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The exposome concept aims to account for the comprehensive and cumulative effects of physical, chemical, biological, and psychosocial influences on biological systems. To date, limited exposome research has explicitly included climate change-related exposures. We define these exposures as those that will intensify with climate change, including direct effects like extreme heat, tropical cyclones, wildfires, downstream effects like air pollution, power outages, and limited or contaminated food and water supplies. These climate change-related exposures can occur individually or simultaneously. Here, we discuss the concept of a climate mixture, defined as three or more simultaneous climate change-related exposures, in the context of the exposome. In a motivating climate mixture example, we consider the impact of a co-occurring tropical cyclone, power outage, and flooding on respiratory hospitalizations. We identify current gaps and future directions for assessing the effect of climate mixtures on health. Mixtures methods allow us to incorporate climate mixtures into exposomics., Competing Interests: The authors have no conflicts of interest to disclose., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Childhood sleep quality is associated with physical, cognitive, and behavioral health and predicts later sleep quality; it has many determinants, including developmental exposures., Objectives: To examine associations between maternal stress during pregnancy and childhood sleep quality and determine whether postnatal stress mediates the association., Method: Data from the Environmental Influences on Child Health Outcomes cohort were used. Perceived Stress Scale (PSS) T-scores were the exposure measure. Outcome measures were preschool Child Behavior Checklist (CBCL) sleep syndrome scale and Patient-Reported Outcomes Measurement Information System Sleep Disturbance Parent Proxy short form 4a (PSD4a) T-scores at ages 4-8 years. Linear mixed-effects regression modeling was performed for each sleep outcome, adjusting for maternal age at delivery and education and child sex, gestational age at birth, and age at outcome ascertainment, with random intercepts for cohorts., Results: Prenatal PSS score was associated with both CBCL (B = 0.09, 95% confidence interval [CI]: 0.06, 0.11; p < 0.01) and PSD4a (B = 0.07, 95% CI: 0.03, 0.12; p < 0.01) scores. Postnatal perceived stress mediated a proportion of the total effect of prenatal stress in both CBCL (66.3%) and PSD4a (95.9%) samples., Conclusions: Both pre- and postnatal maternal perceived stress appear to influence sleep quality during early life., Impact: Prenatal stress significantly associates with child sleep problems and disturbances at ages 4-8 years; postnatal maternal stress is a significant mediator of these associations. Research suggests a range of prenatal affective/distress exposures associated with child sleep problems, but the conclusions remain in doubt due to the mixture of exposures and outcomes employed. Ours is the first US-based effort to explore associations between perceived maternal stress during pregnancy and child sleep problems and disturbance in early and middle childhood. Even a small effect of a prevalent issue like psychosocial stress may have important public health implications at the population level., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Gestational exposure to phthalates, endocrine disrupting chemicals widely used in consumer products, has been associated with poor recognition memory in infancy. Oxidative stress may represent one pathway linking this association. Hence, we examined whether exposure to phthalates was associated with elevated oxidative stress during pregnancy, and whether oxidative stress mediates the relationship between phthalate exposure and recognition memory., Methods: Our analysis included a subset of mother-child pairs enrolled in the Illinois Kids Development Study (IKIDS, N = 225, recruitment years 2013-2018). Concentrations of 12 phthalate metabolites were quantified in 2nd trimester urine samples. Four oxidative stress biomarkers (8-isoprostane-PGF 2α , 2,3-dinor-5,6-dihydro-8-isoPGF 2α , 2,3-dinor-8-isoPGF 2α , and prostaglandin-F 2α ) were measured in 2nd and 3rd trimester urine. Recognition memory was evaluated at 7.5 months, with looking times to familiar and novel stimuli recorded via infrared eye-tracking. Novelty preference (proportion of time looking at a novel stimulus when paired with a familiar one) was considered a measure of recognition memory. Linear mixed effect models were used to estimate associations between monoethyl phthalate (MEP), sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), sum of di(isononyl) phthalate metabolites (ΣDINP), and sum of anti-androgenic phthalate metabolites (ΣAA) and oxidative stress biomarkers. Mediation analysis was performed to assess whether oxidative stress biomarkers mediated the effect of gestational phthalate exposure on novelty preference., Results: The average maternal age at delivery was 31 years and approximately 50 % of participants had a graduate degree. A natural log unit increase in ΣAA, ΣDINP, and ΣDEHP was associated with a statistically significant increase in 8-isoPGF 2α , 2,3-dinor-5,6-dihydro-8-isoPGF 2α , and 2,3-dinor-8-isoPGF 2α . The association was greatest in magnitude for ΣAA and 2,3-dinor-5,6-dihydro-8-isoPGF 2α (β = 0.45, 95 % confidence interval = 0.14, 0.76). The relationship between ΣAA, ΣDINP, ΣDEHP, and novelty preference was partially mediated by 2,3-dinor-8-isoPGF 2α ., Conclusions: Gestational exposure to some phthalates is positively associated with oxidative stress biomarkers, highlighting one mechanistic pathway through which these chemicals may impair early cognitive development., 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 © 2024 Elsevier Inc. All rights reserved.)

Pregnant people are vulnerable to air pollution exposure, including risk of preterm birth, low birth weight, and stillbirth. Understanding the infiltration of outdoor wildfire smoke into a residential space is critical for the accurate assessment of wildfire smoke exposure and associated health effects in pregnant people. Relying on ambient measurements of wildfire smoke alone can result in exposure misclassification. In this study, we examine the role of physical housing characteristics in the relationship between smoke exposure and preterm birth. In particular, we examine the effect of home size, year of construction, cooling type, and renovation status, as effect modifiers in the relationship between smoke exposure during pregnancy and preterm birth from 2007 to 2015 in California. To do this, we combined data on home characteristics from the California Tax Assessor, birth outcomes from the California birth records database, and the number of smoke days for each pregnancy from theNOAA (National Oceanic and Atmospheric Administration) Hazard Mapping System (HMS). We estimated the association between smoke day exposures and odds of preterm birth using logistic regression models and stratified by air basin and housing characteristics. Our findings reveal that cooling type and renovation status are key factors modifying the smoke exposure-preterm birth relationship. Notably, we found elevated associations for people living in unrenovated homes, those using evaporative cooling systems, and those using central air conditioning units. While we observed elevated odds of preterm birth associated with increasing smoke day exposure for residents of large and new homes, this effect does not significantly differ across home size and age quartiles. This study highlights the need to further examine the relative roles of housing characteristics as well as factors not measured here including behavioral factors, time spent outdoors, window use, and occupational exposures in driving adverse birth outcomes related to wildfire smoke exposure., 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 © 2024. Published by Elsevier Ltd.)

