Grantee Research Project Results
2020 Progress Report: Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) Center for Environmental Health Disparities Research
EPA Grant Number: R836158Center: Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) Center for Environmental Health Disparities Research
Center Director: Van Doren Breton, Carrie
Title: Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) Center for Environmental Health Disparities Research
Investigators: Gilliland, Frank D. , Hricko, Andrea M. , Van Doren Breton, Carrie , Bastain, Theresa Frilund , Cockburn, Myles G , Dunton, Genevieve Frilund
Current Investigators: Van Doren Breton, Carrie , Gilliland, Frank D. , Hricko, Andrea M. , Bastain, Theresa Frilund , Cockburn, Myles G , Dunton, Genevieve Frilund
Institution: University of Southern California
EPA Project Officer: Callan, Richard
Project Period: July 1, 2015 through June 30, 2020 (Extended to June 30, 2021)
Project Period Covered by this Report: July 1, 2019 through June 30,2020
Project Amount: $1,500,000
RFA: NIH/EPA Centers of Excellence on Environmental Health Disparities Research (2015) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
Project 1:
We propose to investigate how multiple chemical environmental exposures, coupled with other known psychosocial and behavioral risk factors for obesity, affect overall early childhood growth trajectories as well as infant feeding behaviors and metabolic efficiency. We will do so in a large longitudinal pregnancy cohort design, using cutting-edge technologies of cortisol assessment and fat depot quantification, state-of-the-art statistical methods, and novel methods for evaluating mitochondrial function, to address the following specific aims:
AIM 1. To investigate the cumulative effects of multiple pre- and postnatal chemical exposures (ambient and near-roadway air pollution, arsenic and manganese body burden, and CalEnviroScreen 2.0 index of overall pollutant burden), using spatial and personal monitoring methods during pregnancy. We will examine the effects of these exposures on birth and infant health outcomes including birth weight and 12 month childhood height and weight growth trajectories for 750 low-income, primarily Hispanic infants.
AIM 2. To evaluate whether these environmentally-related birth and infant outcomes are larger in infants of mothers a) with high levels of psychosocial stress during pregnancy as measured by diurnal cortisol profiles; b) who are overweight/obese before pregnancy or gain excess weight during pregnancy; and c) who have greater exposures to negative built (e.g., connectivity, lack of parks) and social (e.g., crime, violence) environments.
AIM 3. To evaluate whether environmentally-related birth and infant outcomes are mediated through altered energy consumption (infant feeding) and mitochondrial function (mtDNAcn and mtDNA methylation).
AIM 4. To examine the cumulative effects of prenatal environmental exposures and cortisol levels on abdominal fat depots of infants at <1 month of age using abdominal MRI scans in a subset of 40 infants.
Project 2:
Project 2 of the MADRES will examine the effects of pre-and postpartum environmental exposures, coupled with exposures to social stressors, on excessive gestational weight gain and postpartum weight retention through altered psychological and behavioral responses. We will test these hypotheses in a longitudinal study of 750 primarily Hispanic, low-income pregnant women with assessments during pregnancy (1st-3rd trimesters) and postpartum (3, 6, 12 months). The specific aims are:
AIM 1: To investigate the cross-sectional and longitudinal independent, cumulative, and interactive effects of multiple pre- and postpartum chemical environmental exposures (e.g., ambient and near-roadway air pollution, water contaminants, toxic releases) on maternal gestational weight gain and postpartum weight retention.
- Hypothesis 1 (main effects): Greater prepartum environmental exposures will be associated with a greater likelihood of excessive gestational weight gain and increased postpartum weight retention. Greater postpartum environmental exposures will lead to greater postpartum weight retention.
- Hypothesis 2 (time specificity): Environmental exposures occurring during the first trimester of pregnancy will have larger effects on gestational weight gain and postpartum weight retention.
- Hypothesis 3 (moderation): The above effects will be larger in women exposed to greater social stressors (e.g., neighborhood crime, violence, personal victimization, income inequality).
- Hypothesis 4 (mediation): Psychological (i.e., perceived stress and cortisol [Hypothalamic–pituitary–adrenal-HPA axis biomarker]) and behavioral (i.e., physical activity and dietary intake) responses will, in part, mediate the above effects.
