The International Collaboration for Autism Registry Epidemiology, known as iCARE, represents a one-of-a-kind research endeavor to study the prevalence and risk factors of autism spectrum disorders (ASD) around the world. What makes it unique is its use of national health registry data, not from one country, but from six international sites including Australia, Denmark, Finland, Norway, Sweden and Israel. In early 2009, Autism Speaks awarded more than $1 million over three years for iCARE to complete a study titled Multi-Registry Analysis of Pre- and Perinatal Risk Factors for Autism (click here for abstract).
National registries are invaluable research resources because they often cover a population-based sample of individuals from a given territory. This is important because it provides a much less biased way of assessing prevalence and risk factors for a condition. In addition, registry data is collected prospectively, and over long periods of time, often from birth through adulthood and sometimes even beginning with pregnancy. What is arguably the most important attribute of a national health registry is its large size, which is especially true when considering the relative rarity of autism and the complexity of its potentially numerous genetic and environmental risk factors. What makes the iCARE study so unique and important to autism research is that the investigators will not study data from just one registry, nor will they study data from multiple registries independently. Instead, they will actually combine data from six national health registries into a single, robust database. When asked about how this study differs from other autism research, iCARE investigator Glenys Dixon, M. Psych (Clin) from the University of Western Australia responded, "It is a unique study in that different countries are committed to working together and 'pooling' their data. The power of the research is far greater and can yield findings that can form the basis for future research." Dr. Dixon is a Psychologist and Senior Research Officer at the Telethon Institute for Child Health Research, and is also a recipient of an Autism Speaks Basic and Clinical research grant to examine international trends in the diagnosis and incidence of autism (click here for abstract). Diana Schendel, Ph.D. Health Research Scientist from the CDC and iCARE investigator added, "The size of the pooled sample that will be created for analyses is unprecedented. As a result of the large sample size, we will be able to perform many analyses of pregnancy and birth risk factors for autism with a very high degree of statistical precision." Dr. Schendel brings nine years of experience in autism research to the iCARE project and plays a key role as the project coordinator. The iCARE proposal is divided into three major aims. The first aim is the actual development of a combined multi-registry database. While it may sound straightforward, linking together six very large databases is a highly complicated task that will require a great deal of teamwork and the benefit of cutting-edge computer-based technology.
Once the pooled database is prepared, the second aim is to investigate the role of potential pre- and perinatal risk factors for the development of autism. Specifically, the iCARE team will examine the relationship between gestational length (the amount of time spent in gestation) and fetal growth (birth weight) and the risk for autism. Previous research has indicated that preterm birth and low birth weight are risk factors for some neurological and psychiatric problems. However, while hinting at a possible relationship between these factors and autism, previous research findings have been inconsistent and inconclusive. A common limitation among previous research projects, which will be addressed by the iCARE study, is small sample size.
The third and final aim of the iCARE project is related to the lasting impact the development of this large combined database will have on future research into the causes of autism. Successful implementation of this combined registry system will provide a valuable resource for future research as it lays the groundwork for the study of additional risk factors potentially associated with autism. This includes parental age, immigration status, as well as numerous other factors surrounding pregnancy and birth. Furthermore, in instances where registry data is or can be linked with biological samples, associations between autism and genetic and environmental risk factors can also be examined.
"The types of analyses that we will be able to perform on this unique data set will provide very detailed answers about the role of many pregnancy and birth risk factors for autism. This new knowledge will add more to our understanding of the causal pathways, most likely starting in pregnancy, that lead to autism," said Dr. Schendel.
"For families, the study findings may provide answers to questions that parents often have about whether events during pregnancy or the characteristics of their newborn had a role in the development of autism in their child. For investigators, the research may highlight factors that really should be studied in greater depth, and the research may also reveal that certain factors really are not involved. Future work can then focus on more promising clues as to the causes of autism."
While the group officially broke ground on the project at last month's International Meeting for Autism Research (IMFAR) in Chicago, the development of iCARE and this study have been many meetings in the making. iCARE began as a subgroup of the International Autism Epidemiology Network (IAEN, www.autismepidemiology.net), a science initiative of Autism Speaks, co-developed in 2004 with the U.S. Centers for Disease Control and Prevention (CDC). IAEN is a network for the exchange of information and collaboration of epidemiology activities across countries, and its central theme is to identify the unique role that epidemiology can play in understanding the causes of autism.
Epidemiology helps us measure the number of people affected by autism in a particular region. This in turn helps researchers, public health professionals, governments, and communities understand the global costs generated by autism both in terms of health and economic impact. Currently, autism prevalence has been well studied in only a few countries around the world, and even those studies have used different research methods making the findings difficult to compare and interoperate. By standardizing epidemiological research methods internationally, findings on autism prevalence and risk factors can be compared across countries. This research can also help us better understand the causes of autism. By looking for regional similarities and differences in the number of people with autism, we can begin to parse environmental and genetic risk factors in the different populations around the world.
Over four years, IAEN formed subgroups based on the differing methodologies used to do epidemiological research. One method is to use large, population-based health registries that maintain information on individuals with autism. The members of IAEN that came from countries with such databases formed a registry-focused workgroup that developed into iCARE and ultimately submitted a proposal to Autism Speaks in 2008 to help further their research efforts.
So what about the name you ask? For the International Collaboration for Autism Registry Epidemiology, iCARE says it all. While the 'i' may be lower case, emphasis should be placed on the fact that this is among the largest international research projects in autism today. On the other hand, the lower case 'i' (which is familiar nomenclature among today's technology) is a tribute to the innovative and complex technological approach the iCARE investigators are taking in combining multi-registry data into a "registry of registries" and in the analysis of that data. Of course the ultimate goal of this research is very much in line with the mission of Autism Speaks which is to change and improve the lives of all those affected by autism worldwide. Thus, for this team of highly dedicated and experienced investigators, "iCARE" is a very befitting name.
iCARE Participating Sites and Investigators
Helen Leonard, MBChB, MPH – Telethon Institute for Child Health Research, University of Western Australia
Glenys Dixon, M.Psych (Clin) – Telethon Institute for Child Health Research, University of Western Australia
Erik Parner, PhD – University of Aarhus, Denmark
Andre Sourander, MD, Dr Med Sci – Turku University, Finland and Columbia University, USA
Mika Gissler, M Soc Sci, PhD – STAKES National Research and Development Centre for Welfare and Health, Finland and University of Oulu, Finland
Raz Gross, MD, MPH – The Gertner Institute for Epidemiology and Health Policy Research, Israel and Columbia University, USA
Abraham Reichenberg, PhD – Institute of Psychiatry, King's College, London, England
Camilla Stoltenberg, MD, PhD – Norwegian Institute of Public Health
Cathrine Dahl, MD – Norwegian Institute of Public Health.
Pål Surén, MD, MPH – Norwegian Institute of Public Health
Christina Hultman, PhD – Karolinska Institutet
Micheline Bresnahan, PhD – Columbia University
Mady Hornig, MD – Columbia University
Ezra Susser, MD/MPH, Dr. PH – Columbia University
Diana Schendel, PhD – National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention