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Background: Phthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological limitations and potential effects of di-2-ethylhexyl phthalate (DEHP) replacements are poorly characterised. Attributable fractions and costs have not been quantified, limiting the ability to weigh trade-offs involved in ongoing use. We aimed to leverage a large, diverse US cohort to study associations of phthalate metabolites with birthweight and gestational age, and estimate attributable adverse birth outcomes and associated costs., Methods: In this prospective analysis we used extant data in the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program from 1998 to 2022 to study associations of 20 phthalate metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores. We also estimated attributable adverse birth outcomes and associated costs. Mother-child dyads were included in the study if there were one or more urinary phthalate measurements during the index pregnancy; data on child's gestational age and birthweight; and singleton delivery., Findings: We identified 5006 mother-child dyads from 13 cohorts in the ECHO Program. Phthalic acid, diisodecyl phthalate (DiDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP) were most strongly associated with gestational age, birth length, and birthweight, especially compared with DEHP or other metabolite groupings. Although DEHP was associated with preterm birth (odds ratio 1·45 [95% CI 1·05-2·01]), the risks per log 10 increase were higher for phthalic acid (2·71 [1·91-3·83]), DiNP (2·25 [1·67-3·00]), DiDP (1·69 [1·25-2·28]), and DnOP (2·90 [1·96-4·23]). We estimated 56 595 (sensitivity analyses 24 003-120 116) phthalate-attributable preterm birth cases in 2018 with associated costs of US$3·84 billion (sensitivity analysis 1·63- 8·14 billion)., Interpretation: In a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class., Funding: National Institutes of Health., Competing Interests: Declaration of interests LT acknowledges honoraria from Houghton Mifflin Harcourt, Audible, Paidos, and Kobunsha; travel support from the Endocrine Society, WHO, United Nations Environment Programme, Japan Environment and Health Ministries, and the American Academy of Pediatrics; and scientific advisory board activities for Beautycounter, IS-Global, and Footprint. MER acknowledges funding from the National Institute of General Medical Sciences, the National Institute of Environmental Health Sciences (NIEHS), and the New Hampshire Department of Environmental Services, as well as honoraria from the National Institutes of Health and UMass-Amherst, and advisory board relationships to the New England Graduate Women in Science and Engineering and Mill Run III Condo. AA acknowledges grant support from NIEHS. CN acknowledges the National Institute of Neurological Disorders and Stroke support. ESB acknowledges honoraria from the University of Rochester and SUNY-Downstate. All the authors have received funding from the NIH ECHO programme., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Synthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1-2 spot samples during pregnancy and limited diversity of populations., Objective: To study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program., Results: While many associations were modest and statistically imprecise, a 1-unit increase in log 10 pregnancy averaged concentration of benzophenone-3 and methylparaben were associated with decreases in birthweight, birthweight adjusted for gestational age and SGA. Increases in the odds of being SGA were 29% (95% CI: 5%, 58%) and 32% (95% CI: 3%, 70%), respectively. Bisphenol S in third trimester was also associated with SGA (OR 1.52, 95% CI 1.08, 2.13). Associations of benzophenone-3 and methylparaben with PTB and LBW were null. In addition, a 1-unit increase in log 10 pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: -67%, -2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: -53%, 8%)., Discussion: In a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In the United States, disparities in gestational age at birth by maternal race, ethnicity, and geography are theorized to be related, in part, to differences in individual- and neighborhood-level socioeconomic status (SES). Yet, few studies have examined their combined effects or whether associations vary by maternal race and ethnicity and United States Census region., Methods: We assembled data from 