Feasibility and Informative Value of Environmental Sample Collection in the National Children\u27s Vanguard Study

Background: Birth cohort studies provide the opportunity to advance understanding of the impact of environmental factors on childhood health and development through prospective collection of environmental samples. Methods: We evaluated the feasibility and informative value of the environmental sample collection methodology in the initial pilot phase of the National Children\u27s Study, a planned U.S. environmental birth cohort study. Environmental samples were collected from January 2009–September 2010 at up to three home visits: pre-pregnancy (n¼306), pregnancy (n¼807), and 6-months postnatal (n¼117). Collections included air for particulate matter r2.5 mm (PM2.5), nitrogen dioxide, ozone, volatile organic compounds (VOCs), and carbonyls; vacuum dust for allergens/endotoxin; water for VOCs, trihalomethanes (THMs), and haloacetic acids (HAAs); and wipe samples for pesticides, semi-volatile organics, and metals. We characterized feasibility using sample collection rates and times and informative value using analyte detection frequencies (DF). Results: Among the 1230 home visits, environmental sample collection rates were high across all sample types (mean¼89%); all samples except the air PM2.5 samples had collection times o30 min. Informative value was low for water VOCs (median DF¼0%) and pesticide floor wipes (median DF¼5%). Informative value was moderate for air samples (median DF¼35%) and high for water THMs and HAAs (median DF¼91% and 75%, respectively). Conclusions: Though collection of environmental samples was feasible, some samples (e.g., wipe pesticides and water VOCs) yielded limited information. These results can be used in conjunction with other study design considerations, such as target population size and hypotheses of interest, to inform the method selection of future environmental health birth cohort studies

Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Facial Features at 5 Years of Age:A Study from the Danish National Birth Cohort

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widespread persistent pollutants. Evidence regarding neurodevelopmental effects of PFAS have been mixed. The relation between PFAS exposure and anatomical markers that have been suggested to correlate with fetal brain development have not been studied. OBJECTIVES: We investigated the association between prenatal PFAS exposures and three craniofacial features in children measured at 5 years of age. METHODS: Measures of palpebral fissure length (PFL), philtrum groove, and upper-lip thickness were generated from standardized digital facial photographs from 656 children in the Danish National Birth Cohort. PFL was classified into two groups (shorter; normal), and the philtrum (grooved; smooth; normal) and upper-lip (thick; thin; normal) measures into three groups each. Six PFAS were measured in maternal plasma ([Formula: see text] gestational wk). Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for each facial feature using the normal group as the reference according to [Formula: see text] concentration (in nanograms per milliliter) or PFAS tertiles, adjusting for potential confounders, including maternal alcohol intake and smoking. Stratified analyses by maternal alcohol intake or child’s sex were performed. RESULTS: Prenatal exposure to each PFAS was associated with elevated odds for a shorter PFL, with the strongest association observed for perfluorodecanoic acid (PFDA; per doubling [Formula: see text]; 95% CI: 1.11, 3.70). Some nonlinear associations were found for philtrum measures: the second tertile of PFDA and perfluorononanoic acid were associated with grooved philtrum, whereas the second tertile of perfluoroheptane sulfonate with smooth philtrum. The associations between PFAS exposure and a shorter PFL were stronger among mothers who consumed alcohol in the first trimester, some sex-specific associations were noted for philtrum and upper-lip measures. DISCUSSION: Prenatal PFAS exposures might influence fetal craniofacial development. A larger study is needed to replicate the potential modifying effects observed for alcohol exposure and to clarify whether associations of craniofacial markers observed reflect specific neurologic deficits. https://doi.org/10.1289/EHP947

Normalizing untargeted periconceptional urinary metabolomics data : a comparison of approaches

Metabolomics studies of the early-life exposome often use maternal urine specimens to investigate critical developmental windows, including the periconceptional period and early pregnancy. During these windows changes in kidney function can impact urine concentration. This makes accounting for differential urinary dilution across samples challenging. Because there is no consensus on the ideal normalization approach for urinary metabolomics data, this study’s objective was to determine the optimal post-analytical normalization approach for untargeted metabolomics analysis from a periconceptional cohort of 45 women. Urine samples consisted of 90 paired pre- and post-implantation samples. After untargeted mass spectrometry-based metabolomics analysis, we systematically compared the performance of three common approaches to adjust for urinary dilution—creatinine adjustment, specific gravity adjustment, and probabilistic quotient normalization (PQN)—using unsupervised principal components analysis, relative standard deviation (RSD) of pooled quality control samples, and orthogonal partial least-squares discriminant analysis (OPLS-DA). Results showed that creatinine adjustment is not a reliable approach to normalize urinary periconceptional metabolomics data. Either specific gravity or PQN are more reliable methods to adjust for urinary concentration, with tighter quality control sample clustering, lower RSD, and better OPLS-DA performance compared to creatinine adjustment. These findings have implications for metabolomics analyses on urine samples taken around the time of conception and in contexts where kidney function may be altered

Urinary paraben concentrations and associations with the periconceptional urinary metabolome : untargeted and targeted metabolomics analyses of participants from the early pregnancy study

BACKGROUND: Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. OBJECTIVES: This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility. METHODS: Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data. RESULTS: Seven metabolites were associated with paraben concentration (variable importance to projection score formula presented , false discovery rate-corrected formula presented ). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations. DISCUSSION: This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment

Associations between self-reported pest treatments and pesticide concentrations in carpet dust

BACKGROUND: Recent meta-analyses demonstrate an association between self-reported residential pesticide use and childhood leukemia risk. Self-reports may suffer from recall bias and provide information only on broad pesticide categories. We compared parental self-reported home and garden pest treatments to pesticides measured in carpet dust. METHODS: Parents of 277 children with leukemia and 306 controls in Northern and Central California (2001–2007) were asked about insect and weed treatments during the previous year. Carpet dust samples were analyzed for 47 pesticides. We present results for the 7 insecticides (carbaryl, propoxur, chlorpyrifos, diazinon, cyfluthrin, cypermethrin, permethrin), 5 herbicides (2,4-dichlorophenoxyacetic acid [2,4-D], chlorthal, dicamba, mecoprop, simazine), and 1 synergist (piperonyl butoxide) that were present in home and garden products during the study period and were detected in ≥25% of carpet dust samples. We constructed linear regression models for the relative change in pesticide concentrations associated with self-reported treatment of pest types in cases and controls separately and combined, adjusting for demographics, housing characteristics, and nearby agricultural pesticide applications. RESULTS: Several self-reported treatments were associated with pesticide concentrations in dust. For example, households with flea/tick treatments had 2.3 (95% Confidence Interval [CI]: 1.4, 3.7) times higher permethrin concentrations than households not reporting this treatment. Households reporting treatment for ants/cockroaches had 2.5 (95% CI: 1.5, 4.2) times higher cypermethrin levels than households not reporting this treatment. Weed treatment by a household member was associated with 1.9 (1.4, 2.6), 2.2 (1.6, 3.1), and 2.8 (2.1, 3.7) times higher dust concentrations of dicamba, mecoprop, and 2,4-D, respectively. Weed treatments by professional applicators were null/inversely associated with herbicide concentrations in dust. Associations were generally similar between cases and controls and were consistent with pesticide active ingredients in these products during the study time period. CONCLUSIONS: Consistency between self-reported pest treatments, concentrations in dust, and pesticides in products lends credibility to the exposure assessment methods and suggests that differential recall by case–control status is minimal. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-015-0015-x) contains supplementary material, which is available to authorized users

Phthalate Exposure from Drinking Water in Romanian Adolescents

Phthalates are plastic softeners that have been linked to several adverse health outcomes. The relative contributions of different sources to phthalate exposure in populations in different regions and at different life stages is unclear. We examined the relationships between water consumption, consumer product use, and phthalate exposure among 40 adolescents (20 males, 20 females) in Cluj-Napoca, Romania. Interviewers administered a questionnaire about drinking water consumption and use of phthalate-containing consumer products. Four common phthalates were measured in representative samples of participants’ municipal drinking water and consumed bottled water using gas chromatography-mass spectrometry. Urine samples were collected from participants and analyzed for the corresponding phthalate metabolites. Relationships between different exposure measures were assessed using nonparametric tests (Spearman rank correlation coefficients and the Kruskal–Wallis test). Diisobutyl phthalate, dibutyl phthalate, and bis(2-ethylhexyl) phthalate were commonly detected in bottled water, but generally not the municipal drinking water samples. Mono-n-butyl phthalate (MnBP) was the most commonly detected urinary metabolite (detected in 92.5% of participants) and had the highest maximum concentration (1139.77 µg/g creatinine). We did not identify any statistically significant associations between water consumption or consumer product use practices and urinary phthalate metabolite concentrations in our adolescent group, and directions of correlation coefficients differed by individual phthalate compound. While phthalate exposure was widespread, these results highlight the challenges in examining phthalate exposure determinants and emphasize the need for further investigation into understanding exposure sources and potential health risks from chronic low-level exposures

A case-control study of exposure to organophosphate flame retardants and risk of thyroid cancer in women

Abstract Background Growing evidence demonstrates that exposure to organophosphate flame retardants (PFRs) is widespread and that these chemicals can alter thyroid hormone regulation and function. We investigated the relationship between PFR exposure and thyroid cancer and whether individual or temporal factors predict PFR exposure. Methods We analyzed interview data and spot urine samples collected in 2010–2013 from 100 incident female, papillary thyroid cancer cases and 100 female controls of a Connecticut-based thyroid cancer case-control study. We measured urinary concentrations of six PFR metabolites with mass spectrometry. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) for continuous and categories (low, medium, high) of concentrations of individual and summed metabolites, adjusting for potential confounders. We examined relationships between concentrations of PFR metabolites and individual characteristics (age, smoking status, alcohol consumption, body mass index [BMI], income, education) and temporal factors (season, year) using multiple linear regression analysis. Results No PFRs were significantly associated with papillary thyroid cancer risk. Results remained null when stratified by microcarcinomas (tumor diameter ≤ 1 cm) and larger tumor sizes (> 1 cm). We observed higher urinary PFR concentrations with increasing BMI and in the summer season. Conclusions Urinary PFR concentrations, measured at time of diagnosis, are not linked to increased risk of thyroid cancer. Investigations in a larger population or with repeated pre-diagnosis urinary biomarker measurements would provide additional insights into the relationship between PFR exposure and thyroid cancer risk

Le Dilettantisme, essai de psychologie, de morale et d'esthétique / Claude Saulnier,...

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