Children's Health Exposure Research Articles

Urinary biomarkers of environmental exposures and asthma morbidity in a school inner city asthma study

BackgroundThe burden of pediatric asthma and other allergic diseases is not evenly distributed among United States populations. ObjectiveTo determine whether urinary biomarkers are associated with asthma morbidity, and if associations vary by child race, ethnicity and sex. MethodsThis study includes n = 152 children with physician-diagnosed asthma who participated in the School Inner-City Asthma Intervention Study (SICAS-2). Metabolites of phenol, paraben, polycyclic aromatic hydrocarbons, and phthalate analytes were analyzed from urine samples collected at baseline. Asthma symptom days over the past 2 weeks were dichotomized to no asthma symptom days or any asthma symptom days. Cross-sectional regression models were adjusted for age, sex, number of colds, household income, prescription control, race and ethnicity, body mass index (BMI) percentile, and smoke exposure. Weighted quantile sum regression was used to analyze each chemical class and a total mixture effect, controlling for the same covariates. Analyses were conducted with the assistance of the National Institute of Environmental Health Sciences Children's Health Exposure Analysis Resource (CHEAR). ResultsParticipants were mostly Hispanic/Latino and low income with an average age of 7.83 years and the average maximum asthma symptom days over the past two weeks of 2.13 (standard deviation: 3.56). The maximum concentrations indicate extreme values for several chemicals, including bisphenol-3, 2,5-dichlorophenol, propyl and methyl parabens, triclosan, methyl paraben and cotinine. We found a significant interaction effect and differing contributions of analytes for children with allergen sensitivity versus those that did not. For stratified analyses assessing effect modification by child race and ethnicity, weighted quantile sum interaction models showed reduced odds of asthma symptoms to a greater magnitude in children of other races and ethnicities compared to Black, Non-Hispanic children. ConclusionsPreliminary analyses of the association between environmental chemical exposure and asthma symptoms among inner-city children revealed an inverse association, which may be due to personal care and medication use and can be understood further in future analyses. Beneficial effects were detected for most of the chemicals.

A cross-validation based approach for estimating specific gravity in elementary-school aged children using a nonlinear model

Environmental research often relies on urinary biomarkers which require dilution correction to accurately measure exposures. Specific gravity (SG) and creatinine (UCr) are commonly measured urinary dilution factors. Epidemiologic studies may assess only one of these measures, making it difficult to pool studies that may otherwise be able to be combined.Participants from the National Health and Nutrition Examination Survey 2007–2008 cycle were used to perform k-fold validation of a nonlinear model estimating SG from UCr. The final estimated model was applied to participants from the School Inner-City Asthma Intervention Study, who submitted urinary samples to the Children's Health Exposure Analysis Resource. Model performance was evaluated using calibration metrics to determine how closely the average estimated SG was to the measured SG. Additional models, with interaction terms for age, sex, body mass index, race/ethnicity, relative time of day when sample was collected, log transformed 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and asthma status were estimated and assessed for improvement. The association between monobenzyl phthalate (MBZP) and asthma symptom days, controlling for measured UCr, measured SG, and each estimated SG were compared to assess validity of the estimated SG.The model estimating SG from UCr alone, resulted in a beta estimate of 1.10 (95% CI: 1.01, 1.19), indicating agreement between model-predicted SG and measured SG. Inclusion of age and sex in the model improved estimation (β = 1.06, 95% CI: 0.98, 1.15). The full model accounting for all interaction terms with UCr resulted in the best agreement (β = 1.01, 95% CI: 0.93,1.09). Associations between MBZP and asthma symptoms days, controlling for each estimated SG, were within the range of effect estimates when controlling for measured SG and measured UCr (Rate ratios = 1.28–1.34). Our nonlinear modeling provides opportunities to estimate SG in studies that measure UCr or vice versa, enabling data pooling despite differences in urine dilution factors.

Quality assurance and harmonization for targeted biomonitoring measurements of environmental organic chemicals across the Children's Health Exposure Analysis Resource laboratory network.