34 cohorts in the Environmental influences on Child Health Outcomes (ECHO) program representing 10,304 participants who delivered a liveborn, singleton infant from 2000 through 2019. We investigated the combined associations of maternal education level, neighborhood deprivation index (NDI), and Index of Concentration at the Extremes for racial residential segregation (ICE Race ) on gestational weeks at birth using linear regression and on gestational age at birth categories (preterm, early term, post-late term relative to full term) using multinomial logistic regression., Results: After adjustment for NDI and ICE Race , gestational weeks at birth was significantly lower among those with a high school diploma or less (-0.31 weeks, 95% CI: -0.44, -0.18), and some college (-0.30 weeks, 95% CI: -0.42, -0.18) relative to a master's degree or higher. Those with a high school diploma or less also had an increased odds of preterm (aOR 1.59, 95% CI: 1.20, 2.10) and early term birth (aOR 1.26, 95% CI: 1.05, 1.51). In adjusted models, NDI quartile and ICE Race quartile were not associated with gestational weeks at birth. However, higher NDI quartile (most deprived) associated with an increased odds of early term and late term birth, and lower ICE Race quartile (least racially privileged) associated with a decreased odds of late or post-term birth. When stratifying by region, gestational weeks at birth was lower among those with a high school education or less and some college only among those living in the Northeast or Midwest. When stratifying by race and ethnicity, gestational weeks at birth was lower among those with a high school education or less only for the non-Hispanic White category., Conclusion: In this study, maternal education was consistently associated with shorter duration of pregnancy and increased odds of preterm birth, including in models adjusted for NDI and ICE Race ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dunlop, Burjak, Dean, Alshawabkeh, Avalos, Aschner, Breton, Charifson, Cordero, Dabelea, D’Sa, Duarte, Elliott, Eick, Ferrara, Fichorova, Ganiban, Gern, Hedderson, Herbstman, Hipwell, Huddleston, Karagas, Karr, Kerver, Koinis-Mitchell, Lyall, Madan, Marsit, McEvoy, Meeker, Oken, O’Shea, Padula, Sathyanarayana, Schantz, Schmidt, Snowden, Stanford, Weiss, Wright, Wright, Zhang and McGrath.)

Phthalate use and the concentrations of their metabolites in humans vary by geographic region, race, ethnicity, sex, product use and other factors. Exposure during pregnancy may be associated with detrimental reproductive and developmental outcomes. No studies have evaluated the predictors of exposure to a wide range of phthalate metabolites in a large, diverse population. We examined the determinants of phthalate metabolites in a cohort of racially/ethnically diverse nulliparous pregnant women. We report on urinary metabolites of nine parent phthalates or replacement compounds-Butyl benzyl phthalate (BBzP), Diisobutyl phthalate (DiBP), Diethyl phthalate (DEP), Diisononyl phthalate (DiNP), D-n-octyl phthalate (DnOP), Di-2-ethylhexyl terephthalate (DEHTP), Di-n/i-butyl phthalate (DnBP), Di-isononyl phthalate (DiNP) and Di-(2-ethylhexyl) phthalate (DEHP) from urine collected up to three times from 953 women enrolled in the Nulliparous Mothers To Be Study. Phthalate metabolites were adjusted for specific gravity. Generalized estimating equations (GEEs) were used to identify the predictors of each metabolite. Overall predictors include age, race and ethnicity, education, BMI and clinical site of care. Women who were Non-Hispanic Black, Hispanic or Asian, obese or had lower levels of education had higher concentrations of selected metabolites. These findings indicate exposure patterns that require policies to reduce exposure in specific subgroups.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States., Objective: We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin., Study Design: This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F 2α , 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F 2α (F 2 -IsoP-M; the major 8-iso-prostaglandin-F 2α metabolite), and prostaglandin-F 2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models., Results: Approximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F 2 -IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F 2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis., Conclusion: Here, oxidative stress, as measured by 8-iso-prostaglandin-F 