The role of exposure to per- and polyfluoroalkyl substances in racial/ethnic disparities in hypertension: Results from the study of Women's health across the nation.

BACKGROUND: Racial/ethnic disparities in hypertension are a pressing public health problem. The contribution of environmental pollutants including PFAS have not been explored, even though certain PFAS are higher in Black population and have been associated with hypertension. OBJECTIVES: We examined the extent to which racial/ethnic disparities in incident hypertension are explained by racial/ethnic differences in serum PFAS concentrations. METHODS: We included 1058 hypertension-free midlife women with serum PFAS concentrations in 1999-2000 from the multi-racial/ethnic Study of Women's Health Across the Nation with approximately annual follow-up visits through 2017. Causal mediation analysis was conducted using accelerated failure time models. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures. RESULTS: During 11,722 person-years of follow-up, 470 participants developed incident hypertension (40.1 cases per 1000 person-years). Black participants had higher risks of developing hypertension (relative survival: 0.58, 95% CI: 0.45-0.76) compared with White participants, which suggests racial/ethnic disparities in the timing of hypertension onset. The percent of this difference in timing that was mediated by PFAS was 8.2% (95% CI: 0.7-15.3) for PFOS, 6.9% (95% CI: 0.2-13.8) for EtFOSAA, 12.7% (95% CI: 1.4-22.6) for MeFOSAA, and 19.1% (95% CI: 4.2, 29.0) for PFAS mixtures. The percentage of the disparities in hypertension between Black versus White women that could have been eliminated if everyone's PFAS concentrations were dropped to the 10th percentiles observed in this population was 10.2% (95% CI: 0.9-18.6) for PFOS, 7.5% (95% CI: 0.2-14.9) for EtFOSAA, and 17.5% (95% CI: 2.1-29.8) for MeFOSAA. CONCLUSIONS: These findings suggest differences in PFAS exposure may be an unrecognized modifiable risk factor that partially accounts for racial/ethnic disparities in timing of hypertension onset among midlife women. The study calls for public policies aimed at reducing PFAS exposures that could contribute to reductions in racial/ethnic disparities in hypertension.

Non-essential and essential trace element mixtures and kidney function in early pregnancy - A cross-sectional analysis in project viva.

Some trace elements are established nephrotoxicants, yet their associations with kidney function remain understudied in the context of pregnancy, a time of substantial change in kidney physiology and function. We aimed to estimate the individual and joint associations of trace element mixtures with maternal kidney function during the 1st trimester of pregnancy (mean 9.7 gestational weeks). 1040 women from Project Viva contributed blood samples which were assessed for erythrocyte non-essential [arsenic (As), cadmium (Cd), cesium (Cs), mercury (Hg), lead (Pb)] and essential [barium (Ba), magnesium (Mg), manganese (Mn), selenium (Se), and Zinc (Zn)] trace elements, and plasma creatinine for kidney function. We estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration (eGFRCKD-EPI) equation without race-adjustment factors. We examined associations of eGFRCKD-EPI with individual trace elements using multivariable linear regression and their mixtures using quantile-based g-computation, adjusting for sociodemographics, pregnancy characteristics, and diet. Participants in our study were predominantly White (75%), college graduates (72%), and had household income >$70,000/year (63%). After adjusting for covariates, higher Pb (ß -3.51 ml/min/1.73 m2; 95% CI -5.83, -1.18) concentrations were associated with lower eGFRCKD-EPI, while higher Mg (ß 10.53 ml/min/1.73 m2; 95% CI 5.35, 15.71), Se (ß 5.56 ml/min/1.73 m2; 95% CI 0.82, 10.31), and Zn (ß 5.88 ml/min/1.73 m2; 95% CI 0.51, 11.26) concentrations were associated with higher eGFRCKD-EPI. In mixture analyses, higher non-essential trace elements mixture concentration was associated with reduced eGFRCKD-EPI (Ψ -1.03 ml/min/1.73 m2; 95% CI: 1.92, -0.14). Conversely, higher essential trace elements mixture concentration was associated with higher eGFR (Ψ 1.42; 95% CI: 0.48, 2.37). Exposure to trace elements in early pregnancy may influence women's kidney function although reverse causation cannot be eliminated in this cross-sectional analysis. These findings have important implications for long-term cardiovascular and postpartum kidney health that warrant additional studies.

