PUBLICATIONS & PRESENTATIONS
Publications
Anderson EC, Foley HB, Levy JJ, Romano ME, Gui J, Bentz JL, Maldonado LE, Farzan SF, Bastain TM, Marsit CJ, Breton CV, Howe CG. Maternal glucose levels and late pregnancy circulating extracellular vesicle and particle miRNAs in the MADRES pregnancy cohort. Epigenetics. 2024 Dec;19(1):2404198. doi: 10.1080/15592294.2024.2404198. Epub 2024 Sep 18. PMID: 39292753.
Maternal hyperglycemia during pregnancy adversely affects maternal and child outcomes. While mechanisms are not fully understood, maternal circulating miRNAs may play a role. We examined whether continuous glucose levels and hyperglycemia subtypes (gestational diabetes, type 2 diabetes, and glucose intolerance) were associated with circulating miRNAs during late pregnancy. Seven miRNAs (hsa-miR-107, hsa-let-7b-5p, hsa-miR-126-3p, hsa-miR-181a-5p, hsa-miR-374a-5p, hsa-miR-382-5p, and hsa-miR-337-5p) were associated (p < 0.05) with either hyperglycemia or continuous glucose levels prior to multiple testing correction. These miRNAs target genes involved in pathways relevant to maternal and child health, including insulin signaling, placental development, energy balance, and appetite regulation.
Yuhong Hu, Zhongzheng Niu, Sandrah P. Eckel, Claudia Toledo-Corral, Tingyu Yang, Xinci Chen, Mario Vigil, Nathan Pavlovic, Fred Lurmann, Erika Garcia, Deborah Lerner, Nathana Lurvey, Brendan Grubbs, Laila Al-Marayati, Jill Johnston, Genevieve F. Dunton, Shohreh F. Farzan, Rima Habre, Carrie Breton, Theresa M. Bastain, Prenatal exposure to ambient air pollution and persistent postpartum depression, Science of The Total Environment, Volume 953, 2024, 176089, ISSN 0048-9697, https://doi.org/10.1016/j.scitotenv.2024.176089.
Background: Ambient air pollution during pregnancy has been linked with postpartum depression up to 12 months, but few studies have investigated its impact on persistent depression beyond 12 months postpartum. This study aimed to evaluate prenatal ambient air pollution exposure and the risk of persistent depression over 3 years after childbirth and to identify windows of susceptibility.
Methods: This study included 361 predominantly low-income Hispanic/Latina participants with full-term pregnancies in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. We estimated daily residential PM2.5, PM10, NO2, and O3 concentrations throughout 37 gestational weeks using inverse-distance squared spatial interpolation from monitoring data and calculated weekly averaged levels. Depression was assessed by the 20-item Center for Epidemiologic Studies-Depression (CES-D) scale at 12, 24, and 36 months postpartum, with persistent postpartum depression defined as a CES-D score ≥16 at any of these timepoints. We performed robust Poisson log-linear distributed lag models (DLM) via generalized estimating equations (GEE) to estimate the adjusted risk ratio (RR).
Results: Depression was observed in 17.8 %, 17.5 %, and 13.4 % of participants at 12, 24, and 36 months, respectively. We found one IQR increase (3.9 ppb) in prenatal exposure to NO2 during the identified sensitive window of gestational weeks 13–29 was associated with a cumulative risk ratio of 3.86 (95 % CI: 3.24, 4.59) for persistent depression 1–3 years postpartum. We also found one IQR increase (7.4 μg/m3) in prenatal exposure to PM10 during gestation weeks 12–28 was associated a cumulative risk ratio of 3.88 (95 % CI: 3.04, 4.96) for persistent depression. No clear sensitive windows were identified for PM2.5 or O3.
Conclusions: Mid-pregnancy PM10 and NO2 exposures were associated with nearly 4-fold increased risks of persistent depression after pregnancy, which has critical implications for prevention of perinatal mental health outcomes.
Yi, L., Habre, R., Mason, T.B. et al. Smartphone GPS-Based Exposure to Greenspace and Walkability and Accelerometer-Assessed Physical Activity During Pregnancy and Early Postpartum—Evidence from the MADRES Cohort. J Urban Health (2024). https://doi.org/10.1007/s11524-024-00903-6
A growing number of studies have associated walkability and greenspace exposure with greater physical activity (PA) in women during pregnancy. However, most studies have focused on examining women’s residential environments and neglected exposure in locations outside the home neighborhood. Using 350 person-days (N = 55 participants) of smartphone global positioning system (GPS) location and accelerometer data collected during the first and third trimesters and 4–6 months postpartum from 55 Hispanic pregnant women from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, we examined the day-level effect of women’s exposure to walkability and greenspace on their PA outcomes during pregnancy and in the early postpartum period. Moderate-to-vigorous physical activity [MVPA] minutes per day was assessed using accelerometers. Walkability and greenspace were measured using geographic information systems (GIS) within women’s daily activity spaces (i.e., places visited and routes taken) recorded using a smartphone GPS and weighted by time spent. We used a generalized linear mixed-effects model to estimate the effects of daily GPS-derived environmental exposures on day-level MVPA minutes. Results showed that women engaged in 23% more MVPA minutes on days when they had some versus no exposure to parks and open spaces in activity spaces (b = 1.23; 95%CI: 1.02–1.48). In addition, protective effects of daily greenspace and walkability exposure on MVPA were stronger in the first and third trimesters, among first-time mothers, and among women who had high pre-pregnancy body mass index (BMI) and lived in least-safe neighborhoods. Our results suggest that daily greenspace and walkability exposure are important for women’s PA and associated health outcomes during pregnancy and early postpartum.
Hernandez-Castro I, Eckel SP, Howe CG, Aung MT, Kannan K, Robinson M, Foley HB, Yang T, Vigil MJ, Chen X, Grubbs B, Al-Marayati L, Toledo-Corral CM, Habre R, Dunton GF, Farzan SF, Morales S, Breton CV, Bastain TM. Organophosphate ester flame retardant chemicals and maternal depression during pregnancy. Environ Res. 2024 Jul 9;259:119581. doi: 10.1016/j.envres.2024.119581. Epub ahead of print. PMID: 38992754.
Background: Depression substantially contributes to pregnancy-related morbidity, and pregnancy is increasingly recognized as a vulnerable window for exposure effects on maternal mental health. Exposures to organophosphate esters (OPEs) are ubiquitous and may have neurotoxic effects; however, their impacts on prenatal depression remain unknown. We evaluated associations of third trimester OPE metabolites on maternal depressive symptoms during pregnancy.
Methods: This study included 422 participants in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort, a prospective pregnancy cohort of primarily low-income and Hispanic participants residing in Los Angeles, California. We measured concentrations of nine OPEs in third trimester spot urine samples (mean gestational age = 31.5 ± 2.0 weeks). Using the Center for Epidemiologic Studies-Depression (CES-D) scale, we classified participants as having probable depression during pregnancy (N = 137) or not (N = 285) if one or more CES-D scores administered at each trimester met the suggested cutoff score for clinically significant depressive symptoms (≥16). We estimated associations of prenatal OPE metabolite concentrations in tertiles and risk of prenatal depression using modified Log-Poisson regression. We examined associations of the OPE mixture on depression during pregnancy using Bayesian kernel machine regression (BKMR).
Results: Participants with the highest tertiles of DPHP and BDCIPP exposure had a 67% (95% CI: 22%, 128%) and 47% (95% CI: 4%, 108%) increased risk of maternal depressive symptoms during pregnancy, respectively. No associations between other OPE metabolites and maternal depression symptoms were observed. In mixture analyses, we observed a positive and linear association between higher exposure to the OPE metabolite mixture and odds of prenatal maternal depression, primarily driven by DPHP.
Conclusions: Our findings provide new evidence of associations between frequently detected OPE metabolites on maternal depression symptoms during pregnancy. Results could inform future intervention efforts aimed at reducing perinatal maternal depression.
Del Real, D., & Ramirez, B. A. (2024). Remitting amid autocracy: Venezuelan migrant remittances to relatives enduring widespread structural violence. Current Sociology, 0(0). https://doi.org/10.1177/00113921241260430
Homeland conditions shape how migrants and refugees perceive the purpose and impact of their remittances (i.e. financial support). Countries of origin with low violence and stable conditions allow migrants to remit with hopes of improving their non-migrant relatives’ long-term material circumstances, while homelands with armed conflict limit remittance objectives to securing recipients’ immediate safety and basic survival. However, scholarship has under-theorized how homelands with widespread structural violence–economic devastation resulting in deprivation for most of the population–impact migrants’ remittance practices and perceptions. Drawing on in-depth interviews with forced Venezuelan migrants in Chile and Argentina–whose homeland has an emerging autocrat and economic sanctions that have resulted in widespread structural violence–we find that interviewees are highly concerned about relatives’ survival in Venezuela. They remit with resignation to secure relatives’ bare subsistence while grappling with their inability to counter the economic deterioration, infrastructural decay, and essential goods shortages that are decreasing their relatives’ lifespan. Broadly, findings indicate that widespread structural violence reshapes migrants’ transnational care; as deprivation spreads in the homeland, migrants are increasingly aware that the impact of their remittances is diminishing and seek to fulfill their relatives’ immediate basic needs.
Hu Y, Chavez T, Eckel SP, 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 GF, Farzan SF, Habre R, Breton C, Bastain TM. Joint effects of traffic-related air pollution and hypertensive disorders of pregnancy on maternal postpartum depressive and anxiety symptoms. J Expo Sci Environ Epidemiol. 2024 May 31. doi: 10.1038/s41370-024-00692-9. Epub ahead of print. PMID: 38822090.
Background: Ambient air pollution has been linked to postpartum depression. However, few studies have investigated the effects of traffic-related NOx on postpartum depression and whether any pregnancy-related factors might increase susceptibility.
Objectives: To evaluate the association between traffic-related NOx and postpartum depressive and anxiety symptoms, and effect modification by pregnancy-related hypertension.
Methods: This study included 453 predominantly low-income Hispanic/Latina women in the MADRES cohort. Daily traffic-related NOx concentrations by road class were estimated using the California LINE-source dispersion model (CALINE4) at participants’ residential locations and averaged across pregnancy. Postpartum depressive and anxiety symptoms were evaluated by a validated questionnaire (Postpartum Distress Measure, PDM) at 1, 3, 6 and 12 months postpartum. Multivariate linear regressions were performed to estimate the associations at each timepoint. Interaction terms were added to the linear models to assess effect modification by hypertensive disorders of pregnancy (HDPs). Repeated measurement analyses were conducted by using mixed effect models.
Results: We found prenatal traffic-related NOx was associated with increased PDM scores. Specifically, mothers exposed to an IQR (0.22 ppb) increase in NOx from major roads had 3.78% (95% CI: 0.53-7.14%) and 5.27% (95% CI: 0.33-10.45%) significantly higher 3-month and 12-month PDM scores, respectively. Similarly, in repeated measurement analyses, higher NOx from major roads was associated with 3.06% (95% CI: 0.43-5.76%) significantly higher PDM scores across the first year postpartum. Effect modification by HDPs was observed: higher freeway/highway and total NOx among mothers with HDPs were associated with significantly higher PDM scores at 12 months postpartum compared to those without HDPs.
Impact: This study shows that prenatal traffic-related air pollution was associated with postpartum depressive and anxiety symptoms. The study also found novel evidence of greater susceptibility among women with HDPs, which advances the understanding of the relationships between air pollution, maternal cardiometabolic health during pregnancy and postpartum mental health. Our study has potential implications for clinical intervention to mitigate the effects of traffic-related pollution on postpartum mental health disorders. The findings can also offer valuable insights into urban planning strategies concerning the implementation of emission control measures and the creation of green spaces.