Previous research has demonstrated that the Reaching Married Adolescents intervention (RMA) was associated with changes in inequitable gender norms, intimate partner violence (IPV), and modern contraceptive use. This study seeks to understand if changes in inequitable gender norms mediate the RMA intervention's effects on contraceptive use and intimate partner violence (IPV). A four-arm cluster randomized control trial was conducted to evaluate effects of the RMA intervention (household visits, small groups, combination, control) on married adolescent girls and their husbands in Dosso, Niger (baseline: 1042 dyads; 24m follow-up: 737 dyads; 2016-2019). Mediation was assessed using inverse odds ratio weighting. In the small group intervention, of the total effect on IPV prevalence (8% reduction), indirect effects via inequitable gender norms is associated with a 2% decrease (95% CI: -0.07, 0.12) and direct effects with a 6% decrease (95% CI: -0.20, -0.02). For household visits, of the total effect on contraceptive use (20% increase), the indirect effect accounts for an 11% decrease (95% CI: -0.18, -0.01) and direct effect, a 32% increase (95% CI: 0.13, 0.44); similar to findings for the combination arm. This experimental evidence informs the value of changing underlying social norms to reduce IPV and increase contraception use., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: The November 2018 Camp fire was the most destructive wildfire in California history, but its effects on reproductive health are not known., Methods: We linked California birth records from 2017-2019 to daily smoke levels using U.S. EPA Air Quality System (AQS) PM2.5 data and NOAA Hazard Mapping System smoke plume polygons during the Camp fire. In the main analysis, pregnancies were considered exposed if they had median AQS PM2.5 levels above 50 μg/m3 for at least 7 days during November 8-22, 2018. We calculated rates of preterm birth and the infant sex ratio based on week of conception and used the generalized synthetic control method to estimate the average treatment effect on the treated and to propose a novel approach to identify potential critical weeks of exposure during pregnancy., Results: We found associations between Camp fire-related smoke exposure and rates of preterm birth, with a risk difference (RD) = 0.005, 95% CI 0.001, 0.010. Exposure during week 10 of pregnancy was consistently associated with increased preterm birth (RD = 0.030, 95% CI 0.004, 0.056). We did not observe differences in the infant sex ratio., Conclusions: Camp fire smoke exposure was associated with increased rates of preterm birth, with sensitive windows in the first trimester., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Fluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA., Objective: To identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women., Methods: The proteomes of 19 archived second-trimester cord blood samples from women living in northern California, USA, and having varied serum fluoride concentrations, were analyzed by quantitative mass spectrometry. The 327 proteins that were quantified were characterized by their abundance relative to maternal serum fluoride concentration, and subjected to pathway analyses using PANTHER and Ingenuity Pathway Analysis processes., Results: Pathway analyses showed significant increases in process related to reactive oxygen species and cellular oxidant detoxification, associated with increasing maternal serum fluoride concentrations. Pathways showing significant decreases included complement cascade, suggesting alterations in alterations in process associated with inflammation., Conclusion: Maternal fluoride exposure, as measured by serum fluoride concentrations in a small, but representative sample of women from northern California, USA, showed significant changes in the second trimester cord blood proteome relative to maternal serum fluoride concentration., (© 2024. The Author(s).)

Preterm birth (PTB) is associated with substantial mortality and morbidity. We describe environmental factors that may influence PTB risks. We focus on exposures associated with an individual's ambient environment, such as air pollutants, water contaminants, extreme heat, and proximities to point sources (oil/gas development or waste sites) and greenspace. These exposures may further vary by other PTB risk factors such as social constructs and stress. Future examinations of risks associated with ambient environment exposures would benefit from consideration toward multiple exposures - the exposome - and factors that modify risk including variations associated with the structural genome, epigenome, social stressors, and diet., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: There is a lack of research on the relationship between water fluoridation and pregnancy outcomes., Objectives: We assessed whether hypothetical interventions to reduce fluoride levels would improve birth outcomes in California., Methods: We linked California birth records from 2000 to 2018 to annual average fluoride levels by community water system. Fluoride levels were collected from consumer confidence reports using publicly available data and public record requests. We estimated the effects of a hypothetical intervention reducing water fluoride levels to 0.7  ppm (the current level recommended by the US Department of Health and Human Services) and 0.5  ppm (below the current recommendation) on birth weight, birth-weight-for-gestational age z -scores, gestational age, preterm birth, small-for-gestational age, large-for-gestational age, and macrosomia using linear regression with natural cubic splines and G-computation. Inference was calculated using a clustered bootstrap with Wald-type confidence intervals. We evaluated race/ethnicity, health insurance type, fetal sex, and arsenic levels as potential effect modifiers., Results: Fluoride levels ranged from 0 to 2.5  ppm , with a median of 0.51  ppm . There was a small negative association on birth weight with the hypothetical intervention to reduce fluoride levels to 0.7  ppm [ - 2.2 g ; 95% confidence interval (CI): - 4.4 , 0.0] and to 0.5  ppm ( - 5.8 g ; 95% CI: - 10.0 , - 1.6 ). There were small negative associations with birth-weight-for-gestational-age z -scores for both hypothetical interventions ( 0.7  ppm : - 0.004 ; 95% CI: - 0.007 , 0.000 and 0.5  ppm : - 0.006 ; 95% CI: - 0.013 , 0.000). We also observed small negative associations for risk of large-for-gestational age for both the hypothetical interventions to 0.7  ppm [ risk difference  ( RD ) = - 0.001 ; 95% CI: - 0.002 , 0.000 and 0.5  ppm ( - 0.001 ; 95% CI: - 0.003 , 0.000)]. We did not observe any associations with preterm birth or with being small for gestational age for either hypothetical intervention. We did not observe any associations with risk of preterm birth or small-for-gestational age for either hypothetical intervention., Conclusion: We estimated that a reduction in water fluoride levels would modestly decrease birth weight and birth-weight-for-gestational-age z -scores in California. https://doi.org/10.1289/EHP13732.