A consortium of laboratories established under the Children's Health Exposure Analysis Resource (CHEAR) used a multifaceted quality assurance program to promote measurement harmonization for trace organics analyses of human biospecimens that included: (1) participation in external quality assurance (EQA)/proficiency testing (PT) programs; (2) analyses of a urine-based CHEAR common quality control (QC) pool with each analytical batch across all participating laboratories; (3) method validation against NIST Standard Reference Materials® (SRMs); and (4) analyses of blinded duplicates and other project-specific QC samples. The capability of five CHEAR laboratories in organic chemical analysis increased across the 4-year period, and performance in the external PT program improved over time - recent challenges reporting >90% analytes with satisfactory performance. The CHEAR QC pools were analyzed for several classes of organic chemicals including phthalate metabolites and environmental phenols by the participating laboratories with every batch of project samples, which provided a rich source of measurement data for the assessment of intra- and inter-laboratory variance. Within-laboratory and overall variabilities in measurements across laboratories were calculated for target chemicals in urine QC pools; the coefficient of variation (CV) was generally below 25% across batches, studies and laboratories and indicated acceptable analytical imprecision. The suite of organic chemicals analyzed in the CHEAR QC pool was broader than those reported for commercially available reference materials. The accuracy of each of the laboratories' methods was verified through the analysis of several NIST SRMs and was, for example, 97±5.2% for environmental phenols and 95±11% for phthalates. Analysis of blinded duplicate samples showed excellent agreement and reliability of measurements. The intra-class correlation coefficients (ICC) for phthalate metabolites analyzed in various batches across three CHEAR laboratories showed excellent reliability (typically >0.90). Overall, the multifaceted quality assurance protocols followed among the CHEAR laboratories ensured reliable and reproducible data quality for several classes of organic chemicals. Increased participation in external PT programs through inclusion of additional target analytes will further enhance the confidence in data quality.

Maternal, neonatal and socio-economic factors associated with intellectual development among children from a coal mining region in Brazil.

Coal is the most aggressive energy sources in the environment. Several adverse outcomes on children's health exposure to coal pollutants have been reported. Pollutants from coal power plants adversely affect the intellectual development and capacity. The present study aimed to evaluate the intellectual development and associated factors among children living a city under the direct influence (DI) and six neighboring municipalities under the indirect influence (II) of coal mining activity in the largest coal reserve of Brazil. A structured questionnaire was completed by the child's guardian, and Raven's Progressive Color Matrices were administered to each child to assess intellectual development. A total of 778 children participated. In general, no significant difference was observed between the two cities. The DI city had better socioeconomic conditions than the II municipalities according to family income (< 0.001). The prevalence of children who were intellectually below average or with intellectual disabilities was 22.9%, and there was no significant difference (p > 0.05) between municipalities. In both unadjusted and adjusted analyses, intellectual development was associated with maternal age, marital situation and maternal education level, birth weight, breast feeding, frequent children's daycare, paternal participation in children's care and child growth. Living in the DI area was not associated with intellectual disability. The results suggest that socioeconomic conditions and maternal and neonatal outcomes are more important than environmental factors for intellectual development of children living in a coal mining area.

Measurement harmonization and traceability for trace element analyses across the Children's Health Exposure Analysis Resource laboratory network

Harmonization and traceability are related metrological principles that are indispensable to assuring measurement comparability across different biomonitoring studies. The Children's Health Exposure Analysis Resource (CHEAR) was established in 2015 with six laboratories providing environmental exposure measurements on biospecimens. To ensure harmonization across studies for trace elements, CHEAR used a multi-faceted approach that included: 1) an initial interlaboratory validation exercise based on the analysis of certified blood and urine reference materials; 2) frequent participation in an established interlaboratory proficiency program for trace elements; and 3) analysis of a common pool of well-characterized biological reference materials with each analytical batch. Method accuracy and precision were established for each laboratory via analysis of NIST SRM 955c Toxic Elements in Caprine Blood, SRM 2668 Toxic Elements in Frozen Human Urine and SRM 3668 Mercury, Perchlorate, and Iodide in Frozen Human Urine. The differences among the six laboratories for As, Cd, Hg, and Mn in urine and Cd, Hg, and Pb in whole blood were judged to be fit-for-purpose. Interlaboratory performance over a 5-year period demonstrated an improvement in performance, such that for 2018–2019, >99% of challenges for urine As, Cd, Hg, and Mn, and 95% for whole blood Cd, Hg, Pb, and Mn, were found to be satisfactory. The CHEAR common reference materials were analyzed by at least 5 laboratories for 22 elements in urine and 13–14 elements in whole blood, thus providing a rich source of data to assess intra- and inter-run performance. The suite of trace elements with assigned values in both blood and urine matrices are more comprehensive than similar reference materials from other sources, and is reflective of the concentrations necessary to support biomonitoring studies. While some areas for future improvement were identified, significant progress was made to improve harmonization of trace element measurements in biological matrices among the CHEAR network labs.

