Karelyn Davis

Phthalate and bisphenol A exposure among pregnant women in Canada — Results from the MIREC study

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: 32.02 μg/L) and MnBP (GM: 11.59 μg/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.

Cohort Profile: The Maternal-Infant Research on Environmental Chemicals Research Platform

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 studys 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.

Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort.

Background: Bisphenol A (BPA) and triclosan (TCS) are two nonpersistent chemicals that have been frequently measured in spot urine samples from the general population but less so in pregnant women; however, data are limited on the free (bioactive) and conjugated forms of these phenols. Objectives: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study addressed these data gaps by utilizing stored maternal urine samples from a large multicenter cohort study of Canadian pregnant women. Methods: Concentrations of free and conjugated forms of BPA and TCS were measured in about 1,890 first-trimester urine samples by ultra performance liquid chromatograpy–tandem mass spectrometry using isotope dilution. Results: The glucuronides of BPA and TCS were the predominant forms of these chemicals measured (detected in 95% and 99% of samples, respectively), whereas the free forms were detected in 43% and 80% of samples, respectively. The geometric mean urinary concentrations for glucuronides of BPA and TCS were 0.80 μg/L (95% CI: 0.75, 0.85) and 12.30 μg/L (95% CI: 11.08, 13.65), respectively. Significant predictors of BPA included maternal age < 25 vs. ≥ 35 years, current smoking, low vs. high household income, and low vs. high education. For TCS, urinary concentrations were significantly higher in women ≥ 25 years of age, never vs. current smokers, and women with high household income and high education. Conclusions: The results from this study represent the largest national-level data on urinary concentrations of free and conjugated forms of BPA and TCS in pregnant women and suggest that maternal characteristics predicting elevated urinary concentrations of these phenols largely act in opposite directions. Citation: Arbuckle TE, Marro L, Davis K, Fisher M, Ayotte P, Bélanger P, Dumas P, LeBlanc A, Bérubé R, Gaudreau É, Provencher G, Faustman EM, Vigoren E, Ettinger AS, Dellarco M, MacPherson S, Fraser WD. 2015. Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort. Environ Health Perspect 123:277–284; http://dx.doi.org/10.1289/ehp.1408187

Umbilical cord blood levels of perfluoroalkyl acids and polybrominated flame retardants

Perfluoroalkyl acids (PFAAs) and polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants representing two classes of environmental contaminants of toxicological concern, especially for infants. Canadian biomonitoring data on these chemicals are limited. The objectives of this study were to measure PFAAs and PBDEs in umbilical cord blood from approximately 100 hospital deliveries in Ottawa (Ontario, Canada) and examine associations with characteristics of the mother and infant. Geometric means were 1.469 ng/mL for perfluorooctanoate (PFOA) (95% confidence interval of 1.292-1.671 ng/mL), 4.443 ng/mL for perfluorooctane sulfonate (PFOS) (95% CI of 3.735-5.285 ng/mL), 0.359 ng/mL for perfluorononanoic acid (PFNA) (95% CI of 0.318-0.404 ng/mL), and 0.579 ng/mL for perfluorohexanesulfonate (PFHxS) (95% CI of 0.473-0.709 ng/mL). The final multiple regression models indicated that lower gravida, term gestational age, smoking during pregnancy and vaginal delivery were significantly associated with higher levels of PFOS. Similarly, a vaginal delivery was significantly associated with higher PFOA, while weak associations were found with lower gravida and birth weight less than 2500 g. Furthermore, higher PFNA concentrations were significantly associated with older mothers, and vaginal delivery, while weakly associated with term gestational age. Elevated PFHxS concentrations were significantly associated with smoking during pregnancy and lower gravida. Similar to reports from other countries, the preponderant PBDE congener measured in the cord blood was PBDE-47. Questions remain on why various studies have reported conflicting results on the association between PFAAs and birth weight.

Indoor air quality in Montréal area day-care centres, Canada.

