When her first child was a baby, Elizabeth Giuliani remembers how happy he was, always full of smiles.

But the Mullica Hill, N.J., mother also cannot forget that Stephen Stout II didn’t coo or babble like other babies. At the time, Giuliani chalked it up to a quieter personality.

By 12 months, though, her son still did not say mom or dad, but he knew all his numbers and letters, repeating sequences over and over, and even found letters in everything he saw. A lamppost was the letter r, for example.

“Why is he so fixated on numbers and letters?” Giuliani, 37, and a special education reading specialist, recalls thinking. Stephen also would spin endlessly in circles, stare at turning wheels and rarely make eye contact with others.

On Sept. 7, 2007, when he was around 2 years old, he was diagnosed with moderate to severe autism. He had all the classic symptoms.

“It was devastating,” says his father, Stephen Stout, 42.

From Conception to Pre-school
That’s why the Stout-Giuliani family jumped at a chance to participate in an unusual, long-term research study on autism being led by Drexel’s A.J. Drexel Autism Institute.

Known as the Early Autism Risk Longitudinal Investigation (EARLI), it focuses specifically on the critical but grossly understudied prenatal time period and the interplay of environmental risk factors with genetic susceptibility for a disorder that has becoming increasingly prevalent in recent decades.

“Whatever we can do,” Giuliani says was her immediate reaction to the study that required a three-year commitment. “Even if it’s 50 years from now,” she says her involvement was well worth it “if the study can alleviate some parents’ angst.”

EARLI, begun six years ago with the support of $10 million in grants from the National Institutes of Health and Autism Speaks, seeks to move the timeline for studying the risk factors of autism from early childhood to before, during and right after pregnancy, explains Craig J. Newschaffer, director of the A.J. Drexel Autism Institute.

“We’d like to develop some solid leads around modifiable exposures, things that families at risk or families in general might be able to avoid and as a result improve the development of their babies and reduce the chances they end up with autism spectrum disorders,” says Newschaffer, who is also a professor of epidemiology and biostatistics in the School of Public Health.

Julie Daniels, an associate professor of epidemiology at the University of North Carolina at Chapel Hill, is familiar with EARLI and views the study as particularly valuable for the time period it researches and the depth of data it collects.

“We’re pretty confident that autism begins prior to birth, and it’s just not identified until 2 or 3 years of age,” Daniels says. “If we’re really trying to get at what causes autism, we really need to get back to what’s happening before birth.

EARLI, she says, is one of the first studies to “look in the prenatal window in a high-quality way.”

“We’d like to develop some solid leads around modifiable exposures, things that families at risk or families in general might be able to avoid and as a result improve the development of their babies and reduce the chances they end up with autism spectrum disorders.”

–Craig J. Newschaffer, director, A.J. Drexel Autism Institute

The study enrolls families in which the mother is currently pregnant and in which an older sibling is already diagnosed with autism. It has enrolled 233 families at four sites around the country. (Enrollment has paused since fall 2012.) Besides Drexel, which has partnered with the Children’s Hospital of Philadelphia and the University of Pennsylvania, the other locations are Johns Hopkins University and its affiliated Kennedy Krieger Institute; the University of California at Davis and its MIND Institute, and Kaiser Permanente in Oakland, Calif.

The Stout-Giuliani family was approached three years ago, when Giuliani was early in her pregnancy with her third child, Gabriella, who recently graduated from the study and shows no signs of autism. (Stephen is now a bright third grader with a passion for Harry Potter novels and sports; he shows few symptoms of autism.)

The study closely follows the pregnant woman through the birth of her child and the first three years of life, checking for autism-like behavior.

Periodic blood and urine samples are collected to study biomarkers that could predict the development of autism. During pregnancy, participants log what they eat and drink, medications they take, any exposure to pesticides and numerous other environmental details. Researchers also visit the home to assess risk factors and collect a dust sample.

When the mother gives birth, her placenta is collected for study. In addition, researchers take samples of cord blood and the newborn’s blood and first, black stool, known as meconium.

Early Clues
So far, the study has not found a smoking gun — though, for a disorder as complicated as autism, no single cause or factor is likely to be the culprit. And it’s still early. The participant babies need to grow older, Newschaffer says. “That’s one reason this type of research is very challenging,” he says. “You invest a lot up front, and you have to wait, wait, wait.”

