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Background: Ambient air pollution during pregnancy has been linked with postpartum depression up to 12 months, but few studies have investigated its impact on persistent depression beyond 12 months postpartum. This study aimed to evaluate prenatal ambient air pollution exposure and the risk of persistent depression over 3 years after childbirth and to identify windows of susceptibility., Methods: This study included 361 predominantly low-income Hispanic/Latina participants with full-term pregnancies in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. We estimated daily residential PM 2.5 , PM 10 , NO 2 , and O 3 concentrations throughout 37 gestational weeks using inverse-distance squared spatial interpolation from monitoring data and calculated weekly averaged levels. Depression was assessed by the 20-item Center for Epidemiologic Studies-Depression (CES-D) scale at 12, 24, and 36 months postpartum, with persistent postpartum depression defined as a CES-D score ≥16 at any of these timepoints. We performed robust Poisson log-linear distributed lag models (DLM) via generalized estimating equations (GEE) to estimate the adjusted risk ratio (RR)., Results: Depression was observed in 17.8 %, 17.5 %, and 13.4 % of participants at 12, 24, and 36 months, respectively. We found one IQR increase (3.9 ppb) in prenatal exposure to NO 2 during the identified sensitive window of gestational weeks 13-29 was associated with a cumulative risk ratio of 3.86 (95 % CI: 3.24, 4.59) for persistent depression 1-3 years postpartum. We also found one IQR increase (7.4 μg/m 3 ) in prenatal exposure to PM 10 during gestation weeks 12-28 was associated a cumulative risk ratio of 3.88 (95 % CI: 3.04, 4.96) for persistent depression. No clear sensitive windows were identified for PM 2.5 or O 3 ., Conclusions: Mid-pregnancy PM 10 and NO 2 exposures were associated with nearly 4-fold increased risks of persistent depression after pregnancy, which has critical implications for prevention of perinatal mental health outcomes., Competing Interests: Declaration of competing interest We declare no actual or potential competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Neighborhood disadvantage is associated with a higher concentration of tobacco, cannabis and alcohol retailers and greater risk of certain substance use behaviors among youth. Less is known about the impact of subjective neighborhood disorder, which captures distinct exposures that may be relevant to substance use outcomes, including neighborhood social processes, safety, physical characteristics, and neighborhood drug use., Methods: Data are from two waves (Feb-Dec 2022) of a prospective cohort of Southern California high school students ( n  = 2,139; mean[SD] age = 15.7.[0.6]). We examined associations of perceived neighborhood disorder at baseline with (a) perceived ease of purchase (continuous scale 0-100) for alcohol, cannabis, e-cigarettes, cigarettes, hookah, cigars/cigarillos, and oral nicotine at baseline and follow-up, and (b) repeated measures of past 6-month and past-30-day alcohol, vaped cannabis, smoked cannabis, cannabis edibles, e-cigarette, cigarette, cigarillo, hookah, and oral nicotine use., Results: E-cigarettes were perceived to be the easiest product to purchase. Participants in the highest (vs. lowest) quartile of neighborhood disorder reported greater mean ease of purchasing scores for all products (mean difference range = 5.43 [95%CI: 1.64-9.21] for mint/menthol oral nicotine products to 9.40 [95%CI: 6.16-12.64] for hookah) and greater odds of e-cigarette, smoked cannabis, edibles, vaped THC, and alcohol use (odds ratio range = 1.52 [95%CI: 1.05 to 2.18] for past 6-month alcohol to 5.40 [95% CI: 3.46 to 8.42] for 30-day smoked cannabis)., Conclusions: Interventions that shape youth perceptions of their neighborhood and reduce youth retail access in disadvantaged neighborhoods are needed and may help to prevent youth substance use.

Introduction: Prospective associations of adolescent cannabis use with nicotine use persistence are not well characterized but are important for informing prevention and policy. This study examined the association of 4 types of cannabis product use with subsequent persistent nicotine product use among adolescents., Methods: We used prospective data from an adolescent cohort (14-17 years) from Southern California surveyed at baseline and at approximately 6-month follow-up (2022-2023). We incorporated three mutually non-exclusive analytic samples comprised of individuals with baseline past 6-month use of: (1) any nicotine product (N=308 [mean[SD] age = 16.3[0.6] years]), (2) e-cigarettes (n = 276), and (3) any combustible tobacco product (n = 137). Baseline past 6-month cannabis smoking, vaping, edible use, cannabidiol [CBD] or hemp product use, and any cannabis product use (yes/no) were separately modeled as predictors of past 6-month persistent use of any nicotine products, e-cigarettes, and combustible tobacco at follow-up., Results: Baseline use of any cannabis product was associated with increased odds of persistent use of e-cigarettes or any nicotine product (adjusted odds ratio[OR] range: 1.96-2.66). Cannabis smoking was positively associated with persistent any nicotine product use (adjusted OR=2.19, 95 % CI=1.20-4.02). Cannabis smoking, vaping, and edible use predicted persistent use of e-cigarettes (adjusted OR range: 2.22-2.79). Cannabis product use did not predict combustible tobacco use persistence. Associations of CBD/hemp product use with nicotine use persistence outcomes were all non-significant., Conclusions: Adolescents who use cannabis may be at elevated risk for persistent nicotine use., 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 Elsevier Ltd. All rights reserved.)

Background and Aims: Young adult cannabis use is common; while cannabis is often marketed as a product that can improve sleep, evidence supporting these claims is limited, and effects may differ for individuals with underlying mental health issues. This study measured the association between cannabis use and sleep problems among young adults and determined whether associations differ by mental health status., Design, Setting and Participants: Using two waves of a young adult cohort study (baseline: March-September 2020; follow-up: January-June 2021), we measured the association of cannabis use frequency with subsequent sleep problems overall and stratified by baseline sleep quality and mental health status in separate moderation analyses. This study was conducted in Southern California, USA, and included 1926 participants aged 20-23 years (mean age = 21; 61% female, 46% Hispanic)., Measurements: Exposure was baseline cannabis use frequency (never use, prior use, 1-5 days/month, 6-19 days/month, ≥ 20 days/month). The outcome was sleep problems at follow-up (range = 4-24, higher score indicating worse sleep). Models were adjusted for socio-demographic factors, baseline sleep problems, mental health symptoms (depression and/or anxiety versus neither) and past 30-day nicotine or alcohol use. In moderation analyses, models were additionally stratified by mental health symptoms and baseline sleep quality (excellent versus imperfect sleep)., Findings: Among the young adult sample, 11% used cannabis ≥ 20 days/month at baseline. For participants without baseline anxiety or depression symptoms, using cannabis ≥ 20 days/month (versus never use) was associated with greater sleep problems at follow-up [mean difference (MD) = 1.66, 95% confidence interval (CI) = 0.59-2.74]. Among participants with anxiety and/or depression and pre-existing sleep problems at baseline, using cannabis ≥ 20 days/month (versus never use) was associated with fewer sleep problems at follow-up (MD = -1.42, 95% CI = -2.81 to -0.02)., Conclusions: The effects of cannabis use on sleep appear to differ by underlying mental health symptoms. Frequent cannabis use may improve sleep for young adults with depression and/or anxiety who have pre-existing sleep problems, but worsen sleep for young adults without depression and/or anxiety., (© 2024 Society for the Study of Addiction.)

In this study, associations between prenatal exposure to fine particulate matter (PM2.5) from 9 sources and development of autism spectrum disorder (ASD) were assessed in a population-based retrospective pregnancy cohort in southern California. The cohort included 318,750 mother-child singleton pairs. ASD cases ( N = 4559) were identified by ICD codes. Source-specific PM2.5 concentrations were estimated from a chemical transport model with a 4 × 4 km 2 resolution and assigned to maternal pregnancy residential addresses. Cox proportional hazard models were used to estimate the hazard ratios (HR) of ASD development for each individual source. We also adjusted for total PM2.5 mass and in a separate model for all other sources simultaneously. Increased ASD risk was observed with on-road gasoline (HR [CI]: 1.18 [1.13, 1.24]), off-road gasoline (1.15 [1.12, 1.19]), off-road diesel (1.08 [1.05, 1.10]), food cooking (1.05 [1.02, 1.08]), aircraft (1.04 [1.01, 1.06]), and natural gas combustion (1.09 [1.06, 1.11]), each scaled to standard deviation increases in concentration. On-road gasoline and off-road gasoline were robust for other pollutant groups. PM2.5 emitted from different sources may have different impacts on ASD. The results also identify PM source mixtures for toxicological investigations that may provide evidence for future public health policies.

Background: Depression substantially contributes to pregnancy-related morbidity, and pregnancy is increasingly recognized as a vulnerable window for exposure effects on maternal mental health. Exposures to organophosphate esters (OPEs) are ubiquitous and may have neurotoxic effects; however, their impacts on prenatal depression remain unknown. We evaluated associations of third trimester OPE metabolites on maternal depressive symptoms during pregnancy., Methods: This study included 422 participants in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort, a prospective pregnancy cohort of primarily low-income and Hispanic participants residing in Los Angeles, California. We measured concentrations of nine OPEs in third trimester spot urine samples (mean gestational age = 31.5 ± 2.0 weeks). Using the Center for Epidemiologic Studies-Depression (CES-D) scale, we classified participants as having probable depression during pregnancy (N = 137) or not (N = 285) if one or more CES-D scores administered at each trimester met the suggested cutoff score for clinically significant depressive symptoms (≥16). We estimated associations of prenatal OPE metabolite concentrations in tertiles and risk of prenatal depression using modified Log-Poisson regression. We examined associations of the OPE mixture on depression during pregnancy using Bayesian kernel machine regression (BKMR)., Results: Participants with the highest tertiles of DPHP and BDCIPP exposure had a 67% (95% CI: 22%, 128%) and 47% (95% CI: 4%, 108%) increased risk of maternal depressive symptoms during pregnancy, respectively. No associations between other OPE metabolites and maternal depression symptoms were observed. In mixture analyses, we observed a positive and linear association between higher exposure to the OPE metabolite mixture and odds of prenatal maternal depression, primarily driven by DPHP., Conclusions: Our findings provide new evidence of associations between frequently detected OPE metabolites on maternal depression symptoms during pregnancy. Results could inform future intervention efforts aimed at reducing perinatal maternal depression., 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 Elsevier Inc. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans., Objective: To investigate associations between PFAS concentrations and miRNA levels in children., Methods: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs., Results: Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis., Conclusion: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vaia Lida Chatzi reports financial support was provided by The National Institute of Environmental Health Sciences. If there are other authors, they 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 Inc.)

