Grantee Research Project Results
2019 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, 2018 through June 30,2019
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:
All of the aims for Project 1 require the babies of the cohort to have been born. To date we have had 372 births and 175 infants have reached 12 months of age. We have just this year obtained a reasonable sample size, with relevant abstracted maternal medical record data, to begin analyses. For Aim1, we have measured urinary arsenic in 1st trimester samples for 164 mothers with another 132 currently underway and we have measured 31 samples at the third trimester. We have additionally just received hair metals data from 177 women for a suite of metals that include As, V, Cd, Pb, Mn, Cr, Cu, Zn which we will begin analyzing immediately. We have also mapped the residences, created timelines and assigned air pollution estimates (as well as previously CES scores) for 315 women for whom their babies had been born by October 2018 (cutoff for our first batch). Residential timelines are shown in Figure 1A and daily air quality in Figure 1B. We have also assayed third trimester saliva samples for cortisol assessment for 100 women, which will be used in Aim 2.
For Aims 1 and 2, we have our first two publications currently under review. The first is an investigation into predictors of prenatal stress and depression in pregnancy (under review in Health Science Reports) and the second is a profile of urinary Arsenic exposure in pregnancy (under review in Environmental Research). We have additional manuscripts under preparation that address dietary predictors of Arsenic exposure in pregnancy as well as a geospatial analysis characterizing patterns in neighborhood level exposures in our low-income primarily Hispanic population. We have begun to analyze the birthweight data with respect to pregnancy questionnaire data and exposure data we currently have. For example, we have conducted preliminary analyses evaluating typical predictors of birthweight in 284 babies, and have found gestational age, delivery method, and birth order to all be important predictors as one might expect. 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 therefore we plan to investigate the use of distributed lag models to better model exposure across the entire pregnancy at the daily level. This work is ongoing.
For Aim 3 we will wait until we have more cord blood samples collected for the mitochondrial assays, and we will begin to evaluate the energy consumption data from the infant questionnaires now that we have babies who have arrived at their first birthday. We currently have data on 64 infants at 12 months of age. 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 these data as our sample size increases.
The substudy for Aim 4 was launched this year in Fall 2018. Instead of using abdominal MRI scans which require a baby to be still in order to image, we are instead using 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 measured 29 infants of the target goal of 40 in the EchoMRI-AH. We have investigated the data from the first 11 infants (Figure 2) 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.
Figure 1. A) Daily residential timelines for air pollution exposure assessment and B) daily air quality
Figure 2. Correlations between measured body weight and EchoMRI measures of A) total weight B) lean mass, C) fat mass, D) free water.
Project 2:
This report covers progress from the onset of Year 4 on 6/1/18 to the preparation of this report on 3/4/19. To date, we have accomplished the following during Year 4 of Project 2 of MADRES:
Planning/Training/Development
- Provided new training opportunities for one local high school student and continued training opportunities for PhD students.
- 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 4, 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 a National Institutes of Health Research Individual Training Grant (F31HL137346). On the current project, this doctoral student was responsible for drafting the MADRES Project 2 protocol manuscript (accepted for publication in BMC Public Health). The third student was supported through a USC research assistantship. Her roles were to program newly added EMA questions in Movisens and to manage and clean the daily cortisol biomarker data. 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.
- We added questions about mothers’ and babies’ momentary and daily sleeping patterns in EMA. These questions include: “Where did your baby sleep (more than 50%) of last night?”, “In what position did you place your baby to sleep last night?”, “Since waking up this morning/over the last 2 hours, have YOU taken a nap?”, and “Since waking up this morning/over the last 2 hours, has your BABY taken a nap?”
- Over Year 4, we continued recruitment and data collection. To date, we have recruited 570 pregnant women into the study.
- Weight, psychosocial stress, and environmental exposures are being collected in the first, second, and third trimester of pregnancy as well as 12-months postpartum.
Recruitment and Data Collection for Project 2 EMA Substudy (AIM 2)
- Over Year 4, we completed collection for the Project 2 EMA substudy. To date, we have recruited 62 women (100% Hispanic, mean age = 28.6 [SD = 6.0], 45% Spanish-speaking). A total of 62 women have completed the first trimester data collection, 49 women have completed third trimester data collection, and 25 women have completed the 5-6.5 months postpartum data collection.
- Overall, average EMA compliance was 82% for the first trimester assessment, 78% for the third trimester assessment, and 77% for the 5-6.5 month assessment.
- During the first trimester assessment, 14.5% of the EMA surveys were not prompted because the phone was turned off, prompt occurred during sleep window, or another app issue. Approximately 21.1% of prompted EMA surveys were ignored (i.e., participant did not respond), and an additional 3.1% of prompted surveys were incomplete (i.e., participant responded to prompt, but did not complete the entire survey).
- To date, EMA data have been processed for 62 women in their first trimester assessment, 49 women in their third trimester, and 25 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 first and third trimester, and tension with children was the most common at post-partum. 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 increased. Sedentary screen activity was common across time-points but increased post-partum; 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 love overall but appeared to increase at post-partum. These preliminary results were presented at the Environmental Health Disparities grantee meeting in Jan. 2019.
Future Activities:
Project 1:
In the next reporting period, our target is to finish recruitment of pregnant women into the cohort study and to continue following their pregnancies, deliveries and babies. We plan to conduct air pollutant exposure assessment in batches and will prepare to obtain the second batch of ambient pollutant data on as many women as we have recruited by midsummer 2019. Data analyses of hair metals on ~180 subjects and air pollution data on the 315 women and infant dyads for whom we have air pollution exposure assessment will continue with a goal of writing several manuscripts from these analyses. We will continue recruiting infants for the aim 4 substudy to conduct infant EchoMRI until we reach our goal of 40. Lastly, in the next year we will continue the pediatric medical record abstraction to obtain the growth trajectories of the babies, as we have more babies reaching their first birthday.
Project 2:
In the next reporting period (Year 5), we plan to finish enrollment of women as well as follow the women enrolled during the current reporting period (AIM 1). We have completed enrollment for the EMA sub-study for Project 2 (AIM 2). N=62 women in the EMA sub-study completed the first trimester assessment, and 49 women completed the third trimester assessment. We anticipate that approximately 75% of women will complete the post-partum assessment (currently 29 women have completed the assessment). EMA sub-study assessments will be performed on a rolling basis as women reach 5-6.5 months post-partum.
Additionally, we plan to process data from EMA, accelerometers, and other collected data; assay salivary cortisol; conduct preliminary data analyses; and prepare publications and conference presentation based on these findings. EMA data will be downloaded from the server, 24-hour nutritional data will be processed using NDSR software, accelerometer data will be downloaded and processed, and salivary cortisol samples will be sent for assaying at the laboratory of Dr. Clemens Kirschbaum at the Technical University of Dresden.
Preliminary analyses will be examined to examine cross-sectional relationships among the key study variables (maternal stress, children's eating and physical activity, and BMI). These findings written up for publication in peer-reviewed journals and presentation at national research conferences.
Journal Articles: 10 Displayed | Download in RIS Format
Other center views: | All 14 publications | 10 publications in selected types | All 10 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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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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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
- 2020 Progress Report
- 2018 Progress Report
- 2017 Progress Report
- 2016 Progress Report
- Original Abstract
10 journal articles for this center