Background: Wildfires in the Western United States are a growing and significant source of air pollution that is eroding decades of progress in air pollution reduction. The effects on preterm birth during critical periods of pregnancy are unknown., Methods: We assessed associations between prenatal exposure to wildland fire smoke and risk of preterm birth (gestational age < 37 weeks). We assigned smoke exposure to geocoded residence at birth for all live singleton births in California conceived 2007-2018, using weekly average concentrations of particulate matter ≤ 2.5 µm (PM 2.5 ) attributable to wildland fires from United States Environmental Protection Agency's Community Multiscale Air Quality Model. Logistic regression yielded odds ratio (OR) for preterm birth in relation to increases in average exposure across the whole pregnancy, each trimester, and each week of pregnancy. Models adjusted for season, age, education, race/ethnicity, medical insurance, and smoking of the birthing parent., Results: For the 5,155,026 births, higher wildland fire PM 2.5 exposure averaged across pregnancy, or any trimester, was associated with higher odds of preterm birth. The OR for an increase of 1 µg/m 3 of average wildland fire PM 2.5 during pregnancy was 1.013 (95 % CI:1.008,1.017). Wildland fire PM 2.5 during most weeks of pregnancy was associated with higher odds. Strongest estimates were observed in weeks in the second and third trimesters. A 10 µg/m 3 increase in average wildland fire PM 2·5 in gestational week 23 was associated with OR = 1.034; 95 % CI: 1.019, 1.049 for preterm birth., Conclusions: Preterm birth is sensitive to wildland fire PM 2.5 ; therefore, we must reduce exposure during pregnancy., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although the US Centers for Disease Control and Prevention (CDC) considers fluoridation of community water systems (CWSs) to be a major public health achievement responsible for reducing dental disease, recent epidemiologic evidence suggests that chronic exposure to population-relevant levels of fluoride may also be associated with adverse child neurodevelopmental outcomes. To our knowledge, a nationally representative database of CWS fluoride concentration estimates that can be readily linked to US epidemiologic cohorts for further study is not publicly available. Our objectives were to evaluate broad regional and sociodemographic inequalities in CWS fluoride concentrations across the US, and to determine if county-level racial/ethnic composition was associated with county-level CWS fluoride., Methods: We generated CWS-level (N = 32,495) and population weighted county-level (N = 2152) fluoride concentration estimates using over 250,000 routine compliance monitoring records collected from the US Environmental Protection Agency's (EPA) Third Six Year Review (2006-2011). We compared CWS-level fluoride distributions across subgroups including region, population size served, and county sociodemographic characteristics. In county-level spatial error models, we also evaluated geometric mean ratios (GMRs) of CWS fluoride per 10% higher proportion of residents belonging to a given racial/ethnic subgroup., Results: 4.5% of CWSs (serving >2.9 million residents) reported mean 2006-2011 fluoride concentrations ≥1500 µg/L (the World Health Organization's guideline for drinking water quality). Arithmetic mean, 90 th , and 95 th percentile contaminant concentrations were greatest in CWSs reliant on groundwater, located in the Southwest and Eastern Midwest, and serving Semi-Urban, Hispanic communities. In fully adjusted spatial error models, the GMR (95% CI) of CWS fluoride per a 10% higher proportion of county residents that were Hispanic/Latino was 1.16 (1.10, 1.23)., Impact Statement: We find that over 2.9 million US residents are served by public water systems with average fluoride concentrations exceeding the World Health Organization's guidance limit. We also find significant inequalities in community water system fluoride concentration estimates (2006-2011) across the US, especially for Hispanic/Latino communities who also experience elevated arsenic and uranium in regulated public drinking water systems. Our fluoride estimates can be leveraged in future epidemiologic studies to assess the potential association between chronic fluoride exposure and related adverse outcomes., (© 2023. The Author(s).)

Background: Two-way fixed effects methods have been used to estimate effects of policies adopted in different places over time, but they can provide misleading results when effects are heterogeneous or dynamic, and alternate methods have been proposed., Methods: We compared methods for estimating the average treatment effect on the treated (ATT) under staggered adoption of policies, including two-way fixed effects, group-time ATT, cohort ATT, and target-trial approaches. We applied each method to assess the impact of Medicaid expansion on preterm birth using the National Center for Health Statistics' birth records. We compared each estimator's performance in a simulation parameterized to mimic the empirical example. We generated constant, heterogeneous, and dynamic effects and calculated bias, mean squared error, and confidence interval coverage of each estimator across 1000 iterations., Results: Two-way fixed effects estimated that Medicaid expansion increased the risk of preterm birth (risk difference [RD], 0.12; 95% CI = 0.02, 0.22), while the group-time ATT, cohort ATT, and target-trial approaches estimated protective or null effects (group-time RD, -0.16; 95% CI = -0.58, 0.26; cohort RD, -0.02; 95% CI = -0.46, 0.41; target trial RD, -0.16; 95% CI = -0.59, 0.26). In simulations, two-way fixed effects performed well when treatment effects were constant and less well under heterogeneous and dynamic effects., Conclusions: We demonstrated why new approaches perform better than two-way fixed effects when treatment effects are heterogeneous or dynamic under a staggered policy adoption design, and created simulation and analysis code to promote understanding and wider use of these methods in the epidemiologic literature., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Nontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications., Objectives: We characterized levels of nine exogenous and endogenous chemicals in maternal and cord blood identified, selected, and confirmed in prior NTA steps, including linear and branched isomers perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), monoethylhexyl phthalate, 4-nitrophenol, tetraethylene glycol, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid. We evaluated relationships between maternal and cord levels and between gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy in a diverse pregnancy cohort in San Francisco., Methods: We collected matched maternal and cord serum samples at delivery from 302 pregnant study participants from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculated distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. We used adjusted logistic regression to calculate the odds of GDM and hypertensive disorders of pregnancy associated with an interquartile range increase in maternal chemical exposures., Results: We detected linear PFOS, PFHxS, octadecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. Correlations ranged between - 0.1 and 0.9. We observed strong correlations between cord and maternal levels of PFHxS, linear PFOS, and branched PFOS ( coefficient = 0.9 , 0.8, and 0.8, respectively). An interquartile range increase in linear and branched PFOS, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid was associated with increased odds ratio (OR) of GDM [ OR = 1.33 (95% CI: 0.89, 2.01), 1.24 (95% CI: 0.86, 1.80), 1.26 (95% CI: 0.93, 1.73), 1.24 (95% CI: 0.86, 1.80), and 1.23 (95% CI: 0.87, 1.75), respectively]. Tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [ OR = 1.28 (95% CI: 0.90, 1.86)]., Discussion: We identified both exogenous and endogenous chemicals seldom quantified in pregnant study participants that were also related to pregnancy complications and demonstrated the utility of NTA to identify chemical exposures of concern. https://doi.org/10.1289/EHP11546.

Background: Differential risks for adverse pregnancy outcomes may be influenced by prenatal chemical exposures, but current exposure methods may not fully capture data to identify harms and differences., Methods: We collected maternal and cord sera from pregnant people in Fresno and San Francisco, and screened for over 2420 chemicals using LC-QTOF/MS. We matched San Francisco participants to Fresno participants (N = 150) and compared detection frequencies. Twenty-six Fresno participants wore silicone wristbands evaluated for over 1500 chemicals using quantitative chemical analysis. We assessed whether living in tracts with higher levels of pollution according to CalEnviroScreen correlated with higher numbers of chemicals detected in sera., Results: We detected 2167 suspect chemical features across maternal and cord sera. The number of suspect chemical features was not different by city, but a higher number of suspect chemicals in cosmetics or fragrances was detected in the Fresno versus San Francisco participants' sera. We also found high levels of chemicals used in fragrances measured in the silicone wristbands. Fresno participants living in tracts with higher pesticide scores had higher numbers of suspect pesticides in their sera., Conclusions: Multiple exposure-assessment approaches can identify exposure to many chemicals during pregnancy that have not been well-studied for health effects., (© 2022. The Author(s).)

Background: Pregnancy is known to induce extensive biological changes in the healthy mother. Little is known, however, about what these changes are at the molecular level. We have examined systemic expression changes in protein-coding genes and long non-coding (lnc) RNAs during and after pregnancy, compared to before pregnancy, among healthy women with term pregnancies., Methods: Blood samples were collected from 14 healthy women enrolled in our prospective pregnancy cohort at 7 time-points (before, during and after pregnancy). Total RNA from frozen whole blood was used for RNA sequencing. Following raw read alignment and assembly, gene-level counts were obtained for protein-coding genes and long non-coding RNAs. At each time-point, cell type proportions were estimated using deconvolution. To examine associations between pregnancy status and gene expression over time, Generalized Estimating Equation (GEE) models were fitted, adjusting for age at conception, and with and without adjusting for changes in cell type proportions. Fold-changes in expression at each trimester were examined relative to the pre-pregnancy baseline., Results: Numerous immune-related genes demonstrated pregnancy-associated expression, in a time-dependent manner. The genes that demonstrated the largest changes in expression included several that were neutrophil-related (over-expressed) and numerous immunoglobulin genes (under-expressed). Estimated cell proportions revealed a marked increase in neutrophils, and less so of activated CD4 memory T cells, during pregnancy, while most other cell type proportions decreased or remained unchanged. Adjusting for cell type proportions in our model revealed that although most of the expression changes were due to changes in cell type proportions in the bloodstream, transcriptional regulation was also involved, especially in down-regulating expression of type I interferon inducible genes., Conclusion: Compared to a pre-pregnancy baseline, there were extensive systemic changes in cell type proportions, gene expression and biological pathways associated with different stages of pregnancy and postpartum among healthy women. Some were due to changes in cell type proportions and some due to gene regulation. In addition to providing insight into term pregnancy among healthy women, these findings also provide a "normal" reference for abnormal pregnancies and for autoimmune diseases that improve or worsen during pregnancy, to assess deviations from normal., 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 Wright, Goin, Smed, Jewell, Nelson, Olsen, Hetland, Zoffmann and Jawaheer.)

There is a critical lack of research on violence experienced by women when meeting their daily water and sanitation needs. This short report describes the cumulative lifetime incidence of exposure to violence when using the toilet or collecting water (water, sanitation, and hygiene [WASH]-related violence) and identifies associated health and behavioral risks. Data from 1,870 participants collected in 2013-2015 from a longitudinal cohort of young women in rural South Africa were included in this analysis. We found that exposure to WASH-related violence was high: 25.9% experienced violence when collecting water or when using the toilet. Those who experienced violence were more likely to report pregnancy, an older partner, unprotected sex, experience of intimate partner violence, engaging in transactional sex, depressive symptoms, and anxiety. Future research should investigate the location and type of violence experienced and examine how WASH-related violence is related to health outcomes to identify gender-centered WASH interventions that reduce violence exposure.

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: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress., Objectives: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships., Methods: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS., Results: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of β = - 0.15 [95% confidence interval (CI): - 0.27 , - 0.03 ], β = - 0.14 (95% CI: - 0.28 , - 0.002 ), β = - 0.22 (95% CI: - 0.23 , - 0.10 ), β = - 0.06 (95% CI: - 0.18 , 0.06), and β = - 0.25 (95% CI: - 0.37 , - 0.14 ), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: OR PFNA = 0.56 (95% CI: 0.38, 0.83), OR PFDA = 0.52 (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [ - 0.28 ; 95% highest posterior density (HPD): - 0.44 , - 0.14 ] and decreased odds of large-for-gestational-age ( OR = 0.49 ; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress., Discussion: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723.

Background: Per- and poly-fluoroalkyl substances (PFAS) are commonly detected in a variety of foods and food packaging materials. However, few studies have examined diet as a potential source of PFAS exposure during pregnancy. In the present cross-sectional study, we examined prenatal PFAS levels in relation to self-reported consumption of meats, dairy products, and processed foods during pregnancy., Methods: Participants were enrolled in the Chemicals in Our Bodies study, a demographically diverse pregnancy cohort in San Francisco, CA (N = 509). Diet was assessed using a self-reported interview questionnaire administered during the second trimester. Participants were asked on average how many times a day, week, or month they ate 11 different foods since becoming pregnant. Responses were categorized as at least once a week or less than once a week and foods were grouped into three categories: processed foods, dairy products, and meats. Twelve PFAS (ng/mL) were measured in second trimester serum samples. We investigated relationships between consumption of individual dairy products, meats, and processed foods and natural log-transformed PFAS using separate linear regression models adjusted for maternal age, education, race/ethnicity, and nativity., Results: Seven PFAS were detected in ≥65% of participants. Consumption of dairy milk and cheese at least once per week was moderately associated with elevated levels of perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDeA) relative to those who ate dairy products less than once week. The strongest associations observed were with PFDeA for dairy milk (β = 0.2, 95% confidence interval [CI] = 0.02, 0.39) and PFNA for cheese (β = 0.22, 95% CI = 0.02, 0.41). Eating fish, poultry, and red meat at least once per week was associated with higher levels of perfluoroundecanoic acid, PFDeA, PFNA, and perflucorooctane sulfonic acid., Conclusions: Results indicate that consumption of animal products may contribute to elevated prenatal PFAS levels., (© 2021. The Author(s).)

Background: Exposure to environmental chemicals during pregnancy adversely affects maternal and infant health, and identifying socio-demographic differences in exposures can inform contributions to health inequities., Methods: We recruited 294 demographically diverse pregnant participants in San Francisco from the Mission Bay/Moffit Long (MB/ML) hospitals, which serve a primarily higher income population, and Zuckerberg San Francisco General Hospital (ZSFGH), which serves a lower income population. We collected maternal and cord sera, which we screened for 2420 unique formulas and their isomers using high-resolution mass spectrometry using LC-QTOF/MS. We assessed differences in chemical abundances across socioeconomic and demographic groups using linear regression adjusting for false discovery rate., Results: Our participants were racially diverse (31% Latinx, 16% Asian/Pacific Islander, 5% Black, 5% other or multi-race, and 43% white). A substantial portion experienced financial strain (28%) and food insecurity (20%) during pregnancy. We observed significant abundance differences in maternal (9 chemicals) and cord sera (39 chemicals) between participants who delivered at the MB/ML hospitals versus ZSFGH. Of the 39 chemical features differentially detected in cord blood, 18 were present in pesticides, one per- or poly-fluoroalkyl substance (PFAS), 21 in plasticizers, 24 in cosmetics, and 17 in pharmaceuticals; 4 chemical features had unknown sources. A chemical feature annotated as 2,4-dichlorophenol had higher abundances among Latinx compared to white participants, those delivering at ZSFGH compared to MB/ML, those with food insecurity, and those with financial strain. Post-hoc QTOF analyses indicated the chemical feature was either 2,4-dichlorophenol or 2,5-dichlorophenol, both of which have potential endocrine-disrupting effects., Conclusions: Chemical exposures differed between delivery hospitals, likely due to underlying social conditions faced by populations served. Differential exposures to 2,4-dichlorophenol or 2,5-dichlorophenol may contribute to disparities in adverse outcomes., 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. Published by Elsevier Inc.)

