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APPENDIX D
Research Needs and Opportunities Related to the Measles-Mumps-Rubella Vaccine and Autism
Jane S. Durch and Kathleen R. Stratton, Institute of Medicine Staff
In October 1998, the Institute of Medicine's Vaccine Safety Forum held an open meeting to hear about emerging research on the newly published hypothesis that Measles-Mumps-Rubella (MMR) vaccine might be related in some way to autism. Researchers were invited to present their data and ideas to the Forum members and to other participants. Several research ideas were suggested by the participants, and these are summarized below.
The discussions highlighted several considerations in pursuing research on a possible vaccine-autism link. It was stressed that a clear case definition will be essential for many types of studies. An argument was made to resist focusing only on childhood disintegrative disorders or regressive autism cases until the full spectrum of the disorder is better understood. Care was also urged in ensuring that case definitions not be biased by prior assumptions about cause. Because diagnosis depends on observation of behavior, studies will also need to rely on well-trained observers to apply standard, validated assessment instruments.
Expertise from a variety of disciplines will be needed to address the questions related to autism and vaccine use. Some activities are already under way. A 5-year, $27 million international collaborative research program supported by the National Institutes of Health is focusing on the neurobiology and genetics of autism. The Metropolitan Atlanta Birth Defects Study has added school-based surveillance for autism and other conditions classified as pervasive developmental disorders. More than 400 cases have been identified between 1995 and 1998. In addition, a multidisciplinary panel has been established to conduct more detailed follow-up studies of autism cases reported to VAERS.
Other suggestions by workshop participants included a formal study of the effectiveness of the intravenous immunoglobulin treatment being given to some children with autism. If the treatment is effective, further study might shed addi-
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tional light on the mechanisms that produce autism. Cross-national studies were also mentioned because autism rates seem to be similar across countries that have differing immunization levels and practices. To gain a better understanding of the basic neuroanatomy and neurochemistry of the autistic brain, systematic and more frequent postmortem examinations should be encouraged. In addition, new technologies, such as noninvasive imaging, have the potential to provide better information on brain function and structure.
Research studies might also explore whether identifiable features of genetics, immune function, or other factors predispose some children to an adverse vaccine reaction and whether the brain can be protected in such children. For example, animal models point to changes in brain vulnerability as neonates age, so the effect of changes in the timing of immunization might be studied. It was noted that although the idea of finding markers for genetic susceptibility is appealing, such tools might be hard to use because of the cost of screening all children.