–11. PBDEs were measured in maternal plasma samples collected early in pregnancy. Cognitive ability was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) in children at age 3 years (mean = 3.4). Multiple linear regression was used to analyze the association between maternal PBDE plasma concentrations (lipid-standardized and log10-transformed) and Verbal, Performance, and Full Scale IQ scores on the whole sample and stratified by sex, adjusting for confounders. The sample was composed of 592 children (291 boys and 301 girls). A tenfold increase in maternal blood PBDE concentration (sum of BDE-47, −99, −100, and −153) was associated with lower Full Scale scores in boys (−3.4 points; 95% CI: −7.0, 0.1), after adjusting for confounders. BDE-47 was the congener with the highest concentrations in maternal blood and a tenfold increase in exposure was associated with significantly lower Full Scale IQ scores in boys (−4.4 points; 95% CI: −7.9, −0.9), after adjusting for confounders. Verbal and Performance IQ scores were similarly associated with PBDE exposure. Maternal blood PBDE concentrations were not associated with IQ scores in girls. Prenatal exposure to background levels of PBDEs, especially BDE-47, was associated with lower IQ scores in boys, but not in girls. Our results support that exposure to PBDEs during early development may be sex-dependent and detrimental to a child's neurodevelopmental trajectory. [ABSTRACT FROM AUTHOR]

The Inuit of Nunavik (Northern Quebec, Canada) are exposed to polychlorinated biphenyls (PCBs) and mercury (Hg) through their consumption of marine country foods. A temporal trend study was initiated in 1992 to monitor circulating levels of PCBs and Hg in pregnant Inuit women, since the fetus is most at risk of adverse health effects. We set out (1) to describe temporal trends of PCBs and Hg levels in pregnant Nunavik women between 1992 and 2017; (2) to determine the prevalence of participants exceeding the guidance values in 2017; (3) to investigate relations between marine country food intake and contaminant levels over the study period. A total of 559 pregnant women provided a blood sample for contaminant analysis from 1992 to 2017. PCB congeners were quantified in plasma (serum) by gas chromatography (GC) coupled to electron capture detection or mass spectrometry (MS). We determined whole blood mercury concentration by cold vapor atomic absorption or inductively-coupled plasma MS. We performed multilevel modeling to assess temporal trends in contaminant levels and relations with marine country food consumption. Concentrations of total PCBs and Hg decreased by 84% and 65% between 1992 and 2017, respectively. Nevertheless, 10% and 22% of women in 2017 exceeded guidance values for PCBs and Hg, respectively. While the decline in marine country food intake is the only factor associated with decreasing Hg levels, other factors may explain the decline in PCB levels. Despite the significant decline in PCBs and Hg levels from 1992 to 2017, exposure to these contaminants is still quite prevalent among pregnant Nunavik women. Most of the decline in Hg exposure is likely due to a shift away from marine country foods to store-bought foods, which is a concern given the cultural and nutritional importance of country foods and the high food insecurity that prevails in Nunavik. Unlabelled Image • PCBs and Hg levels declined significantly between 1992 and 2017 in pregnant Inuit women. • In 2017, 22% of pregnant women exceeded the Canadian guideline for blood Hg levels. • Declines in PCBs and Hg levels are linked to a reduction in country food intake. • Decreasing country food contamination likely contributed to reducing PCBs levels. [ABSTRACT FROM AUTHOR]

Objective: The present study aims at measuring the association between household food insecurity and psychological distress in adolescents in Inuit communities, concurrently and overtime from childhood to adolescence.Design: The study used measures of internalising behaviours (anxiety, withdrawn attitude, somatic complaints and depression) as indicators of psychological distress during adolescence, a concurrent measure of household food insecurity in adolescence and an assessment of longitudinal patterns of household food insecurity from childhood to adolescence. We collected descriptive information at birth, childhood and adolescence on potential confounders.Setting: Inuit communities of Nunavik in northern Quebec, Canada.Participants: The study consisted of 212 participants from the Nunavik Child Development Study, who have been assessed at birth, childhood (mean age = 11 years, range = 9-13 years) and adolescence (mean age = 18 years, range = 16-21 years).Results: Concurrent severe household food insecurity in adolescence was associated with higher measures of psychological distress: depression (βstd = 0·26, P < 0·01) and withdrawn attitude (βstd = 0·20, P = 0·04). Persistent household food insecurity (both at childhood and adolescence) was associated with higher levels of adolescent depression (βstd = 0·18, P = 0·02) and anxiety (βstd = 0·17, P = 0·03).Conclusions: Adolescents from Nunavik living with higher food insecurity and those having experienced food insecurity in both childhood and adolescence were more likely to report symptoms of psychological distress. Considering the high level of distress experienced by young Inuit, existing initiatives to reduce food insecurity in Nunavik communities should be targeted to include children and adolescents. [ABSTRACT FROM AUTHOR]

• Exposure to perfluoroalkyl substances (PFAS) is widespread. • Some PFAS may have androgenic endocrine-disrupting properties. • Prenatal plasma PFOA was associated with small increase in anoscrotal distance. • No evidence of PFOS, PFOA or PFHxS and shorter anogenital distance in males. • No evidence of androgenic effects of PFAS on anogenital distance in females. Exposure to the man-made chemicals perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonate (PFHxS) is widespread. These perfluoroalkyl substances (PFASs) have been associated with androgenic endocrine-disrupting properties; however, the evidence is equivocal and few human studies have examined the association between prenatal exposure to PFASs and markers of androgenic endocrine disruption such as changes in anogenital distance (AGD). In the MIREC cohort, PFOA, PFOS and PFHxS were analyzed in first trimester maternal plasma. AGD was measured in 205 male and 196 female newborns. The change in estimate procedure was used to identify confounders by sex and AGD in multiple linear regression models. Geometric mean plasma concentrations (95% CI) for PFOA, PFOS and PFHxS were 1.71 (1.61, 1.81), 4.40 (4.18, 4.64) and 1.15 (1.06, 1.25) μg/L, respectively. A one-unit increase in natural log transformed PFOA was associated with a 1.36 mm (95% CI 0.30, 2.41) increase in anoscrotal distance, adjusting for household income, active smoking status during pregnancy and gestational age. However, when examined by quartiles, a non-monotonic pattern was observed with wide confidence intervals. No consistent patterns were observed between maternal PFAS concentrations and female AGDs. This study found no clear evidence that maternal plasma concentrations of PFOS, PFOA or PFHxS were associated with shorter infant anogenital distance in males or any change in AGD in females. Whether the positive association observed between longer anoscrotal distance and PFOA is real or would have any long-lasting effect on the reproductive health of males is unknown and needs to be investigated further. [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]

Prenatal and childhood mercury (Hg) exposures have been associated with negative impacts on child neurodevelopment. It is unclear if associations persist at the low Hg exposures typical in Western countries. To examine associations between prenatal/childhood blood Hg concentrations and child IQ in Canadian male and female children while considering the potential modifying role of prenatal fish consumption. We analyzed data from the Maternal-Infant Research on Environmental Chemicals study. Hg was measured in first trimester (n = 527), cord (n = 430), and child (at 3–4 years of age, n = 355) blood and examined sex-stratified associations between blood Hg and children's Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ), and General Language Composite (GLC) scores (assessed with WPPSI-III). Prenatal Hg analyses were further stratified by prenatal fish consumption (low: 0–2, moderate: 3–7, or high: ≥8 times/month). Higher cord blood Hg concentrations were associated with lower PIQ (ß = −3.27; 95%CI: 6.44, −0.09) in male children with the lowest prenatal fish consumption. Progressively stronger positive associations were observed with PIQ in male children for moderate (ß = 1.08; 95%CI: 0.10, 2.26) and high (ß = 3.07; 95%CI: 1.95, 4.19) prenatal fish consumption. Cord blood Hg concentrations were positively associated with female children's FSIQ (ß = 1.29; 95% CI: 0.77, 1.81) and PIQ (ß = 2.01; 95% CI: 1.19, 2.83); however, when stratified only in the highest fish consumption subgroup. Among female children, higher child blood Hg concentrations were associated with an approximately 1-point increase in FSIQ, VIQ, and GLC. Prenatal exposure to low levels of Hg was associated with lower PIQ scores in male children with low prenatal fish intake. Positive associations between cord and child blood Hg concentrations and IQ were primarily observed in female children and may be due to beneficial effects of prenatal fish intake. • Examined associations between prenatal and child blood mercury (Hg) with child IQ. • Cord blood Hg with low fish intake was associated with lower performance IQ in males. • Cord blood Hg with high fish intake was associated with higher IQ in females. • Each doubling of child blood Hg associated with 1-point increase in IQ in females. • Results highlight the beneficial effects of fish intake during pregnancy. [ABSTRACT FROM AUTHOR]

• Prenatal androgen exposure is thought to impact early cochlear development. • Physical indices, e.g. penile length, provide a proxy for fetal androgen exposure. • We find that scrotal pigmentation is inversely associated with inner ear function. • We find that penile length is inversely associated with inner ear function. • These findings are reported for the first time in a sample of human infants. Sex differences in inner-ear function are detectable in infants, notably through the measurement of otoacoustic emissions (OAEs). Prevailing theories posit that prenatal exposure to high levels of androgens in boys may weaken OAEs, and that this phenomenon may predominantly affect the right ear/left hemisphere (Geschwind-Galaburda (GG) hypothesis). Yet, actual tests of these models have been difficult to implement in humans. Here we examined the relationship between markers of fetal androgen exposure collected at birth (anogenital distances (AGD); penile length/width, areolar/scrotal/vulvar pigmentation) and at 6 months of age (2nd to 4th digit ratio (2D:4D)) with two types of OAEs, click-evoked OAEs (CEOAEs) and distortion-product OAEs (DPOAEs) (n = 49; 25 boys; 24 girls). We found that, in boys, scrotal pigmentation was inversely associated with the amplitude and reproducibility of CEOAEs in the right ear at 4 kHz, with trends also present in the same ear for mean CEOAE amplitude and CEOAE amplitude at 2 kHz. Penile length was inversely associated with the mean amplitude of DPOAEs in both the right and left ears, as well as with DPOAE amplitude in the right ear at 2 kHz and the reproducibility of CEOAEs in the left ear at 2.8 kHz. Finally, AGD-scrotum in boys was positively associated in boys with the amplitude of DPOAEs in the left ear at 2.8 kHz. Unexpectedly, there were no sex differences in the amplitude or reproducibility of OAEs, nor, in girls, any associations between androgenic markers and auditory function. Nonetheless, these findings, reported for the first time in a sample of human infants, support both the prenatal-androgen-exposure and GG models as explanations for the masculinization of auditory function in male infants. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a high production volume chemical and because of its use in many consumer products, exposure is ubiquitous. Gestational BPA exposure has been associated with excess adiposity in rodent studies, but not consistently in human studies. We investigated the relation between gestational BPA exposure and early childhood adiposity in a prospective cohort study of 719 mother-child pairs. We used data from the MIREC Study, a prospective Pan-Canadian pregnancy and birth cohort study. We measured BPA in urine samples collected at an average of 12.1 weeks (range: 6.3–15 weeks) gestation and measured children's weight, height, waist/hip circumference, and subscapular/triceps skinfold thickness at an average age of 3.5 years (range: 1.9–6.2). We estimated covariate-adjusted associations of log 2 -transformed BPA concentrations with child adiposity measures and examined whether these associations differed in boys and girls. Median BPA concentrations were 0.8 ng/mL (IQR: 0.5–1.4). Among both boys and girls, each 2-fold increase in BPA concentrations was associated with higher waist-to-hip ratio (β: 0.003; 95% CI: 0.001, 0.005). The association of BPA with waist circumference and subscapular skinfold thickness was modified by sex (sex x BPA interaction p-values<0.2). In girls, each 2-fold increase in BPA concentrations was associated with a 0.2 cm (95% CI: 0.0, 0.5) and 0.15 mm (95% CI: 0.01, 0.30) increase in waist circumference and subscapular skinfolds, respectively. Associations were generally null or slightly inverse in boys. In this cohort, gestational urinary BPA concentrations were associated with subtle increases in girl's central adiposity during early childhood. • Increasing gestational BPA exposure was associated with higher waist-to-hip ratio in early childhood. • Gestational BPA exposure was associated with greater central adiposity in early childhood among girls, but not boys. • Gestational BPA exposure was not associated with child BMI Z-score in either sex. • Gestational environmental chemical exposures may play a role in the development of early childhood obesity. [ABSTRACT FROM AUTHOR]

Abstract Background Lead exposure predicts altered neurodevelopment and lower intelligence quotient (IQ) in children, but few studies have examined this association in children who have relatively low blood lead concentrations. Objectives To test the associations between blood lead concentrations and cognitive function in Canadian preschoolers, with a possible moderation by sex. Methods The data were gathered from 609 mother-child pairs from the Maternal–Infant Research on Environmental Chemicals (MIREC) Study. Lead was measured in umbilical and maternal blood, and in children's venous blood at age 3–4 years. Cognitive function was measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) at 3–4 years. We tested the relationship between WPPSI-III scores and blood lead concentrations with multiple linear regression, adding child sex as a moderator. Results Median blood lead concentrations for the mother at 1st trimester and 3rd trimester of pregnancy, and for cord and child blood were 0.60 μg/dL, 0.58 μg/dL, 0.79 μg/dL and 0.67 μg/dL, respectively. We found no association between cord blood lead concentrations and WPPSI-III scores in multivariable analyses. However, cord blood lead concentrations showed a negative association with Performance IQ in boys but not in girls (B = 3.44; SE = 1.62; 95% CI: 0.82, 5.98). No associations were found between WPPSI-III scores and prenatal maternal blood or concurrent child blood lead concentrations. Conclusions Prenatal blood lead concentrations below 5 μg/dL were still associated with a decline in cognitive function in this Canadian cohort, but only for boys. Highlights • Cord blood lead concentration was associated with lower Performance IQ in boys. • Concurrent child blood lead concentrations were not associated with children's IQ. • Canadian children from middle/upper class families are exposed to low lead levels. [ABSTRACT FROM AUTHOR]

