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BACKGROUND: Toxic metals, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg), may be associated with a higher risk of gestational hypertension and preeclampsia, whereas manganese (Mn) is an essential metal that may be protective. OBJECTIVES: We estimated the individual, independent, and joint associations of Pb, Cd, As, Hg, and Mn on the risk of developing gestational hypertension and preeclampsia in a cohort of Canadian women. METHODS: Metal concentrations were analyzed in first and third trimester maternal blood (푛=1,560). We measured blood pressure after 20 wk gestation to diagnose gestational hypertension, whereas proteinuria and other complications defined preeclampsia. We estimated individual and independent (adjusted for coexposure) relative risks (RRs) for each doubling of metal concentrations and examined interactions between toxic metals and Mn. We used quantile g-computation to estimate the joint effect of trimester-specific exposures. RESULTS: Each doubling of third trimester Pb (RR = 1.54; 95% CI: 1.06, 2.22) and first trimester blood As (RR = 1.25; 95% CI: 1.01, 1.58) was independently associated with a higher risk of developing preeclampsia. First trimester blood As (RR = 3.40; 95% CI: 1.40, 8.28) and Mn (RR = 0.63; 95% CI: 0.42, 0.94) concentrations were associated with a higher and lower risk, respectively, of developing gestational hypertension. Mn modified the association with As such that the deleterious association with As was stronger at lower concentrations of Mn. First trimester urinary dimethylarsinic acid concentrations were not associated with gestational hypertension (RR = 1.31; 95% CI: 0.60, 2.85) or preeclampsia (RR = 0.92; 95% CI: 0.68, 1.24). We did not observe overall joint effects for blood metals. DISCUSSION: Our results confirm that even low blood Pb concentrations are a risk factor for preeclampsia. Women with higher blood As concentrations combined with lower Mn in early pregnancy were more likely to develop gestational hypertension. These pregnancy complications impact maternal and neonatal health. Understanding the contribution of toxic metals and Mn is of public health importance. [ABSTRACT FROM AUTHOR]

Background: Maternal prenatal exposure to air pollution has been associated with adverse birth outcomes. However, previous studies focused on a priori time intervals such as trimesters reported inconsistent associations.Objectives: We investigated time-varying vulnerability of birth weight to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) using flexible time intervals.Methods: We analyzed 1,300 live, full-term births from Maternal-Infant Research on Environmental Chemicals, a Canadian prospective pregnancy cohort spanning 10 cities (2008-2011). Daily PM2.5 and NO2 concentrations were estimated from ground-level monitoring, satellite models, and land-use regression, and assigned to participants from pre-pregnancy through delivery. We developed a flexible two-stage modeling method-using a Bayesian Metropolis-Hastings algorithm and empirical density threshold-to identify time-dependent vulnerability to air pollution without specifying exposure periods a priori. This approach identified critical windows with varying lengths (2-363 days) and critical windows that fell within, or straddled, predetermined time periods (i.e., trimesters). We adjusted the models for detailed infant and maternal covariates.Results: Critical windows associated with reduced birth weight were identified during mid- to late-pregnancy for both PM2.5 and NO2: -6 g (95% credible interval: -11, -1 g) and -5 g (-10, -0.1 g) per µg/m3 PM2.5 during gestational days 91-139 and 249-272, respectively; and -3 g (-5, -1 g) per ppb NO2 during days 55-145.Discussion: We used a novel, flexible selection method to identify critical windows when maternal exposures to air pollution were associated with decrements in birth weight. Our results suggest that air pollution impacts on fetal development may not be adequately captured by trimester-based analyses. [ABSTRACT FROM AUTHOR]

Background Reports on the adequacy of vitamin D status of pregnant women are not available in Canada. Objectives The objectives of this study were to examine vitamin D status across pregnancy and identify the correlates of vitamin D status of pregnant women in Canada. Methods Pregnant women (≥18 years) from 6 provinces (2008–2011) participating in a longitudinal cohort were studied. Sociodemographic data, obstetrical histories, and dietary and supplemental vitamin D intakes were surveyed. Plasma 25-hydroxyvitamin D (25OHD) was measured using an immunoassay standardized to LC-MS/MS from samples collected during the first (n  = 1905) and third trimesters (n  = 1649) and at delivery (n  = 1543). The proportion of women with ≥40 nmol/L of plasma 25OHD (adequate status) was estimated at each time point, and factors related to achieving this cut point were identified using repeated-measures logistic regression. Differences in 25OHD concentrations across trimesters and at delivery were tested a using repeated-measures ANOVA with a post hoc Tukey's test. Results In the first trimester, 93.4% (95% CI: 92.3%–94.5%) of participants had 25OHD ≥40 nmol/L. The mean plasma 25OHD concentration increased from the first to the third trimester and then declined by delivery (69.8 ± 0.5 nmol/L, 78.6 ± 0.7 nmol/L, and 75.7 ± 0.7 nmol/L, respectively; P  < 0.0001). A lack of multivitamin use early in pregnancy reduced the odds of achieving 25OHD ≥40 nmol/L (ORadj = 0.33; 95% CI: 0.25–0.42) across all time points. Factors associated with not using a prenatal multivitamin included multiparity (ORadj = 2.08; 95% CI: 1.42–3.02) and a below-median income (ORadj = 1.39; 95% CI: 1.02–1.89). Conclusions The results from this cohort demonstrate the importance of early multivitamin supplement use to achieve an adequate vitamin D status in pregnant women. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are an especially important population to monitor for environmental exposures given the vulnerability of the developing fetus. During pregnancy and lactation chemical body burdens may change due to the significant physiological changes that occur. Developmental exposures to some persistent organic pollutants (POPs) have been linked with adverse health outcomes.Methods: First trimester maternal and cord blood plasma concentrations of several POPs including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCs), polybrominated diphenyl ethers (PBDE)s and perfluoroalkyl substances (PFASs) were measured in samples from 1983 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. Predictors of exposure were also identified.Results: In maternal plasma, there was >90 % detection for the perfluoroalkyl substances (PFASs) perfluorooctanoic acid (PFOA), perfluoroctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and dichlorodiphenyldichloroethylene (DDE), oxychlordane and PCB 138 and 153. Cord blood plasma had much lower detection rates with low or very limited detection for most PCBs and PBDEs. The PFASs were the most frequently detected (23-64 %) chemical class in cord plasma. In a subset of 1st and 3rd trimester paired samples, PFAS concentrations were found to be strongly correlated and had ICCs ranging from 0.64 (PFOA) to 0.83 (PFHxS). The cord:maternal plasma concentration ratios ranged from 0.14 (PFOS) to 0.87 (oxychlordane, lipid adjusted). Similar to other studies, we found parity, maternal age, income, education, smoking status, pre-pregnancy BMI and fish consumption to be significant predictors for most chemicals. Those participants who were foreign-born had significantly higher concentrations of organochlorinated pesticides and PCBs.Conclusions: In the MIREC study, multiple chemical contaminants were quantified in the plasma of pregnant women. In cord plasma PFOA had the highest detection rate. However, compared to other Canadian and international population studies, the MIREC participants had lower contaminant concentrations of these substances. [ABSTRACT FROM AUTHOR]

