Fluoride-related changes in the fetal cord blood proteome; a pilot study.

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

Comparing Two-way Fixed Effects and New Estimators for Difference-in-Differences: A Simulation Study and Empirical Example.

BACKGROUND: Two-way fixed effects methods have been used to estimate effects of policies adopted in different places over time, but they can provide misleading results when effects are heterogeneous or dynamic, and alternate methods have been proposed. METHODS: We compared methods for estimating the average treatment effect on the treated (ATT) under staggered adoption of policies, including two-way fixed effects, group-time ATT, cohort ATT, and target-trial approaches. We applied each method to assess the impact of Medicaid expansion on preterm birth using the National Center for Health Statistics' birth records. We compared each estimator's performance in a simulation parameterized to mimic the empirical example. We generated constant, heterogeneous, and dynamic effects and calculated bias, mean squared error, and confidence interval coverage of each estimator across 1000 iterations. RESULTS: Two-way fixed effects estimated that Medicaid expansion increased the risk of preterm birth (risk difference [RD], 0.12; 95% CI = 0.02, 0.22), while the group-time ATT, cohort ATT, and target-trial approaches estimated protective or null effects (group-time RD, -0.16; 95% CI = -0.58, 0.26; cohort RD, -0.02; 95% CI = -0.46, 0.41; target trial RD, -0.16; 95% CI = -0.59, 0.26). In simulations, two-way fixed effects performed well when treatment effects were constant and less well under heterogeneous and dynamic effects. CONCLUSIONS: We demonstrated why new approaches perform better than two-way fixed effects when treatment effects are heterogeneous or dynamic under a staggered policy adoption design, and created simulation and analysis code to promote understanding and wider use of these methods in the epidemiologic literature.

Urinary oxidative stress biomarkers are associated with preterm birth: an Environmental Influences on Child Health Outcomes program study.

BACKGROUND: Preterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States. OBJECTIVE: We leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin. STUDY DESIGN: This study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-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. RESULTS: Approximately 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. CONCLUSION: Here, 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.

Disparities in chemical exposures among pregnant women and neonates by socioeconomic and demographic characteristics: A nontargeted approach.

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

California's Mental Health Services Act and Mortality Due to Suicide, Homicide, and Acute Effects of Alcohol: A Synthetic Control Application.

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.

Maternal Experience of Multiple Hardships and Fetal Growth: Extending Environmental Mixtures Methodology to Social Exposures.

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

Occurrence of fatal police violence during pregnancy and hazard of preterm birth in California.

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

Hyperlocalized Measures of Air Pollution and Preeclampsia in Oakland, California.

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).

Mixture effects of prenatal exposure to per- and polyfluoroalkyl substances and polybrominated diphenyl ethers on maternal and newborn telomere length.

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.

The Peril of Power: A Tutorial on Using Simulation to Better Understand When and How We Can Estimate Mediating Effects.

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

Mediation of Firearm Violence and Preterm Birth by Pregnancy Complications and Health Behaviors: Addressing Structural and Postexposure Confounding.

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.

Depression and Incident HIV in Adolescent Girls and Young Women in HIV Prevention Trials Network 068: Targets for Prevention and Mediating Factors.

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.

The Relative Economy and Drug Overdose Deaths.

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.

Maternal and fetal exposures to fluoride during mid-gestation among pregnant women in northern California.

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

Causal Mediation Analysis With Observational Data: Considerations and Illustration Examining Mechanisms Linking Neighborhood Poverty to Adolescent Substance Use.

Understanding the mediation mechanisms by which an exposure or intervention affects an outcome can provide a look into what has been called a "black box" of many epidemiologic associations, thereby providing further evidence of a relationship and possible points of intervention. Rapid methodologic developments in mediation analyses mean that there are a growing number of approaches for researchers to consider, each with its own set of assumptions, advantages, and disadvantages. This has understandably resulted in some confusion among applied researchers. Here, we provide a brief overview of the mediation methods available and discuss points for consideration when choosing a method. We provide an in-depth explication of 2 of the many potential estimators for illustrative purposes: the Baron and Kenny mediation approach, because it is the most commonly used, and a recently developed approach for estimating stochastic direct and indirect effects, because it relies on far fewer assumptions. We illustrate the decision process and analytical procedure by estimating potential school- and peer-based mechanisms linking neighborhood poverty to adolescent substance use in the National Comorbidity Survey Adolescent Supplement.

Exposure to Community Homicide During Pregnancy and Adverse Birth Outcomes: A Within-Community Matched Design.

BACKGROUND: Community violence is an understudied aspect of social context that may affect risk of preterm birth and small-for-gestational age (SGA). METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Homicide exposure during early pregnancy is associated with a small increased risk of SGA.

Firearm and Nonfirearm Violence After Operation Peacemaker Fellowship in Richmond, California, 1996-2016.

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.

Mental and substance use disorders among legal intervention injury cases in California, 2005-2014.

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.

Unconventional natural gas development and adverse birth outcomes in Pennsylvania: The potential mediating role of antenatal anxiety and depression.

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.

Retirements of Coal and Oil Power Plants in California: Association With Reduced Preterm Birth Among Populations Nearby.

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 <37 weeks) birth. We conducted a difference-in-differences analysis using adjusted linear mixed models that included 57,005 births-6.3% of which were preterm-to compare the probability of preterm birth before and after power plant retirement among mothers residing within 0-5 km and 5-10 km of the 8 power plants. We found that power plant retirements were associated with a decrease in the proportion of preterm birth within 5 km (-0.019, 95% CI: -0.031, -0.008) and 5-10 km (-0.015, 95% CI: -0.024, -0.007), controlling for secular trends with mothers living 10-20 km away. For the 0-5-km area, this corresponds to a reduction in preterm birth from 7.0% to 5.1%. Subgroup analyses indicated a potentially larger association among non-Hispanic black and Asian mothers than among non-Hispanic white and Hispanic mothers and no differences in educational attainment. Future coal and oil power plant retirements may reduce preterm birth among nearby populations.