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.

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.

Beauty Inside Out: Examining Beauty Product Use Among Diverse Women and Femme-Identifying Individuals in Northern Manhattan and South Bronx Through an Environmental Justice Framework.

The disproportionate use of chemical straighteners and skin lighteners by women of color is a growing public health concern given the link between product use and adverse health effects. Prior studies examined product use as an individual choice but neglected social-structural factors, which influence beauty perceptions and personal decisions around product use. We used a community-based participatory research approach to characterize product use by demographics and investigated how racialized beauty norms impact use among 297 women and femme-identifying individuals in Northern Manhattan and the South Bronx. Product use varied by race/ethnicity, nativity, and messaging from family and peers. Black respondents were more likely to ever use chemical straighteners than non-Black respondents (OR = 2.0; 95% CI = 1.2-3.2), as were respondents who heard that family members express a preference for straight hair compared with respondents whose family members expressed mixed preferences about hairstyles (OR = 2.0; 95% CI = 1.1-3.7). Compared with non-Asian respondents and respondents born in the United States, Asian respondents and respondents born in other countries, respectively, had threefold higher odds of ever using skin lighteners (Asian: OR = 3.2; 95% CI = 1.4-7.0; born in other countries: OR = 3.4; 95% CI = 1.9-6.1). Respondents' perceptions that others believe straight hair or lighter skin confer benefits such as beauty, professionalism, or youth were associated with greater use of chemical straighteners and skin lighteners. These findings highlight the pervasiveness of racialized beauty norms and point to the need to reduce the demand for and sale of these products through community education, market-based strategies, and public policy.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

Examining differences in menstrual and intimate care product use by race/ethnicity and education among menstruating individuals.

Introduction: United States consumers spend over two billion dollars a year on intimate care products. These products, along with scented menstrual products, are marketed for odor control, perceived "freshness," and vaginal/vulvar cleanliness. However, these scent-altering products may increase exposure to carcinogenic and endocrine-disrupting chemicals. Prior research has not adequately characterized demographic differences in product use. The objective of our study is to examine racial/ethnic and educational differences in menstrual and intimate care product use among people who menstruate. Methods: We pooled data from two US-based cross sectional studies to examine demographic characteristics and product use in 661 participants aged 18-54 years. Participants reported use of scented and unscented menstrual products (tampons, sanitary pads, and menstrual cups) and intimate care products (vaginal douches, sprays, wipes, and powders). We examined differences by race/ethnicity and education using log-binomial regression and latent class analysis (LCA), which can identify groups based on product use patterns. Results: Our sample was 33.4% Black, 30.9% Latina, 18.2% White, and 16.2% another identity. Approximately half the population had a bachelor's degree or more; 1.4% identified as transgender and 1.8% as non-binary. In adjusted models, scent-altering products (i.e., scented menstrual and intimate care products) were more likely to be used by those with less formal education (p < 0.05). Unscented menstrual products were more likely to be used by those with more formal education. Compared to Black participants, White participants were more likely to use unscented tampons and menstrual cups and less likely to use douches and wipes (p < 0.05). Using LCA we identified two groups: one more likely to use scent-altering products, and a second more likely to use unscented menstrual products. Less education and older age, but not race/ethnicity, was significantly associated with membership in the group more likely to use scent-altering products. While sex/gender composition did not statistically vary across groups, all non-binary participants fell in the unscented menstrual product group. Discussion: Lower educational attainment was consistently associated with greater use of scent-altering menstrual and intimate care products. Future research should examine associations between body odor stigma, product use, and health risks at intersections of race, class, and gender.

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 tumor 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 matched between tissues) from 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, and race/ethnicity). Psychosocial stressors were modeled as ordinal variables and results were considered statistically significant if the overall variable significant was below false discovery threshold (FDR < 0.10) and showed a monotonic dose-response (nominal p-trend < 0.05). In the myometrium, 16 miRNAs were significantly associated with total 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 < 0.05) in pathways relevant to cancer/tumor development. Of the 74 differentially expressed miRNAs between myometrium and fibroids (p < 0.05), miR-27a-5p was also associated with stress exposure. Our pilot analysis suggests that psychosocial stress is associated with changes in myometrium miRNAs, and thus, plays a role in the pathogenesis of fibroids from healthy myometrium.

Climate change as a threat multiplier to environmental reproductive justice.

Legacies of racial capitalism and colonialism drive present day racial disparities in perinatal health outcomes. Climate change amplifies existing social inequalities associated with environmental exposures and reproductive health, of which BIPOC (Black, Indigenous, and people of color) communities bear a disproportionate burden. Through case studies, this article summarizes three examples of climate justice issues with reproductive healthcare outcomes: traffic related air pollution exposure, chemical exposures in personal care products and plastics, and natural disaster frequency. We advocate for incorporation of climate justice and environmental health impact into medical school curriculum, increased prenatal screening for environmental toxins, and physician engagement with local environmental issues.

Exposomics as a tool to investigate differences in health and disease by sex and gender.