Background: In California, climate change and competing water demands are intensifying the desiccation of the Salton Sea, a large land-locked "sea" situated near the southeastern rural US-Mexico border region known as the Imperial Valley., Methods: To examine the possible effects of living near a saline lake on children's respiratory health, we analyzed the relationship between respiratory health symptoms and ambient PM concentrations among a predominantly Latino/Hispanic cohort of 722 school age children. Guardians completed a survey of their child's wheeze and respiratory health symptoms over the past 12 months, adapted from the International Study of Asthma and Allergies in Childhood (ISAAC). Exposure to dust storm hours (hourly concentrations >150 μg/m 3 for PM 10 ) was estimated using a network of regulatory monitors., Results: Between 2017 and 2019, children were exposed to 98 to 395 dust event hours annually. We observed disparate effects for dust events and wheeze among children living near the Salton Sea. Every additional 100 dust storm hours per year among children living near the Sea (<11 km) was associated with a 9.5 percentage point increase in wheeze (95% CI: 3.5, 15.4), a 4.6 percentage point increase in bronchitic symptoms (95% CI: 0.18, 10.2) and a 6.7 percentage point increase in sleep disturbance due to wheeze (95% CI: 0.96, 12.4). Similarly, increases in PM 10 were also associated with greater reported wheeze and bronchitic symptoms among those living near the Sea, compared to children living ≥11 km from the Sea. There was no association of dust storms or PM 10 with wheeze or bronchitic symptoms among the children residing farther from the Sea., Conclusion: We observed stronger adverse impacts of PM 10 and dust events on respiratory health among those living closer to the drying Salton Sea, compared to children living farther away. In this community of predominantly low-income residents of color, these impacts raise environmental justice concerns about the effects of the drying Salton Sea on public health., 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 Inc.)

Air pollution is a hazardous contaminant, exposure to which has substantial consequences for health during critical periods, such as pregnancy. MicroRNA (miRNA) is an epigenetic mechanism that modulates transcriptome responses to the environment and has been found to change in reaction to air pollution exposure. The data are limited regarding extracellular-vesicle (EV) miRNA variation associated with air pollution exposure during pregnancy and in susceptible populations who may be disproportionately exposed. This study aimed to identify EV-miRNA expression associated with ambient, residential exposure to PM 2.5 , PM 10 , NO 2 , O 3 and with traffic-related NO x in 461 participants of the MADRES cohort, a low income, predominantly Hispanic pregnancy cohort based in Los Angeles, CA. This study used residence-based modeled air pollution data as well as Nanostring panels for EVmiRNA extracted with Qiagen exoRNeasy kits to evaluate 483 miRNA in plasma in early and late pregnancy. Average air pollution exposures were considered separately for 1-day, 1-week, and 8-week windows before blood collection in both early and late pregnancy. This study identified 63 and 66 EV-miRNA significantly associated with PM 2.5 and PM 10 , respectively, and 2 miRNA associated with traffic-related NO X (False Discovery Rate-adjusted P -value < .05). Of 103 unique EV-miRNA associated with PM, 92% were associated with lung conditions according to HMDD (Human miRNA Disease Database) evidence. In particular, EV-miRNA previously identified with air pollution exposure also associated with PM 2.5 and PM 10 in this study were: miR-126, miR-16-5p, miR-187-3p, miR200b-3p, miR486-3p, and miR-582-3p. There were no significant differences in average exposures in early vs late pregnancy. Significant EV-miRNAs were only identified in late pregnancy with an 8-week exposure window, suggesting a vulnerable timeframe of exposure, rather than an acute response. These results describe a wide array of EV-miRNA for which expression is affected by PM exposure and may be in part mediating the biological response to ambient air pollution, with potential for health implications in pregnant women and their children., Competing Interests: The authors have no competing interests to declare., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Per-and polyfluoroalkyl substances (PFAS) contamination may disrupt sleep through disrupted metabolic and immune functions. The study aims to investigate the association and potential mechanism between PFAS and sleep., Methods: We included 136 young adults recruited between 2014-2018 and 76 were re-assessed between 2020-2022. Additional 8 participants only had complete data between 2020-2022. Plasma PFAS (PFOS, PFOA, PFHxS, PFHpS, PFPeS, PFNA, PFDA) were measured at both visits using liquid-chromatography high-resolution mass spectrometry. Plasma proteins were measured by Olink ® Explore 384 Cardiometabolic and Inflammation Panel I. Sleep duration was self-reported at both visits along with follow-up sleep disturbance and sleep-related impairment using validated instruments. We utilized multiple linear regression to explore the association between individual PFAS (in tertile) and these sleep outcomes. PFAS associated with sleep outcomes were subjected to computational toxicology analysis using the Comparative Toxicogenomics Database and Toxicology in the 21st Century database to identify potential genetic links between them. Mediation analysis using proteomic data was then performed to confirm the findings from computational toxicology analysis., Results: At baseline, one tertile increase in PFDA was associated with 0.39 (95 % CI: 0.05, 0.73) hours of shorter nightly sleep duration, and, at follow-up, PFHxS and PFOA were associated with 0.39 (95 % CI: 0.05, 0.72) and 0.32 (95 % CI: 0.01, 0.63) hours shorter sleep duration, respectively. One tertile increase in PFOS exposure was associated with a 2.99-point increase in sleep disturbance scores (95 % CI: 0.67, 5.31) and a 3.35-point increase in sleep-related impairment scores (95 % CI: 0.51, 6.20). Computational toxicology and mediation analyses identified potential mediating roles for several proteins in the PFAS-sleep associations, including 11-beta-dehydrogenase isozyme 1 (HSD11B1), cathepsin B (CTSB) and several immune system-related proteins., Conclusion: Future large scale epidemiological and mechanistic studies should confirm our findings and test effect measure modification of the associations by age., 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.

Background: To our knowledge, no agreed-upon best practices exist for joining U.S. Census ZIP Code Tabulation Areas (ZCTAs) and U.S. Postal Service ZIP Codes (ZIPs). One-to-one linkage using 5-digit ZCTA identifiers excludes ZIPs without direct matches. "Crosswalk" linkage may match a ZCTA to multiple ZIPs, avoiding losses., Methods: We compared non-crosswalk and crosswalk linkages nationally and for mortality and health insurance in California. To elucidate selection implications, generalized additive models related sociodemographics to whether ZCTAs contained non-matching ZIPs., Results: Nationwide, 15% of ZCTAs had non-matching ZIPs, i.e., ZIPs dropped under non-crosswalk linkage. ZCTAs with non-matching ZIPs were positively associated with metropolitan core location, lower socioeconomics, and non-white population. In California, 34% of ZIPs in the mortality and 25% in the health insurance data had ZCTAs with non-matching ZIPs; however, these ZIPs constitute only 0.03% of total mortality and 0.44% of total insurance enrollees., Conclusions: Our study findings support the use of crosswalk linkages and ZCTAs as a unit of analysis. One-to-one linkage may cause bias by differentially excluding ZIPs with more disadvantaged populations, although affected population sizes appear small., Competing Interests: Conflicts of interest: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain condition creating a wide range of urologic and pain symptoms. There is currently limited evidence to understand the mechanisms of IC/BPS. There have been recent studies suggesting that altered function in brain motor areas, particularly the supplementary motor cortex (SMA), relates to altered bladder sensorimotor control and may play an important role in IC/BPS. This study aims to provide evidence that non-invasive stimulation targeting the motor cortex may help reduce IC/BPS pain, as well as better understand the neural mechanism by which this stimulation targets neuromuscular dysfunction. This study is a two-group quadruple-blinded randomized controlled trial (RCT) of active vs. sham repetitive transmagnetic stimulation (rTMS). In addition, our study will also include functional magnetic resonance imaging (fMRI), pelvic floor electromyography (EMG), pelvic exam, and outcome measures and questionnaires to further study outcomes., Ethics and Dissemination: All aspects of the study were approved by the Institutional Review Board of the University of Southern California (protocol HS-20-01021). All participants provided informed consent by the research coordinator/assistants. The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences., Trial Registration: ClinicalTrials.gov NCT04734847. Registered on February 1, 2021., (© 2024. The Author(s).)

