Grantee Research Project Results
2003 Progress Report: Environmental Factors in the Etiology of Autism; Childhood Autism Risks from Genetics and the Environment (The CHARGE Study)
EPA Grant Number: R829388C004Subproject: this is subproject number 004 , established and managed by the Center Director under grant R829388
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: UC Davis Center for Children's Environmental Health and Disease Prevention
Center Director: Van de Water, Judith
Title: Environmental Factors in the Etiology of Autism; Childhood Autism Risks from Genetics and the Environment (The CHARGE Study)
Investigators: Hertz-Picciotto, Irva , Beckett, Laurel , Hansen, Robin
Current Investigators: Hertz-Picciotto, Irva , Croen, Lisa , Hansen, Robin
Institution: University of California - Davis
EPA Project Officer: Aja, Hayley
Project Period: September 30, 2001 through September 29, 2002
Project Period Covered by this Report: September 30, 2002 through September 29, 2003
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The causes and contributing factors for autism are poorly understood. Evidence suggests that incidence is increasing, but diagnostic changes & improvements may be playing a role. Both genetic and environmental factors appear to play a role. Autopsy studies demonstrate structural changes in the brain and clinical investigations reveal neurophysiologic differences in information processing in autistic vs. normal children. Members of our team recently demonstrated altered levels of certain neuropeptides at birth in children who later developed autism.
The proposed case-control study will be the first large-scale epidemiologic investigation of underlying causes for autism and triggers of regression. This study will capitalize on the strengths of the case-control design, which is well suited to examine a broad array of factors for rare conditions that are thought to be multifactorial. Comparisons will be made with both general population controls and mentally retarded children.
The aims are to assess the influence of exogenous exposures, the role of susceptibility factors, and the interplay between these two in the etiology of autism and its phenotypic variation. Chemicals with known or suspected neurodevelopmental toxicity, such as PCB’s, certain pesticides, and metals, will be investigated. This study will also pursue several hypotheses that have recently gained attention, including the combined measles, mumps, rubella vaccine and mercury present in vaccines given during infancy and early childhood. Additionally, biochemical susceptibility will be examined through characterization of metabolic, immunologic, and neuronal gene expression profiles and genetic polymophisms.
Progress Summary:
During the past funding cycle, the CHARGE study initiated subject recruitment, Regional Center chart abstraction, the clinical assessments, and biological sample collection in both the northern and southern California sites. To reach this stage, year two efforts focused on 1) obtaining Institutional Review Board approvals from the State of California, UC Davis, and UCLA; 2) refining, enhancing, and updating the clinical assessment protocol and instrumentation; 3) developing our protocols for expert review of Regional Center record information; 4) developing the exposure questionnaire; 5) developing, automating and enhancing the biological sample collection, distribution, documentation and archival infrastructure; 6) obtaining Regional Center (RC) participation agreements tailored to subject referral procedures at each Center, and providing continuing RC staff training; 7) obtaining electronic birth certificate records from the State of California and developing a stratified random sample selection, locator, recruitment, interview, and tracking process for the control subject population; 8) designing Web-based data systems for a variety of study-related activities; 9) deepening our relationship with the CHARGE Study Community Advisory Council, and 10) initiating an Oversight Committee to govern the use of data and specimens collected from CHARGE study participants. Highlights are below:
IRB: At this time, we have approval for the conduct of this study. Concerns regarding how we contact controls and how specimens are shared with other researchers delayed the renewal at UCLA. Other delays appeared to have been related to internal problems in the IRB at UCD.
Staffing : We hired an epidemiologic statistical programmer, two survey workers, a Regional Center coordinator/record abstractor, physician fellow, post-graduate researcher, and graduate researcher; a biostatistician (Assistant Adjunct Professor Jacob Wegelin) was added to the CHARGE project team.
Control selection: Random digit dialing was replaced by a more focused strategy, which matches the age, gender and geographic residence distribution of cases with controls, using State Birth Certificate records. Based on children identified as autistic from the RC’s participating in our study, we estimate these distributions. A pool of potential controls is generated through time, and using identifying information from the birth certificate, we attempt to locate most recent addresses, through a person-locator software to which we have subscribed. We then send an introductory mailing and after a week, begin telephoning. Based on our experience with the 50 names, we will modify our locating and contacting protocols.
Biological specimens & interactions with other Cores & Projects in Center: In year 2, we developed protocols for specimen collection, triage, and tracking, in coordination with the various laboratory cores and other projects. Because the children are small, only a limited volume of blood can be drawn, and we have attempted to optimize the information that will be obtained, through careful strategic planning. Since April 2003, biological samples have been transferred to all three of the Center’s Facility Cores.
Information Technology: Web based- systems were designed and implemented for abstraction of Regional Center charts, for subject tracking, and for data entry/storage. The data entry/storage system adopted by the MIND Institute is the ISAAC (Internet System for Assessing Autistic Children); it will be used for data entry of all clinical assessments and other related study forms. In addition, we developed our own in-house system to log all encounters and scheduled appointments. These Web-based systems are accessible from all field sites in southern and northern California by authorized users with passwords; all data are encrypted, and are protected by firewalls having the highest level of security allowed.
