Environmental Exposures and Pediatric Cardiology: A Scientific Statement From the American Heart Association.

Environmental toxicants and pollutants are causes of adverse health consequences, including well-established associations between environmental exposures and cardiovascular diseases. Environmental degradation is widely prevalent and has a long latency period between exposure and health outcome, potentially placing a large number of individuals at risk of these health consequences. Emerging evidence suggests that environmental exposures in early life may be key risk factors for cardiovascular conditions across the life span. Children are a particularly sensitive population for the detrimental effects of environmental toxicants and pollutants given the long-term cumulative effects of early-life exposures on health outcomes, including congenital heart disease, acquired cardiac diseases, and accumulation of cardiovascular disease risk factors. This scientific statement highlights representative examples for each of these cardiovascular disease subtypes and their determinants, focusing specifically on the associations between climate change and congenital heart disease, airborne particulate matter and Kawasaki disease, blood lead levels and blood pressure, and endocrine-disrupting chemicals with cardiometabolic risk factors. Because children are particularly dependent on their caregivers to address their health concerns, this scientific statement highlights the need for clinicians, research scientists, and policymakers to focus more on the linkages of environmental exposures with cardiovascular conditions in children and adolescents.

Cohort profile: The Assessing Imperial Valley Respiratory Health and the Environment (AIRE) study.

BACKGROUND: The Children's Assessing Imperial Valley Respiratory Health and the Environment (AIRE) study is a prospective cohort study of environmental influences on respiratory health in a rural, southeastern region of California (CA), which aims to longitudinally examine the contribution of a drying saline lake to adverse health impacts in children. OBJECTIVES: This cohort was established through a community-academic partnership with the goal of assessing the health effects of childhood exposures to wind-blown particulate matter (PM) and inform public health action. We hypothesize that local PM sources are related to poorer children's respiratory health. POPULATION: Elementary school children in Imperial Valley, CA. DESIGN: Prospective cohort study. METHODS: Between 2017 and 2019, we collected baseline information on 731 children, then follow-up assessments yearly or twice-yearly since 2019. Data have been collected on children's respiratory health, demographics, household characteristics, physical activity and lifestyle, via questionnaires completed by parents or primary caregivers. In-person measurements, conducted since 2019, repeatedly assessed lung function, height, weight and blood pressure. Exposure to air pollutants has been assessed by multiple methods and individually assigned to participants using residential and school addresses. Health data will be linked to ambient and local sources of PM, during and preceding the study period to understand how spatiotemporal trends in these environmental exposures may relate to respiratory health. PRELIMINARY RESULTS: Analyses of respiratory symptoms indicate a high prevalence of allergies, bronchitic symptoms and wheezing. Asthma diagnosis was reported in 24% of children at enrolment, which exceeds both CA state and US national prevalence estimates for children. CONCLUSIONS: The Children's AIRE cohort, while focused on the health impacts of the drying Salton Sea and air quality in Imperial Valley, is poised to elucidate the growing threat of drying saline lakes and wind-blown dust sources to respiratory health worldwide, as sources of wind-blown dust emerge in our changing climate.

Increased Risk of Gestational Hypertension by Periconceptional Exposure to Ambient Air Pollution and Effect Modification by Prenatal Depression.

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 particles (with a diameter of ≤10 µm [PM10] or ≤2.5 µm [PM2.5]), 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 PM2.5 from 1 week preconception to 11 weeks postconception: higher exposure (5 µg/m3) 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 (PM2.5, 16% [95% CI, 3%-31%]; PM10, 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.

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.

Maternal Dietary Patterns During Pregnancy Are Linked to Hypertensive Disorders of Pregnancy Among a Predominantly Low-Income US Hispanic/Latina Pregnancy Cohort.

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]; Ptrend=0.014) and preeclampsia (OR, 4.10 [95% CI, 1.25-13.5]; Ptrend=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]; Ptrend=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 Pinteractions=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.

Effect of parental adverse childhood experiences on intergenerational DNA methylation signatures from peripheral blood mononuclear cells and buccal mucosa.

In this study, the effect of cumulative ACEs experienced on human maternal DNA methylation (DNAm) was estimated while accounting for interaction with domains of ACEs in prenatal peripheral blood mononuclear cell samples from the Maternal and Developmental Risks from Environmental Stressors (MADRES) pregnancy cohort. The intergenerational transmission of ACE-associated DNAm was also explored used paired maternal (N = 120) and neonatal cord blood (N = 69) samples. Replication in buccal samples was explored in the Children's Health Study (CHS) among adult parental (N = 31) and pediatric (N = 114) samples. We used a four-level categorical indicator variable for ACEs exposure: none (0 ACEs), low (1-3 ACEs), moderate (4-6 ACEs), and high (>6 ACEs). Effects of ACEs on maternal DNAm (N = 240) were estimated using linear models. To evaluate evidence for intergenerational transmission, mediation analysis (N = 60 mother-child pairs) was used. Analysis of maternal samples displayed some shared but mostly distinct effects of ACEs on DNAm across low, moderate, and high ACEs categories. CLCN7 and PTPRN2 was associated with maternal DNAm in the low ACE group and this association replicated in the CHS. CLCN7 was also nominally significant in the gene expression correlation analysis among maternal profiles (N = 35), along with 11 other genes. ACE-associated methylation was observed in maternal and neonatal profiles in the COMT promoter region, with some evidence of mediation by maternal COMT methylation. Specific genomic loci exhibited mutually exclusive maternal ACE effects on DNAm in either maternal or neonatal population. There is some evidence for an intergenerational effect of ACEs, supported by shared DNAm signatures in the COMT gene across maternal-neonatal paired samples.

Perceived Stress From Childhood to Adulthood and Cardiometabolic End Points in Young Adulthood: An 18-Year Prospective Study.

BACKGROUND: We investigated how childhood-to-adulthood perceived stress patterns predict adult cardiometabolic risk. METHODS AND RESULTS: This study included 276 participants from the Southern California Children's Health Study (2003-2014), and a follow-up assessment (2018-2021). Perceived stress (Perceived Stress Scale) was initially reported by participants' parents for themselves during early childhood (mean age, 6.3 years), and later self-reported during adolescence (13.3 years) and young adulthood (23.6 years). Participants were grouped into 4 stress patterns: consistently high, decreasing, increasing, and consistently low. Cardiometabolic risk was assessed in young adulthood by carotid artery intima-media thickness, systolic and diastolic blood pressure, obesity, percent body fat, android/gynoid ratio, and glycated hemoglobin. A cardiometabolic risk score was generated by summing the clinically abnormal markers. Multivariable linear and logistic regression models were used to (1) examine the associations between Perceived Stress Scale at 3 time points and adult cardiometabolic risk, and (2) assess the impact of stress pattern on adult cardiometabolic risk. Findings suggested that in adulthood, higher Perceived Stress Scale score was associated with increased overall cardiometabolic risk (ß=0.12 [95% CI, 0.01-0.22]), carotid artery intima-media thickness (ß=0.01 [95% CI, 0.0003-0.02]), systolic blood pressure (ß=1.27 [95% CI, 0.09-2.45]), and diastolic blood pressure (ß=0.94 [95% CI, 0.13-1.75]). Individuals with a consistently high adolescence-to-adulthood stress pattern had greater overall cardiometabolic risk (ß=0.31 [95% CI, 0.02-0.60]), android/gynoid ratio (ß=0.07 [95% CI, 0.02-0.13]), percent body fat (ß=2.59 [95% CI, 0.01-5.17]), and greater odds of obesity (odds ratio, 5.57 [95% CI, 1.62-19.10]) in adulthood, compared with those with a consistently low Perceived Stress Scale score. CONCLUSIONS: Consistently high perceived stress from adolescence to adulthood may contribute to greater cardiometabolic risk in young adulthood.

The Role of Social Support and Acculturation Factors on Postpartum Mental Health Among Latinas in the MADRES Pregnancy Cohort.

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.

Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort.

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 (ORfine = 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 (pinteraction = 0.048) and detected bis(1-chloro-2-propyl) phosphate (BCIPP) with fine motor development (pinteraction = 0.02). Females had greater odds of potential motor delays for both detected DPRP (females vs males ORgross (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 ORfine (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.

Effects of in-utero personal exposure to PM2.5 sources and components on birthweight.