While fine particulate matter (PM 2.5 ) has been associated with autism spectrum disorder (ASD), few studies focused on ultrafine particles (PM 0.1 ). Given that fine and ultrafine particles can be highly correlated due to shared emission sources, challenges remain to distinguish their health effects. In a retrospective cohort of 318,371 mother-child pairs (4549 ASD cases before age 5) in Southern California, pregnancy average PM 2.5 and PM 0.1 were estimated using a California-based chemical transport model and assigned to residential addresses. The correlation between PM 2.5 and PM 0.1 was 0.87. We applied a two-step variance decomposition approach: first, decomposing PM 2.5 and PM 0.1 into the shared and unique variances using ordinary least squares linear regression (OLS) and Deming regression considering errors in both exposures; then assessing associations between decomposed PM 2.5 and PM 0.1 and ASD using Cox proportional hazard models adjusted for covariates. Prenatal PM 2.5 and PM 0.1 each was associated with increased ASD risk. OLS decomposition showed that associations were driven mainly by their shared variance, not by their unique variance. Results from Deming regression considering assumptions of measurement errors were consistent with those from OLS. This decomposition approach has potential to disentangle health effects of correlated exposures, such as PM 2.5 and PM 0.1 from common emissions sources., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anny Xiang reports financial support was provided by National Institutes of Environmental Health Sciences. Rob McConnell reports financial support was provided by National Institute of Environmental Health Sciences. Joel Schwartz reports financial support was provided by US Environmental Protection Agency. Joel Schwartz has testified on behalf of the U.S. Department of Justice in a case involving a Clean Air Act violation If there are other authors, they 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 Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report.

Background: Exposure to pesticides has been linked to adverse respiratory health outcomes in children., Methods: We leveraged the Children's Assessing Imperial Valley Respiratory Health and the Environment cohort located in the rural community of Imperial Valley near the US-Mexico border. We calculated the kilograms of total pesticides applied within 400 m of children's residential addresses for the years 2016-2020. Estimated pesticide usage near homes was categorized into three groups (none vs. low vs. high [split at the median]). All health variables (i.e., asthma status and wheezing) were derived from a parent-reported questionnaire on respiratory health. We used generalized linear models, controlling for child sex, the language of survey, health insurance, respondents' highest education, and exposure to environmental secondhand smoking, to calculate prevalence differences between none versus low and high exposure to agricultural pesticides., Results: Approximately 62% of the 708 children (aged 5-12 years) lived within 400 m of at least one pesticide application within 12 months prior to survey administration. Exposure to pesticides within 400 m of children's residences was associated with 12-month prior wheeze. Those in the "high" exposure group had a prevalence of wheezing that was 10 (95% confidence interval: 2%, 17%) percentage points higher than among children not exposed to pesticide applications. Associations for high exposure to specific categories of pesticide applications, sulfur only, all pesticides except sulfur, chlorpyrifos, and glyphosate, also were observed with a higher prevalence of wheezing than among children not exposed to pesticide applications., Conclusions: We observed associations between living near pesticide applications and more wheeze symptoms among children., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

A growing number of studies have associated walkability and greenspace exposure with greater physical activity (PA) in women during pregnancy. However, most studies have focused on examining women's residential environments and neglected exposure in locations outside the home neighborhood. Using 350 person-days (N = 55 participants) of smartphone global positioning system (GPS) location and accelerometer data collected during the first and third trimesters and 4-6 months postpartum from 55 Hispanic pregnant women from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, we examined the day-level effect of women's exposure to walkability and greenspace on their PA outcomes during pregnancy and in the early postpartum period. Moderate-to-vigorous physical activity [MVPA] minutes per day was assessed using accelerometers. Walkability and greenspace were measured using geographic information systems (GIS) within women's daily activity spaces (i.e., places visited and routes taken) recorded using a smartphone GPS and weighted by time spent. We used a generalized linear mixed-effects model to estimate the effects of daily GPS-derived environmental exposures on day-level MVPA minutes. Results showed that women engaged in 23% more MVPA minutes on days when they had some versus no exposure to parks and open spaces in activity spaces (b = 1.23; 95%CI: 1.02-1.48). In addition, protective effects of daily greenspace and walkability exposure on MVPA were stronger in the first and third trimesters, among first-time mothers, and among women who had high pre-pregnancy body mass index (BMI) and lived in least-safe neighborhoods. Our results suggest that daily greenspace and walkability exposure are important for women's PA and associated health outcomes during pregnancy and early postpartum., (© 2024. The Author(s).)

To address the growing epidemic of liver disease, particularly in pediatric populations, it is crucial to identify modifiable risk factors for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Per- and polyfluoroalkyl substances (PFAS) are persistent ubiquitous chemicals and have emerged as potential risk factors for liver damage. However, their impact on the etiology and severity of MASLD remains largely unexplored in humans. This study aims to bridge the gap between human and in vitro studies to understand how exposure to perfluoroheptanoic acid (PFHpA), one of the emerging PFAS replacements which accumulates in high concentrations in the liver, contributes to MASLD risk and progression. First, we showed that PFHpA plasma concentrations were significantly associated with increased risk of MASLD in obese adolescents. Further, we examined the impact of PFHpA on hepatic metabolism using 3D human liver spheroids and single-cell transcriptomics to identify major hepatic pathways affected by PFHpA. Next, we integrated the in vivo and in vitro multi-omics datasets with a novel statistical approach which identified signatures of proteins and metabolites associated with MASLD development triggered by PFHpA exposure. In addition to characterizing the contribution of PFHpA to MASLD progression, our study provides a novel strategy to identify individuals at high risk of PFHpA-induced MASLD and develop early intervention strategies. Notably, our analysis revealed that the proteomic signature exhibited a stronger correlation between both PFHpA exposure and MASLD risk compared to the metabolomic signature. While establishing a clear connection between PFHpA exposure and MASLD progression in humans, our study delved into the molecular mechanisms through which PFHpA disrupts liver metabolism. Our in vitro findings revealed that PFHpA primarily impacts lipid metabolism, leading to a notable increase of lipid accumulation in human hepatocytes after PFHpA exposure. Among the pathways involved in lipid metabolism in hepatocytes, regulation of lipid metabolism by PPAR-a showed a remarkable activation. Moreover, the translational research framework we developed by integrating human and in vitro data provided us biomarkers to identify individuals at a high risk of MASLD due to PFHpA exposure. Our framework can inform policies on PFAS-induced liver disease and identify potential targets for prevention and treatment strategies.

Background: Prenatal air pollution exposure has been associated with individual inflammatory, cardiovascular, and metabolic biomarkers in mothers and neonates. However, studies of air pollution and a comprehensive panel of biomarkers across maternal and cord blood samples remain limited. Few studies used data-driven methods to identify biomarker groupings that converge biomarkers from multiple biological pathways. This study aims to investigate the impacts of prenatal air pollution on groups of biomarkers in maternal and cord blood samples., Methods: In the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort, 87 biomarkers were quantified from 45 trimester 1 maternal blood and 55 cord blood samples. Pregnancy and trimester 1-averaged concentrations of particulate matter ≤2.5 μm and ≤10 μm in diameter (PM 2.5 and PM 10 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) were estimated, using inverse distance squared weighted spatial interpolation from regulatory air monitoring stations. Traffic-related NO x was assessed using California Line Source Dispersion Model: freeway/highway roads, non-freeway major roads, non-freeway minor roads, and their sum as total NOx. Elastic Net (EN) regression within the rexposome R package was used to group biomarkers and assess their associations with air pollution., Results: In maternal samples, trimester 1-averaged PM 10 was associated with elevated inflammation biomarkers and lowered cardiovascular biomarkers. NO 2 exhibited positive associations with cardiovascular and inflammation markers. O 3 was inversely associated with inflammation, metabolic, and cardiovascular biomarkers. In cord blood, pregnancy-averaged PM 2.5 was associated with higher cardiovascular biomarkers and lower metabolic biomarkers. PM 10 was associated with lower inflammation and higher cardiovascular biomarkers. Total and major road NOx was associated with lower cardiovascular biomarkers., Conclusion: Prenatal air pollution exposure was associated with changes in biomarkers related to inflammation, cardiovascular, metabolic, cancer, and neurological function in both mothers and neonates. This study shed light on mechanisms by which air pollution can influence biological function 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 Elsevier Inc. All rights reserved.)

Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery. Adolescents (Mean age = 17.1 years, SD = 1.5 years) undergoing bariatric surgery were enrolled in the Teen-LABS study. Plasma-PFAS were measured at the time of surgery and then 6-, 12-, and 36 months post-surgery. Linear mixed effect models were used to evaluate longitudinal changes in plasma-PFAS after the time of bariatric surgery. This study included 214 adolescents with severe obesity who had available longitudinal measures of plasma-PFAS and underwent bariatric surgery between 2007 and 2012. Underlying effects related to undergoing bariatric surgery were found to be associated with an initial increase or plateau in concentrations of circulating PFAS up to 6 months after surgery followed by a persistent decline in concentrations of 36 months (p < 0.001 for all plasma-PFAS). Bariatric surgery in adolescents was associated with a decline in circulating PFAS concentrations. Initially following bariatric surgery (0-6 months) concentrations were static followed by decline from 6 to 36 months following surgery. This may have large public health implications as PFAS are known to be associated with numerous metabolic related diseases and the significant reduction in circulating PFAS in individuals who have undergone bariatric surgery may be related to the improvement of such metabolic related diseases following bariatric surgery., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thomas Inge reports a relationship with Standard Bariatrics, Teleflex, and Mediflex, and royalties from Wolters Kluwer (UpToDate) that includes: consulting or advisory. If there are other authors, they 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 Elsevier B.V. All rights reserved.)

