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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]

Depending on the chemical and the outcome, prenatal exposures to environmental chemicals can lead to adverse effects on the pregnancy and child development, especially if exposure occurs during early gestation. Instead of focusing on prenatal exposure to individual chemicals, more studies have taken into account that humans are exposed to multiple environmental chemicals on a daily basis. The objectives of this analysis were to identify the pattern of chemical mixtures to which women are exposed and to characterize women with elevated exposures to various mixtures. Statistical techniques were applied to 28 chemicals measured simultaneously in the first trimester and socio-demographic factors of 1744 participants from the Maternal-Infant Research on Environment Chemicals (MIREC) Study. Cluster analysis was implemented to categorize participants based on their socio-demographic characteristics, while principal component analysis (PCA) was used to extract the chemicals with similar patterns and to reduce the dimension of the dataset. Next, hypothesis testing determined if the mean converted concentrations of chemical substances differed significantly among women with different socio-demographic backgrounds as well as among clusters. Cluster analysis identified six main socio-demographic clusters. Eleven components, which explained approximately 70% of the variance in the data, were retained in the PCA. Persistent organic pollutants (PCB118, PCB138, PCB153, PCB180, OXYCHLOR and TRANSNONA) and phthalates (MEOHP, MEHHP and MEHP) dominated the first and second components, respectively, and the first two components explained 25.8% of the source variation. Prenatal exposure to persistent organic pollutants (first component) were positively associated with women who have lower education or higher income, were born in Canada, have BMI ≥ 25, or were expecting their first child in our study population. MEOHP, MEHHP and MEHP, dominating the second component, were detected in at least 98% of 1744 participants in our cohort study; however, no particular group of pregnant women was identified to be highly exposed to phthalates. While widely recognized as important to studying potential health effects, identifying the mixture of chemicals to which various segments of the population are exposed has been problematic. We present an approach using factor analysis through principal component method and cluster analysis as an attempt to determine the pregnancy exposome. Future studies should focus on how to include these matrices in examining the health effects of prenatal exposure to chemical mixtures in pregnant women and their children. [ABSTRACT FROM AUTHOR]

Phthalates are a group of chemicals found in a number of consumer products; some of these phthalates have been shown to possess estrogenic activity and display anti-androgenic effects. While a number of biomonitoring studies of phthalates in pregnant women and infants have been published, there is a paucity of data based on both multiple sampling periods and in different matrices. Phthalate metabolites were measured in 80 pregnant women and their infants in Ottawa Canada (2009–2010) in urine, meconium and breast milk collected at various time periods pre- and post-parturition. At least 50% of the women had at least one urine sample greater than the limit of detection (LOD) for the various phthalate metabolites, with the exception of mono- n -octyl phthalate (MnOP), mono-isononyl phthalate (MiNP) and mono(carboxy-isooctyl) phthalate (MCiOP). Four major clusters of maternal urinary metabolites were identified. Among infants (n = 61), the following metabolites were rarely (< 10%) detected: mono-cyclohexyl phthalate (MCHP), mono-isononyl phthalate (MiNP), mono-methyl phthalate (MMP), and mono- n -octyl phthalate (MnOP). While mono-benzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), MEHHP, and MEOHP were frequently detected in maternal urines at any time point, these metabolites were rarely detected in breast milk. Maternal urinary concentrations of MEP and the DEHP metabolites were higher in samples collected during pregnancy than postnatally. No statistically significant differences were observed in infant's urinary phthalate concentrations between breast-fed and bottle-fed infants. Significant correlations were observed between maternal urinary MEHHP (r = 0.35), MEOHP (r = 0.35) and MEP (r = 0.37) collected at < 20 weeks gestation with levels in meconium and between MBzP (r = 0.78) and MEP (r = 0.56) in maternal and infant urine collected 2–3 months after birth. These results suggest at least some maternal-fetal-infant transfer of phthalates and that meconium may be a useful matrix for measuring in utero exposure to phthalates. [ABSTRACT FROM AUTHOR]