2α , F 2 -IsoP-M, and prostaglandin-F 2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Melamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects., Objectives: We aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics., Methods: We measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008-2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection., Results: Twelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4'-methylenedianiline, and a composite of o-toluidine and m-toluidine (99-100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4'-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: -11; 95% CI: -19, -1) or time of day, seasonal, and geographic variability., Discussion: Exposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Lower socioeconomic status (SES) and elevated psychosocial stress are known contributors to adverse pregnancy outcomes; however, biological mechanisms linking these factors to adverse pregnancy outcomes are not well-characterized. Oxidative stress may be an important, yet understudied mechanistic pathway. We used a pooled study design to examine biological, behavioral, and social factors as predictors of prenatal oxidative stress biomarkers., Methods: Leveraging four pregnancy cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program spanning multiple geographic regions across the United States (U.S.) (N = 2082), we measured biomarkers of oxidative stress in urine samples at up to three time points during pregnancy, including 8-isoprostane-prostaglandin F 2α (8-isoPGF 2α ), its major metabolite, 2,3-dinor-5,6-dihydro-15-F 2t -isoprostane, and prostaglandin F 2α (PGF 2α ). Maternal age, pre-pregnancy body mass index, marital/partnered status, parity, and smoking status were included as biological and behavioral factors while race/ethnicity, maternal education, and stressful life events were considered social factors. We examined associations between each individual biological, behavioral, and social factor with oxidative stress biomarkers using multivariable-adjusted linear mixed models., Results: Numerous biological, behavioral, and social factors were associated with elevated levels of 8-isoPGF 2α , its major metabolite, and PGF 2α . Pregnant people who were current smokers relative to non-smokers or had less than a high school education relative to a college degree had 11.04% (95% confidence interval [CI] = -1.97%, 25.77%) and 9.13% (95% CI = -1.02%, 20.32%) higher levels of 8-isoPGF 2α , respectively., Conclusions: Oxidative stress biomarkers are elevated among pregnant people with higher socioeconomic disadvantage and may represent one pathway linking biological, behavioral, and social factors to adverse pregnancy and child health outcomes, which should be explored in future work., 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 © 2022 Elsevier B.V. All rights reserved.)

Prenatal chemical exposures can influence maternal and child health; however, few industrial chemicals are routinely biomonitored. We assessed an extensive panel of contemporary and emerging chemicals in 171 pregnant women across the United States (U.S.) and Puerto Rico in the Environmental influences on Child Health Outcomes (ECHO) Program. We simultaneously measured urinary concentrations of 89 analytes (103 total chemicals representing 73 parent compounds) in nine chemical groups: bactericides, benzophenones, bisphenols, fungicides and herbicides, insecticides, organophosphate esters (OPEs), parabens, phthalates/alternative plasticizers, and polycyclic aromatic hydrocarbons (PAHs). We estimated associations of creatinine-adjusted concentrations with sociodemographic and specimen characteristics. Among our diverse prenatal population (60% non-Hispanic Black or Hispanic), we detected 73 of 89 analytes in ≥1 participant and 36 in >50% of participants. Five analytes not currently included in the U.S. biomonitoring were detected in ≥90% of samples: benzophenone-1, thiamethoxam, mono-2-(propyl-6-carboxy-hexyl) phthalate, monocarboxy isooctyl phthalate, and monohydroxy-iso-decyl phthalate. Many analyte concentrations were higher among women of Hispanic ethnicity compared to those of non-Hispanic White women. Concentrations of certain chemicals decreased with the calendar year, whereas concentrations of their replacements increased. Our largest study to date identified widespread exposures to prevalent and understudied chemicals in a diverse sample of pregnant women in the U.S.

