2004 Progress Report: Clinical Sciences Project

EPA Grant Number: R829391C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R829391
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: CECEHDPR - University of Medicine and Dentistry of New Jersey Center for Childhood Neurotoxicology and Assessment
Center Director: Lambert, George H.
Title: Clinical Sciences Project
Investigators: Lambert, George H. , Johnson, William , Mars, Audrey , Moreno, Rosanne , Seshadri, Kapila
Current Investigators: Lambert, George H. , Carmody, Dennis , Johnson, William , Mars, Audrey , Moreno, Rosanne , Seshadri, Kapila
Institution: University of Medicine and Dentistry of New Jersey
EPA Project Officer: Louie, Nica
Project Period: November 1, 2001 through October 31, 2006
Project Period Covered by this Report: November 1, 2003 through October 31, 2004
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Health

Objective:

This project addresses three major hypotheses:

  1. The regression of neurological function observed in some children with autistic spectrum disorder, which occurs at the time the child becomes mobile, is a result of exposure to high levels of neurotoxicants.
  2. In children with autistic spectrum disorder, high levels of neurotoxicants can altar regional brain growth patterns as determined by magnetic resonance imaging (MRI).
  3. Susceptibility to developing autism can be influenced by the child or mother’s genotype of enzymes involved in protecting the developing human from chemical-induced oxidative stress.

The specific objectives of the research project are to: (1) compare and contrast the pattern of exposure to environmental chemicals of children with autism and determine if the pattern is different than that observed in children without autism, including documenting carefully mouthing behaviors (frequency and duration of time objects are in the child’s mouth), exploring their environment, and time on the floor; (2) identify if children with autism have altered body burdens of environmental chemicals as compared to children without autism; (3) determine if children with autism who experience regression or loss of neurological function as compared to children without autism that do not experience regression of function have behaviors that potentially expose the children to higher levels of environmental chemicals and/or have higher body burdens of environmental chemicals; (4) determine if children with autism have specific genetic predisposition to chemical-induced toxic effects; (5) determine if children with autism who experience regression of function have specific pattern of brain development as determined by MRI or have specific genetic susceptibility to chemicals induced biologic effects; and (6) determine if the specific recommendation to the parents regarding home environment or altering the child’s exposure to environmental chemicals, such as hand washing and so forth, can reduce significantly the exposure and body burdens of environmental chemicals in these children.

Progress Summary:

Recruitment

The recruitment of the subjects and their families was helped greatly by an article on the Center’s studies in children with autism in one of the two statewide newspapers. In response to the article, more than 400 families from 8 states contacted the Center to see if they could qualify for the study. Of these families, only 36 appeared qualified on telephone interview and were sent the protocol. About one-half of the families signed the consents and sent them back. Currently, we essentially are booked through July for new research subjects. We have been overwhelmed by the interest of parents, many of whom are severely disappointed that they cannot participate in the study because of exclusion criteria.

Children’s Behavioral Assessment

A total of 14 children have been seen; 11 children have completed the Autism Diagnostic Observation Schedule (ADOS) and psychological testing, and 3 additional children have completed the ADOS and are scheduled to complete the remainder of the psychological testing. Of the 14 children who have completed the ADOS, 11 are males and 3 are females. Regression in either language or social areas was reported in 8 of the 14 children who have completed the ADOS. Of the 11 children who completed the full battery of psychological tests, 8 have cognitive scores within the Very Low category of cognitive ability. One child has a score within the Low category. One child has a score within the Below Average range. One child has a score within the Above Average range. It should be noted that for all children, difficulty with joint attention impacted performance. For the 11 children who completed the full psychological battery, 3 children are reported to have adaptive functioning within the Moderately Low range, 7 children are reported to have adaptive functioning within the Low range, and 1 child is reported to have adaptive functioning within the Adequate range. Of the 14 children who have completed the ADOS, 6 children meet ADOS and clinical criteria for Autistic Disorder (AD), 8 children meet criteria for Autistic Spectrum Disorder (ASD), and all 3 female children meet criteria for AD.

Medical Histories. Medical histories to document regression and developmental histories are being obtained from the subject’s medical caregivers.

Biologic Sample Ascertainment. Initially, our concern for the children was emotional and physical trauma related to blood-drawing. We started using Emula cream (4% lidocaine) to decrease the pain. We subsequently think that the major trauma is not the pain of the needle but just being held. We have had significant problems with getting urine samples because none of the subjects have been toilet trained, and they fight having a U-Bag on. We are exploring the methods to collect first morning diaper samples and assure that the samples are not contaminated.


The turnaround time on the biologics has been very slow. We are amending the way samples are handled and expectations on data turnaround time. We will make the turnaround time a few days on lead and metals and quarterly on other samples. Lead levels of the initial nine subjects are within expected ranges.

Significance

The data set is too small for any meaningful analysis. The number of children with regression is large and we question the validity of the parental recall and are planning additional documentation besides the child’s caregivers. The other surprising result was the amount of enthusiasm the parents displayed to have their children studied.

Future Activities:

Recruitment

The pool of subjects created from the article in late December and their contacts almost has been utilized totally at this point. We have enough subjects for July but will need to start active recruitment for the first time. We have developed a flyer (approved by the Institutional Review Board at the beginning of the study) and a brochure that will be used for active recruitment. We will actively distribute the brochure by mailing it to all new members of COSAC (our community partner) and having all the developmental pediatricians give it to all new families with a child less than 36 months with autism. In addition, 0-3 Applied Behavior Analysis schools in New Jersey will distribute the brochure to the appropriate parents. We also are contacting the newspapers to do another story on autism, but this time the theme will be the children’s exposure to chemicals and how to reduce exposure. In the article, we hope to discuss the autism study and need for volunteers. A concern of the study is selection bias and we have reached out to our colleagues in Newark and Camden to identify minority families that meet the criteria.

Documentation of Regression and Behavioral Assessments

We are obtaining family pictures and videos of the child subject to see if we can document changed behavior. This is in concert with Dr Lewis’ group. We also are adding with Dr Lewis’ group several innovative methods to assess the child’s self-identity and capacity to interact with the environment and social engagement.

Urine Collection and Analysis

The urine collection method most likely will be changed to include obtaining a first morning diaper sample when we are unable to get a urine sample at time of visit or at home during toilet training. These changes have to undergo quality assurance/quality control determination with the Centers for Disease Control and Prevention (CDC). The CDC also has volunteered to run phthalate metabolites in the urine of the subjects. This is most interesting because the children with autism may have higher amounts of phthalates in their urine from increased mouthing of objects. This is compatible with our other studies of phthalates in brain function and development.

MRI Analysis

MRI analysis will be done using the MRI methods for study and analysis of volumetric brain functions employing the National Institute of Child Health and Human Development (NICHD) methods developed by the Brain Imaging Consortium. The NICHD study of 100 children in our age group should be done soon by this consortium. Lisa Freund from NICHD indicated that they will most likely make their methods and normative data available to us for normal controls. We also will have access to their analytical methods. We will make our data available to them for collaborative comparisons between the two groups’ datasets.

fMRI Analysis

We propose to conduct functional MRI (fMRI) neuroimaging of children with ASD to assess brain structure and function. We also are interested in learning how children with ASD process auditory information that is socially relevant. The specific aim is to identify in children with ASD the brain activity during listening tasks. To this end, we plan to conduct MRI studies of brain structure and maturation and an fMRI study measuring brain activity of children with ASD while performing passive listening tasks. We will identify brain regions activated while children respond selectively to a series of auditory events that are socially relevant and compare their brain processing to that of a control group of infants who do not have ASD. We expect brain areas to be activated when hearing sounds of objects such as numbers. The question is, do infants with ASD process the sounds in a similar manner as do control children? Then, do infants process socially meaningful sounds differently than the sounds of objects? Finally, do infants with ASD process sounds with social meaning differently than do control infants?


Journal Articles on this Report : 1 Displayed | Download in RIS Format

Other subproject views: All 9 publications 9 publications in selected types All 8 journal articles
Other center views: All 86 publications 50 publications in selected types All 49 journal articles
Type Citation Sub Project Document Sources
Journal Article Hsu P-C, Huang W, Yao W-J, Wu M-H, Guo YL, Lambert GH. Sperm changes in men exposed to polychlorinated biphenyls and dibenzofurans. Journal of the American Medical Association 2003;289(22):2943-2944. R829391 (2004)
R829391 (2005)
R829391 (2006)
R829391C005 (2004)
  • Abstract from PubMed
  • Full-text: ResearchGate-Full Text PDF
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  • Abstract: JAMA-Abstract
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  • Supplemental Keywords:

    children’s health, disease and cumulative effects, ecological risk assessment, environmental chemistry, health risk assessment, risk assessments, susceptibility/sensitive population/genetic susceptibility, toxicology, genetic susceptibility, assessment of exposure, assessment technology, autism, behavioral assessment, behavioral deficits, childhood learning, children, developmental disorders, developmental effects, environmental health hazard, environmental toxicant, exposure assessment, gene-environment interaction, neurodevelopmental, neurological development, neuropathological damage, neurotoxic, neurotoxicity, outreach and education, public health,, RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Children's Health, genetic susceptability, Biology, Risk Assessment, childhood learning, neurotoxic, gene-environment interaction, developmental effects, children, neurotoxicity, assessment of exposure, public health, behavioral deficits, environmental health hazard, autism, outreach and education, assessment technology, developmental disorders, exposure assessment, neurological development

    Progress and Final Reports:

    Original Abstract
  • 2002
  • 2003
  • 2005 Progress Report
  • Final

  • Main Center Abstract and Reports:

    R829391    CECEHDPR - University of Medicine and Dentistry of New Jersey Center for Childhood Neurotoxicology and Assessment

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R829391C001 Neurotoxicant Effects on Cell Cycle Regulation of Neurogenesis
    R829391C002 Adhesion and Repulsion Molecules in Developmental Neurotoxic Injury
    R829391C003 Disruption of Ontogenic Development of Cognitive and Sensory Motor Skills
    R829391C004 Exposure Assessment and Intervention Project (EAIP)
    R829391C005 Clinical Sciences Project