Previous evidence suggests that exposure to outdoor air pollution during pregnancy could alter fetal metabolic function, which could increase the risk of obesity in childhood. However, to our knowledge, no epidemiologic study has investigated the association between prenatal exposure to air pollution and indicators of fetal metabolic function. We investigated the association between maternal exposure to nitrogen dioxide and fine particulate matter (aerodynamic diameter ≤2.5 urn) and umbilical cord blood leptin and adiponectin levels with mixed-effects linear regression models among 1,257 mother-infant pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, conducted in Canada (2008-2011). We observed that an interquartile-range increase in average exposure to fine particulate matter (3.2 µg/m³) during pregnancy was associated with an 11% (95% confidence interval: 4, 17) increase in adiponectin levels. We also observed 13% (95% confidence interval: 6, 20) higher adiponectin levels per interquartile-range increase in average exposure to nitrogen dioxide (13.6 parts per billion) during pregnancy. Significant associations were seen between air pollution markers and cord blood leptin levels in models that adjusted for birth weight z score but not in models that did not adjust for birth weight z score. The roles of prenatal exposure to air pollution and fetal metabolic function in the potential development of childhood obesity should be further explored. [ABSTRACT FROM AUTHOR]

Background Naphthalene exposures for most non-occupationally exposed individuals occur primarily indoors at home. Residential indoor sources include pest control products (specifically moth balls), incomplete combustion such as cigarette smoke, woodstoves and cooking, some consumer and building products, and emissions from gasoline sources found in attached garages. The study aim was to assess naphthalene exposure in pregnant women from Canada, using air measurements and biomarkers of exposure. Methods Pregnant women residing in Ottawa, Ontario completed personal and indoor air sampling, and questionnaires. During pregnancy, pooled urine voids were collected over two 24-hour periods on a weekday and a weekend day. At 2-3 months post-birth, they provided a spot urine sample and a breast milk sample following the 24-hour air monitoring. Urines were analyzed for 1-naphthol and 2-naphthol and breast milk for naphthalene. Simple linear regression models examined associations between known naphthalene sources, air and biomarker samples. Results Study recruitment rate was 11.2% resulting in 80 eligible women being included. Weekday and weekend samples were highly correlated for both personal (r = 0.83, p < 0.0001) and indoor air naphthalene (r = 0.91, p < 0.0001). Urine specific gravity (SG)-adjusted 2-naphthol concentrations collected on weekdays and weekends (r = 0.78, p < 0.001), and between pregnancy and postpartum samples (r = 0.54, p < 0.001) were correlated. Indoor and personal air naphthalene concentrations were significantly higher post-birth than during pregnancy (p < 0.0001 for signed rank tests); concurrent urine samples were not significantly different. Naphthalene in breast milk was associated with urinary 1-naphthol: a 10% increase in 1-naphthol was associated with a 1.6% increase in breast milk naphthalene (95% CI: 0.2%-3.1%). No significant associations were observed between naphthalene sources reported in self-administered questionnaires and the air or biomarker concentrations. Conclusions Median urinary concentrations of naphthalene metabolites tended to be similar to (1- naphthol) or lower than (2-naphthol) those reported in a Canadian survey of women of reproductive age. Only urinary 1-naphthol and naphthalene in breast milk were associated. Potential reasons for the lack of other associations include a lack of sources, varying biotransformation rates and behavioural differences over time. [ABSTRACT FROM AUTHOR]

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

Biomonitoring is used increasingly as an indicator and quantitative measure of exposure; however, there is a large gap in interpreting and communicating biomonitoring results to study participants. Two separate, national biomonitoring initiatives are under way in Canada; the household recruitment-based Canadian Health Measures Survey (CHMS) and the clinic recruitment-based Maternal-Infant Research on Environmental Chemicals (MIREC) Study. The CHMS provides participants with the option to receive all their results, but this option is not provided to MIREC participants. The approach to reporting results to participants depends on the availability of reference ranges and guidelines for which tissue concentrations may be interpreted as being elevated or associated with increased health risks, how participants are recruited, unique vulnerabilities of the population, legislation governing access to personal information, and decisions of research ethics committees. It is the researchers' responsibility to present the best case for their approach and, once the decision has been made, to inform participants about access to their results through the consent process. [ABSTRACT FROM AUTHOR]