Abstract Background Anogenital distance (AGD) and the second to fourth finger (2D:4D) digit ratio may be early markers of in utero androgen exposure for the infant. Phthalates and phenols have been identified as endocrine disrupting chemicals. Objectives To study the association between prenatal exposure to phthalates, bisphenol A (BPA) and triclosan (TCS) and AGD and the 2D:4D digit ratios. Methods Single spot urine samples were collected in the first trimester from the MIREC Study and analyzed for phthalates and phenols. Anogenital distance (n = 394) at birth and 2D:4D digit ratios (n = 420) at 6 months were measured in male and female infants. Associations between maternal concentrations of phenols and phthalate metabolites and these outcomes were estimated using multiple linear regression models. Results In females, the anoclitoris distance (ACD) was negatively associated with mono-benzyl phthalate (MBzP) (β = −1.24; 95% CI −1.91, −0.57) and positively associated with mono-ethyl phthalate (MEP) (β = 0.65; 95% CI 0.12, 1.18) (masculinizing). In males, anopenile distance (APD) was positively associated with mono-n-butyl phthalate (MnBP) (β = 1.17; 95% CI 0.02, 2.32) and the molar sum of low molecular weight phthalates (ΣLMW). Female 2D:4D of the right hand was positively associated with MnBP and negatively with total BPA (masculinizing). Conclusions Significant associations were only observed for the long AGD metrics. Positive associations were observed between MnBP or LMW phthalates and APD in males. In females, prenatal MEP was associated with a masculinizing effect on ACD, while MBzP was associated with a feminizing effect. No significant associations were observed between prenatal phenols and AGD. Given the paucity of research on digit ratios and prenatal chemical exposures, it is difficult to say whether this metric will be a useful marker of prenatal androgen or anti-androgen exposure. Given the large number of associations examined, the statistical associations observed may have been due to Type 1 error. The inconsistencies in results between studies suggest that this issue is yet to be resolved. Highlights • Anus-clitoris distance was negatively associated with mono-benzyl phthalate. • Anus-clitoris distance was positively associated with mono-ethyl phthalate. • Anopenile distance was positively associated with mono-n-butyl phthalate. • No significant associations between prenatal phenols and anogenital distances. • Given large number of associations examined, results may be due to Type 1 error. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to maternal metabolic complications has been linked to offspring neurodevelopmental problems. However, no studies investigating these links have examined the role of maternal prenatal diet.Aims: To determine if prenatal exposure to maternal adiposity or hyperglycemia is associated with neurodevelopmental problems in 3-4 year old children, and if links persist following adjustment for confounding variables, including prenatal diet.Method: 808 mother-child pairs from the Maternal-Infant Research on Environmental Chemicals-Child Development Plus cohort were used to examine associations between pre-pregnancy body mass index (BMI), hyperglycemia and offspring verbal, performance and full-scale IQ scores, as well as internalizing and externalizing problems. Associations were examined before and after adjustment for prenatal diet along with home environment, maternal depression, education and prenatal smoking. Semi-partial correlations were examined post-hoc to assess the impact of each confounder in the adjusted models.Results: In the unadjusted models, BMI and hyperglycemia predicted lower verbal and full-scale IQ. BMI was also linked to externalizing problems. However, associations were not significant after adjustment. In adjusted models, post-hoc analysis revealed that prenatal diet and home environment accounted for significant variance in verbal and full-scale IQ. The home environment and maternal depression accounted for significant variance in externalizing problems.Conclusion: In the adjusted models, maternal metabolic complications were not associated with offspring neurodevelopment. Even while adjusting for well-known risk factors for adverse offspring cognition (home environment, maternal depression), we show for the first time that maternal prenatal diet is an important confounder of the links between maternal metabolic complications and offspring cognition. [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]

Abstract Background Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with cognitive deficits and behavioral problems in children. To date, no study has examined this exposure in association with neurobehavioral development in infants younger than 12 months assessed with observational tasks. Objectives This study examined the relation between prenatal PBDE concentrations and predisposition to frustration, assessed by the arm restraint task (ART), in Canadian infants. Methods In a prospective longitudinal study conducted in Canada, exposure to nine PBDE congeners was measured in maternal plasma during the first trimester of pregnancy. The ART was used to measure predisposition to frustration in infancy (N = 333; mean age = 6.9 months), as assessed by negative vocalizations (crying and screaming) and physical reactivity (discomfort movements). Results Maternal plasma PBDE-47 concentrations collected during pregnancy were associated with negative vocalizations using the ART (adjusted Relative Risk [aRR] = 1.04, 95% CI: 1.00, 1.09). Prenatal PBDE-99 concentrations during pregnancy were also related to a shift to the left in the tail of the distribution of onset of negative vocalizations as measured by a decrease of 38 s (95% CI: −78.1, 1.3) in the 75th quantile of the distribution for infants whose mothers had detectable levels of PBDE-99 compared to infants of mothers with undetectable levels. Similarly, infants whose mothers had detectable levels of PBDE-100 showed an increase of 24.1 s (95% CI: 4.1, 44.1) in the 75th quantile of the distribution of proportion of time in negative vocalizations compared with infants of mothers with undetectable levels. Finally, the association between PBDE-47 and PBDE-153, and physical reactivity was significantly modified by sex (p < 0.1), with opposite patterns in girls and boys. Conclusions Prenatal exposure to PBDEs was associated with increased incidence of crying and screaming with delayed onset of discomfort movement, which may indicate a predisposition to frustration and lack of habituation in infants younger than 12 months from the general population. Highlights • PBDE concentrations in North Americans is ubiquitous and higher than concentrations in other populations. • We examined associations between prenatal concentrations of PBDEs and infant's behavior using the arm restraint task, a quasi-experimental test. • Prenatal exposure to PBDEs was associated with increased incidence of crying and screaming with delayed onset of discomfort movement in a frustrating situation. • Results indicate a predisposition to frustration and lack of habituation as previously reported in animal studies. [ABSTRACT FROM AUTHOR]

Exposure to perfluoroalkyl substances (PFAS) has been shown to be neurotoxic in experimental studies, but epidemiological evidence linking prenatal PFAS exposure to child neurodevelopment is equivocal and scarce. To quantify associations between prenatal exposure to legacy PFAS and children's intelligence (IQ) and executive functioning (EF) in a Canadian pregnancy and birth cohort and to determine if these associations differ by child sex. We measured first-trimester plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) in the Maternal-Infant Research on Environmental Chemicals (MIREC) study and assessed children's full-scale (n = 522), performance (n = 517), and verbal (n = 519) IQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Children's working memory (n = 513) and ability to plan and organize (n = 514) were assessed using a parent-reported questionnaire, the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). We quantified associations between individual log2-transformed PFAS exposure and children's IQ and EF using multiple linear regression analyses and evaluated effect modification by child sex. We also used Repeated Holdout Weighted Quantile Sum (WQS) regression models with effect modification by child sex to quantify the effect of combined exposure to all three PFAS chemicals on IQ and EF. All models were adjusted for key sociodemographic characteristics. Geometric mean plasma concentrations (IQR) for PFOA, PFOS and PFHxS were 1.68 (1.10–2.50), 4.97 (3.20–6.20) and 1.09 (0.67–1.60) μg/L respectively. We found evidence of effect modification by child sex in all models examining performance IQ (p <.01). Specifically, every doubling of PFOA, PFOS, and or PFHxS was inversely associated with performance IQ, but only in males (PFOA: B = −2.80, 95% CI: −4.92, −0.68; PFOS: B = −2.64, 95% CI: −4.77, −0.52; PFHxS: B = −2.92, 95% CI: −4.72, −1.12). Similarly, every quartile increase in the WQS index was associated with poorer performance IQ in males (B = −3.16, 95% CI: −4.90, −1.43), with PFHxS contributing the largest weight to the index. In contrast, no significant association was found for females (B = 0.63, 95% CI: −0.99, 2.26). No significant associations were found for EF in either males or females. Higher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific. • We assessed associations between PFAS and child neurodevelopment. • PFOS, PFOS and PFHxS were inversely associated with nonverbal IQ in males. • In mixture models, PFHxS was identified as a chemical of concern. • We observed no associations between PFAS and executive functioning. • The association between PFAS and IQ may be sex and domain-specific. [ABSTRACT FROM AUTHOR]