In-utero exposure to fine particulate matter (PM2.5) and specific sources and components of PM2.5 have been linked with lower birthweight. However, previous results have been mixed, likely due to heterogeneity in sources impacting PM2.5 and due to measurement error from using ambient data. Therefore, we investigated the effect of PM2.5 sources and their high-loading components on birthweight using data from 198 women in the 3rd trimester from the MADRES cohort 48-h personal PM2.5 exposure monitoring sub-study. The mass contributions of six major sources of personal PM2.5 exposure were estimated for 198 pregnant women in the 3rd trimester using the EPA Positive Matrix Factorization v5.0 model, along with their 17 high-loading chemical components using optical carbon and X-ray fluorescence approaches. Single- and multi-pollutant linear regressions evaluated the association between personal PM2.5 sources/components and birthweight, adjusting for gestational age, maternal age, race, infant sex, parity, diabetes status, temperature, maternal education, and smoking history. Participants were predominately Hispanic (81%), with a mean (SD) gestational age of 39.1 (1.5) weeks and age of 28.2 (6.0) years. Mean birthweight was 3295.8 g (484.1) and mean PM2.5 exposure was 21.3 (14.4) µg/m3. A 1 SD increase in the mass contribution of the fresh sea salt source was associated with a 99.2 g decrease in birthweight (95% CI - 197.7, - 0.6), and aged sea salt was associated with a 70.1 g decrease in birthweight (95% CI - 141.7, 1.4). Magnesium, sodium, and chlorine were associated with lower birthweight, which remained after adjusting for PM2.5 mass. This study found evidence that major sources of personal PM2.5 including fresh and aged sea salt were negatively associated with birthweight, with the strongest effect on birthweight from Na and Mg. The effect of crustal and fuel oil sources differed by infant sex with negative associations seen in boys compared to positive associations in girls.

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.

A Comparison of Measured Airborne and Self-Reported Secondhand Smoke Exposure in the MADRES Pregnancy Cohort Study.

INTRODUCTION: Secondhand smoke (SHS) exposure during pregnancy is linked to adverse birth outcomes, such as low birth weight and preterm birth. While questionnaires are commonly used to assess SHS exposure, their ability to capture true exposure can vary, making it difficult for researchers to harmonize SHS measures. This study aimed to compare self-reported SHS exposure with measurements of airborne SHS in personal samples of pregnant women. METHODS: SHS was measured on 48-hour integrated personal PM2.5 Teflon filters collected from 204 pregnant women, and self-reported SHS exposure measures were obtained via questionnaires. Descriptive statistics were calculated for airborne SHS measures, and analysis of variance tests assessed group differences in airborne SHS concentrations by self-reported SHS exposure. RESULTS: Participants were 81% Hispanic, with a mean (SD) age of 28.2 (6.0) years. Geometric mean (SD) personal airborne SHS concentrations were 0.14 (9.41) µg/m3. Participants reporting lower education have significantly higher airborne SHS exposure (p=0.015). Mean airborne SHS concentrations were greater in those reporting longer duration with windows open in the home. There was no association between airborne SHS and self-reported SHS exposure; however, asking about the number of smokers nearby in the 48-hour monitoring period was most correlated with measured airborne SHS (Two+ smokers: 0.30µg/m3 vs. One: 0.12µg/m3 and Zero: 0.15µg/m3; p=0.230). CONCLUSIONS: Self-reported SHS exposure was not associated with measured airborne SHS in personal PM2.5 samples. This suggests exposure misclassification using SHS questionnaires and the need for harmonized and validated questions to characterize this exposure in health studies. IMPLICATIONS: This study adds to the growing body of evidence that measurement error is a major concern in pregnancy research, particularly in studies that rely on self-report questionnaires to measure secondhand smoke (SHS) exposure. The study introduces an alternative method of SHS exposure assessment using objective optical measurements, which can help improve the accuracy of exposure assessment. The findings emphasize the importance of using harmonized and validated SHS questionnaires in pregnancy health research to avoid biased effect estimates. This study can inform future research, practice, and policy development to reduce SHS exposure and its adverse health effects.

Is BMI a Useful Indicator of Prenatal Health Among Black American Women?

OBJECTIVE: BMI is commonly used to measure risk to prenatal health but may not be sensitive to adiposity-associated health problems for Black women. The aim of the present study was to test associations between indices of prenatal health and BMI in Black women. METHODS: Data were from 652 women enrolled in two studies. Height and weight were used to calculate BMI. Depression and perceived stress were measured via maternal report, systemic inflammation via C-reactive protein (CRP), and nutrition by the ratio of omega-3 docosahexaenoic acid to omega-6 arachidonic acid fatty acids. RESULTS: Neither perceived stress, depression, nor fatty acids were associated with prenatal BMI. CRP levels were positively associated with BMI (beta = 6.56, t = 13.30, p < .001). The prevalence of high-risk levels of CRP (> 3 mg/L) was below 10% for all weight classes except for BMI ≥ 40. CONCLUSIONS: Results suggest that BMI may not be a sensitive index of adiposity related risk to prenatal health for Black women.

