This post is by Alycia Halladay and Michael Rosanoff, members of the Autism Speaks Science Team.
Twenty years ago, autism affected somewhere around 1 in 2000 children. Today, it affects 1 in 110 children. In other words, autism prevalence has increased dramatically over the past 20 years. In fact, it has increased an estimated 600%. Seems straightforward enough, yet why do we keep hearing the same question…
“But is it a true change in autism prevalence?” That is, how much of the change in autism prevalence is truly due to an increase in autism risk?
In an effort to uncover the answers to this question, Autism Speaks and the CDC co-sponsored a workshop entitled “U.S. Data to Evaluate Changes in the Prevalence of Autism Spectrum Disorders,” held on February 1, 2011 at the CDC Headquarters in Atlanta, GA.
The “Evaluating Change” workshop was designed to bring together stakeholders from the autism community and thought leaders in the fields of autism epidemiology and public health to consider the factors driving the change in autism prevalence over the past two decades. A growing body of epidemiologic research has begun to piece together the prevalence puzzle. Factors such as younger age of diagnosis, broadening of diagnostic criteria, improvements in the availability of services, and better awareness of the disorder have all been attributed to the change in autism prevalence. However, recent epidemiological studies indicated that, while these factors do account for a portion of the change, they cannot account for all of the increase alone (see Figure which was adapted from a presentation by Dr. Peter Bearman at the meeting).
So, where is the rest of the increase coming from? What is causing it? And most importantly, what can be done to identify and quantify the influence of multiple genetic and environmental risk factors, and their interaction, on the change in autism prevalence over time? (For more background, please see “What is Causing the Increase in Autism Prevalence”)
Scientists, advocates, family members, and individuals with autism alike served as expert panelists charged to identify promising directions, scientific priorities, and possible approaches for better understanding ASD prevalence trends in the U.S. The beginning of the workshop focused on existing datasets that have been used to estimate autism prevalence and identify potential environmental risk factors associated with autism diagnosis. These include: the CDC’s Autism Developmental Disability Monitoring Network (ADDM), the California Department of Developmental Services (DDS) system, and Special Education data, as well as data from international health registries such as those from the Scandinavian countries. These surveillance systems, while not designed to study the causes of autism, nonetheless have been helpful in identifying possible risk factors. Not only have these resources provided information about the rising prevalence of autism, but they have also identified and replicated findings relating to parental age, obstetrical complications, certain chemical exposures and even genetic influences.
In addition to presentations on what has been already been done to understand reasons for ASD prevalence changes, examples of approaches to understanding prevalence changes from other health conditions were presented. Scientists from the fields of cancer, Parkinson’s, asthma, and schizophrenia research presented methodologies and models for deciphering prevalence trends in their respective disorders and how these previous efforts may inform autism prevalence research. In all cases it was found that changes in prevalence over time are often the result of a complex relationship between genetic and environmental risk factors, as well as factors related to diagnosis and awareness.
In the afternoon, participants broke out into discussion groups focused on the following topics: 1) How can prevalence information be used by stakeholders including parents, professionals, and policy makers? 2) What more can be done with ADDM data? 3) Where are there other sources of data that can be used for prevalence estimates and 4) What else can be done to understand ASD trends?
As the discussions progressed, a number of overarching themes started to become clear. Risk factors studied in isolation are going to underestimate their true influence. They need to be studied in combination. The influence of these risk factors is unlikely to be simply additive, and sometimes they will overlap. Therefore, the field needs new analytic models that can study a combination of multiple genetic and environmental factors. As Dr. Ezra Susser, from Columbia University said “It is helpful now not to look through the lenses of one side or the other, but rather both, and to use the information for better advocacy and awareness.“
Another participant, Dr. William McMahon from the University of Utah put it this way, “think of this black box of prevalence as a pinball machine. You can’t predict the trajectory of the ball based on just one lever. There are dozens of other factors that influence where that ball is going to go”.
Other recurring themes included the need for data on well-defined autism phenotypes, as well as the importance of data quality and accuracy.
Throughout the meeting public attendees contributed their ideas through thoughtful, careful comments. Stakeholders expressed their ideas and their hopes for the way prevalence data would be used – these included lingering and existing concerns about different environmental exposures, need for facilities for adults, societal treatment and acceptance, and reasons for differences in developmental patterns.