Development of a multidimensional housing and environmental quality index (HEQI): application to the American Housing Survey.

BACKGROUND: Substandard housing conditions and hazardous indoor environmental exposures contribute to significant morbidity and mortality worldwide. Housing indices that capture the multiple dimensions of healthy housing are important for tracking conditions and identifying vulnerable households. However, most indices focus on physical deficiencies and repair costs and omit indoor environmental exposures, as few national data sources routinely collect this information. METHODS: We developed a multidimensional Housing and Environmental Quality Index (HEQI) based on the World Health Organization's Housing and Health Guidelines and applied it to the 2019 American Housing Survey (AHS). The HEQI consisted of ten domains associated with poor health: household fuel combustion, dampness and mold, pests and allergens, lead paint risk, high indoor temperatures, low indoor temperatures, household crowding, injury hazards, inadequate water and sanitation, and ventilation. We evaluated the validity and performance of the HEQI against three housing characteristics (i.e., year built, monthly rent costs, unit satisfaction rating) and two established indices (i.e., Adequacy Index, Poor Quality Index). RESULTS: Approximately 79% (92 million) of U.S. households reported at least one HEQI domain associated with poor health (mean per household: 1.3; range: 0,8). Prevalent domains included household fuel combustion (61.4%), dampness and mold (15.9%), inadequate water and sanitation (14.3%), and injury hazards (11.9%). Pests and allergens, low indoor temperatures, and injury hazards were consistently associated with older homes, lower rent costs, and lower unit satisfaction. Compared to established housing indices, the HEQI captured four new environmental domains which enabled the identification of 57.7 million (63%) more households with environmental risk factors like mold, cockroaches, crowding, household fuel combustion, and higher building leakage. CONCLUSIONS: Indoor environmental exposures are prevalent in U.S. households and not well-captured by existing housing indices. The HEQI is a multidimensional tool that can be used to monitor indoor environmental exposures and housing quality trends in the U.S. Some domains, including radon, pesticides, asbestos, noise, and housing accessibility could not be assessed due to the lack of available data in the AHS. The mounting evidence linking residential environmental exposures with adverse health outcomes underscore the need for this data in the AHS and other national surveys.

Integrating Intersectionality Into the Exposome Paradigm: A Novel Approach to Racial Inequities in Uterine Fibroids.

Intersectionality is a critical theoretical framework that emphasizes the influence of intersecting systems of oppression on the lived experiences of people marginalized by inequity. Although applications of intersectionality are increasing in public health, this framework is absent in environmental health, which has instead focused on the exposome, a paradigm that considers the totality of an individual's environmental exposures across the life course.Despite advancements in the biological complexity of exposome models, they continue to fall short in addressing health inequities. Therefore, we highlight the need for integrating intersectionality into the exposome. We introduce key concepts and tools for environmental health scientists interested in operationalizing intersectionality in exposome studies and discuss examples of this innovative approach from our work on racial inequities in uterine fibroids.Our case studies illustrate how interlocking systems of racism and sexism may affect Black women's exposure to environmental chemicals, their epigenetic regulation of uterine fibroids, and their clinical care. Because health relies on biological and social-structural determinants and varies across different intersectional positions, our proposed framework may be a promising approach for understanding environmental health inequities and furthering social justice.

Neurotoxicity of Ortho-Phthalates: Recommendations for Critical Policy Reforms to Protect Brain Development in Children.