Prenatal Dietary Intake and Blood Metal Concentrations During the 1st Trimester of Pregnancy in Project Viva

Abstract Objectives To identify foods associated with blood metal concentrations during the 1st trimester of pregnancy. Methods In early pregnancy (11.3 ± 2.8 gestational week), 1206 women from Project Viva completed food frequency questionnaire and provided a blood sample to measure essential and non-essential metals. This analysis included 135 food items and 14 metals (As, Cd, Hg, Pb, Co, Cu, Mg, Mn, Se, Zn, Ba, Cs, Sb, Sn) in red blood cells (RBC). We perform a diet-wide association study (DWAS) of all bivariate relationships between each food-metal combination. Additionally, we used machine learning models with elastic-net regularization to estimate the % variation in metal concentrations explained by diet. Results Mean (standard deviation [SD]) age was 32.5 (4.5) years and pre-pregnancy BMI was 24.8 (5.4) kg/m2. Most participants were white (76.0%), not current smokers (88.5%), completed a college degree (75.5%), and had a household income &amp;gt;$70 K/year (66.8%). Compared to other US-based cohorts, the overall diet quality of participants was higher, and levels of toxic metals were lower. DWAS identified significant associations between several food items with As, Hg, Pb, Cs and Se; among the positives associations, for example, each SD increase in fresh fruit, white rice, and seafood was associated with 4%, 8%, and 18% higher median concentrations of As, respectively; and fresh fruits (12%), eggs (12%), white rice (15%), green vegetables (17%), and seafood (64%) was associated with Hg. Elastic net models identified significant positive and negative dietary predictors of As, Cs, and Hg, but not other metals. The % variation explained by the selected dietary variables was 21% for As, 7% for Cs, and 11% for Hg. Conclusions DWAS provides systematic evaluation of diet-metal relationship and can uncover potential dietary sources of prenatal metal exposure. In this population, we found positive associations between fruit, green vegetable, white rice and seafood consumption with As and Hg. Prenatal diet may be an important source of metals exposures, including As, Hg, and Cs. Funding Sources This work was supported by the US National Institutes of Health grants R01HD034568, UH3OD023286, U2CES026561and U2CES026555, and metal analysis was conducted by the Children's Health Exposure Analysis Resource (CHEAR award #2017–1740).

Quantitative methods for metabolomic analyses evaluated in the Children's Health Exposure Analysis Resource (CHEAR).

With advances in technologies that facilitate metabolome-wide analyses, the incorporation of metabolomics in the pursuit of biomarkers of exposure and effect is rapidly evolving in population health studies. However, many analytic approaches are limited in their capacity to address high-dimensional metabolomics data within an epidemiologic framework, including the highly collinear nature of the metabolites and consideration of confounding variables. In this Children’s Health Exposure Analysis Resource (CHEAR) network study, we showcase various analytic approaches that are established as well as novel in the field of metabolomics, including univariate single metabolite models, least absolute shrinkage and selection operator (LASSO), random forest, weighted quantile sum (WQSRS) regression, exploratory factor analysis (EFA) and latent class analysis (LCA). Here, in a Bangladeshi birth cohort (n=199), we illustrate research questions that can be addressed by each analytic method in the assessment of associations between cord blood metabolites (1H NMR measurements) and birth anthropometric measurements (birth weight and head circumference).

First trimester maternal exposures to endocrine disrupting chemicals and metals and fetal size in the Michigan Mother-Infant Pairs study.

