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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.

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.

Author(s): Goin, Dana E; Izano, Monika A; Eick, Stephanie M; Padula, Amy M; DeMicco, Erin; Woodruff, Tracey J; Morello-Frosch, Rachel | Abstract: 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.

Objectives. To evaluate whether the Operation Peacemaker Fellowship, an innovative firearm violence-prevention program implemented in Richmond, California, was associated with reductions in firearm and nonfirearm violence. Methods. We compiled city- and jurisdiction-level quarterly counts of violent firearm and nonfirearm incidents from statewide records of deaths from and hospital visits for homicide and assault (2005–2016) and from nationwide crime records of homicides and aggravated assaults (1996–2015). We applied a generalization of the synthetic control method to compare observed patterns in firearm and nonfirearm violence after implementation of the program (June 2010) to those predicted in the absence of the program, using a weighted combination of comparison cities or jurisdictions. Results. The program was associated with reductions in firearm violence (annually, 55% fewer deaths and hospital visits, 43% fewer crimes) but also unexpected increases in nonfirearm violence (annually, 16% more deaths and hospital visits, 3% more crimes). These associations were unlikely to be attributable to chance for all outcomes except nonfirearm homicides and assaults in crime data. Conclusions. The Operation Peacemaker Fellowship may have been effective in reducing firearm violence in Richmond but may have increased nonfirearm violence.

Exposure to nitrogen dioxide (NO(2)), black carbon (BC), and ultrafine particles (UFP) during pregnancy may increase risk of preeclampsia, but previous studies have not assessed hyper-localized 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 UFP every 30-meters 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-meters of monitoring data (N=1,095) to identify preeclampsia cases. We used G-computation with log-binomial regression to estimate risk differences (RD) associated with hypothetical interventions reducing pollutant levels to 25(th) percentiles 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 UFP 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 25(th) percentile was 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 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).

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 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.

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 (20-27weeks), early (28-31weeks), moderate (32-33weeks), and late (32-36weeks) 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.

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.

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.

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.

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.

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.

BackgroundPrevious 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 (MUFSG), maternal serum fluoride (MSF), amniotic fluid fluoride (AFF) concentrations during pregnancy, and community water fluoridation in Northern California.MethodsArchived 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.ResultsFluoride 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), MUFSG(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).ConclusionsWe 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.

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.

Background Community violence may affect a broad range of health outcomes through physiologic stress responses and changes in health behaviors among residents. However, existing research on the health impacts of community violence suffers from problems with bias. Methods We examined the relations of acute changes in community violence with hospital visits and deaths due to stress-responsive diseases (mental, respiratory, and cardiac conditions) in statewide data from California 2005-2013. The community violence exposure was measured as both binary spikes and continuous acute changes. We applied a combined fixed-effects and time-series design that separates the effects of violence from those of community- and individual-level confounders more effectively than past research. Temporal patterning was removed from community violence rates and disease rates in each place using a Kalman smoother, resulting in residual rates. We used linear regression with place fixed-effects to examine within-place associations of acute changes in community violence with residual rates of each outcome, controlling for local time-varying covariates. Results We found acute increases in hospital visits and deaths due to anxiety disorders (0.31 per 100,000; 95% confidence interval [CI] = 0.02, 0.59), substance use (0.47 per 100,000; 95% CI = 0.14, 0.80), asthma (0.56 per 100,000; 95% CI = 0.16, 0.95), and fatal acute myocardial infarction (0.09 per 100,000; 95% CI = 0.00, 0.18) co-occurring with violence spikes. The pattern of findings was similar for the exposure of continuous acute violence changes. Conclusions Although the associations were small, the identified increases in stress-responsive conditions suggest the possibility of health impacts of acute changes in community violence.