AIM 2: To examine the daily effects of chemical environmental exposures and social stressors on pre- and postpartum psychological stress and energy-balance behaviors using personal, real-time, in situ data capture strategies (e.g., personal exposure sampling, geolocation monitoring, real-time electronic surveys [ecological momentary assessment-EMA], accelerometry) in a subset of 60 women (720 person-days of monitoring).
- Hypothesis 5: On any given day, greater personal environmental exposures (e.g., black carbon, PM2.5) and social stressors (e.g., arguments with spouse, demands made by family) will be associated with greater perceived stress, sedentary activity, and high-fat/high-sugar intake; flatter slope of cortisol decline across the day; and lower physical activity and fruit/vegetable/fiber intake.
Progress Summary:
Project 1:
We have been actively analyzing data over the past year. For Aim 1, we have measured urinary arsenic in 1st trimester samples as well as hair metals data from 177 women for a suite of metals that include As, V, Cd, Pb, Mn, Cr, Cu, Zn. We have also mapped the residences, created timelines and assigned air pollution estimates (as well as previously CES scores) for women for whom their babies had been born by October 2019. We have also assayed third trimester saliva samples for cortisol assessment, which will be used in Aim 2.
For Aims 1 and 2, we have now published our first two publications evaluating metals in this population and we have an additional 3 publications under review. The first was published in Environmental Research and aimed to 1) examine the impact of early pregnancy exposure to arsenic on birth weight and gestational age at birth and 2) compare multiple biomarkers of arsenic exposure (blood, urine, and hair) assessed in early pregnancy. We found that a doubling in hair arsenic was associated with a 72.2 g (95% CI: -144.3, -0.1, P=0.05) lower birth weight, after adjusting for potential confounders and gestational age at birth. A similar but non-significant trend was observed for blood arsenic, but not urine arsenic. The inverse association between hair arsenic and birth weight was more pronounced among infants whose mothers gained greater amounts of weight during pregnancy (Pinteraction=0.02). The association between urinary monomethyl arsenic and GA at birth differed by pre-pregnancy BMI (Pinteraction<0.01). The second paper evaluated demographic predictors of arsenic exposure and was published in JESEE. We found that foreign-born Hispanic women had 8.6% higher %DMA and 7.7% lower %iAs than non-Hispanic women. Maternal age was also associated with higher %iAs.
The four papers currently under review address predictors of stress (PSS and CESD) in pregnancy, the association between cortisol levels in third trimester and infant birthweight, and metal mixtures in pregnancy on fetal biometry.
We have also investigated maternal stress (PSS) and depression (CESD) in relation to birthweight and observe no significant associations at this time. An initial evaluation of pregnancy levels of O3, NO2, PM2.5 and PM10 suggests that patterns of exposure may change across trimesters and we are investigating these associations further using a distributed lag model with birthweight and also with infant weight at 12 months.
For Aim 3, we have begun to evaluate the energy consumption data from the infant questionnaires in the first year of life. An initial profile of these infants shows that their weight at 12 months is minimally correlated with their birthweight (Pearson r= 0.27, p=0.06). We will continue to explore data on infant feeding practices in the first year of life in relation to maternal exposures and stress in association with infant weight at 12 months.
The substudy for Aim 4 was launched in Fall 2018 and recruitment was completed during this reporting period. Instead of using abdominal MRI scans which require a baby to be still in order to image, we used the Adolescent Humans Body Composition Analyzer (EchoMRI-AH, Echo Medical System, Houston, TX), which uses quantitative nuclear magnetic resonance (QMR) to measure whole body composition, fat and lean mass, and free water and total body water. The EchoMRI-AH accommodates infants and children up to 80 kg. EchoMRI is a body composition assessment method that uses a low strength magnetic field to count hydrogen atoms and therefore measure water and fat mass with remarkable precision. Additionally, EchoMRI has several advantages including rapid assessment time (<3.2 minutes) and measures that are not affected by subject movement. To date we have completed the target goal of 40 in the EchoMRI-AH. We have investigated the data from these 40 infants and see that estimated weight and measured body weight have an excellent correlation (r=0.96). We also observe that lean mass is more highly correlated with measured weight than is fat mass. We have begun evaluating associations between air pollutants and ECHO MRI measures of fat and lean mass at 1 month of age. We have found that when stratified there is a marginal inverse univariate association in females with NOx for non-freeway minor roads (B= -0.06, p=0.06) whereas nothing is seen in males (B=0.01 p=0.92). After adjusting for days old at scan and GA the beta estimate remains constant, but loses marginal significance (B -0.06, b=0.12). We are continuing to explore these analyses with a manuscript in mind.
Project 2:
This report covers progress from 7/1/19 through 6/31/20 (Year 5). To date, we have accomplished the following during Year 5 of Project 2 of MADRES:
Planning/Training/Development
- Convened the Project 2 research team including the Principal Investigator, research staff, and students for bi-weekly meetings to guide study development and review progress.
- In Year 5, Project 2 of MADRES provided a training opportunity for three PhD students. These doctoral trainees are students in Health Behavior Research in the Department of Preventive Medicine at USC, which prepares students as independent researchers in behavioral science. The first student was supported as a data manager on the Project 2 budget. His role was to clean, merge, and manage all EMA, accelerometer, personal air pollution, 24-hour dietary recall, and GPS data for the EMA sub-study. The second PhD student was supported through the NIH-funded ECHO Program, of which the MADRES cohort is a part of. On Project 2, this doctoral student was responsible for conducting statistical analyses and writing up manuscripts with the maternal daily cortisol data and its association with maternal gestational weight gain and perceived stress. The third student was supported through a USC Center for Translational Science Institute (CTSI) pilot grant. His role was to develop algorithms and a software program for linking EMA, GPS, and accelerometer data on the Project 2 sub-study. All three PhD student trainees participated in weekly Real-time Eating Activity and Children’s Health (REACH) laboratory meetings for all of the PI’s trainees (including undergraduates, pre-docs, and post-docs) to read and discuss important journal articles in the field, share trainee-generated research results, practice presentations for upcoming job talks and conferences, and generally offer support for and critical feedback on ongoing trainee research efforts. Individual Development Plans (IDPs) are used to help manage the training for these students. These IDPs include individualized yearly goals for completing coursework, developing critical research skills, publishing peer-reviewed papers and presenting at national conferences. At the end of each academic year, the three trainees working on this project meet with the PI and two other faculty members in the department to discuss their progress towards these goals and overall professional development.
Recruitment for Project 2 (AIM 1)
- We successfully reached our target of enrolling 750 pregnant women into the MADRES cohort.
- Weight, psychosocial stress, and environmental exposures are being collected in the first, second, and third trimester of pregnancy as well as 12-months postpartum.
Data Collection and Analysis for Project 2 EMA Substudy (AIM 2)
- Over Year 5, we finished data collection for the Project 2 EMA substudy. In total, we recruited 63 women (100% Hispanic, mean age = 28.6 [SD = 6.0], 45% Spanish-speaking). A total of 63 women completed the first trimester data collection, 52 women completed third trimester data collection, and 51 women have completed the 5-6.5 months postpartum data collection.
- To date, EMA data have been cleaned and processed for 63 women in their first trimester assessment, 51 women in their third trimester, and 49 women at the 5-6.5 months postpartum assessment. Descriptive statistics were computed for the EMA data in order to understand the distribution of the responses. Table 1 shows that work at home was the most frequently reported stressor by moms at all timepoints, and tension with children the second most frequently reported. Also, as shown in Table 2, consumption of fruits and vegetables was very common during pregnancy but appeared to decrease from first trimester to post-partum whereas unhealthy eating remained constant or increased. Reported sedentary screen activity was mostly constant across all timepoints with a slight dip at the third trimester; sports and exercise were reported very infrequently across timepoints. Accelerometer activity data reveal that sedentary behavior was common across all timepoints (approx. 10 hours a day); minutes spent in moderate-to-vigorous physical activity (MVPA) was low overall but appeared to remain constant across all timepoints.
First Trimester n (%) | Third Trimester n (%) | Post-Partum n (%) | Total n (%) | |
Work at home | 92 (10.40%) | 90 (12.93%) | 71 (11.08%) | 253 (11.39%) |
Work at a job | 25 (2.82%) | 16 (2.30%) | 11 (1.72%) | 52 (2.34%) |
Demands made by your family | 54 (6.10%) | 21 (3.02%) | 20 (3.12%) | 95 (4.28%) |
Tension with a coworker | 4 (0.45%) | 3 (0.42%) | 2 (0.31%) | 9 (0.41%) |
Tension with your partner/ spouse | 62 (7.01%) | 30 (4.31%) | 34 (5.30%) | 126 (5.67%) |
Tension with your children | 85 (9.60%) | 34 (4.89%) | 54 (8.42%) | 173 (7.79%) |
Table 1. In the past 2 hours (since waking up this morning), which of these things caused you stress?
First Trimester n (%) | Third Trimester n (%) | Post-Partum n (%) | Total n (%) | |
TV, Videos, Video Games | 404 (46.01%) | 301 (43.12%) | 291 (46.12%) | 996 (45.13%) |
Exercise or Sports | 72 (8.20%) | 67 (9.60%) | 41 (6.50%) | 180 (8.16%) |
Eaten chips or fries | 58 (6.61%) | 46 (6.59%) | 56 (8.87%) | 160 (7.25%) |
Eaten pastries, Pan Dulce, sweets | 98 (11.16%) | 117 (16.76%) | 74 (11.73%) | 289 (13.09%) |
Eaten fast food | 74 (8.43%) | 66 (9.46%) | 65 (10.30%) | 205 (9.29%) |
Eaten fruits or vegetables | 278 (31.66%) | 180 (25.79%) | 128 (20.29%) | 586 (26.55%) |
Drank soda or energy drinks | 105 (11.96%) | 70 (10.03%) | 105 (16.64%) | 280 (12.69%) |
Table 2. In the past 2 hours (since waking up this morning), which of these things have you done?
First Trimester | First Trimester | Third Trimester | Third Trimester | Post-Partum | Post-Partum | |
Mean (SD) | Range | Mean (SD) | Range | Mean (SD) | Range | |
Valid Days | 3.14 (1.00) | 1 - 4 | 2.84 (1.17) | 1 - 4 | 3.12 (1.07) | 1 - 4 |
Average Daily Sedentary Minutes | 627.0 (137.0) | 376 - 1287 | 623.0 (172.0) | 378 - 1228 | 618.0 (158.0) | 332 - 1166 |
Average Daily MVPA Minutes | 30.1 (22.8) | 1 - 112 | 31.4 (19.1) | 1.67 - 85.2 | 32.4 (24.1) | 3.67 - 147 |
Table 3. Accelerometer measured activity
Future Activities:
Project 1:
We will continue to wrap up analyses related the main aims of this grant and submit several more publications.
Project 2:
In the next reporting period (no-cost extension), we plan conduct analyses on data from EMA, accelerometers, and other collected data; assay salivary cortisol; and prepare publications and conference presentation based on these findings. Analyses will test our primary aims regarding the effects of environmental exposures and stress on gestational weight gain, postpartum weight retention, physical activity, and eating behaviors in women. These findings will be written up for publication in peer-reviewed journals and presentation at national research conferences.