As understanding autism prevalence can help us identify priorities in research, services, outreach, and advocacy, the outcomes of this meeting will be published in a meeting report to inform future strategic planning. This workshop was only a first step in better understanding the changes in autism prevalence over time and characterizing the potentially responsible risk factors. Ultimately, as risk factors related to increased autism prevalence are uncovered and if those risk factors are modifiable, then researchers will have new targets for better treatments and prevention measures. The bottom line is that the dramatic increase in the prevalence of autism calls for urgent action to understand why the increase in occurring. It also underscores the crucial need for more and improved services to address the needs of people with autism spectrum disorders and their families.
by Sallie Bernard, Autism Speaks’ Board Member, co-founder and Executive Director of Safe Minds
Given the historic inattention of the scientific establishment to the environmental contributions to autism, it was nice to see a day-long conference on the topic held this week by a major research center. “Exploring the Environmental Causes of Autism and Learning Disabilities” was put together by the Children’s Center for Environmental Health at the Mount Sinai School of Medicine in New York City. The center is run by Dr. Phil Landrigan, who has been a prominent researcher on the harmful effects of environmental toxicants for decades. He told the incredible story of the harms of lead exposure on children’s cognition and behavior, and how the successful effort to remove leaded gasoline from the market in the 1970s resulted in rising IQ scores and economic gain to the country. I hope this same massive effort will be applied to autism and the chemicals which underlie the increase in its prevalence.
Also of note was the presence at the meeting of Linda Birnbaum. Dr. Birnbaum is the director of the National Institute of Environmental Health Sciences (NIEHS) which holds the autism/environment portfolio at NIH. The Mt. Sinai meeting follows on a workshop held at NIEHS several months ago which explored the role of the environment in autism. Large scientific initiatives in the field fall to the NIH, so without its support, gains will be painfully slow. Hopefully Dr. Birnbaum’s personal involvement signals a heightened interest at NIEHS to look at autism. Although Dr. Birnbaum stated at the conference that her institute spends $30 million on children’s environmental health, at a Senate hearing earlier this year, it was shown that just $8 million of this is for autism specifically.
A few interesting bits of information came out of the conference. One was the definition of “environment” that the insiders use. It covers synthetic chemicals like pesticides, flame retardants and plasticizers; heavy metals like arsenic, lead and mercury; combustion and industrial by-products; diet and nutrients; medications, medical interventions, and substance abuse; infections; the microbiome; heat and radiation; and lifestyle factors. Some may be harmful; others protective. They may operate before conception, during pregnancy or in early life, and some may alter gene expression through epigenetic modifications to chemicals surrounding our genes. Craig Newshaffer, who runs the EARLI study to look at environmental factors among younger autism siblings, referred to the concept of the “exposome”, that is, everything we are exposed to and its effects on health. Dr. Birnbaum’ made the point that health does not equal medicine, and prevention through reduction in chemical exposures is of equal importance to health. Colleen Boyle from the CDC stated that the next prevalence report will be issued in April 2011. We will see if the 1 in 110 number from last year’s report has changed. New research from Korea was unable to confirm increased risk of autism due to parental age or low birth weight, which have been identified as risk factors in Western studies.
The most informative talk was by Dr. Irva Hertz-Picciotto from UC-Davis. She explained how changes in diagnosis do not account for most of the increase in autism rates, and how recent research by their group on mercury and flame retardant blood levels do not address whether these substances are causative for autism because the blood samples were taken years after the autism diagnosis. A paper out this week from UC-Davis found that proximity to traffic air pollution during pregnancy almost doubles the risk of autism. Another paper just accepted by a journal has found higher antibodies to cerebellar tissue in children with autism relative to controls, highlighting the immune component in autism.
Other than these interesting items, the conference covered minimal new ground as far as the science goes. Rather, the points of the meeting seemed to be to make the case that environmental factors research in autism must now be considered mainstream science and to showcase the work being done or about to be done to investigate the issue. Dr. Landrigan made the case for an environmental role by noting that the rate of autism has increased too much to be solely genetic, and that at most, genetics alone will end up explaining 40% of autism cases with the likely percentage much lower.
Autism Speaks provided funding for the conference so that families could attend for free. Alycia Halladay, who runs our environmental science portfolio, noted that environmental factors and how they interact with genetics became one of Autism Speaks 5 priority areas for science in 2010. Autism Speaks also co-funded the NIEHS workshop on the environment earlier this year. Mt. Sinai plans to make video excerpts of the conference available in a few weeks.
