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BackgroundThere is a lack of research on the relationship between water fluoridation and pregnancy outcomes.ObjectivesWe assessed whether hypothetical interventions to reduce fluoride levels would improve birth outcomes in California.MethodsWe 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.ResultsFluoride 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 [-2.2g; 95% confidence interval (CI): -4.4, 0.0] and to 0.5 ppm (-5.8g; 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.ConclusionWe 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.

BackgroundFluoride 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.ObjectiveTo identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women.MethodsThe 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.ResultsPathway 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.ConclusionMaternal 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.

BackgroundNontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications.ObjectivesWe 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.MethodsWe 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.ResultsWe 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)].DiscussionWe 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.

BackgroundDifferential 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.MethodsWe 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.ResultsWe 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.ConclusionsMultiple exposure-assessment approaches can identify exposure to many chemicals during pregnancy that have not been well-studied for health effects.

BackgroundPreterm 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.ObjectiveWe 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 designThis 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-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α 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.ResultsApproximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-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-F2α 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.ConclusionHere, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation.

BackgroundPer- 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.ObjectivesWe estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships.MethodsWe 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.ResultsWe 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: ORPFNA=0.56 (95% CI: 0.38, 0.83), ORPFDA=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.DiscussionOur 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.

Synopsis: Fossil fuels contribute to climate change and petrochemicals, both of which increase maternal and child disease. Reducing fossil fuels can reap a double benefit for climate change and improved health.

BackgroundPer- 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.MethodsParticipants 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.ResultsSeven 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.ConclusionsResults indicate that consumption of animal products may contribute to elevated prenatal PFAS levels.

In the original publication of this article [1], the new reference citation has been included in the body text repeatedly and not added as an endnote.

This letter responds to the US Environmental Protection Agency's Integrated Risk Information System (IRIS) program letter by Radke et al. (2021) that was published in response to the application of the IRIS risk of bias tool in our recent study "Assessing risk of bias in human environmental epidemiology studies using three tools: different conclusions from different tools." Their letter stated that we misrepresented the IRIS approach. Here, we respond to their three points raised and how we did not misrepresent their tool and also identified areas for improvement: (1) why it should be expected that different reviewers could reach different conclusions with the IRIS tool, as ratings are subject to reviewer judgment; (2) why our interpretation that "low" or "uninformative" studies could be excluded from a body of evidence was reasonable; and (3) why we believe the use of a rating system that generates an overall rating based on an individual domain or a combination of identified deficiencies essentially acts as a score and assumes that we know empirically how much each risk of bias domain should contribute to the overall rating for that study. We have elaborated on these points in our letter.

BackgroundExposure to environmental chemicals during pregnancy adversely affects maternal and infant health, and identifying socio-demographic differences in exposures can inform contributions to health inequities.MethodsWe 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.ResultsOur 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.ConclusionsChemical 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.

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. 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. 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. 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.

BackgroundPrenatal 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.MethodsUsing 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.ResultsAn 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.ConclusionsThis 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.

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.MethodsParticipants 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.ResultsIn 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).ConclusionsIn the Chemicals in Our Bodies study population, extrinsic and perceived neighborhood quality measures were inconsistently associated with adverse birth outcomes.

BackgroundPer- 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.MethodsStudy 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.ResultsT/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.ConclusionsOur findings suggest that PFAS and PBDEs may be positively associated with newborn telomere length.

Exposure to nitrogen dioxide (NO2), 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 NO2, 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 NO2, BC, and UFPs were 10.8 ppb (9.0, 13.0), 0.34 μg/m3 (0.27, 0.42), and 29.2 # × 103/cm3 (26.6, 32.6), respectively. Changes in the risk of preeclampsia achievable by limiting each pollutant to the 25th percentile were NO2 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: NO2 RD = -2.8 (95% CI: -5.2, -0.3) and BC RD = -3.0 (95% CI: -6.4, 0.4).

BackgroundPer- 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.MethodsParticipants 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.ResultsSeven 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.ConclusionsResults indicate that consumption of animal products may contribute to elevated prenatal PFAS levels.

BackgroundExposure to fatal police violence may play a role in population-level inequities in risk for preterm delivery.ObjectiveTo 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.MethodsWe 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.ResultsExposure 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.ConclusionsPreventing police use of lethal force may reduce preterm delivery in communities where such violence occurs.

BackgroundUS 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.MethodsWe 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.ResultsThere 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.ConclusionsExposure to TRAP, especially black carbon, may increase the risk of preterm birth for Latina and Black women but not for Asian and White women.

BackgroundPrenatal 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.MethodsUsing 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.ResultsAn 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.ConclusionsThis 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.

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.MethodsWe 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.ResultsDepletion 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).ConclusionsIn simulations, hazardous environmental exposures induced live-birth bias and the bias was larger for socially vulnerable women.

BackgroundWomen 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.MethodsWe 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.ResultsFood 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).ConclusionsOur 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.

BackgroundFirearm 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.MethodsWe 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.ResultsFirearm 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.ConclusionWe 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.

BackgroundSystematic 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.MethodsWe 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.ResultsThe 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.ConclusionsTools 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 registrationThis 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 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.

BackgroundTelomere 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.MethodsIn 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.ResultsIn 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.ConclusionsThis study is the first to examine the joint effect of multiple stressors during pregnancy on newborn TL using a flexible modeling approach.

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.

BackgroundStudies have reported associations between unconventional natural gas development (UNGD) and adverse birth outcomes. None have evaluated potential mediating mechanisms.ObjectivesTo evaluate associations between (1) UNGD and antenatal anxiety and depression and (2) antenatal anxiety and depression and preterm birth (

BackgroundCommunity violence is an understudied aspect of social context that may affect risk of preterm birth and small-for-gestational age (SGA).MethodsWe matched California mothers with live singleton births who were exposed to a homicide in their Census tract of residence in 2007-2011 to unexposed mothers within the same tract. We estimated risk differences with a weighted linear probability model, with weights corresponding to the matched data structure. We estimated the average treatment effect on the treated of homicide exposure on the risk of preterm birth and SGA during the preconception period and first and second trimester.ResultsWe found a small increase in risk of SGA associated with homicide exposure in the first trimester (0.14% [95% confidence interval (CI) = -0.01%, 0.30%]), but not for exposure during the preconception period (-0.01% [95% CI = -0.17%, 0.15%]) or the second trimester (-0.06% [95% CI = -0.23%, 0.11%]). Risk of preterm birth was not affected by homicide exposure. When women were exposed to homicides during all three exposure windows, there was a larger increase in risk of SGA (1.09% [95% CI = 0.15%, 2.03%]) but not preterm birth (0.14% [95% CI = -0.74%, 1.01%]). Exposure to three or more homicides was also associated with greater risk of SGA (0.78% [95% CI = 0.15%, 1.40%]). Negative controls indicated that residual confounding by temporal patterning was unlikely.ConclusionsHomicide exposure during early pregnancy is associated with a small increased risk of SGA.

Police use of force is an important public health issue in the US. Recent high-profile incidents suggest a potential link between mental disorders and police use of force, however little research has examined their co-occurrence in the general population. We aimed to assess the overall association between specific mental and substance use disorders (MSUDs) and nonfatal legal intervention injury. We identified nonfatal legal intervention injury cases (n = 90,099) and MSUD diagnoses from all hospital and emergency department (ED) records in California between 2005 and 2014. Age-, sex-, and race-standardized MSUD prevalence estimates among legal intervention injury cases, stratified by inpatient status, were compared to general US population-based estimates from the National Comorbidity Survey Replication. Compared to the general US population, nonaffective psychoses, mood disorders, alcohol use disorders, and drug use disorders were substantially overrepresented among inpatient legal intervention injuries (prevalence difference [PD]: 19.2%, (95% confidence interval [CI]: 18.0, 20.4); PD: 15.3%, (95% CI: 13.9, 16.7); PD: 21.1%, (95% CI: 19.8, 22.4); PD: 29.7%, (95% CI: 28.4, 31.0), respectively). Associations for all except mood disorders were similar but attenuated among ED injury cases. In contrast, anxiety disorders were underrepresented in both inpatient and ED injury cases. Results for mood disorders and suicidal ideation were mixed. In summary, MSUDs characterized by more overt behavioral symptoms were substantially overrepresented among legal intervention injury cases. Findings support the potential importance of interventions to improve treatment and law enforcement recognition of such disorders. Additional research should disentangle the complex relationship between MSUDs and legal intervention injury.

