Pregnant mother's immunity tied to behavioral, emotional challenges for kids with autism
Study finds that male offspring are at higher risk to maternal immunity activation
August 14, 2020
Science Daily/University of California - Davis Health
Children with autism born to mothers who had immune conditions during their pregnancy are more likely to have behavioral and emotional problems, a UC Davis Health study has found. The study examined maternal immune history as a predictor of symptoms in children with autism.
"We tested the ability of maternal immune history to predict ASD symptoms and the possible role that the sex of the offspring plays," said Paul Ashwood, professor of microbiology and immunology and faculty member at the UC Davis MIND Institute.
Published Aug. 14 in Translational Psychiatry, the study found that offspring sex may interact with maternal immune conditions to influence outcomes, particularly in terms of a child's cognition.
Maternal immunity conditions and autism
Maternal immune conditions are caused by a dysfunction of the mother's immune system. They include allergies, asthma, autoimmune diseases, autoinflammatory syndromes and immunological deficiency syndromes. Previous studies have shown that maternal immune conditions are more prevalent in mothers of children with autism spectrum disorder (ASD).
The researchers enrolled 363 mothers and their children (252 males and 111 females) from the Autism Phenome Project (APP) and Girls with Autism Imaging of Neurodevelopment (GAIN) study at the UC Davis MIND Institute. The median age of the children was three years.
The researchers measured the children's autism severity and assessed a set of behavioral and emotional problems such as aggression and anxiety. They also measured the children's development and cognitive functioning.
The study found that around 27% of the mothers had immune conditions during their pregnancy. Of these mothers, 64% reported a history of asthma, the most common immune condition. Other frequent conditions included Hashimoto's thyroiditis (hypothyroidism), Raynaud's disease (blood circulation disease), alopecia (hair loss), psoriasis (skin disease) and rheumatoid arthritis (joint tissue inflammation).
The study also found that maternal immune conditions are associated with increased behavioral and emotional problems but not reduced cognitive functioning in children with autism.
Does the sex of the offspring interact with the influence of maternal immune conditions on autism symptoms?
According to the Centers for Disease Control and Prevention (CDC), ASD is four times more common among boys than among girls.
"Our study explored whether offspring sex interacts with the presence of maternal immune conditions to influence behavioral outcomes in children," said Ashwood. "Maternal immune conditions may be one environmental factor which contributes to the higher male prevalence seen in ASD."
The study found that a history of maternal immune conditions was more common in male children with ASD (31%) compared to female (18%). Specifically, asthma was twice as common in mothers of male children with ASD than in mothers of female children with ASD.
The study also showed that in cases of ASD where maternal immune conditions are present, female offspring are less likely to be susceptible to adverse cognitive outcomes in response to maternal inflammation than male offspring.
"This critical finding links offspring sex and maternal immune conditions to autism," said Ashwood. "It provides more evidence that male offspring are at higher risk of adverse outcomes due to maternal immunity activation compared to female offspring."
Future studies would include identifying the type, severity and gestational timing of immune conditions, and then examining offspring outcomes over time.
Co-authors on this study are Brianna Heath, Christine Nordahl and Sally Rogers in the department of psychiatry at UC Davis and at the UC Davis MIND Institute, Destanie Rose in the department of medical microbiology and immunology and at the UC Davis MIND Institute, Shrujna Patel, Russell Dale and Adam Guastella in the Children's Hospital Westmead Clinical School at the University of Sydney.
https://www.sciencedaily.com/releases/2020/08/200814163307.htm
Sleep difficulties linked to altered brain development in infants who later develop autism
May 7, 2020
Science Daily/University of Washington
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 University of Washington finds that sleep problems in a baby's 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 study 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.
"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.
However, this is the first study we are aware of to find an association in infants as young as 6 months of age," said lead author Kate MacDuffie, a postdoctoral researcher at the UW Autism Center.
