I previously mentioned that maternal diabetes during pregnancy has been related to an increased risk of autism, an idea that has been shown in my own family as my Mom has Type 1 Diabetes and my brother is diagnosed with ASD Level 1. The role of inflammation in type 1 and type 2 diabetes pathophysiology may be the underlying role of the associated autism risk in the fetus. Early brain development during the critical period of a child’s life is very important in the shaping of the child’s neuropsychological characteristics. Any issues in the intrauterine environment during pregnancy, such as maternal alcohol use or in this case inflammation, can lead to long-term conditions in the newborn child.
Money et al. concluded that gestational diabetes and maternal immune activation can disrupt the in utero environment and affect fetal neurodevelopment, as suggested by numerous animal models. This maternal immune activation (MIA) hypothesis proposes that inflammatory perturbations, or inflammatory alterations, in utero play a role in the pathogenesis of autism spectrum disorder and ADHD. Additionally, maternal immune activation-induced aberrant immune programming can result in a loss of immune homeostasis, which is associated with behavioral abnormalities. Lombardo et al. examined how maternal immune activation, experimentally induced via immunogens, dysregulates rat fetal brain gene expression in ways that are relevant to ASD pathophysiology. The researchers of this study found evidence that MIA-induced effects may contribute to the pathways that are disturbed by highly penetrant ASD mutations and the downregulation of synaptic-related processes. Though this is a very interesting link between diabetes, inflammation as an intermediary, and ASD, questions still remain on how maternal immune activation can affect the fetal brain genetically or even epigenetically.
In Rudolph et al., brain networks in newborn babies and their cognitive abilities reflected the degree of inflammation that their mothers had experienced during pregnancy. The findings of this study showed high association of gestational inflammation with the developing functional architecture and overall functioning of the brain of the newborn. Based on the theory that one potential cause of autism is linked to neuroinflammation, a team of Harvard Medical School researchers provided an important insight into the origins of autism with the idea that young men with autism have low levels of translocator protein, a substance that appears to play a role in inflammation and metabolism.
This idea still needs to be researched thoroughly to identify a potential causative relationship but overall several lines of evidence support a possible link between maternal inflammation from diabetes and the increased likelihood of neurodevelopmental disorders in the offspring.
Carpita, B., Muti, D., & Dell’Osso, L. (2018). Oxidative Stress, Maternal Diabetes, and Autism Spectrum Disorders. Oxidative Medicine and Cellular Longevity, 2018, 1–9. https://doi.org/10.1155/2018/3717215
Inflammation link for autism. (2020, February). Harvard Medicine Magazine. Retrieved May 8, 2022, from https://hms.harvard.edu/magazine/pandemic/inflammation-link-autism
Lombardo, M. V., Moon, H. M., Su, J., Palmer, T. D., Courchesne, E., & Pramparo, T. (2017). Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder. Molecular Psychiatry, 23(4), 1001–1013. https://doi.org/10.1038/mp.2017.15
Money, K. M., Barke, T. L., Serezani, A., Gannon, M., Garbett, K. A., Aronoff, D. M., & Mirnics, K. (2017). Gestational diabetes exacerbates maternal immune activation effects in the developing brain. Molecular Psychiatry, 23(9), 1920–1928. https://doi.org/10.1038/mp.2017.191
2 thoughts on “Intrauterine Inflammation, A Link To Autism?”
I am so impressed with this blog. As a developmental pediatrician and child and adolescent psychiatrist I see many children and teens with ASD. I am always looking to educate myself. Well done!