Inflammatory biomarkers as predictors of fetal brain resilience or vulnerability to prenatal maternal anxiety

Abstract

Prenatal maternal anxiety has been associated with altered neurodevelopmental outcomes in offspring, yet the biological mechanisms underlying this relationship remain poorly understood. This study investigated whether maternal inflammatory biomarkers moderate the association between prenatal anxiety and offspring brain and behavioral development. Using data from a prospective longitudinal cohort, we assessed maternal anxiety and circulating inflammatory markers at late mid-pregnancy, followed by neonatal brain MRI (n = 159) and cognitive assessments at 24 months (n = 340). Our findings revealed that interferon-gamma (IFN-γ) moderated the association between prenatal maternal anxiety and neonatal right globus pallidus volume, with higher IFN-γ levels linked to a larger pallidus volume and better cognitive outcomes at 24 months, even in the context of elevated anxiety. Similarly, both high and low levels of maternal monocyte chemoattractant protein-1 (MCP-1) altered the relationship between prenatal anxiety and neonatal brain morphology within the striatal–cortical circuit, including bilateral caudate volumes and cortical thickness in the sensorimotor and temporal regions. These results suggest that extreme MCP-1 levels may amplify vulnerability or promote resilience in fetal brain development. Higher MCP-1 levels were also associated with improved language development at 24 months. Together, these findings highlight the potential roles of inflammatory biomarkers in shaping the fetal brain’s sensitivity to maternal anxiety, offering potential mechanisms for early risk identification and intervention strategies.