Wisconsin Public Television University Place  Prevalence Trends and Risk Factors for Autism  Maureen Durkin  1/26/13 UP827  cc >> It's a group of experts to give you an update on the epidemiology of autism spectrum disorders, specifically an update on what we're seeing in terms of the trends of autism prevalence and also some of what we're learning about the risk factors for autism spectrum disorders. And just like Dr. Lainhart conveyed that we're in our infancy in terms of our understanding of the neurological basis of autism, the same could be said about the epidemiology of autism. We're really just beginning to understand the frequency. Now, for those of you who are not so familiar with epidemiology as a field of study, I'd like to begin by just defining what it is. The most common definition of epidemiology is the study of the frequency of diseases or other health outcomes in populations. And I want to emphasize the world "in populations" here because epidemiologists, rather than studying the frequency or the characteristics of patients who come to a particular clinic for services, we try to account for all of the cases occurring in a defined population and their characteristics and frequency. And this is important for two reasons. First of all, for a condition like autism where we can't assume that everybody with the condition in the population has received a diagnosis and is receiving services, if we just do our studies based on those who do get into services, we could have very skewed impressions of what the frequency is and what the characteristics are. The other reason for studying the frequency in the population is so that we have a comparison group. So, if we only studied children coming for services, we wouldn't know how different they are from children in the population they come from. 

But if you study the frequency in the whole population, then you can compare the characteristics of children with autism to those other children in the population and identify risk factors for the disease and also calculate the prevalence of the proportion in the population affected. So, why do we even study the epidemiology of disorders such as autism? Well, the main reasons are to get insights into what the causes of the disorder are. Also, to understand the proportion of the population affected so that we can plan for service needs and then monitor over time to what extent children needing services are receiving them. Also, epidemiologic studies are used to evaluate the effectiveness of services and the cost effectiveness and to identify public health priorities and use this information for both primary prevention of diseases and also for improving the outcomes of people that have autism and monitoring and improving the quality of life. So, these are the reasons we do it. Now, what's shown in this graph is actually not from an epidemiologic study, even though it looks very much like it would be. It looks like an epidemic or a dramatic increase in the frequency of a condition over time. What it shows, and you might be familiar with this graph, is the number of children in the state of Wisconsin in 1992 and then all the way up to 2008 who were served under the autism category in special education. So it's the number of school-aged children in the state receiving services for autism. And you can see that in 1992, it was only 20 children, and by 2008, it increased to almost 7,000. 

I don't know if you can see down in the footnote, but the most recent data available are from the 2011-2012 school year, and the numbers increase to almost 9,000 children. So, this is almost 400-fold increase in the frequency. But what we have to note is that autism didn't exist as a special education category until 1992. And so what these data show is sort of the adoption of the category and that every year since, the numbers served have increased. Now, this kind of a trend has been used by people to say that we do have an epidemic of autism, and maybe it's due to something like vaccines or some environmental factor in the population that could be increasing. But we can't really say that based on just administrative data of who's receiving services because in order to believe that, you'd have to believe that in 1992 there were only 20 children in the whole state who had autism, and that's just not a tenable assumption. Now, Matthew Maenner, who is a postdoctoral fellow and an epidemiologist here at the Waisman Center, had the idea of looking in the state to see if we can find evidence that the increase is due to this gradual adoption of the category, the autism category over time at the school district level. And so, what's shown here is geographically that each unit is a school district. And the darker blue shades are very low prevalence of children receiving services for autism in the school district. Less than two per thousand. 

And then the darker red districts are those that had high prevalence of over 14 per thousand children receiving special education for autism. And you can see in 2002 most of the state was blue, very low prevalence, and over time it's become increasingly red. And this next slide shows that, it classifies those school districts by whether they were high or low prevalence in 2002. And you can see this tremendous variability across the state, but the group that had high prevalence in 2002 has pretty much stabilized at over, it's about 12 per thousand or a little over 1% of children in the schools receiving services under the autism category. Whereas, what we see with the districts that had low prevalence in the beginning is sort of a catch up phenomenon, and it seems that most of the increase we're seeing in the state over time is due to these districts catching up, so to speak, to the districts that had a high prevalence in the first place. So, these results are at least consistent with the idea that the prevalence may be stabilizing, at least as a school reporting category, at about a little over 1% of children in the school districts needing services under that autism category and that the rates statewide will continue to increase until all the other districts catch up to this level. At least that's what we would predict. Now, we don't know for sure. In the future it could rise again, but that's basically the conclusion from these analyses. But those were school administrative data, as I said. 