Prenatal exposure to total mercury (T-Hg) comes from both natural and anthropogenic sources. T-Hg can cross the blood-brain and placental barriers, and may be associated with future neurological and physiological dysfunctions. Scalp hair is an optimal and non-invasive indicator of chronic T-Hg exposure. As part of the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, hair samples from 350 women were collected within weeks after giving birth, to determine temporal variations in T-Hg levels from preconception to delivery, and to compare these levels to corresponding levels measured in other matrices (maternal and umbilical cord blood, and infant's meconium). A maximum of 12 one-cm hair segments were cut starting at the scalp; segments closer to the scalp reflected recent exposure (within the last month). For proper comparison, the hair segments were matched with the collection dates for other matrices. GM hair T-Hg levels greatly decreased during pregnancy, from 0.26 μg g−1 (preconception or full-length hair) to 0.18 μg g−1 (at delivery or segments closer to the scalp). A similar decreasing trend was found for T-Hg in maternal blood: 1st trimester (0.60 μg L−1) to 3rd trimester (0.47 μg L−1). The median hair-to-blood ratios of T-Hg levels varied from 364 (1st trimester), to 408 (3rd trimester), to 229 (cord blood). Very low T-Hg levels were detected in meconium. Mercury levels in blood and hair correlated with consumption of large predatory fish. • Mercury exposure was evaluated in the pan-Canadian MIREC pregnancy cohort. • T-Hg levels in scalp hair significantly decreased during pregnancy, from conception to delivery. • T-Hg levels in hair were significantly correlated with T-Hg levels in blood. • Median hair-to-blood ratios of T-Hg levels increased from 364 to 408 during pregnancy. • Consumption of predatory fish weakly correlated with T-Hg levels in hair and blood. [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 Triclosan (TCS) is an antibacterial agent commonly added to personal care products. Some animal research studies have associated TCS exposure with androgenic and thyroid effects, as well as endocrine disruption, contact dermatitis and skin irritation. Limited Canadian data exist on exposure levels, temporal variability and sources of exposure to TCS, especially among pregnant women. Methods Single and serial spot urine samples ( n = 1249), as well as consumer product use information were collected over 5 study visits across pregnancy and post-partum from 80 healthy pregnant women in Ottawa, Canada. Urine samples were analyzed for TCS by GC–MS–MS. Summary statistics, linear mixed effects models, and surrogate category analysis were used to describe the results. Results Triclosan was detected in 87% of maternal urine samples (LOD = 3.0 μg/L). The geometric mean TCS concentration of all urine samples was 21.6 μg/L (95% CI 18.2–25.7). Triclosan concentrations were significantly higher when the urine was collected before 16:00, in the autumn, and more than 90 min since last void, and in nulliparous women with household incomes greater than $100,000. A significant correlation was observed between maternal urinary TCS concentrations and number of reported uses of TCS-containing products. The ability of a single spot urine sample collected at any time during or post-pregnancy to predict an individual's geometric mean urinary TCS level corresponding to low, medium, or high exposure was 86.7%. Intraclass correlation coefficients indicated high reproducibility within a week-day (0.77) and week-end day (0.79) and moderate reproducibility across the study period (0.50). Conclusions This study provided the first data on temporal variability of urinary TCS concentrations and predictors of exposure in Canadian pregnant women. These results can inform exposure assessments in pregnant women and justify collection of single spot urine samples in epidemiologic studies, especially for women with higher exposures. [ABSTRACT FROM AUTHOR]

Background Results of recent national surveys have shown the high prevalence of exposure to bisphenol A (BPA) and triclosan (TCS) among the general population; however biomonitoring data for pregnant women and infants are limited. Methods Women (n = 80) were recruited from early prenatal clinics and asked to collect urine samples multiple times during pregnancy and once 2–3 months post-partum. Samples of infant urine and meconium as well as breast milk and infant formula were also collected. Biospecimens were analyzed by GC–MS/MS for BPA, TCS and triclocarban (TCC). Results Triclosan was detected in over 80% of the maternal urines (geometric mean (GM): 21.61 μg/L), 60% of the infant urines (GM: 2.8 μg/L), 46% of the breast milk and 80% of the meconium samples. Triclocarban was rarely detected in any of the biospecimens. Median total BPA concentrations were 1.21 and 0.24 μg/L in maternal and infant urines, respectively. Free BPA was detected in only 11% of infant urine samples. The meconium of female infants had significantly higher concentrations of total BPA and TCS than those of males, while no differences were observed in infant urine concentrations by sex. Conclusions We found widespread exposure among pregnant women and infants to environmental phenols, with large inter-individual variability in exposure to triclosan. These data will contribute to the risk assessment of these chemicals, especially in susceptible sub-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]

