Longitudinal Transitions Between Use of Combustible, Noncombustible, and Multiple Cannabis Products From Adolescence to Young Adulthood and Intersections With Nicotine Use.

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.

Prospective study of e-cigarette use and respiratory symptoms in adolescents and young adults.

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.

ZIP Code and ZIP Code Tabulation Area Linkage: Implications for Bias in Epidemiologic Research.

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.

Smartphone GPS-Based Exposure to Greenspace and Walkability and Accelerometer-Assessed Physical Activity During Pregnancy and Early Postpartum-Evidence from the MADRES Cohort.

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.

Prenatal air pollution exposure is associated with inflammatory, cardiovascular, and metabolic biomarkers in mothers and newborns.

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 (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated, using inverse distance squared weighted spatial interpolation from regulatory air monitoring stations. Traffic-related NOx 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 PM10 was associated with elevated inflammation biomarkers and lowered cardiovascular biomarkers. NO2 exhibited positive associations with cardiovascular and inflammation markers. O3 was inversely associated with inflammation, metabolic, and cardiovascular biomarkers. In cord blood, pregnancy-averaged PM2.5 was associated with higher cardiovascular biomarkers and lower metabolic biomarkers. PM10 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.

Air quality and wheeze symptoms in a rural children's cohort near a drying saline lake.

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/m3 for PM10) 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 PM10 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 PM10 with wheeze or bronchitic symptoms among the children residing farther from the Sea. CONCLUSION: We observed stronger adverse impacts of PM10 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.

Exposure to perfluoroalkyl substances and longitudinal changes in bone mineral density in adolescents and young adults: A multi-cohort study.

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/cm2 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/cm2 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.

Per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers and dysregulation of MicroRNA expression in humans and animals-A systematic review.

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.

Organophosphate ester flame retardant chemicals and maternal depression during pregnancy.

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.

Prenatal ambient air pollution exposure and child weight trajectories from the 3rd trimester of pregnancy to 2 years of age: a cohort study.

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 (NO2), particulate matter < 10 µm (PM10), particulate matter < 2.5 µm (PM2.5), and ozone (O3) 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 NO2, PM2.5, PM10, and O3 were 16.4 (2.9) ppb, 12.0 (1.1) µg/m3, 28.5 (4.7) µg/m3, 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 PM2.5 and 1.64% [95%CI 1.27%, 2.13%] for NO2), the growth rate from age 6 months to age 2 years was significantly decreased (0.90% [95%CI 0.82%, 1.00%] for NO2), and the attained weight at age 2 years was significantly lower (- 7.50% [95% CI - 13.57%, - 1.02%] for PM10 and - 7.00% [95% CI - 11.86%, - 1.88%] for NO2). 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.

A Vegetable, Oil, and Fruit Dietary Pattern in Late Pregnancy is Linked to Reduced Risks of Adverse Birth Outcomes in a Predominantly Low-Income Hispanic and Latina Pregnancy Cohort.

BACKGROUND: Studies examining diet and its links to birth outcomes among socioeconomically disadvantaged populations in the United States are scarce. OBJECTIVES: We aimed to identify prenatal dietary patterns, examine their relationships with birth outcomes, and evaluate the variation of these associations by maternal diabetes status [no diabetes, gestational diabetes mellitus (GDM), preexisting diabetes]. METHODS: Women in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study (n = 465)-an ongoing, prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles-completed up to two 24-hour dietary recalls in the third trimester of pregnancy. We identified prenatal dietary patterns via factor analysis and evaluated their associations with infant birth weight and gestational age at birth (GA) z-scores, separately, using linear regression, as well as the associations of the dietary patterns with premature births, having an infant that was small for gestational age (SGA), and having an infant that was large for gestational age, using logistic regression and adjusting for relevant covariates. We additionally tested interaction terms between prenatal dietary patterns and maternal diabetes status in separate models. We adjusted for multiple comparisons using the false discovery rate. RESULTS: We identified 2 dietary patterns: 1) a dietary pattern of solid fats, refined grains, and cheese (SRC); and 2) a dietary pattern of vegetables, oils, and fruit (VOF). Comparing the highest to lowest quartiles, the VOF was significantly associated with a greater infant birth weight (ß = 0.40; 95% CIs: 0.10, 0.70; Ptrend = 0.011), a greater GA (ß = 0.32; 95% CIs: 0.03, 0.61; Ptrend = 0.036), lower odds of a premature birth (OR = 0.31; 95% CIs: 0.10, 0.95; Ptrend = 0.049), and lower odds of having an infant that was SGA (OR = 0.18; 95% CIs: 0.06, 0.58; Ptrend = 0.028). Only among women with GDM, a 1-SD score increase in the prenatal SRC was significantly associated with a lower infant birth weight (ß = -0.20; 95% CIs -0.39, -0.02; Pinteraction = 0.040). CONCLUSIONS: Among low-income Hispanic/Latina pregnant women, greater adherence to the prenatal VOF may lower the risk of a premature birth and having an infant that is SGA. Greater adherence to the SRC, however, may adversely affect newborn birth weight among mothers with GDM, but future research is needed to verify our findings.