Malin AJ, Eckel SP, Hu H, Martinez-Mier EA, Hernandez-Castro I, Yang T, Farzan SF, Habre R, Breton CV, Bastain TM. Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months. JAMA Netw Open. 2024 May 1;7(5):e2411987. doi: 10.1001/jamanetworkopen.2024.11987. Erratum in: JAMA Netw Open. 2024 Jun 3;7(6):e2424057. doi: 10.1001/jamanetworkopen.2024.24057. PMID: 38767917; PMCID: PMC11107298.
Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown.
Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US.
Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks’ gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024.
Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure.
Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted.
Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02).
Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.
Ji N, Eckel SP, Foley H, Yang T, Lurmann F, Grubbs BH, Habre R, Bastain TM, Farzan SF, Breton CV. Prenatal air pollution exposure is associated with inflammatory, cardiovascular, and metabolic biomarkers in mothers and newborns. Environ Res. 2024 Mar 28;252(Pt 1):118797. doi: 10.1016/j.envres.2024.118797. Epub ahead of print. PMID: 38555084.
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.
Conclusions: 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.
Niu Z, Habre R, Yang T, Chen X, Vigil M, Barragan K, Lurmann F, Pavlovic NR, Grubbs BH, Toledo-Corral CM, Johnston J, Dunton GF, Lerner D, Lurvey N, Al-Marayati L, Eckel SP, Breton CV, Bastain TM, Farzan SF. Increased Risk of Gestational Hypertension by Periconceptional Exposure to Ambient Air Pollution and Effect Modification by Prenatal Depression. Hypertension. 2024 Mar 27. doi: 10.1161/HYPERTENSIONAHA.123.22272. Epub ahead of print. PMID: 38533642.
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 particulate matters (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.
Yi L, Xu Y, O’Connor S, Cabison J, Rosales M, Chu D, Chavez TA, Johnson M, Mason TB, Eckel SP, Bastain TM, Breton CV, Wilson JP, Dunton GF, Habre R. GPS-derived environmental exposures during pregnancy and early postpartum – Evidence from the MADRES cohort. Sci Total Environ. 2024 Mar 25;918:170551. doi: 10.1016/j.scitotenv.2024.170551. Epub 2024 Feb 8. PMID: 38336080; PMCID: PMC10935580.
The built and natural environment factors (e.g., greenspace, walkability) are associated with maternal and infant health during and after pregnancy. Most pregnancy studies assess exposures to environmental factors via static methods (i.e., residential location at a single point in time, usually 3rd trimester). These do not capture dynamic exposures encountered in activity spaces (e.g., locations one visits and paths one travels) and their changes over time. In this study, we aimed to compare daily environmental exposure estimates using residential and global positioning systems (GPS)-measured activity space approaches and evaluated potential for exposure measurement error in the former. To do this, we collected four days of continuous geolocation monitoring during the 1st and 3rd trimesters of pregnancy and at 4-6 months postpartum in sixty-two pregnant Hispanic women enrolled in the MADRES cohort. We applied residential and GPS-based methods to assess daily exposures to greenspace, access to parks and transit, and walkability, respectively. We assessed potential for exposure measurement error in residential vs GPS-based estimates using Pearson correlations for each measure overall and by study period. We found residential and GPS-based estimates of daily exposure to total areas of parks and open spaces were weakly positively correlated (r = 0.31, P < .001) across pregnancy and postpartum periods. Residential estimates of %greenspace (r = 0.52, P < .001) and tree cover (r = 0.55, P < .001) along walkable roads were moderately correlated with GPS-based estimates. Residential and GPS-based estimates of public transit proximity, pedestrian-oriented intersection density, and walkability index score were all highly positively correlated (r > 0.70, P < .001). We also found associations between residential and GPS-based estimates decreased among participants with greater daily mobility. Our findings suggest the popular approach that assessing the built and natural environment exposures using residential methods at one time point may introduce exposure measurement error in pregnancy studies. GPS-based methods, to the extent feasible, are recommended for future studies.
Maldonado LE, Bastain TM, Toledo-Corral CM, Dunton GF, Habre R, Eckel SP, Yang T, Grubbs BH, Chavez T, Al-Marayati LA, Breton CV, Farzan SF. Maternal Dietary Patterns During Pregnancy Are Linked to Hypertensive Disorders of Pregnancy Among a Predominantly Low-Income US Hispanic/Latina Pregnancy Cohort. J Am Heart Assoc. 2024 Mar 5;13(5):e029848. doi: 10.1161/JAHA.123.029848. Epub 2024 Feb 27. PMID: 38410940; PMCID: PMC10944043.
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]; P trend=0.014) and preeclampsia (OR, 4.10 [95% CI, 1.25–13.5]; P trend=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]; P trend=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 P interactions=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.
Mohazzab-Hosseinian S, Garcia E, Wiemels J, Marconett C, Corona K, Howe CG, Foley H, Farzan SF, Bastain TM, Breton CV. Effect of parental adverse childhood experiences on intergenerational DNA methylation signatures from peripheral blood mononuclear cells and buccal mucosa. Transl Psychiatry. 2024 Feb 12;14(1):89. doi: 10.1038/s41398-024-02747-9. PMID: 38342906; PMCID: PMC10859367.
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.
Xu Y, O’Sharkey K, Cabison J, Rosales M, Chavez T, Johnson M, Yang T, Cho SH, Chartier R, Grubbs B, Lurvey N, Lerner D, Lurmann F, Farzan S, Bastain TM, Breton C, Wilson JP, Habre R. Sources of personal PM2.5 exposure during pregnancy in the MADRES cohort. J Expo Sci Environ Epidemiol. 2024 Feb 7. doi: 10.1038/s41370-024-00648-z. Epub ahead of print. PMID: 38326532.
Background: Personal exposure to fine particulate matter (PM2.5) is impacted by different sources each with different chemical composition. Determining these sources is important for reducing personal exposure and its health risks especially during pregnancy.
Objective: Identify main sources and their contributions to the personal PM2.5 exposure in 213 women in the 3rd trimester of pregnancy in Los Angeles, CA.
Methods: We measured 48-hr integrated personal PM2.5 exposure and analyzed filters for PM2.5 mass, elemental composition, and optical carbon fractions. We used the EPA Positive Matrix Factorization (PMF) model to resolve and quantify the major sources of personal PM2.5 exposure. We then investigated bivariate relationships between sources, time-activity patterns, and environmental exposures in activity spaces and residential neighborhoods to further understand sources.
Results: Mean personal PM2.5 mass concentration was 22.3 (SD = 16.6) μg/m3. Twenty-five species and PM2.5 mass were used in PMF with a final R2 of 0.48. We identified six sources (with major species in profiles and % contribution to PM2.5 mass) as follows: secondhand smoking (SHS) (brown carbon, environmental tobacco smoke; 65.3%), fuel oil (nickel, vanadium; 11.7%), crustal (aluminum, calcium, silicon; 11.5%), fresh sea salt (sodium, chlorine; 4.7%), aged sea salt (sodium, magnesium, sulfur; 4.3%), and traffic (black carbon, zinc; 2.6%). SHS was significantly greater in apartments compared to houses. Crustal source was correlated with more occupants in the household. Aged sea salt increased with temperature and outdoor ozone, while fresh sea salt was highest on days with westerly winds from the Pacific Ocean. Traffic was positively correlated with ambient NO2 and traffic-related NOx at residence. Overall, 76.8% of personal PM2.5 mass came from indoor or personal compared to outdoor sources.
Impact: We conducted source apportionment of personal PM2.5 samples in pregnancy in Los Angeles, CA. Among identified sources, secondhand smoking contributed the most to the personal exposure. In addition, traffic, crustal, fuel oil, fresh and aged sea salt sources were also identified as main sources. Traffic sources contained markers of combustion and non-exhaust wear emissions. Crustal source was correlated with more occupants in the household. Aged sea salt source increased with temperature and outdoor ozone and fresh sea salt source was highest on days with westerly winds from the Pacific Ocean.
O’Sharkey K., Xu Y., Cabison J., Rosales M., Yang T., Chavez T., Johnson M., Grubbs B., Lerner D., Lurvey N., Toledo-Corral C.M., Farzan S.F., Bastain T.M., Breton C.V., Habre R. Effects of In-Utero Personal Exposure to PM2.5 Sources and Components on Birthweight. Scientific Reports, 2023 Dec 11;13(1):21987. doi: 10.1038/s41598-023-48920-w. PMID: 38081912.
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.
Hernandez-Castro I, Eckel SP, Chen X, Yang T, Vigil MJ, Foley HB, Kannan K, Robinson M, Grubbs B, Lerner D, Lurvey N, Al-Marayati L, Habre R, Dunton GF, Farzan SF, Aung MT, Breton CV, Bastain TM. Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort. Environ Pollut. 2023 Dec 11;342:123131. doi: 10.1016/j.envpol.2023.123131. Epub ahead of print. PMID: 38092343.
Corona K, Yang T, Dunton G, Toledo-Corral C, Grubbs B, Eckel SP, Johnston J, Chavez T, Lerner D, Lurvey N, Al-Marayati L, Habre R, Farzan SF, Breton CV, Bastain TM. The Role of Social Support and Acculturation Factors on Postpartum Mental Health Among Latinas in the MADRES Pregnancy Cohort. J Immigr Minor Health. 2024 Feb;26(1):72-80. doi: 10.1007/s10903-023-01542-w. Epub 2023 Oct 28. PMID: 37897652; PMCID: PMC10771371.
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.
Malin AJ, Hu H, Martínez-Mier EA, Eckel SP, Farzan SF, Howe CG, Funk W, Meeker JD, Habre R, Bastain TM, Breton CV. Urinary fluoride levels and metal co-exposures among pregnant women in Los Angeles, California. Environ Health. 2023 Oct 26;22(1):74. doi: 10.1186/s12940-023-01026-2. PMID: 37880740; PMCID: PMC10601173.
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.
O’Sharkey K, Xu Y, Cabison J, Rosales M, Chavez T, Johnson M, Yang T, Cho SH, Chartier R, Lerner D, Lurvey N, Toledo Corral CM, Cockburn M, Franklin M, Farzan SF, Bastain TM, Breton CV, Habre R. A Comparison of Measured Airborne and Self-Reported Secondhand Smoke Exposure in the MADRES Pregnancy Cohort Study. Nicotine Tob Res. 2023 Oct 17:ntad202. doi: 10.1093/ntr/ntad202. Epub ahead of print. PMID: 37846518.
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 (standard deviation [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 = .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: 0.30 µg/m3 vs. One: 0.12 µg/m3 and Zero: 0.15 µg/m3; p = .230).
Bastain T, Naya C, Yang T, Vigil M, Chen C, Chavez T, Toledo-Corral C, Farzan S, Habre R, Lerner D, Lurvey N, Grubbs B, Dunton G, Breton C, Eckel S. Poor Sleep Quality Increases Gestational Weight Gain Rate in Pregnant People: Findings from the MADRES Study. Res Sq [Preprint]. 2023 Sep 25:rs.3.rs-2944456. doi: 10.21203/rs.3.rs-2944456/v1. PMID: 37841879; PMCID: PMC10571604.
Background: Poor sleep quality is associated with weight gain in non-pregnant populations, but evidence in pregnant people is lacking. Our study examined the association between early-to-mid pregnancy sleep quality and weekly gestational weight gain (GWG) rate during mid-to-late pregnancy by pre-pregnancy body mass index (BMI).
Methods: Participants were 316 pregnant participants from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study. During early-to-mid pregnancy, participants reported their sleep quality which was used to construct four categories: very poor, poor, good, and very good. Linear growth curve models examined the association between early-to-mid pregnancy sleep quality and weekly rate of GWG (kg/week) during mid-to-late pregnancy (> 20 weeks gestation), with a three-way cross-level interaction between gestational age, sleep quality, and pre-pregnancy BMI category. Models adjusted for ethnicity by birthplace, hypertensive disorders, perceived stress score, and physical activity level.