As many as 80% of children with autism spectrum disorder have sleep problems, said Annette Estes, director of the UW Autism Center 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 -- and their parents -- the researchers involved in the multicenter Infant Brain Imaging Study Network, or IBIS Network, believed there was more to be examined.
"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," said Estes, who is also a UW 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 -- 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 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 -- the UW, University of North Carolina at Chapel Hill, Washington University in St. Louis and the Children's Hospital of Philadelphia -- evaluated the 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, infants were classified according to their risk for developing autism: Those who were at higher risk of developing autism -- about two-thirds of the study sample -- 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 -- 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 "low risk" 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 "high familial risk," 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 "overgrowth" 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 UW 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't 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.
"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 said.
A focus on early assessment and diagnosis prompted the UW 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 -- just as would happen with older children.
The UW Autism Center has evaluated sleep issues as part of both long-term research studies and in the clinical setting, as part of behavioral intervention.
"If kids aren't sleeping, parents aren't sleeping, and that means sleep problems are an important focus for research and treatment," 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. Dr. Stephen Dager, professor of radiology at the UW School of Medicine and Tanya St. John, research scientist at the UW Autism Center, were co-authors. Additional co-authors, all at IBIS Network institutions, were Mark Shen, Martin Styner, Sun Hyung Kim and Dr. Joseph Piven at the University of North Carolina at Chapel Hill; Sarah Paterson, now at the James S. McDonnell Foundation; Juhi Pandey at the Children's Hospital of Philadelphia; Jed Elison and Jason Wolff at the University of Minnesota; Meghan Swanson at the University of Texas at Dallas; Kelly Botteron at Washington University in St. Louis; and Dr. Lonnie Zwaigenbaum at the University of Alberta.
https://www.sciencedaily.com/releases/2020/05/200507094747.htm
Severe morning sickness associated with higher risk of autism
October 3, 2019
Science Daily/Kaiser Permanente
Children whose mothers had hyperemesis gravidarum -- a severe form of a morning sickness -- during pregnancy were 53% more likely to be diagnosed with autism spectrum disorder, according to Kaiser Permanente research published in the American Journal of Perinatology.
"This study is important because it suggests that children born to women with hyperemesis may be at an increased risk of autism," said lead study author Darios Getahun, MD, PhD, of Kaiser Permanente Southern California Department of Research and Evaluation. "Awareness of this association may create the opportunity for earlier diagnosis and intervention in children at risk of autism."
Hyperemesis gravidarum occurs in less than 5% of pregnancies. Affected women experience intense nausea and are unable to keep down food and fluids. This can lead to dangerous dehydration and inadequate nutrition during pregnancy.
To determine the extent of the association between hyperemesis gravidarum and autism spectrum disorder, researchers reviewed electronic health records of nearly 500,000 pregnant women and their children born between 1991 and 2014 at Kaiser Permanente in Southern California. They compared children whose mothers had a diagnosis of hyperemesis gravidarum during pregnancy to those whose mothers did not.
Other findings from the research included:
· Exposure to hyperemesis gravidarum was associated with increased risk of autism when hyperemesis gravidarum was diagnosed during the first and second trimesters of pregnancy, but not when it was diagnosed only in the third trimester.
· Exposure to hyperemesis gravidarum was associated with risk of autism regardless of the severity of the mother's hyperemesis gravidarum.
· The association between hyperemesis gravidarum and autism spectrum disorder was stronger in girls than boys and among whites and Hispanics than among blacks and Pacific Islanders.
· The medications used to treat hyperemesis gravidarum did not appear to be related to autism risk.
The results are consistent with the hypothesis that women experiencing hyperemesis gravidarum have poor nutritional intake, which may, in turn lead to potential long-term neurodevelopment impairment in their children. The study cannot, however, rule out other possible explanations, such as perinatal exposures to some medications and maternal smoking.
https://www.sciencedaily.com/releases/2019/10/191003092046.htm