Following a 2019 workshop led by the Center for Global Health Studies at the Fogarty International Center on the topic of childhood obesity prevention and research synergies transpiring from cross-border collaborations, we convened a group of experts in the United States and Latin America to conduct a narrative review of the epidemiological literature on the role of obesogenic endocrine disrupting chemicals (EDCs) in the etiology of childhood obesity among Latino youth in the United States and Latin America. In addition to summarizing and synthesizing results from research on this topic published within the last decade, we place the findings within a lifecourse biobehavioral framework to aid in identification of unique exposure-outcome relationships driven by both biological and behavioral research, identify inconsistencies and deficiencies in current literature, and discuss the role of policy regulations, all with the goal of identifying viable avenues for prevention of early life obesity in Latino/Hispanic populations., (© 2021 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Exposure to organophosphate (OP) insecticides may alter reproductive hormone levels in men and increase the risk for poor reductive health and other adverse health outcomes. However, relevant epidemiology studies in men are limited. We evaluated urinary concentrations of OP metabolites (3,5,6-trichloro-2-pyridinol and six dialkyl phosphates) in relation to serum concentrations of testosterone (T) and estradiol among 356 men aged 20-55 years old from the U.S. National Health and Nutrition Examination Survey. Biomarkers were detected in greater than 50% of the samples, except for diethyldithiophosphate, dimethylphosphate, and dimethyldithiophosphate. In adjusted regression models, we observed a statistically significant inverse relationship between diethyl phosphate (DEP) and T when DEP was modeled as either a continuous or categorical variable. These findings add to the limited evidence that exposure to certain OP insecticides is linked to altered T in men, which may have important implications for male health., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To examine the potential associations between biomarkers of metal exposure and serum testosterone in men of reproductive age in the general US population., Design: Cross-sectional epidemiology study with adjustment for potential confounders., Setting: Not applicable., Patient(s): Men recruited in the United States National Health and Nutrition Examination Survey (NHANES)., Intervention(s): Metal concentrations measured in whole blood, urine, and/or serum samples collected from 484 men., Main Outcome Measure(s): Serum T concentration., Result(s): Concentrations of the metals were detected in 69%-100% of the samples. In adjusted analyses where metals were modeled as a continuous variable, we found significant inverse associations between urinary molybdenum and serum copper and serum T, whereas there were significant positive associations between blood lead and cadmium and serum T. When metals were categorized into quartiles, analyses for serum copper and blood lead and cadmium produced significant associations in the same direction as the continuous measures. A suggestive inverse association was observed between quartiles of urinary molybdenum and serum T, but the association was statistically significant when molybdenum was categorized into quintiles. Significant positive associations were also observed for quartiles of blood Se and serum Zn and serum T., Conclusion(s): These findings add to the limited human evidence that exposure to molybdenum and other metals is associated with altered T in men, which may have important implications for male health. More research is needed to confirm the findings of our study., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Context: There is evidence of declining trends in T levels among men in recent decades, as well as trends in related conditions at multiple life stages and in both sexes. There is also animal and limited human evidence that exposure to phthalates, chemicals found in plastics and personal care products, is associated with reduced androgen levels and associated disorders., Objective: To explore relationships between urinary concentrations of 13 phthalate metabolites and serum total T levels among men, women, and children when adjusting for important confounders and stratifying by sex and age (6-12, 12-20, 20-40, 40-60, and 60-80 y)., Design: A cross-sectional study., Setting: US National Health and Nutrition Examination Survey, 2011-2012., Patients or Other Participants: US general population., Interventions: None., Main Outcome Measures: Serum total T measured by isotope dilution-liquid chromatography-tandem mass spectrometry., Results: Multiple phthalates were associated with significantly reduced T in both sexes and in differing age groups. In females, the strongest and most consistent inverse relationships were found among women ages 40-60 years. In boys 6-12 years old, an interquartile range increase in metabolites of di-2-ethylhexyl phthalate was associated with a 29% (95% confidence interval, 6, 47) reduction in T. In adult men, the only significant or suggestive inverse associations between phthalates (metabolites of di-2-ethylhexyl phthalate and dibutyl phthalate) and T were observed among men ages 40-60 years., Conclusions: Because T plays an important role in all life stages for both sexes, future efforts should focus on better defining these relationships and their broader impacts.

