Maternal Immune Activation and Child Brain Development: A Longitudinal Population-based Multimodal Neuroimaging study.

Abstract

Background: Maternal Immune Activation (MIA) has been hypothesized to have an adverse effect on child neurodevelopment, but only a few neuroimaging studies have been performed to date, mostly in neonates. In this population-based cohort study, we investigated the association between MIA and multiple neuroimaging modalities depicting brain development from childhood to adolescence.

Methods: We used data of mother-child pairs from the Generation R Study. To define our exposure, we measured IL-1β, IL-6, IL-17a, IL-23 and IFN-γ, and CRP at two time points during pregnancy. Given that levels of these 5 cytokines were highly correlated, we were able to compute a Cytokine index. We used multiple brain imaging modalities as outcomes, encompassing global and regional measures of brain morphology (structural MRI, volume, n=3,295), white matter microstructure (diffusion MRI, FA and MD, n=3,267), and functional connectivity (functional MRI, graph theory measures and network-level connectivity, n=2,914) at child mean ages 10 and 14 years. We performed mixed-effects models using the child's age as continuous time variable.

Results: We found no significant association or time interaction between MIA and any neuroimaging outcomes in children over time. These associations were similar for the Cytokine index, CRP, and individual cytokines. We observed no evidence for differential effects of timing of prenatal MIA or child sex after multiple testing correction.

Conclusions: This longitudinal population-based study reports no evidence for an association between MIA and child brain development in the general population. Our findings differ from prior research in neonates showing structural and functional brain abnormalities after MIA.