Persistent organic pollutants (POPs) are lipophilic chemicals that persist in the environment, accumulate in the food chain and human tissues, and are likely endocrine disruptors. In 2001, more than 90 countries signed the Stockholm Convention on Persistent Organic Pollutants, committing to eliminate the use of 12 POPs of greatest health concern. An exception was made for use of dichlorodiphenylthrichloroethane (DDT) for malaria control, and this use is increasing in many developing countries. Use of new compounds not covered under the treaty, such as polybrominated diphenyl ether (PBDE) flame retardants, is also increasing. Both DDT and PBDEs are endocrine disruptors and neurotoxicants in animals, but studies in humans are limited. Age at onset of puberty in girls, and possibly boys, has declined in recent decades. One hypothesis is that endocrine-disrupting compounds, including DDT or PBDEs, may be responsible for these trends. These pollutants may also jeopardize children's cognitive development, particularly with exposure during the prenatal and peri-adolescent periods of peak brain growth. We propose to investigate the associations of DDT and PBDE exposure in utero and at age 9 years on pubertal onset and neurodevelopment in the CHAMACOS longitudinal cohort of Mexican-American children in the Salinas Valley, California. The CHAMACOS children, born in 2000 and 2001, received relatively high in utero exposures to DDT from their mothers, who immigrated from areas in Mexico with recent DDT use. At 12 and 24 months of age, we found significant, dose-dependent deficits in cognitive functioning related to in utero DDT blood levels. Through their upbringing in California, CHAMACOS children likely have high exposure to PBDEs used in furniture and electronic products. As CHAMACOS girls approach age 9, we plan to enroll 130 new girls from the same source population as the original cohort, expanding the study from ~170 girls to 300. At the 9-year- old visit, we will collect blood samples from all 300 mother/daughter dyads and measure DDT and PBDEs. We will construct models to estimate in utero levels of DDT and PBDEs in those missing these measures, based on 9-year maternal levels and prenatal levels measured in 140 original participants. We will assess the relationship of in utero (measured or extrapolated) and age 9 (measured) blood concentrations of DDT/E and PBDE with the general cognitive, executive, attention, memory, and social cognition functioning of the girls assessed at ages 9, 101/2, or 12 years and with the timing and tempo of their pubertal onset as assessed by clinical Tanner exams conducted every six months from age 9 to 12 years. This application takes advantage of a rich dataset of Mexican-American children participating in the CHAMACOS longitudinal cohort study and proposes to expand this unique cohort.
We aim to address key data gaps on the human health effects of these currently used compounds crucial for assessing their public health costs and benefits and necessary for national and international regulatory decision-making.

Public Health Relevance

Two persistent organic pollutants, the pesticide, dichlorodiphenylthrichloroethane (DDT), and the industrial flame retardants, polybrominated diphenyl ethers (PBDEs), are widespread in the environment, accumulate in human fat tissue, and have been shown to disrupt hormonal function and neurodevelopment in animals. Few studies have examined the health effects of these chemicals in humans. This grant would examine a cohort of pre-adolescent children who have been followed since before birth to determine whether DDT and PBDE levels in children's blood collected at age 9 or in their mother's blood collected during pregnancy are associated with earlier age at puberty and poorer neurodevelopment in the children between ages 9 and 12 years.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
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Gray, Kimberly A
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University of California Berkeley
Public Health & Prev Medicine
Schools of Public Health
United States
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Gonzales, Nancy A; Johnson, Megan; Shirtcliff, Elizabeth A et al. (2018) The role of bicultural adaptation, familism, and family conflict in Mexican American adolescents' cortisol reactivity. Dev Psychopathol 30:1571-1587
Harley, Kim G; Rauch, Stephen A; Chevrier, Jonathan et al. (2017) Association of prenatal and childhood PBDE exposure with timing of puberty in boys and girls. Environ Int 100:132-138
Warner, Marcella; Ye, Morgan; Harley, Kim et al. (2017) Prenatal DDT exposure and child adiposity at age 12: The CHAMACOS study. Environ Res 159:606-612
Huen, Karen; Harley, Kim; Kogut, Katherine et al. (2016) DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children. Pediatr Res 79:855-62
Heggeseth, Brianna; Harley, Kim; Warner, Marcella et al. (2015) Detecting Associations between Early-Life DDT Exposures and Childhood Growth Patterns: A Novel Statistical Approach. PLoS One 10:e0131443
Gaspar, Fraser W; Harley, Kim G; Kogut, Katherine et al. (2015) Prenatal DDT and DDE exposure and child IQ in the CHAMACOS cohort. Environ Int 85:206-12
Verner, Marc-André; Gaspar, Fraser W; Chevrier, Jonathan et al. (2015) Increasing sample size in prospective birth cohorts: back-extrapolating prenatal levels of persistent organic pollutants in newly enrolled children. Environ Sci Technol 49:3940-8
Warner, Marcella; Wesselink, Amelia; Harley, Kim G et al. (2014) Prenatal exposure to dichlorodiphenyltrichloroethane and obesity at 9 years of age in the CHAMACOS study cohort. Am J Epidemiol 179:1312-22
Blattler, Adam; Yao, Lijing; Witt, Heather et al. (2014) Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes. Genome Biol 15:469
Chevrier, Jonathan (2013) Invited commentary: Maternal plasma polybrominated diphenyl ethers and thyroid hormones--challenges and opportunities. Am J Epidemiol 178:714-9