But Newschaffer says EARLI has yielded some provocative tidbits that offer intriguing areas of future inquiry.

For example, blood samples might provide epigenetic clues as to what variables may trigger autism during pregnancy. (Epigenetics, a relatively new field, maintains that our environmental exposures can actually change our genome and how genes behave, or express themselves.)

Another area of research revolves around the shape of the placenta, the nexus between the mother and child. Normally, it is round. But preliminary comparisons of EARLI placentas with data about placentas from the general population show differences.

On average, EARLI moms’ placentas are a little thinner and a little irregular in shape, he says. Findings also indicate that the more irregular the shape, the higher the child scores on a scale designed to measure autism-like behavior at 12 months of age. “This is very, very preliminary,” he emphasizes. “But it is there.”

In addition, Newschaffer’s team also hopes to receive funding to look at air pollution and its impact on autism as well as at triclosan and triclocarban, both antimicrobials found in personal-care products. The antimicrobial agents have endocrine-disrupting properties and increase the amount of androgen, a hormone that stimulates the development of male characteristics. Autism is almost five times as common in boys as girls, and one theory speculates that autism is, essentially, a “more extreme male brain,” he says.

Measuring fetal androgen levels in EARLI’s meconium samples might provide a pathway to investigate the hormone’s role, if any, in autism.

Newschaffer — along with Nora Lee, an assistant research professor of epidemiology and biostatistics, and Igor Burstyn, an associate professor of environmental and occupational health — plan to investigate further these and several other avenues.

“We’ve … built this incredibly rich resource, and we’re now trying to harvest the fruit,” Newschaffer says.

For Giuliani, the study was “a great experience.” Testing of her youngest child showed her to be “typical” — music to the family’s ears — and the regular access to autism researchers allayed many fears.

“I felt it was a support team throughout the most critical time for your child,” she says. “It almost was a comfort.”

Recently, a study found an association between the use of antidepressants during pregnancy and autism spectrum disorder (ASD). The researchers cautiously worded their findings, explaining that the underlying depression — not just the medication — could be a factor as well. But headlines declared, “Study Links Autism with Antidepressant Use During Pregnancy.”

It would be easy to see how a pregnant woman might want to stop using antidepressants to protect her unborn baby. But is that in her — and the fetus’ — best interest? To further complicate matters, a much larger study released a few months later did not replicate the finding.

Those are the type of risk communication scenarios — and unintended poor outcomes — that Drexel University researchers Michael Yudell and John A. Rossi plan to explore with a one-year, $68,000 Autism Speaks grant recently awarded. Ultimately, they intend to develop a set of ethical principles to guide scientists looking at environmental risks for autism — the first of its kind for the field.

“It’s an area in need of not only good science to unravel what autism is and is not, but also that more sensitively communicates findings to a community hungry for answers, and rightfully so,” says Yudell, who is a fellow at the A.J. Drexel Autism Institute.

“People are constantly engaging in a risk-benefit calculation,” adds Rossi, who is trained in bioethics and veterinary medicine. “You have certain information that’s scientifically very interesting, helps the scientific community understand autism, but that information may not be personally useful to someone.”

Rossi, who also is an Autism Institute fellow, allowed that some bioethicists insist that the public has a right to know all information, no matter how trivial. Others disagree on whether that is in the public’s best interest.

“You get into a bioethical tension, protecting people from harm and letting them make autonomous decisions,” he says.

The research study plans to target three groups: scientists, parents with and without children diagnosed with ASD, and adults with autism. Following a survey, a subset of scientists will be interviewed one on one. Focus groups will be conducted with parents and people with autism.

“We want to figure out a way for scientists to communicate in a language commensurate with the power of their findings,” Yudell says, “and do so in a way that’s responsible, that doesn’t send everybody running for the exits.”

Few researchers have looked at autism risk communication, but it’s an area arguably more critical than ever because of the significant rise in autism diagnoses. In 2000, the prevalence was one in 150; currently, it is one in 88, based on the Centers for Disease Control’s most recent data.

Research into environmental causes has exploded. “We have to ask, ‘What are we going to do with all this information?’” Rossi says. “It’s important to stop and ask, ‘Are there any ethical concerns that might arise with risk communication?’”

Autism’s early history has only heightened interest around ethical concerns. Early on, so-called “refrigerator mothers” who were considered emotionally distant were blamed. Treatment often involved removing autistic children from their homes so they could “thaw.”

Today, scientists are looking to genetic and environmental factors — but those findings often still significantly impact the public.

“I think scientists have a responsibility to do their best to communicate findings of their work in an ethical way, a way that’s both fair to the field and fair to those whom the work impacts,” Yudell says.

In the past two decades, the prevalence of autism appears to have increased astronomically, from one in 10,000 in the 1980s to one in 88 currently, according to the Centers for Disease Control.

Why that is has led to much debate. In fact, some dispute claims of an increase in autism, attributing growing numbers to better diagnosis at younger ages as well as a much broader definition of autism spectrum disorders (ASD).

Researchers such as Drexel University’s Brian K. Lee, however, want to explore the possibility of environmental factors.

“We don’t know whether or not the increase is real, but it’s definitely worth investigating,” says Lee, an assistant professor of epidemiology and biostatistics as well as a fellow at the A.J. Drexel Autism Institute. “If there is a real increase, it’s really important to identify risk factors that may explain the increase.”

Along with Swedish collaborators out of the Karolinska Institutet in Stockholm, he is analyzing large population samples of Swedish children to identify environmental risks for autism. (Genetics alone cannot account for the rapid increase in autism seen in recent years, he says.)

Lee’s work explores many areas, including the role of infection and inflammation in early life as well as the mother’s diet during pregnancy. Another area of interest is parental age at conception.

“Now that we see an association, we want to try and explain it … instead of just guessing why we see these things.”

– Brian Lee, fellow,
A.J. Drexel Autism Institute

Most recently, he looked at parents’ age as a risk factor for autism, with a special — and novel — focus on whether age is a factor for the additional problem of intellectual disabilities in some autistic children. His findings, which were published earlier this year in the International Journal of Epidemiology, were based on data on 417,303 Swedish children born between 1984 and 2003. His work was funded through grants from Autism Speaks and the Swedish Research Council.

“Both the mother’s and father’s age matters in terms of a child’s autism risk,” Lee says. “The older the parent is, the higher the risk the child has.”

But the data also highlighted the differing impact of a mother’s age when compared to a father’s age.

Mothers show a sharp increase in bearing autistic children only after age 30. For fathers, however, the chance of having a child with autism increases linearly for each year of age, Lee says. “It’s a slow, steady climb,” he says.

The research also found that the father’s age has a bigger impact when the mother is 35 years old or younger. In contrast, a mother’s advancing years raised the risk regardless of the father’s age.

“When mothers are younger the father’s risk is more apparent,” Lee says. “But as mothers get older, their risk tends to overshadow any risk from the fathers.”

Much of the recent research on autism has focused on the father’s age and the quality of the sperm, which accumulates mutations over time. Lee, however, notes that his study concludes that “maternal age has greater implications for ASD risk than a similar increase in paternal age.”

Older parental age also correlates with autistic children with intellectual disabilities — and this study is believed to be the first of its kind to look at that aspect, according to Lee.

One reason for this association could be the greater chance of passing along genomic alterations with parental age. But another possibility is environmental factors, such as whether the child was delivered by C-section or vaginally.

“Now that we see an association, we want to try and explain it … instead of just guessing why we see these things,” he says.

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Two decades ago, Gloria Esposito joined other parents in the hard-fought battle for early intervention services for children on the autism spectrum.

Her son, Louis Esposito III, was diagnosed with the developmental disorder when he was almost 2 years old. “I left my business,” says Esposito, 57, who lives in Haverford, Pa. “I started a full-time, at-home treatment model for my son. I had to create it from nothing.”

The parent power of the time made a tremendous difference in the lives of autistic children and eventually won them many services.

Now, as these children — young adults really — age out of high school at 21, they face an uncertain future.

“Where am I now?” Esposito asks. “I’m looking at very few options. It’s back to the drawing board.”

Drexel University researcher Paul T. Shattuck understands only too well the challenges facing many families. Recently appointed associate professor of the A.J. Drexel Autism Institute, he leads the Life Course Outcomes Research Program. Shattuck has conducted pioneering work on the quality of life for autistic adults. His studies are among the first to put real numbers to outcome issues as young adults on the autism spectrum move into the world of college, vocational training or employment as well as living more independently.

What he has found is cause for concern.

“Young adults on the autism spectrum are doing much worse off, way more worse off, than their peers than we ever imagined,” says Shattuck, who has a public health background and came to Drexel this academic year from Washington University in St. Louis, Mo.

By analyzing big data sets, such as from the National Longitudinal Transition Study-2 of special education students, he has pinpointed certain troubling trends. For example, five years after leaving high school, individuals on the autism spectrum were roughly three times more likely to be disengaged from education or employment opportunities than people with serious mental illness or serious cognitive impairments. The findings were published in the journal Pediatrics in 2012.

“That’s a big difference,” he says. One reason, he says, could be shifts in the economy over the past 50 years. Today’s world focuses heavily on service-sector jobs that involve interaction with others — a fact that is particularly challenging for those on the autism spectrum.

Such stark findings can be difficult and discouraging for parents in the autism community to hear. At the same time, advocates on the frontlines welcome solid research that measures the scope of the challenges they know exist anecdotally.

“Parents say, ‘We feel like we’re falling off a cliff,’” Shattuck says of the lack of services post–high school. “Our study has quantified the height of that cliff.”

Stuart Spielman, senior policy adviser and counsel for New York City-based Autism Speaks, applauds the work. “We really do need more information on the life experience of adults on the autism spectrum,” he says. “Paul is helping to fill that void.”

Consider speech therapy. Three-fourths of children on the autism spectrum get this critical service, Shattuck says. But among adults, that number plummets to less than 10 percent.

It can mean huge steps backward in skills — an untenable prospect for parents who have spent years helping and advocating for their children.

“Paul’s research demonstrates time and time again the sorry statistics when the school bus stops coming and the sorry outcome,” says Denise Resnik, co-founder of the Phoenix-based Southwest Autism Research & Resource Center (SARRC). The organization looks to advance research and support families over the lifespan of autism.

As the mother of 22-year-old Matthew Resnik, who is on the autism spectrum, she knows firsthand the frustrations. “I’ll be damned if I’m going to allow all that early intervention to go to waste,” she says. “We can’t afford as parents, we can’t afford as a community, and we can’t afford as a country to let these adults slip through the cracks when they have so much potential.”

Resnik has helped her son create a home-based business of baking biscotti known as SMILE Biscotti. SMILE is an acronym for Supporting Matt’s Independent Living Enterprise. “He’s starting to go on sales calls,” she says with a mother’s pride.

“Young adults on the autism spectrum are doing much worse off, way more worse off, than their peers than we ever imagined. …. Parents say, ‘We feel like we’re falling off a cliff.’”

– Paul Shattuck, A.J. Drexel Autism Institute, Life Course Outcomes

Shattuck’s “work is incredibly important to shine a light on the issue and the importance of doing something about it,” Resnik says. The urgency is made all the more clear by the simple fact that 50,000 children on the autism spectrum will turn 18 this year — some half a million over a decade.

What will become of them? advocates ask.

“I believe we are today for adult concerns where we were 20 years ago for early childhood intervention,” Resnik says. What she means is that parents are once again inventing ways to help their children while social services play catch up.

In his new role at Drexel, Shattuck is focused on developing a strategic research plan and forging strong ties with the autism community. He says he plans to continue to delve into big-data analyses to identify trends and pinpoint promising practices — such as the best educational and employment supports — with the goal to improve quality of life. He also wants to grow the number of researchers studying adults on the autism spectrum in a field traditionally focused on early intervention.

“Until we started our research a few years ago,” he says, “we didn’t have population-level understanding of how many have friends, how many go to college, how many have a job, how many live on their own. … To understand any social problem, we need high-flying, population-level information. This is the benchmark data we need to know if we want to say we’ve moved the needle. If we don’t do that, if all we ever investigate is only at the clinical level, we’ll fundamentally not know if things are getting better.”

Ultimately, his work could help shape national policy. “Solving problems like this is not simple,” says Spielman of Autism Speaks. “The first step is having the research that demonstrates the degree of the challenge.”

Autism groups have recognized Shattuck’s groundbreaking studies over the years.

Both Autism Speaks and the Federal Interagency Autism Coordinating Committee spotlighted his 2009 study on the age of diagnosis as one of the most important autism studies of the year. While research shows that children can be diagnosed as young as 18 to 24 months, Shattuck found that actual diagnosis occurs at a much older age, around 5 years old.