IntroductionAdolescent girls and young women (AGYW) in South Africa bear a disproportionate burden of HIV. Community mobilization (CM), defined as community members taking collective action to achieve a common goal related to health, equity and rights, has been associated with increased HIV testing and condom use and has been called a 'critical enabler' for addressing the HIV epidemic. However, limited research has examined whether CM is associated with HIV incidence among AGYW.MethodsWe examine the association of CM with incident HIV among AGYW (ages 13 to 21) enrolled in the HPTN 068 cohort in the Agincourt Health and socio-Demographic Surveillance System, South Africa. This analysis includes 2292 participants residing in 26 villages where cross-sectional, population-based surveys were conducted to measure CM among 18- to 35-year-old residents in 2012 and 2014. HPTN 068 participants completed up to five annual visits that included an HIV test (2011 to 2016). Household-level data were collected from AGYW parents/guardians and census data is updated annually. Mean village-level CM scores were created using a validated community mobilization measure with seven components (social cohesion, social control, critical consciousness, shared concerns, organizations and networks, leadership and collective action). We used pooled generalized estimating equation regression with a Poisson distribution to estimate risk ratios (RR) for the association of village-level CM score and CM components with incident HIV infection, accounting for village-level clustering and adjusting for key covariates.ResultsThere were 194 incident infections over the follow-up period. For every additional standard deviation of village-level CM there was 12% lower HIV incidence (RR: 0.88, 95% CI: 0.79, 0.98) after adjusting for individual, household and community characteristics. CM components associated with lower HIV incidence included critical consciousness (RR: 0.88; CI: 0.79, 0.97) and leadership (RR: 0.87; CI: 0.79, 0.95); while not statistically significant, social cohesion (RR: 0.91; CI: 0.81, 1.01), shared concerns (RR: 0.90; CI: 0.81, 1.00), and organizations and networks (RR: 0.91; CI: 0.79, 1.03) may also play a protective role.ConclusionsThese results suggest that having strong community social resources will reduce AGYW's risk of HIV acquisition. Work to mobilize communities, focusing on building social cohesion, shared concerns, critical consciousness, and effective and accountable leadership, can fortify prevention programming for AGYW.

Coal and oil power plant retirements reduce air pollution nearby, but few studies have leveraged these natural experiments for public health research. We used California Department of Public Health birth records and US Energy Information Administration data from 2001-2011 to evaluate the relationship between the retirements of 8 coal and oil power plants and nearby preterm (gestational age of

BackgroundFew studies have explored the relationship between air pollution and fertility. We used a natural experiment in California when coal and oil power plants retired to estimate associations with nearby fertility rates.MethodsWe used a difference-in-differences negative binomial model on the incident rate ratio scale to analyze the change in annual fertility rates among California mothers living within 0-5 km and 5-10 km of 8 retired power plants between 2001 and 2011. The difference-in-differences method isolates the portion of the pre- versus post-retirement contrast in the 0-5 km and 5-10 km bins, respectively, that is due to retirement rather than secular trends. We controlled for secular trends with mothers living 10-20 km away. Adjusted models included fixed effects for power plant, proportion Hispanic, Black, high school educated, and aged > 30 years mothers, and neighborhood poverty and educational attainment.ResultsAnalyses included 58,909 live births. In adjusted models, we estimated that after power plant retirement annual fertility rates per 1000 women aged 15–44 years increased by 8 births within 5 km and 2 births within 5-10 km of power plants, corresponding to incident rate ratios of 1.2 (95% CI: 1.1–1.4) and 1.1 (95% CI: 1.0–1.2), respectively. We implemented a negative exposure control by randomly selecting power plants that did not retire and repeating our analysis with those locations using the retirement dates from original 8 power plants. There was no association, suggesting that statewide temporal trends may not account for results.ConclusionsFertility rates among nearby populations appeared to increase after coal and oil power plant retirements. Our study design limited the possibility that our findings resulted from temporal trends or changes in population composition. These results require confirmation in other populations, given known methodological limitations of ecologic study designs.