Objective Prenatal exposure to stress and fever are factors lowering seizure threshold in animal models. The fever effect on seizure threshold is well documented in human infants, however the associations between maternal perinatal stress and infants’ susceptibility to seizures is unknown. This is the first study in humans to investigate longitudinally, whether in humans, the effect of maternal perinatal emotional symptoms such as stress, anxiety and depression that may trigger a biological stress response on age at first seizure occurrence. Method The study sample is a subgroup drawn from a longitudinal follow up cohort (3D cohort study: Design, Develop, Discover, N = 2366 mother-infant dyads). Twenty-nine otherwise healthy infants who had a febrile seizure (FS) episode before the last follow-up visit (around 24 months of age) were studied. Mothers completed questionnaires regarding their emotional health at each pregnancy trimester and at three months postpartum. The link between maternal emotional symptoms and infant age at first FS was assessed through correlations and multiple regressions. Results We found that maternal anxiety symptoms during the second trimester of pregnancy are linked to the age at first FS ( r (23) = −0.459, p = 0.021) and explain 21.1% of its variance. Postnatal maternal depression symptoms at 3 months postpartum were also associated with the age at first FS ( r (23) = −0.587, p = 0.002) and explained an additional 17.6% of variance. Together, the variables explained 38.7% of the variance in age at first FS. Maternal perceived stress symptoms at 3 months postpartum were also linked to the age at first FS ( r (23) = −0.418, p = 0.038), however, stress did not significantly contribute to the variance of age at first FS.. Significance Our results suggest a link between increased perinatal maternal emotional symptoms and the age at first FS. An earlier age at first FS may be the manifestation of a lower seizure threshold. Early first seizure occurrence is a risk factor for compromised neurological and cognitive development. Further studies should address the mechanisms by which perinatal maternal emotional symptoms may have an impact on seizure threshold in humans. [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]

Background: The 3D Cohort Study (Design, Develop, Discover) was established to help bridge knowledge gaps about the links between various adverse exposures during pregnancy with birth outcomes and later health outcomes in children.Methods: Pregnant women and their partners were recruited during the first trimester from nine sites in Quebec and followed along with their children through to 2 years of age. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, mental health and life style, medical history, psychosocial measures, diet, infant growth, and neurodevelopment. Information on the delivery and newborn outcomes were abstracted from medical charts. Biological specimens were collected from mothers during each trimester, fathers (once during the pregnancy), and infants (at delivery and 2 years of age) for storage in a biological specimen bank.Results: Of the 9864 women screened, 6348 met the eligibility criteria and 2366 women participated in the study (37% of eligible women). Among women in the 3D cohort, 1721 of their partners (1704 biological fathers) agreed to participate (73%). Two thousand two hundred and nineteen participants had a live singleton birth (94%). Prenatal blood and urine samples as well as vaginal secretions were collected for ≥98% of participants, cord blood for 81% of livebirths, and placental tissue for 89% of livebirths.Conclusions: The 3D Cohort Study combines a rich bank of multiple biological specimens with extensive clinical, life style, and psychosocial data. This data set is a valuable resource for studying the developmental etiology of birth and early childhood neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Mixtures of polybrominated diphenyl ethers (PBDEs) are present in indoor environments. Studies of the developmental effects of exposure to these chemicals in large prospective mother-child cohorts are required, with data on prenatal exposure and long-term follow-up of the children. We aimed to investigate the relationship between prenatal and childhood exposure to PBDEs and neurodevelopment at the age of six years. We determined the levels of PBDEs and other neurotoxicants in cord blood and dust collected from the homes of children for 246 families included in the PELAGIE mother-child cohort in France. We assessed two cognitive domains of the six-year-old children using the Wechsler Intelligence Scale for Children-IV. Verbal comprehension scores were lower in children from homes with higher concentrations of BDE99 ( β Detects

A large proportion of Inuit children in Arctic Quebec are adopted in accordance with traditional Inuit customs. In contrast to adoptions in Southern Canada and the United States, the child is adopted at birth and by a close family member; he or she knows who his or her biological parents are, and will typically have contact with them. Studies of other populations have reported an increased incidence of behavior problems in adopted compared with nonadopted children. This study examined the actual extent of the increase in the number of behavior problems seen in Inuit children adopted in accordance with traditional customs. In a prospective longitudinal study conducted in the Canadian Arctic (n = 46 adopted and 231 nonadopted children), prenatal and familial variables were documented at birth and at school age (M = 11.3 years). Behavior problems were assessed on the Teacher Report Form of the Child Behavior Checklist. Adopted children lived in more economically disadvantaged families, but their caregivers were less prone to depression, domestic violence, or alcohol abuse compared with those of the nonadopted children. The adoption status was not related to the teacher's report of attention problems, externalizing or internalizing behaviors, after controlling for confounders. Despite less favorable socioeconomic circumstances, a higher extent of behavioral problems was not seen at school age in Inuit children adopted at birth by a family member. Psychosocial stressors associated with adoption are more likely to be responsible for an association with higher levels of childhood behavior problems rather than adoption per se. [ABSTRACT FROM AUTHOR]

Background Whereas it is well established that prenatal exposure to polychlorinated biphenyls (PCBs) can disrupt children's behavior, early postnatal exposure has received relatively little attention in environmental epidemiology. Objectives To evaluate prenatal and postnatal exposures to PCB-153, a proxy of total PCB exposure, and their relation to inattention and activity in 5-year-old Inuits from the Cord Blood Monitoring Program. Methods Prenatal exposure to PCBs was informed by cord plasma PCB-153 levels. We used a validated pharmacokinetic model to estimate monthly infants' levels across the first year of life. Inattention and activity were assessed by coding of video recordings of children undergoing fine motor testing. We used multivariable linear regression to evaluate the association between prenatal and postnatal PCB-153 levels and inattention (n = 97) and activity (n = 98) at 5 years of age. Results Cord plasma PCB-153 was not associated with inattention and activity. Each interquartile range (IQR) increase in estimated infant PCB-153 levels at 2 months was associated with a 1.02% increase in the duration of inattention (95% CI: 0.04, 2.00). Statistical adjustment for the duration of breastfeeding slightly increased regression coefficients for postnatal level estimates, some of which became statistically significant for inattention (months: 2–4) and activity (months: 2–5). Conclusions Our study adds to the growing evidence of postnatal windows of development during which children are more susceptible to neurotoxicants like PCBs. [ABSTRACT FROM AUTHOR]

Background Perinatal exposure to endocrine-disrupting chemicals may affect thyroid hormones homeostasis and impair brain development. Chlordecone, an organochlorine insecticide widely used in the French West Indies has known estrogenic and progestin properties, but no data is available, human or animal, on its action on thyroid hormone system. Objectives Our aim was to evaluate the impact of perinatal exposure to chlordecone on the thyroid hormone system of a sample of infants from the Timoun mother–child cohort in Guadeloupe and their further neurodevelopment. Methods Chlordecone was measured in cord blood and breast milk samples. Thyroid stimulating hormone (TSH), free tri-iodothyronine (FT3), free thyroxine (FT4) were determined in child blood at 3 months ( n =111). Toddlers were further assessed at 18 months using an adapted version of the Ages and Stages Questionnaire (ASQ). Results Cord chlordecone was associated with an increase in TSH in boys, whereas postnatal exposure was associated with a decrease in FT3 overall, and in FT4 among girls. Higher TSH level at 3 months was positively associated with the ASQ score of fine motor development at 18 months among boys, but TSH did not modify the association between prenatal chlordecone exposure and poorer ASQ fine motor score. Conclusions Perinatal exposure to chlordecone may affect TSH and thyroid hormone levels at 3 months, differently according to the sex of the infant. This disruption however did not appear to intervene in the pathway between prenatal chlordecone exposure and fine motor child development. [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 Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children. Methods We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children ( n =290) were evaluated at birth and at 8–14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood. Results Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and shows a tendency of a smaller head circumference during childhood. Interpretation Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduced growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children. [ABSTRACT FROM AUTHOR]

