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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: Organophosphate pesticides are widely used in agriculture and for other purposes, leading to ubiquitous exposure in human populations. Some studies reported cognitive deficits in children exposed prenatally to organophosphate pesticides, but findings from recent studies were inconsistent. Furthermore, recent biomonitoring studies suggest exposure levels have decreased. Hence, the risks from current prenatal exposure to organophosphate pesticides for child neurodevelopment are uncertain. Furthermore, sex-differences also remain to be better documented in relation to potential neurodevelopmental effects., Objective: To examine the association between prenatal exposure to organophosphate pesticides and IQ scores among boys and girls living in several major Canadian cities., Methods: We used data from the MIREC cohort (Maternal-Infant Research on Environmental Chemicals). Women were recruited in 2008-2011 from 10 Canadian cities during their first trimester of pregnancy, and urine spot samples were collected for measurement of three dimethyl alkyl phosphate (DMAP) and three diethyl alkyl phosphate (DEAP) metabolites. When children were 3-4 years of age, we used the Wechsler Preschool and Primary Scales of Intelligence-III (WPPSI-III) to assess cognitive ability of children from 6 out of the 10 cities (Halifax, Hamilton, Kingston, Montreal, Toronto, and Vancouver). We analysed the association between maternal exposure to organophosphate pesticides (DMAP and DEAP urinary metabolites) and children's IQ scores with generalized estimating equations (GEEs) to take into account the clustered-data resulting from the six study sites. All analyses were sex-stratified (n = 296 boys and 311 girls)., Results: The participants were predominantly well-educated, white women, with a relatively high household income. Children had a mean age of 3.4 years at the moment of IQ assessment (range, 3.0-4.1 years). In girls, there was no association between IQ scores and DEAPs or DMAPs. Higher concentrations of DEAPs were significantly associated with poorer Verbal IQ scores (for a 10-fold increase in concentrations, -6.28; 95% CIs, -12.13, -0.43) in boys. The association for Performance IQ in boys also indicated poorer scores with higher DEAP concentrations, but the confidence intervals included the null value (-4.05; 95% CIs, -10.19, 2.10). The relation between DMAPs and IQ scores in boys was also negative, but association estimates were small and not significant., Conclusion: Urinary metabolites of organophosphate pesticides were not associated with IQ in girls, but we observed that higher maternal urinary DEAPs were associated with poorer Verbal IQ in boys. However, exposure misclassification may be an issue as only one urine sample per woman was analysed. The present study contributes to the accumulating evidence linking exposure to organophosphate pesticides during fetal development with poorer cognitive function in children, bringing data on the risks in a context of low exposure levels encountered in primarily urban populations from Canada., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Studies report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Environmental chemicals may increase the risk of diabetes through impacts on glucose metabolism, mitochondrial dysfunction, and endocrine-disrupting mechanisms including effects on pancreatic β-cell function and adiponectin release., Objectives: To determine the associations between pesticides, perfluoroalkyl substances (PFASs) and polychlorinated biphenyls (PCBs) measured in early pregnancy and impaired glucose tolerance (IGT) and GDM in a Canadian birth cohort., Methods: Women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Exposure variables included three organophosphorus (OP) pesticide metabolites detected in first-trimester urine samples, as well as three organochlorine (OC) pesticides, three PFASs, and four PCBs in first-trimester blood samples. Gestational IGT and GDM were assessed by chart review in accordance with published guidelines. Adjusted logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for the association between quartiles of environmental chemicals and both gestational IGT and GDM., Results: Of the 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome and biomonitoring data available. Significantly lower odds of GDM were observed in the third and fourth quartiles of dimethylphosphate (DMP) and in the fourth quartile of dimethylthiophosphate (DMTP) in adjusted analyses (DMP Q3: OR=0.2, 95% CI=0.1-0.7; DMP Q4: OR=0.3, 95% CI=0.1-0.8; DMTP: OR=0.3, 95% CI=0.1-0.9). Significantly elevated odds of gestational IGT was observed in the second quartile of perfluorohexane sulfonate (PFHxS) (OR=3.5, 95% CI=1.4-8.9). No evidence of associations with GDM or IGT during pregnancy was observed for PCBs or OC pesticides., Conclusions: We did not find consistent evidence for any positive associations between the chemicals we examined and GDM or IGT during pregnancy. We observed statistical evidence of inverse relationships between urine concentrations of DMP and DMTP with GDM. We cannot rule out the influence of residual confounding due to unmeasured protective factors, such as nutritional benefits from fruit and vegetable consumption, also associated with pesticide exposure, on the observed inverse associations between maternal OP pesticide metabolites and GDM. These findings require further investigation., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The use of pesticides has enhanced the health and economies of nations around the world by improving crop production. However, pesticides may pose health risks, particularly to the fetus and young children. In a secondary analysis of the Ontario Farm Family Health Study, we explored the relationship between birth defects and parental pesticide exposure during the 3 months prior to conception and the first trimester of pregnancy. A total of 3412 pregnancies were included in the study. Logistic regression fit by maximum likelihood was used in the analysis. The results showed that pre-conception exposure to both cyanazine (odds ratio=4.99, 95% confidence interval: 1.63-15.27) and dicamba (OR=2.42, 95% CI: 1.06-5.53) were associated with increased risk of birth defects in male offspring. Nevertheless, given the self-reported nature of the exposure and outcomes in this study, the present findings should be considered primarily as hypothesis generating, requiring verification in subsequent investigations.