Living in a disadvantaged neighborhood has been associated with adverse birth outcomes. Most prior studies have conceptualized neighborhoods using census boundaries and few have examined the role of neighborhood perceptions, which may better capture the neighborhood environment. In the present study, we examined associations between extrinsic and perceived neighborhood quality measures and adverse birth outcomes., Methods: Participants resided in the San Francisco Bay Area of California and were enrolled in Chemicals in Our Bodies, a prospective birth cohort (N = 817). The Index of Concentration at the Extremes (ICE) for income, Area Deprivation Index (ADI), and the Urban Displacement Project's measure of gentrification were included as census block group-level extrinsic neighborhood quality measures. Poor perceived neighborhood quality was assessed using an interview questionnaire. Linear regression models were utilized to examine associations between extrinsic and perceived neighborhood quality measures, and gestational age and birthweight for gestational age z-scores. Covariates in adjusted models were chosen via a directed acyclic graph (DAG) and included maternal age, education, and marital status., Results: In adjusted models, having poor perceived neighborhood quality was associated with higher birthweight z-scores, relative to those who did not perceive their neighborhood as poor quality (β = 0.21, 95% confidence intervals = 0.01, 0.42). Relative to the least disadvantaged tertile, the upper tertile of the ADI was associated with a modest reduction in gestational age (β = -0.35, 95% confidence intervals = -0.67, -0.02)., Conclusions: In the Chemicals in Our Bodies study population, extrinsic and perceived neighborhood quality measures were inconsistently associated with adverse birth outcomes., Competing Interests: The authors declare that they have no financial conflict of interest with regard to the content of this report., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: US preterm-birth rates are 1.6 times higher for Black mothers than for White mothers. Although traffic-related air pollution (TRAP) may increase the risk of preterm birth, evaluating its effect on preterm birth and disparities has been challenging because TRAP is often measured inaccurately. This study sought to estimate the effect of TRAP exposure, measured at the street level, on the prevalence of preterm birth by race/ethnicity., Methods: We linked birth-registry data with TRAP measured at the street level for singleton births in sampled communities during 2013-2015 in Oakland and San Jose, California. Using logistic regression and marginal standardization, we estimated the effects of exposure to black carbon, nitrogen dioxide and ultrafine particles on preterm birth after confounder adjustment and stratification by race/ethnicity., Results: There were 8823 singleton births, of which 760 (8.6%) were preterm. Shifting black-carbon exposure from the 10th to the 90th percentile was associated with: 6.8%age point higher risk of preterm birth (95% confidence interval = 0.1 to 13.5) among Black women; 2.1%age point higher risk (95% confidence interval = -1.1 to 5.2) among Latinas; and inconclusive null findings among Asian and White women. For Latinas, there was evidence of a positive association between the other pollutants and risk of preterm birth, although effect sizes were attenuated in models that co-adjusted for other TRAP., Conclusions: Exposure to TRAP, especially black carbon, may increase the risk of preterm birth for Latina and Black women but not for Asian and White women., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Prenatal exposure to per- and poly-fluoroalkyl substances (PFAS) and psychosocial stressors has been associated with adverse pregnancy outcomes, including preterm birth. Previous studies have suggested that joint exposure to environmental chemical and social stressors may be contributing to disparities observed in preterm birth. Elevated corticotropin-releasing hormone (CRH) during mid-gestation may represent one biologic mechanism linking chemical and nonchemical stress exposures to preterm birth., Methods: Using data from a prospective birth cohort (N = 497), we examined the cross-sectional associations between five individual PFAS (ng/mL; PFNA, PFOA, PFOS, PFHxS, and Me-PFOSA-AcOH) and CRH (pg/mL) using linear regression. PFAS and CRH were measured during the second trimester in serum and plasma, respectively. Coefficients were standardized to reflect change in CRH associated with an interquartile range (IQR) increase in natural log-transformed PFAS. We additionally examined if the relationship between PFAS and CRH was modified by psychosocial stress using stratified models. Self-reported depression, stressful life events, perceived stress, food insecurity, and financial strain were assessed using validated questionnaires during the second trimester and included as binary indicators of psychosocial stress., Results: An IQR increase in PFNA was associated with elevated CRH (β = 5.17, 95% confidence interval [CI] = 1.79, 8.55). Increased concentrations of PFOA were also moderately associated with CRH (β = 3.62, 95% CI = -0.42, 7.66). The relationship between PFNA and CRH was stronger among women who experienced stressful life events, depression, food insecurity, and financial strain compared to women who did not experience these stressors., Conclusions: This cross-sectional study is the first to examine the relationship between PFAS exposure and CRH levels in mid-gestation. We found that these associations were stronger among women who experienced stress, which aligns with previous findings that chemical and nonchemical stressor exposures can have joint effects on health outcomes., (© 2021. The Author(s).)

Exposure to nitrogen dioxide (NO 2 ), black carbon (BC), and ultrafine particles (UFPs) during pregnancy may increase the risk of preeclampsia, but previous studies have not assessed hyperlocalized differences in pollutant levels, which may cause exposure misclassification. We used data from Google Street View cars with mobile air monitors that repeatedly sampled NO 2 , BC, and UFPs every 30 m in Downtown and West Oakland neighborhoods during 2015-2017. Data were linked to electronic health records of pregnant women in the 2014-2016 Sutter Health population, who resided within 120 m of monitoring data ( N = 1095), to identify preeclampsia cases. We used G-computation with log-binomial regression to estimate risk differences (RDs) associated with a hypothetical intervention reducing pollutant levels to the 25th percentile observed in our sample on preeclampsia risk, overall and stratified by race/ethnicity. Prevalence of preeclampsia was 6.8%. Median (interquartile range) levels of NO 2 , BC, and UFPs were 10.8 ppb (9.0, 13.0), 0.34 μg/m 3 (0.27, 0.42), and 29.2 # × 10 3 /cm 3 (26.6, 32.6), respectively. Changes in the risk of preeclampsia achievable by limiting each pollutant to the 25th percentile were NO 2 RD = -1.5 per 100 women (95% confidence interval (CI): -2.5, -0.5); BC RD = -1.0 (95% CI: -2.2, 0.02); and UFP RD = -0.5 (95% CI: -1.8, 0.7). Estimated effects were the largest for non-Latina Black mothers: NO 2 RD = -2.8 (95% CI: -5.2, -0.3) and BC RD = -3.0 (95% CI: -6.4, 0.4).