Background: Cadmium (Cd), a widespread environmental contaminant, and iron deficiency (ID), the most common nutrient deficiency in the world, are known risk factors for neurodevelopmental delays, as well as other disorders, in infants and children. Studies assessing the cumulative effects of these factors are lacking in children, despite concerns of increased uptake of metals in the presence of ID. Here we sought to determine if blood and urine Cd levels were elevated in ID children compared to non-ID children., Methods: Data for 5224 children, aged 3-19 years, were obtained from the 1999-2002 NHANES. ID was defined as ≥2 of 3 abnormal iron indicators (low serum ferritin [SF], high free erythrocyte protoporphyrin [FEP], low % transferrin saturation [TSAT]); ID anemia (IDA) was defined as ID plus low hemoglobin (Hgb). Logistic regression was used to evaluate associations between ID, IDA, and abnormal iron indicators and categories of blood and urine Cd., Results: Adjusted odds of ID, IDA, low SF, and low TSAT were associated with increasing category of blood Cd but not urine Cd. Adjusted ORs (95% CI) for blood Cd ≥0.5 μg/L versus < LOD were = 1.74 (1.30-2.34), 4.02 (1.92-8.41), 4.08 (2.36-5.89) and 1.78 (1.32-2.39), for ID, IDA, low SF, and low TSAT, respectively. Age and sex specific analyses of blood Cd and ID/abnormal iron indicators revealed that the observed associations were strongest in females aged 16-19 years., Conclusions: Given their shared neurotoxic effects in children, and that many people live in areas with high burdens of both ID and Cd, more research into the complex relationships between nutrient deficiencies and environmental toxicants is vital.

Objective: To evaluate the relationship between urinary bisphenol A (BPA) levels and measures of adiposity and chronic disease risk factors for a nationally representative US pediatric sample., Methods: We used the NHANES 2003-2010 to evaluate cross-sectional associations between urinary BPA and multiple measures of adiposity, cholesterol, insulin, and glucose for children aged 6 to 18 years, adjusting for relevant covariates (eg, demographics, urine creatinine, tobacco exposure, and soda consumption)., Results: We found a higher odds of obesity (BMI ≥95th percentile) with increasing quartiles of BPA for quartiles 2 vs 1 (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.17-2.60, P = .008), 3 vs 1 (OR 1.64, 95% CI 1.09-2.47, P = .02), and 4 vs 1 (OR 2.01, 95% CI 1.36-2.98, P = .001). We also found a higher odds of having an abnormal waist circumference-to-height ratio (quartiles 2 vs 1 [OR 1.37, 95% CI 0.98-1.93, P = .07], 3 vs 1 [OR 1.41, 95% CI 1.07-1.87, P = .02], and 4 vs 1 [OR 1.55, 95% CI 1.12-2.15, P = .01]). We did not find significant associations of BPA with any other chronic disease risk factors., Conclusions: Higher levels of urinary BPA were associated with a higher odds of obesity (BMI >95%) and abnormal waist circumference-to-height ratio. Longitudinal analyses are needed to elucidate temporal relationships between BPA exposure and the development of obesity and chronic disease risk factors in children.

Triclosan and parabens are broad spectrum antimicrobials used in a range of consumer products. In vitro and animal studies have suggested the potential for these compounds to disrupt thyroid function, though studies in humans have been limited. The objective of the study was to assess the relationship of urinary concentrations of triclosan and parabens with serum thyroid measures in a large, representative sample of the US population. We conducted an exploratory, cross-sectional analysis of data on urinary biomarkers of triclosan and paraben exposure and serum thyroid measures obtained from 1831 subjects (ages≥12 years) as part of the 2007-2008 National Health and Nutrition Examination Survey (NHANES). We found evidence of some inverse associations between parabens and circulating thyroid hormone levels in adults, with the strongest and most consistent associations among females. We also observed a positive association between triclosan and total triiodothyonine (T3) concentrations in adolescents. These results, in accordance with the in vitro and animal literature, suggest that paraben, and potentially triclosan, exposures may be associated with altered thyroid hormone levels in humans. Further research is needed for confirmation and to determine the potential clinical and public health significance of these findings., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Exposure to exogenous chemicals can affect endocrine function at multiple sites and through numerous specific modes of action, which may have far-reaching effects on human health and development. Widespread human exposure to known or suspected endocrine disrupting chemicals (EDCs) has been documented in the United States and worldwide, as have trends for increased rates of endocrine-related diseases and disorders among children. While human epidemiology studies of exposure to EDCs and children's health remain extremely limited, a growing body of evidence shows that exposure to a number of chemicals commonly found in consumer goods, personal care products, food, drinking water, and other sources may adversely affect child development through altered endocrine function. This narrative review provides a brief introduction to several common EDCs (with a specific focus on persistent organic pollutants, phthalates, bisphenol A, and contemporary-use pesticides, which represent only a small number of all known or suspected EDCs), an overview of the state of the human evidence for adverse effects of EDCs on child development (fetal growth, early reproductive tract development, pubertal development, neurodevelopment, and obesity), guidance for health care providers based on current knowledge, and recommendations for future research.