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.

Preconceptional and prenatal exposure to air pollutants and risk of gestational diabetes in the MADRES prospective pregnancy cohort study.

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 (PM10; PM2.5), nitrogen dioxide (NO2), and ozone (O3) 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 PM2.5, PM10, and NO2 in a periconceptional window ranging from 5 weeks before to 5 weeks after conception: interquartile-range increases in PM2.5, PM10, and NO2 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/m2, 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.

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.

Cardiovascular health and proximity to urban oil drilling in Los Angeles, California.

BACKGROUND: Although ~18 million people live within a mile from active oil and gas development (OGD) sites in the United States, epidemiological research on how OGD affects the health of nearby urban residents is sparse. Thousands of OGD sites are spread across Los Angeles (LA) County, California, home to the largest urban oil production in the country. Air pollution and noise from OGD may contribute to cardiovascular morbidity. OBJECTIVE: We examined the association between proximity to OGD and blood pressure in a diverse cohort of residents in LA. METHODS: We recruited residents in South LA who lived <1 km from an OGD site. We collected three blood pressure measurements for each participant and used the second and third measurements to calculate averages for systolic blood pressure (SBP) and diastolic blood pressure (DBP) separately. We conducted multivariable linear regression to examine the relationship between distance to OGD sites and continuous SBP and DBP, adjusting for BMI, smoking status, distance to freeway, sex, age, and use of antihypertension medications, with a random effect for household. We examined effect measure modification by BMI category and smoking category. RESULTS: Among the 623 adult participants, we found that for every 100 meter increase in distance from the OGD site, DBP was reduced by an average of 0.73 mmHg (95% CI: -1.26, -0.21) in this population. We observed stronger effects of proximity to OGD site on DBP among never smokers and among participants with a healthy BMI. The associations observed between proximity to OGD site and SBP were weaker but followed the same patterns as those for DBP. IMPACT: Our study suggests that living near urban oil drilling sites is significantly associated with greater diastolic blood pressure in urban Los Angeles communities. This research improves understanding of impacts from living nearby drilling operations on the health and welfare of this community, which is critical to inform public health relevant strategies.

Agricultural burning in Imperial Valley, California and respiratory symptoms in children: A cross-sectional, repeated measures analysis.

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.

Associations between area-level arsenic exposure and adverse birth outcomes: An Echo-wide cohort analysis.

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

Effects of In-Utero Personal Exposure to PM2.5 Sources and Components on Birthweight.

Background: In-utero exposure to fine particulate matter (PM2.5) and specific sources and components of PM2.5 have been linked with lower birthweight. However, previous results have been mixed, likely due to heterogeneity in sources impacting PM2.5 and due to measurement error from using ambient data. Therefore, we investigated the effect of PM2.5 sources and their high-loading components on birthweight using data from 198 women in the 3rd trimester from the MADRES cohort 48-hour personal PM2.5 exposure monitoring sub-study. Methods: The mass contributions of six major sources of personal PM2.5 exposure were estimated for 198 pregnant women in the 3rd trimester using the EPA Positive Matrix Factorization v5.0 model, along with their 17 high-loading chemical components using optical carbon and X-ray fluorescence approaches. Single- and multi-pollutant linear regressions were used to evaluate the association between personal PM2.5 sources and birthweight. Additionally, high-loading components were evaluated with birthweight individually and in models further adjusted for PM2.5 mass. Results: Participants were predominately Hispanic (81%), with a mean (SD) gestational age of 39.1 (1.5) weeks and age of 28.2 (6.0) years. Mean birthweight was 3,295.8g (484.1) and mean PM2.5 exposure was 21.3 (14.4) µg/m3. A 1 SD increase in the mass contribution of the fresh sea salt source was associated with a 99.2g decrease in birthweight (95% CI: -197.7, -0.6), while aged sea salt was associated with lower birthweight (ß =-70.1; 95% CI: -141.7, 1.4). Magnesium sodium, and chlorine were associated with lower birthweight, which remained after adjusting for PM2.5 mass. Conclusions: This study found evidence that major sources of personal PM2.5 including fresh and aged sea salt were negatively associated with birthweight, with the strongest effect on birthweight from Na and Mg. The effect of crustal and fuel oil sources differed by infant sex with negative associations seen in boys compared to positive associations in girls.