California's Mental Health Services Act (MHSA) substantially expanded funding of county mental health services through a state tax, and led to broad prevention efforts and intensive services for individuals experiencing serious mental disorders. We estimated the associations between MHSA and mortality due to suicide, homicide, and acute effects of alcohol. Using annual cause-specific mortality data for each US state and the District of Columbia from 1976-2015, we used a generalization of the quasi-experimental synthetic control method to predict California's mortality rate for each outcome in the absence of MHSA using a weighted combination of comparison states. We calculated the association between MHSA and each outcome as the absolute difference and percentage difference between California's observed and predicted average annual rates over the postintervention years (2007-2015). MHSA was associated with modest decreases in average annual rates of homicide (-0.81/100,000 persons, corresponding to a 13% reduction) and mortality from acute alcohol effects (-0.35/100,000 persons, corresponding to a 12% reduction). Placebo test inference suggested that the associations were unlikely to be due to chance. MHSA was not associated with suicide. Protective associations with mortality due to homicide and acute alcohol effects provide evidence for modest health benefits of MHSA at the population level., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Exposure to fatal police violence may play a role in population-level inequities in risk for preterm delivery., Objective: To evaluate whether exposure to fatal police violence during pregnancy affects the hazard of preterm delivery and whether associations differ by race/ethnicity and fetal sex., Methods: We leveraged temporal variation in incidents of fatal police violence within census tracts to assess whether occurrence of fatal police violence in a person's tract during pregnancy was associated with increased hazard of extremely (20-27 weeks), early (28-31 weeks), moderate (32-33 weeks), and late (32-36 weeks) preterm delivery in California from 2007 to 2015. We used both death records and the Fatal Encounters database to identify incidents of fatal police violence. We estimated hazard ratios (HR) using time-varying Cox proportional hazard models stratified by census tract, controlling for age, race/ethnicity, educational attainment, health insurance type, parity, and the year and season of conception. We further stratified by race/ethnicity and infant sex to evaluate whether there were differential effects by these characteristics., Results: Exposure to an incident of fatal police violence was associated with a small increase in the hazard of late preterm birth using both the death records (N = 376,029; hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.00, 1.10) and the Fatal Encounters data (N = 938,814; HR 1.03, 95% CI 1.00, 1.06). We also observed an association for moderate preterm birth in the Fatal Encounters data (HR 1.06, 95% CI 0.98, 1.15). We did not observe associations for early or extremely preterm birth in either data source. Larger relative hazards of moderate (HR 1.25, 95% CI 0.93, 1.68) and late preterm delivery (HR 1.18, 95% CI 1.05, 1.33) were observed among Black birth parents with female births in the Fatal Encounters data., Conclusions: Preventing police use of lethal force may reduce preterm delivery in communities where such violence occurs., (© 2021 John Wiley & Sons Ltd.)

Background: Per- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are endocrine disrupting chemicals with widespread exposures across the U.S. given their abundance in consumer products. PFAS and PBDEs are associated with reproductive toxicity and adverse health outcomes, including certain cancers. PFAS and PBDEs may affect health through alternations in telomere length. In this study, we examined joint associations between prenatal exposure to PFAS, PBDEs, and maternal and newborn telomere length using mixture analyses, to characterize effects of cumulative environmental chemical exposures., Methods: Study participants were enrolled in the Chemicals in Our Bodies (CIOB) study, a demographically diverse cohort of pregnant people and children in San Francisco, CA. Seven PFAS (ng/mL) and four PBDEs (ng/g lipid) were measured in second trimester maternal serum samples. Telomere length (T/S ratio) was measured in delivery cord blood of 292 newborns and 110 second trimester maternal whole blood samples. Quantile g-computation was used to assess the joint associations between groups of PFAS and PBDEs and newborn and maternal telomere length. Groups considered were: (1) all PFAS and PBDEs combined, (2) PFAS, and (3) PBDEs. Maternal and newborn telomere length were modeled as separate outcomes., Results: T/S ratios in newborn cord and maternal whole blood were moderately correlated (Spearman ρ = 0.31). In mixtures analyses, a simultaneous one quartile increase in all PFAS and PBDEs was associated with a small increase in newborn (mean change per quartile increase = 0.03, 95% confidence interval [CI] = -0.03, 0.08) and maternal telomere length (mean change per quartile increase = 0.03 (95% CI = -0.03, 0.09). When restricted to maternal-fetal paired samples (N = 76), increasing all PFAS and PBDEs combined was associated with a strong, positive increase in newborn telomere length (mean change per quartile increase = 0.16, 95% CI = 0.03, 0.28). These associations were primarily driven by PFAS (mean change per quartile increase = 0.11 [95% CI = 0.01, 0.22]). No associations were observed with maternal telomere length among paired samples., Conclusions: Our findings suggest that PFAS and PBDEs may be positively associated with newborn telomere length.

Background: Firearm dealer density is correlated with firearm interpersonal violence, but no quasi-experimental studies have assessed whether changes in dealer density lead to changes in firearm self-harm injuries and deaths. We assessed whether openings of firearm dealers are associated with short-term changes in local firearm self-harm injury rates., Methods: We identified 718 openings of firearm dealers in California using licensing data, 2014-2016. We defined exposure regions based on aggregations of zip codes defined by proximity to firearm dealer openings and matched each opening to four control regions on time and determinants of firearm injury. We applied a differences-in-differences approach to compare rates of firearm self-harm, in the month before and after each opening, in places with and without openings., Results: Firearm dealer openings were not associated with acute, local changes in firearm self-harm relative to places without openings (ratio of rate ratio: 0.90 [95% CI:0.68-1.19]). Results were robust to numerous sensitivity and secondary analyses., Conclusion: We found no associations of firearm dealer openings with acute, localized firearm self-harm deaths and injuries. Our focus on acute, local effects; broad availability of dealers and firearms; durability of firearms; or strong confounding-control may explain these null findings., Competing Interests: The authors have declared that no competing interests exist.

The epidemiologic study of pregnancy and birth outcomes may be hindered by several unique and challenging issues. Pregnancy is a time-limited period in which severe cohort attrition takes place between conception and birth and adverse outcomes are complex and multi-factorial. Biases span those familiar to epidemiologists: selection, confounding and information biases. Specific challenges include conditioning on potential intermediates, how to treat race/ethnicity, and influential windows of prolonged, seasonal and potentially time-varying exposures. Researchers studying perinatal outcomes should be cognizant of the potential pitfalls due to these factors and address their implications with respect to formulating questions of interest, choice of an appropriate analysis approach and interpretations of findings given assumptions. In this article, we catalogue some of the more important potential sources of bias in perinatal epidemiology that have more recently gained attention in the literature, provide the epidemiologic context behind each issue and propose practices for dealing with each issue to the extent possible., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Restricting to live births can induce bias in studies of pregnancy and developmental outcomes, but whether this live-birth bias results in underestimating disparities is unknown. Bias may arise from collider stratification due to an unmeasured common cause of fetal loss and the outcome of interest, or depletion of susceptibles, where exposure differentially causes fetal loss among those with underlying susceptibility., Methods: We conducted a simulation study to examine the magnitude of live-birth bias in a population parameterized to resemble one year of conceptions in California (N = 625,000). We simulated exposure to a non-time-varying environmental hazard, risk of spontaneous abortion, and time to live birth using 1000 Monte Carlo simulations. Our outcome of interest was preterm birth. We included a social vulnerability factor to represent social disadvantage, and estimated overall risk differences for exposure and preterm birth using linear probability models and stratified by the social vulnerability factor. We calculated how often confidence intervals included the true point estimate (CI coverage probabilities) to illustrate whether effect estimates differed qualitatively from the truth., Results: Depletion of susceptibles resulted in a larger magnitude of bias compared with collider stratification, with larger bias among the socially vulnerable group. Coverage probabilities were not adversely affected by bias due to collider stratification. Depletion of susceptibles reduced coverage, especially among the socially vulnerable (coverage among socially vulnerable = 46%, coverage among nonsocially vulnerable = 91% in the most extreme scenario)., Conclusions: In simulations, hazardous environmental exposures induced live-birth bias and the bias was larger for socially vulnerable women., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Women can be exposed to a multitude of hardships before and during pregnancy that may affect fetal growth, but previous approaches have not analyzed them jointly as social exposure mixtures., Methods: We evaluated the independent, mutually adjusted, and pairwise joint associations between self-reported hardships and birthweight for gestational age z-scores in the Chemicals in Our Bodies-2 prospective birth cohort (N = 510) using G-computation. We examined financial hardship, food insecurity, job strain, poor neighborhood environment, low community standing, caregiving, high burden of stressful life events, and unplanned pregnancy collected via questionnaire administered in the second trimester of pregnancy. We used propensity scores to ensure our analyses had sufficient data support and estimated absolute differences in outcomes., Results: Food insecurity was most strongly associated with reduced birthweight for gestational age z-scores individually, with an absolute difference of -0.16, 95% confidence interval (CI) -0.45, 0.14. We observed an unexpected increase in z-scores associated with poor perceived neighborhood environment (0.18, 95% CI -0.04, 0.41). Accounting for coexposures resulted in similar findings. The pairwise joint effects were strongest for food insecurity in combination with unplanned pregnancy (-0.45, 95% CI -0.93, 0.02) and stressful life events (-0.42, 95% CI -0.90, 0.05). Poor neighborhood environment in combination with caregiving was associated with an increase in z-scores (0.47, 95% CI -0.01, 0.95)., Conclusions: Our results are consistent with the hypothesis that experiencing food insecurity during pregnancy, alone and in combination with stressful life events and unplanned pregnancy, may affect fetal growth.