Results: Overall, poorer early-to-mid pregnancy sleep quality was associated with increased weekly weight gain during mid-to-late pregnancy. For example, amongst normal weight participants, mid-to-late pregnancy weight gain was, on average, 0.39 kg (95% CI: 0.29, 0.48) per week for those with very good sleep quality, 0.53 kg (95% CI: 0.44, 0.61) per week for those with poor sleep quality, and 0.54 kg (95% CI: 0.46, 0.62) per week for those with very poor sleep quality during early-to-mid pregnancy. This difference in GWG rate was statistically significantly comparing very good to poor sleep (0.14 kg/week, 95% CI: 0.01, 0.26) and very good to very poor sleep (0.15kg/week, 85% CI: 0.02, 0.27). This association between sleep quality and GWG rate did not statistically differ by pre-pregnancy BMI.
Conclusion: Our study found very poor early-to-mid pregnancy sleep quality was associated with higher mid-to-late pregnancy GWG rate. Incorporating pregnancy-specific sleep recommendations into routine obstetric care may be a critical next step in promoting healthy GWG
Hernandez-Castro I, Eckel SP, Howe CG, Niu Z, Kannan K, Robinson M, Foley HB, Yang T, Vigil MJ, Chen X, Grubbs B, Lerner D, Lurvey N, Al-Marayati L, Habre R, Dunton GF, Farzan SF, Aung MT, Breton CV, Bastain TM. Prenatal exposures to organophosphate ester metabolite mixtures and children’s neurobehavioral outcomes in the MADRES pregnancy cohort. Environ Health. 2023 Sep 22;22(1):66. doi: 10.1186/s12940-023-01017-3. PMID: 37737180; PMCID: PMC10515433.
Background: Studies examining diet and its link to birth outcomes among socioeconomically disadvantaged populations in the U.S. are scarce.
Objectives: We aimed to identify prenatal dietary patterns, examine their relationships with birth outcomes, and evaluate the variation of these associations by maternal diabetes status (none, gestational [GDM], pre-existing).
Methods: Women in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study (n = 465)-an ongoing, prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles-completed up to two 24-hour dietary recalls in the third trimester of pregnancy. We identified prenatal dietary patterns (DPs) via factor analysis and evaluated their associations with birth weight and gestational age at birth (GA) z-scores, separately, using linear regression and premature birth, small-for-gestational age (SGA), and large-for-gestational-age (LGA) using logistic regression adjusting for relevant covariates. We additionally tested interaction terms between prenatal DPs and maternal diabetes status in separate models. We adjusted for multiple comparisons using false discovery rate.
Results: We identified two dietary patterns: (1) solid fats, refined grains, and cheese (SRC) and (2) vegetables, oils, and fruit (VOF). Comparing highest-to-lowest quartiles, the VOF DP was significantly associated with greater birth weight (β = 0.40, 95% CIs: 0.10, 0.70; Ptrend = 0.011), GA (β = 0.32, 95% CIs: 0.03, 0.61; Ptrend = 0.036) and lower odds of premature birth (OR = 0.31, 95% CIs: 0.10, 0.95; Ptrend = 0.049) and SGA (OR = 0.18, 95% CIs: 0.06, 0.58; Ptrend= 0.028). Only among women with GDM, a 1-SD score increase in the SRC prenatal DP was significantly associated with lower birth weight (β = -0.20, 95% CIs -0.39, -0.02; Pinteraction = 0.040).
Conclusions: Among low-income Hispanic/Latina pregnant women, greater adherence to the VOF prenatal DP may lower the risk of premature birth and SGA. Greater adherence to the SRC DP, however, may adversely affect newborn birth weight among mothers with GDM but future research is needed to verify our findings.
Keywords: 24-h dietary recalls; MADRES; birth outcomes; diet; dietary patterns; health disparities; hispanics/latinas.
Ji N, Johnson M, Eckel SP, Gauderman WJ, Chavez TA, Berhane K, Faham D, Lurmann F, Pavlovic NR, Grubbs BH, Lerner D, Habre R, Farzan SF, Bastain TM, Breton CV. Prenatal ambient air pollution exposure and child weight trajectories from the 3rd trimester of pregnancy to 2 years of age: a cohort study. BMC Med. 2023 Sep 7;21(1):341. doi: 10.1186/s12916-023-03050-y. PMID: 37674158; PMCID: PMC10483706.
Niu Z, Habre R, Yang T, Grubbs BH, Eckel SP, Toledo-Corral CM, Johnston J, Dunton GF, Lurvey N, Al-Marayati L, Lurmann F, Pavlovic N, Bastain TM, Breton CV, Farzan SF. Preconceptional and prenatal exposure to air pollutants and risk of gestational diabetes in the MADRES prospective pregnancy cohort study. Lancet Reg Health Am. 2023 Aug 21;25:100575. doi: 10.1016/j.lana.2023.100575. PMID: 37727593; PMCID: PMC10505827.
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
Niu Z, Mohazzab-Hosseinian S, Breton CV. Transgenerational epigenetic inheritance: Perspectives and challenges. J Allergy Clin Immunol. 2023 Jun;151(6):1474-1476. doi: 10.1016/j.jaci.2023.02.027. Epub 2023 Mar 8. PMID: 36893860.
Hernandez-Castro I, Eckel SP, Howe CG, Niu Z, Kannan K, Robinson M, Foley HB, Grubbs B, Al-Marayati L, Lerner D, Lurvey N, Aung MT, Habre R, Dunton GF, Farzan SF, Breton CV, Bastain TM. 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. Environ Res. 2023 Jun 1;226:115703. doi: 10.1016/j.envres.2023.115703. Epub 2023 Mar 17. PMID: 36934865; PMCID: PMC10101931.
Background: Organophosphate esters (OPEs) are used as flame retardants and plasticizers in various consumer products. Limited prior research suggests sex-specific effects of prenatal OPE exposures on fetal development. We evaluated overall and sex-specific associations between prenatal OPE exposures and gestational age (GA) at birth and birthweight for gestational age (BW for GA) z-scores among the predominately low-income, Hispanic MADRES cohort.
Methods: Nine OPE metabolite concentrations were measured in 421 maternal urine samples collected during a third trimester visit (GA=31.5±2.0 weeks). We examined associations between single urinary OPE metabolites and GA at birth and BW for GA z-scores using linear regression models and Generalized Additive Models (GAMs) and effects from OPE mixtures using Bayesian Kernel Machine Regression (BKMR). We also assessed sex-specific differences in single metabolite analyses by evaluating statistical interactions and stratifying by sex.
Results: We did not find significant associations between individual OPE metabolites and birth outcomes in the full infant sample; however, we found that higher bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with earlier GA at birth among male infants (p=0.04), and a nonlinear, inverted U-shape association between the sum of dibutyl phosphate and di-isobutyl phosphate (DNBP+DIBP) and GA at birth among female infants (p=0.03). In mixtures analysis, higher OPE metabolite mixture exposures was associated with lower GA at birth, which was primarily driven by female infants. DNBP+DIBP were the most important predictors for GA at birth in mixtures models both overall and among females; however, BDCIPP was the most important predictor for males.
Conclusion: Higher BDCIPP concentrations in prenatal maternal urine were associated with earlier GA at birth among males and higher DNBP+DIBP concentrations were associated with earlier GA at birth among female infants. Higher exposure to OPE mixtures was associated with earlier GA at birth, particularly among female infants, suggesting sex-specific impacts of OPEs on birth outcomes.
Kamai EM, Calderon A, Van Horne YO, Bastain TM, Breton CV, Johnston JE. Perceptions and experiences of environmental health and risks among Latina mothers in urban Los Angeles, California, USA. Environ Health. 2023 Jan 14;22(1):8. doi: 10.1186/s12940-023-00963-2. PMID: 36641468; PMCID: PMC9840262.
Background: Environmental exposures during pregnancy and early childhood can have acute and chronic adverse health impacts. As minoritized populations are more likely to reside in areas with greater pollution, it is important to understand their views and lived experiences to inform action. The purpose of this community-driven qualitative research study was to understand how urban Latina mothers in Los Angeles County, California perceived environmental health and risks.
Methods: We conducted semi-structured individual interviews with Latina pregnant women and mothers of young children, recruited through existing collaborations with community organizations. Interviews conducted in either English or Spanish and were coded inductively according to a modified grounded theory approach.
Results: Thirty-six Latina mothers completed interviews between August-October 2016. Participants lived primarily in low-income communities of South-Central Los Angeles and East Los Angeles. We identified three major themes based on the participants’ responses during interviews: Defining the Environment, Environment & Health Risks, and Social & Political Responsibility. Women defined their environment in terms of both “nature” and “hazards.” They consistently identified foul odors, dirtiness, noise, trash, bugs, smoke, and other visible blights as indicators of household and neighborhood environmental hazards. They expressed fear and uncertainty about how their environment could affect their health and that of their children, as well as specific concerns about respiratory health, asthma, allergies, cancer, and adverse pregnancy outcomes. Mothers often changed individual behaviors around diet and cleaning during pregnancy but were frustrated by power imbalances that left them unable to change their home or neighborhood environments, despite their desire to do so.
Discussion: Our study is among the first to describe how urban Latina mothers perceive and experience environmental health risks during pregnancy and early childhood. Our research suggests additional attention is needed by public health professionals and researchers to address the environmental health risks that matter most to urban Latina mothers. They also highlight the tension that many urban Latina mothers feel between wanting to protect their families’ health and well-being and feeling powerless to change their environment. Broad policy changes, rather than additional individual recommendations, are needed to address the concerns of this vulnerable population.
Maldonado LE, Farzan SF, Toledo-Corral CM, Dunton GF, Habre R, Eckel SP, Johnson M, Yang T, Grubbs BH, Lerner D, Chavez T, Breton CV, Bastain TM. 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. J Nutr. 2023 Jan 14;152(12):2837-2846. doi: 10.1093/jn/nxac209. PMID: 36055799; PMCID: PMC9840002.
Background: Studies examining diet and its link to birth outcomes among socioeconomically disadvantaged populations in the U.S. are scarce.
Objectives: We aimed to identify prenatal dietary patterns, examine their relationships with birth outcomes, and evaluate the variation of these associations by maternal diabetes status (none, gestational [GDM], pre-existing).
Methods: Women in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study (n = 465)-an ongoing, prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles-completed up to two 24-hour dietary recalls in the third trimester of pregnancy. We identified prenatal dietary patterns (DPs) via factor analysis and evaluated their associations with birth weight and gestational age at birth (GA) z-scores, separately, using linear regression and premature birth, small-for-gestational age (SGA), and large-for-gestational-age (LGA) using logistic regression adjusting for relevant covariates. We additionally tested interaction terms between prenatal DPs and maternal diabetes status in separate models. We adjusted for multiple comparisons using false discovery rate.
Results: We identified two dietary patterns: (1) solid fats, refined grains, and cheese (SRC) and (2) vegetables, oils, and fruit (VOF). Comparing highest-to-lowest quartiles, the VOF DP was significantly associated with greater birth weight (β = 0.40, 95% CIs: 0.10, 0.70; Ptrend = 0.011), GA (β = 0.32, 95% CIs: 0.03, 0.61; Ptrend = 0.036) and lower odds of premature birth (OR = 0.31, 95% CIs: 0.10, 0.95; Ptrend = 0.049) and SGA (OR = 0.18, 95% CIs: 0.06, 0.58; Ptrend= 0.028). Only among women with GDM, a 1-SD score increase in the SRC prenatal DP was significantly associated with lower birth weight (β = -0.20, 95% CIs -0.39, -0.02; Pinteraction = 0.040).
Conclusions: Among low-income Hispanic/Latina pregnant women, greater adherence to the VOF prenatal DP may lower the risk of premature birth and SGA. Greater adherence to the SRC DP, however, may adversely affect newborn birth weight among mothers with GDM but future research is needed to verify our findings.
Keywords: 24-h dietary recalls; MADRES; birth outcomes; diet; dietary patterns; health disparities; hispanics/latinas.
