2015 Progress Report: Center for Children’s Environmental Health and Disease Prevention Research (P01) (joint EPA and NIEHS) - CHAMACOS

EPA Grant Number: R834513
Center: Center for the Health Assessment of Mothers and Children of Salinas - UC Berkeley School of Public Health: CHAMACOS Office, Berkeley, CA
Center Director: Eskenazi, Brenda
Title: Center for Children’s Environmental Health and Disease Prevention Research (P01) (joint EPA and NIEHS) - CHAMACOS
Investigators: Eskenazi, Brenda , Arora, Manish , Barcellos, Lisa , Barlow, Janice , Blum, Arlene , Bradman, Asa , Crinella, Frank , Eisen, Ellen , Fenster, Laura , Harley, Kim , Harnly, Martha , Holland, Nina T. , Hubbard, Alan , Jerrett, Michael , Johnson, Caroline , Lustig, Robert , McKone, Thomas , Minkler, Meredith , Molitor, John , Rosas, Lisa Goldman , Salvatore, Alicia , Sjodin, Andreas , Smith, Donald , Wallerstein, Nina
Current Investigators: Eskenazi, Brenda , Arora, Manish , Barcellos, Lisa , Barlow, Janice , Blum, Arlene , Bradman, Asa , Crinella, Frank , Eisen, Ellen , Fenster, Laura , Harley, Kim , Harnly, Martha , Holland, Nina T. , Hubbard, Alan , Jerrett, Michael , Johnson, Caroline , Lustig, Robert , McKone, Thomas , Minkler, Meredith , Molitor, John , Rosas, Lisa Goldman , Salvatore, Alicia L. , Sjodin, Andreas , Smith, Donald , Wallerstein, Nina
Institution: University of California - Berkeley
EPA Project Officer: Louie, Nica
Project Period: August 1, 2009 through July 31, 2014 (Extended to July 31, 2017)
Project Period Covered by this Report: August 1, 2014 through July 31,2015
Project Amount: $3,585,543
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

Project A: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior & Puberty

In Project A, we are examining the association of DDT, Mn, and PBDEs with neurodevelopment and onset of puberty in boys in the CHAMACOS cohort. This study directly addresses worldwide concerns that changes in onset of sexual maturation may be related to endocrine disruptors in the environment and fills a large data gap on boys. It also addresses concerns that exposure to DDT/E, PBDEs and Mn may compromise neurodevelopment.

Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children

In Project B, we are examining novel methods of examining prenatal exposure to Mn, PBDE, and DDT/E compounds. For Mn, we are developing methods to measure Mn in shed deciduous teeth and in hair collected when the children were 10.5 years of age. For PBDEs and DDT/E, we are developing models to back-extrapolate prenatal exposure levels from 9-year measured levels and other determinants of exposure.

Project C: Epigenetics Project: Epigenetic Effects of DDT/E and PBDEs on Puberty

In Project C, we are investigating molecular mechanisms with a main focus on epigenetic effects associated with prenatal and childhood exposure to persistent organic pollutants (DDT and PBDEs). We are also characterizing the differences in multiple epigenetic marks by host factors like age and sex in children from birth to 12 years of age and assessing relationships of epigenetic modifications in children with hormone levels and pubertal onset.

Community Outreach and Translation Core (COTC)

The COTC Core enables Center scientists and community partners to communicate study findings in a culturally appropriate manner, to raise awareness of children’s environmental health within and beyond the Salinas Valley, and to support policies that will improve the health of low-income Latino residents locally in Monterey County and throughout the state and nation. Because we achieved all major objectives in the first 5 years of Center funding and are operating in a no-cost extension year with reduced COTC staffing, we have limited our Center COTC activities in the past year to general community outreach. However, community outreach activities established under the Center have attracted outside funding which has supported several other local environmental health projects, which we report upon below.

Progress Summary:

Project A: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior & Puberty

 1. To maintain and expand the CHAMACOS cohort as children begin the critical transition to puberty, assessing neurodevelopment and pubertal development in 300 boys from 9 to 13 years of age.

We have successfully met our goal of expanding the CHAMACOS cohort to 300 boys. We assessed 326 boys at age 9 years, 310 boys at age 10½, and 304 boys at age 12. To date, we have assessed 225 boys at the final visit point of this project, age 12¾, and plan to assess an additional 40 boys by the end of this visit point in late July. The lower rate of participation at 12¾ is discussed in Difficulties Encountered, below.
 
2. To determine whether prenatal and childhood exposure to DDT/E, PBDEs, and Mn are associated with neurobehavioral functioning at age 9, 10½, and 12 years.
 
Note: This Center grant includes the follow-up of boys only. We received another NIEHS grant (ES017054) to assess the girls in the CHAMACOS cohort. To increase statistical power, we have combined boys and girls from the CHAMACOS cohort for all analyses of neurobehavioral functioning, though we have assessed for heterogeneous associations by sex (i.e., interaction). For both DDT/E and PBDEs, measured maternal pregnancy serum concentrations were used as the exposure variable for the majority of CHAM1 participants (i.e., members of the original CHAMACOS cohort followed since pregnancy), while back-extrapolated pregnancy concentrations were used for all CHAM2 participants (i.e., members of the CHAMACOS cohort enrolled at child age 9) as well as for CHAM1 participants who were missing pregnancy or delivery serum samples. Prenatal concentrations were back-extrapolated from DDT/E and/or PBDE levels measured in maternal serum collected when the child was 9 years old using the SuperLearner algorithm, which is an ensemble machine learning technique that uses the weighted combination of algorithms to return a prediction function that minimizes the cross-validated mean squared error (see Project B). In validation models, which used maternal serum concentrations to back-extrapolate values in women for whom measured pregnancy values were also available, the model R2 for models comparing extrapolated and measured values was 0.95 for both p,p’-DDT and p,p’-DDE, and ranged from 0.58-0.84 for the four highest-detected PBDE congeners in this population (PBDE-47, 99, 100, 153; see Verner, et al., 2015).
 
DDT/E: Generalized estimating equation (GEE) models and multivariable linear models were used to test relationships between prenatal p,p’-DDT/E and children’s WISC full scale IQ as well as four composite scales (verbal comprehension, perceptual reasoning, working memory, and processing speed. In sex-combined analyses, GEE models revealed significant inverse associations between DDT/E and processing speed scores only, though separate linear models by age indicated that this association was present at 7 but not 10½ years of age. Our analyses suggest heterogeneous associations by sex, with girls exhibiting more negative associations between in utero DDT/E exposure and age 7 outcomes in particular. At age 10½, however, boys but not girls exhibited borderline-significant inverse associations between in utero DDT/E exposure and working memory scores. A manuscript by Gaspar, et al., regarding associations between prenatal p,p’-DDT/E serum concentrations and children’s Wechsler Intelligence Scales for Children-IV (WISC) scores at ages 7 and 10½ is undergoing minor revisions for publication in the journal Environment International.
 
PBDEs: GEE models and multivariable linear models were used to test relationships between prenatal and childhood concentrations of the sum of four congeners (PBDE-47, 99, 100, 153) and multiple indicators of attention and executive functioning. Key attention indicators included the Conners’ Continuous Performance Test (CPT), completed by children at ages 9 and 12, the WISC processing speed scale, completed by children at age 10½, and the Conners’ ADHD/DSM-IV Scales (CADS), completed by parents at child ages 9 and 12. Key executive function indicators included, but were not limited to, the Wisconsin Card Sort Task (WCST), completed by children at ages 9 and 12, the WISC working memory scale, completed by children at age 10½, and the Behavior Rating Inventory of Executive Function, completed by parents at child ages 9 and 12.
 
Attention GEE analyses showed borderline-significant adverse associations between prenatal PBDE concentrations and parent-reported (CADS) attention problems, as well as significant increase in CPT hit rate standard error across blocks, indicating a shortcoming in maintaining attention and consistent responding over the duration of a low-interest task. Linear models by age indicated that parent-report (CADS) associations were present at age 9 but not 12, whereas CPT associations were relatively consistent at both time points. Linear models also showed a statistically significant adverse association between prenatal PBDE concentrations and WISC processing speed scores at age 10½ (β:-4.2; 95% CI:-7.1,-1.3). Executive function GEE models showed adverse associations between prenatal PBDE concentrations and parent-reported (BRIEF) executive function problems, as well as increased errors on the WCST. Associations were more pronounced in the subset of participants with measured prenatal PBDE serum concentrations than in the full sample which included back extrapolated values. In the subset with measured PBDE values, statistically significant associations were seen for parent-reported emotional control and working memory subscales of the BRIEF, as well as for perseverative and overall errors on the WCST. Linear models by age indicated that parent-report (BRIEF) associations were present at age 9 but absent or attenuated at age 12, whereas WCST associations were relatively consistent at both time points. WISC working memory at age 10½ and other indicators of executive functioning were not associated with PBDE concentrations. Though child age 9 PBDE concentrations were not associated with attention or executive function measures in any sex-combined models, there was evidence of differential associations of child age 9 PBDE concentrations with parent reported attention (CADS) and executive function (BRIEF) problems by child sex, with more adverse associations seen for girls than for boys. Prenatal PBDE models showed little evidence of interaction by sex. A manuscript by Sagiv, et al., regarding associations between prenatal and child age 9 PBDE serum concentrations and children’s attention and executive functioning between ages 9 and 12 has been accepted pending minor revisions with the journal Neurotoxicology and Teratology.
 
Mn: As described in previous progress reports and publications (e.g., Gunier, et al., 2013), Mn was measured in dentine from children’s shed teeth, with the neonatal line used to distinguish prenatal (~13-16 weeks gestation through delivery) from early postnatal exposure (birth- ~10-11 months old). In Project A, GEE models and multivariable linear models were used to test relationships between prenatal and early postnatal Mn exposure and neurobehavioral, cognitive, memory, and motor tests. Key behavior and attention indicators included teacher-report CADs at age 7 and parent-report CADs at ages 7 and 9; teacher-report Behavior Assessment System for Children (BASC) scores at age 7, parent-report BASC at ages 7 and 10½, and youth self report BASC at age 10½; and child CPT scores at age 9. Cognition indicators included WISC full scale IQ and subscale scores from ages 7 and 10½. Memory indicators included the NEPSY-II Memory for Designs test completed at age 9 and the Children’s Auditory Verbal Learning Test, 2nd edition (CAVLT-2) completed at age 10½. Motor indicators included fingertapping and pegboard tasks completed at age 7, plus select subtests of the Luria Nebraska Motor Battery completed at ages 9 and 10½.
 
Results of these analyses suggested heterogeneous exposure-outcome associations by sex. With regards to behavior/attention measures, prenatal Mn exposure showed adverse associations with maternally reported internalizing, externalizing, and hyperactivity problems at age 10½ for boys but not girls, whereas postnatal Mn exposure was associated with these outcomes for both boys and girls. Cognition, memory, and motor analyses indicated positive associations between both prenatal and postnatal Mn exposure for performance outcomes in boys, that is, improved performance as a function of Mn exposure; by contrast, girls tended to show null associations between either prenatal or postnatal Mn exposure and performance in these domains. For cognitive and memory measures, an interaction between prenatal Mn and prenatal lead levels was also detected. Children of mothers with above-median (≥0.8 μg/dL) prenatal lead levels demonstrated poorer performance in these domains as a function of increasing prenatal Mn exposure.
 
A manuscript by Mora, et al., regarding associations between prenatal and early postnatal Mn exposure and children’s behavior/attention, cognition, memory, and motor functioning at ages 7, 9, and/or 10½ years has been accepted pending minor revision by the journal Environment International.
 
As part of dissertation research, Gunier, et al., examined the relationship of Mn in dentine and CHAMACOS children’s performance on the Bayley Scales of Infant Development and found that postnatal Mn levels were associated with small decreases in MDI at 6-months and 12-months of age with stronger associations among girls for both MDI and PDI. In addition, girls whose mothers had lower hemoglobin levels experienced larger decreases in MDI and PDI associated with prenatal Mn levels than girls whose mothers had higher hemoglobin levels. This paper is being revised for publication in Environmental Research.
 
In preliminary analyses, we did not observe an association between hair Mn concentrations and 10.5 year IQ or behavior in models adjusted for child’s exact age, maternal education, poverty status, language of assessment and HOME score. We are currently preparing a manuscript for publication using the Mn hair analyses.
 
3. To determine whether prenatal and childhood exposure to DDT/E, PBDEs, and Mn are associated with timing of pubertal development in boys between age 9 and 13 years.
 
DDT/E and PBDEs: We are currently preparing a manuscript regarding prenatal and child age 9 PBDE, DDT/E, and hexachlorobenzene (HCB) exposure levels in association with timing of pubertal onset. Though these analyses will not be finalized until we have completed data collection at 12¾, we nonetheless have a significant body of longitudinal data on which to base initial analyses. Our analyses indicate statistically significant earlier onset of male puberty in association with each family of compounds investigated. We present results for CHAM1 boys, whose more accurate maternal pregnancy exposure measures showed statistically significant associations with puberty outcomes. In boys from the CHAM1 cohort, maternal prenatal PBDE concentrations were significantly associated with earlier onset of pubic hair development for ΣPBDEs, BDE-99, BDE-100, and BDE-153. BDE-47 concentrations were marginally associated with earlier development. Prenatal HCB concentrations were also associated with earlier pubic hair development. Prenatal concentrations of DDT and DDE were associated with earlier genital development, as was prenatal BDE-153. Boys' serum PBDE and organochlorine pesticide concentrations at 9 years were not associated with age of pubertal onset.
 
Our analysis also assesses associations between these chemicals and timing of pubertal onset in girls, for whom we gathered data under separate funding (Grant number NIH ES017054). In girls, PBDE concentrations were not associated with the onset of puberty for either breast or pubic hair development, although the non-significant results suggested later puberty. In the CHAM1 cohort, higher prenatal maternal PBDEs were associated with later menarche for ΣPBDEs, BDE-47, and BDE-99, and marginally associated for BDE-100 and BDE-153. For girls in both cohorts, prenatal DDE concentrations were associated with earlier menarche. Age 9 BDE-153 concentrations were associated with late menarche, with marginal associations for ΣPBDEs and BDE-99.
 
Mn: To date, we have only run preliminary analyses of prenatal and postnatal Mn exposure in association with pubertal onset. Among 103 boys with available exposure and outcome data, our preliminary analyses indicate a marginally significant association of prenatal Mn with later onset of genital development. Among girls (N = 113), higher postnatal (i.e., infancy) Mn exposure was associated with significantly earlier onset of pubic hair development.
 
4. To determine whether prenatal and childhood exposure to DDT/E, PBDEs, and Mn are associated with hormone levels in boys at age 12.
 
DDT/E and PBDEs: We are currently preparing a manuscript regarding prenatal PBDE, DDT/E, and polychlorinated biphenyls (PCB) exposure levels in association with luteinizing hormone (LH), testosterone (T), and follicle stimulating hormone (FSH) in boys at age 12. Concentrations of FSH, LH, and T were measured in first-morning blood samples collected from 229 boys at age 12. All hormones and exposures were log10-transformed for statistical analysis; exposures were lipid-adjusted as well. Linear regression models were adjusted for child age, BMI, cohort, gestational age at birth, smoking, and alcohol use. In utero exposure to certain PBDEs and PCBs but not DDT/E was associated with elevations in sex hormones suggestive of earlier onset of puberty. Specifically, BDE-153 was associated with significant increases in FSH, LH, and T. BDE-100 also was positively associated with LH, and total PCBs was positively associated with FSH. Analyses are complete and we expect to submit this manuscript by the end of the summer.
 
Mn: To date, we have only run preliminary analyses of prenatal and postnatal Mn exposure in association with hormones in boys. Among 78 boys included in these preliminary analyses, we observed no association between either prenatal or postnatal Mn exposure and LH, T, or FSH at age 12. These data have been presented at scientific conferences but given the small numbers of boys with Mn measured, we will likely not submit this as a separate manuscript.

Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children

Specific Aim 1. To measure Mn, PBDEs, and DDT/E in shed deciduous teeth. (Population: CHAMACOS children participating since birth.)

Mn: We have successfully developed a method for measuring Mn in human teeth by laser ablation ICP-mass spectrometry (LA/ICP/MS), including analysis of 307 teeth collected from the CHAMACOS cohort. Rather than calculate one estimate of cumulative exposure over the entire prenatal period, we have used a method to distinguish Mn exposure experienced in the 2nd trimester from that experienced in the 3rd trimester. We observed a significant association (rSpearman = 0.36, p = 0.001, n = 77) between Mn levels in the entire prenatally-formed dentine [as defined by 55Mn:43Ca area under the curve (AUC)] with floor dust Mn loading (μg Mn/m2 floor area) and a stronger relationship with Mn levels in dentine formed only in the second trimester (rSpearman = 0.40; p = 0.0005; n = 72), likely because dust samples were collected in the second trimester. We have also compared Mn levels in cord blood and mantle dentine. While there was no significant association of 55Mn:43Ca AUC of all prenatal sampling points with cord blood Mn (rSpearman = -0.01; p = 0.99), 55Mn:43Ca in the sampling point immediately adjacent to the neonatal line in each tooth showed a significant positive correlation with cord blood Mn (rSpearman = 0.70;  p = 0.003; n = 16). These findings were published in Environmental Science & Technology (Arora, et al., 2012) and the measurements were used in subsequent studies examining exposure and health outcomes (see below and Progress Report A).

PBDEs and DDT/E: As a pilot investigation, we assessed the feasibility of measuring persistent organic pollutants in deciduous teeth. Dr. Andreas Sjödin at the CDC in Atlanta attempted to measure PBDEs and DDT in anonymous deciduous teeth collected from dental patients demographically similar to the CHAMACOS cohort. Using whole tooth digestion, neither PBDEs nor DDT were detected. Additional anonymous deciduous teeth were obtained from a local clinic and Dr. Arora extracted the dentine from these teeth to determine if more sensitive analyses could be employed to measure PBDEs and organochlorine (OC) compounds including DDT. Initial results were not promising. Specifically, low detection frequencies for the typically prevalent congeners PBDE-47 and -99 and high concentrations of PBDE-183 for all samples suggested possible contamination with PBDE-183. One challenge in the interpretation of xenobiotic measurements in dentine is the likelihood that dentine tissue, which is vasculated, may be in equilibrium with child exposures when the teeth are shed and may not reflect prenatal exposures. Some compounds, such as metals, are incorporated into the chemical structure of the dentine, but many organic compounds are not. Additional research is needed to broadly screen for chemicals in dentine strata and validate measurements against maternal and child biomonitoring.

Specific Aim 2. To determine the relationship between Mn, PBDE, and DDT/E levels in teeth with other relevant biological measures.

For a subset of CHAMACOS participants, we conducted laboratory measurements of Mn in multiple biological samples, including 202 whole blood samples (maternal blood, cord blood, child’s blood), 128 urine samples (maternal at 26-week gestation and child at 24 months), and 62 teeth and examined the interrelationships of Mn levels in all matrices. Mn levels (Mn:Ca ratio) were higher in prenatal than postnatal dentine (geometric mean (GM) = 0.51 vs. 0.16, p<0.0001). Maternal blood Mn concentrations increased from 26 weeks gestation to delivery (GM = 14.6 to 20.7 μg/L, p = 0.001) and child blood Mn concentrations decreased from cord blood to 24-month blood samples (39.9 vs. 25.0 μg/L, p = 0.005).

Mn levels in tooth dentine during the 3rd trimester were positively correlated with Mn concentrations in cord blood (rs = 0.31), while there was a negative correlation between prenatal Mn levels in enamel and concentrations in maternal blood at 26-weeks’ gestation (rs = -0.36). We did not find any significant differences in Mn urine concentrations over time and did not observe significant correlations between Mn levels in teeth and urine, suggesting that urinary concentrations are not a useful measure of environmental Mn exposure.

We observed significantly higher (p < 0.05) levels of Mn in prenatal dentine, prenatal maternal blood, and 24-month urine from children if there was a farm worker living in the home during the corresponding time period compared to no farmworker living in the home. Prenatal Mn levels in dentine and cord blood were also correlated with Mn loading in prenatal house dust samples (rs = 0.27 and 0.29, respectively; p < 0.1). Tooth dentine and blood Mn concentrations had the strongest associations with potential sources of Mn exposure in the home. These findings were published in Environmental Science & Technology (Gunier, et al., 2014).

Specific Aim 3. To quantify the contribution of agricultural pesticide use to Mn levels in house dust, teeth, hair and child blood.

Mn in dust: We collected house dust samples from 378 CHAMACOS participant residences, with a second sample collected approximately nine months later from 90 of the residences. House dust samples were analyzed for Mn using inductively coupled plasma optical emission spectroscopy. Information from interviews, home inspections, and pesticide use reports was used to identify potential predictors of Mn dust concentrations and loadings. Mn was detectable in all dust samples. The median Mn concentration was 171 μg/g and median Mn loading was 1,910 μg/m2 at first visit. In multivariable models, Mn dust concentrations and loadings increased with the number of farmworkers in the home and the amount of agricultural Mn fungicides applied within three kilometers of the residence during the month prior to dust sample collection. Dust concentrations of Mn and other metals (lead, cadmium and chromium) were higher in residences located in the southern Salinas Valley compared to those located in other areas of the Salinas Valley. Dust loadings of Mn and other metals were also higher in residences located on Antioch Loam soil than other soil types, and in homes with poor or average housekeeping practices (Figure 1). Agricultural use of Mn-containing fungicides was associated with Mn dust concentrations and loadings in nearby residences and farmworker homes. Housekeeping practices and soil type at residence were also important factors related to dust metal concentrations and loadings. These findings were published in Science of the Total Environment (Gunier, et al., 2014).

Mn in teeth: We examined environmental and lifestyle factors associated with prenatal tooth dentine Mn concentrations for 207 CHAMACOS children.We found that storage of farmworkers’ shoes in the home, maternal farm work, agricultural use of Mn-containing fungicides within 3 km of the residence, residence built on Antioch Loam soil and Mn dust loading (μg/m2 of floor area) during pregnancy were associated with higher Mn levels in prenatal dentine (p < 0.05). Maternal smoking during pregnancy was inversely related to Mn levels in prenatal dentine (p < 0.01). Multivariable regression models explained 22 – 29% of the variability of Mn in prenatal dentine (Table 1). Our results suggest that Mn measured in prenatal dentine provides retrospective and time-specific levels of fetal exposure resulting from environmental and occupational sources. These findings were published in Environmental Science & Technology (Gunier, et al., 2013).

