The fetal brain is uniquely sensitive and environmental chemical exposures and dysregulation of the endocrine system may increase the risk of adverse neurobehavioral outcomes like autism, attention-deficit/hyperactivity disorder, or depression. Under the mentorship of Drs. Bellinger and Hauser, this training and research plan will build upon Dr. Braun's expertise as an environmental epidemiologist and prepare him for a career studying endocrine disrupting compounds (EDCs) and their impact on hormonal systems and childhood neurodevelopment. Dr. Braun has never received formal training in these areas and few researchers possess this unique cross-disciplinary expertise. During the K99-phase of this award Dr. Braun will use tutorials, seminars/conferences, and didactic instruction to gain additional training in: 1) endocrinology concepts and the impact of environmental chemicals on the endocrine system;2) psychometric test selection, administration, validation, and interpretation;and 3) childhood neurodevelopment. This training will be applied in an original research project where Dr. Braun will administer computerized tests of visuospatial ability to 25 children from Dr. Hauser's Environment and Reproductive Health (EARTH) study under the guidance of both Drs. Hauser and Bellinger. These computerized tests are analogues of the Morris Water Maze and Radial Arm Maze, which are used in animal studies of neurotoxicity. Using these new skills and the prospective Health Outcomes and Measures of the Environment (HOME) birth cohort, Dr. Braun will address two specific aims during the R00- phase of this award: 1) determine if gestational BPA/phthalate exposure is associated with visuospatial ability in 300 children and if sex modifies these associations and 2) determine if gestational BPA/phthalate exposure is associated with meconium sex steroid concentrations in 330 infants. Dr. Braun is well suited to carry out this research because of his prior training and the unique resources offered by his mentors, advisors, and institution. This proposed training and research will enable him to study the impact of EDCs on other hormonal systems and whether they increase the risk of adverse childhood behavioral outcomes. The examination of sex steroids will advance our knowledge of potential biological mechanisms of EDC action and the use of neurobehavioral tests with animal analogues will improve comparisons between epidemiological and animal studies. Public Health Relevance: Neurobehavioral disorders place an enormous burden on educational and medical resources. Thus, priority to understand factors associated with these disorders. The proposed studies could inform public health interventions by addressing important research gaps in our knowledge of BPA and phthalate neurotoxicity and its impact on human neurobehavior.

Public Health Relevance

The fetus may be susceptible to endocrine disrupting compounds like bisphenol A (BPA) and phthalates. Exposure to these compounds may be detrimental to childhood neurodevelopment by disrupting gestational sex steroid metabolism. This proposal will use an integrated training plan in endocrine disruption and childhood neurodevelopment to prepare Dr. Joe M. Braun to produce high-quality research studying the impact of gestational BPA/phthalate exposures on fetal sex steroids and childhood visuospatial ability.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Transition Award (R00)
Project #
5R00ES020346-04
Application #
8619626
Study Section
Special Emphasis Panel (NSS)
Program Officer
Gray, Kimberly A
Project Start
2013-02-14
Project End
2016-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
4
Fiscal Year
2014
Total Cost
$244,996
Indirect Cost
$80,458
Name
Brown University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Li, Nan; Yolton, Kimberly; Lanphear, Bruce P et al. (2018) Impact of Early-Life Weight Status on Cognitive Abilities in Children. Obesity (Silver Spring) 26:1088-1095
Romano, Megan E; Eliot, Melissa N; Zoeller, R Thomas et al. (2018) Maternal urinary phthalate metabolites during pregnancy and thyroid hormone concentrations in maternal and cord sera: The HOME Study. Int J Hyg Environ Health 221:623-631
Messerlian, Carmen; Williams, Paige L; Ford, Jennifer B et al. (2018) The Environment and Reproductive Health (EARTH) Study: A Prospective Preconception Cohort. Hum Reprod Open 2018:
Zhang, Hongmei; Yolton, Kimberly; Webster, Glenys M et al. (2018) Prenatal and childhood perfluoroalkyl substances exposures and children's reading skills at ages 5 and 8years. Environ Int 111:224-231
Wu, Shaowei; Gennings, Chris; Wright, Rosalind J et al. (2018) Prenatal Stress, Methylation in Inflammation-Related Genes, and Adiposity Measures in Early Childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study. Psychosom Med 80:34-41
Millenson, Marisa E; Braun, Joseph M; Calafat, Antonia M et al. (2017) Urinary organophosphate insecticide metabolite concentrations during pregnancy and children's interpersonal, communication, repetitive, and stereotypic behaviors at 8 years of age: The home study. Environ Res 157:9-16
Zhang, Hongmei; Yolton, Kimberly; Webster, Glenys M et al. (2017) Prenatal PBDE and PCB Exposures and Reading, Cognition, and Externalizing Behavior in Children. Environ Health Perspect 125:746-752
Vuong, Ann M; Yolton, Kimberly; Xie, Changchun et al. (2017) Childhood polybrominated diphenyl ether (PBDE) exposure and neurobehavior in children at 8 years. Environ Res 158:677-684
Braun, Joseph M (2017) Early-life exposure to EDCs: role in childhood obesity and neurodevelopment. Nat Rev Endocrinol 13:161-173
Shoaff, Jessica; Papandonatos, George D; Calafat, Antonia M et al. (2017) Early-Life Phthalate Exposure and Adiposity at 8 Years of Age. Environ Health Perspect 125:097008

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