Foley HB, Howe CG, Eckel SP, Chavez T, Gevorkian L, Reyes EG, Kapanke B, Martinez D, Xue S, Suglia SF, Bastain TM, Marsit C, Breton CV. Depression, perceived stress, and distress during pregnancy and EV-associated miRNA profiles in MADRES. J Affect Disord. 2023 Feb 15;323:799-808. doi: 10.1016/j.jad.2022.12.039. Epub 2022 Dec 20. PMID: 36563790; PMCID: PMC9844263
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.
Niu Z, Habre R, Chavez TA, Yang T, Grubbs BH, Eckel SP, Berhane K, Toledo-Corral CM, Johnston J, Dunton GF, Lerner D, Al-Marayati L, Lurmann F, Pavlovic N, Farzan SF, Bastain TM, Breton CV. Association Between Ambient Air Pollution and Birth Weight by Maternal Individual- and Neighborhood-Level Stressors. JAMA Netw Open. 2022 Oct 3;5(10):e2238174. doi: 10.1001/jamanetworkopen.2022.38174. Erratum in: JAMA Netw Open. 2022 Nov 1;5(11):e2245389. PMID: 36282504; PMCID: PMC9597392.
Importance: Fetal growth is precisely programmed and could be interrupted by environmental exposures during specific times during pregnancy. Insights on potential sensitive windows of air pollution exposure in association with birth weight are needed.
Objective: To examine the association of sensitive windows of ambient air pollution exposure with birth weight and heterogeneity by individual- and neighborhood-level stressors.
Design, Setting, and Participants: Data on a cohort of low-income Hispanic women with singleton term pregnancy were collected from 2015 to 2021 in the ongoing Maternal and Developmental Risks from Environmental and Social Stressors cohort in Los Angeles, California.
Exposures: Daily ambient particulate matter with aerodynamic diameter less than 10 μm (PM10) and aerodynamic diameter less than 2.5 μm (PM2.5), nitrogen dioxide (NO2), and 8-hour maximum ozone were assigned to residential locations. Weekly averages from 12 weeks before conception to 36 gestational weeks were calculated. Individual-level psychological stressor was measured by the Perceived Stress Scale. Neighborhood-level stressor was measured by the CalEnviroScreen 4.0.
Main Outcomes and Measures: Sex-specific birth weight for gestational age z score (BWZ). The associations between air pollutant and BWZ were estimated using distributed lag models to identify sensitive windows of exposure, adjusting for maternal and meteorologic factors. We stratified the analyses by Perceived Stress Scale and CalEnviroScreen 4.0. We converted the effect size estimation in BWZ to grams to facilitate interpretation.
Results: The study included 628 pregnant women (mean [SD] age, 28.18 [5.92] years) and their newborns (mean [SD] BWZ, −0.08 [1.03]). On average, an interquartile range (IQR) increase in PM2.5 exposure during 4 to 22 gestational weeks was associated with a −9.5 g (95% CI, −10.4 to −8.6 g) change in birth weight. In stratified models, PM2.5 from 4 to 24 gestational weeks was associated with a −34.0 g (95% CI, −35.7 to −32.4 g) change in birth weight and PM10 from 9 to 14 gestational weeks was associated with a −39.4 g (95% CI, −45.4 to −33.4) change in birth weight in the subgroup with high Perceived Stress Scale and high CalEnviroScreen 4.0 scores. In this same group, NO2 from 9 to 14 gestational weeks was associated with a −40.4 g (95% CI, −47.4 to −33.3 g) change in birth weight and, from 33 to 36 gestational weeks, a −117.6 g (95% CI, −125.3 to −83.7 g) change in birth weight. Generally, there were no significant preconception windows for any air pollutants or ozone exposure with birth weight.
Conclusions and Relevance: In this cohort study, early pregnancy to midpregnancy exposures to PM2.5, PM10, and NO2 were associated with lower birth weight, particularly for mothers experiencing higher perceived stress and living in a neighborhood with a high level of stressors from environmental pollution.
Peterson AK, Eckel SP, Habre R, Yang T, Faham D, Amin M, Grubbs BH, Farzan SF, Kannan K, Robinson M, Lerner D, Al-Marayati LA, Walker DK, Grant EG, Breton CV, Bastain TM. 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. Environ Adv. 2022 Oct;9:100286. doi: 10.1016/j.envadv.2022.100286. Epub 2022 Sep 8. PMID: 36507367; PMCID: PMC9731234.
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 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: β= -3.5, 95% CI -5.8, -1.4; BPD: β = -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.
Yi L, Xu Y, Eckel SP, O’Connor S, Cabison J, Rosales M, Chu D, Chavez TA, Johnson M, Mason TB, Bastain TM, Breton CV, Dunton GF, Wilson JP, Habre R. Time-activity and daily mobility patterns during pregnancy and early postpartum – evidence from the MADRES cohort. Spat Spatiotemporal Epidemiol. 2022 Jun;41:100502. doi: 10.1016/j.sste.2022.100502. Epub 2022 Mar 24. PMID: 35691658; PMCID: PMC9198358
Introduction: Pregnant women’s daily time-activity and mobility patterns determine their environmental exposures and subsequently related health effects. Most studies ignore these and assess pregnancy exposures using static residential measures.
Methods: We conducted 4-day continuous geo-location monitoring in 62 pregnant Hispanic women, during pregnancy and early post-partum then derived trips by mode and stays, classified by context (indoor/outdoor, type). Generalized mixed-effect models were used to examine whether these patterns changed over time.
Results: Women spent on average 17.3 h/day at home. Commercial and service locations were the most popular non-home destinations, while parks and open spaces were seldom visited. Women made 3.5 daily trips (63.7 min/day and approximately 25% were pedestrian-based). Women were less likely to visit commercial and services locations and make vehicle-based trips postpartum compared to the 3rd trimester.
Conclusion: Our findings suggest time-activity patterns vary across pregnancy and postpartum, thus assessing exposures at stationary locations might introduce measurement error.
Hernandez-Castro I, Eckel SP, Chavez T, Johnson M, Lerner D, Grubbs B, Toledo-Corral CM, Farzan SF, Habre R, Dunton GF, Breton CV, Bastain TM. Household pesticide exposures and infant gross motor development in the MADRES cohort. Paediatr Perinat Epidemiol. 2022 Mar;36(2):220-229. doi: 10.1111/ppe.12850. Epub 2021 Dec 29. PMID: 34964501; PMCID: PMC8881403.
Background: The development of motor skills in infancy is a vital neurodevelopmental milestone. Although previous studies have explored the neurotoxic effects of agricultural pesticides on infants’ motor development, limited research has examined early postnatal household pesticide use on infants’ motor development, particularly among urban communities.
Objective: This study examined the association between early postnatal household pesticide use and infants’ gross and fine motor development at 6 months of age.
Methods: Questionnaires were administered via telephone to 296 mother-infant dyads in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort. Early life household pesticide use was assessed via questionnaire administered when infants turned 3 months old and gross and fine motor development was assessed by the Ages and Stages Questionnaire (ASQ-3) at 6 months old. Infant gross motor scores were reverse coded so that higher scores indicated lower gross motor performance. Negative binomial regressions were performed to assess the relationship between household pesticide use and infant gross motor development.
Results: Infants were predominantly Hispanic (78.7%) and full term (gestational age at birth: 39.0 ± 1.9 weeks), with 22.3% of maternal participants reporting household use of rodent and insect pesticides. Adjusting for recruitment site, maternal age, ethnicity, household income, education, infant corrected age, infant sex, and home type, infants with maternal-reported household use of rodent and insect pesticides had 1.30 times higher expected gross motor scores (95% confiidence interval 1.05, 1.61) than infants with no reported use of household pesticides, with higher scores indicating reduced gross motor performance.
Conclusions: Our results suggest household use of rodent and insect pesticides may harm infants’ gross motor development in early childhood. Future research should evaluate the impact of specific household chemicals in infant biospecimens and their associations with infant motor development to confirm these findings.
Niu Z, Naya CH, Reynaga L, Toledo-Corral CM, Johnson M, Yang T, Grubbs B, Lurvey N, Lerner D, Dunton GF, Habre R, Breton CV, Bastain TM, Farzan SF. Association of Breastfeeding Duration with 12-Month Postpartum Blood Lipids in a Predominately Lower-Income Hispanic Pregnancy Cohort in Los Angeles. Int J Environ Res Public Health. 2022 Mar 4;19(5):3008. doi: 10.3390/ijerph19053008. PMID: 35270701; PMCID: PMC8910591.
Breast feeding may protect women’s long-term cardiovascular health; however, breast feeding related postpartum lipid changes remain unclear. We aim to examine associations of breastfeeding duration with maternal lipids at 12 months postpartum. In a subsample (n = 79) of the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort, breastfeeding status and duration at 3, 6, and 12 months postpartum were self-reported. Serum levels of lipids, including total cholesterol, triglycerides (TG), high-, low-, and very low-density lipoprotein cholesterol (HDL-C, LDL-C, VLDL-C), were measured from blood samples collected at 12 months postpartum. We used linear regression models to compare lipids by breastfeeding duration, adjusting for potential confounders. Women who were breastfeeding at 12 months had higher HDL-C (mean: 41.74 mg/dL, 95% CI: 37.27–46.74 vs. 35.11 mg/dL, 95% CI: 31.42–39.24), lower TG (80.45 mg/dL, 95% CI: 66.20–97.77 vs. 119.11 mg/dL, 95% CI: 98.36–144.25), and lower VLDL-C (16.31 mg/dL, 95% CI: 13.23, 20.12 vs. 23.09 mg/dL, 95% CI: 18.61–28.65) compared to women who breastfed for <6 months. No lipids were significantly different between women who breastfed for 6–11 months and for <6 months. Each month’s increase in breastfeeding duration was significantly, inversely associated with TG and VLDL-C and positively with HDL-C. Adjusting for fasting status, demographics, pre-pregnancy body mass index, breastfeeding frequency, and pregnancy complications did not appreciably change effect estimates. Breastfeeding at 12 months postpartum and a longer duration of breastfeeding in the first year postpartum were both associated with increased HDL-C and decreased TG and VLDL-C at 12 months postpartum.
Hernandez-Castro I, Toledo-Corral CM, Chavez T, Habre R, Grubbs B, Al-Marayati L, Lerner D, Lurvey N, Lagomasino I, Eckel SP, Dunton GF, Farzan SF, Breton CV, Bastain TM. Perceived vulnerability to immigration policies among postpartum Hispanic/Latina women in the MADRES pregnancy cohort before and during the COVID-19 pandemic. Womens Health (Lond). 2022 Jan-Dec;18:17455057221125103. doi: 10.1177/17455057221125103. PMID: 36148937; PMCID: PMC9511002.
Introduction and objectives: Research suggests that perceived immigration policy vulnerability has important health implications. Coupled with the mental and physical stressors accompanying the postpartum period and a growing awareness of the discrimination and structural racism experienced by marginalized communities globally, the coronavirus disease 2019 period may have exacerbated stress among vulnerable populations, specifically postpartum Hispanic/Latina women. This study evaluated perceived immigration policy vulnerability (i.e. discrimination, social isolation, and family threats) in early postpartum Hispanic/Latina women in Los Angeles before and during the coronavirus disease 2019 pandemic.
Methods: The Perceived Immigration Policy Effects Scale (PIPES) was administered cross-sectionally at 1 month postpartum to 187 Hispanic/Latina women in the MADRES cohort. Respondents between September 2018 and March 2020 were classified as “pre-pandemic” (N = 128), between March 2020 and July 2020 as “early pandemic” (N = 38), and between August 2020 and November 2021 as “later pandemic” (N = 21). Average PIPES subscale scores were dichotomized into “higher” and “lower” groups (⩽median, >median) and logistic regression models were performed.