The Interagency Autism Coordinating Committee also found his 2011 work on the use of services by adults on the autism spectrum one of the 20 most impactful scientific studies in the field. And Autism Speaks praised his 2012 paper on postsecondary job and education outcomes as one of the Top 10 research advances of the year, out of the more than 3,000 published annually.

“Paul has a real passion for what he does,” Spielman says. “He wants solutions.”

So, too, does Esposito. Her son, who suffers serious communication issues, has benefited from intensive intervention from his earliest years. Louis is able to function independently with the help of schedules and supervision. She is convinced he could hold a job with the right support.

“A lot of kids are starting to sit at home. There’s nothing out there,” she says. “We have to create it.”

With research such as Shattuck’s pointing the way and highlighting the urgency of the matter, she is forging ahead. Esposito is deep into classes that help her better understand the system and navigate the paperwork maze for services for her son.

“I know we’re going to find a solution,” says Esposito.

At Drexel, students who are on the autism spectrum benefit from services designed for their needs. The Drexel Autism Support Program (DASP) pairs mentors with participants to help with personal, social, academic and professional challenges.

Joseph Wahl III, a senior majoring in business and marketing, has Asperger syndrome. He says he has found DASP helpful in finding clubs to join and a tutor for math.

“It helped me get more involved in school,” says Wahl, 23, who hails from Clarks Summit, Pa.

Shattuck’s goal is to use his research program to develop and add to the range of strategies that leads to best outcomes for Wahl and the many others on the autism spectrum.

“People with autism are valuable members of our communities,” he says. “Like all people, they have dreams, roles to play, contributions to make. … We need to know what experiences, beyond clinical interventions, promote positive outcomes and prevent negative ones — both for people on the autism spectrum and the families and communities they are part of.”

A diagnosis of autism takes a toll on individuals, families — and also society. By some estimates, autism spectrum disorders account for more than $35 million in direct and indirect costs to the United States each year. Individuals with the condition are more likely to need health care services, behavioral treatment and have difficulty sustaining employment and transitioning into independent adulthood.

But estimates are just that — no comprehensive count of autism prevalence exists. Without a reliable count, states and social services organizations are in the dark about how to respond to this public health problem. Who needs services? Where do the services recipients reside? What services are most urgently needed?

In Pennsylvania, at least, public health officials are closer to an answer. A Drexel researcher is leading a first-of-its-kind administrative census of the number of individuals diagnosed with autism living in Pennsylvania. Lindsay Lawer Shea, senior manager and project director at the A.J. Drexel Autism Institute, is working with the Bureau of Autism Services in the Pennsylvania Department of Public Welfare to understand the true size and demographic characteristics of the state’s autism population receiving services.

The project will use data it gathers to determine the need for autism-specific services and programs, which policymakers can use to design more effective services.

The original Pennsylvania Autism Census Project was published in 2009 using data from 2005. At that time, the census counted close to 20,000 Pennsylvanians receiving autism services. Preliminary findings based on 2011 data show almost triple that number, for a total of over 55,000 children and adults on the autism spectrum statewide receiving services.

These numbers are on the low side, because they don’t include individuals not receiving services through state programs or who are misdiagnosed or never formally diagnosed.

“The Centers for Disease Control estimate that more than 1 percent of the population has autism; with the numbers we’ve counted, we’re still missing tens of thousands of Pennsylvanians, mostly adults, because we’re only counting people who receive services,” says Shea.

She says that official estimates suggest the number to be around 130,000. Still, Pennsylvania’s is one of the most
comprehensive tallies in the country and the first of its kind to date.

“Numbers like these are really powerful,” says Shea. “They help when we think about things like resource allocation and where to implement programs.”

For example, the Adult Community Autism Program is one of two programs in Pennsylvania that helps adults on the autism spectrum participate in their communities through physical, behavioral and community services.

“ACAP is the first of its kind in the United States and results like the census can help to figure out where to expand programs like that to maximize their impact,” Shea says.

The census can also identify vulnerable population groups that need extra attention, such as people who don’t speak English, or where rates of diagnosis are rising the fastest. The ASERT Collaborative, which Shea directs in the Eastern region of Pennsylvania, is a unique partnership between government and academic institutions working to understand and meet these needs.

“We’re guessing on how to take care of this group, which is growing, and we need to spend time and energy with this data to have an evidence-based way to do so,” Shea says.