Robust data from longitudinal birth cohort studies and experimental studies of perinatally exposed animals indicate that exposure to ortho-phthalates can impair brain development and increase risks for learning, attention, and behavioral disorders in childhood. This growing body of evidence, along with known adverse effects on male reproductive tract development, calls for immediate action.Exposures are ubiquitous; the majority of people are exposed to multiple ortho-phthalates simultaneously. We thus recommend that a class approach be used in assessing health impacts as has been done with other chemical classes. We propose critically needed policy reforms to eliminate ortho-phthalates from products that lead to exposure of pregnant women, women of reproductive age, infants, and children. Specific attention should be focused on reducing exposures among socially vulnerable populations such as communities of color, who frequently experience higher exposures.Ortho-phthalates are used in a vast array of products and elimination will thus necessitate a multipronged regulatory approach at federal and state levels. The fact that manufacturers and retailers have already voluntarily removed ortho-phthalates from a wide range of products indicates that this goal is feasible.

Persistent organic pollutants and maternal glycemic outcomes in a diverse pregnancy cohort of overweight women.

BACKGROUND: Animal and human studies suggest certain persistent organic pollutants (POPs) may impact glucose metabolism; however, few epidemiologic studies have examined environmental determinants of glycemic outcomes during pregnancy. Our objective is to evaluate associations between exposures to individual and mixture of POPs and measures of prenatal fasting glucose, insulin, and insulin resistance during pregnancy in overweight women. METHODS: A cohort of overweight and obese pregnant women (N = 95) was recruited from California. Blood samples were collected during late first or second trimester (median = 16 weeks' gestation; range = 10-24 weeks). Exposures included serum concentrations of polybrominated diphenyl ethers (PBDEs) and hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs). Outcomes included serum concentrations of fasting plasma glucose, fasting plasma insulin, and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Generalized linear models were used to evaluate cross-sectional associations between individual and aggregate POPs and mean percent difference in fasting glucose, fasting insulin, and HOMA-IR. Bayesian kernel machine regression (BKMR) was used to assess the relative importance of each exposure to the association with our outcomes, using conditional and group posterior inclusion probabilities (PIPs). RESULTS: Study participants were racially/ethnically diverse and nearly half were below the federal poverty level. Across PBDEs and OH-PBDEs, the direction of associations with fasting glucose, fasting insulin and HOMA-IR were varied. A doubling of PCB-138, PCB-153, PCB-180, and ∑PCBs concentrations was associated with a 2.10% mmol/L (95%CI: 0.49%, 3.74%), 2.10% mmol/L (95%CI: -0.14%, 4.39%), 2.10% mmol/L (95%CI: 0.12%, 4.12%), and 2.81% mmol/L (95%CI: 0.38%, 5.31%) increase in fasting glucose, respectively. Exposure to individual PCBs was positively associated with both fasting insulin and HOMA-IR. All PFAS were inversely associated with fasting glucose, fasting insulin, and HOMA-IR. In BKMR models of fasting glucose, all four chemical classes were important contributors to the overall mixture, with PFASs identified as the most important contributor. DISCUSSION: Prenatal PCB exposure was positively associated while certain PBDE and PFAS analytes were inversely associated with fasting glucose concentrations in overweight women. Further examination of the relationship between POPs exposure and glycemic functioning in a larger study population of women during pregnancy is warranted.

An overview of methods to address distinct research questions on environmental mixtures: an application to persistent organic pollutants and leukocyte telomere length.

BACKGROUND: Numerous methods exist to analyze complex environmental mixtures in health studies. As an illustration of the different uses of mixture methods, we employed methods geared toward distinct research questions concerning persistent organic chemicals (POPs) as a mixture and leukocyte telomere length (LTL) as an outcome. METHODS: With information on 18 POPs and LTL among 1,003 U.S. adults (NHANES, 2001-2002), we used unsupervised methods including clustering to identify profiles of similarly exposed participants, and Principal Component Analysis (PCA) and Exploratory Factor Analysis (EFA) to identify common exposure patterns. We also employed supervised learning techniques, including penalized, weighted quantile sum (WQS), and Bayesian kernel machine (BKMR) regressions, to identify potentially toxic agents, and characterize nonlinear associations, interactions, and the overall mixture effect. RESULTS: Clustering separated participants into high, medium, and low POP exposure groups; longer log-LTL was found among those with high exposure. The first PCA component represented overall POP exposure and was positively associated with log-LTL. Two EFA factors, one representing furans and the other PCBs 126 and 118, were positively associated with log-LTL. Penalized regression methods selected three congeners in common (PCB 126, PCB 118, and furan 2,3,4,7,8-pncdf) as potentially toxic agents. WQS found a positive overall effect of the POP mixture and identified six POPs as potentially toxic agents (furans 1,2,3,4,6,7,8-hxcdf, 2,3,4,7,8-pncdf, and 1,2,3,6,7,8-hxcdf, and PCBs 99, 126, 169). BKMR found a positive linear association with furan 2,3,4,7,8-pncdf, suggestive evidence of linear associations with PCBs 126 and 169, and a positive overall effect of the mixture, but no interactions among congeners. CONCLUSIONS: Using different methods, we identified patterns of POP exposure, potentially toxic agents, the absence of interaction, and estimated the overall mixture effect. These applications and results may serve as a guide for mixture method selection based on specific research questions.

Serum Folate, Vitamin B-12, Vitamin A, γ-Tocopherol, α-Tocopherol, and Carotenoids Do Not Modify Associations between Cadmium Exposure and Leukocyte Telomere Length in the General US Adult Population.

Background: Leukocyte telomere length (LTL) is a biomarker of the aging process and is associated with the risk of chronic disease. Higher exposure to cadmium may be associated with shorter LTL, and adequate nutrient concentrations may be associated with longer LTL; however, the potential interaction between metals and nutrients on LTL has yet to be examined.Objectives: The objective of this study was to evaluate whether serum concentrations of vitamins and carotenoids were associated with LTL, and whether they modified the association between blood cadmium and LTL in the US NHANES (1999-2002).Methods: We evaluated cross-sectional associations between LTL and serum concentrations of vitamin A, γ-tocopherol, α-tocopherol, folate, and vitamin B-12 (1999-2002; n = 7458) and α-carotene, ß-carotene, ß-cryptoxanthin, lutein + zeaxanthin, and lycopene (2001-2002; n = 4018) in a nationally representative sample of US adults (≥20 y of age) with the use of multivariable linear regression. We further investigated whether vitamin and carotenoid concentrations modified associations between blood cadmium and LTL with models stratified by serum nutrient concentrations and the inclusion of an interaction term.Results: Blood cadmium was inversely associated with LTL (percentage of LTL difference per 1 µg/L = -3.74; 95% CI: -5.35, -2.10). Serum vitamin A was positively associated (percentage of LTL difference per 1 µg/L = 4.01; 95% CI: 0.26, 7.90) and γ-tocopherol was inversely associated (percentage of LTL difference per 1 µg/dL = -2.49; 95% CI: -4.21, -0.73) with LTL. Serum folate (P-trend = 0.06) and α-tocopherol (P-trend = 0.10) were marginally positively associated with LTL, whereas vitamin B-12 (P-trend = 0.78) was not associated with LTL. Serum carotenoids were generally positively associated with LTL. Serum vitamin and carotenoid concentrations did not modify blood cadmium and LTL associations (P-interaction > 0.10).Conclusions: Results from this cross-sectional study suggest that exposure to cadmium and certain nutrients may be associated with LTL in US adults, but the serum concentrations of the vitamins and carotenoids evaluated did not modify cross-sectional associations between cadmium exposure and LTL.

The environmental injustice of beauty: framing chemical exposures from beauty products as a health disparities concern.

The obstetrics-gynecology community has issued a call to action to prevent toxic environmental chemical exposures and their threats to healthy human reproduction. Recent committee opinions recognize that vulnerable and underserved women may be impacted disproportionately by environmental chemical exposures and recommend that reproductive health professionals champion policies that secure environmental justice. Beauty product use is an understudied source of environmental chemical exposures. Beauty products can include reproductive and developmental toxicants such as phthalates and heavy metals; however, disclosure requirements are limited and inconsistent. Compared with white women, women of color have higher levels of beauty product-related environmental chemicals in their bodies, independent of socioeconomic status. Even small exposures to toxic chemicals during critical periods of development (such as pregnancy) can trigger adverse health consequences (such as impacts on fertility and pregnancy, neurodevelopment, and cancer). In this commentary, we seek to highlight the connections between environmental justice and beauty product-related chemical exposures. We describe racial/ethnic differences in beauty product use (such as skin lighteners, hair straighteners, and feminine hygiene products) and the potential chemical exposures and health risks that are associated with these products. We also discuss how targeted advertising can take advantage of mainstream beauty norms to influence the use of these products. Reproductive health professionals can use this information to advance environmental justice by being prepared to counsel patients who have questions about toxic environmental exposures from beauty care products and other sources. Researchers and healthcare providers can also promote health-protective policies such as improved ingredient testing and disclosure for the beauty product industry. Future clinical and public health research should consider beauty product use as a factor that may shape health inequities in women's reproductive health across the life course.

