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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.

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.

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 2,420 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.

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.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.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-FApproximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of FHere, oxidative stress, as measured by 8-iso-prostaglandin-F

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.

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

BackgroundNon-targeted Analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications.ObjectivesWe characterize 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 evaluate relationships between maternal and cord levels and the relationship 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 from 302 pregnant people at delivery from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculate distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. We used 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 (coefficient = 0.9), linear PFOS (0.8), and branched PFOS (0.8). An IQR increase in linear PFOS, branched PFOS, and octadecanedioic acid is associated with increased odds of GDM [OR (95%CI): 1.43 (0.96, 2.14), 1.56 (1.00, 2.44), and 1.26 (0.83, 1.92) respectively] and tridecanedioic acid positively associated with hypertensive disorders of pregnancy [1.28 (0.90, 1.86)].DiscussionWe identified both exogenous and endogenous chemicals, two of which (octadecanedioic acid and tridecanedioic acid) have both endogenous and exogenous sources, and which have seldom been quantified in pregnant people or related to pregnancy complications.

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.

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.

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.

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

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.

BACKGROUND: Firearm homicides occur less frequently in US states with more firearm control laws. However, firearms are easily transported across state lines, and laws in one location may affect firearm violence in another. This study examined associations between within-state firearm laws and firearm homicide while accounting for interference from laws in other nearby states. METHODS: The units of analysis were 3,107 counties in the 48 contiguous US states, arrayed in 15 yearly panels for 2000–2014 (n = 46,605). The dependent measure was firearm homicides accessed from CDC Compressed Mortality Data. The main independent measures were counts of firearm laws and the proportion of laws within categories (e.g., background checks, child access prevention laws). We calculated these measures for interstate laws using a geographic gravity function between county centroids. Bayesian conditional autoregressive Poisson models related within-state firearm laws and interstate firearm laws to firearm homicides. RESULTS: There were 172,726 firearm homicides in the included counties over the 15 years. States had between 3 and 100 firearm laws. Within-state firearm laws (IRR [Incidence rate ratio] = 0.995, 95%CI: 0.992, 0.997) and interstate firearm laws (IRR = 0.993, 95%CI: 0.990, 0.996) were independently associated with fewer firearm homicides, and associations for within-state laws were strongest where interstate laws were weakest. CONCLUSIONS: Additional firearm laws are associated with fewer firearm homicides both within the states where the laws are enacted and elsewhere in the US. Interference from interstate firearm laws may bias associations for studies of within-state laws and firearm homicide.

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.

Identification of unexpectedly high values in a time series is useful for epidemiologists, economists, and other social scientists interested in the effect of an exposure spike on an outcome variable. However, the best method to identify spikes in time series is not known. This paper aims to fill this gap by testing the performance of several spike detection methods in a simulation setting. We created simulations parameterized by monthly violence rates in nine California cities that represented different series features, and randomly inserted spikes into the series. We then compared the ability to detect spikes of the following methods: ARIMA modeling, Kalman filtering and smoothing, wavelet modeling with soft thresholding, and an iterative outlier detection method. We varied the magnitude of spikes from 10-50% of the mean rate over the study period and varied the number of spikes inserted from 1 to 10. We assessed performance of each method using sensitivity and specificity. The Kalman filtering and smoothing procedure had the best overall performance. We applied Kalman filtering and smoothing to the monthly violence rates in nine California cities and identified spikes in the rate over the 2005-2012 period.

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.

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.