Mn in hair: In the absence of a validated methodology for the accurate determination of hair Mn without external contamination, we developed and validated a method to analyze Mn in hair which included thorough sample cleanup, showing in the process that prior published studies of hair Mn are likely erroneous (Eastman, et al., 2013). We have collected hair samples from 455 children (145 boys and 310 girls). Due to costs associated with the extensive cleanup procedure necessary to analyze the hair properly, we were only able to analyze hair from a subsample of children. Dr. Smith at UCSC has analyzed samples from 135 participants. The Mn hair concentrations in our cohort were similar to the only other published study using the same cleaning methodology, which focused on children exposed to Mn through proximity to a ferroalloy plant (Eastman, et al., 2013). In bivariate analyses, we found that Mn hair concentrations were related to location of the hair sample soil type at the child’s residence, location of the residence in the Southern portion of Monterey County and agricultural use of Mn fungicides within 3 km of the child’s residence during the 6 months prior to sample collection. Hair Mn concentrations were not related to demographic variables, the presence of agricultural workers in the home or the use of hair care products prior to sample collection. Location of hair sample, residence in Southern Monterey County and agricultural use of Mn fungicides near the child’s residence remained significant in multivariate models. In preliminary analyses, we did not observe an association between hair Mn concentrations and 10.5 year IQ or behavior in models adjusted for child’s exact age, maternal education, poverty status, language of assessment and HOME score. We are currently preparing a manuscript for publication on our Mn hair analyses.

Specific Aim 4. To identify population correlates of PBDEs and DDT/E exposure in 9-year-old boys.

CDC has analyzed CHAMACOS blood samples for PBDEs, DDT/E and PCBs in 412 mothers during pregnancy, 277 children at the 7-year visit, and 145 mothers and 552 children at the 9-year visit. The geometric means for these compounds decreased in the children from age seven to nine years. Assuming that at least in the case of PCB-153 and p,p’-DDE there has not been a meaningful decrease in dietary intake during the time period investigated, it is assumed that the decrease observed is mainly related to dilution from an increasing body mass with age. This hypothesis is supported by a significant correlation between percent weight increase and percent decreased serum concentration between seven and nine years of age. Dr. Andreas Sjödin is preparing a manuscript examining determinants of PBDE and DDT/E exposures in 9-year-olds. The statistical analysis for this paper is complete and includes comparison of the CHAMACOS serum concentration data with a published cohort of Texas children (Sjodin, et al., 2014). CHAMACOS participants had significantly higher exposures to PBDEs than children from Texas. Concentrations of PCB-153 were comparable in the CHAMACOS and Texas children while p,p’-DDE concentrations were higher in the primarily Mexican population of the CHAMACOS cohort.

Back-extrapolation of DDT/E and PBDEs: We evaluated three modeling approaches (physiologically-based pharmacokinetic modeling (PBPK), deletion substitution algorithms, and SuperLearner) to estimate maternal DDT/E and PBDE exposures during pregnancy when measurements were collected from the mothers 9 years after birth. To accomplish this, we used the models to predict serum levels measured at 26 weeks gestation in the pregnant mothers (n = 161) from levels measured in the mothers and the child when the child was 9. For each model, we assessed whether the nine-year maternal (n = 94) or child (n = 161) measurements alone, or levels in both mothers and children (n = 89) at age 9, predicted the levels in the mothers during pregnancy. Model performance was assessed using the root mean squared error (RMSE) and coefficient of determination (R2) of log10-transformed back-extrapolated versus measured levels. For all compounds and subsets, SuperLearner outperformed the other approaches with RMSEs and R2s ranging from 0.10-0.31 log10 ng/g and 0.58-0.97, respectively. Typically, model RMSEs were lower and R2s were higher for p,p’-DDT/E than PBDE congeners, and estimations using maternal levels (when their child was 9 years) were more accurate for back extrapolation to pregnancy levels than using child levels at 9 years. The PBPK model performed well but not as well as SuperLearner when back-extrapolating prenatal levels from maternal levels for compounds with longer half-lives such as p,p’-DDE and BDE-153 (RMSEs = 0.21 and 0.28 log10 ng/g and R2s= 0.88 and 0.57, respectively). Overall, our results demonstrate the ability to accurately back-extrapolate prenatal levels from maternal levels 9 years after delivery, with SuperLearner performing the best based on our fit criteria. These findings were published in Environmental Science & Technology (Verner, et al., 2015).

Project C: Epigenetics Project: Epigenetic Effects of DDT/E and PBDEs on Puberty(i.e., interaction). For both DDT/E and PBDEs, measured maternal pregnancy serum

1. To analyze global DNA methylation in newborn children by three different assays.
Previously we reported on a novel method of normalization of genome-wide site-specific methylation data obtained by 450K BeadChip arrays for birth cohort and other longitudinal population studies (Yousefi, et al., 2013). Another important methodological question we have addressed using the 450K data from the CHAMACOS cohort is the potential confounding in methylation studies by blood composition since methylation levels can differ among white blood cell types. One of the most commonly used methods to estimate cell composition in blood specimens assessed by 450K BeadChip is an algorithm known as the Houseman adjustment that is implemented by the Bioconductor package minfi. However, the algorithm is based on the methylation profiles of 6 Swedish men that may not be comparable to young children because the immune profiles in young children, especially newborns, are vastly different than those of adults. We estimated white blood cell type percentages by two methods, minfi and direct differential cell count (DCC), at two time points in childhood (birth and 12 years of age). We found that both minfi and DCC had similar trends as children aged, and neither count method differed by sex among newborns (p > 0.10) (Figure 2). However, minfi estimates did not correlate well with DCC in samples from newborns (ρ = -0.05 for granulocytes; ρ = -0.03 for lymphocytes). In older children, correlation improved substantially (ρ = 0.77 for granulocytes; ρ = 0.75 for lymphocytes), likely due to increasing similarity with minfi’s adult reference data as children aged. Our findings suggest that the minfi method may provide suitable estimates of white blood cell composition for samples from adults and older children, but may not be appropriate for EWAS involving newborns or young children. A manuscript on the estimation of blood cell heterogeneity in children for epigenome-wide studies has been provisionally accepted for publication by Environmental and Molecular Mutagenesis (Yousefi et al., 2015).
 

All proposed analyses of global methylation (Alu, LINE-1) were completed in 246 newborns and 246 9-year old children who had blood samples available for DNA isolations. These samples, which had been previously collected and banked in the CHAMACOS study biorepository, provided a unique opportunity to explore epigenetic effects of prenatal exposure and of sex and age from birth to near the onset of puberty. We did not observe significant correlations between the two different assays used for analysis of global methylation, most likely because they characterize complementary parts of the epigenome and thus together assure its more complete evaluation. A paper on global repeats (Alu and LINE-1) has been published (Huen, et al., 2014).

2.To determine ontogenetic changes in global DNA methylation in blood of children between birth and 12 years.

To determine the longitudinal changes in repetitive element DNA methylation (Alu and LINE-1), pyrosequencing assays were performed in >600 blood samples collected from CHAMACOS children at delivery and ages 2, 5, 7 and 9. We used generalized estimating equations (GEE) to assess differences in LINE-1 and Alu methylation by age while accounting for within subject correlations. LINE-1 global DNA methylation was found to decrease 0.3% per month increase in child age (95% CI: 0.2 – 0.6%). A similar decreasing trend was found for Alu methylation but this association was not statistically significant (p = 0.18). Although these differences are not large, previous studies have shown that even small differences in methylation can be biologically meaningful. Comparison of the data for boys and girls at birth and 9 years of age has been published (Huen, et al., 2014). We also are finalizing a detailed age-related comparison of epigenetic marks by the 450K assay for submission to PLoS ONE (Yousefi, et al.).

3. To investigate the relationship of in utero and 9-year-old blood concentrations of DDT/E and PBDEs with global DNA methylation.

We observed a consistent trend of lower Alu and LINE-1 methylation in fetal blood with higher prenatal DDT/E exposure, particularly after adjusting for cell type composition (Figure 3). Prenatal PBDE exposure was not significantly associated with Alu methylation. There was a trend of lower levels of LINE-1 methylation with prenatal PBDE exposures but this relationship did not reach statistical significance. Since mothers were exposed to both PBDEs and DDT/E during pregnancy, we also examined the potential association of co-exposure to these chemicals with levels of Alu and LINE-1 methylation. When we included both classes of chemicals in the same model, we found a significant interaction between sum of PBDEs and o,p’-DDT and p,p’-DDE (p = 0.12 and 0.06, respectively) on LINE-1 but not Alu methylation in fetal cord blood. Similar but non-significant interaction was seen for the sum of PBDE congeners with p,p’-DDT. These data suggest that the significant association of prenatal PBDE exposure with LINE-1 methylation in cord blood was only observed after considering exposure to both classes of compounds (PBDEs and DDT/E). Our data demonstrate that prenatal exposure to POPs may be linked to hypomethylation in fetal blood and that accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies. These results were recently published (Huen, et al., 2014).

4.To determine whether global methylation is associated with onset of puberty and hormonal changes.

This Center grant includes the follow-up of boys only. However, we received an NIEHS grant (ES017054) to assess pubertal onset in the girls in the CHAMACOS cohort. Although we found no significant relationship between pubertal onset as determined by Tanner staging (testicular volume or pubic hair) and either LINE-1 or Alu measures in boys, we observed a non-significantly higher odds of girls entering puberty by age 9 years (Tanner stage > B1) with higher LINE-1 methylation (but not Alu methylation) in cord blood. Similarly, we also found a suggestive trend of an increased odds of having entered puberty by 9 years (Tanner stage > B1) in girls with higher Alu methylation in 9-year old blood.

We also measured concentrations of luteinizing hormone (LH), testosterone (T), and follicle stimulating hormone (FSH) in first-morning serum samples collected from the boys at 12 years that demonstrate that hormone levels in CHAM1 boys were comparable to the normal reference ranges. We found a positive albeit non-significant relationship between Alu methylation in cord blood and levels of T in boys 12 years later. In addition, we observed a significant positive relationship between LINE-1 and ln LH. We are currently finalizing a manuscript regarding the relationship of LINE-1 and Alu repetitive element methylation with onset of puberty (boys and girls) and hormonal levels (boys only) in CHAM1 children.

5. To examine site-specific methylation in relation to age, sex, exposure to DDT/E and PBDEs and puberty onset.

We observed that ~3% of CpG sites interrogated by the 450K BeadChip in umbilical cord blood specimens were differentially methylated between girls and boys at birth (FDR P<0.05), after adjusting for cell composition. Of those CpGs, 3,031 were located on autosomes, and 82.9% of those were hypermethylated in girls compared to boys. Beyond individual CpGs, we found 3,604 sex-associated differentially methylated regions (DMRs) where the majority (75.8%) had higher methylation in girls. Using pathway analysis, we found that sex-associated autosomal CpGs were significantly enriched for gene ontology terms related to nervous system development and behavior. Among hits in our study, 35.9% had been previously reported as sex-associated CpG sites in other published studies. Further, for almost all replicated hits, the direction of the association with methylation was concordant with previous studies. Although there is a comprehensive meta-analysis of 76 studies using 27K site-specific methylation data, no such study has been published using the more comprehensive 450K assay. Ours is the first to look at differential methylation over regions of CpG sites and adjusting for potential confounding by blood cell composition. We recently submitted a manuscript on the associations of sex with site-specific methylation measured by 450K BeadChip assay (Yousefi, et al., BMC Genomics).

We conducted a detailed analysis of the relationship of epigenetic data with the gene expression and genetic polymorphisms, that was recently published (Dave, et al., 2015), providing additional “proof of principal” validation to our epigenetic findings.

We previously reported associations of methylation at several CpG sites in multiple genes with in utero exposure to PBDEs. As a confirmation step, we are now performing real-time quantitative PCR (qRT-PCR) for the top 6 hits identified by the 450K methylation analysis. Total RNA was isolated from CHAMACOS newborns using mirVana miRNA Isolation Kit (Life Technologies, Waltham, MA, USA). Two different methods were used, the Applied Biosystems® (Applied Biosystems Life Technologies, Grand Island, NY, USA) TaqMan® RNA-to-Ct™ 1-Step Kit and QuantiTect SYBR Green PCR Kit (Qiagen, Valencia, CA). The expression of six genes (ITSN1, CRYZL1, HSPA2, FGF3, KCNMB4 and CREB3L1) and 2 housekeeping genes (ACTB and TBP) were measured in 94 newborns in June 2015. To complete the validation efforts, a detailed analysis of the relationship of expression with CpG-sites methylation in the same genes will be performed during the next year.

Core 3: Community Outreach and Translation Core (COTC)

1. To disseminate Center research findings to study participants, the Salinas Valley community, and other stakeholders.

Newsletter: We recently disseminated the 2015 CHAMACOS newsletter, La Semilla, to participants. The newsletter is in Spanish and English and is written at a level accessible to low-literacy readers. Our intent is to provide a means for parents and children to discuss the newsletter content. (Parents mostly speak Spanish and children mostly speak English). This issue of La Semilla featured a letter from Dr. Eskenazi, information on recent research findings, and an announcement recruiting new members to our Youth Community Council.

Electronic Newsletter: We sent out two e-newsletters from June 2014-May 2015 to over 900 subscribers. The first newsletter was sent out in December before the holiday break to express our appreciation for the many research participants and collaborators who are essential to the success of our projects. The second newsletter was sent out in March 2015 to inform our subscribers of new changes to California’s Healthy Schools Act (HSA) and of a new resource developed by CERCH to help pest management professionals abide by the HSA and incorporate Integrated Pest Management Principles in their work.

Dissemination to larger community and targeted groups: We continued our efforts to share Center research findings with the Salinas Valley community through targeted meetings with community groups and key stakeholders, participation in community events, and media interviews about our work. We held 115 meetings with a wide range of groups, most of them in the Salinas Valley, to discuss recent Center findings and other environmental health issues. Center staff also attended several local health-related events such as health fairs and town hall meetings to discuss the Center’s research. Through these efforts we made contact with 1,291 men, 2,883 women, and 1,405 children for a total of 5,579 people from June 1, 2014, to May 31, 2015.

Dissemination to the scientific community: A list of pertinent scientific publications is listed for each Core in its respective progress report, along with a list of presentations at professional and scientific meetings. We have also presented our findings at local meetings and universities. As a result of knowledge gained from this Center, Dr. Eskenazi has continued to provide consultation across the world in pesticide research and in the conduct of birth cohort studies – in Chile, Israel, Bangladesh, South Africa, Costa Rica, Spain, Ecuador, New Zealand – this year alone.

Website: On our website, www.cerch.org, we have developed an online resource center where specific audience groups can access information on environmental health hazards with tips on ways to protect themselves. These audiences include adults, families, parents of young children, teens, community groups, and health professionals. As new resources are developed by our center, they are posted to the ORC to facilitate rapid dissemination to these audience groups. From June 1, 2014, to May 31, 2015, www.cerch.org had 19,989 unduplicated visitors for a total of 49,101 page views.

2. To increase awareness about children’s environmental health among low-income Latino communities, clinicians, and service providers through widespread dissemination of innovative outreach and educational programs.

Outreach to childcare providers: We continue to provide education and outreach addressing environmental quality in child-care settings in the Salinas Valley and throughout California. In the Salinas Valley region, we collaborated with the Migrant Education Office in Watsonville, CA to conduct 3 trainings for child-care providers, reaching 53 directors and teachers. We also completed our California Department of Pesticide Regulation (DPR)-funded project to develop an integrated pesticide management (IPM) training course for licensed pest management professionals serving child care facilities and schools in California. This course provides required continuing education units for pest management professionals and involved close collaboration with child care professionals, the UC Cooperative Extension IPM program, DPR, and the Pest Control Operators of California, the lead trade organization for pest management professionals. A total of 647 pest management professionals completed the course, including 511 during nine in-person trainings and 136 using our online version. The online version will be operated permanently by the University of California (UC) IPM program and will become a long-term resource for California pest management professionals. Dr. Bradman also participates on the Science Advisory Board for the Children’s Environmental Health Network Eco Healthy Child Care (EHCC) program and has provided extensive review of their educational materials.

Outreach to social service organizations: Center staff continues to provide presentations to community groups in Monterey County on the following topics: Preventing Pesticide Exposure, CHAMACOS Findings Overview, Healthy Homes, Heat Illness Prevention, and Environmental Quality in Early Childcare Environments. Through these trainings and presentations we have reached 3,158 individuals in the Salinas Valley this year.

Outreach to farmworkers: The greatest educational need we have identified in our community outreach work is accessible, quality training for farmworkers about the hazards of pesticide exposure and means to prevent exposure. To address this need, Clinica de Salud del Valle de Salinas (our main community partner) and California Department of Education, Migrant Education Program have worked to obtain an EPA Environmental Justice Small Grant. This grant, entitled “Proyecto La Semilla: Pesticide Safety Leadership Training for Farmworker Parents”, will allow our team’s primary health educator to train parent leaders in eight agricultural counties throughout California on how to educate other parents on pesticide safety using strategies and teaching materials developed and tested through our Center (i.e., a train-the-trainer program).

Outreach to growers and the agricultural industry and regulators: During the last year, we have continued to actively engage growers and the agricultural industry in the Salinas Valley, throughout California, and beyond. The Agricultural Commissioner, the Central Coast Grower Shipper Association, and the Monterey County Farm Bureau are active members of the CHAMACOS Community Advisory Board (CAB). We have also formed an Agricultural Council that includes the CAB industry representatives as well as the California Strawberry Commission and Jacobs Farms, an organic producer, as well as a Farmworker Council comprised of farmworker leaders. Last summer, we also met with Mr. Tom Nunes, President of the Nunes Company, one of the largest growers in the Salinas Valley, and a representative of the company will be participating in future Agriculture Council meetings. Due to limited funds, we have not met in-person as a group with the CAB or Councils this year but we have continued to communicate with the CAB and Councils at least on a semi-annual basis, including by phone and email. We have continued to share all methods and results and to provide pre-publication abstracts and draft manuscripts for review and input.

We also continue to meet regularly with those involved with pesticide regulation such as the Agricultural Commissioner and the California Department of Pesticide Regulation (DPR). We have had at least a dozen calls/meetings with the Monterey County Agricultural Commissioner this year and Drs. Bradman and Eskenazi gave a “grand rounds” presentation in Sacramento for DPR (January 2015). In addition, Dr. Eskenazi has provided review to DPR as a key member of the National Research Council of the National Academies’ Committee to Review California’s Risk Assessment for Pesticides, which required meetings with DPR and EPA officials around pesticide regulation in the United States and, specifically, in California. This review was requested by the DPR in response to a California Department of Public Health (CDPH) report examining pesticide use near schools released in April 2014. This report received tremendous community, policy, and press attention in California and raised concerns about exposures to children. Dr. Bradman provided external peer review of the CDPH report and has been contacted on a regular basis by press and community members to comment on the report.

Dr. Bradman also participates on the Board of Trustees for The Organic Center, a nonprofit organization addressing scientific concerns about organic agriculture and food. In April 2015, Dr. Bradman presented our CHAMACOS research at the Organic Trade Organization Policy Conference, including findings that sulfur use was associated with poorer lung function among CHAMACOS children. Because sulfur is heavily used as a fungicide in both conventional and organic agriculture, these findings will be of interest to both sectors. Finally, Dr. Bradman, Harley, and Eskenazi were funded through the UC Berkeley-Chile Seed Grant program to travel to Chile, and meet with agricultural officials, researchers, and health officials. Dr. Bradman toured greenhouse operations with growers and reviewed strategies to reduce worker pesticide exposures, and presented CHAMACOS research findings to a large audience at the Catholic University in Talca, including growers and agricultural officials. These meetings and presentations were widely covered in the local press.

3. To build the capacity of Salinas Valley youth to promote healthy environmental policies in their community.

The goal of the Youth Community Council (YCC) is to build youth capacity in environmental health and to engage youth in promoting healthy environmental policies in Salinas. During this no-cost extension year, we have successfully garnered support of the YCC through funding from the California Breast Cancer Research Program and the Monterey County Health Department. The HERMOSA project (Harley, PI, California Breast Cancer Research Program) was initiated in 2012 to study the levels of exposure of Latina youth to endocrine disrupting chemicals (EDC) used in cosmetics and personal care products. Over the summer of 2013, members of the YCC and research staff conducted an intervention study to investigate whether using low-chemical cosmetics could lower EDCs in these girls. The study was conducted with community-based participatory approaches to involve youth members in each phase of the research project from the development of the study, to conducting the study, to disseminating results. In Summer 2014, the YCC members disseminated the results of the study to participants and community members. They presented on radio, television, at health fairs, and developed content for the Center’s website (www.cerch.org/hermosastudy). The YCC members created health education materials for their peers about chemicals in make-up and distributed this material at various meetings. They also developed recipes for Do-it-yourself remedies for personal care products, such as using egg whites to stiffen your hair instead of mouse or gels with chemicals. On July 26, 2014, the youth put on a community forum for participants of the HERMOSA study where they gave overall results of the study as well as individual results to the participants. Through this process youth members had to become well-versed in the environmental health topic and be confident enough to share this information with their peers. In addition, members of the YCC visited the State capital to educate lawmakers about the results of their study (see below).

In addition to their work on the walkability report (in previous Progress Reports) and the HERMOSA Study, YCC members have worked on other projects with the Monterey County Health Department. This spring they initiated the Healthy Retail Project, which is a direct development of the YCC’s Photovoice project conducted in Summer 2011. The Photovoice project highlighted the lack of access to healthy food in Salinas corner stores as well as the high rates of obesity in the population. We have been funded by the Monterey County Health Department to survey local store-owners and customers in Salinas about their willingness to provide and purchase healthier foods. This grant provides stipends for YCC members to collect these data and to prepare a report for Monterey County, under our supervision. Our projects that have engaged youth in the research have become an effective model to train future researchers in the community and provide meaningful summer employment for low-income high school students. In addition, we write letters of recommendation for our YCC members as they apply to universities and we help to review their applications. This year, four members of our YCC have been accepted to the University of California, and most others will be attending colleges – as the first generation in their families to attend.

4. To educate policy makers at the local, state, and national levels about Center research findings and children’s environmental health priorities.

Our research was shared at the national level when our Center provided comments to the proposed changes to the Worker Protection Standard (WPS). The WPS was introduced in 1992 and was designed to protect farmworkers from pesticides. New changes in the WPS have been proposed to make the regulation more effective. We submitted comments to the EPA that included CHAMACOS research findings. Insights from exposure and health outcome studies by CHAMACOS can help EPA staff develop regulations that will prevent exposure to pesticides and protect the health of farmworkers and their families.

In Spring 2015, three YCC representatives and research staff visited the capital to educate policymakers about the importance of environmental research and about the HERMOSA Project, how it was conducted, and what the study found. The group met with the staff of four state legislators and of the governor of California. The YCC representatives described our work at the Center and the HERMOSA Study and expressed their concern about chemicals in personal care products. Specifically, they met with Assembly member Lorena Gonzalez as well as with staffers from the offices of Assembly members Tony Thurmond, David Chiu, Lorena Gonzalez and Senator Mark Leno. They also met with two staffers from the Governor's office (Martha Guzman-Aceves, Deputy Legislative Secretary, Environment and Donna Campbell, Deputy Legislative Secretary, Health and Human Services).

Future Activities:

Project A: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior & Puberty

In the next 4 months, we will complete 12¾ visits as well as data entry and cleaning of Tanner data collected from the final ~100 boys seen at this visit, so that we can finalize puberty analyses that rely on these data. Over the next year, we anticipate publishing all manuscripts noted above that are currently in preparation or under revision, and preparing a manuscript related to Mn and pubertal development.

Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children

In the next year, we will complete analyses of correlates of PBDE and DDT/E exposure in children. We also will complete analyses of determinants of Mn concentrations in hair at 10.5 years of age. We expect to submit at least two manuscripts this year on correlates of PBDEs and DDT/E in children and determinants of Mn concentrations in hair.

Project C: Epigenetics Project: Epigenetic Effects of DDT/E and PBDEs on Puberty

In the next year, we plan to finalize data analysis of qPCR expression experiments performed for validation of hits identified by 450K array. We have already completed all the data analyses and will submit during next year manuscripts on: (a) 450K methylation and PBDE exposure; (b) 450K methylation and age; and (c) pubertal onset and hormone levels with global methylation

Core 3: Community Outreach and Translation Core (COTC)

All of the primary activities described above will continue in the next year. We will continue active engagement with our Youth Community Council including ongoing activities as part of the Healthy Retail and new Peer-to Peer Study. We will continue targeted outreach to community groups, and respond to invitations for presentations. Targeted outreach will focus on farmworkers, teachers, and child care providers. We will maintain ongoing contact with our Community Advisory Board and Agriculture and Farmworker Councils.


Journal Articles: 137 Displayed | Download in RIS Format

Other center views: All 666 publications 138 publications in selected types All 137 journal articles
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Journal Article Alkon A, Boyce WT, Davis NV, Eskenazi B. Developmental changes in autonomic nervous system resting and reactivity measures in Latino children from 6 to 60 months of age. Journal of Developmental and Behavioral Pediatrics 2011;32(9):668-677. R834513 (2012)
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  • Journal Article Alkon A, Boyce WT, Tran L, Harley KG, Neuhaus J, Eskenazi B. Prenatal adversities and Latino children's autonomic nervous system reactivity trajectories from 6 months to 5 years of age. PLoS One 2014;9(1):e86283. R834513 (2012)
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  • Journal Article Alkon A, Harley KG, Neilands TB, Tambellini K, Lustig RH, Boyce WT, Eskenazi B. Latino children's body mass index at 2-3.5 years predicts sympathetic nervous system activity at 5 years. Childhood Obesity 2014;10(3):214-224. R834513 (2012)
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  • Journal Article Arora M, Bradman A, Austin C, Vedar M, Holland N, Eskenazi B, Smith D. Determining fetal manganese exposure from mantle dentine of deciduous teeth. Environmental Science & Technology 2012;46(9):5118-5125. R834513 (Final)
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  • Journal Article Arora M, Bradman A, Austin C, Vedar M, Holland N, Eskenazi B, Smith DR. Determining fetal manganese exposure from mantle dentine of deciduous teeth. Environmental Science & Technology 2012;46(9):5118-5125. R834513 (2010)
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  • Journal Article Audelo J, Kogut K, Harley KG, Rosas LG, Stein L, Eskenazi B. Maternal depression and childhood overweight in the CHAMACOS Study of Mexican-American children. Maternal and Child Health Journal 2016;20(7):1405-1414. R834513 (2014)
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  • Journal Article AugsJoost B, Jerman P, Deardorff J, Harley K, Constantine NA. Factors associated with parent support for condom education and availability. Health Education & Behavior 2014;41(2):207-215. R834513 (2014)
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  • Journal Article Austin C, Smith TM, Bradman A, Hinde K, Joannes-Boyau R, Bishop D, Hare DJ, Doble P, Eskenazi B, Arora M. Barium distributions in teeth reveal early-life dietary transitions in primates. Nature 2013;498(7453):216-219. R834513 (2013)
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  • Journal Article Beamer PI, Canales RA, Bradman A, Leckie JO. Farmworker children’s residential non-dietary exposure estimates from micro-level activity time series. Environment International 2009;35(8):1202-1209. R834513 (2010)
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  • Journal Article Beamer PI, Canales RA, Ferguson AC, Leckie JO, Bradman A. Relative pesticide and exposure route contribution to aggregate and cumulative dose in young farmworker children. International Journal of Environmental Research and Public Health 2012;9(1):73-96. R834513 (2013)
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  • Journal Article Beamer P, Canales RA, Leckie JO. Developing probability distributions for transfer efficiencies for dermal exposure. Journal of Exposure Science and Environmental Epidemiology 2009;19(3):274-283. R834513 (2010)
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  • Journal Article Bouchard MF, Chevrier J, Harley KG, Kogut K, Vedar M, Calderon N, Trujillo C, Johnson C, Bradman A, Barr DB, Eskenazi B. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environmental Health Perspectives 2011;119(8):1189-1195. R834513 (2010)
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  • Journal Article Bradman A, Fenster L, Sjodin A, Jones RS, Patterson Jr DG, Eskenazi B. Polybrominated diphenyl ether levels in the blood of pregnant women living in an agricultural community in California. Environmental Health Perspectives 2007;115(1):71-74. R834513 (2010)
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  • Journal Article Bradman A, Castorina R, Barr DB, Chevrier J, Harnly ME, Eisen EA, McKone TE, Harley K, Holland N, Eskenazi B. Determinants of organophosphorus pesticide urinary metabolite levels in young children living in an agricultural community. International Journal of Environmental Research and Public Health 2011;8(4):1061-1083. R834513 (2010)
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  • Journal Article Bradman A, Castorina R, Sjodin A, Fenster L, Jones RS, Harley KG, Chevrier J, Holland NT, Eskenazi B. Factors associated with serum polybrominated diphenyl ether (PBDE) levels among school-age children in the CHAMACOS cohort. Environmental Science & Technology 2012;46(13):7373-7381. R834513 (2012)
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  • Journal Article Bradman A, Kogut K, Eisen EA, Jewell NP, Quiros-Alcala L, Castorina R, Chevrier J, Holland NT, Barr DB, Kavanagh-Baird G, Eskenazi B. Variability of organophosphorous pesticide metabolite levels in spot and 24-hr urine samples collected from young children during 1 week. Environmental Health Perspectives 2013;121(1):118-124. R834513 (2011)
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  • Journal Article Bradman A, Castorina R, Gaspar F, Nishioka M, Colon M, Weathers W, Egeghy PP, Maddalena R, Williams J, Jenkins PL, McKone TE. Flame retardant exposures in California early childhood education environments. Chemosphere 2014;116:61-66. R834513 (2014)
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  • Journal Article Bradman A, Quiros-Alcala L, Castorina R, Schall RA, Camacho J, Holland NT, Barr DB, Eskenazi B. Effect of organic diet intervention on pesticide exposures in young children living in low-income urban and agricultural communities. Environmental Health Perspectives 2015;123(10):1086-1093. R834513 (2014)
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  • Journal Article Castorina R, Bradman A, Fenster L, Barr DB, Bravo R, Vedar MG, Harnly ME, McKone TE, Eisen EA, Eskenazi B. Comparison of current-use pesticide and other toxicant urinary metabolite levels among pregnant women in the CHAMACOS cohort and NHANES. Environmental Health Perspectives 2010;118(6):856-863. R834513 (2010)
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  • Journal Article Castorina R, Bradman A, Sjodin A, Fenster L, Jones RS, Harley KG, Eisen EA, Eskenazi B. Determinants of serum polybrominated diphenyl ether (PBDE) levels among pregnant women in the CHAMACOS cohort. Environmental Science & Technology 2011;45(15):6553-6560. R834513 (2010)
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  • Journal Article Castorina R, Bradman A, Stapleton HM, Butt C, Avery D, Harley KG, Gunier RB, Holland N, Eskenazi B. Current-use flame retardants: maternal exposure and neurodevelopment in children of the CHAMACOS cohort. Chemosphere 2017;189:574-580. R834513 (Final)
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  • Journal Article Castorina R, Butt C, Stapleton HM, Avery D, Harley KG, Holland N, Eskenazi B, Bradman A. Flame retardants and their metabolites in the homes and urine of pregnant women residing in California (the CHAMACOS cohort). Chemosphere 2017;179:159-166. R834513 (Final)
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  • Journal Article Chadwick LH, Sawa A, Yang IV, Baccarelli A, Breakefield XO, Deng H-W, Dolinoy DC, Fallin MD, Holland NT, Houseman EA, Lomvardas S, Rao M, Satterlee JS, Tyson FL, Vijayanand P, Greally JM. New insights and updated guidelines for epigenome-wide association studies. Neuroepigenetics 2015;1:14-19. R834513 (2014)
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  • Journal Article Chevrier J, Harley KG, Bradman A, Gharbi M, Sjodin A, Eskenazi B. Polybrominated diphenyl ether (PBDE) flame retardants and thyroid hormone during pregnancy. Environmental Health Perspectives 2010;118(10):1444-1449. R834513 (2010)
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  • Journal Article Chevrier J, Harley KG, Bradman A, Sjodin A, Eskenazi B. Prenatal exposure to polybrominated diphenyl ether flame retardants and neonatal thyroid-stimulating hormone levels in the CHAMACOS study. American Journal of Epidemiology 2011;174(10):1166-1174. R834513 (2010)
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  • Journal Article Chevrier J, Harley KG, Kogut K, Holland N, Johnson C, Eskenazi B. Maternal thyroid function during the second half of pregnancy and child neurodevelopment at 6, 12, 24, and 60 months of age. Journal of Thyroid Research 2011;2011:426427 (13 pp.). R834513 (2011)
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  • Journal Article Chevrier J, Gunier RB, Bradman A, Holland NT, Calafat AM, Eskenazi B, Harley KG. Maternal urinary bisphenol A during pregnancy and maternal and neonatal thyroid function in the CHAMACOS study. Environmental Health Perspectives 2013;121(1):138-144. R834513 (2012)
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  • Journal Article Chevrier J, Warner M, Gunier RB, Brambilla P, Eskenazi B, Mocarelli P. Serum dioxin concentrations and thyroid hormone levels in the Seveso Women’s Health Study. American Journal of Epidemiology 2014;180(5):490-498. R834513 (2014)
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  • Journal Article Chopra V, Harley K, Lahiff M, Eskenazi B. Association between phthalates and attention deficit disorder and learning disability in U.S. children, 6-15 years. Environmental Research 2014;128:64-69. R834513 (2014)
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  • Journal Article Coker E, Gunier R, Bradman A, Harley K, Kogut K, Molitor J, Eskenazi B. Association between Pesticide Profiles Used on Agricultural Fields near Maternal Residences during Pregnancy and IQ at Age 7 Years. International Journal of Environmental Research and Public Health 2017;14(5):506 (20 pp.). R834513 (Final)
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  • Journal Article Dannemiller KC, Mendell MJ, Macher JM, Kumagai K, Bradman A, Holland N, Harley K, Eskenazi B, Peccia J. Next-generation DNA sequencing reveals that low fungal diversity in house dust is associated with childhood asthma development. Indoor Air 2014;24(3):236-247. R834513 (2014)
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  • Journal Article Dave V, Yousefi P, Huen K, Volberg V, Holland N. Relationship between expression and methylation of obesity-related genes in children. Mutagenesis 2015;30(3):411-420. R834513 (2013)
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  • Journal Article Dave V, Street K, Francis S, Bradman A, Riley L, Eskenazi B, Holland N. Bacterial microbiome of breast milk and child saliva from low-income Mexican-American women and children. Pediatric Research 2016;79(6):846-854. R834513 (Final)
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  • Journal Article Duramad P, Holland NT. Biomarkers of immunotoxicity for environmental and public health research. International Journal of Environmental Research and Public Health 2011;8(5):1388-1401. R834513 (2010)
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  • Journal Article Eastman RR, Jursa TP, Benedetti C, Lucchini RG, Smith DR. Hair as a biomarker of environmental manganese exposure. Environmental Science & Technology 2013;47(3):1629-1637. R834513 (2012)
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  • Journal Article Ehrlich SF, Rosas LG, Ferrara A, King JC, Abrams B, Harley KG, Hedderson MM, Eskenazi B. Pregnancy glucose levels in women without diabetes or gestational diabetes and childhood cardiometabolic risk at 7 years of age. Journal of Pediatrics 2012;161(6):1016-1021. R834513 (2012)
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  • Journal Article Ehrlich SF, Rosas LG, Ferrara A, King JC, Abrams B, Harley KG, Hedderson MM, Eskenazi B. Pregnancy glycemia in Mexican-American women without diabetes or gestational diabetes and programming for childhood obesity. American Journal of Epidemiology 2013;177(8):768-775. R834513 (2012)
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  • Journal Article Engel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, Barr DB, Yolton K, Vedar MG, Xu Y, Hornung RW, Wetmur JG, Chen J, Holland NT, Perera FP, Whyatt RM, Lanphear BP, Eskenazi B. Prenatal organophosphorus pesticide exposure and child neurodevelopment at 24 months: an analysis of four birth cohorts. Environmental Health Perspectives 2016;124(6):822-830. R834513 (2014)
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  • Journal Article Erkin-Cakmak A, Harley KG, Chevrier J, Bradman A, Kogut K, Huen K, Eskenazi B. In utero and childhood polybrominated diphenyl ether exposures and body mass at age 7 years: the CHAMACOS Study. Environmental Health Perspectives 2015;123(6):636-642. R834513 (2015)
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  • Journal Article Eskenazi B, Huen K, Marks A, Harley KG, Bradman A, Barr DB, Holland N. PON1 and neurodevelopment in children from the CHAMACOS study exposed to organophosphate pesticides in utero. Environmental Health Perspectives 2010;118(12):1775-1781. R834513 (2010)
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  • Journal Article Eskenazi B, Fenster L, Castorina R, Marks AR, Sjodin A, Rosas LG, Holland N, Guerra AG, Lopez-Carrillo L, Bradman A. A comparison of PBDE serum concentrations in Mexican and Mexican-American children living in California. Environmental Health Perspectives 2011;119(10):1442-1448. R834513 (2010)
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  • Journal Article Eskenazi B, Chevrier J, Rauch SA, Kogut K, Harley KG, Johnson C, Trujillo C, Sjodin A, Bradman A. In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study. Environmental Health Perspectives 2013;121(2):257-262. R834513 (2012)
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  • Journal Article Eskenazi B, Bradman A, Finkton D, Purwar M, Noble JA, Pang R, Burnham O, Cheikh Ismail L, Farhi F, Barros FC, Lambert A, Papageorghiou AT, Carvalho M, Jaffer YA, Bertino E, Gravett MG, Altman DG, Ohuma EO, Kennedy SH, Bhutta ZA, Villar J, International Fetal and Newborn Growth Consortium for the 21st Century. A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21st Project. BJOG: An International Journal of Obstetrics & Gynaecology 2013;120(Suppl 2):129-138. R834513 (2014)
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  • Journal Article Eskenazi B, Warner M, Sirtori M, Fuerst T, Rauch SA, Brambilla P, Mocarelli P, Rubinacci A. Serum dioxin concentrations and bone density and strucure in the Seveso Women’s Health Study. Environmental Health Perspectives 2014;122(1):51-57. R834513 (2014)
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  • Journal Article Eskenazi B, Quiros-Alcala L, Lipsitt JM, Wu LD, Kruger P, Ntimbane T, Nawn JB, Bornman R, Seto E. mSpray: a mobile phone technology to improve malaria control efforts and monitor human exposure to malaria control pesticides in Limpopo, South Africa. Environment International 2014;68:219-226. R834513 (2014)
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  • Journal Article Eskenazi B, Kogut K, Huen K, Harley KG, Bouchard M, Bradman A, Boyd-Barr D, Johnson C, Holland N. Organophosphate pesticide exposure, PON1, and neurodevelopment in school-age children from the CHAMACOS study. Environmental Research 2014;134:149-157. R834513 (2014)
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  • Journal Article Eskenazi B, Rauch SA, Tenerelli R, Huen K, Holland NT, Lustig RH, Kogut K, Bradman A, Sjödin A, Harley KG. In utero and childhood DDT, DDE, PBDE and PCBs exposure and sex hormones in adolescent boys: the CHAMACOS study. International Journal of Hygiene and Environmental Health 2017;220(2 Pt B):364-372. R834513 (Final)
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  • Journal Article Gaspar FW, Castorina R, Maddalena RL, Nishioka MG, McKone TE, Bradman A. Phthalate exposure and risk assessment in California child care facilities. Environmental Science & Technology 2014;48(13):7593-7601. R834513 (2014)
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  • Journal Article Gaspar FW, Harley KG, Kogut K, Chevrier J, Mora AM, Sjodin A, Eskenazi B. Prenatal DDT and DDE exposure and child IQ in the CHAMACOS cohort. Environment International 2015;85:206-212. R834513 (2014)
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  • Journal Article Gemmill A, Gunier RB, Bradman A, Eskenazi B, Harley KG. Residential proximity to methyl bromide use and birth outcomes in an agricultural population in California. Environmental Health Perspectives 2013;121(6):737-743. R834513 (2013)
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  • Journal Article Gomez N, Guendelman S, Harley KG, Gomez SL. Nativity and neighborhood characteristics and cervical cancer stage at diagnosis and survival outcomes among Hispanic women in California. American Journal of Public Health 2015;105(3):538-545. R834513 (Final)
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  • Journal Article Guerrero J, Madrigal DS, Minkler M. What is…?: a research ethics Jeopardy™ game to help community partners understand human subjects protections and their importance. Progress in Community Health Partnerships: Research, Education, and Action 2014;8(3):405-411. R834513 (2014)
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  • Journal Article Gunier RB, Bradman A, Jerrett M, Smith DR, Harley KG, Austin C, Vedar M, Arora M, Eskenazi B. Determinants of manganese in prenatal dentin of shed teeth from CHAMACOS children living in an agricultural community. Environmental Science & Technology 2013;47(19):11249-11257. R834513 (2013)
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  • Journal Article Gunier RB, Mora AM, Smith D, Arora M, Austin C, Eskenazi B, Bradman A. Biomarkers of manganese exposure in pregnant women and children living in an agricultural community in California. Environmental Science & Technology 2014;48(24):14695-14702. R834513 (2011)
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  • Journal Article Gunier RB, Jerrett M, Smith DR, Jursa T, Yousefi P, Camacho J, Hubbard A, Eskenazi B, Bradman A. Determinants of manganese levels in house dust samples from the CHAMACOS cohort. Science of the Total Environment 2014;497-498:360-368. R834513 (2012)
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  • Journal Article Gunier RB, Arora M, Jerrett M, Bradman A, Harley KG, Mora AM, Kogut K, Hubbard A, Austin C, Holland N, Eskenazi B. Manganese in teeth and neurodevelopment in young Mexican-American children. Environmental Research 2015;142:688-695. R834513 (2014)
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  • Journal Article Gunier RB, Bradman A, Harley KG, Eskenazi B. Will buffer zones around schools in agricultural areas be adequate to protect children from the potential adverse effects of pesticide exposure? PLoS Biology 2017;15(12):e2004741 (7 pp.). R834513 (Final)
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  • Journal Article Gunier RB, Bradman A, Harley KG, Kogut K, Eskenazi B. Prenatal residential proximity to agricultural pesticide use and IQ in 7-year-old children. Environmental Health Perspectives 2017;125(5):057002 (8 pp.). R834513 (Final)
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  • Journal Article Gunier RB, Bradman A, Castorina R, Holland NT, Avery D, Harley KG, Eskenazi B. Residential proximity to agricultural fumigant use and IQ, attention and hyperactivity in 7-year old children. Environmental Research 2017;158:358-365. R834513 (Final)
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  • Journal Article Gunier RB, Raanan R, Castorina R, Holland NT, Harley KG, Balmes JR, Fouquette L, Eskenazi B, Bradman A. Residential proximity to agricultural fumigant use and respiratory health in 7-year old children. Environmental Research. 2018;164:93-99. R834513 (Final)
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  • Journal Article Harley KG, Marks AR, Chevrier J, Bradman A, Sjodin A, Eskenazi B. PBDE concentrations in women’s serum and fecundability. Environmental Health Perspectives 2010;118(5):699-704. R834513 (2010)
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  • Journal Article Harley KG, Huen K, Aguilar Schall R, Holland NT, Bradman A, Barr DB, Eskenazi B. Association of organophosphate pesticide exposure and paraoxonase with birth outcome in Mexican-American women. PLoS ONE 2011;6(8):e23923 (10 pp.). R834513 (2010)
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  • Journal Article Harley KG, Chevrier J, Schall RA, Sjodin A, Bradman A, Eskenazi B. Association of prenatal exposure to polybrominated diphenyl ethers and infant birth weight. American Journal of Epidemiology 2011;174(8):885-892. R834513 (2010)
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  • Journal Article Harley KG, Aguilar Schall R, Chevrier J, Tyler K, Aguirre H, Bradman A, Holland NT, Lustig RH, Calafat AM, Eskenazi B. Prenatal and postnatal bisphenol A exposure and body mass index in childhood in the CHAMACOS cohort. Environmental Health Perspectives 2013;121(4):514-520. R834513 (2012)
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  • Journal Article Harley KG, Gunier RB, Kogut K, Johnson C, Bradman A, Calafat AM, Eskenazi B. Prenatal and early childhood bisphenol A concentrations and behavior in school-aged children. Environmental Research 2013;126:43-50. R834513 (2014)
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  • Journal Article Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. Prenatal exposure to organophosphate pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environmental Health Perspectives 2016;124(7):1084-1092. R834513 (2014)
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  • Journal Article Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. Prenatal exposure to organophosphorous pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environmental Health Perspectives 2016;124(7):1084-1092. R834513 (Final)
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  • Journal Article Harley KG, Kogut K, Madrigal DS, Cardenas M, Vera IA, Meza-Alfaro G, She J, Gavin Q, Zahedi R, Bradman A, Eskenazi B, Parra KL. Reducing phthalate, paraben, and phenol exposure from personal care products in adolescent girls: findings from the HERMOSA Intervention Study. Environmental Health Perspectives 2016;124(10):1600-1607. R834513 (Final)
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  • Journal Article Harley KG, Rauch SA, Chevrier J, Kogut K, Parra KL, Trujillo C, Lustig RH, Greenspan LC, Sjodin A, Bradman A, Eskenazi B. Association of prenatal and childhood PBDE exposure with timing of puberty in boys and girls. Environment International 2017;100:132-138. R834513 (2014)
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  • Journal Article Harley KG, Berger K, Rauch S, Kogut K, Henn BC, Calafat AM, Huen K, Eskenazi B, Holland N. Association of prenatal urinary phthalate metabolite concentrations and childhood BMI and obesity. Pediatric Research 2017;82(3):405-415. R834513 (Final)
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  • Journal Article Harnly ME, Bradman A, Nishioka M, McKone TE, Smith D, McLaughlin R, Kavanagh-Baird G, Castorina R, Eskenazi B. Pesticides in dust from homes in an agricultural area. Environmental Science & Technology 2009;43(23):8767-8774. R834513 (2010)
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  • Journal Article Heggeseth B, Harley K, Warner M, Jewell N, Eskenazi B. Detecting associations between early-life DDT exposures and childhood growth patterns: a novel statistical approach. PLoS ONE 2015;10(6):e0131443 (13 pp.). R834513 (2015)
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  • Journal Article Holland N, Lizarraga D, Huen K. Recent progress in the genetics and epigenetics of paraoxonase: why it is relevant to children's environmental health. Current Opinion in Pediatrics 2015;27(2):240-247. R834513 (2013)
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  • Journal Article Holland N, Huen K, Tran V, Street K, Nguyen B, Bradman A, Eskenazi B. Urinary phthalate metabolites and biomarkers of oxidative stress in a Mexican-American cohort: variability in early and late pregnancy. Toxics 2016;4(1):7 (18 pp.). R834513 (Final)
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  • Journal Article Huen K, Richter R, Furlong C, Eskenazi B, Holland N. Validation of PON1 enzyme activity assays for longitudinal studies. Clinica Chimica Acta 2009;402(1-2):67-74. R834513 (2010)
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  • Journal Article Huen K, Harley K, Brooks J, Hubbard A, Bradman A, Eskenazi B, Holland N. Developmental changes in PON1 enzyme activity in young children and effects of PON1 polymorphisms. Environmental Health Perspectives 2009;117(10):1632-1638. R834513 (2010)
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  • Journal Article Huen K, Harley K, Bradman A, Eskenazi B, Holland N. Longitudinal changes in PON1 enzymatic activities in Mexican-American mothers and children with different genotypes and haplotypes. Toxicology and Applied Pharmacology 2010;244(2):181-189. R834513 (2010)
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  • Journal Article Huen K, Barcellos L, Beckman K, Rose S, Eskenazi B, Holland N. Effects of PON polymorphisms and haplotypes on molecular phenotype in Mexican-American mothers and children. Environmental and Molecular Mutagenesis 2011;52(2):105-116. R834513 (2010)
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  • Journal Article Huen K, Bradman A, Harley K, Yousefi P, Boyd Barr D, Eskenazi B, Holland N. Organophosphate pesticide levels in blood and urine of women and newborns living in an agricultural community. Environmental Research 2012;117:8-16. R834513 (2010)
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  • Journal Article Huen K, Harley K, Beckman K, Eskenazi B, Holland N. Associations of PON1 and genetic ancestry with obesity in early childhood. PLoS One 2013;8(5):e62565. R834513 (2013)
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  • Journal Article Huen K, Yousefi P, Bradman A, Yan L, Harley KG, Kogut K, Eskenazi B, Holland N. Effects of age, sex, and persistent organic pollutants on DNA methylation in children. Environmental and Molecular Mutagenesis 2014;55(3):209-222. R834513 (2012)
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  • Journal Article Huen K, Yousefi P, Street K, Eskenazi B, Holland N. PON1 as a model for integration of genetic, epigenetic, and expression data on candidate susceptibility genes. Environmental Epigenetics 2015;1(1):dvv003. R834513 (2015)
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  • Journal Article Huen K, Calafat AM, Bradman A, Yousefi P, Eskenazi B, Holland N. Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children. Environmental Research 2016;148:55-62. R834513 (Final)
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  • Journal Article Huen K, Harley K, Kogut K, Rauch S, Eskenazi B, Holland N. DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children. Pediatric Research 2016;79(6):855-862. R834513 (2014)
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  • Journal Article Johnson M, Deardorff J, Davis EL, Martinez W, Eskenazi B, Alkon A. The relationship between maternal responsivity, socioeconomic status, and resting autonomic nervous system functioning in Mexican American children. International Journal of Psychophysiology 2017;116:45-52. R834513 (Final)
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  • Journal Article Lizarraga D, Huen K, Combs M, Escudero-Fung M, Eskenazi B, Holland N. miRNAs differentially expressed by next-generation sequencing in cord blood buffy coat samples of boys and girls. Epigenomics 2016;8(12):1619-1635. R834513 (Final)
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  • Journal Article Lopez-Espinosa M-J, Mondal D, Armstrong BG, Eskenazi B, Fletcher T. Perfluoroalkyl substances, sex hormones, and insulin-like growth factor-1 at 6-9 years of age: a cross-sectional analysis within the C8 Health Project. Environmental Health Perspectives 2016;124(8):1269-1275. R834513 (2014)
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  • Journal Article Macher JM, Mendell MJ, Kumagai K, Holland NT, Camacho JM, Harley KG, Eskenazi B, Bradman A. Higher measured moisture in California homes with qualitative evidence of dampness. Indoor Air 2016;26(6):892-902. R834513 (Final)
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  • Journal Article Madrigal DS, Salvatore A, Casillas G, Casillas C, Vera I, Eskenazi B, Minkler M. Health in my community: conducting and evaluating PhotoVoice as a tool to promote environmental health and leadership among Latino/a youth. Progress in Community Health Partnerships: Research, Education, and Action 2014;8(3):317-329. R834513 (2014)
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  • Journal Article Marks AR, Harley K, Bradman A, Kogut K, Barr DB, Johnson C, Calderon N, Eskenazi B. Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS Study. Environmental Health Perspectives 2010;118(12):1768-1774. R834513 (2010)
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  • Journal Article Mora AM, van Wendel de Joode B, Mergler D, Cordoba L, Cano C, Quesada R, Smith DR, Menezes-Filho JA, Lundh T, Lindh CH, Bradman A, Eskenazi B. Blood and hair manganese concentrations in pregnant women from the Infants’ Environmental Health Study (ISA) in Costa Rica. Environmental Science & Technology 2014;48(6):3467-3476. R834513 (2014)
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  • Journal Article Mora AM, van Wendel de Joode B, Mergler D, Cordoba L, Cano C, Quesada R, Smith DR, Menezes-Filho JA, Eskenazi B. Maternal blood and hair manganese concentrations, fetal growth, and length of gestation in the ISA cohort in Costa Rica. Environmental Research 2015;136:47-56. R834513 (2014)
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  • Journal Article Mora AM, Arora M, Harley KG, Kogut K, Parra K, Hernandez-Bonilla D, Gunier RB, Bradman A, Smith DR, Eskenazi B. Prenatal and postnatal manganese teeth levels and neurodevelopment at 7, 9, and 10.5 years in the CHAMACOS cohort. Environment International 2015;84:39-54. R834513 (2014)
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  • Journal Article Payne-Sturges D, Cohen J, Castorina R, Axelrad DA, Woodruff TJ. Evaluating cumulative organophosphorus pesticide body burden of children: a national case study. Environmental Science & Technology 2009;43(20):7924-7930. R834513 (2010)
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  • Journal Article Quiros-Alcala L, Bradman A, Nishioka M, Harnly ME, Hubbard A, McKone TE, Eskenazi B. Concentrations and loadings of polybrominated diphenyl ethers in dust from low-income households in California. Environment International 2011;37(3):592-596. R834513 (2010)
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  • Journal Article Quiros-Alcala L, Bradman A, Nishioka M, Harnly ME, Hubbard A, McKone TE, Ferber J, Eskenazi B. Pesticides in house dust from urban and farmworker households in California: an observational measurement study. Environmental Health 2011;10:19 (15 pp.). R834513 (2010)
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  • Journal Article Quiros-Alcala L, Alkon AD, Boyce WT, Lippert S, Davis NV, Bradman A, Barr DB, Eskenazi B. Maternal prenatal and child organophosphate pesticide exposures and children's autonomic function. NeuroToxicology 2011;32(5):646-655. R834513 (2010)
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  • Journal Article Quiros-Alcala L, Bradman A, Smith K, Weerasekera G, Odetokun M, Barr DB, Nishioka M, Castorina R, Hubbard AE, Nicas M, Hammond SK, McKone TE, Eskenazi B. Organophosphorous pesticide breakdown products in house dust and children's urine. Journal of Exposure Science & Environmental Epidemiology 2012;22(6):559-568. R834513 (2012)
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  • Journal Article Quiros-Alcala L, Eskenazi B, Bradman A, Ye X, Calafat AM, Harley K. Determinants of urinary bisphenol A concentrations in Mexican/Mexican-American pregnant women. Environment International 2013;59:152-160. R834513 (2013)
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  • Journal Article Quiros-Alcala L, Mehta S, Eskenazi B. Pyrethroid pesticide exposure and parental report of learning disability and attention deficit/hyperactivity disorder in U.S. children: NHANES 1999-2002. Environmental Health Perspectives 2014;122(12):1336-1342. R834513 (2014)
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  • Journal Article Raanan R, Harley KG, Balmes JR, Bradman A, Lipsett M, Eskenazi B. Early-life exposure to organophosphate pesticides and pediatric respiratory symptoms in the CHAMACOS cohort. Environmental Health Perspectives 2015;123(2):179-185. R834513 (2010)
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  • Journal Article Raanan R, Balmes JR, Harley KG, Gunier RB, Magzamen S, Bradman A, Eskenazi B. Decreased lung function in 7-year-old children with early-life organophosphate exposure. Thorax 2016;71(2):148-153. R834513 (2015)
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  • Journal Article Raanan R, Gunier RB, Balmes JR, Beltran AJ, Harley KG, Bradman A, Eskenazi B. Elemental sulfur use and associations with pediatric lung function and respiratory symptoms in an agricultural community (California, USA). Environmental Health Perspectives 2017;125(8):087007 (8 pp.). R834513 (Final)
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  • Journal Article Rosas LG, Harley K, Fernald LC, Guendelman S, Mejia F, Neufeld LM, Eskenazi B. Dietary associations of household food insecurity among children of Mexican descent: results of a binational study. Journal of the American Dietetic Association 2009;109(12):2001-2009. R834513 (2010)
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  • Journal Article Rosas LG, Harley KG, Guendelman S, Fernald LC, Mejia F, Eskenazi B. Maternal perception of child weight among Mexicans in California and Mexico. Maternal and Child Health Journal 2010;14(6):886-894. R834513 (2010)
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  • Journal Article Rosas LG, Guendelman S, Harley K, Fernald LC, Neufeld L, Mejia F, Eskenazi B. Factors associated with overweight and obesity among children of Mexican descent:results of a binational study. Journal of Immigrant and Minority Health 2011;13(1):169-180. R834513 (2010)
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  • Journal Article Rosas LG, Trujillo C, Camacho J, Madrigal D, Bradman A, Eskenazi B. Acceptability of health information technology aimed at environmental health education in a prenatal clinic. Patient Education and Counseling 2014;97(2):244-247. R834513 (2014)
    R834513 (2015)
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    R834513C004 (2014)
    R834513C004 (2015)
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  • Journal Article Rowe C, Gunier R, Bradman A, Harley KG, Kogut K, Parra K, Eskenazi B. Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children. Environmental Research 2016;150:128-137. R834513 (2015)
    R834513 (Final)
    R834513C001 (2015)
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  • Journal Article Sagiv SK, Kogut K, Gaspar FW, Gunier RB, Harley KG, Parra K, Villasenor D, Bradman A, Holland N, Eskenazi B. Prenatal and childhood polybrominated diphenyl ether (PBDE) exposure and attention and executive function at 9-12 years of age. Neurotoxicology and Teratology 2015:52(Pt B):151-161. R834513 (2014)
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    R834513C001 (2014)
    R834513C001 (2015)
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  • Journal Article Salvatore AL, Chevrier J, Bradman A, Camacho J, Lopez J, Kavanagh-Baird G, Minkler M, Eskenazi B. A community-based participatory worksite intervention to reduce pesticide exposures to farmworkers and their families. American Journal of Public Health 2009;99(Suppl 3):S578-S581. R834513 (2010)
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  • Journal Article Salvatore AL, Castorina R, Camacho J, Morga N, Lopez J, Nishioka M, Barr DB, Eskenazi B, Bradman A. Home-based community health worker intervention to reduce pesticide exposures to farmworkers’ children: a randomized-controlled trial. Journal of Exposure Science & Environmental Epidemiology 2015;25(6):608-615. R834513 (2014)
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    R834513C002 (2014)
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    R834513C004 (2015)
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  • Journal Article Scholtz, RI, McLaughlin KR, Cirillo PM, Petreas M, Park J-S, Wolff MS, Factor-Litvak P, Eskenazi B, Krigbaum N, Cohn BA. Assaying organochlorines in archived serum for a large, long-term cohort:implications of combining assay results from multiple laboratories over time. Environment International 2011;37(4):709-714. R834513 (2010)
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    R831710 (Final)
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  • Journal Article Sermondade N, Faure C, Fezeu L, Shayeb AG, Bonde JP, Jensen TK, Van Wely M, Cao J, Martini AC, Eskandar M, Chavarro JE, Koloszar S, Twigt JM, Ramlau-Hansen CH, Borges Jr. E, Lotti F, Steegers-Theunissen RPM, Zorn B, Polotsky AJ, La Vignera S, Eskenazi B, Tremellen K, Magnusdottir EV, Fejes I, Hercberg S, Levy R, Czernichow S. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Human Reproduction Update 2013;19(3):221-231. R834513 (2014)
    R834513C001 (2014)
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  • Journal Article Sjodin A, Jones RS, Gunier RB, Wong LY, Holland N, Eskenazi B, Bradman, A. Polybrominated diphenyl ethers, polychlorinated biphenyls, and 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene in 7-and 9-year-old children and their mothers in the Center for the Health Assessment of Mothers and Children of Salinas Cohort. Environmental Science & Technology 2018;52(4):2287-2294. R834513 (Final)
    R834513C002 (2015)
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  • Journal Article Sly PD Eskenazi B, Pronczuk J, Sram R, Diaz-Barriga F, Machin DG, Carpenter DO, Surdu S, Meslin EM. Ethical issues in measuring biomarkers in children's environmental health. Environmental Health Perspectives 2009;117(8):1185-1190. R834513 (2010)
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    R832734 (2009)
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  • Journal Article Solomon O, Yousefi P, Huen K, Gunier RB, Escudero-Fung M, Barcellos LF, Eskenazi B, Holland N. Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood. Environmental and Molecular Mutagenesis 2017;58(6):398-410. R834513 (Final)
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  • Journal Article Stein LJ, Gunier RB, Harley K, Kogut K, Bradman A, Eskenazi B. Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: the CHAMACOS cohort. Neurotoxicology 2016;56:180-187. R834513 (2015)
    R834513 (Final)
    R834513C001 (2015)
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  • Journal Article Torres JM, Deardorff J, Gunier RB, Harley KG, Alkon A, Kogut K, Eskenazi B. Worry about deportation and cardiovascular disease risk factors among adult women: the Center for the Health Assessment of Mothers and Children of Salinas Study. Annals of Behavioral Medicine 2018;52(2):186-193. R834513 (Final)
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  • Journal Article Tran V, Tindula G, Huen K, Bradman A, Harley K, Kogut K, Calafat AM, Nguyen B, Parra K, Ye X, Eskenazi B, Holland N. Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity. Journal of Developmental Origins of Health and Disease 2017;8(2):196-205. R834513 (Final)
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  • Journal Article van Wendel de Joode B, Mora AM, Cordoba L, Cano JC, Quesada R, Faniband M, Wesseling C, Ruepert C, Oberg M, Eskenazi B, Mergler D, Lindh CH. Aerial application of mancozeb and urinary ethylene thiourea (ETU) concentrations among pregnant women in Costa Rica: the Infants’ Environmental Health Study (ISA). Environmental Health Perspectives 2014;122(12):1321-1328. R834513 (2014)
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    R834513C002 (2014)
    R834513C002 (2015)
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  • Journal Article Verner M-A, Gaspar FW, Chevrier J, Gunier RB, Sjodin A, Bradman A, Eskenazi B. Increasing sample size in prospective birth cohorts:back-extrapolating prenatal levels of persistent organic pollutants in newly enrolled children. Environmental Science & Technology 2015;49(6):3940-3948. R834513 (2014)
    R834513 (2015)
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    R834513C001 (2015)
    R834513C002 (2014)
    R834513C002 (2015)
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  • Journal Article Volberg V, Harley KG, Aguilar RS, Rosas LG, Huen K, Yousefi P, Dave V, Phan N, Lustig RH, Eskenazi B, Holland N. Associations between perinatal factors and adiponectin and leptin in 9-year-old Mexican-American children. Pediatric Obesity 2013;8(6):454-463. R834513 (2013)
    R834513 (2014)
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    R834513C001 (2013)
    R834513C003 (2014)
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  • Journal Article Volberg V, Heggeseth B, Harley K, Huen K, Yousefi P, Dave V, Tyler K, Vedar M, Eskenazi B, Holland N. Adiponectin and leptin trajectories in Mexican-American children from birth to 9 years of age. PLoS One 2013;8(10):e77964 (8 pp.). R834513 (2014)
    R834513C003 (2014)
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  • Journal Article Volberg V, Harley K, Calafat AM, Dave V, McFadden J, Eskenazi B, Holland N. Maternal bisphenol A exposure during pregnancy and its association with adipokines in Mexican-American children. Environmental and Molecular Mutagenesis 2013;54(8):621-628. R834513 (2014)
    R834513C001 (2014)
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  • Journal Article Warner M, Mocarelli P, Brambilla P, Wesselink A, Samuels S, Signorini S, Eskenazi B. Diabetes, metabolic syndrome, and obesity in relation to serum dioxin concentrations: the Seveso Women's Health Study. Environmental Health Perspectives 2013;121(8):906-911. R834513 (2013)
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  • Journal Article Warner M, Schall RA, Harley KG, Bradman A, Barr D, Eskenazi B. In utero DDT and DDE exposure and obesity status of 7-year-old Mexican-American children in the CHAMACOS cohort. Environmental Health Perspectives 2013;121(5):631-636. R834513 (2013)
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    R834513C001 (2013)
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  • Journal Article Warner M, Wesselink A, Harley KG, Bradman A, Kogut K, Eskenazi B. Prenatal exposure to dichlorodiphenyltrichloroethane and obesity at 9 years of age in the CHAMACOS Study cohort. American Journal of Epidemiology 2014;179(11):1312-1322. R834513 (2014)
    R834513C001 (2014)
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  • Journal Article Warner M, Mocarelli P, Brambilla P, Wesselink A, Patterson Jr. DG, Turner WE, Eskenazi B. Serum TCDD and TEQ concentrations among Seveso women, 20 years after the explosion. Journal of Exposure Science & Environmental Epidemiology 2014;24(6):588-594. R834513 (2014)
    R834513C002 (2014)
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  • Journal Article Warner M, Ye M, Harley K, Kogut K, Bradman A, Eskenazi B. Prenatal DDT exposure and child adiposity at 12 years of age in the CHAMACOS cohort. Environmental Research 2017;159:606-612. R834513 (Final)
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  • Journal Article Waters SF, Boyce WT, Eskenazi B, Alkon A. The impact of maternal depression and overcrowded housing on associations between autonomic nervous system reactivity and externalizing behavior problems in vulnerable Latino children. Psychophysiology 2016;53(1):97-104. R834513 (Final)
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  • Journal Article Weerasekera G, Smith KD, Quiros-Alcala L, Fernandez C, Bradman A, Eskenazi B, Needham LL, Barr DB. A mass spectrometry-based method to measure dialkylphosphate degradation products of organophosphorous insecticides in dust and orange juice. Journal of Environmental Monitoring 2009;11(7):1345-1351. R834513 (2010)
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    R831710 (Final)
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  • Journal Article Weldon RH, Webster M, Harley KG, Bradman A, Fenster L, Davis MD, Hubbard A, Barr DB, Holland N, Eskenazi B. Serum persistent organic pollutants and duration of lactation among Mexican-American women. Journal of Environmental and Public Health 2010;2010:861757 (11 pp.). R834513 (2010)
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  • Journal Article Weldon RH, Barr DB, Trujillo C, Bradman A, Holland N, Eskenazi B. A pilot study of pesticides and PCBs in the breast milk of women residing in urban and agricultural communities of California. Journal of Environmental Monitoring 2011;13(11):3136-3144. R834513 (2011)
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    R834513C001 (2012)
    R834513C002 (2012)
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  • Journal Article Wesselink A, Warner M, Samuels S, Parigi A, Brambilla P, Mocarelli P, Eskenazi B. Maternal dioxin exposure and pregnancy outcomes over 30 years of follow-up in Seveso. Environment International 2014;63:143-148. R834513 (2014)
    R834513C001 (2014)
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  • Journal Article Yousefi P, Huen K, Schall RA, Decker A, Elboudwarej E, Quach H, Barcellos L, Holland N. Considerations for normalization of DNA methylation data by Illumina 450K BeadChip assay in population studies. Epigenetics 2013;8(11):1141-1152. R834513 (2012)
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    R834513C003 (2012)
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  • Journal Article Yousefi P, Huen K, Quach H, Motwani G, Hubbard A, Eskenazi B, Holland N. Estimation of blood cellular heterogeneity in newborns and children for epigenome-wide association studies. Environmental and Molecular Mutagenesis 2015;56(9):751-758. R834513 (2015)
    R834513C003 (2015)
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  • Journal Article Yousefi P, Huen K, Dave V, Barcellos L, Eskenazi B, Holland N. Sex differences in DNA methylation assessed by 450 K BeadChip in newborns. BMC Genomics 2015;16:911. R834513C003 (2015)
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  • Supplemental Keywords:

    Community outreach and translation, community-based research, environmental justice

    Relevant Websites:

    Center for Environmental Research and Children's Health Exit
    Environmental Quality in California Child Care Exit
    Green Cleaning Toolkit Exit (PDF,68pp, 2.39MB)

    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2011 Progress Report
  • 2012 Progress Report
  • 2013 Progress Report
  • 2014 Progress Report
  • Final Report
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834513C001 CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty
    R834513C002 Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children
    R834513C003 Epigenetics Project
    R834513C004 Community Outreach and Translation Core