In humans, immune development begins early in embryonic life and continues throughout the early postnatal period. Although a number of pesticides have been observed to induce developmental immunotoxicity in mice, few human studies have examined the long term effects of in utero pesticide exposure on childhood morbidity. Empirical evidence suggests that the vulnerable period for toxic insults to the developing immune system extends from early gestation to adolescence in humans and animals. Using data from the Ontario Farm Family Health Study, we examined the relationship between farm couple exposures to pesticides during pregnancy and subsequent health outcomes in their offspring, including: persistent cough or bronchitis, asthma, and allergies or hayfever. No strong associations between pesticide exposures during pregnancy and persistent cough or bronchitis, or asthma were found. There was suggestive evidence that allergies and hayfever appeared to be more common in offspring, especially male offspring, exposed to certain specific pesticides during the period of pregnancy. Nevertheless, given the indirect indicators of pesticide exposure used in this study, and the scarcity of human studies on in utero exposure to pesticides and the development of allergies and other child health outcomes, these findings serve primarily to generate hypotheses for future research.

Background: Recent studies have suggested that agricultural occupations or exposure to pesticides may impair female fertility., Methods: The Fertility Risk Factor Study retrospectively examined agricultural and residential exposures and the risk of female infertility. Cases and controls (N = 322 each) came from women who sought treatment at a large group medical clinic in Wisconsin. Women and their male partners provided information on health, occupational and lifestyle exposures in response to a telephone interview during 1997-2001., Results: Mixing and applying herbicides 2 years before attempting conception was more common among infertile women (odds ratio [OR] = 27; 95% confidence interval [CI] = 1.9-380), as was the use of fungicides (OR = 3.3; CI = 0.8-13). Residing on a farm, ranch or in a rural area during this time period was protective of female fertility. Households supplied with central Wisconsin groundwater were at less risk for infertility than households using municipal sources (OR = 0.6; CI = 0.4-0.9). Behavioral risk factors included alcohol consumption (OR = 1.8; 1.2-2.5), smoking (1.6; 0.9-2.9), passive smoke exposure (1.8; 1.2-2.5), steady weight gain in adult life (3.5; 2.0-6.1), and having a male partner over the age of 40 (4.5; 1.2-16.3). Drinking 3 or more glasses of milk per day was protective of female fertility (0.3; 0.1-0.7)., Conclusion: These results suggest that certain agricultural, residential and lifestyle choices may modify the risk of female infertility.

Objectives: Most epidemiological studies of pesticides have used self-reports rather than quantitative measurements to assess exposures. The purpose of this study was to identify factors likely to affect exposure under actual field conditions and to measure the sensitivity and specificity of self-reported indications of exposure against urinary measures of herbicide exposure., Methods: A sub-set of the participants in a retrospective cohort study of Ontario farm families volunteered for a pesticide exposure assessment study. Immediately prior, and subsequent to, handling the phenoxy-herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) or 4-chloro-2-methylphenoxyacetic acid (MCPA) for the first time during the season, 126 pesticide applicators provided pre-exposure spot urine samples and a subsequent consecutive 24-h urine sample. At the same time, they completed a questionnaire on pesticide use and handling practices for the first day of pesticide application., Results: Assuming that the presence of 2,4-D in the urine was a measure of true exposure and that questionnaire indications of 2,4-D use were the exposure classification subject to error, then the questionnaire's prediction of exposure had a sensitivity of 56.7% and specificity of 86.4%. The comparable values for MCPA were sensitivity and specificity of 91.6% and 67.4%, respectively. In multivariate models, the variables pesticide formulation, protective clothing/gear, application equipment, handling practice, and personal hygiene practice were significant as predictors of urinary herbicide levels in the first 24 h after application (or spraying) had been initiated (adjusted R(2)=44% for MCPA and 39% for 2,4-D)., Conclusions: Although similar domains of factors were associated with exposure in both models, the specific factors identified and the signs of the coefficients were sufficiently different between the final models for each herbicide that additional investigations appear to be warranted to determine the sources of the differences and assess the validity of the models and their ability to be generalised.

