Grantee Research Project Results

2014 Progress Report: Novel Methods to Assess the Effects of Chemicals on Child Development

Objective:

Project 1: Joint Effects of Endocrine Disruptors, Diet and BMI on Child Development

The major goals of this project are to: (1) assess sources of exposure to phthalates, bisphenol A (BPA) and other endocrine disrupting chemicals (EDCs) during prenatal and adolescent periods; (2) examine the association of prenatal or adolescent exposure to phthalates, BPA and other EDCs (and interactions among these exposures) with physical, behavioral and cognitive development in infants and adolescents; (3) assess the potential for a high fat diet (HFD)/obesity during two critical periods -- prenatal or adolescent -- to interact with chemical exposure to influence physical, behavioral and cognitive development; and (4) investigate the association of prenatal exposure to phthalates, BPA and other EDCs with markers of oxidative stress or inflammation in maternal and cord blood. In addition, we hypothesize that associations of exposure with these outcomes will vary by child sex.

Project 2: Endocrine Disrupting Chemicals, Diet and Gonadal Toxicity

The proposed studies were designed to test the hypothesis that BPA, phthalate, and high fat diet exposure interact to increase oxidative stress in developing and adolescent gonads, leading to infertility, early reproductive senescence, and transgenerational effects on fertility in the offspring. To test this hypothesis, the following specific aims will be completed: (1) determine if a high fat diet and BPA/phthalate/phthalate mixture exposure increase oxidative stress in the gonads of female and male mice, (2) determine if a high fat diet and BPA/phthalate/phthalate mixture exposure destroy germ cells and cause epigenetic changes known to reduce germ cell quality in the gonads of female and male mice, and (3) determine if a high fat diet and BPA/phthalate/phthalate mixture exposure cause infertility and early reproductive senescence in the first and subsequent generations in mice.

Project 3: Endocrine Disruptors and Diet, Effects on the Developing Cortex

Community Outreach and Translation Core:

Aim 1. To develop a strong Community Outreach and Translation Core (COTC) that is informed by the Community Advisory Board (CAB) and Dr. Susan Korrick, the Center’s Pediatric Health Specialist, and that works bi-directionally with the PIs of the Center. The CAB and PIs will work together in an iterative manner using feedback from stakeholders in developing dissemination materials.

Progress Summary:

Project 1: Joint Effects of Endocrine Disruptors, Diet and BMI on Child Development

For the prospective birth cohort component of this project, the second reporting period has been devoted to four things: (1) continued recruitment of pregnant women into the study, (2) tracking of enrolled women throughout pregnancy, (3) setting up the infant cognition lab and beginning the infant cognitive assessments in babies born to study participants, and (4) preparation of the dataset collected during the earlier Formative Center stage of our research for statistical analysis and publication. As of July 31, 2015, 254 pregnant women have been enrolled in the study. Of those, 8 became ineligible during pregnancy and 13 withdrew from the study during pregnancy. Another 11 women withdrew after their infants were born. Thus, as of July 31, 2015, there were 222 women actively enrolled in the new phase of the study. A total of 165 of study participants had given birth and 154 of those infants were still actively enrolled in the study.

During the reporting period, we successfully set up and implemented new state-of-the-art procedures for assessing cognition of infants during the first year of life. We are currently assessing cognitive functions including recognition memory, attention and information processing speed at 1-5 weeks of age, 4-5 months of age and 7-8 months of age in infants born to women in this study. All assessments are computer automated and the 4-5 and 7-8 month assessments make use of infrared eye tracking technology to track the infant’s looking behavior. We also recently began follow-up assessments of children recruited during the initial Formative Center phase of our research as they research 46-48 months of age. The test battery includes assessments of working memory, attention, inhibition, cognitive flexibility, numbers and counting, and language development.

For the adolescent component of this project, the second reporting period has been devoted to completion of data collection. We have leveraged data from an ongoing prospective birth cohort, the New Bedford Cohort (NBC), in combination with work performed as part of our previous Children's Formative Center. For the current project, a key component of this leveraged work was collection of urine samples (for EDC exposure measurements) on 200 NBC adolescents. We successfully completed adolescent urine sample collection in 2014 and now have samples on 205 NBC participants in keeping with our project goal of 200 urine samples. Eighty one % of adolescents examined during the data collection provided at least one urine sample and 144 (70%) of these provided 2 urines, collected approximately one week apart. As part of the parent study assessments, we have completed prospectively collected neurobehavioral assessments, home assessments, height, weight, diet, medical, demographic, lifestyle and exposure information available on these 205 children all of which are key data for this project's analyses. The urine samples are now pending EDC analyses at the CDC where levels of 11 common phthalate metabolites and 8 phenols (BPA, triclosan, butyl paraben, methyl paraben, propyl paraben, benzophenone-3, 2,4-dichlorophenol and 2,5-dichlorophenol) will be measured.

In August of this past year, we successfully recruited a postdoctoral fellow, Dr. Mahsa Yazdy, to work on this project. Dr. Yazdy is trained as an Epidemiologist with particular expertise in risk factors for birth defects and related developmental abnormalities. She has been an outstanding addition to our research group, contributing quantitative expertise, data analysis and data management skills, and her rapidly growing insights into the exposures and child outcomes we are studying. She is working with Drs. Korrick and Schantz on data analyses building on our Formative Center and ongoing P01 work.

Project 2: Endocrine Disrupting Chemicals, Diet and Gonadal Toxicity

Project 3: Endocrine Disruptors and Diet, Effects on the Developing Cortex

Community Outreach and Translation Core:

(a) Community Advisory Board (CAB): The CAB for the Illinois COTC includes leaders in early care and education, parenting, child advocacy, and public health in Illinois. In addition, a national leader in online Extension education is on the Board. The CAB was instrumental in providing feedback on the development of the child care survey for our formative research project as well as for the development of the first video public service announcement. They met once in Year 2 of the project with another meeting scheduled for the very beginning of Year 3.

(b) Design and IRB approval of a formative research protocol. Findings of formative research will inform COTC outreach strategy to stakeholders in child care, parenting and public health. As Year 2 of the Illinois COTC begins, a survey and series of interviews is underway with child care providers (Head Start, Center, and licensed family child care) across Illinois. The aim is to inform the development of COTC translation practices, by (1) defining baseline practices related to child endocrine disruptor exposures via plastics, food, drinks, packaging, cleaning products, fragrances, and personal care products, and (2) illuminating policies amenable to intervention at the state level, as one step in reducing children’s risk. We currently have responses from 89 providers.

(c) Spring 2015 Illinois COTC conference held. On April 21, 2015, the Illinois COTC co-presented a two-day conference in Springfield, Illinois to address environmental health in child care. The primary focus was on curtailing exposures to endocrine disruptors and was co-hosted by Illinois Action for Children, the child care licensing agency for Chicago and Cook County, and preeminent statewide advocacy organization. The keynote speaker for the conference was Dr. Susan Buchanan, MD, Illinois COTC CAB member and Director, Region 5 PEHSU. Her talk, “Children’s Environmental Health: How pollutants affect children’s growth and development,” was followed by breakout sessions, in which child care providers participated in semi-structured discussions about current resources and beliefs on protecting children’s environmental health in child care settings. Additionally, there was an opportunity for conference attendees to participate in an interactive learning activity that focused on strategies to reduce exposures based on the Eco-Friendly Child Care checklist.

(d) Deliberate outreach to fellow COTC’s. To understand past and present activity, the Illinois COTC has continued dialogue with COTC leaders from other Children’s Environmental Health Centers whose research also focuses on endocrine disruption, child care as an everyday risk setting for infants and children, and/or medical care as a site for outreach messaging. The COTC has also participated in monthly Children’s Environmental Health Center ETOCC & COTC conference calls hosted by NIEHS.

Future Activities:

Project 1: Joint Effects of Endocrine Disruptors, Diet and BMI on Child Development

Over the coming year, we will continue to recruit pregnant women into the cohort, and will assess infants at 1-5 weeks, 4-5 months and 7-8 months. We will also continue our assessments of 46-48 month-old children recruited during the earlier Formative phase, and we will analyze data collected during the Formative phase. We will focus the adolescent research on two main activities: (1) measurement of urine EDC concentrations on 155 adolescents to achieve our target of 200 adolescents with biomarkers of exposure. The first 50 were already analyzed via our Formative Children's Center; (2) once urine EDC concentrations are available, begin full scale data analyses to address study aims

Project 2: Endocrine Disrupting Chemicals, Diet and Gonadal Toxicity

During the next funding period, we will examine whether prenatal BPA and DEHP exposure cause oxidative stress in the gonads. Further, we will conduct studies to further determine the effects of BPA and DEHP on the developing gonads and fertility of mice in the second and third generation of mice. Finally, we will continue studies to assess the effects of the phthalate mixture on the gonads. Specifically, we will determine if the phthalate mixture causes germ cell loss and oxidative stress in the gonads.

Project 3: Endocrine Disruptors and Diet, Effects on the Developing Cortex

There are 2 major objectives for the next year: 1) finish the cohorts for the perinatal BPA exposure described above, publish the behavioral results and make significant progress on the neuroanatomical and epigenetic analyses; 2) raise all of the cohorts for the study of perinatal exposure to phthalates plus high fat diet and finish the behavioral testing on them.

Community Outreach and Translation Core:

Supplemental Keywords:

Relevant Websites:

Children's Environmental Health Research Center at Illinois Exit
Illinois Children's Environmental Health Research Center Community Outreach & Translation Core Exit

Progress and Final Reports: