Infants spend most of their first year of life asleep. Those hours are prime time for brain development, when neural connections form and sensory memories are encoded.

But when sleep is disrupted, as occurs more often among children with autism, brain development may be affected, too. New research led by the 91探花 finds that sleep problems in a baby鈥檚 first 12 months may not only precede an autism diagnosis, but also may be associated with altered growth trajectory in a key part of the brain, the hippocampus.

In a published May 7 in the American Journal of Psychiatry, researchers report that in a sample of more than 400 6- to 12-month-old infants, those who were later diagnosed with autism were more likely to have had difficulty falling asleep. This sleep difficulty was associated with altered growth trajectories in the hippocampus.

鈥淭he hippocampus is critical for learning and memory, and changes in the size of the hippocampus have been associated with poor sleep in adults and older children. However, this is the first study we are aware of to find an association in infants as young as 6 months of age,鈥� said lead author , a postdoctoral researcher at the 91探花Autism Center.

As many as 80% of children with autism spectrum disorder have sleep problems, said , director of the and senior author on the study. But much of the existing research, on infants with siblings who have autism, as well as the interventions designed to improve outcomes for children with autism, focus on behavior and cognition. With sleep such a critical need for children 鈥� and their parents 鈥� the researchers involved in the multicenter , or IBIS Network, believed there was more to be examined.

鈥淚n our clinical experience, parents have a lot of concerns about their children鈥檚 sleep, and in our work on early autism intervention, we observed that sleep problems were holding children and families back,鈥� said Estes, who is also a 91探花professor of speech and hearing sciences.

Researchers launched the study, Estes said, because they had questions about how sleep and autism were related. Do sleep problems exacerbate the symptoms of autism? Or is it the other way around 鈥� that autism symptoms lead to sleep problems? Or something different altogether?

鈥淚t could be that altered sleep is part-and-parcel of autism for some children. One clue is that behavioral interventions to improve sleep don鈥檛 work for all children with autism, even when their parents are doing everything just right. This suggests that there may be a biological component to sleep problems for some children with autism,鈥� Estes said.

To consider links among sleep, brain development and autism, researchers at the IBIS Network looked at MRI scans of 432 infants, surveyed parents about sleep patterns, and measured cognitive functioning using a standardized assessment. Researchers at four institutions 鈥� the UW, University of North Carolina at Chapel Hill, Washington University in St. Louis and the Children鈥檚 Hospital of Philadelphia 鈥� evaluated the children at 6, 12 and 24 months of age and surveyed parents about their child鈥檚 sleep, all as part of a longer questionnaire covering infant behavior. Sleep-specific questions addressed how long it took for the child to fall asleep or to fall back asleep if awakened in the middle of the night, for example.

At the outset of the study, infants were classified according to their risk for developing autism: Those who were at higher risk of developing autism 鈥� about two-thirds of the study sample 鈥� 聽had an older sibling who had already been diagnosed. Infant siblings of children with autism have a 20 percent chance of developing autism spectrum disorder 鈥� a much higher risk than children in the general population.

A 2017 study by the IBIS Network found that infants who had an autistic older sibling and who also showed expanded cortical surface area at 6 and 12 months of age were more likely to be diagnosed with autism compared with infants without those indicators.

In the current study, 127 of the 432 infants were identified as 鈥渓ow risk鈥� at the time the MRI scans were taken because they had no family history of autism. They later evaluated all the participants at 24 months of age to determine whether they had developed autism. Of the roughly 300 children originally considered 鈥渉igh familial risk,鈥� 71 were diagnosed with autism spectrum disorder at that age.

Those results allowed researchers to re-examine previously collected longitudinal brain scans and behavioral data and identify some patterns. Problems with sleep were more common among the infants later diagnosed with autism spectrum disorder, as were larger hippocampi. No other subcortical brain structures were affected, including the amygdala, which is responsible for certain emotions and aspects of memory, or the thalamus, a signal transmitter from the spinal cord to the cerebral cortex.

The UW-led sleep study is the first to show links between hippocampal growth and sleep problems in infants who are later diagnosed with autism.

Other studies have found that 鈥渙vergrowth鈥� in different brain structures among infants who go on to develop those larger structures has been associated, at different stages of development, with social, language and behavioral aspects of autism.

While the 91探花sleep study found a pattern of larger hippocampal volume, and more frequent sleep problems, among infants who went on to be diagnosed with autism, what isn鈥檛 yet known is whether there is a causal relationship. Studying a broader range of sleep patterns in this population or of the hippocampus in particular may help determine why sleep difficulties are so prevalent and how they impact early development in children with autism spectrum disorder.

鈥淥ur findings are just the beginning 鈥� they place a spotlight on a certain period of development and a particular brain structure but leave many open questions to be explored in future research,鈥� MacDuffie said.

A focus on early assessment and diagnosis prompted the 91探花Autism Center to establish an infant clinic in 2017. The clinic provides evaluations for infants and toddlers, along with psychologists and behavior analysts to create a treatment plan with clinic- and home-based activities 鈥� just as would happen with older children.

