Maternal immune activation during pregnancy is associated with worst socio-adaptive behaviors in autism spectrum disorders

Abstract

Background Autism spectrum disorders (ASD) are neurodevelopmental disorders characterised by deficits in social communication or interaction and repetitive behaviours. Maternal immune activation (MIA) during the mid-pregnancy is a known risk factor for ASD. Although reported in 15% of affected individuals, little is known about the specificity of their clinical profiles. Adaptive skills represent a holistic approach to a person's competencies and reflect specifically in autism, their strengths and difficulties. Methods In this study, we hypothesised that individual with ASD with a history of MIA (MIA+) could be more severely socio-adaptively impaired than those without MIA during pregnancy (MIA−). To answer this question, we considered two independent cohorts of individuals with ASD (PARIS study and FACE ASD) screened for pregnancy history, and used a supervised and unsupervised statistical approach. Results We included 295 mother-child dyads with 14% of them with MIA+. We found that ASD-MIA+ individuals displayed more severe maladaptive behaviors, specifically in their socialization abilities. MIA+ directly influenced individual's socio-adaptive skills, independent of other covariates, including ASD severity. Interestingly, MIA+ may affected persistently the socio-adaptive behavioral trajectories of individuals with ASD. Limitations : The current study has a retrospective design with possible recall bias regarding the MIA event and, even if pooled from two cohorts, has a relatively small population. In addition, we were limited by the number of covariables available potentially impacted socio-adaptive behaviors. Larger prospective study with additional dimensions related to ASD is needed to confirm our results Conclusions Specific pathophysiological pathways may explain these clinical peculiarities of ASD- MIA+ individuals, and may open the way to new perspectives in deciphering the phenotypic complexity of autism and for the development of specific immunomodulatory strategies.

Maternal Immune Activation and Autism Spectrum Disorder: Complex Interactions and Therapeutic Possibilities

“…One emerging area of research on the environmental factors contributing to ASD is maternal immune activation (MIA) [5,6]. Maternal immune responses during pregnancy, particularly those resulting in inflammation, have been proposed as potential contributors to atypical neurodevelopment and increased ASD risk in offspring [7,8].…”