suggestions regarding the collection of speci-
mens and information from younger siblings
of affected children were incorporated into
the study design. The CAC meets regularly to
hear updates on study progress and provide
input. CAC members have given critical
advice on data collection instruments, ways to
make the clinical protocol as child-friendly
and special-needs–friendly as possible, and
strategies to enhance recruitment.
The CHARGE study is building an infrastruc-
ture that will support multiple investigations
of autism and related neurodevelopmental dis-
orders. The psychometric evaluations and
clinical examinations combined with extensive
exposure information and biologic specimens
represent rich resources for research on etiol-
ogy and phenotypic expression of these disor-
ders and make possible the comprehensive
approach needed to advance understanding of
autism and DD. In our clinical assessments of
> 300 children identified with autism in the
California DDS system, we have confirmed
the diagnosis in 87%, suggesting that the large
increases in DDS system clients with autism
over the last decade or two is unlikely to be
due to overdiagnosis in younger cohorts.
Although several large birth cohort studies
recently initiated or in progress will be able to
examine factors that predict autism, the num-
ber of cases of autism in the CHARGE study
may be comparable with what is expected in
birth cohorts of 100,000 (i.e., we have enrolled
> 360 children with autism and are continuing
recruitment). In contrast with large cohort
studies with dispersed populations, we are able
to conﬁrm diagnoses using standardized instru-
ments administered by a small, well-trained
clinical assessment team. Additionally, in
cohort studies attempting to address a wide
range of health and developmental outcomes,
the exposures and factors measured will not
necessarily have been chosen for relevance
The specimen bank is currently being used
by several laboratories that are part of the UC
Davis CCEH. In this first stage, xenobiotic
and biochemical profiles of children with
autism are being compared with those of unaf-
fected children, and comparisons are being
made between different autism phenotypes. As
distinguishing features emerge, the second
stage will be to determine whether any differ-
ences in biomarkers were present at birth,
using the neonatal blood spots where possible.
Data and specimens will be made available to
qualiﬁed researchers with targeted, worthwhile
hypotheses not being addressed by CCEH and
Limitations of this study must be
recognized. Much of the information will be
gathered retrospectively. The only biologic
specimens prospectively collected (i.e., before
diagnosis) are the newborn blood spots and, for
some children, baby hair locks. Similarly, ques-
tionnaires on use of pesticides and other house-
hold products will be retrospective and hence
subject to reporting/recall bias. Thus, the large
birth cohort studies under way or in prepara-
tion will complement the CHARGE study by
providing fully prospective data, although they
are subject to the limitations described above.
Nevertheless, in the CHARGE study, medical
records will yield prospectively recorded data on
treatments, illnesses, and prescription medi-
cations. Other unbiased, relevant sources of
information on xenobiotics include blood
measurements that represent cumulative expo-
sures for persistent compounds and California’s
Pesticide Use Reporting system, which docu-
ments commercial pesticide applications that
can be linked to participant residences during
critical time windows.
Although sporadic studies have identified
speciﬁc environmental factors that have been
associated with autism, no previous effort has
attempted to address the broad spectrum of
environmental factors that may, in combina-
tion with genetic susceptibility, affect develop-
ment and severity of this condition in the
population. The CHARGE study is charting
new territory in the investigation of etiologic
factors for autism and DD. The goal of the
CHARGE study is to understand causes of
autism and DD, both genetic and environmen-
tal, in order to reduce their incidence in the
future. The design combines a large popula-
tion-based sample of children with different
patterns of development; standardized diagnos-
tic assessments of autism, cognitive develop-
ment, and adaptive behavior by trained
assessors; medical and neurologic examinations;
detailed reviews of medical records; and an
extensive set of questionnaires describing phe-
notypic characteristics and environmental expo-
sures from preconception through early
childhood. Currently, it is unique in its empha-
sis on environmental factors and its tight link-
age with state-of-the-art laboratories of the UC
Davis CCEH that enable us to address biologic
markers of xenobiotic exposures, immunologic
responses, and gene expression. Other features
include active community involvement, an eth-
nically diverse pool of participants, and inclu-
sion of developmentally delayed children in
addition to general population controls. Finally,
the collaboration by CHARGE study investi-
gators with other population-based autism
epidemiologic efforts currently under way, such
as the national Centers for Autism and
Developmental Disabilities Research and
Epidemiology (CADDRE) study, will create
valuable opportunities for replication and
perhaps data pooling.
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VOLUME 114 | NUMBER 7 | July 2006
Environmental Health Perspectives