Background: Telomere length in early life predicts later length, and shortened telomere length among adults and children has been linked to increased risk of chronic disease and mortality. Maternal stress during pregnancy may impact telomere length of the newborn., Methods: In a diverse cohort of 355 pregnant women receiving prenatal and delivery care services at two hospitals in San Francisco, California, we investigated the relationship between self-reported maternal psychosocial stressors during the 2nd trimester of pregnancy and telomere length (T/S ratio) in newborn umbilical cord blood leukocytes. We examined financial strain, food insecurity, high job strain, poor neighborhood quality, low standing in one's community, experience of stressful/traumatic life events, caregiving for a dependent family member, perceived stress, and unplanned pregnancy. We used linear regression and Targeted Minimum Loss-Based Estimation (TMLE) to evaluate the change in the T/S ratio associated with exposure to each stressor controlling for maternal age, education, parity, race/ethnicity, and delivery hospital., Results: In TMLE analyses, low community standing (-0.09; 95% confidence interval [CI]-0.19 to 0.00) and perceived stress (-0.07; 95% CI -0.15 to 0.021 was marginally associated with shorter newborn telomere length, but the associations were not significant after adjusting for multiple comparisons. All linear regression estimates were not statistically significant. Our results also suggest that the association between some maternal stressors and newborn telomere length varies by race/ethnicity and infant sex., Conclusions: This study is the first to examine the joint effect of multiple stressors during pregnancy on newborn TL using a flexible modeling approach., Competing Interests: Jue Lin is a co-founder and consultant to Telomere Diagnostics, Inc. The company played no role in this study. The authors declare they have no actual or potential competing financial interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Mediation analyses are valuable for examining mechanisms underlying an association, investigating possible explanations for nonintuitive results, or identifying interventions that can improve health in the context of nonmanipulable exposures. However, designing a study for the purpose of answering a mediation-related research question remains challenging because sample size and power calculations for mediation analyses are typically not conducted or are crude approximations. Consequently, many studies are probably conducted without first establishing that they have the statistical power required to detect a meaningful effect, potentially resulting in wasted resources. In an effort to advance more accurate power calculations for estimating direct and indirect effects, we present a tutorial demonstrating how to conduct a flexible, simulation-based power analysis. In this tutorial, we compare power to estimate direct and indirect effects across various estimators (the Baron and Kenny estimator (J Pers Soc Psychol. 1986;51(6):1173-1182), inverse odds ratio weighting, and targeted maximum likelihood estimation) using various data structures designed to mimic important features of real data. We include step-by-step commented R code (R Foundation for Statistical Computing, Vienna, Austria) in an effort to lower implementation barriers to ultimately improving power assessment in mediation studies., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Systematic reviews are increasingly prevalent in environmental health due to their ability to synthesize evidence while reducing bias. Different systematic review methods have been developed by the US National Toxicology Program's Office of Health Assessment and Translation (OHAT), the US Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS), and by the US EPA under the Toxic Substances Control Act (TSCA), including the approach to assess risk of bias (ROB), one of the most vital steps which is used to evaluate internal validity of the studies. Our objective was to compare the performance of three tools (OHAT, IRIS, TSCA) in assessing ROB., Methods: We selected a systematic review on polybrominated diphenyl ethers and intelligence quotient and/or attention deficit hyperactivity disorder because it had been endorsed by the National Academy of Sciences. Two reviewers followed verbatim instructions from the tools and independently applied each tool to assess ROB in 15 studies previously identified. We documented the time to apply each tool and the impact the ROB ratings for each tool had on the final rating of the quality of the overall body of evidence., Results: The time to complete the ROB assessments varied widely (mean = 20, 32, and 40 min per study for the OHAT, IRIS, and TSCA tools, respectively). All studies were rated overall "low" or "uninformative" using IRIS, due to "deficient" or "critically deficient" ratings in one or two domains. Similarly, all studies were rated "unacceptable" using the TSCA tool because of one "unacceptable" rating in a metric related to statistical power. Approximately half of the studies had "low" or "probably low ROB" ratings across all domains with the OHAT and Navigation Guide tools., Conclusions: Tools that use overall ROB or study quality ratings, such as IRIS and TSCA, may reduce the available evidence to assess the harms of environmental exposures by erroneously excluding studies, which leads to inaccurate conclusions about the quality of the body of evidence. We recommend using ROB tools that circumvents these issues, such as OHAT and Navigation Guide., Systematic Review Registration: This review has not been registered as it is not a systematic review.

