Pregnant women with high levels of inflammation during the second trimester may be at significantly greater risk of having a child with autism combined with intellectual disability, according to a new study at the University of California (UC) Davis MIND Institute.
Specifically, these moms were found to have higher levels of inflammatory cytokines and chemokines, proteins that control communication between cells of the immune system.
The study was designed to evaluate biomarkers for autism. Because these specific markers of inflammation were starkly linked to autism with intellectual disability, the researchers suggest a potential immune profile for autism combined with intellectual disability as distinct from either autism or developmental disability alone.
“Inflammation during the second trimester in the mothers of children with autism who also have intellectual disability was significantly greater than in mothers of children autism without intellectual disability in our study,” said senior author Dr. Judy Van de Water, professor of Internal Medicine in the Division of Rheumatology, Allergy and Clinical Immunology and a researcher affiliated with the UC Davis MIND Institute.
“However, equally significant was that profiles of mothers whose children go on to be diagnosed with autism and intellectual disability differed markedly from those whose children have intellectual disability without autism, as well as from the typically developing general population,” said Van de Water, also director of the UC Davis Center for Children’s Environmental Health.
“Their profiles are distinct from all of the other groups that we studied, based on their cytokine and chemokine profiles. This finding suggests an avenue that we will explore to potentially identify possible markers to separate sub-phenotypes in the autism population.”
The researchers believe that changes in the gestational immune environment may lead to alterations in the neurodevelopmental growth of the developing fetus, which may result in the specific symptoms noted in children with autism and intellectual disability.
The activation of the pregnant mom’s immune system is one of several pathways that can result in differences in maternal cytokines, the researchers said. This activation may be due to environmental toxicants such as pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers. The cytokine and chemokine levels also may interact with other potential risk factors, such as parental genetics.
“This study is incredibly valuable because it helps us understand more about the sources of variability within autism spectrum disorder, providing important insights into the different neurobiological mechanisms underlying important subtypes of the disorder,” said Dr. Leonard Abbeduto, director of the MIND Institute.
“At the same time, the study reinforces the importance of the maternal immune system in to a host of child outcomes. Most importantly, this study brings us closer to knowing how to prevent adverse developmental outcomes,” he said.
Chemokines have been shown to regulate the migration, proliferation, and differentiation of neuronal cells, and studies have identified the roles of specific cytokines during neurodevelopment, such as influencing neurogenesis, neuronal and glial cell migration, proliferation, differentiation, and synaptic maturation and pruning.
For the study, the researchers examined the mid-gestational blood serum levels of 184 women whose children developed autism and intellectual disability (previously known as mental retardation), 201 who had children with autism without intellectual disability, 188 whose children had developmental disability alone, and 428 general population control participants.
“The fact that we see this increase in inflammatory markers with the autism/intellectual disability group compared with all of the other reference groups is striking, because the ones we’re seeing that are affected are usually down-regulated during the second trimester of pregnancy,” said Dr. Karen L. Jones, study first author and a postdoctoral fellow in the Division of Rheumatology, Allergy and Clinical Immunology.
“This really is suggesting that there is a lack of the immune regulation in these moms that is typically associated with a healthy pregnancy. It is particularly exciting that this work does start to tease apart a potential source of differences in autism with and without intellectual disability, as well as from intellectual disability without autism,” Jones said.
The findings are published online in the journal Molecular Psychiatry.