Staff bloggers Alycia Halladay, Ph.D., Director of Environmental Sciences and Leanne Chukoskie, Ph.D., Assistant Director of Science Communication and Special Projects
A study published on Monday in Pediatrics revealed that newborns who experienced jaundice were at greater risk for a later diagnosis of autism spectrum disorders. Jaundice is a common condition where bilirubin is not properly excreted by the liver, builds up in the blood and leads to a slight yellow pigment of the skin. Bilirubin is a neurotoxin and it is well established that untreated severe jaundice can lead to brain damage and even death. Fortunately, despite the fact that jaundice is very common in newborns, it usually resolves with minimal or no intervention within a few days of birth.
Previous studies have investigated the potential for increased risk of ASD following jaundice with mixed conclusions. The advantage of this study is that the researchers used a large health registry database in Denmark including over 700,000 birth and associated developmental health records. The researchers looked at the development of 35,766 children diagnosed with perinatal jaundice (4.9% of the entire study population). They looked for children diagnosed with ASD as well as a broader definition of disorders of psychological development, which included speech delay. The risk of an ASD was found to be about 52% greater in children who experienced jaundice as newborns versus those who did not.
This may be an overestimate because factors such as season of birth, gestational age, parental age, gender, and the birth order of the child were not considered in this comparison. When these factors were considered, the overall risk increase was no longer statistically reliable. However an interesting pattern emerged from individually considering the factors.
Although preterm children typically experience a greater risk of autism by virtue of the challenges of prematurity, it is the full term babies that have an increased risk for ASD after exposure to jaundice. The authors speculate that there may be some unique window of vulnerability in brain development around 40 weeks gestational age that can explain this finding.
Another interesting relationship emerged from looking at cases from mothers who had previously had children versus those giving birth for the first time. Jaundice increased the risk for developing an ASD in children who were second or later born, but conveyed no increased risk for first born children. This effect is also a bit of a scientific mystery, however we do know that second and later-born children can be exposed to maternal antibodies that accumulate from previous pregnancies.
Lastly, the authors found that birth during the winter months was statistically associated with greater ASD risk than birth in the summer months. Exposure to daylight helps to break down bilirubin, so it is possible that individuals born in summer months, though diagnosed with jaundice had lower levels of bilirubin in their blood simply because they were exposed to more sunlight. The authors also note that sunlight is required for Vitamin D synthesis and low light levels in the winter may alter the body’s ability to as synthesize Vitamin D. Vitamin D deficiency is another autism risk factor under investigation. Autism Speaks is currently supporting a study examining how Vitamin D levels at birth and genes for the Vitamin D receptor are related to a later autism diagnosis.
In summary, it is important to note that although this paper brings many new considerations, it does not establish that jaundice causes autism. Instead, this paper reports on the risk of developing ASD after exposure to jaundice. This risk is significantly modified by several factors. Data from this study suggests that babies with jaundice who were born prior to 37 weeks gestation have little to no increased risk of ASD. However, the data also indicate a substantially elevated risk for full-term babies born to mothers with previous pregnancies and also full-term babies that were born during winter months. Hopefully, this and other information about medical conditions at birth will lead to the further development of screening tools to identify individuals at risk for a later autism diagnosis. Before that is done, scientists need to determine the mechanism by which jaundice may be contributing to the risk of developing ASD. Further research will been needed to determine whether bilirubin is itself an environmental risk factor, or if jaundice is a consequence of both genetic and environmental effects that elevate the risk of developing autism.
This was one of the major questions addressed at the International Meeting for Autism Research Meeting this week. Researchers from around the world – the U.S., UK and Canada, presented their research on the effects of early intense behavioral interventions to treat, and sometimes prevent, symptoms of autism spectrum disorders. Both parent training and clinic-based models were assessed. In many cases, a mix of both was used. While one study found that parent training alone was not effective in improving the symptoms of autism, a group in Canada found that parental training in applied behavioral analysis in children as young as 19 months, together with participation in the intervention process allowed parents to feel more empowered, independent, and reduced stress levels. Another randomized clinical trial in children screened and enrolled as young as 12 months showed that targeting social communication skills increased communication at follow up and decreased hypresponsiveness to sensory stimuli, possibly reducing symptoms of anxiety in children at risk for autism.
