2013 Progress Report: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty

EPA Grant Number: R834513C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834513
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

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: CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty
Investigators: Eskenazi, Brenda , Arora, Manish , Bradman, Asa , Chevrier, Jonathan , Eisen, Ellen , Harley, Kim , Holland, Nina T. , Johnson, Caroline , Lustig, Robert , Sjodin, Andreas , Smith, Donald
Current Investigators: Eskenazi, Brenda , Arora, Manish , Bradman, Asa , Chevrier, Jonathan , Harley, Kim , Holland, Nina T. , Johnson, Caroline , Lustig, Robert , Sjodin, Andreas , Smith, Donald
Institution: University of California - Berkeley
Current Institution: University of California - Berkeley , Centers for Disease Control and Prevention , Mount Sinai School of Medicine , University of California - San Francisco , University of California - Santa Cruz
EPA Project Officer: Louie, Nica
Project Period: August 1, 2009 through July 31, 2014 (Extended to July 31, 2016)
Project Period Covered by this Report: June 1, 2012 through May 31,2013
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

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.

Progress Summary:

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 been successful in maintaining CHAM1 participants (the boys in the CHAMACOS cohort who were followed from birth) and in recruiting CHAM2 participants (new boys enrolled at age 9). We met our goal of enrolling 300 boys, assessing 319 boys at age 9 years and 300 at age 10½. We have now completed CHAMACOS visits at 9, 9¾, 10½ years of age; visits at 11¼, 12, and 12¾ are still underway. We are currently halfway through the 12-year visits with the CHAMACOS cohort, with 147 boys assessed to date.
 
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.
Collection of neurodevelopmental test data at 9 and 10½ years of age is now complete. In preliminary analyses of prenatal Mn exposure measured in teeth, we have found no association with cognition, fine motor coordination, or behavioral outcomes. Similarly, we did not observe any evidence of interaction between prenatal Mn and lead, DAPs, or PBDEs on neurodevelopment. Analyses of prenatal Mn exposure and neurobehavioral functioning at later ages will be conducted once data entry and cleaning are completed. Analysis of childhood Mn exposure with neurobehavioral outcomes will be conducted once Mn measurements in child hair are finalized.
 
We have recently published a paper showing associations of prenatal and childhood PBDE exposure with cognitive functioning and behavior (Eskenazi et al, EHP, 2012). We report that prenatal PBDE concentrations are associated with impaired attention as measured both by maternal report and direct assessment of the child using a continuous performance task. Prenatal PBDE concentrations are also associated with decrements in Verbal and Full-Scale IQ by school age. Additionally, PBDE concentrations in children were significantly or marginally associated with teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ.
 
Prenatal and childhood DDT/E concentrations do not appear to be associated with any parameters of IQ in this population. DDT/E were also not associated with any domains of child behavior, with the exception of prenatal DDE and anxiety. Prenatal DDE concentrations were associated with increased anxiety based on maternal report (OR = 2.3, 95% CI = 1.2, 4.5) but not teacher report. However, we find more convincing evidence of interaction between prenatal DDT/E and PBDEs on child neurodevelopment. Maternal DDT/E appeared to potentiate the association of PBDEs on fine motor coordination (βInter = -1.7; 95% CI = -3.6, 0.3) and teacher report of internalizing problems (βInter = 4.9; 95% CI = 0.8, 9.1; Figure 1), particularly for anxiety (βInter = 4.5; 95% CI = 0.4, 8.7) and somatization (βInter = 6.7; 95% CI = 2.1, 11.3). For instance, maternal PBDE concentrations were associated with an 8.2 point (95% CI: 0.4, 16.1) increase in scores on the BASC somatization problems scale at the 95th percentile of maternal DDT, but no significant association was observed at the 50th percentile of maternal DDT (β = -4.6; 95% CI = -9.2, 0.1). We found no evidence of interaction for postnatal exposure.
 
 
Figure 1. Interaction between prenatal DDT and PBDEs and teacher report
                 of internalizing problems at 7-years.
 