They're not counts of all the children in the population with autism based on epidemiologic survey. Now, it turns out that the first epidemiologic study ever done of autism in the United States was conducted here in Wisconsin by Darrell Treffert, a psychiatrist who went around the state in the 1960s, when he conducted the study, and reviewed records and actually examined children in the age range of three to 12 years. And he identified a total of 280 cases, statewide, meeting criteria that were used at the time to diagnose autism. And this corresponds to a prevalence of about three per 10,000 children, or in other words, about one in every more than 3,000 children. So autism, during this time period, the first epidemiologic studies, was considered a very rare neurologic condition that, for example, most pediatricians might never even see a child with autism in their practice. That's how rare it was. But referral centers, like the Waisman Center of course, would be seeing them. This was our first estimate from the United States, and what's shown in this graph are kind of the prevalence estimates since the very first study in 1967. Here's our second study in Wisconsin, 1970. And then all the way up to the latest data from 2012. 

And you see, this is the total number of children in the population that meet criteria for an autism disorder. So, it's per 10,000 children. And you can see that it's extremely rare early on. It wasn't until the 1990s that we started seeing a gradual increase and then a steeper increase. These are color coded. So, the blue bars represent North America, or sorry, European studies. And this yellow bar is a study from South Korea that sort of shocked the world in 2011 when it was published. They found that over 2% of children in South Korea in an epidemiologic study where they screened everybody and assessed met diagnostic criteria for autism. So, this is really now out there as sort of the new benchmark that people are thinking we might be finding prevalences that high in the US as well. So, these studies, it's difficult to compare over time because there has been some change in diagnostic criteria, but these at least are all epidemiologic studies where they did try to count everybody, whether they had a previous diagnosis or not, in the population. 

Now, the intense concern beginning in the 1990s that the epidemiologic studies seemed to be showing such an increase, really it was parents of children with autism, mainly, and their concern about it. They lobbied congress to order the CDC, the Centers for Disease Control and Prevention, which usually monitors infectious diseases and things like that all the time, and they were monitoring some developmental disabilities but not autism. But they called in the CDC, congress then, based on the parent concerns, called on the CDC to begin monitoring autism in the population to figure out whether we can see whether there's, even when you hold the methods and diagnostic criteria constant, what are we seeing in terms of the prevalence and trends over time. So, the CDC launched the Autism and Developmental Disabilities Monitoring Network in 2000, and here in Wisconsin we've been part of this network since 2003. We've been monitoring the prevalence because we do it retrospectively somewhat. So we've been monitoring the prevalence since 2002 in the state every two years and publishing reports. Most of the data I'm going to show you are from this effort. Basically, what we do is we assume that every child by the age of eight years who has an autism disorder will have received some kind of services. They might not have a diagnosis of autism, but they would have some encounter with the healthcare system having developmental assessments or concerns about their development or they might be in special education. And so we search the records of children who have received any services for developmental disorders or developmental assessments. 

And then we screen them. A team of abstracters reviews them to see if there's any indication of autism. They abstract the information from the records into an anonymous de-identified data file. And then an expert review team evaluates all these records to determine whether children meet diagnostic criteria for autism or not. And here's a diagram of what, so for the year 2008, our most recent surveillance year, nationally, we've done prevalence study in a population of over 300,000 children in the various states participating. We reviewed over 40,000 records for over 30,000 children and then did detailed abstractions  on about almost 7,000 and identified 3820 children meeting diagnostic criteria for autism for that year. As I said, we do this every two years, and we publish them in a publication called the MMWR. That stands for the Morbidity and Mortality Weekly Report. This is a publication CDC does. Every week they publish something on this where they monitor rabies and influenza and food poisonings and things like that. 

They can monitor them, identify changes, and then address them promptly is the whole idea behind the MMWR reports. But beginning in about 2007, they started doing every couple of years doing a report on the prevalence of autism based on the surveillance data that we're collecting. And what is shown here is just sort of a summary. So, since 2000, every two years we've published, we've generated a prevalence estimate. And the thing about these data that are different, I think, from the international data I showed you or the school data is we haven't changed the methodology at all over time. So, we use exact same methodology, same diagnostic criteria, and every two years we try to count the number of children that meet criteria, eight-year-old children. And so when we do this, we can't really say that change over time is due to changes in methods or anything like that. And what we've found, in 2000 the prevalence was estimated at 6.7 per thousand children. A little more than a half a percent of children. And then it was very similar in 2002. 