The health and disease of an individual is mediated by their genetics, a lifetime of environmental exposures, and interactions between the two. Genetic or biological sex, including chromosome composition and hormone expression, may influence both the types and frequency of environmental exposures an individual experiences, as well as the biological responses an individual has to those exposures. Gender identity, which can be associated with social behaviors such as expressions of self, may also mediate the types and frequency of exposures an individual experiences. Recent advances in exposome-level analysis have progressed our understanding of how environmental factors affect health outcomes; however, the relationship between environmental exposures and sex- and gender-specific health remains underexplored. The comprehensive, non-targeted, and unbiased nature of exposomic research provides a unique opportunity to systematically evaluate how environmental exposures interact with biological sex and gender identity to influence health. In this forward-looking narrative review, we provide examples of how biological sex and gender identity influence environmental exposures, discuss how environmental factors may interact with biological processes, and highlight how an intersectional approach to exposomics can provide critical insights for sex- and gender-specific health sciences.

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.

Persistent organic pollutant exposure contributes to Black/White differences in leukocyte telomere length in the National Health and Nutrition Examination Survey.

Despite racial disparities in diseases of aging and premature mortality, non-Hispanic Black Americans tend to have longer leukocyte telomere length (LTL), a biomarker of cellular aging, than non-Hispanic White Americans. Previous findings suggest that exposure to certain persistent organic pollutants (POPs) is both racially-patterned and associated with longer LTL. We examine whether Black/White differences in LTL are explained by differences in exposure to 15 POPs by estimating the indirect effect (IE) of self-reported race on LTL that is mediated through nine polychlorinated biphenyls (PCBs), three furans, and three dioxins, as well as their mixtures. Our study population includes 1,251 adults from the 1999-2000 and 2001-2002 cycles of the cross-sectional National Health and Nutrition Examination Survey. We characterized single-pollutant mediation effects by constructing survey-weighted linear regression models. We also implemented various approaches to quantify a global mediation effect of all POPs, including unpenalized linear regression, ridge regression, and examination of three summary exposure scores. We found support for the hypothesis that exposure to PCBs partially mediates Black/White differences in LTL. In single-pollutant models, there were significant IEs of race on LTL through six individual PCBs (118, 138, 153, 170, 180, and 187). Ridge regression (0.013, CI 0.001, 0.023; 26.0% mediated) and models examining summative exposure scores with linear combinations derived from principal components analysis (0.019, CI 0.009, 0.029; 34.8% mediated) and Toxic Equivalency Quotient (TEQ) scores (0.016, CI 0.005, 0.026; 28.8% mediated) showed significant IEs when incorporating survey weights. Exposures to individual POPs and their mixtures, which may arise from residential and occupational segregation, may help explain why Black Americans have longer LTL than their White counterparts, providing an environmental explanation for counterintuitive race differences in cellular aging.

Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts.

Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. Objective: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. Design, Setting, and Participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. Exposures: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. Main Outcomes and Measures: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. Results: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. Conclusions and Relevance: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

Environmentally Just Futures: A Collection of Community-Driven African Environmental Education and Improvement Initiatives.

Advocating for healthy environments is a matter of justice. Changes in environments have tremendous impacts on the health of communities, and oftentimes, individuals are unable to safeguard themselves through individual actions alone. Efforts frequently require collective action and are often most effective when led by the communities most impacted. In this spirit, we launched "Vibrations", an African environment photo essay contest. Through funding and publicity, we aimed to support community-led environmental improvement and education initiatives presently taking place on the continent. We received nearly two dozen submissions and selected eight winners. The winners come from five countries (Ghana, Kenya, Mozambique, Nigeria, and South Africa) and have taken on a range of projects aimed at improving environments across a variety of African regions. Projects included efforts to combat pollution, create environmentally conscious school curricula, utilize clean energy sources, and spread awareness about environmental justice concerns in local communities. It is our hope that this report highlights these transformative community-driven efforts, promotes continued conversations on environmental justice in Africa, and encourages meaningful action via policy changes and collaborations throughout the African continent and beyond.

Early-pregnancy plasma per- and polyfluoroalkyl substance (PFAS) concentrations and hypertensive disorders of pregnancy in the Project Viva cohort.