 
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.
At age 9, only 11% of boys had begun genital development and 4% had begun pubic hair development. Data entry and data cleaning of Tanner staging data at 9¾ and 10½ is currently underway but is available for a subset of 101 boys. Based on preliminary data, we expect that more boys will have started puberty by age 10½ (51% for genital development and 12% for pubic hair development). Preliminary analyses of the 10½-year old data suggest that both prenatal DDT/E and PBDE exposure are associated with earlier puberty in boys. Childhood DDE exposure was also associated with earlier puberty in boys and associations with childhood DDT and PBDEs are in the direction of earlier puberty, but are not statistically significant. As presented in Table 1, each 10-fold increase in prenatal DDT and DDE concentrations was associated with more than a two-fold increase in odds of having begun genital development by age 10 (OR = 2.3 for DDT; OR = 2.8 for DDE). Each 10-fold increase in prenatal BDE-153 was also associated with increased odds of genital development (OR = 3.9). Models controlled for mother’s years of residence in the United States, marital status, household income, child BMI, birth order, child age, child examiner, and cohort (CHAM1 vs. 2). No associations were seen with pubic hair development. Analyses of Mn and timing of puberty are in progress.
 
 
 
 
4. To determine whether prenatal and childhood exposure to DDT/E, PBDEs, and Mn are associated with hormone levels in boys at age 12.
Blood sample collection at age 12 for analysis of hormones began in March 2012. Thus far, we have collected early morning blood samples from 125 boys (112 CHAM1, 13 CHAM2). We are currently preparing to ship our first batch of age 12 blood samples to the Esoterix laboratory in Calabasas Hills, CA, for measurement of testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH).
 
Significance: Animal studies suggest that PBDEs, DDT/E, and Mn may impact both neurodevelopment and pubertal development, but there have only been a limited number of human studies. Boys have been largely overlooked in studies on endocrine disruptors and onset of puberty. This study directly addresses worldwide concerns that changes in onset of sexual maturation may be related to endocrine disruptors in the environment. It also addresses concerns that exposure to DDT/E, PBDEs and Mn may compromise neurodevelopment. This study will fill important data gaps in our knowledge of the health effects of these widespread exposures.

Future Activities:

In year 5, we will complete the 11¼-year and 12-year assessments, and will complete as many 12¾ visits as we are able before funding expires. We will complete data entry and cleaning of the 10½-year questionnaire and neurodevelopment data, as well as for age 9¾, 10½, and 11¼ Tanner data. We anticipate that PBPK models to back-extrapolate levels during pregnancy for CHAM2 will be completed by March 2014. Statistical analyses of prenatal PBDEs and DDT/E exposure in CHAM2 study participants (Aims 2 and 3) will begin when these PBPK models are available.


Journal Articles on this Report : 10 Displayed | Download in RIS Format

Other subproject views: All 137 publications 67 publications in selected types All 67 journal articles
Other center views: All 666 publications 138 publications in selected types All 137 journal articles
Type Citation Sub Project Document Sources
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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  • Other: EHP-Full Text PDF
  • 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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  • Abstract: Journal of Pediatrics-Abstract
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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)
    R834513 (2013)
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  • Full-text: OUP-Full Text HTML
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  • Abstract: OUP-Abstract
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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 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 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)
    R834513 (2013)
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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 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)
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  • Abstract: Wiley-Abstract
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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)
    R834513 (2014)
    R834513 (Final)
    R834513C001 (2013)
    R834513C001 (2014)
    R834513C003 (2013)
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  • Supplemental Keywords:

    Behavior, children's health, CHAMACOS, DDT, DDE, flame retardants, maneb,manganese, neurodevelopment, PBDEs, puberty, RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, Health Risk Assessment, Biochemistry, Children's Health, Environmental Policy, Biology, pesticide exposure, farmworkers, flame retardants, PBDE, children's vulnerablity, neurochemical effects, harmful environmental agents, biological markers, agricultural community

    Relevant Websites:

    http://cerch.org/

    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2011 Progress Report
  • 2012 Progress Report
  • 2014 Progress Report
  • 2015 Progress Report
  • Final

  • Main Center Abstract and Reports:

    R834513    Center for the Health Assessment of Mothers and Children of Salinas - UC Berkeley School of Public Health: CHAMACOS Office, Berkeley, CA

    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