Tran, P. V.; Harris, A. C.; Maxim, Z. L.; Munirathinam, M.; Muelken, P.; Javadova, N.; Kruttiventi, S.; Kling, P. J.; Baack, M. L.; Georgieff, M. K.

Maternal adiposity induces inflammation that may cause fetal neuroinflammation and brain iron deficiency, and thus neurodevelopmental risk. Currently, there is a lack of brain-specific biomarkers that identify neonates who are at risk, limiting the ability to screen and intervene early in life, when interventions may have the greatest impact on neurodevelopment. Leveraging emerging technology that purifies nanoparticles secreted from the brain into circulation, this study assessed the feasibility of quantifying inflammatory and iron markers carried within these nanoparticles to index brain inflammatory and iron status using a small volume of cord blood. Newborns of overweight-obese mothers exhibit evidence of low-level peripheral pro-inflammation with normal systemic iron status. In contrast, the brain shows anti-inflammatory responses and functional iron deficiency demonstrating that peripheral biomarkers may not accurately reflect brain processes. The discovery of quantifiable brain-derived biomarkers in blood samples serves as proof-of-concept that infants at-risk for long-term adverse health outcomes could be identified by non-invasive assays before becoming apparent later in life.