Results: Approximately half of participants had incomes of <$50,000 (50.3%) and were Latin American born (54.6%). After adjusting for age, nativity, education, income, postpartum distress, and employment status, early pandemic respondents had 5.05 times the odds of a higher score on the perceived discrimination subscale (95% CI: 1.81, 14.11), 6.47 times the odds of a higher score on the social isolation subscale (95% CI: 2.23, 18.74), 2.66 times the odds of a higher score on the family threats subscale (95% CI: 0.97, 7.32), and 3.36 times the odds of a higher total score (95% CI: 1.19, 9.51) when compared to pre-pandemic respondents. There were no significant subscale score differences between later pandemic and pre-pandemic periods.
Conclusion: Higher perceived immigration policy vulnerability was reported among postpartum women during the early coronavirus disease 2019 pandemic versus pre-pandemic periods. This suggests greater social inequities during the early pandemic period.
Bastain TM, Chavez T, Habre R, Hernandez-Castro I, Grubbs B, Toledo-Corral CM, Farzan SF, Lurvey N, Lerner D, Eckel SP, Lurmann F, Lagomasino I, Breton C. Prenatal ambient air pollution and maternal depression at 12 months postpartum in the MADRES pregnancy cohort. Environ Health. 2021 Nov 27;20(1):121. doi: 10.1186/s12940-021-00807-x. PMID: 34838014; PMCID: PMC8626870.
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).
Yan Xu, Li Yi, Jane Cabison, Marisela Rosales, Karl O’Sharkey, Thomas A. Chavez, Mark Johnson, Frederick Lurmann, Nathan Pavlovic, Theresa M. Bastain, Carrie V. Breton, John P. Wilson, Rima Habre, The impact of GPS-derived activity spaces on personal PM2.5 exposures in the MADRES cohort, Environmental Research, Volume 214, Part 2, 2022
Background: In-utero exposure to particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5) is associated with low birth weight and health risks later in life. Pregnant women are mobile and locations they spend time in contribute to their personal PM2.5 exposures. Therefore, it is important to understand how mobility and exposures encountered within activity spaces contribute to personal PM2.5 exposures during pregnancy.
Methods: We collected 48-h integrated personal PM2.5 samples and continuous geolocation (GPS) data for 213 predominantly Hispanic/Latina pregnant women in their 3rd trimester in Los Angeles, CA. We also collected questionnaires and modeled outdoor air pollution and meteorology in their residential neighborhood. We calculated three GPS-derived activity space measures of exposure to road networks, greenness (NDVI), parks, traffic volume, walkability, and outdoor PM2.5 and temperature. We used bivariate analyses to screen variables (GPS-extracted exposures in activity spaces, individual characteristics, and residential neighborhood exposures) based on their relationship with personal, 48-h integrated PM2.5 concentrations. We then built a generalized linear model to explain the variability in personal PM2.5 exposure and identify key contributing factors.
Results: Indoor PM2.5 sources, parity, and home ventilation were significantly associated with personal exposure. Activity-space based exposure to roads was associated with significantly higher personal PM2.5 exposure, while greenness was associated with lower personal PM2.5 exposure (β = −3.09 μg/m3 per SD increase in NDVI, p-value = 0.018). The contribution of outdoor PM2.5 to personal exposure was positive but relatively lower (β = 2.05 μg/m3 per SD increase, p-value = 0.016) than exposures in activity spaces and the indoor environment. The final model explained 34% of the variability in personal PM2.5 concentrations.
Conclusions: Our findings highlight the importance of activity spaces and the indoor environment on personal PM2.5 exposures of pregnant women living in Los Angeles, CA. This work also showcases the multiple, complex factors that contribute to total personal PM2.5 exposure.
Naya, C.H., Toledo-Corral, C., Chavez, T., Lerner, D., Lurvey, N., Eckel, S.P., Peterson, A., Grubbs, B.H., Dunton, G.F., Breton, C.V., Bastain, T.M. (2020) Third Trimester Cortisol is Positively Associated with Gestational Weight Gain in Pregnant Women with Class One Obesity. International Journal of Obesity.
Prevalence of pre-pregnancy obesity and excessive gestational weight gain (GWG) are higher among women of color with low SES. Dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and its end-product, cortisol, during pregnancy is hypothesized to be associated with excessive GWG. However, past studies have produced inconsistent findings and often did not include health disparities populations. This study examined the association between pre-pregnancy body mass index (BMI), third trimester diurnal cortisol, and GWG in low-income, predominantly Hispanic women. The MADRES study is an ongoing prospective cohort study of primarily Hispanic, low-income pregnant women and their children in Los Angeles, California. Data from 176 participants were included in this study. Total cortisol secretion (area under the curve, AUC) was quantified using four salivary cortisol samples (awakening, 30 min after awakening, afternoon, and bedtime) that were collected at home on one day during the third trimester of pregnancy. Moderation of the association between total cortisol and GWG by pre-pregnancy BMI was tested using multiple linear regression with a multiplicative interaction term. There was no association between total cortisol secretion and GWG overall (p = 0.82), but the association between total cortisol and GWG was stronger for women with class 1 pre-pregnancy obesity compared to women with normal pre-pregnancy BMI (interaction term p = 0.04). Results suggest that obesity status before pregnancy may be exacerbating the physiological impact of cortisol on GWG.
Peterson AK, Eckel SP, Habre R, Yang T, Faham D, Farzan SF, Grubbs BH, Kannan K, Robinson M, Lerner D, Al-Marayati LA, Walker DK, Grant EG, Bastain TM and Breton CV (2022) Prenatal Perfluorooctanoic Acid (PFOA) Exposure Is Associated With Lower Infant Birthweight Within the MADRES Pregnancy Cohort. Front. Epidemiol.
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: β= -3.5, 95% CI -5.8, -1.4; BPD: β = -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.
Karl O’Sharkey, Yan Xu, Thomas Chavez, Mark Johnson, Jane Cabison, Marisela Rosales, Brendan Grubbs, Claudia M. Toledo-Corral, Shohreh F. Farzan, Theresa Bastain, Carrie V. Breton, Rima Habre. In-utero personal exposure to PM2.5 impacted by indoor and outdoor sources and birthweight in the MADRES cohort, Environmental Advances, Volume 9, 2022
Background: In-utero exposure to outdoor particulate matter with aerodynamic diameter less than 2.5µm (PM2.5) is linked with low birthweight. However, previous results are mixed, likely due to measurement error introduced by estimating personal exposure from ambient data. We investigated the effect of total personal PM2.5 exposure on birthweight and whether it differed when it was more heavily impacted by sources of indoor vs outdoor origin in the MADRES cohort.
Methods: Personal PM2.5 exposure was measured in 205 pregnant women in the 3rd trimester using 48-hour integrated, filter-based sampling. Linear regression was used to test the association between personal PM2.5 exposure and birthweight, adjusting for key covariates. Interactions of PM2.5 with variables representing indoor sources of PM2.5, home ventilation, or time spent indoors tested whether the effect of total PM2.5 on birthweight varied when it was more impacted by sources of indoor vs outdoor origin.
Results: In a sample of largely Hispanic (81%) pregnant women, total personal PM2.5 was not significantly associated with birthweight (β=38.6 per 1SD increase in PM2.5 ; 95% CI:-21.1, 98.2). This association however, differed by home type (single family home: 156.9 (26.9, 287.0), 2-4 attached units:16.6 (-111.9, 78.7), 5+ units:-62.6 (-184.9, 59.6), missing: 145.4 (-4.1, 294.9), interaction p=0.028) and by household air conditioner use (none of the time: -27.6 (-101.5, 46.3) vs. some of the time: 139.9 (42.9, 237.0), interaction p=0.008). Additionally, the effect of personal PM2.5 on birthweight varied by time spent indoors (none or little of the time:-45.1 (-208.3, 118.1) vs. most or all of the time: 57.1 (-7.3, 121.6), interaction p=0.255).
Conclusions: While we found no significant association between total personal PM2.5 exposure and birthweight, there was evidence that multi-unit housing (vs. single-family homes), candle and/or incense smoke, and greater outdoor source contributions to personal PM2.5 were more strongly associated with lower birthweight.
Howe CG, Foley HB, Farzan SF, Chavez TA, Johnson M, Meeker JD, Bastain TM, Marsit CJ, Breton CV. Urinary metals and maternal circulating extracellular vesicle microRNA in the MADRES pregnancy cohort. Epigenetics. 2021
Exposure to metals increases risk for pregnancy complications. Extracellular vesicle (EV) miRNA contribute to maternal-foetal communication and are dysregulated in pregnancy complications. However, metal impacts on maternal circulating EV miRNA during pregnancy are unknown. Our objective was to investigate the impact of multiple metal exposures on EV miRNA in maternal circulation during pregnancy in the MADRES Study. Associations between urinary concentrations of nine metals and 106 EV miRNA in maternal plasma during pregnancy were investigated using robust linear regression (N = 231). Primary analyses focused on metal-miRNA associations in early pregnancy (median: 12.3 weeks gestation). In secondary analyses, we investigated associations with late pregnancy miRNA counts (median: 31.8 weeks gestation) in a subset of participants (N = 184) with paired measures. MiRNA associated with three or more metals (PFDR<0.05) were further investigated using Bayesian Kernel Machine Regression (BKMR), an environmental mixture method. Thirty-five miRNA were associated (PFDR<0.05) with at least one metal in early pregnancy. One association (an inverse association between cobalt and miR-150-5p) remained statistically significant when evaluating late pregnancy miRNA counts. Eight miRNA (miR-302b-3p, miR-199a-5p, miR-188-5p, miR-138-5p, miR-212-3p, miR-608, miR-1272, miR-19b-3p) were associated with three metals (barium, mercury, and thallium) in early pregnancy, and their predicted target genes were enriched in pathways important for placental development. Results were consistent when using BKMR. Early pregnancy exposure to barium, mercury, and thallium may have short-term impacts on a common set of EV miRNA which target pathways important for placental development.
Foley HB, Howe CG, Eckel SP, Chavez T, Gevorkian L, Reyes EG, Kapanke B, Martinez D, Xue S, Suglia SF, Bastain TM, Marsit C, Breton CV. Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort. PLoS One. 2021 May 12;16(5):e0251259.
MicroRNA (miRNA) circulating in plasma have been proposed as biomarkers for a variety of conditions and diseases, including complications during pregnancy. During pregnancy, about 15-25% of maternal plasma exosomes, a small size-class of EVs, are hypothesized to originate in the placenta, and may play a role in communication between the fetus and mother. However, few studies have addressed changes in miRNA over the course of pregnancy with repeated measures, nor focused on diverse populations. We describe changes in miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, CA. miRNA derived from extracellular-vesicles (EVs) were isolated from maternal blood plasma samples collected in early and late pregnancy. In this study, we identified 64 of 130 detectable miRNA which significantly increased with gestational age at the time of collection (GA), and 26 which decreased with GA. Possible fetal sex-specific associations were observed for 30 of these 90 significant miRNA. Predicted gene targets for miRNA significantly associated with GA were identified using MirDIP and were found to be enriched for Gene Ontology categories that included energetic and metabolic processes but were underrepresented in immune-related categories. Circulating EV-associated miRNA during pregnancy are likely important for maternal-fetal communication, and may play roles in supporting and maintaining a healthy pregnancy, given the changing needs of the fetus.
Howe CG, Claus Henn B, Eckel SP, Farzan SF, Grubbs BH, Chavez TA, Hodes TL, Faham D, Al-Marayati L, Lerner D, Quimby A, Twogood S, Richards MJ, Meeker JD, Bastain TM, Breton CV. Prenatal Metal Mixtures and Birth Weight for Gestational Age in a Predominately Lower-Income Hispanic Pregnancy Cohort in Los Angeles. Environmental health perspectives. 2020 Nov 3;128(11):117001.
Background: Reduced fetal growth increases the risk for adverse health outcomes. Growing evidence suggests that metal exposures contribute to reduced fetal growth, but little is known about the effects of complex metal mixtures.