But then each year since, it's been increasing kind of steadily so that our most recent year, 2008, we have over 1% of children, or 11.3 per thousand children meeting diagnostic criteria based on this national surveillance system. And what we see here is differences by sex. So, just as every epidemiologic study, including the Treffert study I showed you from Wisconsin earlier, finds that boys have a much higher prevalence of autism than girls. So we see here in gray it's the male. The prevalence from 2002 to 2008. And it's increased in males and less so in females, but still somewhat of an increase. The blue line is overall. So, overall, we've seen a 78% increase in the prevalence between 2002 and 2008. And then if we look at autism prevalence by race or ethnicity, based on these national data, we find that there are some differences. So, it seems that non-Hispanic whites have the highest prevalence. 

It's increasing in every group, but there are the differences between ethnicities. And Hispanics have the lowest prevalence, at least as reported in our surveillance system. And the other thing we've found is not every site has information on IQ or intellectual functioning of the children. We don't in Wisconsin because we've used school records here. But the sites listed that do include Arizona, Arkansas, Georgia, New Jersey, North and South Carolina, and Utah. And what we see is that, what this shows is in boys and girls, the proportion of children with autism who also have intellectual disability, essentially. So, the darker bars is the proportion that have IQ below 85, in the gray, and then down here is below 70. And, basically, what this shows is that in every state, a higher proportion of girls with autism have intellectual disability than boys. And we don't really know why that is, but it's sort of a clue that gives us something. Maybe that would give a clue to better understanding of the underlying disorder in autism that would produce that. 

Here's just another summary of what we've found across the sites in 2008. Each of these circles represents a different study site. So these are the different states participating. Here we are in Wisconsin. And the size of the circle indicates how big the study area was. So, some of these that have really small study areas had very high prevalence. So, here's prevalence. I think this is Utah with over 20 per thousand, so that's really getting up there just like South Korea, at over 2% of eight-year-old children in their study area meeting diagnostic criteria for autism. But it's a very small study area. Here in Wisconsin, we're in kind of the low end in terms of prevalence at about seven per thousand children. 

So it's still under 1% in our full study area in 2008. I want to just convey some of the things we've been learning from these surveillance data in addition to just the trends and the numbers of children affected. Paul Shattuck, who was also previously a postdoctoral fellow here at the Waisman Center, is now at Washington University in St. Louis, and he led this study where he looked to see what we could determine, as I mentioned, not everybody in the epidemiologic study would necessarily have a diagnosis of autism in the community. They may have never been told, the parents may have never been told the child had autism. But the review of their clinical condition indicates that they did meet criteria. And what Dr. Shattuck did was he identified that, overall, 27% of children participating in this national surveillance effort that did meet criteria for autism did not have a diagnosis previously by the age of eight years. And then he looked at what factors influenced the later age of diagnosis. And, basically, identified this large gap between the age that children actually first received services for autism, even those that did have a diagnosis, the median age that they got it was 5.7 years. So they've missed an entire opportunity for early intervention. So that's just another way of using these surveillance data to monitor access to services and the timing of access to services. 

We can't possibly make much progress if children aren't receiving services until an average median age of five, almost six years old. But also, what we did see, at least in our Wisconsin data, is that 89% of the children who eventually by age eight met criteria for an autism disorder had some kind of developmental concern noted in their medical record by the age of three years. And the most commonly documented concern was language delay, followed by delays in social development. So these children were getting screened and monitored but no diagnosis. Many of them, no diagnosis of autism until much later. Now, just to give you a little more information about our results for Wisconsin from the surveillance system for the year 2008, basically we're only monitoring autism in this 10-county area of southeastern Wisconsin, and that's just because we had to pick an area that had at least 30,000 births a year to qualify for the CDC funding. This is the most efficient way to get that number because it's the most densely populated portion of the state. If we had funding, we would probably want to do it statewide, but this is what we have so far. And it's a fairly diverse population. About 35,000 children overall, eight years old, and about 65% are non-Hispanic white, 17% black non-Hispanic, and 14% Hispanic, 4% Asian. 