Background: The developing fetus and pregnant woman can be exposed to a variety of environmental chemicals that may adversely affect their health. Moreover, environmental exposure and risk disparities are associated with different social determinants, including socioeconomic status (SES) and demographic indicators. Our aim was to investigate whether and how maternal concentrations of a large panel of persistent and non-persistent environmental chemicals vary according to sociodemographic and lifestyle characteristics in a large pregnancy and birth cohort.Methods: Data were analyzed from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a cohort of pregnant women (N=2001) recruited over four years (2008-2011) in 10 cities across Canada. In all, 1890 urine and 1938 blood samples from the first trimester (1st and 3rd trimester for metals) were analysed and six sociodemographic and lifestyle indicators were assessed: maternal age, household income, parity, smoking status, country of birth and pre-pregnancy body mass index (BMI).Results: We found these indicators to be significantly associated with many of the chemicals measured in maternal blood and urine. Women born outside Canada had significantly higher concentrations of di-2-ethylhexyl and diethyl phthalate metabolites, higher levels of all metals except cadmium (Cd), as well as higher levels of polychlorinated biphenyls (PCBs) and legacy organochlorine pesticides (OCPs). Nulliparity was associated with higher concentrations of dialkyl phosphates (DAPs), arsenic, dimethylarsinic acid (DMAA), perfluoroalkyl substances (PFASs) and many of the persistent organic pollutants. Smokers had higher levels of bisphenol A, Cd and perfluorohexane sulfonate, while those women who had never smoked had higher levels of triclosan, DMAA, manganese and some OCPs.Conclusion: Our results demonstrated that inequitable distribution of exposure to chemicals among populations within a country can occur. Sociodemographic and lifestyle factors are an important component of a thorough risk assessment as they can impact the degree of exposure and may modify the individual's susceptibility to potential health effects due to differences in lifestyle, cultural diets, and aging. [ABSTRACT FROM AUTHOR]

Background Lead, mercury, cadmium and arsenic are some of the most common toxic metals to which Canadians are exposed. The effect of exposure to current low levels of toxic metals on fetal growth restriction is unknown. Objective: The aim of this study was to examine relationships between exposure to lead, mercury, cadmium and arsenic during pregnancy, and risk of small for gestational age (SGA) birth. Methods: Lead, mercury, cadmium and arsenic levels were measured in blood samples from the first and third trimesters in 1835 pregnant women from across Canada. Arsenic species in first trimester urine were also assessed. Relative risks and 95% confidence intervals were estimated using log binomial multivariate regression. Important covariates including maternal age, parity, pre-pregnancy BMI, and smoking, were considered in the analysis. An exploratory analysis was performed to examine potential effect modification of these relationships by single nucleotide polymorphisms (SNPs) in GSTP1 and GSTO1 genes. Results No association was found between blood lead, cadmium or arsenic and risk for SGA. We observed an increased risk for SGA for the highest compared to the lowest tertile of exposure for mercury (>1.6 µg/L, RR=1.56.; 95% CI=1.04–2.58) and arsenobetaine (>2.25 µg/L, RR=1.65; 95% CI=1.10–2.47) after adjustment for the effects of parity and smoking. A statistically significant interaction was observed in the relationship between dimethylarsinic acid (DMA) levels in urinary arsenic and SGA between strata of GSTO1 A104A ( p for interaction=0.02). A marginally significant interaction was observed in the relationship between blood lead and SGA between strata of GSTP1 A114V ( p for interaction=0.06). Conclusions These results suggest a small increase in risk for SGA in infants born to women exposed to mercury and arsenic. Given the conflicting evidence in the literature this warrants further investigation in other pregnant populations. [ABSTRACT FROM AUTHOR]

Background: Parabens are chemical substances used as preservatives for their antibacterial and antifungal properties in many personal care products, and sometimes in pharmaceutical and food products. Concerns for adverse human health effects arise from animal studies showing endocrine disrupting effects, such as changes in the timing of puberty and alterations in reproductive hormone activity. Our objective was to examine the association between urinary concentrations of parabens and serum concentrations of estradiol, progesterone, follicle stimulating hormone [FSH], and luteinizing hormone [LH]) in girls from the general population.Methods: We conducted a cross-sectional study in girls ages 6-17 years, using data from the Canadian Health Measures Survey (2014-2015). The association between concentrations of creatinine-standardized urinary parabens and serum hormone concentrations was analyzed with multivariable linear regressions, adjusting for potential confounders (i.e., age, body mass index, ethnicity, household income, sampling season; prenatal exposure to cigarette smoke for girls 6-11 years).Results: The 382 girls and teens included in the study had a mean age of 11.0 years; 76% were white and 73% had a body mass index in the range normal/underweight. Most participants (92%) had least one paraben detected in their urine. Girls with higher urinary paraben concentrations had significantly lower serum concentrations of estradiol, LH, and FSH, but not of progesterone. A doubling in the sum of urinary parabens was associated with 5.8% lower estradiol (95% CI -9.3, -2.1), 4.2% lower FSH (95% CI -7.9, -0.3), and 10.8% lower LH (95% CI -17.4, -3.7). The analysis of individual compounds showed that all four parabens were similarly associated with lower concentrations of estradiol, FSH, and LH. We further analyzed younger girls (6-11 years) and found that urinary parabens were similarly associated with lower estradiol and LH (doubling in the sum of parabens associated with 5.9% lower estradiol [95% CI -10.5, -1.0] and 10.9% lower LH [95% CI -20.2, -0.6]). In this younger subgroup, the association estimate for FSH, however, was attenuated and no longer statistically significant.Discussion: We observed that exposure to parabens was associated with reduced concentrations of circulating reproductive hormones, suggesting that these chemicals could alter the development and function of the endocrine system in girls. Further prospective research using long-term assessment of parabens exposure and of reproductive development may better determine endocrine disrupting effects of parabens. [ABSTRACT FROM AUTHOR]