Environmental Exposure Questionnaire: The CHARGE Study Environmental Exposure Questionnaire was developed. Initially, we reviewed existing questionnaires from numerous other studies of birth and early childhood outcomes. Next, topic areas of potential relevance to autism were outlined. Items were selected, and the draft questionnaire composed. It was then distributed to over 20 persons to obtain feedback, and revised. The final Questionnaire includes: 1) Mothers medical history; 2) pregnancy & reproductive history; 3) diet and metals; 4) household product use; 5) index child pregnancy; 6) maternal illnesses, procedures, and medications during pregnancy; 7) index child illness/medication history; 8) demographic information; 9) residential history; 10) occupational history; and 11) maternal depression
Community Advisory Committee (CAC) : The CHARGE study has utilized the parent and professional members of the CAC from its inception. During the past funding cycle, the CAC has met twice in formal meetings. At these meetings, the progress of the study, and an introduction to the Center, have been presented. Isaac Pessah (Project 3, Center Director, Cell Signaling Core), Judy van de Water (Core 3 Molecular Biomarkers Core), and Bob Berman (Project 2, Animal Models) have made presentations for the CAC members. Discussion topics have included: 1) how to enhance recruitment, 2) hypotheses of interest, 3) approaches to outreach. Additionally, several of the CAC members (parents, scientists and service providers) have met individually and in small groups to complete a variety of tasks. The CAC has been instrumental in several other activities, including 1) reviewing and improving the clinical flow and “family friendly” experience for children and families participating in the study; 2) recommending content and language editing of the CHARGE Study informational brochures; 3) participating in the development of the agenda for the upcoming national environmental center meeting; 4) developing and prioritizing the list of community outreach and communication goals and then providing recommended activities to meet those goals; 5) participating in scientific discussions; 6) providing editorial input and a “Parent Point of View” article for the CHARGE study newsletter; and 7) giving parents’ perspectives on what information is provided back to families who participate in the study.
Outreach : The first issue of the CHARGE study newsletter was written and widely distributed to the autism community and others. UC Davis Public Affairs office issued a press release at the start of data collection. Major television/newspaper/magazine coverage about the CHARGE Study was also provided in the Sacramento and Los Angeles markets.
Future Activities:
The main activity for the upcoming year is recruitment and data collection for approximately 600 subjects, including clinical assessment, biological sample collection, and administration of the environmental questionnaire for all three subject groups (autistic, developmentally delayed, typically developing). Other supporting activities include: 1) identify the resources and develop a strategy to enhance the collaborative relationship with the Regional Center Agencies in Northern and Southern California and in turn accelerate the recruitment of children affected by autism and developmental delays; 2) fine-tune our protocols for recruitment of typical controls; 3) work with the MIND Institute as well as the university funding and marketing departments to identify the resource to enhance the CHARGE study outreach/communication activities in the identified communities to promote effective subject recruitment; 4) explore development opportunities for remote sites for clinical evaluation to minimize travel time and inconvenience for subject families coming to the University Clinic; 5) Fill staffing needs, including personnel to carry out clinical assessments, interviews, and medical record abstraction, as needed.
Journal Articles:
No journal articles submitted with this report: View all 2 publications for this subprojectSupplemental Keywords:
Autism, environmental epidemiology, neurodevelopment, neurotoxicology,, RFA, Scientific Discipline, Health, PHYSICAL ASPECTS, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Chemistry, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Disease & Cumulative Effects, Physical Processes, Children's Health, genetic susceptability, Biology, Risk Assessment, chemical exposure, neurotoxic, xenobiotics, biomarkers, gene-environment interaction, neurodevelopment, pesticides, exposure, halogenated aromatics, children, neurobehavioral, neurodevelopmental, neurotoxicity, etiology, susceptibility, human exposure, neurobehavioral effects, autism, biological markers, mechanisms, exposure assessment, neurological development, biomarker, synergistic interactionsProgress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R829388 UC Davis Center for Children's Environmental Health and Disease Prevention Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R829388C001 Environmental Factors in the Etiology of Autism; Analytic Biomakers (xenobiotic) Core
R829388C002 Environmental Factors in the Etiology of Autism; Cell Activation/Signaling Core
R829388C003 Environmental Factors in the Etiology of Autism; Molecular Biomakers Core
R829388C004 Environmental Factors in the Etiology of Autism; Childhood Autism Risks from Genetics and the Environment (The CHARGE Study)
R829388C005 Environmental Factors in the Etiology of Autism; Animal Models of Autism
R829388C006 Environmental Factors in the Etiology of Autism; Molecular and Cellular Mechanisms of Autism
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
2 journal articles for this subproject
Main Center: R829388
175 publications for this center
157 journal articles for this center