Background: Air pollution has been associated with gestational hypertension (GH) and preeclampsia, but susceptible windows of exposure and potential vulnerability by comorbidities, such as prenatal depression, remain unclear., Methods: We ascertained GH and preeclampsia cases in a prospective pregnancy cohort in Los Angeles, CA. Daily levels of ambient particulate matters (with a diameter of ≤10 μm [PM 10 ] or ≤2.5 μm [PM 2.5 ]), nitrogen dioxide, and ozone were averaged for each week from 12 weeks preconception to 20 gestational weeks. We used distributed lag models to identify susceptible exposure windows, adjusting for potential confounders. Analyses were additionally stratified by probable prenatal depression to explore population vulnerability., Results: Among 619 participants, 60 developed preeclampsia and 42 developed GH. We identified a susceptible window for exposure to PM 2.5 from 1 week preconception to 11 weeks postconception: higher exposure (5 µg/m 3 ) within this window was associated with an average of 8% (95% CI, 1%-15%) higher risk of GH. Among participants with probable prenatal depression (n=179; 32%), overlapping sensitive windows were observed for all pollutants from 8 weeks before to 10 weeks postconception with increased risk of GH (PM 2.5 , 16% [95% CI, 3%-31%]; PM 10 , 39% [95% CI, 13%-72%]; nitrogen dioxide, 65% [95% CI, 17%-134%]; and ozone, 45% [95% CI, 9%-93%]), while the associations were close to null among those without prenatal depression. Air pollutants were not associated with preeclampsia in any analyses., Conclusions: We identified periconception through early pregnancy as a susceptible window of air pollution exposure with an increased risk of GH. Prenatal depression increases vulnerability to air pollution exposure and GH., Competing Interests: Disclosures None.

Background: Ambient air pollution has been linked to postpartum depression. However, few studies have investigated the effects of traffic-related NO x on postpartum depression and whether any pregnancy-related factors might increase susceptibility., Objectives: To evaluate the association between traffic-related NO x and postpartum depressive and anxiety symptoms, and effect modification by pregnancy-related hypertension., Methods: This study included 453 predominantly low-income Hispanic/Latina women in the MADRES cohort. Daily traffic-related NO x concentrations by road class were estimated using the California LINE-source dispersion model (CALINE4) at participants' residential locations and averaged across pregnancy. Postpartum depressive and anxiety symptoms were evaluated by a validated questionnaire (Postpartum Distress Measure, PDM) at 1, 3, 6 and 12 months postpartum. Multivariate linear regressions were performed to estimate the associations at each timepoint. Interaction terms were added to the linear models to assess effect modification by hypertensive disorders of pregnancy (HDPs). Repeated measurement analyses were conducted by using mixed effect models., Results: We found prenatal traffic-related NO x was associated with increased PDM scores. Specifically, mothers exposed to an IQR (0.22 ppb) increase in NO x from major roads had 3.78% (95% CI: 0.53-7.14%) and 5.27% (95% CI: 0.33-10.45%) significantly higher 3-month and 12-month PDM scores, respectively. Similarly, in repeated measurement analyses, higher NO x from major roads was associated with 3.06% (95% CI: 0.43-5.76%) significantly higher PDM scores across the first year postpartum. Effect modification by HDPs was observed: higher freeway/highway and total NO x among mothers with HDPs were associated with significantly higher PDM scores at 12 months postpartum compared to those without HDPs., Impact: This study shows that prenatal traffic-related air pollution was associated with postpartum depressive and anxiety symptoms. The study also found novel evidence of greater susceptibility among women with HDPs, which advances the understanding of the relationships between air pollution, maternal cardiometabolic health during pregnancy and postpartum mental health. Our study has potential implications for clinical intervention to mitigate the effects of traffic-related pollution on postpartum mental health disorders. The findings can also offer valuable insights into urban planning strategies concerning the implementation of emission control measures and the creation of green spaces., (© 2024. The Author(s).)

Background: Extreme heat and air pollution is associated with increased mortality. Recent evidence suggests the combined effects of both is greater than the effects of each individual exposure. Low neighborhood socioeconomic status ("socioeconomic burden") has also been associated with increased exposure and vulnerability to both heat and air pollution. We investigated if neighborhood socioeconomic burden or the combination of socioeconomic and environmental exposures ("socioenvironmental burden") modified the effect of combined exposure to extreme heat and particulate air pollution on mortality in California., Methods: We used a time-stratified case-crossover design to assess the impact of daily exposure to extreme particulate matter <2.5 μm (PM 2.5 ) and heat on cardiovascular, respiratory, and all-cause mortality in California 2014-2019. Daily average PM 2.5 and maximum temperatures based on decedent's residential census tract were dichotomized as extreme or not. Census tract-level socioenvironmental and socioeconomic burden was assessed with the CalEnviroScreen (CES) score and a social deprivation index (SDI), and individual educational attainment was derived from death certificates. Conditional logistic regression was used to estimate associations of heat and PM 2.5 with mortality with a product term used to evaluate effect measure modification., Results: During the study period 1,514,292 all-cause deaths could be assigned residential exposures. Extreme heat and air pollution alone and combined were associated with increased mortality, matching prior reports. Decedents in census tracts with higher socioenvironmental and socioeconomic burden experienced more days with extreme PM 2.5 exposure. However, we found no consistent effect measure modification by CES or SDI on combined or separate extreme heat and PM 2.5 exposure on odds of total, cardiovascular or respiratory mortality. No effect measure modification was observed for individual education attainment., Conclusion: We did not find evidence that neighborhood socioenvironmental- or socioeconomic burden significantly influenced the individual or combined impact of extreme exposures to heat and PM 2.5 on mortality in California., Impact: We investigated the effect measure modification by socioeconomic and socioenvironmental of the co-occurrence of heat and PM 2.5 , which adds support to the limited previous literature on effect measure modification by socioeconomic and socioenvironmental burden of heat alone and PM 2.5 alone. We found no consistent effect measure modification by neighborhood socioenvironmental and socioeconomic burden or individual level SES of the mortality association with extreme heat and PM 2.5 co-exposure. However, we did find increased number of days with extreme PM 2.5 exposure in neighborhoods with high socioenvironmental and socioeconomic burden. We evaluated multiple area-level and an individual-level SES and socioenvironmental burden metrics, each estimating socioenvironmental factors differently, making our conclusion more robust., (© 2024. The Author(s).)

Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown., Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US., Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024., Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure., Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted., Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02)., Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.

Objective: Dichlorodiphenyldichloroethylene (DDE), an obesogen accumulating in adipose tissue, is released into circulation with weight loss, although its impact is underexplored among adolescents. We tested the association using an integrative translational approach of epidemiological analysis among adolescents with obesity and in vitro measures exploring the impact of DDE on adipogenesis via preadipocytes., Methods: We included 63 participants from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. We assessed 4,4'-DDE in visceral adipose tissue at surgery and BMI and waist circumference at surgery and 0.5, 1, 3, and 5 years after. We conducted longitudinal analysis to estimate the interaction on weight loss between DDE and time since surgery. In vitro analysis quantified adipogenic differentiation in commercial human preadipocytes exposed to 4,4'-DDE via fluorescent staining and imaging., Results: A dose-response relationship was observed, with the low-exposure group having a greater reduction in BMI during the first year compared to higher-exposure groups and showing smaller regains compared to higher-exposure groups after the first year. In vitro analysis of preadipocytes treated with 4,4'-DDE during adipogenic differentiation for 12 days showed a concentration-dependent increase in lipid accumulation., Conclusions: DDE could contribute to weight trajectory among adolescents undergoing bariatric surgery, potentially mediated via promoted adipogenesis in preadipocytes., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Understanding transitions across use of different types of cannabis products and multiple cannabis products and how they intersect with nicotine use in young people can inform etiology and prevention. In this study, we examined transitions across use of combustible and noncombustible forms of cannabis and multiple types of cannabis from adolescence to young adulthood and the role of nicotine use in transitions. In a Southern California longitudinal cohort study (n = 3,298; baseline mean age = 16.1 (standard deviation, 0.4) years) with 9 semiannual survey waves (2015-2021), we used Markov multistate transition modeling to estimate short-term (2-wave) and long-term (9-wave) probabilities of transition across 5 cannabis use states: never use of any product, prior use with no past-6-month (P6M) use of any product, and P6M use of exclusively noncombustible products, exclusively combustible products, and multiple (noncombustible + combustible) products. Sizable transition probabilities from prior and exclusive P6M noncombustible or combustible cannabis use to P6M poly-cannabis-product use were observed in short-term (10.7%-38.9%) and long-term (43.4%-43.8%) analyses. P6M nicotine use increased risk of transitioning from never and prior use to exclusive P6M noncombustible and combustible cannabis use. Cannabis use in any form, even temporary use, during midadolescence may often be followed by poly-cannabis-product use. Nicotine use may amplify the probability of future cannabis use onset or recurrence., (© The Author(s) 2023. 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: Strong epidemiological evidence shows positive associations between exposure to per- and polyfluoroalkyl substances (PFAS) and adverse cardiometabolic outcomes (e.g., diabetes, hypertension, and dyslipidemia). However, the underlying cardiometabolic-relevant biological activities of PFAS in humans remain largely unclear., Aim: We evaluated the associations of PFAS exposure with high-throughput proteomics in Hispanic youth., Material and Methods: We included 312 overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) between 2001 and 2012, along with 137 young adults from the Metabolic and Asthma Incidence Research (Meta-AIR) between 2014 and 2018. Plasma PFAS (i.e., PFOS, PFOA, PFHxS, PFHpS, PFNA) were quantified using liquid-chromatography high-resolution mass spectrometry. Plasma proteins (n = 334) were measured utilizing the proximity extension assay using an Olink Explore Cardiometabolic Panel I. We conducted linear regression with covariate adjustment to identify PFAS-associated proteins. Ingenuity Pathway Analysis, protein-protein interaction network analysis, and protein annotation were used to investigate alterations in biological functions and protein clusters., Results: Results after adjusting for multiple comparisons showed 13 significant PFAS-associated proteins in SOLAR and six in Meta-AIR, sharing similar functions in inflammation, immunity, and oxidative stress. In SOLAR, PFNA demonstrated significant positive associations with the largest number of proteins, including ACP5, CLEC1A, HMOX1, LRP11, MCAM, SPARCL1, and SSC5D. After considering the mixture effect of PFAS, only SSC5D remained significant. In Meta-AIR, PFAS mixtures showed positive associations with GDF15 and IL6. Exploratory analysis showed similar findings. Specifically, pathway analysis in SOLAR showed PFOA- and PFNA-associated activation of immune-related pathways, and PFNA-associated activation of inflammatory response. In Meta-AIR, PFHxS-associated activation of dendric cell maturation was found. Moreover, PFAS was associated with common protein clusters of immunoregulatory interactions and JAK-STAT signaling in both cohorts., Conclusion: PFAS was associated with broad alterations of the proteomic profiles linked to pro-inflammation and immunoregulation. The biological functions of these proteins provide insight into potential molecular mechanisms of PFAS toxicity., 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.)

The built and natural environment factors (e.g., greenspace, walkability) are associated with maternal and infant health during and after pregnancy. Most pregnancy studies assess exposures to environmental factors via static methods (i.e., residential location at a single point in time, usually 3rd trimester). These do not capture dynamic exposures encountered in activity spaces (e.g., locations one visits and paths one travels) and their changes over time. In this study, we aimed to compare daily environmental exposure estimates using residential and global positioning systems (GPS)-measured activity space approaches and evaluated potential for exposure measurement error in the former. To do this, we collected four days of continuous geolocation monitoring during the 1st and 3rd trimesters of pregnancy and at 4-6 months postpartum in sixty-two pregnant Hispanic women enrolled in the MADRES cohort. We applied residential and GPS-based methods to assess daily exposures to greenspace, access to parks and transit, and walkability, respectively. We assessed potential for exposure measurement error in residential vs GPS-based estimates using Pearson correlations for each measure overall and by study period. We found residential and GPS-based estimates of daily exposure to total areas of parks and open spaces were weakly positively correlated (r = 0.31, P < .001) across pregnancy and postpartum periods. Residential estimates of %greenspace (r = 0.52, P < .001) and tree cover (r = 0.55, P < .001) along walkable roads were moderately correlated with GPS-based estimates. Residential and GPS-based estimates of public transit proximity, pedestrian-oriented intersection density, and walkability index score were all highly positively correlated (r > 0.70, P < .001). We also found associations between residential and GPS-based estimates decreased among participants with greater daily mobility. Our findings suggest the popular approach that assessing the built and natural environment exposures using residential methods at one time point may introduce exposure measurement error in pregnancy studies. GPS-based methods, to the extent feasible, are recommended for future studies., 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 Elsevier B.V. All rights reserved.)

Background: Diet during pregnancy may be a potential intervention for preventing hypertensive disorders of pregnancy that disproportionally burdens Hispanic/Latina women., Methods and Results: The MADRES (Maternal And Developmental Risks from Environmental and Social stressors) study (n=451) is a prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles, California, who completed up to 2 staff-administered 24-hour dietary recalls in the third trimester of pregnancy. Hypertensive disorders of pregnancy were abstracted from medical records and based on a physician's diagnosis or systolic or diastolic blood pressure (≥140 or ≥90 mm Hg, respectively) at ≥2 consecutive prenatal visits. Using multivariable logistic regression, we evaluated associations of 2 previously derived dietary patterns in this population (solid fats, refined grains, and cheese and vegetables, oils, and fruit) and the Healthy Eating Index 2015 with (1) gestational hypertension, (2) preeclampsia, and (3) any hypertensive disorder of pregnancy (either gestational hypertension or preeclampsia). In separate models, we additionally tested interactions with prepregnancy body mass index. Comparing highest-to-lowest quartiles, the solid fats, refined grains, and cheese dietary pattern was associated with an increased odds of any hypertensive disorder of pregnancy (odds ratio [OR], 3.99 [95% CI, 1.44-11.0]; P trend =0.014) and preeclampsia (OR, 4.10 [95% CI, 1.25-13.5]; P trend =0.036), whereas the vegetables, oils, and fruit pattern was associated with reduced odds of preeclampsia (OR, 0.32 [95% CI, 0.10-0.99]; P trend =0.041). Among the overweight prepregnancy body mass index category, inverse associations of vegetables, oils, and fruit and Healthy Eating Index 2015 with preeclampsia were more pronounced (both P interactions =0.017). Healthy Eating Index 2015 findings were generally nonsignificant., Conclusions: While the solid fats, refined grains, and cheese diet was strongly associated with preeclampsia during pregnancy, findings suggest the vegetables, oils, and fruit diet may be more relevant than Healthy Eating Index 2015 for preventing preeclampsia among low-income Hispanic/Latina women.

Background: Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is associated with microRNA (miRNA) dysregulation. miRNA are key regulators in many physiological processes. It is thus of public health concern to understand the relationships between POPs and miRNA as related to health outcomes., Objectives: This systematic review evaluated the relationship between widely recognized, intentionally manufactured, POPs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB]), with miRNA expression in both human and animal studies., Methods: We used PubMed and Embase to systematically search the literature up to September 29th, 2023. Search results for human and animal studies were included if they incorporated at least one POP of interest in relation to at least one miRNA. Data were synthesized to determine the direction and significance of associations between POPs and miRNA. We utilized ingenuity pathway analysis to review disease pathways for miRNA that were associated with POPs., Results: Our search identified 38 eligible studies: 9 in humans and 29 in model organisms. PFAS were associated with decreased expression of miR-19, miR-193b, and miR-92b, as well as increased expression of miR-128, miR-199a-3p, and miR-26b across species. PCBs were associated with increased expression of miR-15a, miR-1537, miR-21, miR-22-3p, miR-223, miR-30b, and miR-34a, as well as decreased expression of miR-130a and let-7b in both humans and animals. Pathway analysis for POP-associated miRNA identified pathways related to carcinogenesis., Discussion: This is the first systematic review of the association of POPs with miRNA in humans and model organisms. Large-scale prospective human studies are warranted to examine the role of miRNA as mediators between POPs and health 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Health care accounts for 9-10% of greenhouse gas (GHG) emissions in the United States. Strategies for monitoring these emissions at the hospital level are needed to decarbonize the sector. However, data collection to estimate emissions is challenging, especially for smaller hospitals. We explored the potential of gradient boosting machines (GBM) to impute missing data on resource consumption in the 2020 survey of a consortium of 283 hospitals participating in Practice Greenhealth. GBM imputed missing values for selected variables in order to predict electricity use and beef consumption (R 2 =0.82) and anesthetic gas desflurane use (R 2 =0.51), using administrative data readily available for most hospitals. After imputing missing consumption data, estimated GHG emissions associated with these three examples totaled over 3 million metric tons of CO 2 equivalent emissions (MTCO 2 e). Specifically, electricity consumption had the largest total carbon footprint (2.4 MTCO 2 e), followed by beef (0.6 million MTCO 2 e) and desflurane consumption (0.03 million MTCO 2 e) across the 283 hospitals. The approach should be applicable to other sources of hospital GHGs in order to estimate total emissions of individual hospitals and to refine survey questions to help develop better intervention strategies.

Background: Per- and polyfluoroalkyl substances (PFAS) may impair bone development in adolescence, which impacts life-long bone health. No previous studies have examined prospective associations of individual PFAS and their mixture with bone mineral density (BMD) changes in Hispanic young persons, a population at high risk of osteoporosis in adulthood., Objectives: To examine associations of individual PFAS and PFAS mixtures with longitudinal changes in BMD in an adolescent Hispanic cohort and examine generalizability of findings in a mixed-ethnicity young adult cohort (58.4% Hispanic)., Methods: Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n = 304; mean follow-up = 1.4 years) and young adults from the Southern California Children's Health Study (CHS; n = 137; mean follow-up = 4.1 years) were included in this study. Plasma PFAS were measured at baseline and dual x-ray absorptiometry scans were performed at baseline and follow-up to measure BMD. We estimated longitudinal associations between BMD and five PFAS via separate covariate-adjusted linear mixed effects models, and between BMD and the PFAS mixture via quantile g-computation., Results: In SOLAR adolescents, baseline plasma perfluorooctanesulfonic acid (PFOS) was associated with longitudinal changes in BMD. Each doubling of PFOS was associated with an average -0.003 g/cm 2 difference in change in trunk BMD per year over follow-up (95% CI: -0.005, -0.0002). Associations with PFOS persisted in CHS young adults, where each doubling of plasma PFOS was associated with an average -0.032 g/cm 2 difference in total BMD at baseline (95% CI -0.062, -0.003), though longitudinal associations were non-significant. We did not find associations of other PFAS with BMD; associations of the PFAS mixture with BMD outcomes were primarily negative though non-significant., Discussion: PFOS exposure was associated with lower BMD in adolescence and young adulthood, important periods for bone development, which may have implications on future bone health and risk of osteoporosis in adulthood., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

We examined the associations between social support and postpartum mental health in 137 U.S. and foreign-born Latinas in the MADRES pregnancy cohort. We also examined whether language, years in the U.S., and country of birth moderates these relationships. Participants were administered PROMIS support measures 1 month postpartum; the Perceived Stress and Postpartum Distress Measure 3, 6, and 12 months postpartum; and the CESD scale 12 months postpartum. Perceived stress was lower at 6 months postpartum for women reporting higher emotional (p = 0.01), informational (p = 0.03), and instrumental support (p < 0.001); and lower at 12 months postpartum for women reporting higher emotional support (p = 0.01). Distress at 6 months was lower in women reporting higher emotional support (p = 0.03). Interactions suggest that associations were stronger for mothers that speak Spanish, spent fewer years in the U.S., and were born in Central America., (© 2023. The Author(s).)