Associations of per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers with oxidative stress markers: A systematic review and meta-analysis.

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 7th, 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 ß [95%CI]. Sign tests showed a significant positive association between PCBs and malondialdehyde (pone-tailed = 0.03). Additionally, we found significant negative associations of OCPs with acetylcholine esterase (pone-tailed = 0.02) and paraoxonase-1 (pone-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.

Sex-specific effects of prenatal organophosphate ester (OPE) metabolite mixtures and adverse infant birth outcomes in the maternal and developmental risks from environmental and social stressors (MADRES) pregnancy cohort.

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.

Urinary fluoride levels and metal co-exposures among pregnant women in Los Angeles, California.

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.

Prenatal exposures to organophosphate ester metabolite mixtures and children's neurobehavioral outcomes in the MADRES pregnancy cohort.

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.

Ambient Air Pollutant Exposures and COVID-19 Severity and Mortality in a Cohort of Patients with COVID-19 in Southern California.

Rationale: Ecological studies have shown air pollution associations with coronavirus disease (COVID-19) outcomes. However, few cohort studies have been conducted. Objectives: To conduct a cohort study investigating the association between air pollution and COVID-19 severity using individual-level data from the electronic medical record. Methods: This cohort included all individuals who received diagnoses of COVID-19 from Kaiser Permanente Southern California between March 1 and August 31, 2020. One-year and 1-month averaged ambient air pollutant (particulate matter ⩽2.5 µm in aerodynamic diameter [PM2.5], NO2, and O3) exposures before COVID-19 diagnosis were estimated on the basis of residential address history. Outcomes included COVID-19-related hospitalizations, intensive respiratory support (IRS), and ICU admissions within 30 days and mortality within 60 days after COVID-19 diagnosis. Covariates included socioeconomic characteristics and comorbidities. Measurements and Main Results: Among 74,915 individuals (mean age, 42.5 years; 54% women; 66% Hispanic), rates of hospitalization, IRS, ICU admission, and mortality were 6.3%, 2.4%, 1.5%, and 1.5%, respectively. Using multipollutant models adjusted for covariates, 1-year PM2.5 and 1-month NO2 average exposures were associated with COVID-19 severity. The odds ratios associated with a 1-SD increase in 1-year PM2.5 (SD, 1.5 µg/m3) were 1.24 (95% confidence interval [CI], 1.16-1.32) for COVID-19-related hospitalization, 1.33 (95% CI, 1.20-1.47) for IRS, and 1.32 (95% CI, 1.16-1.51) for ICU admission; the corresponding odds ratios associated with 1-month NO2 (SD, 3.3 ppb) were 1.12 (95% CI, 1.06-1.17) for hospitalization, 1.18 (95% CI, 1.10-1.27) for IRS, and 1.21 (95% CI, 1.11-1.33) for ICU admission. The hazard ratios for mortality were 1.14 (95% CI, 1.02-1.27) for 1-year PM2.5 and 1.07 (95% CI, 0.98-1.16) for 1-month NO2. No significant interactions with age, sex or ethnicity were observed. Conclusions: Ambient PM2.5 and NO2 exposures may affect COVID-19 severity and mortality.

Secondhand nicotine vaping at home and respiratory symptoms in young adults.

RATIONALE: Despite high prevalence of e-cigarette use (vaping), little is currently known regarding the health effects of secondhand nicotine vape exposure. OBJECTIVE: To investigate whether exposure to secondhand nicotine vape exposure is associated with adverse respiratory health symptoms among young adults. METHOD: We investigated the effect of secondhand nicotine vape exposure on annually reported wheeze, bronchitic symptoms and shortness of breath in the prospective Southern California Children Health Study cohort. Data were collected from study participants (n=2097) with repeated annual surveys from 2014 (average age: 17.3 years) to 2019 (average age: 21.9). We used mixed effect logistic regression to evaluate the association between secondhand nicotine vape and respiratory symptoms after controlling for relevant confounders. RESULTS: Prevalence of secondhand nicotine vape increased from 11.7% to 15.6% during the study period in this population. Prevalence of wheeze, bronchitic symptoms and shortness of breath ranged from 12.3% to 14.9%, 19.4% to 26.0% and 16.5% to 18.1%, respectively, during the study period. Associations of secondhand nicotine vape exposure with bronchitic symptoms (OR 1.40, 95% CI 1.06 to 1.84) and shortness of breath (OR 1.53, 95% CI 1.06 to 2.21) were observed after controlling for vaping, active and passive exposure to tobacco or cannabis, and demographic characteristics (age, gender, race/ethnicity and parental education). Stronger associations were observed when analysis was restricted to participants who were neither smokers nor vapers. There were no associations with wheezing after adjustment for confounders. CONCLUSION: Secondhand nicotine vape exposure was associated with increased risk of bronchitic symptoms and shortness of breath among young adults.

Third trimester cortisol is positively associated with gestational weight gain in pregnant women with class one obesity.

BACKGROUND/OBJECTIVE: Prevalence of pre-pregnancy obesity and excessive gestational weight gain (GWG) are higher among women of color with low SES. Dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and its end-product, cortisol, during pregnancy is hypothesized to be associated with excessive GWG. However, past studies have produced inconsistent findings and often did not include health disparities populations. This study examined the association between pre-pregnancy body mass index (BMI), third trimester diurnal cortisol, and GWG in low-income, predominantly Hispanic women. SUBJECTS/METHODS: The MADRES study is an ongoing prospective cohort study of primarily Hispanic, low-income pregnant women and their children in Los Angeles, California. Data from 176 participants were included in this study. Total cortisol secretion (area under the curve, AUC) was quantified using four salivary cortisol samples (awakening, 30 min after awakening, afternoon, and bedtime) that were collected at home on one day during the third trimester of pregnancy. Moderation of the association between total cortisol and GWG by pre-pregnancy BMI was tested using multiple linear regression with a multiplicative interaction term. RESULTS: There was no association between total cortisol secretion and GWG overall (p = 0.82), but the association between total cortisol and GWG was stronger for women with class 1 pre-pregnancy obesity compared to women with normal pre-pregnancy BMI (interaction term p = 0.04). CONCLUSIONS: Results suggest that obesity status before pregnancy may be exacerbating the physiological impact of cortisol on GWG.

Household pesticide exposures and infant gross motor development in the MADRES cohort.

BACKGROUND: The development of motor skills in infancy is a vital neurodevelopmental milestone. Although previous studies have explored the neurotoxic effects of agricultural pesticides on infants' motor development, limited research has examined early postnatal household pesticide use on infants' motor development, particularly among urban communities. OBJECTIVE: This study examined the association between early postnatal household pesticide use and infants' gross and fine motor development at 6 months of age. METHODS: Questionnaires were administered via telephone to 296 mother-infant dyads in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort. Early life household pesticide use was assessed via questionnaire administered when infants turned 3 months old and gross and fine motor development was assessed by the Ages and Stages Questionnaire (ASQ-3) at 6 months old. Infant gross motor scores were reverse coded so that higher scores indicated lower gross motor performance. Negative binomial regressions were performed to assess the relationship between household pesticide use and infant gross motor development. RESULTS: Infants were predominantly Hispanic (78.7%) and full term (gestational age at birth: 39.0 ± 1.9 weeks), with 22.3% of maternal participants reporting household use of rodent and insect pesticides. Adjusting for recruitment site, maternal age, ethnicity, household income, education, infant corrected age, infant sex, and home type, infants with maternal-reported household use of rodent and insect pesticides had 1.30 times higher expected gross motor scores (95% confiidence interval 1.05, 1.61) than infants with no reported use of household pesticides, with higher scores indicating reduced gross motor performance. CONCLUSIONS: Our results suggest household use of rodent and insect pesticides may harm infants' gross motor development in early childhood. Future research should evaluate the impact of specific household chemicals in infant biospecimens and their associations with infant motor development to confirm these findings.

Asthma clustering methods: a literature-informed application to the children's health study data.

OBJECTIVE: The heterogeneity of asthma has inspired widespread application of statistical clustering algorithms to a variety of datasets for identification of potentially clinically meaningful phenotypes. There has not been a standardized data analysis approach for asthma clustering, which can affect reproducibility and clinical translation of results. Our objective was to identify common and effective data analysis practices in the asthma clustering literature and apply them to data from a Southern California population-based cohort of schoolchildren with asthma. METHODS: As of January 1, 2020, we reviewed key statistical elements of 77 asthma clustering studies. Guided by the literature, we used 12 input variables and three clustering methods (hierarchical clustering, k-medoids, and latent class analysis) to identify clusters in 598 schoolchildren with asthma from the Southern California Children's Health Study (CHS). RESULTS: Clusters of children identified by latent class analysis were characterized by exhaled nitric oxide, FEV1/FVC, FEV1 percent predicted, asthma control and allergy score; and were predictive of control at two year follow up. Clusters from the other two methods were less clinically remarkable, primarily differentiated by sex and race/ethnicity and less predictive of asthma control over time. CONCLUSION: Upon review of the asthma phenotyping literature, common approaches of data clustering emerged. When applying these elements to the Children's Health Study data, latent class analysis clusters-represented by exhaled nitric oxide and spirometry measures-had clinical relevance over time.