Leukocyte Telomere Length in Relation to 17 Biomarkers of Cardiovascular Disease Risk: A Cross-Sectional Study of US Adults.

BACKGROUND: Leukocyte telomere length (LTL) is a putative biological marker of immune system age, and there are demonstrated associations between LTL and cardiovascular disease. This may be due in part to the relationship of LTL with other biomarkers associated with cardiovascular disease risk. However, the strength of associations between LTL and adiposity, metabolic, proinflammatory, and cardiovascular biomarkers has not been systematically evaluated in a United States nationally representative population. METHODS AND FINDINGS: We examined associations between LTL and 17 cardiovascular biomarkers, including lipoproteins, blood sugar, circulatory pressure, proinflammatory markers, kidney function, and adiposity measures, in adults ages 20 to 84 from the cross-sectional US nationally representative 1999-2002 National Health and Nutrition Examination Survey (NHANES) (n = 7,252), statistically adjusting for immune cell type distributions. We also examine whether these associations differed systematically by age, race/ethnicity, gender, education, and income. We found that a one unit difference in the following biomarkers were associated with kilobase pair differences in LTL: BMI -0.00478 (95% CI -0.00749--0.00206), waist circumference -0.00211 (95% CI -0.00325--0.000969), percentage of body fat -0.00516 (95% CI -0.00761--0.0027), high density lipoprotein (HDL) cholesterol 0.00179 (95% CI 0.000571-0.00301), triglycerides -0.000285 (95% CI -0.000555--0.0000158), pulse rate -0.00194 (95% CI -0.00317--0.000705), C-reactive protein -0.0363 (95% CI 0.0601--0.0124), cystatin C -0.0391 (95% CI -0.0772--0.00107). When using clinical cut-points we additionally found associations between LTL and insulin resistance -0.0412 (95% CI -0.0685--0.0139), systolic blood pressure 0.0455 (95% CI 0.00137-0.0897), and diastolic blood pressure -0.0674 (95% CI -0.126--0.00889). These associations were 10%-15% greater without controlling for leukocyte cell types. There were very few differences in the associations by age, race/ethnicity, gender, education, or income. Our findings are relevant to the relationships between these cardiovascular biomarkers in the general population but not to cardiovascular disease as a clinical outcome. CONCLUSIONS: LTL is most strongly associated with adiposity, but is also associated with biomarkers across several physiological systems. LTL may thus be a predictor of cardiovascular disease through its association with multiple risk factors that are physiologically correlated with risk for development of cardiovascular disease. Our results are consistent with LTL being a biomarker of cardiovascular aging through established physiological mechanisms.

A Novel Method for Calculating Potency-Weighted Cumulative Phthalates Exposure with Implications for Identifying Racial/Ethnic Disparities among U.S. Reproductive-Aged Women in NHANES 2001-2012.

Phthalates are ubiquitous chemicals linked to hormonal disruptions that affect reproduction and development. Multiple antiandrogenic phthalates exposure during fetal development can have greater impacts than individual exposure; thus, the National Academy of Sciences (NAS) recommends them for cumulative assessment. Using National Health and Nutrition Examination Survey data (NHANES, 2001-2012), we developed a potency-weighted sum of daily intake (∑androgen-disruptor; µg/kg/day) of di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), butyl benzyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP) based on NAS recommendations, and included diethyl phthalate (DEP) and diisononyl phthalate (DiNP) in additional metrics (2005-2012). We compared racial/ethnic differences in ∑androgen-disruptor among 2842 reproductive-aged women. In sensitivity analyses, we assessed the influence of potency assumptions, alternate urine dilution adjustment methods, and weighting phthalate metabolites directly rather than daily intake estimates of parent compounds. We found that DEHP contributed most to ∑androgen-disruptor (48-64%), and that ∑androgen-disruptor decreased over time. Black women generally had higher cumulative exposures than white women, although the magnitude and precision of the difference varied by model specification. Our approach provides a blueprint for combining chemical exposures linked to common adverse outcomes, and should be considered in future exposure, risk, and epidemiological studies.