Importance: Family socioeconomic status has been associated with autism spectrum disorder (ASD) diagnoses. Less is known regarding the role of neighborhood disadvantage in the United States, particularly when children have similar access to health insurance., Objective: To evaluate the association between neighborhood disadvantage and the diagnosis of ASD and potential effect modification by maternal and child demographic characteristics., Design, Setting, and Participants: This cohort study examined a retrospective birth cohort from Kaiser Permanente Southern California (KPSC), an integrated health care system. Children born in 2001 to 2014 at KPSC were followed up through KPSC membership records. Electronic medical records were used to obtain an ASD diagnosis up to December 31, 2019, or the last follow-up. Data were analyzed from February 2022 to September 2023., Exposure: Socioeconomic disadvantage at the neighborhood level, an index derived from 7 US census tract characteristics using principal component analysis., Main Outcomes and Measures: Clinical ASD diagnosis based on electronic medical records. Associations between neighborhood disadvantage and ASD diagnosis were determined by hazard ratios (HRs) from Cox regression models adjusted for birth year, child sex, maternal age at delivery, parity, severe prepregnancy health conditions, maternal race and ethnicity, and maternal education. Effect modification by maternal race and ethnicity, maternal education, and child sex was assessed., Results: Among 318 372 mothers with singleton deliveries during the study period, 6357 children had ASD diagnoses during follow-up; their median age at diagnosis was 3.53 years (IQR, 2.57-5.34 years). Neighborhood disadvantage was associated with a higher likelihood of ASD diagnosis (HR, 1.07; 95% CI, 1.02-1.11, per IQR = 2.70 increase). Children of mothers from minoritized racial and ethnic groups (African American or Black, Asian or Pacific Islander, Hispanic or Latinx groups) had increased likelihood of ASD diagnosis compared with children of White mothers. There was an interaction between maternal race and ethnicity and neighborhood disadvantage (difference in log-likelihood = 21.88; P < .001 for interaction under χ24); neighborhood disadvantage was only associated with ASD among children of White mothers (HR, 1.17; 95% CI, 1.09-1.26, per IQR = 2.00 increase). Maternal education and child sex did not significantly modify the neighborhood-ASD association., Conclusions and Relevance: In this study, children residing in more disadvantaged neighborhoods at birth had higher likelihood of ASD diagnosis among a population with health insurance. Future research is warranted to investigate the mechanisms behind the neighborhood-related disparities in ASD diagnosis, alongside efforts to provide resources for early intervention and family support in communities with a higher likelihood of ASD.