Exposures to endocrine disrupting chemicals and metals are near ubiquitous worldwide, and their potential impact on children is a major public health concern. This pilot study was designed to characterize exposures to phthalates, phenols and metals among pregnant women in the first trimester, and to examine associations with fetal biometrics and birth weight. A total of 41 chemicals and elements were analyzed in urine from 56 mothers with full-term newborns from the Michigan Mother-Infant Pairs study. Bivariate analyses identified predictors of exposure biomarkers. Associations between birth weight, Fenton z-scores and second trimester fetal biometrics with toxicants were examined via multivariable linear regression. An average of 30 toxicants were detected in maternal urine. Fast food consumption was associated with several phthalate metabolites, phenols and metals, and canned food consumption with bisphenol F (P &lt;0.05). Mono (3-carboxypropyl) phthalate was significantly associated with higher birth weight and Fenton z-score while the opposite was observed for bisphenol S. Estimated femur length from ultrasonography was significantly inversely associated with arsenic, barium and lead. While limited by sample size, this study is one of the first to evaluate birth outcomes with respect to emerging endocrine disrupting chemicals and to examine associations between toxicants and fetal biometrics. Exposure assessment was provided by the National Institute of Environmental Health Sciences' Children's Health Exposure Analysis Resource (NIEHS CHEAR), a resource available to children's studies with the goal of combining data across cohorts in an effort to characterize the impact of toxicants on child health from birth and beyond.

The child health exposure analysis resource as a vehicle to measure environment in the environmental influences on child health outcomes program.

Demonstrate the role of environment as a predictor of child health. The children's health exposure analysis resource (CHEAR) assists the Environmental influences on child health outcomes (ECHO) program in understanding the time sensitive and dynamic nature of perinatal and childhood environment on developmental trajectories by providing a central infrastructure for the analysis of biological samples from the ECHO cohort awards. CHEAR will assist ECHO cohorts in defining the critical or sensitive period for effects associated with environmental exposures. Effective incorporation of these principles into multiple existing cohorts requires extensive multidisciplinary expertise, creativity, and flexibility. The pursuit of life course - informed research within the CHEAR/ECHO structure represents a shift in focus from single exposure inquiries to one that addresses multiple environmental risk factors linked through shared vulnerabilities. CHEAR provides ECHO both targeted analyses of inorganic and organic toxicants, nutrients, and social-stress markers and untargeted analyses to assess the exposome and discovery of exposure-outcome relationships. Utilization of CHEAR as a single site for characterization of environmental exposures within the ECHO cohorts will not only support the investigation of the influence of environment on children's health but also support the harmonization of data across the disparate cohorts that comprise ECHO.

The Children's Health Exposure Analysis Resource: enabling research into the environmental influences on children's health outcomes

The Children's Health Exposure Analysis Resource (CHEAR) is a new infrastructure supported by the National Institute of Environmental Health Sciences to expand the ability of children's health researchers to include analysis of environmental exposures in their research and to incorporate the emerging concept of the exposome. There is extensive discussion of the potential of the exposome to advance understanding of the totality of environmental influences on human health. Children's health is a logical choice to demonstrate the exposome concept due to the extensive existing knowledge of individual environmental exposures affecting normal health and development and the short latency between exposures and observable phenotypes. Achieving this demonstration will require access to extensive analytical capabilities to measure a suite of exposures through traditional biomonitoring approaches and to cross-validate these with emerging exposomic approaches. CHEAR is a full-service exposure assessment resource, linking up-front consultation with both laboratory and data analysis. Analyses of biological samples are intended to enhance studies by including targeted analysis of specific exposures and untargeted analysis of small molecules associated with phenotypic endpoints. Services provided by CHEAR are made available without cost but require a brief application and adherence to policies detailed on the CHEAR web page at https://chearprogram.org/.

Tobacco, e-cigarettes, and child health.

The availability of the Children's Health Exposure Assessment Resource funded by the National Institute of Environmental Health Sciences provides new opportunities for exploring the role of tobacco smoke exposure in causing harm to children. Children of smokers are exposed to nicotine and other harmful tobacco smoke chemicals in utero as well as in their environment. This passive exposure to tobacco smoke has a variety of negative effects on children. In-utero exposure to tobacco smoke causes poor birth outcomes and influences lung, cardiovascular, and brain development, placing children at increased risk of a number of adverse health outcomes later in life, such as obesity, behavioral problems, and cardiovascular disease. Furthermore, most smokers start in their adolescence, an age of increased nicotine addiction risk. Biomarkers of tobacco exposure helps clarify the role tobacco chemicals play in influencing health both in childhood and beyond. Although electronic cigarettes (e-cigarettes) appear to be a nicotine delivery device of reduced harm, it appears to be a gateway to the use of combustible cigarette smoking in adolescents. Pediatric researchers interested in elucidating the role of tobacco smoke exposure in adverse outcomes in children should incorporate biomarkers of tobacco exposure in their studies.

The Children's Health Exposure Analysis Resource

The Children's Health Exposure Analysis Resource