Search

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

Pregnant people are vulnerable to air pollution exposure, including risk of preterm birth, low birth weight, and stillbirth. Understanding the infiltration of outdoor wildfire smoke into a residential space is critical for the accurate assessment of wildfire smoke exposure and associated health effects in pregnant people. Relying on ambient measurements of wildfire smoke alone can result in exposure misclassification. In this study, we examine the role of physical housing characteristics in the relationship between smoke exposure and preterm birth. In particular, we examine the effect of home size, year of construction, cooling type, and renovation status, as effect modifiers in the relationship between smoke exposure during pregnancy and preterm birth from 2007 to 2015 in California. To do this, we combined data on home characteristics from the California Tax Assessor, birth outcomes from the California birth records database, and the number of smoke days for each pregnancy from theNOAA (National Oceanic and Atmospheric Administration) Hazard Mapping System (HMS). We estimated the association between smoke day exposures and odds of preterm birth using logistic regression models and stratified by air basin and housing characteristics. Our findings reveal that cooling type and renovation status are key factors modifying the smoke exposure-preterm birth relationship. Notably, we found elevated associations for people living in unrenovated homes, those using evaporative cooling systems, and those using central air conditioning units. While we observed elevated odds of preterm birth associated with increasing smoke day exposure for residents of large and new homes, this effect does not significantly differ across home size and age quartiles. This study highlights the need to further examine the relative roles of housing characteristics as well as factors not measured here including behavioral factors, time spent outdoors, window use, and occupational exposures in driving adverse birth outcomes related to wildfire smoke exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

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

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

Background: Wildfires in the Western United States are a growing and significant source of air pollution that is eroding decades of progress in air pollution reduction. The effects on preterm birth during critical periods of pregnancy are unknown., Methods: We assessed associations between prenatal exposure to wildland fire smoke and risk of preterm birth (gestational age < 37 weeks). We assigned smoke exposure to geocoded residence at birth for all live singleton births in California conceived 2007-2018, using weekly average concentrations of particulate matter ≤ 2.5 µm (PM 2.5 ) attributable to wildland fires from United States Environmental Protection Agency's Community Multiscale Air Quality Model. Logistic regression yielded odds ratio (OR) for preterm birth in relation to increases in average exposure across the whole pregnancy, each trimester, and each week of pregnancy. Models adjusted for season, age, education, race/ethnicity, medical insurance, and smoking of the birthing parent., Results: For the 5,155,026 births, higher wildland fire PM 2.5 exposure averaged across pregnancy, or any trimester, was associated with higher odds of preterm birth. The OR for an increase of 1 µg/m 3 of average wildland fire PM 2.5 during pregnancy was 1.013 (95 % CI:1.008,1.017). Wildland fire PM 2.5 during most weeks of pregnancy was associated with higher odds. Strongest estimates were observed in weeks in the second and third trimesters. A 10 µg/m 3 increase in average wildland fire PM 2·5 in gestational week 23 was associated with OR = 1.034; 95 % CI: 1.019, 1.049 for preterm birth., Conclusions: Preterm birth is sensitive to wildland fire PM 2.5 ; therefore, we must reduce exposure during pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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

Background: Pregnancy is known to induce extensive biological changes in the healthy mother. Little is known, however, about what these changes are at the molecular level. We have examined systemic expression changes in protein-coding genes and long non-coding (lnc) RNAs during and after pregnancy, compared to before pregnancy, among healthy women with term pregnancies., Methods: Blood samples were collected from 14 healthy women enrolled in our prospective pregnancy cohort at 7 time-points (before, during and after pregnancy). Total RNA from frozen whole blood was used for RNA sequencing. Following raw read alignment and assembly, gene-level counts were obtained for protein-coding genes and long non-coding RNAs. At each time-point, cell type proportions were estimated using deconvolution. To examine associations between pregnancy status and gene expression over time, Generalized Estimating Equation (GEE) models were fitted, adjusting for age at conception, and with and without adjusting for changes in cell type proportions. Fold-changes in expression at each trimester were examined relative to the pre-pregnancy baseline., Results: Numerous immune-related genes demonstrated pregnancy-associated expression, in a time-dependent manner. The genes that demonstrated the largest changes in expression included several that were neutrophil-related (over-expressed) and numerous immunoglobulin genes (under-expressed). Estimated cell proportions revealed a marked increase in neutrophils, and less so of activated CD4 memory T cells, during pregnancy, while most other cell type proportions decreased or remained unchanged. Adjusting for cell type proportions in our model revealed that although most of the expression changes were due to changes in cell type proportions in the bloodstream, transcriptional regulation was also involved, especially in down-regulating expression of type I interferon inducible genes., Conclusion: Compared to a pre-pregnancy baseline, there were extensive systemic changes in cell type proportions, gene expression and biological pathways associated with different stages of pregnancy and postpartum among healthy women. Some were due to changes in cell type proportions and some due to gene regulation. In addition to providing insight into term pregnancy among healthy women, these findings also provide a "normal" reference for abnormal pregnancies and for autoimmune diseases that improve or worsen during pregnancy, to assess deviations from normal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wright, Goin, Smed, Jewell, Nelson, Olsen, Hetland, Zoffmann and Jawaheer.)

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

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

Background: Exposure to environmental chemicals during pregnancy adversely affects maternal and infant health, and identifying socio-demographic differences in exposures can inform contributions to health inequities., Methods: We recruited 294 demographically diverse pregnant participants in San Francisco from the Mission Bay/Moffit Long (MB/ML) hospitals, which serve a primarily higher income population, and Zuckerberg San Francisco General Hospital (ZSFGH), which serves a lower income population. We collected maternal and cord sera, which we screened for 2420 unique formulas and their isomers using high-resolution mass spectrometry using LC-QTOF/MS. We assessed differences in chemical abundances across socioeconomic and demographic groups using linear regression adjusting for false discovery rate., Results: Our participants were racially diverse (31% Latinx, 16% Asian/Pacific Islander, 5% Black, 5% other or multi-race, and 43% white). A substantial portion experienced financial strain (28%) and food insecurity (20%) during pregnancy. We observed significant abundance differences in maternal (9 chemicals) and cord sera (39 chemicals) between participants who delivered at the MB/ML hospitals versus ZSFGH. Of the 39 chemical features differentially detected in cord blood, 18 were present in pesticides, one per- or poly-fluoroalkyl substance (PFAS), 21 in plasticizers, 24 in cosmetics, and 17 in pharmaceuticals; 4 chemical features had unknown sources. A chemical feature annotated as 2,4-dichlorophenol had higher abundances among Latinx compared to white participants, those delivering at ZSFGH compared to MB/ML, those with food insecurity, and those with financial strain. Post-hoc QTOF analyses indicated the chemical feature was either 2,4-dichlorophenol or 2,5-dichlorophenol, both of which have potential endocrine-disrupting effects., Conclusions: Chemical exposures differed between delivery hospitals, likely due to underlying social conditions faced by populations served. Differential exposures to 2,4-dichlorophenol or 2,5-dichlorophenol may contribute to disparities in adverse outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2018.)

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., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

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.

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

Climate and weather have been linked to criminal activity. The connection between climatological conditions and crime is of growing importance as we seek to understand the societal implications of climate change. This study describes the mechanisms theorized to link annual variations in climate to crime in California and examines the effect of drought on statewide crime rates from 2011-2015. California has suffered severe drought since 2011, resulting in intensely dry winters and several of the hottest days on record. It is likely that the drought increased economic stress and shifted routine activities of the population, potentially increasing the likelihood of crime. We used a synthetic control method to estimate the impact of California's drought on both property and violent crimes. We found a significant increase in property crimes during the drought, but no effect on violent crimes. This result was robust to several sensitivity analyses, including a negative control.

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 (pregDAS improved ) overlap substantially with changes observed among healthy women and differ from changes observed among women with RA who worsen during pregnancy (pregDAS worse )., 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 pregDAS improved 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<0.05, FC≥2). Additionally, a small cluster of genes demonstrated contrasting changes in expression between the pregDAS improved and pregDAS worse groups, all of which were inducible by type I interferon (IFN). These IFN-inducible genes were over-expressed at T3 compared to the T0 baseline among the pregDAS improved women., Conclusions: In our pilot RNA-seq dataset, increased pregnancy-induced expression of type I IFN-inducible genes was observed among women with RA who improved during pregnancy, but not among women who worsened. These findings warrant further investigation into expression of these genes in RA pregnancy and their potential role in modulation of disease activity. These results are nevertheless preliminary and should be interpreted with caution until replicated in a larger sample.

Objective: To assess the effects of past Medicaid eligibility expansions to parents on coverage, access to care, out-of-pocket (OOP) spending, and mental health outcomes, and consider implications for the Affordable Care Act (ACA) Medicaid expansion., Data Sources: Person-level data from the National Health Interview Survey (1998-2010) is used to measure insurance coverage and related outcomes for low-income parents. Using state identifiers available at the National Center for Health Statistics Research Data Center, we attach state Medicaid eligibility thresholds for parents collected from a variety of sources to NHIS observations., Study Design: We use changes in the Medicaid eligibility threshold for parents within states over time to identify the effects of changes in eligibility on low-income parents., Principal Findings: We find that expanding Medicaid eligibility increases insurance coverage, reduces unmet needs due to cost and OOP spending, and improves mental health status among low-income parents. Moreover, our findings suggest that uninsured populations in states not currently participating in the ACA Medicaid expansion would experience even larger improvements in coverage and related outcomes than those in participating states if they chose to expand eligibility., Conclusions: The ACA Medicaid expansion has the potential to improve a wide variety of coverage, access, financial, and health outcomes for uninsured parents in states that choose to expand coverage., (© Health Research and Educational Trust.)

Matching methods are common in studies across many disciplines. However, there is limited evidence on how to optimally combine matching with subsequent analysis approaches to minimize bias and maximize efficiency for the quantity of interest. We conducted simulations to compare the performance of a wide variety of matching methods and analysis approaches in terms of bias, variance, and mean squared error (MSE). We then compared these approaches in an applied example of an employment training program. The results indicate that combining full matching with double robust analysis performed best in both the simulations and the applied example, particularly when combined with machine learning estimation methods. To reduce bias, current guidelines advise researchers to select the technique with the best post-matching covariate balance, but this work finds that such an approach does not always minimize mean squared error (MSE). These findings have important implications for future research utilizing matching. To minimize MSE, investigators should consider additional diagnostics, and use of simulations tailored to the study of interest to identify the optimal matching and analysis combination.