Early Behavioral Intervention may not only lead to improvements in functioning (as many as 50 percent of those enrolled in one study went on to a more mainstreamed school system) but also produce long lasting improvements. At the Kennedy Krieger Institute, using a 10 hour/week, 6 month classroom based curricula focusing on shared affect, shared affect and joint attention compared to an intervention protocol that did not target these behaviors, those in the treatment group showed improvements on more aspects of functioning, and these improvements lasted 2-6 years after starting in the study. An additional study at the University of Washington reported follow up data from the Early Start Denver Model, which is a comprehensive protocol targeting cognition, motor, language and social domains. Looking at what may have affected improved outcome using this model, researchers found that while individuals with less severe autism were more responsive to intervention, both those with mild and severe autism, and those who had high and low IQ at the start of the study all showed some response to treatment. What was exciting about the Early Start Denver Model was a presentation by a researcher at the University of California Davis who is adapting the training and implementation of the protocol using a web-based application, providing live 2-way interaction to families that lived miles, or thousands of miles away from a treatment facility. This affords more flexibility and accessibility to families on waitlists for early intervention treatments.
So is earlier better? The scientific consensus is yes, but what does “early” mean, and in what settings? The research is promising and encouraging, but more needs to be done, not only in identifying candidates for early intervention of autism, but in delivering evidence-based interventions that will be beneficial for the entire family.
The conference continues through Saturday. To read complete coverage from IMFAR, please visit http://www.autismspeaks.org/science/science_news/imfar_2010.php
This post is by Leanne Chukoskie, Ph.D. Dr. Chukoskie is the Asst. Director Science Communication and Special Projects at Autism Speaks and Asst. Project Scientist, Institute for Neural Computation, UCSD.
Having not previously interacted with the National Institutes of Environmental Health Sciences (NIEHS), I didn’t know what to expect. I must admit a tendency to equate the National Institutes of Health with the pinnacle of ivory tower research and a somewhat “stuffy” perspective on science. I could not have been more off base in describing the inaugural meeting of the Partners in Environmental Public Health (PEPH).
The initiative aims to bring together academia and community stakeholders as partners in improving environmental health, and this was clearly a charge that the leadership and participants took seriously (read a description of the meeting). The passion of the people participating in this meeting was palpable. Many of the community organizers and research partners in attendance have been seeking solutions for local environmental problems for years. Spontaneous applause and whoops from the audience erupted in response to community-empowering comments or discussion. This wasn’t your typical scientific conference! After each discussion session, the moderators had to actively intervene to end the questions and suggest that the conversation continue over the next break, lest we get horribly off our time schedule.
At the meeting my colleague, Alycia Halladay, and I conversed with other public health advocates about what we and other organizations are doing to disseminate research findings to members of the community. How were we learning what issues concern the community most? How do we use that information to address those concerns? How are we delivering scientific information about autism to the public and are they “getting it”? These other groups wanted to learn from us, and we from them.
We learned about an exceptional program that trained portreros (trusted communicators in the local Hispanic community) in various aspects of environmental science understanding using hands-on science demonstrations. The portreros then met with other members of their community to convey needed information about local environmental risks surrounding a superfund clean-up site. Could we develop the resources to train our team of volunteer Science Ambassadors at Autism Speaks similarly?
We also heard an important presentation from Michael Yudell, Ph.D., M.P.H. of Drexel University who spoke about communicating autism research findings to the public in a clear, direct and useful manner. Citing the history of how “blame” has been used by different ways and different groups to identify the causes of autism, Dr. Yudell offered recommendations for improving the dissemination of research based on a meeting organized at Drexel last year
It is in meetings like this is where the rubber meets the road. There are so many areas of opportunity for autism, which is one of NIEHS’ priority areas of investigation, including opportunities for organizations and other community advocates to partner with academia and apply for grants. Most importantly, however, this initiative enjoys ongoing support from the government.. We look forward to making the most of the opportunities offered and working with you, the autism community, to make the changes we need most.
This is a guest post by Alycia Halladay, Ph.D. and Leanne Chukoskie, Ph.D. Dr. Halladay is Autism Speaks’ Director, Research for Enivronmental Services. Leanne earned her Ph.D. at NYU’s Center for Neural Science studying the neural mechanisms that mediate vision during eye movements. During her postdoctoral training at the Salk Institute she studied search behavior in both humans and animals. A family connection as well as the curious manner in which people with autism tend to scan a visual scene led her to work for Autism Speaks as the Assistant Director of Science Communication and Special Projects. Leanne also continues her research as a Project Scientist at UCSD.
This is a guest post by Alycia Halladay, Ph.D. Dr. Halladay is Autism Speaks’ Director, Research for Enivronmental Services.
Instead of focusing on just genetics or just environmental factors, autism researchers have been studying gene-environment interactions as possible risk factors of the disorder. A next series of posts will begin to try and explain why this is an important concept, and how it is changing the way scientists think about causes.
Why is this concept important?