Background: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women., Objective: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study., Methods: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001-2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment-estimated insulin resistance, and glycosylated hemoglobin A1c., Results: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance., Discussion: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.

Thyroid hormones are vital to a host of human physiological functions in both children and adults. Exposures to chemicals, including chlorpyrifos, have been found to modify thyroid signaling at environmentally relevant levels in animal studies. The aim of this study was to examine circulating T4 and TSH levels in relation to urinary concentrations of 3, 5, 6-trichloro-2-pyridinol (TCPY), a metabolite of the organophosphorus insecticides chlorpyrifos and chlorpyrifos-methyl, using data from individuals 12 years and older from the U.S. National Health and Nutrition Examination Surveys (NHANES). NHANES datasets from 1999 to 2000 and 2001-2002 were combined, and individuals with thyroid disease, those taking thyroid medications, and pregnant women were excluded (N = 3249). Multivariable linear regression models for relationships between log-transformed urinary TCPY and serum total T(4) or log (TSH) were constructed adjusting for important covariates. Models were stratified by sex and a categorical age variable (12-18, 18-40, 40-60, and >60 years). In male participants, an interquartile range (IQR) increase in urinary TCPY was associated with statistically significant increases in serum T(4) of 3.8% (95th CI 0.75 to 7.0) among those 12-18 years of age and 3.5% (95th CI 0.13 to 7.0) in the 18-40 year age group, relative to median T4 levels using unweighted models. An IQR increase in TCPY was also associated with decreases in TSH of 10.7% (-18.7-2.05) among men 18-40 years old and 20.0% (95th CI -28.9 to -9.86) among men >60 years old. Conversely, urinary TCPY was positively associated with TSH in females >60 years of age. Further research to confirm these findings, elucidate mechanisms of action, and explore the clinical and public health significance of such alterations in thyroid hormones is needed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Phthalate esters are a class of compounds utilized extensively in widely-distributed consumer goods, and have been associated with various adverse health outcomes in previous epidemiologic research. Some of these health outcomes may be the result of phthalate-induced increases in oxidative stress or inflammation, which have been demonstrated in animal studies. The aim of this study was to explore the relationship between urinary phthalate metabolite concentrations and serum markers of inflammation and oxidative stress (C-reactive protein (CRP) and gamma glutamyltransferase (GGT), respectively). Subjects were participants in the National Health and Nutrition Examination Survey (NHANES) between the years 1999 and 2006. In multivariable linear regression models, we observed significant positive associations between CRP and mono-benzyl phthalate (MBzP) and mono-isobutyl phthalate (MiBP). There were CRP elevations of 6.0% (95% confidence interval (CI) 1.7-10.8%) and 8.3% (95% CI 2.9-14.0%) in relation to interquartile range (IQR) increases in urinary MBzP and MiBP, respectively. GGT was positively associated with mono(2-ethylhexyl) phthalate (MEHP) and an MEHP% variable calculated from the proportion of MEHP in comparison to other di(2-ethylhexyl) phthalate (DEHP) metabolites. IQR increases in MEHP and MEHP% were associated with 2.5% (95% CI 0.2-4.8%) and 3.7% (95% CI 1.7-5.7%) increases in GGT, respectively. CRP and GGT were also inversely related to several phthalate metabolites, primarily oxidized metabolites. In conclusion, several phthalate monoester metabolites that are detected in a high proportion of urine samples from the US general population are associated with increased serum markers of inflammation and oxidative stress. On the other hand, several oxidized phthalate metabolites were inversely associated with these markers. These relationships deserve further exploration in both experimental and observational studies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Epidemiologic studies of pesticides have been subject to important biases arising from exposure misclassification. Although turf applicators are exposed to a variety of pesticides, these exposures have not been well characterized. This paper describes a repeated measures study of 135 TruGreen applicators over three spraying seasons via the collection of 1028 urine samples. These applicators were employed in six cities across the United States. Twenty-four-hour estimates (μg) were calculated for the parent compounds 2,4-D, MCPA, mecoprop, dicamba, and imidacloprid and for the insecticide metabolites MPA and 6-CNA. Descriptive statistics were used to characterize the urinary levels of these pesticides, whereas mixed models were applied to describe the variance apportionment with respect to city, season, individual, and day of sampling. The contributions to the overall variance explained by each of these factors varied considerably by the type of pesticide. The implications for characterizing exposures in these workers within the context of a cohort study are discussed.