In this study area overall, about 15% of children receive special education services overall, not necessarily for autism. And what we've found is, like everywhere else, that boys were over three times more likely than girls to be identified as having autism. And these show our Wisconsin trends. The yellow is us and the purple is overall network sites. And you can see that, well, what's not shown here is the racial difference. But here in Wisconsin, we found white, non-Hispanic white children to have a prevalence of 8.6 per thousand, black children 5 per thousand, and Hispanic children 3.8 per thousand. We also have found huge differences between, say, Dane County and Milwaukee County with the prevalence of autism in Dane County being about more than three times higher than it is in Milwaukee County. And we don't know how much that could be due to people migrating here for services or to other factors. From our surveillance system we can't really tell. But there's been so much attention to this phenomenon of the rising prevalence of autism, so not only in the school data but even when we conduct epidemiologic studies using standard methods over time. 

And this shows just a list of the reasons for this increase that have been considered. And one of them is that the diagnostic criteria for autism have expanded over time, and so we're identifying more and more children. And want to show you a slide here that sort of counters that notion a little bit. As you know, the DSM, the Diagnostic and Statistic Manual of the American Psychiatric Association is what's used to diagnose all mental health disorders in the United States, and they change it every few years and change the diagnostic criteria. And they're in the process of changing it again to DSM V. But the first time autism was included was in the DSM III and then IV and now we're working on V. But what's shown here is how the prevalence in different studies around the world has varied since the '60s up to now, and what's coded here are when different criteria were used. And the reason I point this out, in the latest version of the DSM, we still have this huge variation from very rare, low prevalence to very high. So it isn't simply a matter of changing diagnostic criteria that's accounting for this trend, we think. Just going back to the other reasons, another set of reasons is that there's a change in the diagnostic practices for autism. 

And specifically things like diagnostic substitution which is this idea that clinicians are diagnosing some disorders less and diagnosing more autism. So there's not really more cases occurring, it's just that there's more children with disabilities getting the label of autism instead of something like intellectual disability. And we do have some evidence of that which I'll show you in just a second. The other thing is diagnostic accretion which is the idea that it used to be that you'd only have one disorder almost. For example, if you had Down syndrome, you wouldn't be evaluated for autism. But now we routinely diagnose both conditions in the same children, and we just heard in the previous talk about co-occurring conditions in children with autism. So, this process of you don't rule out autism just because they have another disorder could be one of the things contributing to this increase. And then, there's been a huge expansion of developmental screening, especially in the last few years. And the American Academy of Pediatrics is promoting routine screening for autism disorders in pediatric visits. And this could account for some of the increased measuring of prevalence and attention to autism. 

And we talked already about the gradual adoption of autism as a special ed category. So, once services for something become available, you'd expect an increase in the diagnosis. What's the point of diagnosing it in the absence of services? So this could be contributing. I said I'd give you, this is, I think, it's hard to look at this slide and not think that there is some of this diagnostic substitution going on. What's shown here is based just on the special education data for the state of Wisconsin from 1997 to 2011. And in yellow is the number of children served under the autism category, and the red is the number served under the cognitive disability. And you can see that the decline in cognitive disability doesn't fully account for this rise, but it seems to account for a good part of it. So that might be some of what's going on in our trends over time. Let me go back and see. So, just in terms of other possible explanations, the one I'd like to focus on now is changes in risk factors. 

Could it be that there's risk factors for autism that are changing over time that could account for the increase or at least part of the increase we're seeing. So, we've been working, the other colleagues at CDC and I in this network that we're involved in, have been looking at a number of possible risk factors and then monitoring them over time to see could they explain some of the trends we're seeing. And some of the risk factors we've looked at are perinatal factors. So, factors associated with birth and pregnancy. And it's been pretty consistent finding now that preterm birth, for example, children born very prematurely are at increased risk for autism. And the proportion of infants born preterm is also increasing over time, and this is partly due to the improved survival of children with very low birth weight, very preterm. So, they didn't used to survive to be counted and now they are. And some extent, some of the rise we're seeing could be attributed to that low birth weight and preterm birth. And then some of the other factors we've looked at, and I have a few slides to show you about, are birth spacing or what we call the interpregnancy interval, the interval between the birth of one child and then the conception of the next child. And there's one paper out there suggesting that a very short interval, less than 12 months, is associated with an increased risk of autism. 

The one study showed that children born less than 12 months, or conceived less than 12 months after the birth of their older sibling were more than three times likely than other children to develop autism. So, we tried to look at that, and I'll give you some results. And then birth order and advance parental age are other factors we've looked at. So, this shows the results just from our Wisconsin data on the interpregnancy interval, and you can see that this is the prevalence of autism in children who were conceived less than 12 months after the birth of their older sibling. And then it goes down and then it rises again with the long pregnancy interval. And we don't really know. We're still investigating this. We don't really know what it is, but if there was no association, you wouldn't see this kind of a difference. It should be the same. So, we're thinking some of this increase in the long interval could be due to fertility problems, which there is some evidence that infertility is also associated with risk of autism, and possibly the infertility treatments. 

But an older maternal age is associated with a long interval and that could explain some of that. But why we see this increase in the under 12 months we don't know. One of the reasons we're interested in this is because in contrast to a lot of the other risk factors, for example, genetic factors and so on, this is something that is potentially modifiable. If we knew that this was contributing to autism, you could make recommendations about pregnancy spacing. So that's why it's of particular interest. The other ones I mentioned were parental age. Now, there have been reports over time, a lot of inconsistency in the literature, some studies find that increasing father's age increases the risk of autism. Other studies suggested it wasn't father's age, it's mother's age. So since those two are often very correlated, it's difficult to tease them apart, but, with our large epidemiologic studies were we have thousands of cases, it is possible to measure the separate effects of maternal and paternal age. What we found, now this has been replicated in a number of studies, is both the mother's age, so increasing prevalence with increasing mother's age, especially 35 and up, and also with father's age. 

Even controlling for the other parent's age. So, with father's it's age above 40. Now, it's not a dramatic increase. It's a pretty steady, it's a clue to maybe understanding the ideology of the disorder. It's not such a strong risk factor that it has implications for prevention because the vast majority of births to older parents don't have autism. So it's not such a strong association. But as a clue to what's going on, it's very interesting for an epidemiologist. The other thing we found is that the birth order is associated. So, first born children have a higher risk of autism than later born, overall in the population. And it goes down with each birth order. 

There's a number of implications of these findings, both public health implications and possible clues to ideology. So, as you probably know, since the 1970s with the greater availability of birth control methods and woman entering the workforce and so on, there's been a steady increase in the mean age of both mothers and fathers, and the proportion of infants that are first-born infants to mothers over age 35 increased by more than threefold between 1970 and 2004. That's this one. And then there's also, well, although these changes have been pretty dramatic, these could only explain a small portion of the really huge percent increase we've seen in autism. So, these could be contributing, but they're not explaining the steep increases in autism. But in terms of ideology, especially the male increase, the association between father's age and autism risk suggests gene mutations in the male germ cells that are more frequent as father's age. And there's evidence that these kinds of mutations might more common in children with autism. There's other evidence of that. So, putting it all together, it suggests that that could be a mechanism for that association. For the mother's age association, maybe there's chromosomal changes, pregnancy complications, cumulative environmental exposures that increase body burden of disorders over time. 

And then, factors that lead to delayed parenting such as infertility or psychological traits in the parents that might explain it. There's been a suggestion as well that stoppage could explain the birth order effect. That's the idea that if parents have one child with autism, they might decide not to have more children. We don't have any evidence that that could explain it, but that could contribute to why first-born infants in a family are more likely to have autism than later born. Children with autism are more likely to be first-born than later. Another risk factor I wanted to emphasize here that we've studied here using the autism surveillance data is the possible link between autism and socioeconomic status. This idea has been around since the very first clinical descriptions of autism as a disorder in the 1940s by Leo Kanner. He noted in all of his cases, he said the interesting common denominator in the background of these children, they all come from highly intelligent families, and then he goes on to describe the educational background and accomplishments of all the parents in his series. And this kind of, even Treffert noted it in Wisconsin as well in his 1970 paper. So, it's been around for a long time. 

