Developing a National-Scale Exposure Index for Combined Environmental Hazards and Social Stressors and Applications to the Environmental Influences on Child Health Outcomes (ECHO) Cohort.

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless combined exposure index, which collapses census-tract level data into a single relative measure of exposure ranging from 0-1 (where higher values indicate higher exposure to hazards), includes indicators for major air pollutants and air toxics, features of the built environment, traffic exposures, and social determinants of health (e.g., lower educational attainment) drawn from existing data sources. We observed temporal and geographic variations in index values, with exposures being highest among participants living in the West and Northeast regions. Pregnant people who identified as Black or Hispanic (of any race) were at higher risk of living in a "high" exposure census tract (defined as an index value above 0.5) relative to those who identified as White or non-Hispanic. Index values were also higher for pregnant people with lower educational attainment. Several recommendations follow from our work, including that environmental and social stressor datasets with higher spatial and temporal resolutions are needed to ensure index-based tools fully capture the total environmental context.

Opportunities for understanding the COVID-19 pandemic and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) program.

Objective: Ongoing pediatric cohort studies offer opportunities to investigate the impact of the COVID-19 pandemic on children's health. With well-characterized data from tens of thousands of US children, the Environmental influences on Child Health Outcomes (ECHO) Program offers such an opportunity. Methods: ECHO enrolled children and their caregivers from community- and clinic-based pediatric cohort studies. Extant data from each of the cohorts were pooled and harmonized. In 2019, cohorts began collecting data under a common protocol, and data collection is ongoing with a focus on early life environmental exposures and five child health domains: birth outcomes, neurodevelopment, obesity, respiratory, and positive health. In April of 2020, ECHO began collecting a questionnaire designed to assess COVID-19 infection and the pandemic's impact on families. We describe and summarize the characteristics of children who participated in the ECHO Program during the COVID-19 pandemic and novel opportunities for scientific advancement. Results: This sample (n = 13,725) was diverse by child age (31% early childhood, 41% middle childhood, and 16% adolescence up to age 21), sex (49% female), race (64% White, 15% Black, 3% Asian, 2% American Indian or Alaska Native, <1% Native Hawaiian or Pacific Islander, 10% Multiple race and 2% Other race), Hispanic ethnicity (22% Hispanic), and were similarly distributed across the four United States Census regions and Puerto Rico. Conclusion: ECHO data collected during the pandemic can be used to conduct solution-oriented research to inform the development of programs and policies to support child health during the pandemic and in the post-pandemic era.

Depression, perceived stress, and distress during pregnancy and EV-associated miRNA profiles in MADRES.

BACKGROUND: MicroRNA (miRNA) circulating in plasma has been proposed as biomarkers for a variety of diseases and stress measures, including depression, stress, and trauma. However, few studies have examined the relationship between stress and miRNA during pregnancy. METHODS: In this study, we examined associations between measures of stress and depression during pregnancy with miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, California. Extracellular-vesicle- (EV-) associated miRNA were isolated from maternal plasma and quantified using the Nanostring nCounter platform. Correlations for stress-associated miRNA were also calculated for 89 matching cord blood samples. RESULTS: Fifty miRNA were nominally associated with depression, perceived stress, and prenatal distress (raw p < 0.05) with 17 miRNA shared between two or more stress measures. Two miRNA (miR-150-5p and miR-148b-3p) remained marginally significant after FDR adjustment (p < 0.10). Fifteen PANTHER pathways were enriched for predicted gene targets of the 50 miRNA associated with stress. Clusters of maternal and neonate miRNA expression suggest a link between maternal and child profiles. LIMITATIONS: The study evaluated 142 miRNA and was not an exhaustive analysis of all discovered miRNA. Evaluations for stress, depression and trauma were based on self-reported instruments, rather than diagnostic tools. CONCLUSIONS: Depression and stress during pregnancy are associated with some circulating EV miRNA. Given that EV miRNA play important roles in maternal-fetal communication, this may have downstream consequences for maternal and child health, and underscore the importance of addressing mental health during pregnancy, especially in health disparities populations.

Detected prenatal perfluorooctanoic acid (PFOA) exposure is associated with decreased fetal head biometric parameters in participants experiencing higher perceived stress during pregnancy in the MADRES cohort.

Background: Perfluoroalkyl substances (PFAS) are ubiquitous synthetic chemicals with long half-lives and are known to cross the placenta during pregnancy. We examined the influence of maternal PFAS levels on in utero fetal growth trajectories and assessed whether maternal stress modified these associations. Methods: Blood serum concentrations of five PFAS (PFOS, PFHxS, PFNA, PFOA, PFDA) were measured in 335 prenatal specimens (mean gestational age (GA): 21±9 weeks) in the MADRES cohort. Fetal growth outcomes (head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL), and estimated fetal weight (EFW)) were abstracted from ultrasound medical records and measured at the 3rd trimester study visit (N = 833 scans, GA range 10-42 weeks, mean 2.4 scans/participant). Adjusted linear mixed models with a GA quadratic growth curve were used for each PFAS exposure and growth outcome. PFOS and PFHxS were modeled continuously (100% sample detection), while PFOA, PFNA, and PFDA were modeled categorically (57-70% sample detection). Scores on the Perceived Stress Scale (PSS) measured in pregnancy were dichotomized at the median (<13 vs. ≥ 13) in stratified models. Results: Participants were on average 29±6 years old and predominately Hispanic (76%). Median serum concentrations of PFOS, PFHxS, PFNA, PFOA and PFDA were 1.34, 1.10, 0.07, 0.12, and 0.04 ng/mL, respectively. Participants with detected PFOA concentrations had fetuses with -2.5 mm (95% CI -4.2, -0.8) smaller HC and-0.7 mm (95% CI -1.3, -0.2) smaller BPD on average for a fixed GA than those without detected PFOA concentrations. In models stratified by PSS level, the effects of PFOA on fetal growth parameters were stronger and only significant in participants with higher stress levels (HC: ß= -3.5, 95% CI -5.8, -1.4; BPD: ß = -0.8, 95% CI -1.6, -1.1). Conclusions: Prenatal PFOA exposure adversely impacted fetal head biometric parameters in participants experiencing higher stress during pregnancy.

Prenatal Perfluorooctanoic Acid (PFOA) Exposure Is Associated With Lower Infant Birthweight Within the MADRES Pregnancy Cohort.

Introduction: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals found in household products that can cross the placenta during pregnancy. We investigated whether PFAS exposure during pregnancy was associated with infant birth outcomes in a predominantly urban Hispanic population. Methods: Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 342 prenatal biospecimens (mean gestational age: 21 ± 9 weeks) from participants in the ongoing Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. PFAS compounds were modeled continuously or categorically, depending on the percentage of samples detected. The birth outcomes assessed were birthweight, gestational age at birth, and birthweight for gestational age (BW-for-GA) z-scores that accounted for parity or infant sex. Single pollutant and multipollutant linear regression models were performed to evaluate associations between PFAS exposures and birth outcomes, adjusting for sociodemographic, perinatal, and study design covariates. Results: Maternal participants (n = 342) were on average 29 ± 6 years old at study entry and were predominantly Hispanic (76%). Infants were born at a mean of 39 ± 2 weeks of gestation and weighed on average 3,278 ± 522 g. PFOS and PFHxS were detected in 100% of the samples while PFNA, PFOA, and PFDA were detected in 70%, 65%, and 57% of the samples, respectively. PFAS levels were generally lower in this cohort than in comparable cohorts. Women with detected levels of PFOA during pregnancy had infants weighing on average 119.7 g less (95% CI -216.7, -22.7) than women with undetected levels of PFOA in adjusted single pollutant models. PFOA results were also statistically significant in BW-for-GA z-score models that were specific for sex or parity. In models that were mutually adjusted for five detected PFAS compounds, PFOA results remained comparable; however, the association was only significant in BW-for-GA z-scores that were specific for parity (ß = -0.3; 95% CI -0.6, -0.01). We found no significant adjusted associations with the remaining PFAS concentrations and the birth outcomes assessed. Conclusion: Prenatal exposure to PFOA was associated with lower birthweight in infants, suggesting that exposure to these chemicals during critical periods of development might have important implications for children's health.