Objectives: We investigated the impact of a complex mixture of metals on birth weight for gestational age (BW for GA) in the Maternal and Developmental Risks from Environmental and Social Stressors study, a predominately lower-income Hispanic pregnancy cohort in Los Angeles, California.
Methods: Cadmium (Cd), cobalt (Co), mercury (Hg), nickel (Ni), molybdenum (Mo), lead (Pb), antimony (Sb), tin (Sn), and thallium (Tl) were measured by inductively coupled plasma mass spectrometry (ICP-MS) in maternal urine samples collected in early pregnancy (median GA: 13.1 wk). Speciated urinary arsenic (As) (inorganic+monomethyl+dimethyl As) was measured by high-performance liquid chromatography coupled to ICP-MS. Primary analyses focused on a mixture of seven metals that have previously been associated individually with fetal growth (i.e., As, Cd, Co, Hg, Ni, Pb, Tl) (n=262). In exploratory analyses, we additionally examined three metals that have been less studied in relation to fetal growth (i.e., Mo, Sb, Sn). Covariate-adjusted Bayesian kernel machine regression was used to investigate metal mixture associations with BW for GA z-scores.
Results: In primary analyses, Hg and Ni ranked highest as predictors of BW for GA. An inverse linear association was estimated for Hg, whereas a positive association was estimated for Ni at low-to-moderate concentrations. A potential interaction between Hg and Ni was also identified. In our exploratory analysis, Sb ranked highest as a predictor of BW for GA, followed by Hg and Ni.
Conclusions: Our findings suggest that in this understudied population, Hg may reduce fetal growth, whereas Ni may promote fetal growth. We also identified Sb as a potential metal of concern for this population, which merits additional investigation.
Howe CG, Henn BC, Farzan SF, Habre R, Eckel SP, Grubbs BH, Chavez TA, Faham D, Al-Marayati L, Lerner D, Quimby A, Twogood S, Richards MJ, Meeker JD, Bastain TM, Breton CV. Prenatal Metal Mixtures and Fetal Size in Mid-Pregnancy in the MADRES Study. Environmental Research. 2020 Oct 28:110388.
Background: Fetal growth is predictive of health later in life. Both toxic and essential metals influence fetal growth, but most studies have focused on these elements individually and used birth weight as an indicator of fetal growth. The objective of the current study was to investigate the impact of a mixture of metals on fetal size in mid-pregnancy in a predominately lower income Hispanic pregnancy cohort in Los Angeles.
Methods: For our primary analysis, we focused on six elements that have previously been associated individually with fetal size, including arsenic (As), barium (Ba), cadmium (Cd), mercury (Hg), molybdenum (Mo), and tin (Sn), measured in maternal urine samples collected in early pregnancy (median: 12.4 weeks gestation). In an exploratory analysis, we additionally included cobalt (Co), nickel (Ni), antimony (Sb), and thallium (Tl). Using covariate-adjusted Bayesian Kernel Machine Regression (BKMR) as our main mixture modeling approach, we examined the impact of these metals on fetal biometry measures obtained between 18 and 22 weeks gestation, with a focus on estimated fetal weight (EFW).
Results: BKMR identified Mo and Ba as the mixture components that contributed most to associations with EFW. Linear associations were observed for both metals. An increase in Mo from the 25th to 75th percentile was associated with a 0.114 (95% credible interval (CI): 0.019, 0.247) SD higher EFW, equivalent to a 7.4 g difference. Similar associations were observed between Mo and the other fetal measures evaluated. In contrast, an increase in Ba from the 25th to 75th percentile was associated with a −0.076 (95% CI: 0.217, 0.066) SD lower EFW, equivalent to a 4.9 g difference. Similar inverse associations were observed for Ba in relation to abdominal circumference and biparietal diameter. BKMR also identified a possible interaction between Ba and Mo in relation to head circumference, suggesting that the positive associations between Mo and this outcome may be attenuated at high levels of Ba, which was consistent with findings from linear regression (Pinteraction = 0.03). In an exploratory analysis accounting for a larger mixture of metals, Mo and Ba consistently contributed most to associations with EFW. An inverse association was also identified between Sb and EFW.
Conclusions: Our results suggest that Mo may promote fetal growth, while Ba and Sb may reduce fetal growth, in this population.
Peterson AK, Toledo-Corral CM, Chavez TA, Naya CH, Johnson M, Eckel SP, Lerner D, Grubbs BH, Farzan SF, Dunton GF, Bastain TM, Breton CV. Prenatal Maternal Cortisol Levels and Infant Birth Weight in a Predominately Low-Income Hispanic Cohort. International journal of environmental research and public health. 2020 Jan;17(18):6896.
Infant birth weight influences numerous health outcomes throughout the life course including childhood obesity and metabolic morbidities. Maternal experience of stress, both before and during pregnancy, has been hypothesized to influence fetal growth and birth outcomes. However, these associations currently are not fully understood, due to conflicting results in the published literature. Salivary cortisol is often used as a biological biomarker to assess the diurnal pattern of the hypothalamic–pituitary–adrenal axis (HPA-axis) functioning. Cortisol metrics include both the total cortisol concentration secreted during waking hours, reflected by the area under the curve (AUC), and cortisol dynamics, which include the diurnal cortisol slope (DCS) and the cortisol awakening response (CAR). This study examined the association of these cortisol metrics measured during the third trimester of pregnancy and infant birth weight among 240 mother-infant dyads participating in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort study, which is predominately comprised of Hispanic low-income women. There were no significant associations with the maternal biological stress response and infant birth weight in this study. More research is needed in larger studies to better understand how the biological stress response influences birth weight in populations facing health disparities.
Farzan SF, Howe CG, Chavez TA, Hodes TL, Johnston JE, Habre R, Dunton G, Bastain TM, and 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 Jul 27:1-4.
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.
Girguis MS, Li L, Lurmann F, Wu J, Breton C, Gilliland F, Stram D, Habre R. Exposure measurement error in air pollution studies: the impact of shared, multiplicative measurement error on epidemiological health risk estimates. Air Quality, Atmosphere and Health. 2020 May 15.
Spatiotemporal air pollution models are increasingly being used to estimate health effects in epidemiological studies. Although such exposure prediction models typically result in improved spatial and temporal resolution of air pollution predictions, they remain subject to shared measurement error, a type of measurement error common in spatiotemporal exposure models which occurs when measurement error is not independent of exposures. A fundamental challenge of exposure measurement error in air pollution assessment is the strong correlation and sometimes identical (shared) error of exposure estimates across geographic space and time. When exposure estimates with shared measurement error are used to estimate health risk in epidemiological analyses, complex errors are potentially introduced, resulting in biased epidemiological conclusions. We demonstrate the influence of using a three-stage spatiotemporal exposure prediction model and introduce formal methods of shared, multiplicative measurement error (SMME) correction of epidemiological health risk estimates. Using our three-stage ensemble learning-based nitrogen oxides (NOx) exposure prediction model, we quantified SMME. We conducted an epidemiological analysis of wheeze risk in relation to NOx exposure among school-aged children. To demonstrate the incremental influence of exposure modeling stage, we iteratively estimated the health risk using assigned exposure predictions from each stage of the NOx model. We then determined the impact of SMME on the variance of health risk estimates under various scenarios. Depending on the stage of the spatiotemporal exposure model used, we found that wheeze odds ratio ranged from 1.16 to 1.28 for an interquartile range increase in NOx. With each additional stage of exposure modeling, the health effect estimate moved further away from the null (OR = 1). When corrected for observed SMME, the health effects confidence intervals slightly lengthened, but our epidemiological conclusions were not altered. When the variance estimate was corrected for the potential “worst case scenario” of SMME, the standard error further increased, having a meaningful influence on epidemiological conclusions. Our framework can be expanded and used to understand the implications of using exposure predictions subject to shared measurement error in future health investigations.
Howe CG, Farzan SF, Garcia E, Jursa T, Iyer R, Berhane K, Chavez TA, Hodes TL, Grubbs BH, Funk WE, Smith DR, Bastain TM, Breton CV. Arsenic and birth outcomes in a predominately lower income Hispanic pregnancy cohort in Los Angeles. Environmental Research. 2020 Feb 27:109294.
Prenatal arsenic exposure has been associated with reduced fetal growth and increased risk for preterm birth, but most studies have been conducted in highly exposed populations outside the U.S. or in non-Hispanic populations in the rural U.S. The objectives of the current study were to: 1) examine the impact of early pregnancy exposure to arsenic on birth weight and gestational age at birth in a predominately lower income Hispanic pregnancy cohort in urban Los Angeles and 2) compare multiple biomarkers of arsenic exposure (blood, urine, and hair) assessed in early pregnancy (mean ± SD gestational age at biospecimen collection: 14 ± 4 weeks). Total arsenic (blood, hair) was measured by ICP-MS and speciated arsenic (urine) was measured by HPLC coupled to ICP-MS. Associations between log2-transformed arsenic measures and birth outcomes were evaluated using multivariable linear regression. 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). This study provides evidence that even at relatively low levels of exposure, arsenic exposure (measured in hair samples collected in early pregnancy) may adversely affect fetal growth in this understudied population, particularly in combination with greater gestational weight gain. Future studies with larger sample sizes are needed to confirm these findings and to further investigate some of the inconsistencies observed for the different arsenic biomarkers evaluated.
Yi L, Wilson JP, Mason TB, Habre R, Wang S, Dunton GF. Methodologies for assessing contextual exposure to the built environment in physical activity studies: A systematic review. Health & Place. 2019 Nov 1;60:102226.
Growing research has integrated Global Positioning Systems (GPS), Geographic Information Systems (GIS), and accelerometry in studying effects of built environment on physical activity outcomes. This systematic review aimed to summarize current geospatial methods of assessing contextual exposure to the built environment in these studies. Based on reviewing 79 eligible articles, methods were identified and grouped into three main categories based on similarities in their approaches as follows: domain-based (67% of studies), buffer-based (22%), and activity space-based (11%). Additionally, technical barriers and potential sources of uncertainties in each category were discussed and recommendations on methodological improvements were made.
Bastain TM, Chavez T, Habre R, Girguis MS, Grubbs B, Toledo-Corral C, Amadeus M, Farzan SF, Al-Marayati L, Lerner D, Noya D, Quimby A, Twogood S, Wilson M, Chatzi L, Cousineau M, Berhane K, Eckel SP, Lurmann F, Johnston J, Dunton GF, Gilliland F, Breton CV. Study design, protocol and profile of the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort: A prospective cohort study in predominantly low-income Hispanic women in urban Los Angeles. BMC pregnancy and childbirth. 2019 Dec 1;19(1):189.
Background: The burden of childhood and adult obesity disproportionally affects Hispanic and African-American populations in the US, and these groups as well as populations with lower income and education levels are disproportionately affected by environmental pollution. Pregnancy is a critical developmental period where maternal exposures may have significant impacts on infant and childhood growth as well as the future health of the mother. We initiated the “Maternal And Developmental Risks from Environmental and Social Stressors (MADRES)” cohort study to address critical gaps in understanding the increased risk for childhood obesity and maternal obesity outcomes among minority and low-income women in urban Los Angeles.
Methods: The MADRES cohort is specifically examining whether pre- and postpartum environmental exposures, in addition to exposures to psychosocial and built environment stressors, lead to excessive gestational weight gain and postpartum weight retention in women and to perturbed infant growth trajectories and increased childhood obesity risk through altered psychological, behavioral and/or metabolic responses. The ongoing MADRES study is a prospective pregnancy cohort of 1000 predominantly lower-income, Hispanic women in Los Angeles, CA. Enrollment in the MADRES cohort is initiated prior to 30 weeks gestation from partner community health clinics in Los Angeles. Cohort participants are followed through their pregnancies, at birth, and during the infant’s first year of life through a series of in-person visits with interviewer-administered questionnaires, anthropometric measurements and biospecimen collection as well as telephone interviews conducted with the mother.