Prenatal cigarette smoke exposure (PCSE) has been linked to problems in behavioral inhibition and attention deficit hyperactivity disorder in children in several epidemiological studies. We used event-related potentials (ERPs) to examine the effects of PCSE on neural correlates of inhibitory control of behavior. In a prospective longitudinal study on child development in the Canadian Arctic, we assessed 186 Inuit children (mean age = 11.3 years) on a visual Go/No-go response inhibition paradigm. PCSE was assessed through maternal recall. Potential confounders were documented from a maternal interview, and exposure to neurotoxic environmental contaminants was assessed from umbilical cord and child blood samples. PCSE was not related to behavioral performance on this simple response inhibition task. Nevertheless, this exposure was associated with smaller amplitudes of the N2 and P3 components elicited by No-go stimuli, suggesting an impairment in the neural processes underlying response inhibition. Amplitude of the No-go P3 component was also inversely associated with behavioral measures of externalizing problems and hyperactivity/impulsivity in the classroom. This study is the first to report neurophysiological evidence of impaired response inhibition in school-aged children exposed to tobacco smoke in utero . Effects were found on ERP components associated with conflict processing and inhibition of a prepotent response, indicating neurophysiological deficits that may play a critical role in the attention and behavior problems observed in children with PCSE. [ABSTRACT FROM AUTHOR]

Abstract: Background: Smoking during pregnancy is common among Inuit women from the Canadian Arctic. Yet prenatal cigarette smoke exposure (PCSE) is seen as a major risk factor for childhood behavior problems. Recent data also suggest that co-exposure to neurotoxic environmental contaminants can exacerbate the effects of PCSE on behavior. This study examined the association between PCSE and behavior at school age in a sample of Inuit children from Nunavik, Québec, where co-exposure to environmental contaminants is also an important issue. Interactions with lead (Pb) and mercury (Hg), two contaminants associated with behavioral problems, were also explored. Methods: Participants were 271 children (mean age=11.3years) involved in a prospective birth-cohort study. PCSE was assessed through maternal recall. Assessment of child behavior was obtained from the child's classroom teacher on the Teacher Report Form (TRF) and the Disruptive Behavior Disorders Rating Scale (DBD). Exposure to contaminants was assessed from umbilical cord and child blood samples. Other confounders were documented by maternal interview. Results: After control for contaminants and confounders, PCSE was associated with increased externalizing behaviors and attention problems on the TRF and higher prevalence of attention deficit hyperactivity disorder (ADHD) assessed on the DBD. No interactions were found with contaminants. Interpretation: This study extends the existing empirical evidence linking PCSE to behavioral problems in school-aged children by reporting these effects in a population where tobacco use is normative rather than marginal. Co-exposure to Pb and Hg do not appear to exacerbate tobacco effects, suggesting that these substances act independently. [Copyright &y& Elsevier]

Abstract: Background: Several studies have reported negative associations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and mercury (Hg) with duration of gestation and fetal growth in fish eating populations. Docosahexaenoic acid (DHA) from fish, seafood and marine mammal intake has been reported to be positively related with pregnancy duration and fetal growth. So far, it remains unclear, however, if the associations of environmental contaminants (ECs) with growth are direct or mediated through their relation with the duration of gestation and the degree to which DHA intake during pregnancy attenuates the negative association of ECs with fetal growth. Objectives: To investigate direct and indirect associations of in utero exposure to ECs with fetal growth and pregnancy duration while taking into account the possible positive effects of DHA. Methods: Pregnant Inuit women (N =248) from Arctic Quebec were recruited and cord blood samples were analyzed for PCBs, HCB, Hg and DHA. Anthropometric measurements were assessed at birth. Path models were used to evaluate direct and indirect associations. Results: Cord concentrations of PCB 153, HCB and Hg were significantly associated with shorter duration of pregnancy (β varying from −0.17 to −0.20, p <0.05). Path models indicated that the associations of PCBs, HCB and Hg with reduced fetal growth (β varying from −0.09 to −0.13, p <0.05) were mediated through their relations with shorter gestation duration. Cord DHA was indirectly related to greater growth parameters (β varying from 0.17 to 0.20, p <0.05) through its positive association with gestation duration. Conclusion: Prenatal exposure to ECs was associated with reduced gestation duration, which is a recognized determinant of fetal growth. DHA intake during pregnancy appeared to have independent positive association with fetal growth by prolonging gestation. Whether these associations are causal remains to be elucidated. [Copyright &y& Elsevier]

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: 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]

Rationale: Early exposure to stress and teratogenic substances have an impact on brain structures involved in cognition and mental health. While moderate-to-high levels of prenatal alcohol exposure (PAE) have repeatedly been associated with long-term neurodevelopmental deficits, no consensus has yet been reached on the detrimental effects of low-to-moderate PAE on the children's functioning, including the limbic-hypothalamic-pituitary-adrenal axis. Objectives: The study aims to examine the association between low PAE and cortisol response to unfamiliar situations in 19-month-old children and to determine whether this association was moderated by sex and testosterone levels. Methods: Information regarding PAE, cortisol response to unfamiliar situations, and testosterone activity was available in a total of 130 children participating to the Québec Newborn Twin Study (Montréal, QC, Canada). Mother alcohol consumption during pregnancy was assessed via a semistructured interview conducted when the children were 6 months of age. The contribution of prenatal and postnatal confounds were examined. Results: Disrupted patterns of cortisol activity were observed only in PAE males. Testosterone tended to be negatively associated with the cortisol response, but not for PAE males, suggesting an altered sensitivity to the inhibitory effects of testosterone in these participants. Conclusions: Low levels of PAE were associated with disrupted cortisol activity, and males may be at higher risk. These findings challenge the existence of a 'safe level' of alcohol consumption during pregnancy and have public health implications. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Background: Several prospective studies have revealed that prenatal exposure to polychlorinated biphenyls (PCBs) and other organochlorine compounds (OCs) affect neurodevelopment during infancy. One of the mechanisms by which PCBs might interfere with neurodevelopment is a deficit in thyroid hormone (TH) concentrations. Objectives: We investigated the potential impact of transplacental exposure to PCBs and hexachlorobenzene (HCB) on TH concentrations in neonates from two remote coastal populations exposed to OCs through the consumption of seafood products. Methods: Blood samples were collected at birth from the umbilical cord of neonates from Nunavik (n=410) and the Lower North Shore of the St. Lawrence River (n=260) (Québec, Canada) for thyroid parameters [thyroid-stimulating hormone (TSH), free T4 (fT4), total T3 (tT3), and thyroxine-binding globuline (TBG)] and contaminants analyses. Results: In multivariate models, umbilical cord plasma concentrations of PCB 153, the predominant PCB congener, were not associated with TH and TSH levels in both populations. Prenatal exposure to HCB was positively associated with fT4 levels at birth in both populations (Nunavik, β=0.12, p=0.04; St. Lawrence, β=0.19, p<0.01), whereas TBG concentrations were negatively associated with PCB 153 concentrations (β=−0.13, p=0.05) in the St. Lawrence cohort. Conclusion: OCs levels were not associated to a reduction in THs in neonates from our two populations. Essential nutrients derived from seafood such as iodine may have prevented the negative effects of OCs on the thyroid economy during fetal development. [Copyright &y& Elsevier]