Background Little is known about gene expression changes induced by pregnancy in women with rheumatoid arthritis (RA) and healthy women because the few studies previously conducted did not have pre-pregnancy samples available as baseline. We have established a cohort of women with RA and healthy women followed prospectively from a pre-pregnancy baseline. In this study, we tested the hypothesis that pregnancy-induced changes in gene expression among women with RA who improve during pregnancy (pregDASimproved) overlap substantially with changes observed among healthy women and differ from changes observed among women with RA who worsen during pregnancy (pregDASworse). Methods Global gene expression profiles were generated by RNA sequencing (RNA-seq) from 11 women with RA and 5 healthy women before pregnancy (T0) and at the third trimester (T3). Among the women with RA, eight showed an improvement in disease activity by T3, whereas three worsened. Differential expression analysis was used to identify genes demonstrating significant changes in expression within each of the RA and healthy groups (T3 vs T0), as well as between the groups at each time point. Gene set enrichment was assessed in terms of Gene Ontology processes and protein networks. Results A total of 1296 genes were differentially expressed between T3 and T0 among the 8 pregDASimproved women, with 161 genes showing at least two-fold change (FC) in expression by T3. The majority (108 of 161 genes) were also differentially expressed among healthy women (q

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.

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.

Supplemental Digital Content is available in the text., Background: 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.

© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society. Introduction: Adolescent 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. Methods: We 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. Results: There 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. Conclusions: These 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

Interpersonal firearm violence is a leading cause of death and injuries in the United States. Identifying community characteristics associated with firearm violence is important to improve confounder selection and control in health research, to better understand community-level factors that are associated with firearm violence, and to enhance community surveillance and control of firearm violence. The objective of this research was to use machine learning to identify an optimal set of predictors for urban interpersonal firearm violence rates using a broad set of community characteristics. The final list of 18 predictive covariates explain 77.8% of the variance in firearm violence rates, and are publicly available, facilitating their inclusion in analyses relating violence and health. This list includes the black isolation and segregation indices, rates of educational attainment, marital status, indicators of wealth and poverty, longitude, latitude, and temperature.

Background/Aim: Many studies have identified increased air pollution as a risk factor for preterm birth. However, given the multifactorial etiology of preterm birth, systematic differences–e.g., lo...

Objectives. We examined preventive care use by nonelderly adults (aged 18–64 years) before the Affordable Care Act (ACA) and considered the contributions of insurance coverage and other factors to service use patterns. Methods. We used data from the 2005–2010 Medical Expenditure Panel Survey to measure the receipt of 8 recommended preventive services. We examined gaps in receipt of services for adults with incomes below 400% of the federal poverty level compared with higher incomes. We then used a regression-based decomposition analysis to consider factors that explain the gaps in service use by income. Results. There were large income-related disparities in preventive care receipt for nonelderly adults. Differences in insurance coverage explain 25% to 40% of the disparities in preventive service use by income, but education, age, and health status are also important drivers. Conclusions. Expanding coverage to lower-income adults through the ACA is expected to increase their preventive care use. However, the importance of education, age, and health status in explaining income-related gaps in service use indicates that the ACA cannot address all barriers to preventive care and additional interventions may be necessary.

The Health Reform Monitoring Survey (HRMS) was launched in 2013 as a mechanism to obtain timely information on the Affordable Care Act (ACA) during the period before federal government survey data for 2013 and 2014 will be available. Based on a nationally representative, probability-based Internet panel, the HRMS provides quarterly data for approximately 7,400 nonelderly adults and 2,400 children on insurance coverage, access to health care, and health care affordability, along with special topics of relevance to current policy and program issues in each quarter. For example, HRMS data from summer 2013 show that more than 60 percent of those targeted by the health insurance exchanges struggle with understanding key health insurance concepts. This raises concerns about some people's ability to evaluate trade-offs when choosing health insurance plans. Assisting people as they attempt to enroll in health coverage will require targeted education efforts and staff to support those with low health insurance literacy.

Background During pregnancy, most women do not meet gestational weight gain (GWG) guidelines, potentially resulting in adverse maternal and infant health consequences. Social environment determinants of GWG have been identified, but evidence on the relationship between neighbourhood violence and GWG is scant. Our study aims to examine the relationship between neighbourhood violence and GWG outside the recommended range. Methods We used statewide vital statistics and health care utilization data from California for 2006–12 (n = 2 364 793) to examine the relationship of neighbourhood violence (quarters of zip-code rates of homicide and assault) in the first 37 weeks of pregnancy with GWG (categorized using the Institute of Medicine's pregnancy weight gain guidelines). We estimated risk ratios (RR) and marginal risk differences, and analyses were stratified by maternal race/ethnicity and prepregnancy body mass index. Results Residence in neighbourhoods with the highest quartile of violence was associated with more excessive GWG (adjusted RR 1.04, 95% confidence interval CI 1.03, 1.05), compared to the lowest quartile of violence; violence was not associated with inadequate GWG. On the difference scale, this association translates to 2.3% more women gaining weight excessively rather than adequately if all women were exposed to high violence compared to if all women were exposed to low violence. Additionally, associations between neighbourhood violence and excessive GWG were larger in non-white women than in white women. Conclusions These findings support the hypothesis that violence can affect weight gain during pregnancy, emphasizing the importance of neighbourhood violence as a public health issue.

BACKGROUND: Studies have reported associations between unconventional natural gas development (UNGD) and adverse birth outcomes. None have evaluated potential mediating mechanisms. OBJECTIVES: To evaluate associations between (1) UNGD and antenatal anxiety and depression and (2) antenatal anxiety and depression and preterm birth (< 37 weeks gestation) and reduced term birth weight, (3) stochastic direct and indirect effects of UNGD on preterm birth and term birth weight operating through antenatal anxiety and depression, and (4) effect modification by family-level socioeconomic status. METHODS: This retrospective cohort study included mothers without prevalent anxiety or depression at time of conception, who delivered at Geisinger in Pennsylvania between January 2009–January 2013. We assembled phase-specific UNGD activity data from public sources. Mothers were categorized as exposed (quartile 4) or unexposed (quartiles 1–3) based on average daily inverse distance-squared UNGD activity metric between conception and the week prior to anxiety or depression (cases) or the pregnancy-average daily metric (non-cases). We estimated associations with a doubly robust estimator (targeted minimum loss-based estimation) and adjusted for potential individual- and community-level confounding variables. RESULTS: Analyses included 8,371 births to 7,715 mothers, 12.2% of whom had antenatal anxiety or depression. We found 4.3 additional cases of antenatal anxiety or depression per 100 women (95% CI: 1.5, 7.0) under the scenario where all mothers lived in the highest quartile of UNGD activity versus quartiles 1–3. The risk difference appeared larger among mothers receiving Medical Assistance (indicator of low family income) compared to those who did not, 5.6 (95% CI: 0.5, 10.6) versus 2.9 (95% CI: −0.7, 6.5) additional cases of antenatal anxiety or depression per 100 women. We found no relationship between antenatal anxiety or depression and adverse birth outcomes and no mediation effect either overall or when stratifying by Medical Assistance. CONCLUSION: We observed a relationship between UNGD activity and antenatal anxiety and depression, which did not mediate the overall association between UNGD activity and adverse birth outcomes.

The pending Supreme Court decision on the Affordable Care Act and the fall presidential election raise concerns about what would happen if the insurance expansion promised by the landmark health reform law were to be curtailed. This paper's analysis of national survey estimates found that access to health care and use of health services for adults ages 19-64--the primary targets of the Affordable Care Act--deteriorated between 2000 and 2010, particularly among those who were uninsured. More than half of uninsured US adults did not see a doctor in 2010, and only slightly more than a quarter of these adults were seen by a dentist. We also found that children--many of whom qualify for public coverage through Medicaid and the Children's Health Insurance Program--generally maintained or improved their access to care during the same period. This provides a reason for optimism about the ability of the coverage expansion in the Affordable Care Act to improve access for adults, but it suggests that eliminating the law or curtailing the coverage expansion could result in continued erosion of adults' access to care.