Investigating the Association Between Maternal Infection and Inflammation and Child Autistic Traits in a Large Population BasedCohort Study

Abstract

Objective: Maternal immune activation during pregnancy has been proposed as a mechanism linking prenatal inflammatory exposures to autism pathogenesis. While preclinical and epidemiological studies suggest a role for maternal inflammation and infection, findings in population-based cohorts are inconsistent. This study examined the associations between multiple prenatal inflammatory exposures and autistic traits, accounting for gene-environment interactions in the general pediatric population.

Methods: We leveraged data from 5.075 mother-child dyads participating in Generation R. a population-based pregnancy cohort in the Netherlands. Prenatal inflammatory exposures included 1) maternal serum cytokines; 2) high-sensitivity CRP: 3) self-reported fever during pregnancy; 4) a maternal polygenic score for CRP: and 5) a methylation profile score of CRP in cord blood. Child autistic traits were measured with the Social Responsiveness Scale at mean ages 16 and 13 years. Linear mixed models were applied to estimate associations adjusted for maternal, child and technical covariates. Interaction terms tested whether child polygenic score for autism moderated associations.

Results: No significant associations were observed between prenatal inflammatory exposures and autistic traits, both as a continuous measure and above a clinical threshold. No evidence was found for interactions between prenatal inflammatory exposures and the child polygenic score for autism in influencing autistic traits.

Conclusion: Our findings suggest that typical fluctuations in maternal inflammation are unlikely to represent a major pathway linking prenatal environment to autism risk. We found no evidence that gene-environment interactions conferred additional risk for autistic traits.