Discussion: In this paper, we outline the study rationale and data collection protocol for the MADRES cohort, and we present a profile of demographic, health and exposure characteristics for 291 participants who have delivered their infants, out of 523 participants enrolled in the study from November 2015 to October 2018 from four community health clinics in Los Angeles. Results from the MADRES cohort could provide a powerful rationale for regulation of targeted chemical environmental components, better transportation and urban design policies, and clinical recommendations for stress-coping strategies and behavior to reduce lifelong obesity risk.
Girguis MS, Li L, Lurmann F, Wu J, Urman R, Rappaport E, Breton C, Gilliland F, Stram D, Habre R. Exposure measurement error in air pollution studies: A framework for assessing shared, multiplicative measurement error in ensemble learning estimates of nitrogen oxides. Environment international. 2019 Apr 1;125:97-106.
Background: Increasingly ensemble learning-based spatiotemporal models are being used to estimate residential air pollution exposures in epidemiological studies. While these machine learning models typically have improved performance, they suffer from exposure measurement error that is inherent in all models. Our objective is to develop a framework to formally assess shared, multiplicative measurement error (SMME) in our previously published three-stage, ensemble learning-based nitrogen oxides (NOx) model to identify its spatial and temporal patterns and predictors.
Methods: By treating the ensembles as an external dosimetry system, we quantified shared and unshared, multiplicative and additive (SUMA) measurement error components in our exposure model. We used generalized additive models (GAMs) with a smooth term for location to identify geographic locations with significantly elevated SMME and explain their spatial and temporal determinants.
Results: We found evidence of significant shared and unshared multiplicative error (p < 0.0001) in our ensemble-learning based spatiotemporal NOx model predictions. Unshared multiplicative error was 26 times larger than SMME. We observed significant geographic (p < 0.0001) and temporal variation in SMME with the majority (43%) of predictions with elevated SMME occurring in the earliest time-period (1992–2000). Densely populated urban prediction regions with complex air pollution sources generally exhibited highest odds of elevated SMME.
Conclusions: We developed a novel statistical framework to formally evaluate the magnitude and drivers of SMME in ensemble learning-based exposure models. Our framework can be used to inform building future improved exposure models.
Howe CG, Zhou M, Wang X, Pittman GS, Thompson IJ, Campbell MR, Bastain TM, Grubbs BH, Salam MT, Hoyo C, Bell DA, Smith AD, Breton CV. Associations between Maternal Tobacco Smoke Exposure and the Cord Blood CD4+ DNA Methylome. Environmental health perspectives. 2019 Apr 30;127(4):047009.
Background: Maternal tobacco smoke exposure has been associated with altered DNA methylation. However, previous studies largely used methylation arrays, which cover a small fraction of CpGs, and focused on whole cord blood.
Objectives:
The current study examined the impact of in utero exposure to maternal tobacco smoke on the cord blood CD4+ DNA methylome.
Methods: The methylomes of 20 Hispanic white newborns (n=10 exposed to any maternal tobacco smoke in pregnancy; n=10 unexposed) from the Maternal and Child Health Study (MACHS) were profiled by whole-genome bisulfite sequencing (median coverage: 6.5×). Statistical analyses were conducted using the Regression Analysis of Differential Methylation (RADMeth) program because it performs well on low-coverage data (minimizes false positives and negatives).
Results: We found that 10,381 CpGs were differentially methylated by tobacco smoke exposure [neighbor-adjusted p-values that are additionally corrected for multiple testing based on the Benjamini-Hochberg method for controlling the false discovery rate (FDR) (pFDR)<0.05]. From these CpGs, RADMeth identified 557 differentially methylated regions (DMRs) that were overrepresented (p<0.05) in important regulatory regions, including enhancers. Of nine DMRs that could be queried in a reduced representation bisulfite sequencing (RRBS) study of adult CD4+ cells (n=9 smokers; n=10 nonsmokers), four replicated (p<0.05). Additionally, a CpG in the promoter of SLC7A8 (percent methylation difference: −9.4% comparing exposed to unexposed) replicated (p<0.05) in an EPIC (Illumina) array study of cord blood CD4+ cells (n=14 exposed to sustained maternal tobacco smoke; n=16 unexposed) and in a study of adult CD4+ cells across two platforms (EPIC: n=9 smokers; n=11 nonsmokers; 450K: n=59 smokers; n=72 nonsmokers).
Conclusions: Maternal tobacco smoke exposure in pregnancy is associated with cord blood CD4+ DNA methylation in key regulatory regions, including enhancers. While we used a method that performs well on low-coverage data, we cannot exclude the possibility that some results may be false positives. However, we identified a differentially methylated CpG in amino acid transporter SLC7A8 that is highly reproducible, which may be sensitive to cigarette smoke in both cord blood and adult CD4+ cells.
O’Connor SG, Habre R, Bastain TM, Toledo-Corral CM, Gilliland FD, Eckel SP, Cabison J, Naya CH, Farzan SF, Chu D, Chavez TA, Breton CV, Dunton GF. 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.
Background: Disproportionately high rates of maternal overweight and obesity among the Hispanic population before, during, and after pregnancy pose serious health concerns for both mothers (e.g., preeclampsia, gestational diabetes, weight retention) and children (e.g., elevated lifelong obesity risk). A growing body of evidence implicates environmental exposures (e.g., air pollution, metals) and social stressors (e.g., poverty, violence) in contributing to obesity-related biobehavioral processes, such as physical activity, dietary intake, perceived stress, and cortisol regulation. However, current understanding of the role of environmental exposures and social stressors on obesity-related biobehavioral processes is limited by infrequent, inter-individual measurement, and lack of personal exposure monitoring.
Methods: The “Maternal and Developmental Risks from Environmental and Social Stressors” (MADRES) real-time and personal sampling study examines the within-subject day-level effects of environmental and social stressors on maternal pre- and post-partum obesity-related biobehavioral responses. Among a cohort of 65 low-income, Hispanic women in urban Los Angeles, this study uses innovative personal, real-time data capture strategies (e.g., ecological momentary assessment [EMA], personal exposure monitoring, geolocation monitoring, accelerometry) to repeatedly assess obesity-related processes during the 1st and 3rd trimester, and at 4–6 months postpartum. Day-level effects of environmental exposures and social stressors on women’s physical activity, diet, perceived stress and salivary cortisol measured across repeated days will be tested using multilevel modeling.
Discussion: Hispanic women of childbearing age bear a disproportionately high burden of obesity, and this population is also unduly exposed to numerous obesogenic settings. By using innovative real-time data capture strategies, the current study will uncover the daily impacts of environmental and social stressor exposures on women’s obesity-related biobehavioral responses, which over time can lead to excessive gestational weight gain, postpartum weight retention and can pose serious consequences for both mother and child. Findings from the real-time and personal sampling study will identify key mechanistic targets for policy, clinical, and programmatic interventions, with the potential for broad-reaching public health impacts.
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 Jun;13(6):348-56.
Objective: Studies suggest that prenatal exposure to traffic-related air pollution (TRAP) may contribute to childhood obesity. While exact mechanisms for this association are unknown, circulating adipokines are hypothesized to contribute to early-life weight gain.
Methods: The Maternal and Child Health Study birth cohort included 136 women from the Los Angeles County + University of Southern California Medical Center. This study estimated prenatal residential TRAP exposure and used linear regression analysis to examine associations between adipokines with TRAP exposure and infant weight change (birth to 6 months).
Results: A one standard deviation (1-SD: 2 ppb) increase in prenatal non-freeway NOx was associated with 33% (p=0.01) higher leptin and 9% higher high molecular weight (HMW) adiponectin levels (p=0.07) in cord blood. Leptin levels were 71% higher in mothers who lived <75 meters than those living >300 meters from major roadways (p=0.03). A 1-SD (10 ng/ml) increase in leptin was associated with a significant increase in infant weight change in females (0.62 kg, p=0.02) but not males (0.11 kg, p=0.48).
Conclusions: Higher TRAP exposures were associated with higher cord blood levels of leptin and HMW adiponectin. These adipokines were associated with increased infant weight change in females, which may have implications for future obesity risk.
Felix JF, Joubert BR, Baccarelli AA, Sharp GC, Almquist C, Annesi-Maesano I, Arshad H, Baiz N, Bakermans-Kranenburg MJ, Bakulski KM, Binder EB, Bouchard L, Breton CV, Brunekreef B, Brunst KJ, Burchard EG, Bustamante M, Chatzi L … Agha G, Relton CL, Jaddoe VWV, London SJ. Cohort Profile: Pregnancy and Childhood Epigenetics (PACE) Consortium. International journal of epidemiology. 2018 Feb 1;47(1):22-3u.
Alderete TL, Habre R, Toledo-Corral CM, Berhane K, Chen Z, Lurmann F, Weigensberg MJ, Goran MI, Gilliland FD. Longitudinal associations between ambient air pollution with insulin sensitivity, β-cell function, and adiposity in Los Angeles Latino children. Diabetes. 2017 Jul 1;66(7):1789-96.
Evidence suggests that ambient air pollution (AAP) exposure may contribute to the development of obesity and type 2 diabetes. The objective of this study was to determine whether exposure to elevated concentrations of nitrogen dioxide (NO2) and particulate matter with aerodynamic diameter <2.5 (PM2.5) had adverse effects on longitudinal measures of insulin sensitivity (SI), β-cell function, and obesity in children at high risk for developing diabetes. Overweight and obese Latino children (8–15 years; n = 314) were enrolled between 2001 and 2012 from Los Angeles, CA, and followed for an average of 3.4 years (SD 3.1 years). Linear mixed-effects models were fitted to assess relationships between AAP exposure and outcomes after adjusting for covariates including body fat percent. Higher NO2 and PM2.5 were associated with a faster decline in SI and a lower SI at age 18 years, independent of adiposity. NO2 exposure negatively affected β-cell function, evidenced by a faster decline in disposition index (DI) and a lower DI at age 18 years. Higher NO2 and PM2.5 exposures over follow-up were also associated with a higher BMI at age 18 years. AAP exposure may contribute to development of type 2 diabetes through direct effects on SI and β-cell function.
Xu Y., Yi L., Cabison J., O’Sharkey K., Chavez T., Lurmann F., Bastain T.M., Breton C.V., Wilson J.P., Habre R. (2021, April). Using GPS-derived Time-Activity Patterns to Estimate Personal Particulate Air Pollution Exposure in MADRES. Abstract presented at the American Association of Geographers 2021 Annual Meeting.
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Yi L., Habre R., Xu Y., Mason T., Naya C.H., Chu D., Chavez T., Wilson J.P., Bastain T.M., Breton C.V., Dunton G.F. (2021, April). A Study of Context-Specific Physical Activity Patterns of Low-Income Hispanic Women During Pregnancy Using GPS And Accelerometer Data. Abstract presented at the 2021 Annual Active Living Conference.
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Yi, L., Xu Y, O’Connor S.G., Cabison J., Chu D., Chavez T., Mason T.B., Bastain T.M.,. Breton C.V., Dunton G.F., Wilson J.P., and Habre R. (2021, April). Integrating mobility and time-activity patterns in assessing environmental exposures during pregnancy and early postpartum. Abstract presented at the American Association of Geographers 2021 Annual Meeting.
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Xu Y., Cabison J., Chavez T., Wilson J.P., Bastain T.M., Breton C.V., Habre R. (2020, September). Sources of Personal PM2.5 Exposure in the MADRES Cohort during the Third Trimester of Pregnancy. Abstract presented at the International Society of Exposure Science 2020 Annual Meeting.
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Habre, R., Yi, L., Xu, Y., Naya, C., O’Connor, S., Cabison, J., Chu, D., Mason, T., Chavez, T., Bastain, T., Breton, C., Dunton, G. (2020, September). Personal PM2.5 air pollution exposure, time-activity patterns and momentary geospatial exposures across pregnancy and early postpartum in low income, Hispanic women. Abstract presented at the International Society of Exposure Science 2020 Annual Meeting.