Epidemiological studies have hypothesized that both insufficient and excess blood manganese (Mn) levels during pregnancy are associated with reduced fetal growth. This literature is characterized by inconsistent results and a limited focus on women with exposures representative of the general North American population. We examined the relationship between maternal and cord blood Mn levels and fetal growth among women enrolled in the Maternal-Infant Research on Environmental Chemicals Study (MIREC). Mothers with singleton, term infants and complete maternal first and third trimester blood Mn data were eligible for inclusion in the present study (n = 1519). Mean birth weight and odds ratios of small for gestational age (SGA) births according to maternal and cord blood Mn levels (low (<10), referent (10-<90), high (≥90) percentiles) were estimated. We also evaluated the association between the ratio of cord and maternal blood Mn and birth weight. Women with low (<0.82 μg/dL) maternal blood third trimester Mn levels had infants that weighed an average of 64.7 g (95% CI: -142.3,12.8) less than infants born to women in the referent exposure group. This association was strengthened and became statistically significant when adjusted for toxic metals (lead, mercury, arsenic, and cadmium) [-83.3 g (95% CI: -162.4, -4.1)]. No statistically significant associations were observed in models of maternal first trimester or cord blood Mn. A one unit increase in the cord/maternal blood Mn ratio was associated with a 29.4 g (95% CI: -50.2, -8.7), when adjusted for maternal and neonatal characteristics. Our findings motivate additional research regarding the relation between Mn exposure and fetal growth. Further inquiry is necessary to determine whether an exposure threshold exists, how growth related effects of maternal and fetal Mn may differ, and how concurrent exposure to other toxic metals may impact the association between Mn and growth. [ABSTRACT FROM AUTHOR]

Background: Respiratory distress is the leading cause of neonatal morbidity and mortality worldwide, and prenatal exposure to air pollution is associated with adverse long-term respiratory outcomes; however, the impact of prenatal air pollution exposure on neonatal respiratory distress has not been well studied., Objectives: We examined associations between prenatal exposures to fine particular matter ( PM 2.5 ) and nitrogen dioxide ( NO 2 ) with respiratory distress and related neonatal outcomes., Methods: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a prospective pregnancy cohort ( n = 2,001 ) recruited in the first trimester from 10 Canadian cities. Prenatal exposures to PM 2.5 ( n = 1,321 ) and NO 2 ( n = 1,064 ) were estimated using land-use regression and satellite-derived models coupled with ground-level monitoring and linked to participants based on residential location at birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between air pollution and physician-diagnosed respiratory distress in term neonates in hierarchical logistic regression models adjusting for detailed maternal and infant covariates., Results: Approximately 7 % of newborns experienced respiratory distress. Neonates received clinical interventions including oxygen therapy (6%), assisted ventilation (2%), and systemic antibiotics (3%). Two percent received multiple interventions and 4% were admitted to the neonatal intensive care unit (NICU). Median PM 2.5 and NO 2 concentrations during pregnancy were 8.81   μ g / m 3 and 18.02  ppb , respectively. Prenatal exposures to air pollution were not associated with physician-diagnosed respiratory distress, oxygen therapy, or NICU admissions. However, PM 2.5 exposures were strongly associated with assisted ventilation (OR per 1 - μ g / m 3 increase in PM 2.5 = 1.17 ; 95% CI: 1.02, 1.35), multiple clinical interventions (OR per 1 - μ g / m 3 increase in PM 2.5 = 1.16 ; 95% CI: 1.07, 1.26), and systemic antibiotics, (OR per 1 - μ g / m 3 increase in PM 2.5 = 1.12 ; 95% CI: 1.04, 1.21). These associations were consistent across exposure periods-that is, during prepregnancy, individual trimesters, and total pregnancy-and robust to model specification. NO 2 exposure was associated with administration of systemic antibiotics (OR per 1-ppb increase in NO 2 = 1.03 ; 95% CI: 1.00, 1.06)., Discussion: Prenatal exposures to PM 2.5 increased the risk of severe respiratory distress among term newborns. These findings support the development and prioritization of public health and prenatal care strategies to increase awareness and minimize prenatal exposures to air pollution. https://doi.org/10.1289/EHP12880.

Background: Pyrethroid insecticides are used both residentially and agriculturally and their toxicity targets the nervous system of insects. They might also interfere with development and function of the human brain. A few epidemiological studies suggest that exposure to pyrethroids may be associated with neurobehavioral problems in children but there is little data on potential associations with cognitive outcomes. Furthermore, many studies showed that the neurotoxic effects of several pesticides are modified by sex, hence, considerations of potential sex-differences are important to investigate., Objective: To study the cross-sectional association between urinary levels of pyrethroid metabolites and neurodevelopment, including neurobehavioral and cognitive outcomes, in preschool-age children, and to examine whether sex might modify these associations., Methods: We used data from a follow-up examination of the Maternal-Infant Research on Environmental Chemicals (MIREC), the MIREC Child Development study (MIREC-CD Plus) on children at age 3-4 years living in 6 Canadian cities. For each participant, we collected a urine sample for measurements of pyrethroids metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA, 4-F-3-PBA). We assessed neurodevelopment with the Wechsler Primary and Preschool Scale of Intelligence-III (WPPSI-III) and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's behavior using the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale-2 (SRS-2). We examined associations between children's urinary pyrethroid metabolite concentrations and neurodevelopmental scores with multiple linear regression models, adjusting for confounders, in boys and girls separately., Results: The study included 179 children (mean age: 3.2 y, range 2.8-4.0). The detection frequencies were high for most pyrethroid metabolites (83-100%), but lower for 4-F-3-PBA (36%). Higher concentrations of cis-DBCA were significantly associated with lower verbal, performance and full-scale IQ scores in boys (e.g., for a 2-fold increase in cis-DBCA, β = -2.0; 95% CI: -3.4, -0.6 for full-scale IQ). In girls, the only metabolite associated with cognitive scores was 3-PBA, which was associated with lower verbal IQ scores (β = -1.3, 95% CI: -2.6, -0.1). For neurobehavioral outcomes in boys, there were associations between poorer BASC-2 Adaptive Skills scores with higher concentrations of cis-DCCA (β = -1.6, 95% CI: -2.3, -0.9), trans-DCCA (β = -1.5, 95% CI: -2.2, -0.8), 3-PBA (β = -1.7, 95% CI: -2.5, -0.9), and sum of pyrethroid metabolites (β = -1.8, 95% CI: -2.6, -0.9). In girls, we observed a significant association between higher concentration of cis-DCCA and better BASC-2 Adaptive Skills score (β = 1.0; 95% CI, 0.2, 1.8), but not with other urinary pyrethroids metabolites. Scores on the SRS-2 and BRIEF-P were not associated with pyrethroid metabolites., Conclusion: There were associations between some pyrethroid pesticide metabolites and indicators of neurodevelopmental disorder, especially among boys. These associations are in agreement with previous studies and could suggest that exposure to pyrethroid pesticides represents a risk of potential toxicity for the cognitive development of children, and a risk for behavioral development. However, the cross-sectional nature of this study limits causal inferences., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women., Objectives: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood., Population: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits., Preliminary Results: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO)., Conclusions: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development., (© 2023 His Majesty the King in Right of Canada and The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Health.)

Background: 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., Objective: 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., Methods: 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)., Results: 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., Conclusions: 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Copyright His Majesty the King in Right of Canada, as represented by the Minister of Health, 2023. Published by Elsevier Inc. All rights reserved.)

Organophosphate esters (OPEs) are widely used in numerous consumer products for their flame retardant and plasticizing properties. Despite potential widespread exposure, biomonitoring data during critical windows of development are scarce and limited to the most widely studied metabolites. We quantified urinary concentrations of multiple OPE metabolites in a vulnerable Canadian population. Using data and biobanked specimens from the Maternal-Infant Research on Environmental Chemicals (MIREC) study (2008-2011), we measured first trimester urinary concentrations of 15 OPE metabolites as well as one flame retardant metabolite and quantified associations with sociodemographic and sample collection characteristics in 1865 pregnant participants. We applied 2 different analytical methods to quantify OPEs, one using UItra-Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) and the other using Atmospheric Pressure Gas Chromatography coupled to mass spectrometry (APGC-MS/MS) with sensitive limits of detection (0.008-0.1 μg/L). We modelled associations between sociodemographic and sample collection characteristics and specific gravity-standardized chemical concentrations. Six OPE metabolites were detected in the majority (68.1-97.4 %) of participants. Bis-(2-chloroethyl) hydrogen phosphate had the highest detection rate (97.4 %). Diphenyl phosphate had the highest geometric mean concentration (0.657 μg/L). Metabolites of tricresyl phosphate were detected in few participants. Associations between sociodemographic characteristics varied according to each OPE metabolite. Pre-pregnancy body mass index tended to be positively associated with OPE metabolite concentrations whereas age tended to be inversely associated with OPE concentrations. OPE concentrations were, on average, higher in urine samples collected in the summer than other seasons the winter. We present the largest biomonitoring study of OPE metabolites in pregnant people to date. These findings demonstrate widespread exposure to OPEs and their metabolites and identify subpopulations who may experience heightened exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Background: 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., Objective: 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., Methods: 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., Results: 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., Conclusions: Higher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: Toxic metals, like lead, are risk factors for preterm birth (PTB), but few studies have examined low levels found in most Canadians. Vitamin D, which may have antioxidant activity, protects against PTB., Objectives: In this study, we investigated the impact of toxic metals (lead, mercury, cadmium and arsenic) on PTB and examined if maternal plasma vitamin D concentrations modify these associations., Methods: We investigated whether concentrations of metals in whole blood measured in early and late pregnancy were associated with PTB (<37 weeks) and spontaneous PTB in 1851 live births from the Maternal-Infant Research on Environmental Chemicals Study using discrete time survival analysis. We also investigated whether the risk of PTB was modified by first-trimester plasma 25-hydroxyvitamin D (25OHD) concentrations., Results: Of 1851 live births, 6.1% (n = 113) were PTBs and 4.9% (n = 89) were spontaneous PTB. A 1 μg/dL increase in blood lead concentrations during pregnancy was associated with an increased risk of PTB (relative risk [RR] 1.48, 95% confidence interval [CI] 1.00, 2.20) and spontaneous PTB (RR 1.71, 95% CI 1.13, 2.60). The risk was higher in women with insufficient vitamin D concentrations (25OHD <50 nmol/L) for both PTB (RR 2.42, 95% CI 1.01, 5.79) and spontaneous PTB (RR 3.04, 95% CI 1.15, 8.04). However, an interaction on the additive scale was not present. Arsenic was associated with a higher risk of PTB (RR 1.10, 95% CI 1.02, 1.19) and spontaneous PTB (RR 1.11, 95% CI 1.03, 1.20) per 1 μg/L., Conclusions: Gestational exposure to low levels of lead and arsenic may increase the risk of PTB and spontaneous PTB; individuals with insufficient vitamin D may be more susceptible to the adverse effects of lead. Given our relatively small number of cases, we encourage testing of this hypothesis in other cohorts, especially those with vitamin D-deficient populations., (© 2023 His Majesty the King in Right of Canada and The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Health.)

Background: Glyphosate is the most widely applied herbicide in agriculture. Glufosinate is a broad spectrum herbicide used to manage glyphosate-resistant weeds. Despite the widespread use of these herbicides, biomonitoring data - which inform risk assessment and management - are sparse., Objectives: To identify determinants of urinary concentrations of these herbicides and their metabolites in pregnancy., Methods: We measured urinary concentrations of glyphosate, glufosinate, and their primary metabolites aminomethylphosphonic acid (AMPA) and 3-methylphosphinicopropionic acid (3-MPPA) in a single spot urine specimen collected during the first trimester of pregnancy from the Maternal-Infant Research on Environmental Chemicals (MIREC) study. MIREC recruited about 2000 pregnant women from 10 Canadian cities between 2008 and 2011. We used UItra-Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) with sensitive limits of detection to quantify analyte concentrations. We examined urinary concentrations according to maternal sociodemographics, sample collection characteristics, reported pesticide use, and consumption of fruits, vegetables, legumes, and grain products. We used ANOVA models with specific gravity-standardized chemical concentrations as the dependent variable to determine associations with maternal and sample determinants., Results: Among women with biobanked urine samples (n = 1829-1854), 74% and 72% had detectable concentrations of glyphosate and AMPA, respectively. In contrast, one and six percent of women had detectable concentrations of glufosinate and 3-MPPA, respectively. The specific gravity-standardized geometric mean (95% CI) concentrations of glyphosate and AMPA were 0.112 (0.099-0.127) μg/L and 0.159 (0.147-0.172) μg/L, respectively. We observed a dose-response relationship between consumption of whole grain bread and higher urinary glyphosate concentrations. Season of urine collection and self-reported pesticide use were not associated with increased concentrations of any analyte., Conclusions: We detected glyphosate and AMPA in the majority of pregnant women from this predominantly urban Canadian cohort. Diet was a probable route of exposure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Warren G. Foster reports a relationship with Hollingsworth LLC that includes: paid expert testimony., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

National health and nutrition monitoring is an important federal effort in the United States and Canada, and the basis for many of their nutrition and health policies. Understanding of child exposures through human milk (HM) remains out of reach due to lack of current and representative data on HM's composition and intake volume. This article provides an overview of the current national health and nutrition monitoring activities for HM-fed children, HM composition (HMC) and volume data used for exposure assessment, categories of potential measures in HM, and associated variability factors. In this Perspective, we advocate for a framework for collection and reporting of HMC data for national health and nutrition monitoring and programmatic needs, including a shared vision for a publicly available Human Milk Composition Data Repository (HMCD-R) to include essential metadata associated with HMC. HMCD-R can provide a central, integrated platform for researchers and public health officials for compiling, evaluating, and sharing HMC data. The compiled compositional and metadata in HMCD-R would provide pertinent measures of central tendency and variability and allow use of modeling techniques to approximate compositional profiles for subgroups, providing more accurate exposure assessments for purposes of monitoring and surveillance. HMC and related metadata could facilitate understanding the complexity and variability of HM composition, provide crucial data for assessment of infant and maternal nutritional needs, and inform public health policies, food and nutrition programs, and clinical practice guidelines., (Published by Oxford University Press on behalf of the American Society for Nutrition 2022.)

Background: Perfluoroalkyl substances can disrupt hepatic metabolism and may be associated with liver function biomarkers. We examined individual and mixture associations of PFAS on liver function biomarkers in a representative sample of Canadian adults. We explored the potential for effect modification by sex and body mass index, as well as by physical activity level which may attenuate the deleterious effect of PFAS on metabolic disorders., Methods: We analyzed data from participants aged 20-74 from the Canadian Health Measures Survey. We used linear regression to examine associations between plasma concentrations of PFOA, PFOS, PFHxS, PFNA, PFDA, and PFUDA on serum concentrations of aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bilirubin. We used quantile g-computation to estimate associations with a PFAS mixture for each simultaneous, one-quartile change in PFAS concentrations., Results: Each doubling of PFOA, PFOS, PFHxS, or PFNA concentrations was associated with higher AST, GGT, and ALP concentrations. Each doubling of PFOA concentrations was associated with 16.5% (95%CI: 10.4, 23.0) higher GGT concentrations among adults not meeting Canada's physical activity guidelines vs. 6.6% (95%CI: -1.6, 15.5) among those meeting these guidelines. Sex and BMI also modified some associations, though to a lesser extent. We did not observe associations between ALT and PFOA (1.2% change; 95%CI: -2.5, 4.9), PFOS (2.2% change; 95%CI: -0.8, 5.3), or PFHxS (1.5% change; 95%CI: -0.4, 3.4). We also did not observe consistent associations for PFDA and PFUDA or with total bilirubin. In quantile g-computation models, each simultaneous one-quartile increase in the PFAS mixture was positively associated with AST (7.5% higher; 95%CI: 4.0, 10.4), GGT (9.7% higher; 95%CI: 1.7, 17.0), and ALP (2.8% higher; 95%CI: 0.5, 5.4)., Conclusion: Higher plasma concentrations of PFOA, PFOS, PFHxS, and PFNA - both individually and as a mixture - were associated with higher serum concentrations of liver function biomarkers. These results contribute to emerging evidence suggesting that higher levels of physical activity appear to be protective against the hepatotoxic effects of PFOA. This work contributes to a growing body of evidence supporting the hepatotoxic effects of PFAS., (© 2022. The Author(s).)

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

Biomonitoring data of N,N-diethyl-meta-toluamide (DEET) in children is scarce and limited to controlled exposure and surveillance studies. We conducted a 24-hour observational exposure and human biomonitoring study designed to estimate use of and exposure to DEET-based insect repellents by Canadian children in an overnight summer camp setting. Here, we present our study design and methodology. In 2019, children between the ages of 7 and 13 took part in the study (n = 126). Children controlled their use of DEET-based insect repellents, and provided an account of their activities at camp that could impact insect repellent absorption. Children provided a total of 389 urine samples throughout the study day, and reported the time that they applied insect repellent, which allowed us to contextualize urinary DEET and metabolite concentrations with respect to the timing of insect repellent application. DEET (2.3%

Low 25-hydroxyvitamin D (25OHD), a biomarker of vitamin D status, is associated with reduced immune function and adverse pregnancy outcomes, such as preterm birth. Observational studies indicate that long-term, high level exposure to metals such as cadmium (Cd) and lead (Pb) can impact a person's vitamin D status. However, the directionality of the association is uncertain, particularly for low-level exposures. We used three distinct longitudinal data analysis methods to investigate cross-sectional, longitudinal and bidirectional relationships of Cd and Pb biomarkers with 25-hydroxyvitamin D (25OHD) in a Canadian pregnancy cohort. Maternal whole blood Cd and Pb and plasma 25OHD concentrations were measured in the 1st (n = 1905) and 3rd (n = 1649) trimester and at delivery (25OHD only, n = 1542). Our multivariable linear regression analysis showed weak inverse associations between Cd and 25OHD concentrations cross-sectionally and longitudinally while the latent growth curve models showed weak associations with Pb on the 25OHD intercept. In the bidirectional analysis, using cross lagged panel models, we found no association between 1st trimester metals and 3rd trimester 25OHD. Instead, 1st trimester 25OHD was associated with 9% (-15%, -3%) lower 3rd trimester Cd and 3% (-7, 0.1%) lower Pb. These findings suggest the 25OHD may modify metal concentrations in pregnancy and demonstrates the value of controlling for contemporaneous effects and the persistence of a biomarker over time, in order to rule out reverse causation., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

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., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological and toxicological evidence suggests that maternal total arsenic (As) levels are associated with an elevated risk of gestational diabetes (GDM). Uncertainty remains regarding the metabolic toxicity of specific arsenic species, comprised of both organic and inorganic sources of arsenic exposure., Objectives: We assessed associations between speciated As and GDM using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study., Methods: Concentrations of speciated As [(inorganic (trivalent, pentavalent)), methylated arsenic species metabolites (monomethylarsonic acid (MMA), dimethylarsinic acid (DMA)), and organic (arsenobetaine)] were measured in first trimester maternal urine samples. GDM cases were identified in accordance with Canadian guidelines. Multivariable regression models were used to estimate associations between speciated As and GDM, evaluate potential interaction between speciated As exposures, and assess fetal sex-specific findings., Results: Among 1243 women who had a live, singleton birth and no previous history of diabetes, 4% met the diagnostic criteria for GDM. Our analyses focused on DMA and arsenobetaine as these were the subtypes with detectable concentrations in at least 40% of samples. Compared to women in the lowest tertile of DMA (<1.49 μg As/L), women with concentrations exceeding 3.52 μg As/L (3rd tertile) experienced an increased risk of GDM (aOR = 3.86; 95% CI: 1.18, 12.57) (p-value for trend across tertiles = 0.04). When restricted to women carrying male infants, the magnitude of this association increased (aOR 3rd tertile = 4.71; 95% CI: 1.05, 21.10)., Conclusions: These results suggest a positive relation between DMA and GDM; potential differences in risk by fetal sex requires further investigation., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Given that prenatal exposure to tobacco smoke can lead to increased risks of adverse health effects, having valid measures of exposure is important. In a Canadian cohort (n = 2000), maternal and infant biospecimens were analysed for cotinine. Sensitivity and specificity of self-reported active smoking status were estimated. Regression modelling was used to identify potential predictors of maternal and infant plasma cotinine in non-smoking women. During the first trimester, 60.6% of the women reported never smoking, 27.3% were former smokers, 6.1% had quit when they found out they were pregnant, 5.8% were smokers and 42% of the non-smokers reported exposure to secondhand smoke (SHS). Low detection of tobacco biomarkers in meconium limited its ability to identify exposure to SHS. The sensitivity and specificity for self-reported smoking during the 1st trimester were 85.37 and 99.45%, respectively. The lowest sensitivity was found in participants with the highest level of education and income, oldest women and those born outside Canada. Non-smoking women living in an apartment had 1.7 times higher odds of detectable plasma cotinine than those living in a single home after adjusting for other variables. Our results suggest that while self-reports are fairly accurate, they may be less so in populations with higher socio-economic status. This investigation underscores the need to consider the participant socio-economic characteristics and dwelling type when using questionnaires to estimate active and passive tobacco exposure.

Background: Triclosan is a phenolic biocide used in a multitude of consumer products and in health care settings. It is widely detected in the American and Canadian populations and has been shown in animal models to act as an endocrine disrupting agent. However, there has been little examination to date of the effects of triclosan exposure in pregnancy on perinatal metabolic outcomes in human populations., Methods: Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a Canadian pregnancy cohort, we measured associations of first-trimester urinary triclosan concentrations with total gestational weight gain, gestational diabetes mellitus and impaired glucose tolerance in pregnancy, and fetal markers of metabolic function. Leptin and adiponectin were measured in plasma from umbilical cord blood samples in term neonates and categorized into low (< 10th percentile), intermediate (10th-90th percentile) and high (> 90th percentile) levels. Triclosan concentrations were grouped into quartiles and associations with study outcomes were examined using logistic regression models with adjustment for maternal age, race/ethnicity, pre-pregnancy BMI, education and urinary specific gravity. Restricted cubic spline analysis was performed to help assess linearity and shape of any dose-response relationships. All analyses for leptin and adiponectin levels were performed on the entire cohort as well as stratified by fetal sex., Results: Triclosan measures were available for 1795 MIREC participants with a live born singleton birth. Regression analyses showed a non-significant inverse association between triclosan concentrations and leptin levels above the 90th percentile that was restricted to female fetuses (OR for highest quartile of triclosan compared to lowest quartile = 0.4 (95% CI 0.2-1.1), p-value for trend across quartiles = 0.02). Triclosan concentrations in the second quartile were associated with elevated odds of adiponectin below the 10th percentile in male fetuses (OR for Q2 compared to Q1 = 2.5, 95% CI 1.1-5.9, p-value for trend across quartiles = 0.93). No significant linear associations between triclosan concentrations and leptin or adiponectin levels in overall or sex-specific analyses were observed from restricted cubic spline analyses. No significant associations were observed in adjusted analyses between triclosan concentrations and gestational diabetes mellitus, impaired glucose tolerance or gestational weight gain., Conclusions: This study does not support an association between triclosan concentrations in pregnancy and fetal metabolic markers, glucose disorders of pregnancy, or excessive gestational weight gain., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

The Canadian population is currently subject to low, chronic lead exposure and an understanding of its effects is of great significance to the population's health. Such low exposure is difficult to measure directly; approximation by physiologically based modeling may provide a preferable approach to population analysis. The O'Flaherty model of lead kinetics is based on an age-dependent approach to human growth and development and devotes special attention to bone turnover rates. Because lead is a bone-seeking element, the model was deemed ideal for such an analysis. Sample from 263 individuals of various ages from the Greater Toronto Area were selected to evaluate the applicability of the current version of the O'Flaherty model to populations with low lead exposure. For each individual, the input value of lead exposure was calibrated to match the output value of cortical bone lead to the individual's measured tibia lead concentration; the outputs for trabecular bone, blood, and plasma lead concentrations obtained from these calibrations were then compared with the subjects' measured calcaneus, blood, and serum lead concentrations, respectively. This indicated a need for revision of the model parameters; those for lead binding in blood and lead clearance from blood to bone were adjusted and new outputs were obtained in the same fashion as before. Model predictions of trabecular lead concentration did not agree with measurements in the calcaneus. The outputs for blood and plasma lead concentrations were highly scattered and, on an individual level, inconsistent with corresponding measurements; however, the general trends of the outputs matched those of the measurements reasonably well, which indicates that the revised blood lead binding and lead clearance parameters may be useful in future studies. Overall, the analysis showed that with the revisions to the model discussed here, the model should be a useful tool in the analysis of human lead kinetics and body burden in populations characterized by low, chronic exposure to lead from the general environment.

A (109)Cd K X-ray fluorescence (KXRF) measurement system consisting of four detectors in clover-leaf geometry is a non-invasive, low-radiation-dose method of measuring bone lead concentration. Its high precision in estimating the bone lead content makes it a promising tool for the determination of the low levels of lead currently found in the general population. After developing the clover-leaf geometry system, the system was used for the first time in a major survey in 2008 to measure the lead levels of 497 smelter employees (an occupationally exposed group with high lead levels). Since the delivered effective dose of the bone lead system in clover-leaf geometry is small (on the order of nSv), the technique can be used to measure the bone lead of sensitive populations such as the elderly and children. This detector system was used from 2009 to 2011, in a pilot study that measured the bone lead concentration of 263 environmentally exposed individuals (termed the EG group) residing in Toronto, Ontario, Canada. In this paper, the factors that influence uncertainties in lead content in tibia (cortical bone) and calcaneus (trabecular bone) are discussed based on gender, age, and body mass index (BMI) by using analysis of variance (ANOVA) and multiple linear regression models. Results from the two study groups (the EG group versus the occupationally exposed smelter employees) are compared where appropriate (i.e. for males older than 20). Results from univariate analyses showed that females have higher tibia uncertainty compared to males. We observed significant differences for both calcaneus and tibia uncertainty measures (p < 0.0005) among different age groups, where the uncertainties were highest in the lowest age group (<11 years). Lastly, and perhaps most significantly, we found that the product of source activity and measurement time influenced the precision of measurements greatly, and that this factor alone could account for the higher uncertainties observed for the male cohort of the EG group versus the smelter employees.

Background: Obesity and type-2 diabetes are on the rise and in utero exposure to environmental contaminants is a suspected contributing factor. Our objective was to examine associations between prenatal exposure to potential endocrine disrupting chemicals and markers of fetal metabolic dysfunction., Methods: The Maternal-Infant Research on Environmental Chemicals Study (MIREC) recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. First trimester maternal urine was measured for 11 phthalate metabolites and bisphenol A (BPA). Leptin and adioponectin measured in 1,363 available umbilical cord blood samples served as markers of metabolic function. Restricted cubic spline curves were used to assess the relationship between continuous measures of phthalate and BPA levels and cord blood adipokines. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between phthalates and BPA and both high (≥90th percentile) and low (≤10th percentile) fetal adiponectin and leptin, adjusting for confounding factors. Analyses were conducted for all subjects, overall, and separately by fetal sex., Results: Leptin was significantly higher in female than male infants. We observed an inverse, non-linear relationship between BPA and adiponectin among males in the restricted cubic spline and linear regression analysis. Mono-(3-carboxypropyl) (MCPP) was associated with increased odds of high leptin among males in the polytomous logistic regression models (4th quartile OR = 3.5 95% CI: 1.1-11.6)., Conclusion: Our findings contribute to the growing body of evidence examining the influence of early life exposure on metabolic regulation and function. Associations between maternal exposure to chemicals and markers of metabolic function appear to be potentially sex specific. However, further investigation is required to determine whether in utero and childhood exposure to BPA and phthalates are associated with metabolic dysfunctions later in life.