Grantee Research Project Results
2012 Progress Report: The Role of Endocrine Disruptors in Neurodevelopmental Disorders
EPA Grant Number: R834509C002Subproject: this is subproject number 002 , established and managed by the Center Director under grant R834509
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Water Environment and Reuse Foundation's National Center for Resource Recovery and Nutrient Management
Center Director: Olabode, Lola
Title: The Role of Endocrine Disruptors in Neurodevelopmental Disorders
Investigators: Perera, Frederica P. , Rauh, Virginia
Institution: Columbia University in the City of New York
EPA Project Officer: Callan, Richard
Project Period: September 24, 2009 through September 23, 2014 (Extended to September 23, 2015)
Project Period Covered by this Report: August 1, 2011 through September 24,2012
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
(1) Determine whether prenatal exposures to the endocrine disruptors, polycyclic aromatic hydrocarbons (PAH) and Bisphenol A (BPA), are associated with adverse neurobehavioral outcomes in peri-pubertal children, as measured by diagnostic assessment of child psychopathology and cognitive functioning; (2) Determine whether prenatal exposure to PAH or BPA is associated with epigenetic changes in candidate genes, selected as being of a priori interest based on the literature, is associated with endocrine disruption and immune dysregulation, and whether altered methylation/gene expression in these candidates is associated with the neurobehavioral outcomes; (3) Using GIS, determine the extent to which neighborhood-level conditions contribute to neurobehavioral outcomes and/or moderate the individual-level associations between exposure to PAH or BPA and child neurodevelopment.
Progress Summary:
1) We previously reported that prenatal exposure to PAH at levels encountered in NYC air adversely affected child IQ scores at 5 years of age (Perera 2009). Multiple regression analyses of IQ test scores (on the more informative Weschler Intelligence Scale for children, WISC) for the same children who were re-tested at ages 7 and 9 found that PAH exposure (also monitored in maternal prenatal air) was significantly inversely associated with full score IQ and working memory at both 7 and 9, and with verbal IQ and processing speed at age 9 (manuscrpts in preparation).
(2) In addition, we recently reported results of analyses of behavioral outcomes using both PAH exposure measured both via prenatal air monitoring and maternal and cord adducts measured using the high performance liquid chromatography (HPLC)/fluorescence method specific to benzo[a]pyrene (B[a]P)-DNA adducts. B[a]P is considered a representative PAH. We found found that PAH exposure, whether characterized by personal air monitoring or maternal and cord HPLC adducts, was positively associated with symptoms of Anxious/Depressed and Attention Problems (p value < 0.05, Perera 2012a). These results provide evidence that environmental PAH at levels encountered in NYC air can adversely affect child behavior, especially internalizing problems that could affect school performance.
(3) We analyzed the association between maternal prenatal BPA exposure (dichotomized into high/low groups at the upper quartile) and child behavior at ages 3-4 (assessed via the CBCL), using generalized linear models, adjusting for postnatal BPA exposure and other potential confounders (Perera 2012b). We observed significant interactions (p < 0.05) between prenatal BPA urinary concentrations (adjusting for postnatal BPA exposure and other covariates) and child sex on Emotionally Reactive, Aggressive Behavior, and Internalizing Problems scales of the CBCL. After stratifying on sex, the BPA effects were positive and significant among boys on Emotionally Reactive and Aggressive Behavior and positive and borderline significant (p < 0.1) on Sleep Problems, Withdrawn, Internalizing Problems and Externalizing Problems, indicating that boys with prenatal BPA exposure in the highest concentration quartile had, on average, more reported symptoms of problems in these areas. In contrast, among girls, high BPA exposure was associated with lower scores for Anxious/Depressed and Aggressive Behavior (p < 0.05), and Internalizing Problems (p < 0.1), indicating that girls in the high prenatal BPA exposure group had, on average, fewer reported problems in these areas than girls in the low exposure group. Postnatal BPA urinary concentration alone had a significant negative effect only on Emotionally Reactive within the entire sample. Comparison of results before and after adjusting for postnatal BPA exposure found the effect estimates to be similar, suggesting that the prenatal period may be a more sensitive window for BPA exposure. This manuscript was published by Environmental Health Perspectives.
Our current battery of neurodevelopmental tests at age 9-11 consists of 9 tests and subtests (CPT-Continuous Performance Test, Child’s Memory Scales (5 subtests), NEPSY-II (6 subtests), Edinburgh, Weather Prediction Task, Purdue Pegboard, Mental Rotation Task-Clock Test, Water Level Task and Draw a Spiral Task), 5 clinician rating scales/questionnaires (Children’s Depression Rating Scale, Social Responsiveness Scale, Social Communication Questionnaire, Revised Children’s Manifest Anxiety Scale, and the DuPaul-Barkley ADHD Scale) and a semi-structured diagnostic interview (K-SADS). We have completed the full battery of neurodevelopmental tests on 170 who have reached the age of 9 to date. An additional 13 children have completed the tests but are missing the clinical scales.
In the past several months, we have been examining the association between HPLC cord adducts, psychosocial stress, and IQ. These results are currently being written up in a manuscript. We are also examining the association between PAH and IQ at later ages, as well as the association between BPA and various behavior and developmental outcomes.
(4) We have successfully completed pyrosequencing assays to assess the methylation of COX-2, ERα, CEBPα, PDE4D, and TH. We are currently analyzing the association between prenatal PAH and COX-2 and between prenatal BPA and ERα, CEBPα, PDE4D, and TH, respectively. We are also analyzing associations between the methylation of CpG sites on these genes and neurodevelopmental endpoints, including mental and psychomotor developmental indices (from the Bayley Scales at ages 12, 24, and 36 months), IQ (from the WISC at age 7) and child behavior (from the Child Behavior Check List (CBCL) at ages 3, 5, 7, and 11). We are currently working to optimize the analysis of additional CpG sites on the genes listed above and to develop pyrosequencing assays for the remaining gene candidates (NMDAR2b, CCL17, AhR, INF-γ, and THRβ).
(5) We have also geocoded 841 prenatal addresses from the study area in Northern Manhattan and the Bronx and are continuing the process for later ages (currently 4,089 addresses geocoded). Analysis of relationships between exposures and outcomes at older ages using these data is ongoing.
Future Activities:
The research is on schedule, and we plan to continue the research as described in our grant application.
Journal Articles on this Report : 5 Displayed | Download in RIS Format
Other subproject views: | All 45 publications | 29 publications in selected types | All 29 journal articles |
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Other center views: | All 104 publications | 62 publications in selected types | All 60 journal articles |
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Herbstman JB, Tang D, Zhu D, Qu L, Sjodin A, Li Z, Camann D, Perera FP. Prenatal exposure to polycyclic aromatic hydrocarbons, benzo[a]pyrene-DNA adducts, and genomic DNA methylation in cord blood. Environmental Health Perspectives 2012;120(5):733-738. |
R834509 (2012) R834509 (2013) R834509 (2014) R834509 (Final) R834509C002 (2012) R834509C002 (Final) |
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Perera FP, Tang D, Wang S, Vishnevetsky J, Zhang B, Diaz D, Camann D, Rauh V. Prenatal polycyclic aromatic hydrocarbon (PAH) exposure and child behavior at age 6-7 years. Environmental Health Perspectives 2012;120(6):921-926. |
R834509 (2012) R834509 (2013) R834509 (2014) R834509 (Final) R834509C002 (2012) R834509C002 (Final) |
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Perera F, Vishnevetsky J, Herbstman JB, Calafat AM, Xiong W, Rauh V, Wang S. Prenatal bisphenol A exposure and child behavior in an inner-city cohort. Environmental Health Perspectives 2012;120(8):1190-1194. |
R834509 (2012) R834509 (2013) R834509 (2014) R834509 (Final) R834509C002 (2012) R834509C002 (Final) |
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Tang WY, Levin L, Talaska G, Cheung YY, Herbstman J, Tang D, Miller RL, Perera F, Ho SM. Maternal exposure to polycyclic aromatic hydrocarbons and 5'-CpG methylation of interferon-γ in cord white blood cells. Environmental Health Perspectives 2012;120(8):1195-1200. |
R834509 (2012) R834509 (2013) R834509 (2014) R834509 (Final) R834509C002 (2012) R834509C002 (Final) |
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Wang S, Xiong W, Ma W, Chanock S, Jedrychowski W, Wu R, Perera FP. Gene-environment interactions on growth trajectories. Genetic Epidemiology 2012;36(3):206-213. |
R834509 (2012) R834509 (2013) R834509 (2014) R834509 (Final) R834509C002 (2012) R834509C002 (Final) |
Exit Exit |
Supplemental Keywords:
Bisphenol A, BPA, polycyclic aromatic hydrocarbons, PAH, obesity, neurodevelopment, children , RFA, Scientific Discipline, Health, INTERNATIONAL COOPERATION, ENVIRONMENTAL MANAGEMENT, POLLUTANTS/TOXICS, Chemicals, Biochemistry, Children's Health, Environmental Policy, Biology, Risk Assessment, air toxics, developmental neurotoxicity, air pollution, childhood obesity, endocrine disruptors, assessment of exposure, children's vulnerablity, children's environmental health, growth & developmentRelevant Websites:
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R834509 Water Environment and Reuse Foundation's National Center for Resource Recovery and Nutrient Management Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834509C001 The Role of Endocrine Disruptors in Childhood Obesity
R834509C002 The Role of Endocrine Disruptors in Neurodevelopmental Disorders
R834509C003 The Mechanisms of Endocrine Disruptors in Laboratory Mice
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
29 journal articles for this subproject
Main Center: R834509
104 publications for this center
60 journal articles for this center