Restrictions on the use of polybrominated diphenyl ethers (PBDEs) have resulted in the increased use of alternate flame retardant chemicals to meet flammability standards. However, it has been difficult to determine which chemical formulations are currently being used in high volumes to meet flammability standards since the use of flame retardant formulations in consumer products is not transparent (i.e., not provided to customers). To investigate chemicals being used as replacements for PentaBDE in polyurethane foam, we analyzed foam samples from 26 different pieces of furniture purchased in the United States primarily between 2003 and 2009. Samples included foam from couches, chairs, mattress pads, pillows, and, in one case, foam from a sound-proofing system of a laboratory-grade dust sieve, and were analyzed using gas chromatography mass spectrometry. Fifteen of the foam samples contained the flame retardanttris(1,3-dichloro-2-propyl) phosphate (TDCPP; 1-5% by weight), four samples contained tris(1-chloro-2-propyl) phosphate (TCPP; 0.5 -22% by weight), one sample contained brominated chemicals found in a new flame retardant mixture called Firemaster 550 (4.2% by weight), and one foam sample collected from a futon likely purchased prior to 2004 contained PentaBDE (0.5% by weight). Due to the high frequency of detection of the chlorinated phosphate compounds in furniture foam,we analyzed extracts from 50 house dust samples collected between 2002 and 2007 in the Boston, MA area for TDCPP, TCPP, and another high volume use organophosphate-based flame retardant used in foam, triphenylphosphate (TPP). Detection frequencies for TDCPP and TPP in the dust samples were > 96% and were log normally distributed, similar to observations for PBDEs. TCPP was positively detected in dust in only 24% of the samples, but detection was significantly limited by a coelution problem. The geometric mean concentrations for TCPP, TDCPP, and TPP in house dust were 570, 1890, and 7360 ng/g, respectively, and maximum values detected in dust were 5490, 56,080 and 1,798,000 ng/g, respectively. These data suggest that levels of these organophosphate flame retardants are comparable, or in some cases greater than, levels of PBDEs in house dust. The high prevalence of these chemicals in foam and the high concentrations measured in dust (as high as 1.8 mg/g) warrant further studies to evaluate potential health effects from dust exposure, particularly for children.

An investigation of 24 buildings in the Greater Boston Area revealed that one-third (8 of 24) contained caulking materials with polychlorinated biphenyl (PCB) content exceeding 50 ppm by weight, which is the U.S. Environmental Protection Agency (U.S. EPA) specified limit above which this material is considered to be PCB bulk product waste. These buildings included schools and other public buildings. In a university building where similar levels of PCB were found in caulking material, PCB levels in indoor air ranged from 111 to 393 ng/m3; and in dust taken from the building ventilation system, < 1 ppm to 81 ppm. In this building, the U.S. EPA mandated requirements for the removal and disposal of the PCB bulk product waste as well as for confirmatory sampling to ensure that the interior and exterior of the building were decontaminated. Although U.S. EPA regulations under the Toxic Substances Control Act stipulate procedures by which PCB-contaminated materials must be handled and disposed, the regulations apparently do not require that materials such as caulking be tested to determine its PCB content. This limited investigation strongly suggests that were this testing done, many buildings would be found to contain high levels of PCBs in the building materials and potentially in the building environment. The presence of PCBs in schools is of particular concern given evidence suggesting that PCBs are developmental toxins.