Fluoride has been associated with IQ deficits during early brain development, but the period in which children are most sensitive is unknown. We assessed effects of fluoride on IQ scores across prenatal and postnatal exposure windows. We used repeated exposures from 596 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals pregnancy and birth cohort. Fluoride was measured in urine (mg/L) collected from women during pregnancy and in their children between 1.9 and 4.4 years; urinary fluoride was adjusted for specific gravity. We estimated infant fluoride exposure (mg/day) using water fluoride concentration and duration of formula-feeding over the first year of life. Intelligence was assessed at 3–4 years using the Wechsler Preschool and Primary Scale of Intelligence-III. We used generalized estimating equations to examine the associations between fluoride exposures and IQ, adjusting for covariates. We report results based on standardized exposures given their varying units of measurement. The association between fluoride and performance IQ (PIQ) significantly differed across prenatal, infancy, and childhood exposure windows collapsing across child sex (p =.001). The strongest association between fluoride and PIQ was during the prenatal window, B = −2.36, 95% CI: −3.63, −1.08; the association was also significant during infancy, B = −2.11, 95% CI: −3.45, −0.76, but weaker in childhood, B = −1.51, 95% CI: −2.90, −0.12. Within sex, the association between fluoride and PIQ significantly differed across the three exposure windows (boys: p =.01; girls: p =.01); among boys, the strongest association was during the prenatal window, B = −3.01, 95% CI: −4.60, −1.42, whereas among girls, the strongest association was during infancy, B = −2.71, 95% CI: −4.59, −0.83. Full-scale IQ estimates were weaker than PIQ estimates for every window. Fluoride was not significantly associated with Verbal IQ across any exposure window. Associations between fluoride exposure and PIQ differed based on timing of exposure. The prenatal window may be critical for boys, whereas infancy may be a critical window for girls. • The association between fluoride and performance IQ significantly differed across exposure windows. • The strongest association between fluoride and PIQ was during the prenatal window. • Within sex, the association between fluoride and PIQ significantly differed across exposure windows. Among boys, the prenatal window appeared critical, while for girls, infancy was critical. • Full-scale IQ estimates were weaker than PIQ estimates for every window. • Fluoride was not significantly associated with Verbal IQ across any exposure window. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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 μg/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. [Copyright &y& Elsevier]

This study describes the time trends of organochlorines [OCs; 14 polychlorinated biphenyls (PCBs) and 11 chlorinated pesticides] in umbilical cord plasma of newborns in a remote Canadian coastal population. We analyzed 408 cord blood samples collected between 1993 and 2000 for PCBs, chlordanes, dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyltrichloroethylene (DDE), hexachlorobenzene (HCB), and n-3 fatty acids. We also gathered information on the mothers (age, past and present residence, ethnic group, use of tobacco during pregnancy, and breast-feeding during previous pregnancies). From 1993 to 2000, mean concentrations of PCBs, chlordanes, DDT/DDE, and HCB in cord blood decreased by 63%, 25%, 66%, and 69%, respectively (p < 0.0001). Multiple regression analysis with the year of birth as the main independent variable yielded a strong significant exponential decrease for all contaminants (in all age and ethnic groups). We detected no monthly or seasonal pattern. We used n-3 fatty acids concentration as a surrogate of maternal fish consumption. Fish consumption declined only slightly between 1993 and 2000, but this decrease did not contribute significantly to the reduction of OCs. These results show that prenatal exposure to persistent OCs has declined significandy between 1993 and 2000 in this population. [ABSTRACT FROM AUTHOR]

Studies of prenatal per- and polyfluoroalkyl substances (PFAS) and attention deficit hyperactivity disorder (ADHD)-related behaviors in children are inconsistent. To examine associations between maternal serum PFAS concentrations and child behavior in 241 mother-child dyads within the Health Outcomes and Measures of the Environment (HOME) Study. We quantified perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) in maternal serum collected during pregnancy or at delivery. We evaluated a total of 17 outcomes of child behavior using the Behavioral Assessment System for Children-2 (BASC-2) at 5 and 8 years (n = 240) and ADHD diagnostic symptoms and criteria with the Diagnostic Interview Schedule for Children–Young Child (DISC-YC) at 5 years (n = 190). We used linear mixed models and logistic regression with generalized estimating equations to assess associations between PFAS and continuous or dichotomous "at risk" BASC-2 scores; negative binomial regression to calculate incident rate ratios for counts of ADHD symptoms; and Poisson regression with robust standard errors to calculate relative risks of meeting ADHD diagnostic criteria. Each ln-unit increase in PFOS, PFHxS, and PFNA was associated with higher BASC-2 scores and increased odds of "at-risk" scores for externalizing behaviors, including hyperactivity (PFOS: odds ratio [OR] 2.7, 95% confidence interval [CI] 1.2, 5.9; PFHxS: OR 2.5, 95% CI 1.5, 4.3; PFNA: OR 3.2, 95% CI 1.3, 8.0). PFHxS was also associated with internalizing problems (OR 2.0, 95% CI 1.1, 3.4) and somatization (OR 2.2, 95% CI 1.2, 4.0). PFOS and PFNA were significantly associated with 50–80% more DISC-YC symptoms and diagnostic criteria related to hyperactive-impulsive type ADHD. Prenatal PFNA was associated with increased risk of any-type ADHD. Prenatal PFOS and PFNA were consistently associated with measures related to hyperactive-impulsive type ADHD across two validated assessment instruments. PFHxS was associated with increased problems with both externalizing and internalizing behaviors. No associations were noted between PFOA and child neurobehavior. • Prenatal PFOS, PFHxS, and PFNA were associated with increased externalizing behaviors. • Prenatal PFHxS were associated with more internalizing behavior problems. • PFOS and PFNA were associated with more symptoms and diagnostic criteria related to ADHD. • Null associations were observed between PFOA and neurobehavior in school-aged children. [ABSTRACT FROM AUTHOR]

Childhood exposure to phthalates, a class of chemicals with known reproductive and developmental effects, has been hypothesized to increase the risk of obesity, but this association is not well understood in preschool children. We examined the association between urinary concentrations of phthalate metabolites and concurrently measured body mass index (BMI) and skinfolds among children between the ages of two and five years. We collected anthropometric measures and biomonitoring data on approximately 200 children enrolled in the Maternal-Infant Research on Environmental Chemicals Child Development Plus study. We measured 22 phthalate metabolites in children's urine and used the 19 metabolites detected in at least 40% of samples. Our primary outcome was BMI z-scores calculated using the World Health Organization growth standards. Skinfold z-scores were secondary outcomes. We used multivariable linear regression to evaluate the association between tertiles of phthalate concentrations and each anthropometric measure. We also used weighted quantile sum regression to identify priority exposures of concern. Our analytic sample included 189 singleton-born children with complete anthropometric data. Children with concentrations of the parent compound di-n-butyl phthalate (∑DnBP) in the third tertile had 0.475 (95% CI: 0.068, 0.883) higher BMI z-scores than those in the lower tertile. ∑DnBP was identified as a priority exposure in the weighted quantile sum regression BMI model. In this population of Canadian preschool aged children, we identified DnBP as a potential chemical of concern in regard to childhood obesity. Future research with serial phthalate measurements and anthropometric measurements in young children will help confirm these findings. [ABSTRACT FROM AUTHOR]

Among populations living in close connection with the sea, rivers and lakes for subsistence, diet varies according to local monthly wildlife species availability and food preferences. This may lead to variations in methylmercury (MeHg) exposure over a year, although no biomonitoring studies have documented this issue in Circumpolar populations, the most exposed to international Hg emissions. Our aim was to characterize seasonal variations in MeHg exposure among pregnant Inuit women from Nunavik and to identify country foods responsible for these variations. Between October 2016 and March 2017, 97 participants were recruited. Blood mercury (Hg) was tested and hair Hg was measured by centimeter as a surrogate for monthly MeHg exposure over the past year. Latent class growth analysis was conducted to identify groups of pregnant women with similar hair Hg monthly trajectories. Country foods consumption was documented by season. Seasonal daily intakes of MeHg were estimated based on concentrations in country foods. Retrospective monthly hair Hg analyses revealed that MeHg exposure was lowest in winter, and highest in summer and early fall months. Three latent classes (groups) of pregnant women with similar trajectories of monthly hair Hg variations were identified: high (n = 20, 21%), moderate (n = 38, 41%) and low variation (n = 35, 38%). Beluga meat was the country food contributing to most of daily MeHg intake, primarily during summer and fall, and was the only one associated with the odds of being classified into moderate and high variation groups (OR 95% CI: 1.19 [1.01–1.39] and 1.25 [1.04–1.50]). These findings underscore the importance of monthly variations in exposure to MeHg due to the seasonality of local foods consumed and responsible for elevated MeHg exposure. Further studies critically need to understand local diet fluctuations over a year to adequately assess MeHg exposure, adopt timely preventive interventions and evaluate the effectiveness of the Minamata Convention. Unlabelled Image • Elevated MeHg exposure remains a concern for pregnant women in Nunavik. • Levels of Hg in hair were lower in winter and higher in summer/fall. • Three different trajectories of monthly hair Hg variations were identified. • Beluga meat was the primary source of MeHg exposure, particularly in summer. • Only beluga meat consumption was associated with changing annual hair Hg trajectories. [ABSTRACT FROM AUTHOR]

Serum composition of PFAAs congeners in Nunavik pregnant women from the NQN study in 2016–2017 compared to women from the Canadian general population who participated in the Canadian Health Measure Survey (CHMS) cycle 5. • In pregnant women from Nunavik, exposure to long-chain PFAAs is increasing. • Nunavimmiut women exposure to PFOS, PFNA, PFDA and PFuDA was higher than in the Canadian general population. • The results suggest that 8:2 FTOH contributes to the exposure profile in the Arctic. • Marine country food consumption is associated with higher exposure to PFAAs. Perfluoroalkyl acids (PFAAs) are persistent and ubiquitous environmental contaminants that potentially disrupt endocrine system functions. While some PFAAs (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA)) are regulated, currently used fluorotelomer alcohols (FTOHs) can be transported to the Arctic and are degraded in a number of PFAAs which biomagnify in Arctic wildlife (e.g. perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA)). From 2004 to 2017, 279 pregnant Inuit women were recruited as part of biomonitoring projects in Nunavik. Our goal was to evaluate: (i) time-trends in plasma/serum PFAAs levels in pregnant Nunavimmiut women between 2004 and 2017; (ii) compare plasma/serum PFAAs levels in Nunavimmiut women in 2016–2017 to those measured in women of childbearing age in the Canadian Health Measure Survey (CHMS); and (iii) evaluate the associations of PFAAs levels with the consumption of country foods and pregnancy and maternal characteristics during pregnancy in the 97 participants recruited in 2016–2017. Individual blood sample were collected for serum or plasma PFAAs (PFOS, PFOA, pentafluorobenzoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorobutanesulfonic acid (PFBS), perfluorohexane-1-sulfonic acid (PFHxS), PFNA, PFDA, PFUdA) analyses. Socio-demographic data, pregnancy and maternal characteristics and country foods consumption were documented using a questionnaire. Omega-3 and −6 polyunsaturated fatty acids (PUFA) were measured in red blood cell membranes and their ratio used as a biomarker of marine country foods consumption. Time-trends in PFAAs levels were evaluated using ANCOVA models adjusted for relevant co-variables. Serum/plasma levels of PFAAs in the 97 pregnant women aged 16 to 40 years old and recruited in 2016–2017 were compared to those measured in women aged 18 to 40 years old from the CHMS cycle 5 (2016–2017) using the geometric means (GM) and 95% confidence intervals (95% CI). Multivariate regression analyses were performed to examine associations between concentrations of PFAAs and country foods consumption data. Statistically-significant downward time trends were noted for concentrations of PFOS, PFOA and PFHxS in pregnant Nunavik women between 2004 and 2017. Conversely, between 2011 and 2016–2017, PFNA, PFDA and PFUdA maternal serum levels increased by 19, 13 and 21% respectively. Among participants in 2016–2017, mean concentrations for PFNA (GM: 2.4 μg/L), PFDA (0.53 μg/L) and PFUdA (0.61 μg/L) were higher than those measured in women aged 18–40 years old in the Cycle 5 (2016–2017) of the CHMS. PFOA (0.53 μg/L) and PFHxS (0.26 μg/L) were lower than in CHMS, whereas PFBA, PFHxA and PFBS were not detected in 2016–2017. Ratios of serum/plasma levels of PFNA/PFOA, PFNA/PFOS, PFNA/PFHxS and PFUdA/PFDA were significantly higher in the 97 pregnant women from Nunavik recruited in 2016–2017 compared to CHMS, highlighting their distinct exposure profile. In multivariate models, PFHxS, PFOS, PFNA, PFDA and PFUdA levels in 2016–2017 were strongly associated with the omega-3/omega-6 PUFA ratio, indicating a positive association between marine country foods consumption and higher exposure to PFAAs. The exposure of pregnant women to long-chain PFAAs (PFNA, PFDA and PFUdA) increased from 2004 to 2017 in Nunavik. Associations noted between PFAAs levels and the omega-3/omega-6 ratio highlights the importance of implementing additional strict regulations on PFAAs and their precursors to protect the high nutritional quality and cultural importance of country foods in Nunavik. [ABSTRACT FROM AUTHOR]

Given that their traditional lifestyle and diet still relies on fish and other marine species for sustenance, the Inuit are highly exposed to polychlorinated biphenyls (PCBs) and PCBs are increasingly linked to obesity. However, evidence is not consistent regarding which periods of exposure are most relevant. In this study, we examine whether in utero, childhood, and adolescent exposure to PCBs are related to physical growth at adolescence. Inuit adolescents from Canada (N=212) enrolled in a prospective longitudinal cohort study since birth were assessed for height, weight, body mass index (BMI), fat mass index (FMI) and fat free mass index (FFMI) at 18 years of age. PCB 153 concentrations were quantified in blood samples obtained at birth (umbilical cord), 11, and 18 years of age. Maternal anthropometrics were measured and those for the newborns collected from medical records. Data on biological mothers and participants' sociodemographic characteristics and food security were collected using interviews. Multiple linear regression analyses were used to test associations between PCB 153 concentrations and adolescent anthropometric measures. Cord PCB 153 was not related to height or FFMI at adolescence. By contrast, analyses showed that cord PCB 153 was related to higher BMI, FMI and marginally to weight in girls but not boys. Child PCB 153 was not related to height, weight or FFMI in adolescence. Child PCB 153 was related to lower BMI and FMI at adolescence in both sexes, particularly among those considered overweight or obese during childhood. Adolescent PCB 153 was not associated with any outcome. This study suggests that prenatal exposure to PCBs may have a long-term effect on growth in early adulthood among girls and identifies the peri-pubertal period as another window of sensitivity for the action of PCBs. Our findings also suggest that exposure to PCBs and body size be documented in multiple time periods from infancy to adulthood. • Prenatal exposure to PCBs may have a long-term effect on growth among girls. • Peri-pubertal period identified as a window of sensitivity for PCBs. • Exposure to PCBs and body size be documented in multiple time periods. [ABSTRACT FROM AUTHOR]

Summary: Background: Though the physiological roles of adipokines in metabolism, insulin resistance and satiety are clear, literature regarding associations between cord blood adipokine levels and childhood adiposity is equivocal. Objectives: To determine whether cord blood levels of leptin and adiponectin are associated with adiposity in children 2 to 5 years of age, and whether such associations are modified by sex. Methods: Leptin and adiponectin levels were measured in cord blood and anthropometric measures were completed on 550 children enrolled in the Maternal–Infant Research on Environmental Chemicals Child Development Plus study (MIREC‐CD Plus). We used multivariable linear and Poisson regression models to determine associations between cord blood adipokine levels and child body mass index (BMI), triceps and subscapular skinfold thickness and risk of overweight/obesity and to assess effect modification by child sex. Results: Cord blood adiponectin was significantly associated with modest increases in BMI and the sum of triceps and subscapular skinfold z‐scores in boys but not girls. A doubling of adiponectin levels was associated with a 30% increased risk of overweight/obesity in boys (RR = 1.30; 95% CI: 1.02, 1.64). Leptin was not associated with anthropometric measures in either sex. Conclusions: The observed associations between adiponectin and adiposity in boys were statistically significant, of moderate magnitude, and underscore the value of considering sex‐specific patterns. [ABSTRACT FROM AUTHOR]

• Consumption of formula reconstituted with fluoridated water can lead to excessive fluoride intake. • Breastfed infants receive very low intake of fluoride. • We compared IQ scores in 398 children who were formula-fed versus breastfed during infancy. • IQ scores were lower with higher levels of fluoride in tap water. • The effect was more pronounced among formula-fed children, especially for nonverbal skills. Infant consumption of formula reconstituted with fluoridated water can lead to excessive fluoride intake. We examined the association between fluoride exposure in infancy and intellectual ability in children who lived in fluoridated or non-fluoridated cities in Canada. We examined 398 mother-child dyads in the Maternal-Infant Research on Environmental Chemicals cohort who reported drinking tap water. We estimated water fluoride concentration using municipal water reports. We used linear regression to analyze the association between fluoride exposure and IQ scores, measured by the Wechsler Primary and Preschool Scale of Intelligence-III at 3–4 years. We examined whether feeding status (breast-fed versus formula-fed) modified the impact of water fluoride and if fluoride exposure during fetal development attenuated this effect. A second model estimated the association between fluoride intake from formula and child IQ. Thirty-eight percent of mother-child dyads lived in fluoridated communities. An increase of 0.5 mg/L in water fluoride concentration (approximately equaling the difference between fluoridated and non-fluoridated regions) corresponded to a 9.3- and 6.2-point decrement in Performance IQ among formula-fed (95% CI: −13.77, −4.76) and breast-fed children (95% CI: −10.45, −1.94). The association between water fluoride concentration and Performance IQ remained significant after controlling for fetal fluoride exposure among formula-fed (B = −7.93, 95% CI: −12.84, −3.01) and breastfed children (B = −6.30, 95% CI: −10.92, −1.68). A 0.5 mg increase in fluoride intake from infant formula corresponded to an 8.8-point decrement in Performance IQ (95% CI: −14.18, −3.34) and this association remained significant after controlling for fetal fluoride exposure (B = −7.62, 95% CI: −13.64, −1.60). Exposure to increasing levels of fluoride in tap water was associated with diminished non-verbal intellectual abilities; the effect was more pronounced among formula-fed children. [ABSTRACT FROM AUTHOR]

Fetal exposure to some toxic metals has been associated with reduced fetal growth, but the impact of contemporary, low-level metals on anthropometric measures in childhood is not well understood. Our primary objective was to quantify associations between childhood levels of toxic metals and concurrently measured body mass index (BMI) in a population of Canadian preschool-aged children. We collected biomonitoring data and anthropometric measures on 480 children between the ages of two and five years in the Maternal-Infant Research on Environmental Chemicals (MIREC) Child Development Plus study. Concentrations of four toxic metals (lead, arsenic, cadmium, and mercury) were measured in whole blood collected from pregnant women and their children. Blood levels of key essential elements were also measured in children. Children's weight, height, and BMI z-scores were calculated using the World Health Organization growth standards. We used a series of linear regression models, adjusted for potential parental confounders, concurrently measured metals and elements, and prenatal blood metal levels, to evaluate associations between tertiles of each toxic metal and anthropometric measures. We tested for effect modification by sex. Of the 480 children, 449 (94%) were singleton births and had complete biomonitoring and anthropometric data. The majority of children had detectable concentrations of metals. In the adjusted models, girls with blood lead concentrations in the highest tertile (>0.82 μg/dL) had, on average, 0.26 (95% Cl: -0.55, 0.03) lower BMI z-scores than those in the referent category. In contrast, boys with lead levels in the highest tertile had, on average, 0.14 higher BMI z-scores (95% Cl: -0.14, 0.41) (p-value heterogeneity = 0.04). In this population of Canadian preschool-aged children with low-level blood lead concentrations, we observed effect modification by sex in the association between Pb and BMI but no statistically significant associations in the sex-specific strata. Child blood levels of As, Cd, and Hg were not associated with childhood BMI, weight, or height in boys or girls. • We measured blood levels of four metals in 480 pre-school aged children. • We quantified associations between toxic metals and body mass index. • The association between lead and body mass index was modified by sex. • Girls with higher lead levels tended to have lower body mass index z-scores. [ABSTRACT FROM AUTHOR]

Lead (Pb) exposure is associated with adverse neurological development. Most notably, it has been observed through externalizing behavior symptoms, as observed among Inuit children from northern Québec. Evidence for a persistent neurological impact of early Pb exposure later in life is however scarce. Pb exposure may initiate a developmental cascade that increases the risk of long-term behavior problems. Testing for direct associations between childhood Pb concentrations and adolescent externalizing symptoms and substance use, as well as indirect associations through childhood behavior assessments. The study sample is a longitudinal cohort of Inuit children (n = 212) followed since birth. Blood Pb concentrations were measured during childhood (median age = 11.4 years) and adolescence (median age = 18.5 years). Externalizing/inattentive behavior were teacher-assessed through the Teacher Report Form and the Disruptive Behavior Disorders Rating Scale for children. At the adolescence follow-up, behavior problems were self-reported by filling Achenbach's Youth Self-Report, the Barkley Adult ADHD-IV Rating Scale, and the Diagnostics Interview Schedule for Children. Adolescent substance use was also self-assessed through the DEP-ADO. Direct and indirect associations of child Pb concentrations with adolescent outcomes were tested through mediation models. Child blood Pb concentrations were not directly associated with any adolescent outcomes. On the contrary, childhood Pb exposure was indirectly associated, through childhood externalizing behavior assessments, with adolescent externalizing behaviors, binge drinking, and cannabis use. These indirect associations held after controlling for adolescents' concurrent Pb blood concentrations. Our results highlight the indirect but lasting effects of child Pb exposure on adolescent behavior problems, and the importance of childhood externalizing behavior in this relationship. Adverse early-life environment put children on a riskier developmental trajectory, increasing their likelihood of lifelong psychological, social and health problems. • Child Pb associated with adolescent externalizing behavior and substance use. • These associations mediated by child externalizing behaviors. • Early-life impairments may put children on a riskier developmental trajectory. [ABSTRACT FROM AUTHOR]