Prenatal exposure to maternal disadvantage-related inflammatory biomarkers: Associations with neonatal white matter connectivity

Abstract Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated the relationships among socioeconomic disadvantage, gestational inflammation, and neonatal white matter connectivity in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal serum levels of four cytokines (IL-6, IL-8, IL-10, and TNF-α) over the course of pregnancy in relation to offspring white matter connectivity and socioeconomic disadvantage. Higher average maternal IL-6 was associated with very low socioeconomic status (SES; INR < 200% poverty line) and lower neonatal corticospinal and uncinate FA and, in most tracts, lower AD. Higher average maternal IL-10 was associated with lower FA but higher RD in corticospinal and inferior cingulum tracts. Family SES moderated the relationship between average maternal TNF-α levels during gestation and neonatal white matter diffusivity, such that the association was significant and positive in the lower-to-higher SES (INR ≥ 200% poverty line) neonates for superior cingulum MD, but significant and negative in the very low SES neonates for inferior cingulum and fornix AD. Taken together, these findings suggest that the relationship between prenatal cytokine exposure and white matter development differs as a function of SES. This raises important public health questions regarding how biological mechanisms diverge depending upon foundational resources in utero.