Organophosphate esters (OPEs) are increasingly considered neurotoxicants which may impact gross and fine motor development. We evaluated associations between prenatal OPE exposures and infant motor development. Third trimester urinary concentrations of nine OPE metabolites were measured in 329 mother-infant dyads participating in the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. Child gross and fine motor development at 6, 9, 12, and 18-months were assessed with the Ages and Stages Questionnaire-3 (ASQ-3) and operationalized in models using dichotomous instrument-specific cutoffs for typical motor development. Five OPE metabolites with >60% detection were specific-gravity-adjusted, natural log-transformed, and modeled continuously, while four metabolites with <60% detection were modeled dichotomously (detected/not-detected). We fit mixed effects logistic regression between OPE metabolites and fine/gross motor development and assessed sex-specific effects using a statistical interaction term and sex-stratified models. Among children, 31% and 23% had gross and fine motor scores, respectively, below the ASQ-3 at-risk cutoffs at least once across infancy. A doubling in prenatal diphenyl phosphate (DPHP) exposure was associated with 26% increased odds of potential fine motor delays (OR fine  = 1.26, 95% CI: 1.02, 1.57, p = 0.04). We also observed significant interactions by infant sex for associations of detected dipropyl phosphate (DPRP) with gross motor development (p interaction  = 0.048) and detected bis(1-chloro-2-propyl) phosphate (BCIPP) with fine motor development (p interaction  = 0.02). Females had greater odds of potential motor delays for both detected DPRP (females vs males OR gross (95% CI) = 1.48 (0.71, 3.09), p = 0.30 vs 0.27 (0.06, 1.29), p = 0.10) and detected BCIPP (females vs males OR fine (95% CI) = 2.72 (1.27, 5.85), p = 0.01 vs 0.76 (0.31, 1.90), p = 0.56). There were no other significant associations between other metabolites and motor development, despite similar patterns. We found evidence of adverse effects of prenatal OPE exposures on infant motor development with greater adverse effects among female infants with some OPE metabolites., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents., Aim: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD., Methods: This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD., Results: We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B., Conclusion: Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Rationale: Electronic cigarette (e-cigarette) aerosol contains volatile aldehydes, including flavourings and oxidant metals with known pulmonary toxicity., Objectives: To evaluate the associations of e-cigarette use with symptoms of wheeze, bronchitic symptoms and shortness of breath (SOB) across 4 years of prospective data., Methods: Participants completed questionnaires on respiratory symptoms and past 30-day e-cigarette, cigarette and cannabis use in 2014 (wave 1; N=2094; mean age 17.3 years, SD=0.6 years). Follow-up information was collected in 2015 (wave 2; n=1609), 2017 (wave 3; n=1502) and 2018 (wave 4; n=1637) using online surveys. Mixed-effects logistic regression models evaluated associations of e-cigarette use with respiratory symptoms., Measurements and Main Results: Participants were mostly Hispanic white (51.8%) and evenly representative by sex (49.6% female; 50.4% male). Compared with never e-cigarette users, past 30-day e-cigarette users reported increased odds of wheeze (OR 1.81; 95% CI 1.28, 2.56), bronchitic symptoms (OR 2.06; 95% CI 1.58, 2.69) and SOB (OR 1.78; 95% CI 1.23, 2.57), adjusting for study wave, age, sex, race, lifetime asthma diagnosis and parental education. Effect estimates were attenuated (wheeze (OR 1.41; 95% CI 0.99, 2.01), bronchitic symptoms (OR 1.55; 95% CI 1.18, 2.05), SOB (OR 1.48; 95% CI 1.01, 2.18)), after adjusting additionally for current cigarette use, cannabis use and secondhand exposure to e-cigarettes/cigarettes/cannabis., Conclusions: E-cigarette use in young adults was associated with respiratory symptoms, independent of combustible cannabis and cigarette exposures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) are intentionally produced persistent organic pollutants (POPs) that are resistant to environmental degradation. Previous in-vitro and in-vivo studies have shown that POPs can induce oxidative stress, which is linked to neurodegenerative diseases, cardiovascular diseases, and cancer. However, findings in epidemiological studies are inconsistent and an evidence synthesis study is lacking to summarize the existing literature and explore research gaps., Objective: We evaluated the effects of PFAS, PCBs, OCPs, and PBDEs, on oxidative stress biomarkers in epidemiological studies., Methods: A literature search was conducted in PubMed, Embase, and Cochrane CENTRAL to identify all published studies related to POPs and oxidative stress up to December 7 th , 2022. We included human observational studies reporting at least one exposure to POPs and an oxidative stress biomarker of interest. Random-effects meta-analyses on standardized regression coefficients and effect direction plots with one-tailed sign tests were used for quantitative synthesis., Results: We identified 33 studies on OCPs, 35 on PCBs, 49 on PFAS, and 12 on PBDEs. Meta-analyses revealed significant positive associations of α-HCH with protein carbonyls (0.035 [0.017, 0.054]) and of 4'4-DDE with malondialdehyde (0.121 [0.056, 0.187]), as well as a significant negative association between 2'4-DDE and total antioxidant capacity (TAC) (-0.042 [-0.079, -0.004]), all β [95%CI]. Sign tests showed a significant positive association between PCBs and malondialdehyde (p one-tailed  = 0.03). Additionally, we found significant negative associations of OCPs with acetylcholine esterase (p one-tailed  = 0.02) and paraoxonase-1 (p one-tailed  = 0.03). However, there were inconsistent associations of OCPs with superoxide dismutase, glutathione peroxidase, and catalase., Conclusions: Higher levels of OCPs were associated with increased levels of oxidative stress through increased pro-oxidant biomarkers involving protein oxidation, DNA damage, and lipid peroxidation, as well as decreased TAC. These findings have the potential to reveal the underlying mechanisms of POPs toxicity., 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 © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: It is unknown whether young adults who vape nicotine and have poor mental health have greater risk of smoking initiation than expected based on individual risks of vaping and mental health alone. This study aimed to estimate the joint association of vaping and mental health symptoms with smoking initiation among young adults, and test for additive interaction between vaping and mental health in smoking initiation risk., Design: Using five waves of the Population Assessment of Tobacco and Health (wave 1, 2013-2014; wave 2, 2014-2015; wave 3, 2015-2016; wave 4, 2016-2018; wave 5, 2018-2019), we estimated risk differences (RD) for the association of time-varying and time-lagged vaping and internalizing (e.g., anxiety, depressive) and externalizing (e.g., inattention/hyperactivity) mental health symptoms with cigarette smoking initiation at follow-up, over four 1-year intervals. We calculated interaction contrasts (IC) to estimate the excess risk of smoking initiation attributable to the interaction of vaping and mental health symptoms., Setting: United States., Participants: A total of 6908 cigarette-naïve individuals aged 18-24 years., Measurements: Exposures included current (past-30 day) vaping and internalizing and externalizing mental health symptoms (high vs moderate/low symptoms). The outcome was smoking initiation (ever cigarette use) after 1 year., Findings: The per-interval risk of smoking initiation was 7.6% (1039 cases/13 712 person-intervals). Compared with noncurrent vaping and moderate/low mental health symptoms, adjusted RDs for current vaping and high mental health symptoms were 17.2% (95% confidence interval [CI]: 7.2% to 27.3%) for internalizing and 18.7% (95%CI: 8.1% to 29.2%) for externalizing symptoms. The excess risk attributed to interaction of current vaping and high externalizing symptoms was IC = 11.3% (95%CI: 1.3% to 21.2%; P = 0.018), with inconclusive findings for internalizing symptoms (IC = 7.7% [95%CI: -2.2% to 17.7%; P = 0.097])., Conclusions: There is possible, but inconclusive, superadditivity between vaping and mental health in risk of smoking initiation among young adults in the United States., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Burning of agricultural fields is an understudied source of air pollution in rural communities in the United States. Smoke from agricultural burning contains air toxics that adversely impact respiratory health. Imperial County in southeastern California is a highly productive agricultural valley that heavily employs agricultural burning to clear post-harvest crop remnants. We related individual-level exposure to agricultural burns to parent-reported respiratory symptoms in children. We leveraged the Children's Assessing Imperial Valley Respiratory Health and the Environment (AIRE) cohort of 735 predominantly Hispanic low-income elementary school students in Imperial County. Parents reported children's respiratory health symptoms and family demographic characteristics in questionnaires collected at enrollment and in annual follow-up assessments from 2017 to 2019. Permitted agricultural burns in Imperial County from 2016 to 2019 were spatially linked to children's geocoded residential addresses. We used generalized estimating equations to evaluate prevalence differences (PDs) in respiratory symptoms with increasing exposure to agricultural burning within 3 km in the 12 months prior to each assessment. Nearly half of children (346, 49 %) lived within 3 km of at least one agricultural burn in the year prior to study enrollment. In adjusted models, each additional day of agricultural burning in the prior year was associated with a one percentage point higher prevalence of wheezing (PD 1.1 %; 95 % CI 0.2 %, 2.0 %) and higher bronchitic symptoms (PD 1.0 %; 95 % CI -0.2 %, 2.1 %). Children exposed to four or more days of burning had an absolute increased prevalence of wheezing and bronchitic symptoms of 5.9 % (95 % CI -0.3 %, 12 %) and 5.6 % (95 % CI -1.8 %, 13 %), respectively, compared to no burn exposure. Associations with wheezing were stronger among children with asthma (PD 14 %; 95 % CI -1.4 %, 29 %). To our knowledge, this is the first U.S. study of agricultural burning and children's respiratory health. This work suggests that reducing agricultural burning could improve children's respiratory health., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Fluoride is ubiquitous in the United States (US); however, data on biomarkers and patterns of fluoride exposure among US pregnant women are scarce. We examined specific gravity adjusted maternal urinary fluoride (MUFsg) in relation to sociodemographic variables and metal co-exposures among pregnant women in Los Angeles, California., Methods: Participants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. There were 293 and 490 women with MUFsg measured during first and third trimesters, respectively. An intra-class correlation coefficient examined consistency of MUFsg between trimesters. Kruskal-Wallis and Mann-Whitney U tests examined associations of MUFsg with sociodemographic variables. Covariate adjusted linear regression examined associations of MUFsg with blood metals and specific gravity adjusted urine metals among a subsample of participants within and between trimesters. A False Discovery Rate (FDR) correction accounted for multiple comparisons., Results: Median (IQR) MUFsg was 0.65 (0.5) mg/L and 0.8 (0.59) mg/L, during trimesters one and three respectively. During both trimesters, MUFsg was higher among older participants, those with higher income, and White, non-Hispanic participants than Hispanic participants. MUFsg was also higher for White, non-Hispanic participants than for Black, non-Hispanic participants in trimester three, and for those with graduate training in trimester one. MUFsg was negatively associated with blood mercury in trimester one and positively associated with blood lead in trimester three. MUFsg was positively associated with various urinary metals, including antimony, barium, cadmium, cobalt, copper, lead, nickel, tin, and zinc in trimesters one and/or three., Conclusions: MUFsg levels observed were comparable to those found in pregnant women in Mexico and Canada that have been associated with poorer neurodevelopmental outcomes. Lower urinary fluoride levels among Hispanic and non-Hispanic Black participants in MADRES compared to non-Hispanic White participants may reflect lower tap water consumption or lower fluoride exposure from other sources. Additional research is needed to examine whether MUFsg levels observed among pregnant women in the US are associated with neurodevelopmental outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Evidence suggests organophosphate esters (OPEs) are neurotoxic; however, the epidemiological literature remains scarce. We investigated whether prenatal exposures to OPEs were associated with child neurobehavior in the MADRES cohort., Methods: We measured nine OPE metabolites in 204 maternal urine samples (gestational age at collection: 31.4 ± 1.8 weeks). Neurobehavior problems were assessed among 36-month-old children using the Child Behavior Checklist's (CBCL) three composite scales [internalizing, externalizing, and total problems]. We examined associations between tertiles of prenatal OPE metabolites (> 50% detection) and detect/non-detect categories (< 50% detection) and CBCL composite scales using linear regression and generalized additive models. We also examined mixtures for widely detected OPEs (n = 5) using Bayesian kernel machine regression., Results: Maternal participants with detectable versus non-detectable levels of bis(2-methylphenyl) phosphate (BMPP) had children with 42% (95% CI: 4%, 96%) higher externalizing, 45% (-2%, 114%) higher internalizing, and 35% (3%, 78%) higher total problems. Participants in the second versus first tertile of bis(butoxethyl) phosphate (BBOEP) had children with 43% (-1%, 109%) higher externalizing scores. Bis(1-chloro-2-propyl) phosphate (BCIPP) and child sex had a statistically significant interaction in internalizing (p = 0.02) and total problems (p = 0.03) models, with 120% (23%, 295%) and 57% (6%, 134%) higher scores in the third versus first BCIPP tertile among males. Among females, detectable vs non-detectable levels of prenatal BMPP were associated with 69% higher externalizing scores (5%, 170%) while the third versus first tertile of prenatal BBOEP was associated with 45% lower total problems (-68%, -6%). Although the metabolite mixture and each CBCL outcome had null associations, we observed marginal associations between di-n-butyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and higher internalizing scores (0.15; 95% CrI: -0.02, 0.32), holding other metabolites at their median., Conclusions: Our results generally suggest adverse and sex-specific effects of prenatal exposure to previously understudied OPEs on neurobehavioral outcomes in 36-month children, providing evidence of potential OPE neurotoxicity., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Prenatal air pollution exposure may increase risk for childhood obesity. However, few studies have evaluated in utero growth measures and infant weight trajectories. This study will evaluate the associations of prenatal exposure to ambient air pollutants with weight trajectories from the 3rd trimester through age 2 years., Methods: We studied 490 pregnant women who were recruited from the Maternal and Development Risks from Environmental and Social Stressors (MADRES) cohort, which comprises a low-income, primarily Hispanic population in Los Angeles, California. Nitrogen dioxide (NO 2 ), particulate matter < 10 µm (PM 10 ), particulate matter < 2.5 µm (PM 2.5 ), and ozone (O 3 ) concentrations during pregnancy were estimated from regulatory air monitoring stations. Fetal weight was estimated from maternal ultrasound records. Infant/child weight measurements were extracted from medical records or measured during follow-up visits. Piecewise spline models were used to assess the effect of air pollutants on weight, overall growth, and growth during each period., Results: The mean (SD) prenatal exposure concentrations for NO 2 , PM 2.5 , PM 10 , and O 3 were 16.4 (2.9) ppb, 12.0 (1.1) μg/m 3 , 28.5 (4.7) μg/m 3 , and 26.2 (2.9) ppb, respectively. Comparing an increase in prenatal average air pollutants from the 10th to the 90th percentile, the growth rate from the 3rd trimester to age 3 months was significantly increased (1.55% [95%CI 1.20%, 1.99%] for PM 2.5 and 1.64% [95%CI 1.27%, 2.13%] for NO 2 ), the growth rate from age 6 months to age 2 years was significantly decreased (0.90% [95%CI 0.82%, 1.00%] for NO 2 ), and the attained weight at age 2 years was significantly lower (- 7.50% [95% CI - 13.57%, - 1.02%] for PM 10 and - 7.00% [95% CI - 11.86%, - 1.88%] for NO 2 )., Conclusions: Prenatal ambient air pollution was associated with variable changes in growth rate and attained weight from the 3rd trimester to age 2 years. These results suggest continued public health benefits of reducing ambient air pollution levels, particularly in marginalized populations., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Autism Spectrum Disorder (ASD) risk is highly heritable, with potential additional non-genetic factors, such as prenatal exposure to ambient particulate matter with aerodynamic diameter < 2.5 µm (PM 2.5 ) and maternal immune activation (MIA) conditions. Because these exposures may share common biological effect pathways, we hypothesized that synergistic associations of prenatal air pollution and MIA-related conditions would increase ASD risk in children., Objectives: This study examined interactions between MIA-related conditions and prenatal PM 2.5 or major PM 2.5 components on ASD risk., Methods: In a population-based pregnancy cohort of children born between 2001 and 2014 in Southern California, 318,751 mother-child pairs were followed through electronic medical records (EMR); 4,559 children were diagnosed with ASD before age 5. Four broad categories of MIA-related conditions were classified, including infection, hypertension, maternal asthma, and autoimmune conditions. Average exposures to PM 2.5 and four PM 2.5 components, black carbon (BC), organic matter (OM), nitrate (NO 3 - ), and sulfate (SO 4 2- ), were estimated at maternal residential addresses during pregnancy. We estimated the ASD risk associated with MIA-related conditions, air pollution, and their interactions, using Cox regression models to adjust for covariates., Results: ASD risk was associated with MIA-related conditions [infection (hazard ratio 1.11; 95% confidence interval 1.05-1.18), hypertension (1.30; 1.19-1.42), maternal asthma (1.22; 1.08-1.38), autoimmune disease (1.19; 1.09-1.30)], with higher pregnancy PM 2.5 [1.07; 1.03-1.12 per interquartile (3.73 μg/m 3 ) increase] and with all four PM 2.5 components. However, there were no interactions of each category of MIA-related conditions with PM 2.5 or its components on either multiplicative or additive scales., Conclusions: MIA-related conditions and pregnancy PM 2.5 were independently associations with ASD risk. There were no statistically significant interactions of MIA conditions and prenatal PM 2.5 exposure with ASD risk., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Air pollution has been associated with gestational diabetes mellitus (GDM). We aim to investigate susceptible windows of air pollution exposure and factors determining population vulnerability., Methods: We ascertained GDM status in the prospective Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort from Los Angeles, California, USA. We calculated the relative risk of GDM by exposure to ambient particulate matter (PM 10 ; PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) in each week from 12 weeks before to 24 weeks after conception, adjusting for potential confounders, with distributed lag models to identify susceptible exposure windows. We examined effect modification by prenatal depression, median-split pre-pregnancy BMI (ppBMI) and age., Findings: Sixty (9.7%) participants were diagnosed with GDM among 617 participants (mean age: 28.2 years, SD: 5.9; 78.6% Hispanic, 11.8% non-Hispanic Black). GDM risk increased with exposure to PM 2.5 , PM 10 , and NO 2 in a periconceptional window ranging from 5 weeks before to 5 weeks after conception: interquartile-range increases in PM 2.5 , PM 10 , and NO 2 during this window were associated with increased GDM risk by 5.7% (95% CI: 4.6-6.8), 8.9% (8.1-9.6), and 15.0% (13.9-16.2), respectively. These sensitive windows generally widened, with greater effects, among those with prenatal depression, with age ≥28 years, or with ppBMI ≥27.5 kg/m 2 , than their counterparts., Interpretation: Preconception and early-pregnancy are susceptible windows of air pollutants exposure that increased GDM risk. Prenatal depression, higher age, or higher ppBMI may increase one's vulnerability to air pollution-associated GDM risk., Funding: National Institutes of Health, Environmental Protection Agency., Competing Interests: The authors declare they have no actual or potential competing financial interests., (© 2023 The Author(s).)

Background: There is increasing evidence for adverse health effects associated with aircraft-emitted particulate matter (PM) exposures, which are largely in the ultrafine (PM 0.1 ) size fraction, but no previous study has examined neurodevelopmental outcomes., Objective: To assess associations between maternal exposure to aircraft ultrafine particles (UFP) during pregnancy and offspring autism spectrum disorder (ASD) diagnosis., Methods: This large, representative cohort study included 370,723 singletons born in a single healthcare system. Demographic data, maternal health information, and child's ASD diagnosis by age 5 were extracted from electronic medical records. Aircraft exposure estimates for PM 0.1 were generated by the University of California Davis/California Institute of Technology Source Oriented Chemical Transport model. Cox proportional hazard models were used to assess associations between maternal exposure to aircraft PM 0·1 in pregnancy and ASD diagnosis, controlling for covariates., Results: Over the course of follow-up, 4,554 children (1.4 %) were diagnosed with ASD. Increased risk of ASD was associated with maternal exposure to aircraft PM 0.1 [hazard ratio, HR: 1.02, (95 % confidence interval (CI): 1.01-1.03) per IQR = 0.02 µg/m 3 increase during pregnancy. Associations were robust to adjustment for total PM 0.1 and fine particulate matter (PM 2.5 ), near-roadway air pollution, and other covariates. Noise adjustment modestly attenuated estimates of UFP effects, which remained statistically significant., Discussion: The results strengthen the emerging evidence that maternal particulate matter exposure during pregnancy is associated with offspring ASD diagnosis and identify aircraft-derived PM 0.1 as novel targets for further study and potential regulation., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Organophosphate esters (OPEs) are used as flame retardants and plasticizers in various consumer products. Limited prior research suggests sex-specific effects of prenatal OPE exposures on fetal development. We evaluated overall and sex-specific associations between prenatal OPE exposures and gestational age (GA) at birth and birthweight for gestational age (BW for GA) z-scores among the predominately low-income, Hispanic MADRES cohort., Methods: Nine OPE metabolite concentrations were measured in 421 maternal urine samples collected during a third trimester visit (GA = 31.5 ± 2.0 weeks). We examined associations between single urinary OPE metabolites and GA at birth and BW for GA z-scores using linear regression models and Generalized Additive Models (GAMs) and effects from OPE mixtures using Bayesian Kernel Machine Regression (BKMR). We also assessed sex-specific differences in single metabolite analyses by evaluating statistical interactions and stratifying by sex., Results: We did not find significant associations between individual OPE metabolites and birth outcomes in the full infant sample; however, we found that higher bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with earlier GA at birth among male infants (p = 0.04), and a nonlinear, inverted U-shape association between the sum of dibutyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and GA at birth among female infants (p = 0.03). In mixtures analysis, higher OPE metabolite mixture exposures was associated with lower GA at birth, which was primarily driven by female infants. No associations were observed between OPE mixtures and BW for GA z-scores., Conclusion: Higher BDCIPP and DNBP + DIBP concentrations were associated with earlier GA at birth among male and female infants, respectively. Higher exposure to OPE mixtures was associated with earlier GA at birth, particularly among female infants. However, we saw no associations between prenatal OPEs and BW for GA. Our results suggest sex-specific impacts of prenatal OPE exposures on GA at birth., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Higher ambient temperature and air pollution may contribute to increased risk of behaviors harmful to oneself or to others; however, quantitative evidence is limited. We examined the relationship of deaths due to suicide and homicide with temperature and air pollution in California-a state prone to high levels of both exposures., Method: California death certificates from 2014 to 2019 were used to identify deaths due to suicide and homicide. Residential data for decedents were used to assign exposure to daily temperature (maximum[T max ], minimum[T min ]) and daily average air pollution concentrations (particulate matter <10 μm[PM 10 ] and < 2.5 μm[PM 2.5 ], nitrogen dioxide[NO 2 ], ozone[O 3 ]). T min served as a surrogate for nighttime temperature. A time-stratified case-crossover study design using conditional logistic regression was used to assess the effects of daily exposure to temperature and air pollutants on suicide and homicide mortality, adjusting for relative humidity. Effect modification by sex and age was assessed., Results: We observed 24,387 deaths due to suicide and 10,767 deaths due to homicide. We found a monotonic temperature association for both outcomes. A 5 °C increase in T max at lag-2 and T min at lag-0 was associated with 3.1 % (95 % confidence interval [CI]: 1.1 %-5.2 %) and 3.8 % (95%CI: 0.9 %-6.8 %) increased odds of death due to suicide, respectively. The increased odds of homicide mortality per 5 °C increase in T max at lag-0 and T min at lag-1 were 4.9 % (95%CI: 1.6 %-8.1 %) and 6.2 % (95%CI: 1.6 %-11.0 %), respectively. No air pollutant associations were statistically significant. Temperature associations were robust after adjustment for PM 2.5 . Some temperature effects were larger among women for suicide and men for homicide mortality, and among those over age 65 years for both outcomes., Conclusion: Risk of suicide and homicide mortality increases with increasing daily ambient temperatures. Findings have public health relevance given anticipated increases in temperatures due to global climate change., 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 © 2023 Elsevier B.V. All rights reserved.)

Lay Abstract: Autism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.

Biomarkers such as exhaled nitric oxide (FeNO), a marker of airway inflammation, have applications in the study of chronic respiratory disease where longitudinal studies of within-participant changes in the biomarker are particularly relevant. A cutting-edge approach to assessing FeNO, called multiple flow FeNO, repeatedly assesses FeNO across a range of expiratory flow rates at a single visit and combines these data with a deterministic model of lower respiratory tract NO to estimate parameters quantifying airway wall and alveolar NO sources. Previous methodological work for multiple flow FeNO has focused on methods for data from a single participant or from cross-sectional studies. Performance of existing ad hoc two-stage methods for longitudinal multiple flow FeNO in cohort or panel studies has not been evaluated. In this paper, we present a novel longitudinal extension to a unified hierarchical Bayesian (L&#95;U&#95;HB) model relating longitudinally assessed multiple flow FeNO to covariates. In several simulation study scenarios, we compare the L&#95;U&#95;HB method to other unified and two-stage frequentist methods. In general, L&#95;U&#95;HB produced unbiased estimates, had good power, and its performance was not sensitive to the magnitude of the association with a covariate and correlations between NO parameters. In an application relating height to longitudinal multiple flow FeNO in schoolchildren without asthma, unified analysis methods estimated positive, statistically significant associations of height with airway and alveolar NO concentrations and negative associations with airway wall diffusivity while estimates from two-stage methods were smaller in magnitude and sometimes non-significant., (© 2023. The Author(s).)