Consumer Product Chemicals in Indoor Dust: A Quantitative Meta-analysis of U.S. Studies.

Indoor dust is a reservoir for commercial consumer product chemicals, including many compounds with known or suspected health effects. However, most dust exposure studies measure few chemicals in small samples. We systematically searched the U.S. indoor dust literature on phthalates, replacement flame retardants (RFRs), perfluoroalkyl substances (PFASs), synthetic fragrances, and environmental phenols and estimated pooled geometric means (GMs) and 95% confidence intervals for 45 chemicals measured in ≥3 data sets. In order to rank and contextualize these results, we used the pooled GMs to calculate residential intake from dust ingestion, inhalation, and dermal uptake from air, and then identified hazard traits from the Safer Consumer Products Candidate Chemical List. Our results indicate that U.S. indoor dust consistently contains chemicals from multiple classes. Phthalates occurred in the highest concentrations, followed by phenols, RFRs, fragrance, and PFASs. Several phthalates and RFRs had the highest residential intakes. We also found that many chemicals in dust share hazard traits such as reproductive and endocrine toxicity. We offer recommendations to maximize comparability of studies and advance indoor exposure science. This information is critical in shaping future exposure and health studies, especially related to cumulative exposures, and in providing evidence for intervention development and public policy.

Direct measurement of Bisphenol A (BPA), BPA glucuronide and BPA sulfate in a diverse and low-income population of pregnant women reveals high exposure, with potential implications for previous exposure estimates: a cross-sectional study.

BACKGROUND: Bisphenol A (BPA) is a ubiquitous, endocrine-disrupting environmental contaminant that increases risk of some adverse developmental effects. Thus, it is important to characterize BPA levels, metabolic fate and sources of exposure in pregnant women. METHODS: We used an improved liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytic method to directly and simultaneously measure unconjugated BPA (uBPA), BPA glucuronide and BPA sulfate in the urine of a population of ethnically and racially diverse, and predominately low-income pregnant women (n = 112) in their second trimester. We also administered a questionnaire on dietary and non-dietary sources of exposure to BPA. RESULTS: We found universal and high exposure to uBPA and its metabolites: median concentrations were 0.25, 4.67, and 0.31 µg/g creatinine for uBPA, BPA glucuronide, and BPA sulfate, respectively. The median Total BPA (uBPA + BPA in glucuronide and sulfate forms) level was more than twice that measured in U.S. pregnant women in NHANES 2005-2006, while 30 % of the women had Total BPA levels above the 95th percentile. On average, Total BPA consisted of 71 % BPA in glucuronide form, 15 % BPA in sulfate form and 14 % uBPA, however the proportion of BPA in sulfate form increased and the proportion of uBPA decreased with Total BPA levels. Occupational and non-occupational contact with paper receipts was positively associated with BPA in conjugated (glucuronidated + sulfated) form after adjustment for demographic characteristics. Recent consumption of foods and beverages likely to be contaminated with BPA was infrequent among participants and we did not observe any positive associations with BPA analyte levels. CONCLUSION: The high levels of BPA analytes found in our study population may be attributable to the low-income status of the majority of participants and/or our direct analytic method, which yields a more complete evaluation of BPA exposure. We observed near-universal exposure to BPA among pregnant women, as well as substantial variability in BPA metabolic clearance, raising additional concerns for effects on fetal development. Our results are consistent with studies showing thermal paper receipts to be an important source of exposure, point to the difficulty pregnant women have avoiding BPA exposure on an individual level, and therefore underscore the need for changes in BPA regulation and commerce.

Associations of cadmium and lead exposure with leukocyte telomere length: findings from National Health and Nutrition Examination Survey, 1999-2002.

Cadmium and lead are ubiquitous environmental contaminants that might increase risks of cardiovascular disease and other aging-related diseases, but their relationships with leukocyte telomere length (LTL), a marker of cellular aging, are poorly understood. In experimental studies, they have been shown to induce telomere shortening, but no epidemiologic study to date has examined their associations with LTL in the general population. We examined associations of blood lead and cadmium (n = 6,796) and urine cadmium (n = 2,093) levels with LTL among a nationally representative sample of US adults from the National Health and Nutrition Examination Survey (1999-2002). The study population geometric mean concentrations were 1.67 µg/dL (95% confidence interval (CI): 1.63, 1.70) for blood lead, 0.44 µg/L (95% CI: 0.42, 0.47) for blood cadmium, and 0.28 µg/L (95% CI: 0.27, 0.30) for urine cadmium. After adjustment for potential confounders, the highest (versus lowest) quartiles of blood and urine cadmium were associated with -5.54% (95% CI: -8.70, -2.37) and -4.50% (95% CI: -8.79, -0.20) shorter LTLs, respectively, with evidence of dose-response relationship (P for trend < 0.05). There was no association between blood lead concentration and LTL. These findings provide further evidence of physiological impacts of cadmium at environmental levels and might provide insight into biological pathways underlying cadmium toxicity and chronic disease risks.

Vaginal douching and racial/ethnic disparities in phthalates exposures among reproductive-aged women: National Health and Nutrition Examination Survey 2001-2004.

BACKGROUND: Diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) are industrial chemicals found in consumer products that may increase risk of adverse health effects. Although use of personal care/beauty products is known to contribute to phthalate exposure, no prior study has examined feminine hygiene products as a potential phthalate source. In this study, we evaluate whether vaginal douching and other feminine hygiene products increase exposure to phthalates among US reproductive-aged women. METHODS: We conducted a cross-sectional study on 739 women (aged 20-49) from the National Health and Nutrition Examination Survey 2001-2004 to examine the association between self-reported use of feminine hygiene products (tampons, sanitary napkins, vaginal douches, feminine spray, feminine powder, and feminine wipes/towelettes) with urinary concentrations of monoethyl phthalate (MEP) and mono-n-butyl phthalate (MnBP), metabolites of DEP and DnBP, respectively. RESULTS: A greater proportion of black women than white and Mexican American women reported use of vaginal douches, feminine spray, feminine powder, and wipes/towelettes in the past month whereas white women were more likely than other racial/ethnic groups to report use of tampons (p < 0.05). Douching in the past month was associated with higher concentrations of MEP but not MnBP. No other feminine hygiene product was significantly associated with either MEP or MnBP. We observed a dose-response relationship between douching frequency and MEP concentrations (p(trend) < 0.0001); frequent users (≥2 times/month) had 152.2% (95% confidence intervals (CI): (68.2%, 278.3%)) higher MEP concentrations than non-users. We also examined whether vaginal douching mediates the relationship between race/ethnicity and phthalates exposures. Black women had 48.4% (95% CI: 16.8%, 88.6%; p = 0.0002) higher MEP levels than white women. Adjustment for douching attenuated this difference to 26.4% (95% CI:-0.9%, 61.2%; p = 0.06). Mediation effects of douching were statistically significant for black-white differences (z = 3.71, p < 0.001) but not for differences between Mexican Americans and whites (z = 1.80, p = 0.07). CONCLUSIONS: Vaginal douching may increase exposure to DEP and contribute to racial/ethnic disparities in DEP exposure. The presence of environmental chemicals in vaginal douches warrants further examination.

Federal Housing Assistance and Blood Lead Levels in a Nationally Representative US Sample Age 6 and Older: NHANES, 1999-2018.

BACKGROUND: Federal housing assistance is an important policy tool to ensure housing security for low-income households. Less is known about its impact on residential environmental exposures, particularly lead. OBJECTIVES: We conducted a quasi-experimental study to investigate the association between federal housing assistance and blood lead levels (BLLs) in a nationally representative US sample age 6 y and older eligible for housing assistance. METHODS: We used the 1999-2018 National Health and Nutrition Examination Survey (NHANES) linked with US Department of Housing and Urban Development (HUD) administrative records to assess BLLs of NHANES participants with concurrent HUD housing assistance (i.e., current recipients, n=3,071) and those receiving assistance within 2 y after the survey (i.e., pseudo-waitlist recipients, n=1,235). We estimated BLL least squares geometric means (LSGMs), odds ratio (OR) for BLL ≥3.5µg/dL, and percent differences in LSGMs by HUD housing assistance status adjusting for age, sex, family income-to-poverty ratio, education, country of birth, race/ethnicity, region, and survey year. We also examined effect modification using interaction terms and stratified analyses by program type [i.e., public housing, multifamily, housing choice vouchers (HCV)], and race/ethnicity. RESULTS: Current HUD recipients had a significantly lower LSGM [1.07µg/dL; 95% confidence interval (CI): 1.02, 1.12] than pseudo-waitlist recipients (1.21 µg/dL; 95% CI: 1.14, 1.28), with an adjusted OR of 0.60 (95% CI: 0.42, 0.87) for BLL ≥3.5µg/dL. Some effect modification were observed: The protective association of HUD assistance on BLL was strongest among public housing (-19.5% LSGM; 95% CI: -27.5%, -10.7%), multifamily (-12.5% LSGM; 95% CI: -20.7%, -3.5%), and non-Hispanic White (-20.6% LSGM; 95% CI: -29.8%, -10.3%) recipients. It was weaker to null among HCV (-5.7% LSGM; 95% CI: -12.7, 1.7%), non-Hispanic Black (-1.6% LSGM; 95% CI: -8.1%, 5.4%), and Mexican American (-12.5% LSGM; 95% CI: -31.9%, 12.5%) recipients. DISCUSSION: Our research underscores the importance of social-structural determinants like federal housing assistance in providing affordable, stable, and healthy housing to very low-income households. More attention is needed to ensure housing quality and racial equity across HUD's three major housing assistance programs. https://doi.org/10.1289/EHP12645.

Psychosocial Stress and MicroRNA Expression Profiles in Myometrial Tissue of Women Undergoing Surgical Treatment for Uterine Fibroids.

Uterine leiomyomas (fibroids) are the most common non-cancerous tumors affecting women. Psychosocial stress is associated with fibroid risk and severity. The relationship between psychosocial stress and fibroid pathogenesis may involve alterations in microRNAs (miRNAs) although this has yet to be examined. We investigated associations between two psychosocial stress measures, a composite measure of recent stressful life events and perceived social status, with expression levels of 401 miRNAs in myometrium (n = 20) and fibroids (n = 44; 20 with paired fibroid and myometrium samples) among pre-menopausal women who underwent surgery for fibroid treatment. We used linear regressions to identify psychosocial stressors associated with miRNAs, adjusting for covariates (age, body mass index, race/ethnicity, and oral contraceptive use). The association between psychosocial stressors and miRNAs was considered statistically significant at an FDR p < 0.10 and showed a monotonic response (nominal p-trend < 0.05). In the myometrium, 21 miRNAs were significantly associated with a composite measure of recent stressful events, and two miRNAs were associated with perceived social status. No fibroid miRNAs were associated with either stress measure. Pathway analyses revealed miRNA-mRNA targets were significantly enriched (FDR p < 0.05) in pathways relevant to cancer/tumor development. Of the 74 differentially expressed miRNAs between myometrium and fibroids, miR-27a-5p and miR-301b were also associated with stress exposure. Our pilot analysis suggests that psychosocial stress is associated with myometrial miRNA expression and, thus, may have a role in the pathogenesis of fibroids from healthy myometrium.

First trimester plasma PER- AND Polyfluoroalkyl Substances (PFAS) and blood pressure trajectories across the second and third trimesters of pregnancy

BACKGROUND: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. OBJECTIVES: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. METHODS: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. RESULTS: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. CONCLUSION: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother.