Influence of Maternal Immune-Related Conditions on Neurodevelopmental and Neuropsychiatric Outcomes in Offspring: Building a Conceptual Model

Maternal health during pregnancy contributes substantially to the lifelong health and well-being of offspring. Growing evidence suggests that perturbations to the maternal immune system during gestation can interfere with typical foetal developmental trajectories. Specifically, maternal immune-related conditions during pregnancy, such as infections, autoimmune conditions, asthma, and allergies have been associated with increased risk of neurodevelopmental and neuropsychiatric disorders in offspring. This thesis investigated associations between maternal immune-related conditions and neurodevelopmental and neuropsychiatric outcomes in offspring. The first two empirical studies focussed on the influence of maternal asthma, allergies, and autoimmune conditions on symptom outcomes in children with autism spectrum disorder (ASD). The third empirical study considered the influence of maternal infections, asthma, allergies, and atopy on broad neuropsychiatric outcomes in a general population cohort across childhood and adolescence. Maternal immune-related conditions were associated with increased severity of caregiver-reported social, behavioural, and emotional problems in children with ASD. They were also a general risk factor for adverse neuropsychiatric outcomes throughout childhood and adolescence, conferring risk to offspring development in a cumulative manner. These findings led to the proposition of a conceptual model to visualise and understand the cumulative influence of all maternal immune-related exposures on foetal neurodevelopment. Overall, this work highlights the importance of the maternal immune system in the context of foetal brain development and its potential role in the aetiology of neurodevelopmental and neuropsychiatric disorders. Advancement of knowledge regarding the mechanisms by which the maternal immune system influences neurodevelopment may open new avenues for early detection and intervention in children affected by these disorders