Neurodevelopmental Impact of Maternal Immune Activation and Autoimmune Disorders, Environmental Toxicants and Folate Metabolism on Autism Spectrum Disorder.

Abstract

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social communication, repetitive behaviors, and sensory sensitivities. While genetic factors contribute significantly to ASD risk, a growing body of evidence implicates environmental exposures and immune-mediated mechanisms in the etiology and severity of ASD. This review synthesizes peer-reviewed findings on (1) maternal immune activation, (2) environmental toxicant co-exposures, (3) maternal autoimmune disease, and (4) cerebral folate deficiency (via folate receptor alpha autoantibodies), detailing their mechanistic contributions to core and associated ASD symptoms. Collectively, these findings illuminate converging neuroimmune and metabolic pathways that, when disrupted in utero, substantially alter the developmental trajectory of the brain and increase the likelihood of ASD. Such interruptions leading to developmental changes can trigger immune activation from environmental sources of infection and pollution, with these triggers compounded in cases of autoimmune disease or cerebral folate deficiency. Understanding these mechanisms provides a foundation for early identification, stratified risk assessment, and the development of targeted prenatal interventions. Thus, a lesson we learn from autism is that neurodevelopmental disorders should be understood as the product of combined genetic vulnerabilities and modifiable prenatal and postnatal influences. Further exploration of this framework will open paths for precision intervention and prevention.