Prenatal ambient air pollution and maternal depression at 12 months postpartum in the MADRES pregnancy cohort.

BACKGROUND: Depression is the leading cause of mental health-related morbidity and affects twice as many women as men. Hispanic/Latina women in the US have unique risk factors for depression and they have lower utilization of mental health care services. Identifying modifiable risk factors for maternal depression, such as ambient air pollution, is an urgent public health priority. We aimed to determine whether prenatal exposure to ambient air pollutants was associated with maternal depression at 12 months after childbirth. METHODS: One hundred eighty predominantly low-income Hispanic/Latina women participating in the ongoing MADRES cohort study in Los Angeles, CA were followed from early pregnancy through 12 months postpartum through a series of phone questionnaires and in-person study visits. Daily prenatal ambient pollutant estimates of nitrogen dioxide (NO2), ozone (O3), and particulate matter (PM10 and PM2.5) were assigned to participant residences using inverse-distance squared spatial interpolation from ambient monitoring data. Exposures were averaged for each trimester and across pregnancy. The primary outcome measure was maternal depression at 12 months postpartum, as reported on the 20-item Center for Epidemiologic Studies-Depression (CES-D) scale. We classified each participant as depressed (n = 29) or not depressed (n = 151) based on the suggested cutoff of 16 or above (possible scores range from 0 to 60) and fitted logistic regression models, adjusting for potential confounders. RESULTS: We found over a two-fold increased odds of depression at 12 months postpartum associated with second trimester NO2 exposure (OR = 2.63, 95% CI: 1.41-4.89) and pregnancy average NO2 (OR = 2.04, 95% CI: 1.13-3.69). Higher second trimester PM2.5 exposure also was associated with increased depression at 12 months postpartum (OR = 1.56, 95% CI: 1.01-2.42). The effect for second trimester PM10 was similar and was borderline significant (OR = 1.58, 95% CI: 0.97-2.56). CONCLUSIONS: In a low-income cohort consisting of primarily Hispanic/Latina women in urban Los Angeles, we found that prenatal ambient air pollution, especially mid-pregnancy NO2 and PM2.5, increased the risk of depression at 12 months after childbirth. These results underscore the need to better understand the contribution of modifiable environmental risk factors during potentially critical exposure periods.

Demographic predictors of urinary arsenic in a low-income predominantly Hispanic pregnancy cohort in Los Angeles.

BACKGROUND: Arsenic (As) is a contaminant of top public health concern, due to its range of detrimental health effects. Arsenic exposure has not been well-characterized among the US Hispanic populations and has been particularly understudied in this population during pregnancy. METHODS: As part of the MADRES ongoing pregnancy cohort of predominantly lower-income, Hispanic women in Los Angeles, CA, we examined levels of maternal first trimester urinary As, including total As and As metabolites (inorganic (iAs), monomethylated (MMA) and dimethylated As (DMA)), in relation to participant demographics, lifestyle characteristics, and rice/seafood consumption, to identify factors that may influence As exposure and its metabolites during pregnancy (N = 241). RESULTS: Total As concentrations ranged from low to high (0.8-506.2 µg/L, mean: 9.0 µg/L, SD: 32.9) in our study population. Foreign-born Hispanic women had 8.6% higher %DMA (95% CI: 3.3%, 13.9%) and -7.7% lower %iAs (95% CI: -12.6%, -2.9%) than non-Hispanic women. A similar trend was observed for US-born Hispanic women. In addition, maternal age was associated with 0.4% higher %iAs (95% CI: 0.1%, 0.6%) and 0.4% lower %DMA (95% CI: -0.7%, -0.1%) per year, which may indicate poor As methylation capacity. CONCLUSION: Individual factors may predict As exposure and metabolism in pregnancy, and in turn, greater risk of adverse health effects.