BACKGROUND: Hypertensive disorders of pregnancy (HDP), defined here as hypertensive disorders with onset in pregnancy (i.e., gestational hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension), affect up to 10% of pregnancies in the United States and are associated with substantial maternal and neonatal morbidity and mortality. Per- and polyfluoroalkyl substances (PFAS) are associated with adverse cardiometabolic outcomes during pregnancy, but associations between PFAS and HDP are inconsistent and joint effects of PFAS mixtures have not been evaluated. METHODS: We studied 1,558 pregnant individuals from the Project Viva cohort, recruited during 1999-2002. We quantified concentrations of eight PFAS in plasma samples (median 9.7 weeks of gestation). Using clinical records, we calculated trimester-specific mean systolic (SBP) and diastolic (DBP) blood pressure and categorized HDP status [no HDP (normotensive & chronic hypertension), gestational hypertension, preeclampsia]. We estimated associations of individual PFAS with HDP using multinomial logistic regression and estimated associations with blood pressure using linear regression. We used Bayesian kernel machine regression (BKMR) and quantile g-computation to assess joint effects of the PFAS mixture on HDP and blood pressure measures. RESULTS: Four percent of participants developed preeclampsia and 7% developed gestational hypertension. We observed higher odds of gestational hypertension, but not preeclampsia, per doubling of perfluorooctanoate (PFOA) [OR = 1.51 (95% confidence interval: 1.12, 2.03)], perfluorooctane sulfonate (PFOS) [OR = 1.38 (1.04, 1.82)], and perfluorohexane sulfonate [OR = 1.28 (1.06, 1.54)] concentrations. We observed higher mean DBP per doubling of PFOA [2nd trimester (T2): 0.39 mmHg (-0.01, 0.78); 3rd trimester (T3): 0.56 mmHg (0.14, 0.98)] and PFOS [T2: 0.46 mmHg (0.11, 0.82); T3: 0.43 mmHg (0.05, 0.80)]. The PFAS mixture was positively associated with odds of gestational hypertension [75th vs. 50th percentile: OR = 1.14 (95% credible interval:1.03, 1.25), BKMR] and mean DBP [T2 = 0.17 mmHg (-0.06, 0.40); T3 = 0.22 mmHg (-0.03, 0.48), BKMR]. CONCLUSIONS: These findings suggest that exposure to certain PFAS may increase the odds of gestational hypertension during pregnancy, with potential implications for subsequent maternal and child health outcomes.

Report of Exosomes Isolated from a Human Uterine Leiomyoma Cell Line and Their Impact on Endometrial Vascular Endothelial Cells.

Uterine leiomyomas are the most common pelvic tumor in women of reproductive age; they cause irregular heavy menstrual bleeding leading to anemia and subsequent negative effects on quality of life. Exosomes have arisen as main players of disease progression in several illnesses, including a range of benign and malignant conditions; however, their role in leiomyomas' pathophysiology remains unknown. We investigated the effect of exosomes derived from human uterine leiomyoma tumor cells (HULM) and human myometrial cells (UTSM) on the behavior of human endometrial microvascular endothelial cells (HEMEC). HULM- and UTSM-derived exosomes were isolated and cocultured with HEMECs. Then, cell proliferation, mRNA expression, tube formation assay, and RNA-seq were performed. Treatment of HEMEC with HULM-derived exosomes increased cell proliferation by 60% compared to control untreated cells, upregulated C-MYC and VEGFA expression levels, and increased tube formation, length, and branching (markers of angiogenesis). Profiling of miRNA revealed that 84 miRNAs were significantly downregulated and 71 were upregulated in HULM-derived exosomes compared to UTSM-derived exosomes. These findings suggest that HULM-derived exosomes might have effects on HEMEC function, containing factors that enhance endometrial proliferation and angiogenesis, which may contribute to heavy menstrual bleeding. Further research on exosomes in uterine leiomyoma may identify possible novel biomarkers for treatment.

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.

Phthalate and novel plasticizer concentrations in food items from U.S. fast food chains: a preliminary analysis.

BACKGROUND: Fast food consumption is associated with biomarkers of ortho-phthalates exposures. However, the chemical content of fast food is unknown; certain ortho-phthalates (i.e., di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP)) have been phased out and replaced with other plasticizers (e.g., dioctyl terephthalate (DEHT)). OBJECTIVE: We conducted a preliminary study to examine ortho-phthalate and replacement plasticizer concentrations in foods and food handling gloves from U.S. fast food restaurants. METHODS: We obtained hamburgers, fries, chicken nuggets, chicken burritos, cheese pizza (n = 64 food samples) and gloves (n = 3) from restaurants and analyzed them for 11 chemicals using gas chromatography mass spectrometry. RESULTS: We found DEHT at the highest concentrations in both foods (n = 19; median = 2510 µg/kg; max = 12,400 µg/kg) and gloves (n = 3; range: 28-37% by weight). We detected DnBP and DEHP in 81% and 70% of food samples, respectively. Median DEHT concentrations were significantly higher in burritos than hamburgers (6000 µg/kg vs. 2200 µg/kg; p < 0.0001); DEHT was not detected in fries. Cheese pizza had the lowest levels of most chemicals. SIGNIFICANCE: To our knowledge, these are the first measurements of DEHT in food. Our preliminary findings suggest that ortho-phthalates remain ubiquitous and replacement plasticizers may be abundant in fast food meals. IMPACT STATEMENT: A selection of popular fast food items sampled in this study contain detectable levels of replacement plasticizers and concerning ortho-phthalates. In addition, food handling gloves contain replacement plasticizers, which may be a source of food contamination. These results, if confirmed, may inform individual and regulatory exposure reduction strategies.