• 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]

Abstract 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. Highlights • We evaluated associations between maternal arsenic and gestational diabetes (GDM). • Primary exposure was maternal urinary concentrations of dimethylarsinic acid (DMA). • Elevated (3rd tertile) DMA was associated with a three fold elevated risk of GDM. • Maternal exposure to a methylated arsenic metabolite may contribute to GDM risk. [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]

Phthalates are non-persistent chemicals measured as metabolites in urine. Over time, new metabolites have been identified. In the original Maternal-Infant Research on Environmental Chemicals (MIREC) study (2008–2011), we measured 11 phthalate metabolites in first trimester urine samples. The goal of the present study was to develop a method to measure new metabolites, to increase the sensitivity for some previously measured metabolites, and to measure these new metabolites in biobanked urine samples from MIREC participants. Using Ultra Performance Liquid Chromatography with a tandem mass spectrometer, we developed a method to measure 24 metabolites from 10 different parent phthalates. Chromatographic interpretation of some of the di-iso-decyl phthalate metabolites (mono-(2-propyl-6oxoheptyl) phthalate (MOiDP), mono-(2,7-methyl-7-carboxyheptyl) phthalate (MCiNP), mono-(2-propyl-6-hydroxy-heptyl) phthalate (MHiDP)) and di-iso-nonyl phthalate metabolites (mono(oxo-isononyl) phthalate (MOiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxy-isononyl) phthalate (MHiNP) and mono-isononyl phthalate (MiNP)) was challenging as these are complex isomeric mixtures. To validate and confirm our quantitation peaks, an assay using a high-resolution detection technique was developed on a Quadrupole Time-of-Flight (QToF) system. This system has a mass resolution of at least 0.005 amu, compared to 0.5 amu for the MS/MS detector. Using the QToF system, the distinction between an isomer and possible interference was achieved with the use of the exact mass. In about 1800 MIREC samples, mono-cyclo-hexyl phthalate (MCHP), mono-(7-carboxy-n-heptyl) phthalate (MCHpP), mono-iso-decyl phthalate (MiDP), and mono-n-octyl phthalate (MnOP) were rarely detected, while detection of MMP was improved. MCiOP, MiNP and MCiNP had to be reported semi-quantitatively. Given the complexity of isomeric mixtures of some phthalates, researchers must be careful in their determination of the analytes and the approach used in their quantification when generating biomonitoring data. This study produced biomonitoring data for a large population of pregnant people that can be used in risk assessment of phthalates. Future work will examine associations with birth and child outcomes. [Display omitted] • Methods developed to measure 24 urinary phthalate metabolites. • Improved sensitivity for MMP. • MCHP, MCHpP, MiDP, and MnOP rarely detected. • Due to isomeric mixtures, MCiOP, MiNP and MCiNP reported semi-quantitatively. • When comparing results, reporting algorithms and lab methods need to be considered. [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]

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]

N,N-diethyl-m-toluamide (DEET) is an ingredient found in many consumer insect repellents and its use is recommended to Canadians by government agencies, including Health Canada, for protection against insect bites including mosquitos and ticks. The majority of research on DEET exposure and toxicokinetics in humans has focused on adult populations with little information from vulnerable populations, including children. We aimed to fill this knowledge gap by examining real-world exposure data for DEET and its metabolite 3-diethylcarbamoyl benzoic acid (DCBA) in a sample population of Canadian children. We conducted a 24-h observational exposure human biomonitoring study at three overnight summer camps in Ontario, Canada through July and August 2019. Participating children aged 7–13 years provided multiple spot urine samples over a 24-h period and completed a journal to document insect repellent use and factors that could influence absorption of DEET. Children were instructed to use insect repellent as they usually would while attending a summer camp. Exposure was quantified using the information from the participant's journal and the change in the mass of their insect repellent containers over the course of the study. A total of 389 urine samples were collected from 124 children. Among participants using insect repellent, urinary levels of DEET were elevated between 2 and 8 h post-application and decreased thereafter but remained qualitatively higher than concentrations in participants who did not use insect repellent on the study day, even at 18–22 h post-application. DCBA was the predominant metabolite of DEET exposure in urine. DCBA was elevated between 8 and 14 h post-application, and declined thereafter, but not to the level observed among those who did not use insect repellent on the study day. Children who used more insect repellent, or used higher concentration insect repellent (10%–30% DEET) excreted higher levels of DEET and DCBA. Excreted DEET and DCBA accounted for 0.001% (median) and 1.3% (median) of the estimated applied DEET, respectively. Children did not reach an undetectable level of DEET or DCBA in urine, even among those not using insect repellent during the study day, indicating a potentially complex multi-route exposure to insect repellents in a real world scenario. This work provides targeted biomonitoring data for children intentionally using DEET-based insect repellents for normal protective use, and will support the risk re-evaluation of DEET by Health Canada. [Display omitted] • The first observational biomonitoring study measuring DEET in children's urine. • Children using more insect repellent excreted higher levels of DEET and metabolites. • Using >10% DEET repellent results in higher levels of DEET and metabolites excreted. • Commercial repellents used in this study were not highly absorbed by children. • Excreted compounds represent a small proportion of estimated DEET applied. [ABSTRACT FROM AUTHOR]

Given the susceptibility of the fetus to toxicants, it is important to estimate their exposure. Approximately 2000 pregnant women were recruited in 2008–2011 from 10 cities across Canada. Cd, Pb, Mn and total Hg were measured in maternal blood from the 1st and 3rd trimesters, umbilical cord blood, and infant meconium. Nutrient intakes of vitamin D, iron, and calcium (Ca) were assessed using a food frequency questionnaire and a dietary supplement questionnaire. Median concentrations in 1st trimester maternal blood (n = 1938) were 0.20, 8.79 and 0.70 μg/L for Cd, Mn and Hg, respectively, and 0.60 μg/dL for Pb. While the median difference between the paired 1st and 3rd trimester concentrations of Cd was 0, there was a significant decrease in Pb (0.04 μg/dL) and Hg (0.12 μg/L) and an increase in Mn (3.30 μg/L) concentrations over the course of the pregnancy. While Cd was rarely detected in cord blood (19%) or meconium (3%), median Pb (0.77 μg/dL), Mn (31.87 μg/L) and Hg (0.80 μg/L) concentrations in cord blood were significantly higher than in maternal blood. Significant negative associations were observed between estimated Ca intake and maternal Cd, Pb, Mn and Hg, as well as cord blood Pb. Vitamin D intake was associated with lower maternal Cd, Pb, and Mn as well as Pb in cord blood. Even at current metal exposure levels, increasing dietary Ca and vitamin D intake during pregnancy may be associated with lower maternal blood Pb and Cd concentrations and lower Pb in cord blood. [ABSTRACT FROM AUTHOR]

While it is known that in utero exposure to environmental toxicants, namely heavy metals, can adversely affect the neonate, there remains a significant paucity of information on maternal biological changes specific to metal exposures during pregnancy. This study aims at identifying associations between maternal metal exposures and matrix metalloproteinases (MMPs) that are known to be engaged in pregnancy process. Third trimester maternal plasma (n = 1533) from a pregnancy cohort (Maternal-Infant Research on Environmental Chemicals Study, MIREC) were analyzed for MMP-1,-2,-7,-9 and -10 by affinity-based multiplex protein array analyses. Maternal metal concentrations (mercury, cadmium, lead, arsenic and manganese) in 1st and 3rd trimesters exhibited strong correlations (p < 0.05). Multivariate regression models were used to estimate odds ratio (OR) for the association between metal concentrations in quartiles and high (90%) and low (10%) maternal MMP levels. Significant (p < 0.05) metal exposure-related effects were observed with the different MMP isoform responses. MMP profiles were specific to the trimester at which the maternal blood metals were analyzed. Our findings suggest that the profiles of these MMP isoforms vary with the type of metal exposure, blood metal concentrations and the trimester at which metal levels were determined. These new findings on maternal metal-MMP relationships can guide future explorations on toxicity mechanisms relevant to metal exposure-mediated adverse birth outcomes. [ABSTRACT FROM AUTHOR]

Organophosphate (OP) insecticides are commonly used in agriculture. Their use decreased in recent years as they were gradually replaced by other pesticides, but some OPs are still among the insecticides most used in Canada. Exposure to elevated levels of OPs during pregnancy has been associated with adverse birth outcomes and poorer neurodevelopment in children. The objective of the present study was to examine the relationship between the concentrations of OP pesticides urinary dialkyl phosphate (DAP) metabolites and various factors that are potential sources of exposure or determinants of DAP levels. In the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, six DAPs were measured in 1st trimester urine samples of 1884 pregnant women living in Canada. They were grouped into sums of dimethyl alkyl phosphates (DMAP) and diethyl alkyl phosphates (DEAP) for statistical analysis. We found that 93% of women had at least one DAP detected in their urine. Geometric means (GM) of specific gravity-corrected levels for urine dilution were 59 (95% CI 56–62) and 21 (95% CI 20–22) nmol/L for DMAP and DEAP, respectively. The following characteristics were significantly associated with higher urinary concentrations of DMAP or DEAP: higher education, nulliparous, normal pre-pregnancy body mass index, non-smoker, not fasting at sampling, winter season at sampling, and early and late day collection times. Dietary items that were significantly related with higher urinary concentrations included higher intake of citrus fruits, apple juice, sweet peppers, tomatoes, beans and dry peas, soy and rice beverages, whole grain bread, white wine and green and herbal teas. This study indicates that exposure to these compounds is quasi-ubiquitous. The factors associated with greater DAP levels identified here could be useful to regulatory agencies for risk analysis and management. However, some exposure misclassification might occur due to the single DAP measurement available, and to the presence of preformed DAPs in the environment. [ABSTRACT FROM AUTHOR]

Abstract: Bisphenol A (BPA) and phthalates are endocrine disruptors possibly linked to adverse reproductive and neurodevelopmental outcomes. These chemicals have commonly been measured in urine in population surveys; however, such data are limited for large populations of pregnant women, especially for the critical first trimester of pregnancy. The aim of the study was to measure BPA and phthalate metabolites in first trimester urine samples collected in a large national-scale pregnancy cohort study and to identify major predictors of exposure. Approximately 2000 women were recruited in the first trimester of pregnancy from ten sites across Canada. A questionnaire was administered to obtain demographic and socio-economic data on participants and a spot urine sample was collected and analyzed for total BPA (GC–MS/MS) and 11 phthalate metabolites (LC–MS/MS). The geometric mean (GM) maternal urinary concentration of total BPA, uncorrected for specific gravity, was 0.80 (95% CI 0.76–0.85) μg/L. Almost 88% of the women had detectable urinary concentrations of BPA. An analysis of urinary concentrations of BPA by maternal characteristics with specific gravity as a covariate in the linear model showed that the geometric mean concentrations: (1) decreased with increasing maternal age, (2) were higher in current smokers or women who quit during pregnancy compared to never smokers, and (3) tended to be higher in women who provided a fasting urine sample and who were born in Canada, and had lower incomes and education. Several of the phthalate metabolites analyzed were not prevalent in this population (MCHP, MMP, MiNP, MOP), with percentages detectable at less than 15%. The phthalate metabolites with the highest measured concentrations were MEP (GM: 32.02μg/L) and MnBP (GM: 11.59μg/L). MBzP urinary concentrations decreased with maternal age but did not differ by time of urine collection; whereas the DEHP metabolites tended to be higher in older women and when the urine was collected later in the day. This study provides the first biomonitoring results for the largest population of pregnant women sampled in the first trimester of pregnancy. The results indicate that exposure among this population of pregnant women to these chemicals is comparable to or even lower than that observed in a Canadian national population-based survey. [Copyright &y& Elsevier]