Journal Articles: 12 Displayed | Download in RIS Format
Other center views: | All 16 publications | 12 publications in selected types | All 12 journal articles |
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Alderete TL, Song AY, Bastain T, Habre R, Toledo-Corral CM, Salam MT, Lurmann F, Gilliland FD, Breton CV. Prenatal traffic-related air pollution exposures, cord blood adipokines and infant weight. Pediatric Obesity 2018:13(6):348-356. |
R836158 (2017) R836158 (2018) R836158 (2019) R836158 (2020) R835441 (2018) |
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Farzan SF, Howe CG, Chavez TA, Hodes TL, Johnston JE, Habre R, Dunton G, Bastain TM, Breton CV. Demographic predictors of urinary arsenic in a low-income predominantly Hispanic pregnancy cohort in Los Angeles. Journal of exposure science & environmental epidemiology 2020:1-4. |
R836158 (2020) |
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Hernandez-Castro I, Eckel S, Howe C, Niu Z, Kannan K, Robinson M, Foley H, Grubbs B, Al-Marayati L, Lerner D, Lurvey N, Aung M, Habre R, Dunton G, Farzan S, Breton C, Bastain T. 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. ENVIRONMENTAL RESEARCH 2023;226(115703) |
R836158 (Final) |
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Hernandez-Castro I, Eckel S, Chen X, Yang T, Vigil M, Foley H, Kannan K, Robinson M, Grubbs B, Lerner D, Lurvey N, Al-Marayati L, Habre R, Dunton G, Farzan S, Aung M, Brexton C, Bastain T. Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort. ENVIRONMENTAL POLLUTION 2024;342(123131) |
R836158 (Final) |
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Hu Y, Chavez T, Eckel S, Yang T, Chen X, Vigil M, Pavlovic N, Lurmann F, Lerner D, Lurvey N, Grubbs B, Al-Marayati L, Toledo-Corral C, Johnston J, Dunton G, Farzan S, Habre R, Breton C, Bastain T. Joint effects of traffic-related air pollution and hypertensive disorders of pregnancy on maternal postpartum depressive and anxiety symptoms. JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY 2024; |
R836158 (Final) |
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Maldonado L, Farzan S, Toledo-Corral C, Dunton G, Habre R, Eckel S, Johnson M, Yang T, Grubbs B, Lerner D, Chavez T, Breton C, Bastain T. 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. JOURNAL OF NUTRITION 2022;. |
R836158 (Final) |
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Maldonado L, Bastain T, Toledo-Corral C, Dunton G, Habre R, Eckel S, Yang T, Grubbs B, Chavez T, Al-Marayati L, Breton C, Farzan S. Maternal Dietary Patterns During Pregnancy Are Linked to Hypertensive Disorders of Pregnancy Among a Predominantly Low-Income US Hispanic/Latina Pregnancy Cohort. JOURNAL OF THE AMERICAN HEART ASSOCIATION 2024;13(5):E029848. |
R836158 (Final) |
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Niu Z, Habre R, Chavez T, Yang T, Grubbs B, Eckel S, Berhane K, Toledo-Corral C, Johnston J, Dunton G. Association Between Ambient Air Pollution and Birth Weight by Maternal Individual- and Neighborhood-Level Stressors. JAMA NETWORK OPEN 2022;5(10) |
R836158 (Final) |
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Peterson A, Habre R, Niu Z, Amin M, Yang T, Eckel S, Farzan S, Lurman F, Pavlovic N, Grubbs B, Walker D, Al-Marayati L, Grant E, Lerner D, Bastain T, Breton C. Identifying pre-conception and pre-natal periods in which ambient air pollution exposure affects fetal growth in the predominately Hispanic MADRES cohort. NATURE HUMAN BEHAVIOR 2022;21(1):115 |
R836158 (Final) |
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Zhang Y, Chen Z, Berhane K, Urman R, Chatzi V, Breton C, Gilliland F. The Dynamic Relationship Between Asthma and Obesity in Schoolchildren. American Journal of Epidemiology 2020;189(6):583-591. |
R836158 (Final) R826708 (Final) |
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O’Connor SG, Habre R, Bastain TM, Toledo-Corral CM, Gilliland FD, Eckel SP, Cabison J, Naya CH, Farzan SF, Chu D, Chavez TA. Within-subject effects of environmental and social stressors on pre-and post-partum obesity-related biobehavioral responses in low-income Hispanic women:protocol of an intensive longitudinal study. BMC Public Health 2019;19(1):253. |
R836158 (2019) R836158 (2020) |
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Howe CG, Farzan SF, Garcia E, Jursa T, Iyer R, Berhane K, Chavez TA, Hodes TL, Grubbs BH, Funk WE, Smith DR. Arsenic and birth outcomes in a predominately lower income Hispanic pregnancy cohort in Los Angeles. Environmental Research 2020:109294. |
R836158 (2020) |
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Progress and Final Reports:
Original Abstract Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836158C001 Cumulative prenatal and infant environmental exposures and early childhood obesity risk
R836158C002 Environmental Exposures, Stress, and Maternal Pregnancy-Related Weight Outcomes
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final Report
- 2019 Progress Report
- 2018 Progress Report
- 2017 Progress Report
- 2016 Progress Report
- Original Abstract
12 journal articles for this center