Firearm violence may indirectly affect health among pregnant women living in neighborhoods where it is endemic. We used birth, death, emergency department, and hospitalization data from California from 2007-2011 to estimate the association between living in a neighborhood with high firearm violence and preterm delivery, and assessed whether there was mediation by diagnoses of pregnancy complications and health behaviors during pregnancy. We used an ensemble machine learning algorithm to predict the propensity for neighborhoods to be classified as having a high level of firearm violence. Risk differences for the total effect and stochastic direct and indirect effects were estimated using targeted maximum likelihood. Residence in high-violence neighborhoods was associated with higher prevalence of preterm birth (risk difference (RD) = 0.46, 95% confidence interval (CI): 0.13, 0.80), infections (RD = 1.34, 95% CI: -0.17, 2.86), asthma (RD = 0.76, 95% CI: 0.03, 1.48), and substance use (RD = 0.74, 95% CI: 0.00, 1.47). The largest indirect effects for the association between violence and preterm birth were observed for infection (stochastic indirect effect = 0.04, 95% CI: 0.00, 0.08) and substance use (stochastic indirect effect = 0.04, 95% CI: 0.01, 0.06). Firearm violence was associated with risk of preterm delivery, and this association was partially mediated by infection and substance use., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Overdose deaths increased exponentially in the United States to be the leading cause of adult injury deaths, and declining economic opportunity may contribute. To our knowledge, there has been no quantitative research into the impact of relative economic measures on overdose risk. Prior longitudinal studies on impact of socioeconomic conditions used fixed effects approaches that can result in biased estimates in the presence of time-varying confounders., Methods: We estimated county-level longitudinal associations between drug overdose deaths and unemployment and labor-force nonparticipation rates by gender and racial/ethnic subgroup using longitudinal g-computation and the clustered bootstrap., Results: We find evidence for associations between both overall and relative aspects of unemployment and labor-force nonparticipation and drug overdose mortality; patterns of associations differed, sometime qualitatively, across subgroups. For males across racial-ethnic groups, greater overall and relative unemployment rates were generally associated with greater overdose mortality in both the short and long terms [e.g., for white males, increasing the overall percentage of unemployed adults by 5% points in 2000, 2009, and 2015 is associated with an increase of 3.2 overdose deaths (95% confidence interval [CI] = -2.8, 14) in 2015, and increasing the ratio by 0.5 in 2000, 2009, and 2015 is associated with an increase of 9.1 overdose deaths (95% CI = 1.6, 24)]., Conclusions: These findings point to important complexity in how the economic and contextual landscape differentially shapes overdose risks, underscoring a need for increased understanding of the mechanisms operating for women and minority groups.

Pregnant women who experience psychosocial stressors, such as stressful life events, poor neighborhood quality, and financial hardship, are at an increased risk for adverse pregnancy outcomes. Yet, few studies have examined associations between multiple stressors from different sources, which may be helpful to better inform causal pathways leading to adverse birth outcomes. Using path analysis, we examined associations between multiple self-reported stressor exposures during and before pregnancy in the Chemicals in Our Bodies-2 study (N = 510), a demographically diverse cohort of pregnant women in San Francisco. We examined associations between eight self-reported exposures to stressors and three responses to stress which were assessed via interview questionnaire at the 2nd trimester. Stressors included: neighborhood quality, stressful life events, caregiving, discrimination, financial strain, job strain, food insecurity, and unplanned pregnancy. Perceived stress, depression, and perceived community status were included as indicators of self-reported stress response. Our model indicated that women who experienced discrimination and food insecurity had a 3.76 (95% confidence interval [CI] = 1.60, 5.85) and 2.67 (95% CI = 1.31, 4.04) increase in depression scale scores compared to women who did not experience discrimination and food insecurity, respectively. We additionally identified job strain and caregiving for an ill family member as strong predictors of increased depressive symptoms (β = 1.63, 95% CI = 0.29, 3.07; β = 1.48, 95% CI = 0.19, 2.70, respectively). Discrimination, food insecurity, and job strain also influenced depression indirectly through the mediating pathway of increasing perceived stress, although indirect effects were less precise. In our study population, women who experienced discrimination, food insecurity, job strain and caregiving for an ill family member had an increased number of depressive symptoms compared to women who did not experience these stressors. Results from our study highlight the complex relationships between stressors and stress responses and may help to identify possible mediating pathways leading to adverse pregnancy outcomes., Competing Interests: The authors have declared that no competing interests exist.

The human immunodeficiency virus (HIV) epidemic among adolescent girls and young women (AGYW) in sub-Saharan Africa is a critical public health problem. We assessed whether depressive symptoms in AGYW were longitudinally associated with incident HIV, and identified potential social and behavioral mediators. Data came from a randomized trial of a cash transfer conditional on school attendance among AGYW (ages 13-21 years) in rural Mpumalanga Province, South Africa, during 2011-2017. We estimated the relationship between depressive symptoms and cumulative HIV incidence using a linear probability model, and we assessed mediation using inverse odds ratio weighting. Inference was calculated using the nonparametric bootstrap. AGYW with depressive symptoms had higher cumulative incidence of HIV compared with those without (risk difference = 3.5, 95% confidence interval (CI): 0.1, 7.0). The strongest individual mediators of this association were parental monitoring and involvement (indirect effect = 1.6, 95% CI: 0.0, 3.3) and reporting a partner would hit her if she asked him to wear a condom (indirect effect = 1.5, 95% CI: -0.3, 3.3). All mediators jointly explained two-thirds (indirect effect = 2.4, 95% CI: 0.2, 4.5) of the association between depressive symptoms and HIV incidence. Interventions addressing mental health might reduce risk of acquiring HIV among AGYW., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Previous studies have shown a correlation between fluoride concentrations in urine and community water fluoride concentrations. However, there are no studies of the relationship between community water fluoridation, urine, serum, and amniotic fluid fluoride concentrations in pregnant women in the US. The aim of this study was to determine the relationship between maternal urine fluoride (MUF), maternal urine fluoride adjusted for specific gravity (MUF SG ), maternal serum fluoride (MSF), amniotic fluid fluoride (AFF) concentrations during pregnancy, and community water fluoridation in Northern California., Methods: Archived samples of urine, serum and amniotic fluid collected from second trimester pregnant women in Northern California from 47 different communities in Northern California and one from Montana (n = 48), were analyzed for fluoride using an ion specific electrode following acid microdiffusion. Women's addresses were matched to publicly reported water fluoride concentrations. We examined whether fluoride concentrations in biospecimens differed by fluoridation status of the community water, and determined the association between water fluoride concentrations and biospecimen fluoride concentrations using linear regression models adjusted for maternal age, smoking, Body Mass Index (BMI), race/ethnicity, and gestational age at sample collection., Results: Fluoride concentrations in the community water supplies ranged from 0.02 to 1.00 mg/L. MUF, MSF , and AFF concentrations were significantly higher in pregnant women living in communities adhering to the U.S. recommended water fluoride concentration (0.7 mg/L), as compared with communities with less than 0.7 mg/L fluoride in drinking water. When adjusted for maternal age, smoking status, BMI, race/ethnicity, and gestational age at sample collection, a 0.1 mg/L increase in community water fluoride concentration was positively associated with higher concentrations of MUF (B = 0.052, 95% CI:0.019,0.085), MUF SG (B = 0.028, 95% CI: -0.006, 0.062), MSF (B = 0.001, 95% CI: 0.000, 0.003) and AFF (B = 0.001, 95% CI: 0.000, 0.002)., Conclusions: We found universal exposure to fluoride in pregnant women and to the fetus via the amniotic fluid. Fluoride concentrations in urine, serum, and amniotic fluid from women were positively correlated to public records of community water fluoridation. Community water fluoridation remains a major source of fluoride exposure for pregnant women living in Northern California.