Sleep problems in a baby’s first 12 months may not only precede autism diagnosis, but also associate with an altered growth trajectory in the hippocampus, a new study suggests.

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

But disrupted sleep, which occurs more often among children with autism, may affect brain development, too.

In a sample of more than 400 6- to 12-month-old infants, those later diagnosed with autism had a higher likelihood of difficulty falling asleep. Researchers associated this sleep difficulty with altered growth trajectories in the hippocampus.

“The 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,” says Kate MacDuffie, a postdoctoral researcher at the University of Washington Autism Center and lead author of the paper in the American Journal of Psychiatry. “However, this is the first study we are aware of to find an association in infants as young as 6 months of age.”

As many as 80% of children with autism spectrum disorder have sleep problems, says senior author Annette Estes, professor of speech and hearing sciences and director of the University of Washington Autism Center. 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—and their parents—the researchers involved in the multicenter Infant Brain Imaging Study Network, or IBIS Network, believe they needed to do more study.

“In our clinical experience, parents have a lot of concerns about their children’s sleep, and in our work on early autism intervention, we observed that sleep problems were holding children and families back,” Estes says.

SLEEP-AUTISM CONNECTION
Researchers launched the study because they had questions about how sleep and autism related to each other, she says. Do sleep problems exacerbate the symptoms of autism? Or is it the other way around—that autism symptoms lead to sleep problems? Or something different altogether?

“It could be that altered sleep is part-and-parcel of autism for some children. One clue is that behavioral interventions to improve sleep don’t 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,” Estes says.

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—the University of Washington, the University of North Carolina at Chapel Hill, Washington University in St. Louis, and the Children’s Hospital of Philadelphia—evaluated children at 6, 12, and 24 months of age and surveyed parents about their child’s 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, researchers classified infants according to their risk for developing autism: Those classified at higher risk of developing autism—about two-thirds of the study sample—had an older sibling who had already received a diagnosis.

Infant siblings of children with autism have a 20% chance of developing autism spectrum disorder—a much higher risk than children in the general population.

CAUSAL RELATIONSHIP?
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 had a higher likelihood of receiving an autism diagnosis compared with infants without those indicators.

“IF KIDS AREN’T SLEEPING, PARENTS AREN’T SLEEPING, AND THAT MEANS SLEEP PROBLEMS ARE AN IMPORTANT FOCUS FOR RESEARCH AND TREATMENT.”

In the current study, researchers identified 127 of the 432 infants as “low risk” at the time they took the MRI scans 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 “high familial risk,” 71 received an autism diagnosis at that age.

Those results allowed researchers to re-examine previously collected longitudinal brain scans and behavioral data and identify some patterns. They more commonly found problems with sleep—and larger hippocampi—in infants later diagnosed with autism spectrum disorder.

No other subcortical brain structures showed an effect, including the amygdala, responsible for certain emotions and aspects of memory, or the thalamus, a signal transmitter from the spinal cord to the cerebral cortex.

Researchers say the study is the first to show links between hippocampal growth and sleep problems in infants later diagnosed with autism.

Other studies have found that “overgrowth” in different brain structures among infants who go on to develop those larger structures have associated, at different stages of development, with social, language, and behavioral aspects of autism.

While the study found a pattern of larger hippocampal volume, and more frequent sleep problems, among infants who went on to be diagnosed with autism, researchers don’t yet know if a causal relationship exists.

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.

“Our findings are just the beginning—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,” MacDuffie says. “If kids aren’t sleeping, parents aren’t sleeping, and that means sleep problems are an important focus for research and treatment.”

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 says, researchers can’t interpret challenges with sleep as an early sign of increased risk for autism.

Source: University of Washington

Original Study DOI: 10.1176/appi.ajp.2019.19060666