The 91探花Autism Center has evaluated sleep issues as part of both long-term research studies and in the clinical setting, as part of behavioral intervention.

鈥淚f kids aren鈥檛 sleeping, parents aren鈥檛 sleeping, and that means sleep problems are an important focus for research and treatment,鈥� said MacDuffie.

The authors note that while parents reported more sleep difficulties among infants who developed autism compared to those who did not, the differences were very subtle and only observed when looking at group averages across hundreds of infants. Sleep patterns in the first years of life change rapidly as infants transition from sleeping around the clock to a more adult-like sleep/wake cycle. Until further research is completed, Estes said, it is not possible to interpret challenges with sleep as an early sign of increased risk for autism.

The study was funded by the National Institutes of Health, Autism Speaks and the Simons Foundation. , professor of radiology at the 91探花School of Medicine and , research scientist at the 91探花Autism Center, were co-authors. Additional co-authors, all at IBIS Network institutions, were , , and at the University of North Carolina at Chapel Hill; , now at the James S. McDonnell Foundation; at the Children鈥檚 Hospital of Philadelphia; and at the University of Minnesota; at the University of Texas at Dallas; at Washington University in St. Louis; and at the University of Alberta.

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For more information, contact Estes at estesa@uw.edu.

To new parents, a baby’s every gurgle and glance are fascinating, from a smile at mom or dad to a reach for a colorful toy.

But when a baby doesn’t look at parents and caregivers, imitate gestures and sounds, or engage in play, parents have questions. And a growing number are bringing their babies to the for answers.

As autism diagnoses have increased over the years 鈥� an estimated has autism spectrum disorder 鈥� parents have looked for signs earlier in their children’s lives, especially if they have an older child with autism. While the in the United States is around 4 years, a growing body of and practice suggests accurate assessment of children as young as 12 months old, though rare, is not only possible, but also useful.

“Many people have an unfounded belief that you have to wait until 36 months of age to diagnose autism. That is not the case,” said , who directs the 91探花Autism Center and is a research affiliate at the . “There is a great deal of value in diagnosing as soon as symptoms emerge 鈥� it gives parents a great deal of relief and allows appropriate intervention to begin.”

With only a few infant autism clinics scattered around the country, families have brought their 聽infants to the 91探花Autism Center from elsewhere in the United States, and in a few cases, the world, Estes said. The natural next step was to dedicate services to them.

The center’s , officially established this spring, provides four clinical psychologists to evaluate infants and toddlers up to 24 months of age, along with teams of behavior analysts to create a treatment plan with clinic- and home-based activities 鈥� just as would happen with older children. The difference, Estes explained, is the specific expertise with the infant population.

The Autism Center, part of the , has conducted a number of studies into the signs of autism and the effectiveness of intervention strategies. Earlier this year, Nature published from the center’s involvement in a North American effort that examined brain biomarkers in infants, including those with at least one autistic sibling. The study showed that magnetic resonance imaging (MRI) helped correctly identify 80 percent of babies who would go on to be diagnosed with autism at 2 years of age Researchers are wrapping up another study, focused on toddlers 12 to 24 months old, that looks at structured intervention activities versus a more play-based approach.

That work bolsters the center’s diagnostic and treatment capacity with infants, Estes explained.

For older infants and toddlers, psychologists focus on social and communication deficits, said , a research scientist and clinical psychologist at the center. Typically-developing infants and toddlers spend time engaging and interacting with their caregivers, which helps them learn language and fosters their social development.

“Children showing the early signs of autism don’t do those things as much as expected, or they don’t do them at all,” St. John said. “We look at a repertoire of other behaviors as well: Do they do the same thing over and over? Do they pick up a toy and inspect it closely? Do they have a hard time when you change activities?”

It is less common to diagnose a very young child, St. John said, but when that happens, it’s typically because the symptoms are clear.

“Most people are hesitant to give a diagnosis to a child who isn’t showing clear signs of ASD. We tend to give early diagnoses to children who meet all of the criteria for a diagnosis, and if they’re not, we take an assessment-and-monitoring approach, where we give parents specific recommendations based on the child鈥檚 current challenges, and then see the child back 3 to 6 months later,” she explained.

Treatment would follow the same general trajectory, depending on the infant’s symptoms and development, as toddlers and older children. Specialists might work on communication, for instance, through strategies to encourage eye contact. As children age, they work with specialists on cognitive, social and motor skills, both individually and in peer groups. Much of the Autism Center’s approach is designed to give parents tools that they can use at home, Estes said.

Spotting the signs of autism early is critical, she added, so that a family can connect with the right services, whether in the clinic or out in the community.

A little over three years ago, the Autism Center accurately diagnosed its youngest client: a 10-month-old boy. Thanks to subsequent intervention activities, Estes said, he has developed communication skills, engages socially and is thriving in preschool.

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For more information, contact Annette Estes, estesa@uw.edu; 206-543-1051.