First, in the context of risk factors, if only the separate contributions of genetics and environmental influences is calculated without considering the interaction, the proportion of the disorder that is attributable to both is underestimated. For example, environmental factors may play an important role in the development of some diseases. However, in others, the effect is only seen in susceptible individuals. Studies that examine gene-environment interactions can do the following (taken from Hunter, 2005)
- Obtain a better estimate of the risk associated with genetic and environmental risk factors
- Strengthen the association between environmental risk factors and disease
- Help researchers understand the biological mechanism of disease
- Determine which environmental factors produce risk
- Lead to new prevention and therapeutic strategies
What does it mean?
As most people know, genetics typically refers to the stable sequence of nucleotides on DNA strands in every cell of the human body. The nucleotides are translated to amino acids, which in turn create proteins. The amino acid sequence determines how proteins are configured, which may affect their function. Put in an oversimplistic fashion, these proteins are what affect cell function. Some of the genetic code is inherited from both parents, and will be conferred to their children; another, more recently studied type of genetics, called epigenetics, refers to a change in protein synthesis that is not due to alterations in the DNA code. In other words, the DNA code stays the same but the way it is expressed changes. These concepts will also be discussed in a later chapter. With regards to the term “environment”, this is a term that can refer to many “non-genetic” influences on biology and behavior. Typically when they hear “environment” people think of one of the hundreds of thousands of potential chemicals and toxins that are present in food, air and water. However, environment can also include some demographic characteristics like socioeconomic status, nutritional status and education, as well as medical procedures and illnesses, and exposure to vitamins, pharmaceuticals and/or alternative medicines. It can even refer to exposures that we may not be thinking about every day, like UV sunlight, cosmetics, food additives, and ventilation in the home. While most people think of gene-environment interactions as an environmental risk factor producing more profound effects in a susceptible individuals, some genes may offer protection against deleterious environmental effects. Other genes may promote healthy development and their effects stifled, or even enhanced, in different environments. These concepts will be explored further in a different chapter.
How are these interactions determined and studied?
The best way to determine whether an interaction exists in a human population is an epidemiologic study. One of the biggest challenges is the need for large samples, or many individuals to enroll and participate. Typically, self-report measures are obtained from all participants and family members, and DNA and other biologicals are included to study DNA/RNA and level of exposure. If other measures are available such as medical records, these are also collected throughout the study. Genetic and environmental factors, and their interaction, can be studied retrospectively (after the disease has developed) or prospectively (prior to when the disease appears). Each design has strengths and weaknesses, and in many cases both approaches are taken to identify and then replicate findings. Other study designs include case-control vs. case-case. Case-control refers to studying both individuals with and without the disease. Case-case refers to studying cases (in this case individuals with autism only) both with and without different exposure levels and/or genotypes.
The NCS, or National Children’s Study, was authorized by Congress in 2000 as part of the Children’s Health Act. This study, unprecendented in size and scope in the United States, will seek to recruit hundreds of thousands of pregnant women to ultimately enroll and follow 100,000 children from gestation through adulthood. During the course of the study, parents and children will be studied carefully, with measures of behavioral, psychosocial and medical development tracked. This includes autism and autism spectrum disorders. Recent prevalence estimates suggest that around 1,000 children born to mothers enrolled in the study will develop ASD.
The overarching goal of the study is to examine how genetic and environmental factors affect child health and development. In addition to screening for autism spectrum disorders at 18 and 24 months, the current study protocol will collect multiple measures of genetic factors and environmental exposures, including specimens from mother, father and child at multiple times during development and adolescence, examination of environmental exposures, as well as medical information and medical events. The term environment is used broadly, and the study is very comprehensive in the frequency and specificity of examinations, as well as keeping in mind the magnitude and duration of a variety of exposures (medical, chemical, behavioral, psychosocial, demographic). Autism Speaks is currently working with the NCS to create a more developed and enhanced autism screening and diagnosis protocol, and identify solutions to clinical and ethical questions. This means that the NCS will be an instrumental tool for examining the relationship between genes and the environment and their relation to developmental disorders, including autism.
Because of the comprehensive nature of the study, families are expected to contribute a great deal. However, being enrolled in the NCS also provides an opportunity to contribute to a rich database of health information. This health information will be used to make policies on a statewide and federal level, identify possible intervention and treatment strategies for those enrolled, and provide participants with in depth evaluation and long-term follow up that they might not have received elsewhere. For the study to be successful, families should be willing to participate. Recruitment has already begun, and the study looks forward to talking to families who may be eligible to join – not just from those affected by autism, but those who are not affected. That means that your friends, family and neighbors could enroll even if you do not participate!!