Indoor air quality (IAQ) has been understudied in day-care centres (DCCs), even though it can affect the respiratory health of children. This study was undertaken to assess IAQ in a randomly selected sample of 21 DCCs having space for at least 40 children in Montréal, Canada, and to determine associations between building characteristics and IAQ. Questionnaires on building characteristics and operation of the DCC were administered to managers. Temperature, relative humidity, and concentrations of carbon dioxide (CO(2)), formaldehyde and volatile organic compounds were measured in January and February 2008 in rooms attended by children aged between 18 and 60 months. Most DCCs (81%) had a mechanical ventilation system. Over 85% of the DCCs had a mean CO(2) concentration higher than 1000 ppm, the value generally targeted for comfort in buildings. Mean CO(2) concentrations were significantly lower in DCCs having a floor space meeting the provincial standards. The mean (standard deviation-SD) formaldehyde concentration was 22.9 (8.2) μg/m(3), with all participating DCCs being within Health Canadas Residential IAQ Guideline of 50 μg/m(3). The presence of a mechanical ventilation system and a large surface of play area per child were significantly associated with lower CO(2) levels, explaining 44% of the variance in indoor CO(2) concentrations. The presence of a mechanical ventilation system was also associated with significantly lower formaldehyde and acetaldehyde levels. Moreover, 68% of the variance in indoor acetaldehyde concentrations was explained by CO(2) levels, indicating that CO(2) was a better proxy of ventilation than the presence of a ventilation system, as this latter variable did not imply that the ventilation system was running or functioning adequately. These results demonstrate the need for on-going efforts to ensure sufficient floor space and adequate ventilation in DCCs to maintain good IAQ.

Bisphenol A, phthalates and lead and learning and behavioral problems in Canadian children 6–11 years of age: CHMS 2007–2009

Childhood developmental disorders and related problems such as learning disabilities and attention deficit hyperactivity disorder (ADHD) account for a growing burden on the family, education and health care systems. Exposure to environmental chemicals such as bisphenol A (BPA) and phthalates may play a role in the development of child behavioral problems. Using cross-sectional data from Cycle 1 of the Canadian Health Measures Survey (CHMS), we examined the potential association between urinary concentrations of BPA and various phthalate metabolites and child learning and behavioral problems, considering important covariates such as gender, blood lead and environmental tobacco smoke (ETS). The Strengths and Difficulties Questionnaire (SDQ) outcomes of interest were emotional symptoms, hyperactivity/inattention, and a total difficulties score with borderline and abnormal scores grouped together and compared with children with normal scores. Other outcomes studied included any reported learning disability, a subset of learning disabilities reported as ADD/ADHD (attention deficit disorder) and use of psychotropic medications in the past month. Among children ages 6-11 years, the prevalences of any learning disability, ADD, and ADHD were 8.7%, 1.5% and 2.8%, respectively. Estimated prevalences for SDQ hyperactivity/inattention, emotional symptoms and total difficulties scores were 16.9%, 15.0%, and 13.0%, respectively. Childs urinary BPA was associated with taking psychotropic medications (OR 1.59; 95% CI 1.05-2.40). Urinary MBzP concentration was significantly associated with emotional symptoms in girls (OR 1.38 95% CI 1.09-1.75) but not in boys (OR 1.05 95% CI 0.82-1.36).) Blood lead was significantly associated with several of the outcomes examined, with a significant interaction observed between prenatal smoking and blood lead for the total difficulties score (OR=10.57; 95% CI 2.81-39.69 vs. OR=1.98; 95% CI 1.41-2.79 if mother did not smoke during pregnancy). Although limited by the cross-sectional nature of the study which precludes examining causation, the results suggest that although some indicators of child behavior were significantly associated with their urinary BPA and phthalate concentrations, the major chemical associated with adverse behavioral indicators was lead.

Assessing determinants of maternal blood concentrations for persistent organic pollutants and metals in the eastern and western Canadian Arctic

Aboriginal peoples in the Canadian Arctic are exposed to persistent organic pollutants (POPs) and metals mainly through their consumption of a traditional diet of wildlife items. Recent studies indicate that many human chemical levels have decreased in the north, likely due to a combination of reduced global chemical emissions, dietary shifts, and risk mitigation efforts by local health authorities. Body burdens for chemicals in mothers can be further offset by breastfeeding, parity, and other maternal characteristics. We have assessed the impact of several dietary and maternal covariates following a decade of awareness of the contaminant issue in northern Canada, by performing multiple stepwise linear regression analyses from blood concentrations and demographic variables for 176 mothers recruited from Nunavut and the Northwest Territories during the period 2005-2007. A significant aboriginal group effect was observed for the modeled chemicals, except for lead and cadmium, after adjusting for covariates. Further, blood concentrations for POPs and metals were significantly associated with at least one covariate of older age, fewer months spent breastfeeding, more frequent eating of traditional foods, or smoking during pregnancy. Cadmium had the highest explained variance (72.5%) from just two significant covariates (current smoking status and parity). Although Inuit participants from the Northwest Territories consumed more traditional foods in general, Inuit participants from coastal communities in Nunavut continued to demonstrate higher adjusted blood concentrations for POPs and metals examined here. While this is due in part to a higher prevalence of marine mammals in the eastern Arctic diet, it is possible that other aboriginal group effects unrelated to diet may also contribute to elevated chemical body burdens in Canadian Arctic populations.

Univariate predictors of maternal concentrations of environmental chemicals: The MIREC study

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 individuals susceptibility to potential health effects due to differences in lifestyle, cultural diets, and aging.

Processed data for CHMS 2007–2009: Bisphenol A, phthalates and lead and learning and behavioral problems in Canadian children 6–19 years of age

This article presents processed data from an analysis of cross-sectional data from Cycle 1 of the Canadian Health Measures Survey (CHMS) to examine the potential association between urinary concentrations of BPA and phthalate metabolites and child learning and behavioral problems, considering important covariates such as gender, blood lead and environmental tobacco smoke (ETS). These processed data are related to the research on a subset of the children (Arbuckle et al., 2016) [1]. The Strengths and Difficulties Questionnaire (SDQ) outcomes of interest were emotional symptoms, hyperactivity/inattention, and a total difficulties SDQ score, with borderline and abnormal scores grouped together and compared with children with normal scores. Other outcomes studied included reported learning disability, ADD/ADHD (attention deficit disorder/attention deficit hyperactivity disorder) and use of psychotropic medications to treat behavioral disorders in the past month. Data are presented for all children 6–19 years of age combined. Weighted simple logistic regression estimates for important covariates of each of the outcomes from CHMS Cycle 1 children are reported. Odds ratios based on weighted multiple logistic regression estimates for urinary BPA and phthalate metabolites (including specific gravity as a covariate) and blood lead are presented for the reported outcomes ADD/ADHD, learning disability and psychotropic medications, as well as the SDQ outcomes emotional symptoms, hyperactivity/inattention and total difficulties.

Arsenic levels among pregnant women and newborns in Canada: Results from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort

ABSTRACT Arsenic is a common environmental contaminant from both naturally‐occurring and anthropomorphic sources and human exposure can be detected in various tissues. Its toxicity depends on many factors including the chemical form, valence state, bioavailability, metabolism and detoxification within the human body. Of paramount concern, particularly with respect to health effects in children, is the timing of exposure as the prenatal and early life periods are more susceptible to toxic effects. The Maternal‐Infant Research on Environmental Chemicals (MIREC) cohort was established to obtain national‐level biomonitoring data for approximately 2,000 pregnant women and their infants between 2008 and 2011 from 10 Canadian cities. We measured total arsenic (As) in 1st and 3rd trimester maternal blood, umbilical cord blood, and infant meconium and speciated arsenic in 1st trimester maternal urine. Most pregnant women had detectable levels of total arsenic in blood (92.5% and 87.3%, respectively, for 1st and 3rd trimester); median difference between 1st and 3rd trimester was 0.1124 &mgr;g/L (p<0.0001), but paired samples were moderately correlated (Spearman r=0.41, p<0.0001). Most samples were below the LOD for umbilical cord blood (50.9%) and meconium (93.9%). In 1st trimester urine samples, a high percentage (>50%) of arsenic species (arsenous acid (As‐III), arsenic acid (As‐V), monomethylarsonic acid (MMA), and arsenobetaine (AsB)) were also below the limit of detection, except dimethylarsinic acid (DMA). DMA (>85% detected) ranged from <LOD to 64.42 (95th percentile: 11.99) &mgr;g As/L. There was a weak but significant correlation between total arsenic in blood and specific gravity‐adjusted DMA in urine (Spearman r=0.33, p<0.0001). Among this population of pregnant woman and newborns, levels of arsenic measured in blood and urine were lower than national population figures for Canadian women of reproductive age (20–39 years). In general, higher arsenic levels were observed in women who were older, foreign‐born (predominantly from Asian countries), and had higher education. Further research is needed to elucidate sources of exposure and factors that may influence arsenic exposure in pregnant women and children. HighlightsApproximately 90% of pregnant women had total As in blood >LOD.Inorganic As species in urine rarely detected except for DMA (85%).Sensitivity of maternal blood As to predict detectable cord blood As >90%.Levels higher in women who were older, foreign‐born or had higher education.As levels were lower than national figures for Canadian women of reproductive age.