Autism spectrum disorder, which is characterized by impaired social communication and stereotypic behaviors, affects 1%–2% of children. Although prenatal exposure to toxicants has been associated with autistic behaviors, most studies have been focused on shifts in mean behavior scores. We used Bayesian quantile regression to assess the associations between log2-transformed toxicant concentrations and autistic behaviors across the distribution of behaviors. We used data from the Maternal–Infant Research on Environmental Chemicals study, a pan-Canadian cohort (2008–2011). We measured metal, pesticide, polychlorinated biphenyl, phthalate, bisphenol-A, and triclosan concentrations in blood or urine samples collected during the first trimester of pregnancy. Using the Social Responsiveness Scale (SRS), in which higher scores denote more autistic-like behaviors, autistic behaviors were assessed in 478 children aged 3–4 years old. Lead, cadmium, and most phthalate metabolites were associated with mild increases in SRS scores at the 90th percentile of the SRS distribution. Manganese and some pesticides were associated with mild decreases in SRS scores at the 90th percentile of the SRS distribution. We identified several monotonic trends in which associations increased in magnitude from the bottom to the top of the SRS distribution. These results suggest that quantile regression can reveal nuanced relationships and, thus, should be more widely used by epidemiologists. [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]

Background: The fetal time period is a critical window of immune system development and resulting heightened susceptibility to the adverse effects of environmental exposures. Epidemiologists and toxicologists have hypothesized that persistent organic pollutants, pesticides and metals have immunotoxic properties. Immunotoxic effects may manifest as an altered immune system profile at birth. Immunoglobulin E, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) may be implicated in the etiology of childhood allergy and are detectable at birth. The objective of this study was to examine the potential relationship between maternal concentrations of metals, persistent organic pollutants, and pesticides and elevated umbilical cord blood concentrations of IgE, TSLP, and IL-33 in a Canadian birth cohort. Methods: This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2,001 pregnant women. Of these women, 1258 had a singleton, term birth and cord blood sample. Logistic regression was used to determine associations between log-transformed continuous variables and immune system biomarkers. Results: Inverse relationships were observed between lead, DDE, PCB-118, and a summary index of organophosphorous metabolites and jointly elevated concentrations of IL-33 and TSLP. None of the environmental contaminants were associated with increased odds of a high cord blood immune system biomarker concentration. Conclusions: In this primarily urban Canadian population of pregnant women and their newborns, maternal blood or urine concentrations of persistent organic pollutants, pesticides, and metals were not associated with immunotoxic effects that manifest as increased odds of elevated concentrations of IgE, TSLP or IL-33. [ABSTRACT FROM AUTHOR]

Women living and working on farms would be expected to have higher exposure to pesticides than the general nonoccupationally exposed population. Urinary concentrations of the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and (4-chloro-2-methyl) phenoxyacetic acid (MCPA) were measured in 125 women living on farms in Ontario where these herbicides had recently been used for the first time that growing season. The women collected a spot urine void prior to the start of herbicide handling by spouses, followed by 2 consecutive 24-h urine samples. The pesticide applicator provided questionnaire data on pesticides that were used on the farm. Approximately 80% of the women had no detectable level of either herbicide in their urine. Geometric mean urinary concentrations of 2,4-D and MCPA in the d-2 samples were 0.7 µg/L. The responses to the questions on herbicide use on the farm were compared with urinary levels of the herbicide and the sensitivity for MCPA was determined to be 95–100%; however, the false positive rate for exposure was 70%. For 2,4-D, the sensitivity and specificity were approximately 70%, with a false positive rate of 30%. A simple question on whether the herbicide was used recently can accurately identify people who are likely not exposed; however, further research is required to be able to more validly predict those individuals who are exposed. Based on our study, it was concluded that exposure estimates based on questionnaire data alone may be fraught with uncertainties, which may differ depending on the particular pesticide of interest. [ABSTRACT FROM AUTHOR]

Analyzes the effect of pesticide exposure on the risk of spontaneous abortion in a farm population in Ontario. Creation of pesticide unit variables; Risk factors of spontaneous abortion; Effects of pre-versus postconception exposure to pesticides on spontaneous abortion.