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Li, L., Girguis, M., Lurmann, F., Pavlovic, N., Franklin, M., Wu, J., Oman, L., Breton, C., Gilliland, F., Habre, R. (2020, September). Ensemble-Based Deep Learning for Estimating PM2.5 over California. Abstract presented at the International Society of Exposure Science 2020 Annual Meeting.
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Bastain, T., Chavez, T., Habre, R., Lurmann, F., Farzan, S., Grubbs, B., Dunton, G., Lagomasino, I., Eckel, S., Breton, C. (2020, August). Prenatal Ambient Air Pollutants and Maternal Depressive Symptoms at 12 months Postpartum. Abstract presented at the 32nd Annual Conference of the International Society for Environmental Epidemiology.
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Breton, C.V., Peterson, A.K., Habre, R., Lurmann, F., Amin, M., Eckel, S.P., Grubbs, B., Walker, D., Grant, E., Lerner, D., Al-Marayati, L., Quimby, A., Twogood, S., Bastain, T. (2020, August). Prenatal Ambient Air Pollutants Influence Fetal Blood Flow and Shunting to the Brain in the Third Trimester. Abstract presented at the 32nd Annual Conference of the International Society for Environmental Epidemiology.
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Howe, C.G., Claus Henn, B., Eckel, S.P., Farzan, S.F, Grubbs, B.H., Fernandez, J., Meeker, J.D., Bastain, T.M., Breton, C.V. (2020, August). Prenatal metal mixtures and birth weight for gestational age in a predominately lower income Hispanic pregnancy cohort. Abstract presented at the 32nd Annual Conference of the International Society for Environmental Epidemiology.
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Mohazzab-Hosseinian, S., Howe, C.G., Foley, H., Faham, D., Chavez, T., Weisenberger, D., Bastain, T.M., Breton, C.V. (2020, August). Antibiotic Use during Pregnancy and the Maternal Epigenome. Abstract presented at the 32nd Annual Conference of the International Society for Environmental Epidemiology.
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Peterson A.K., Hodes T., Chavez T.A., Howland, S., Grubbs B., Chatzi L., Gilliland F., Bastain T.M., Breton C.V. (2020, August). Prenatal PFAS exposure influences infant lean and fat mass. Abstract presented at the 32nd Annual Conference of the International Society for Environmental Epidemiology.
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Chavez T.A., Habre R., Farzan S., Toledo-Corral C., Grubbs B., Eckel S., Dunton G.F., Breton C., and Bastain T.M. (2020, March). Prenatal Traffic-Related Air Pollution Exposure and Postpartum Depressive Symptoms in the MADRES Pregnancy Cohort. Abstract accepted at the 59th Annual Meeting of the Society of Toxicology, Anaheim, CA.
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Johnson, M., Chavez, T., Grubbs, B., Berhane, K., Gilliland, F., Habre, R., Bastain, T., and Breton, C. (2020, March). Prenatal Air Pollutant Exposure, Perceived Stress and 12-Month Infant Growth in the MADRES Cohort. Abstract accepted at the 59th Annual Meeting of the Society of Toxicology, Anaheim, CA.
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Mohazzab-Hosseinian, S., Howe, C., Bastain, T., Chavez, T., Breton, C. (2020, March). Epigenetic Effects of Gestational Diabetes: A Prospective Study. Abstract accepted at the 59th Annual Meeting of the Society of Toxicology, Anaheim, CA.
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Naya, C. H., Peterson, A., Chavez, T., Eckel, S. P., Toledo-Corral, C., Mason, T., Bastain, T., Breton, C., & Dunton, G.F. (2019, November). Cortisol awakening response and weight during third trimester pregnancy among predominantly low-income Hispanic mothers. Abstract presented at the 2019 Obesity Week, Las Vegas, NV.
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Peterson, A. K., Naya, C. H., Chavez, T. A., Toledo-Corral, C. M., Habre, R., Howland, S., & Bastain, T. M. (2019, November). The relationship between prenatal stress and newborn body composition. Abstract presented at the 2019 Obesity Week, Las Vegas, NV.
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Howe, C. G., Farzan, S. F., Chavez, T. A., Hodes, T., Bastain, T. L., & Breton, C. V. (2019, October). Arsenic exposure and birth outcomes in a predominately low-income Hispanic pregnancy cohort in Los Angeles. Abstract presented at the 11th DOHaD World Congress, Melbourne, Australia.
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Girguis, M. S., Bastain, T. M., Chavez, T., Gilliland, F., Breton, C., & Habre, R. (2019, July). Where you live matters: Assessing the relationship of socio-environmental neighborhood clusters with stress and depression during pregnancy. Abstract presented at the 31st Annual Conference of the International Society for Environmental Epidemiology, Utrecht, the Netherlands.
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Habre, R., O’Connor, S., Girguis, M. S., Cabison, J., Chu, D., Chavez, T., Bastain, T., Breton, C., & Dunton G. (2019, July). Personal PM2.5 air pollution exposure and mobility patterns in pregnant, low income Hispanic women in MADRES. Abstract presented at the 31st Annual Conference of the International Society for Environmental Epidemiology, Utrecht, the Netherlands.
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Peterson, A. K., Chavez, T. A., Toledo-Corral, C. M., Naya, C. H., Dunton, G. F., Bastain, T. M., & Breton, C. (2019, July). Exploring the association of birth weight with maternal measured and perceived stress. Abstract presented at the 10th Biennial Childhood Obesity Conference, Anaheim, CA.
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Song, A. Y., Habre, R., Girguis, M., Chavez, T., Lurmann, F., Grubbs, B. H., Bastain, T., & Breton, C. (2019, July). Identifying sensitive windows of prenatal exposure to ambient air pollution with birthweight using a distributed lag model. Abstract presented at the 31st Annual Conference of the International Society for Environmental Epidemiology, Utrecht, the Netherlands.
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Song, A. Y., Habre, R., Girguis, M., Dunton, G., Chavez, T., Lurmann, F., Grubbs, B. H., Bastain, T., & Breton, C. (2019, July). Ambient air pollution with birthweight: Modification by maternal stress. Abstract presented at the 10th Biennial Childhood Obesity Conference, Anaheim, CA.
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Bermudez-Foley, H., & Breton, C. (2019, June). miRNA profiles and psychosocial stress during pregnancy in a cohort of urban Hispanic mothers. Abstract presented at the 14th Annual Texas Conference on Health Disparities: Social Epigenomics and Health Disparities, Fort Worth, TX.
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Chavez, T., Bastain, T., & Breton, C. (2019, June). Maternal obesity and risk of gestational diabetes in the MADRES pregnancy cohort: A prospective cohort study in predominantly low-income Hispanic women in urban Los Angeles. Abstract presented at the Annual Meeting of the Society of Epidemiological Research, Minneapolis, MN.
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Mason, T. B., O’Connor, S. G., Cabison, J., Bastain, T., Naya, C. H., Chu, D., Eckel, S. P., Breton, C. V., & Dunton, G. F. (2019, June). Bi-directional associations of affective states and energy balance behaviors among pregnant women using ecological momentary assessment. Abstract presented at the 6th Society for Ambulatory Assessment Conference, Syracuse, NY.
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Girguis, M. S., Bastain, T. M., Chavez, T., Johnston, J. Toledo-Corral, C., Dunton, G., Breton, C., & Habre, R. (2019, May). Where you live matters: Socio-environmental neighborhood level exposome profiles and stress during pregnancy. Abstract presented at the 2nd Annual UNIBS/ISMMS Collaborative Conference, 2019 Exposome Symposium: Emerging Science and Technology for Effective Prevention and Healthy Outcomes, Brescia, Italy.
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Peterson, A. K., Chavez, T. A., Habre, R., Howland, S., Gilliland, F., Bastain, T. M., & Breton, C. V. (2019, May). Preliminary data analysis on novel technology to assess adolescent fat mass. Abstract presented at the Body Composition Measurements from Birth through 5 years: Challenges, Gaps, and Existing and Emerging Technologies of The National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
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Toledo-Corral, C. M., Naya, C., Chavez, T., Habre, R., Bastain, T., Dunton, G., Gilliland, F.D., & Breton, C. (2019, March). Characterizing diurnal cortisol patterns of 3rd trimester pregnant women in Los Angeles. Abstract presented at the 77th Annual Scientific Meeting of the American Psychosomatic Society, Vancouver, British Columbia.
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Girguis, M. S., Bastain, T. M., Chavez, T., Johnston, J. Toledo-Corral, C., Dunton, G., Breton, C., & Habre, R. (2019, January). Where you live matters: Assessing socio-environmental neighborhood level exposures of MADRES participants. Abstract presented at the NIH-EPA Centers of Excellence on Environmental Health Disparities Research Annual Grantees Meeting, Baltimore, MD.
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Howe, C. G., Farzan, S. F., Eckel, S. P., Hodes, T., Chavez, T. A., Bastain, T. L., Gilliland, F. D., & Breton, C. V. (2019, January). Rice and seafood intake and urine arsenic in the MADRES Pregnancy cohort. Abstract presented at the NIH-EPA Centers of Excellence on Environmental Health Disparities Research Annual Grantees Meeting, Baltimore, MD.
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Bastain, T., Gao, L., Toledo-Corral, C., Chavez, T., Habre, R., Farzan, S., Grubbs, B., Johnston, J., Dunton, G., Gilliland, F., & Breton, C. (2018, August). Early descriptive results from the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort study. Abstract presented at the ISES-ISEE 2018 Joint Annual Meeting, Ottawa, Canada.
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Girguis, M. S., Li, L., Lurmann, F., Wu, J., Urman, R., Rappaport, E., Breton, C., Gilliland, F., Stram, D., & Habre, R. (2018, August). Assessment of shared and unshared exposure measurement error in ensemble learning estimates of nitrogen oxides and its implications on epidemiological findings in air pollution studies. Abstract presented at the ISES-ISEE 2018 Joint Annual Meeting, Ottawa, Canada.
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Toledo-Corral, C. M., Gao, L., Chavez, T., Grubbs, B., Habre, R., Bastain, T. M., Dunton, G., Gilliland, F. D., & Breton, C. (2018, August). Correlates of stress and depression in early pregnancy in a low-income minority population. Abstract presented at the ISES-ISEE 2018 Joint Annual Meeting, Ottawa, Canada.
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O’Connor, S.G., Wai-Quan Cabison, J., Ke, W., Breton, C.V., Bastain, T., & Dunton, G.F. (2017, December). Ecological momentary assessment methods to measure stress, mood, and weight-related behaviors in low-Income, Hispanic, post-partum women. Abstract presented at the NIH-EPA Centers of Excellence on Environmental Health Disparities Research Annual Grantees Meeting, Albuquerque, New Mexico.
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O’Connor, S.G., Wai-Quan Cabison, J., Ke, W., Breton, C.V., Bastain, T., & Dunton, G.F. (2017, March). Using ecological momentary assessment methods to measure stress and weight-related behaviors in Hispanic post-partum women. Abstract presented at the 38th Annual Meeting of the Society of Behavioral Medicine, San Diego, CA.
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Breton, C., Bastain, T. M., Dunton, G., Grubbs, B., Eckel, S., Berhane, K., Toledo-Corral, Habre, R., Johnston, J., & Gilliland, F. (2016, September). Maternal And Developmental Risks from Environmental and Social Stressors: An environmental health disparities center. Abstract presented at the 28th Annual Conference of the International Society for Environmental Epidemiology, Rome Italy.
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Habre, R., Bastain, T. M., Dunton, G., Eckel, S., Gilliland, F., & Breton, C. (2016, September). Personal air pollution monitoring in the MADRES cohort of pregnant women: Challenges and lessons learned. Abstract presented at the 28th Annual Conference of the International Society for Environmental Epidemiology, Rome Italy.