But it then went out of favor after the publications by Lorna Wing in 1980. She's a British psychiatrist and epidemiologist, and she really put to rest the idea that it's high social class that favors autism somehow because she said it's just that parents who are more educated are more able to get the diagnosis. They're able to find their way to the Waisman Center or so on. And she provided some evidence from her clinical studies of that. But it really was then put to rest and nobody looked at it for almost 30 years, and then we published a paper in the Wisconsin Medical Journal using our surveillance data. And we found, indeed we found an increasing prevalence with increasing socioeconomic status, whether that's measured in terms of parental education or income or poverty status of the family. A pretty steady dose response kind of association. And we looked at this later using data from all the sites participating in the network, and we stratified it by race ethnicity, and what we could see is that in whites, blacks, Hispanics, and Asian, in every group we see the same pattern of increasing prevalence with increasing socioeconomic status. And in fact, the whole racial difference that we'd shown earlier where blacks have a lower prevalence overall is just because more blacks are in this low SES category that has a low prevalence, but in the high SES well-educated black families, the prevalence of autism is certainly no lower than other groups, it's even higher. So there are a number of implications of these findings I want to just mention, and then we'll wrap up. 

But one is that, if it is, if Lorna Wing is right and it's all due to just selection bias, more educated families are able to get the diagnosis, then it means that there are these huge disparities in access to services in the diagnosis in our country. And that's important to know about. So there's a lot of underidentification of autism in the low SES groups. It would also mean that our current estimate of over 1% of children having autism is an underestimate, and if we added more cases from the lower social classes, we'd have an even much higher prevalence overall of autism. And then, another implication, it's been suggested, and there's some evidence from clinical studies, that clinicians who've been trained in Kanner's criteria where he described children with autism having very educated parents that the clinicians themselves might be more likely to diagnose autism if the parents are highly educated than if they're not. We don't know. The other implications are that maybe it isn't just selection bias, and maybe there's something about the physical or social environments of children growing up in more affluent families that increases their risk for autism. Now, we don't know what those things are. We don't necessarily have evidence for it, but it's been suggested things like immunologic factors, the hygiene hypothesis, the idea that children who are in very clean environments might actually get exposed to certain things at a later age when it causes more immunologic damage. And some people see autism as an immunologic disorder possibly. 

Other biological factors such as parental age, which itself is associated with more education usually, could be contributing to this association. So, one of the things we looked at, we were kind of thinking similar to what we saw with the school data where the districts with low prevalence were catching up as they use the diagnosis more, we thought maybe with all the screening going on for autism, over time we'd see a lessening of this gradient, SES gradient. But, actually, when we compared 2002 to 2006, we saw an increase in the steepness of the gradient. So, the disparity, if it is a disparity, is increasing over time rather than decreasing. And then, just a comment on the diagnostic criteria are just about to change in May of this year. DSM V is being adopted, and it gives new definitions and new criteria for autism diagnosis. And there's a lot of concern that it's going to actually be more stringent. It is more stringent to diagnose autism using these criteria than previously. And this might lead to a reduction in the number of children eligible for services for autism because they might have qualified under DSM IV but not under DSM V. And we looked at, the clinical studies suggest a big range from 19% to up to 75% of patients meeting criteria in some clinics under DSM IV might not meet diagnostic criteria under DSM V. 

We've looked at it with our surveillance data to see what impact this might have on prevalence. So we reclassified all our cases using DSM V criteria, and we found a much more modest effect, nothing like 75%. It's not going to have a huge impact on the trends over time. Whether we use these new criteria or old ones, we still see a much higher prevalence than in previous years. But I think the overriding concern is not so much what the effect on prevalence will be but will there be children needing services who will lose eligibility under DSM V. And this is something that will have to be monitored very carefully, and we will be prepared to do it with our epidemiologic data. So just to summarize and conclude, the prevalence of autism estimated based on special education data, they increased steadily since 1992 when it was a new category, but there's some evidence that it might be leveling off at around somewhere between 1% and 2% of children meeting criteria for autism in the school system. Epidemiologic studies also show a steady increase in prevalence over time that's not due to just access to services or changes in eligibility for services. And it seems that, at least for now, we have a prevalence of over 1% and we don't know, it could be continuing to rise closer to 2% of children. And I just think that our service delivery system is really set up more for the three per 10,000, the kind of prevalence we had back in 1970 when Treffert did his study. 

So, I think these findings are important in that way, at least to show what the real need is out there in the community and hopefully get our service and diagnostic system aligned with that. We'll need to continue this work to monitor the disparities in access to services that we seem to have for autism, and also to monitor changes in risk factors and get a better understanding of what the factors are that contribute to autism. Ultimately, the purpose is to improve the health and the quality of life of children with autism and adults as they age and also the family members, families that care for these children. So, I just want to acknowledge the work I presented is from a very large group of people all across the country. I'm happy to entertain any questions. Thank you. [APPLAUSE]