Role of maternal immune response and placental exosomes in infant cognitive outcome at 12 months of age.

Placental exosomes are released into maternal circulation as key mediators of maternal-fetal crosstalk and act as biomarkers of pregnancy adversities, also influencing the regulation of maternal cytokine levels. However, their role in neurodevelopmental outcomes remains poorly explored. Here we analyzed the association between maternal cytokines and placental exosomes with neurodevelopmental outcomes in a Brazilian sample of socially vulnerable pregnant adolescents. Maternal cytokines were measured in 60 plasma samples using the Luminex technology, and placental exosomes isolated from the maternal circulation were analyzed by flow cytometry. Infant neurodevelopmental outcomes at 12 months were assessed using the Bayley Scales of Infant and Toddler Development-III (BSID-III). Multiple linear regression models were applied to investigate the proportion of exosomes (PLAP+ to CD63 + exosomes ratio) and cytokines as predictors of BSID-III. We found a negative association between exosome ratio and infant sex, with the BSID-III cognitive domain. No association was found for the exosomes with BSID-III language and motor domains. Considering the immunomodulatory components when cytokines IL-10 and IL-6 were included in the BSID-III cognition model, a significant association was observed, being positive for IL-10 and negative for IL-6. Finally, when both cytokines IFN-γ and IL-1β were tested with BSID-III cognitive domain, we observed a negative association for IFN-γ and positive association for IL-1β. In both models, exosome ratio, infant sex, and the interaction effect of infant sex on exosome ratio remained significant. Our results underscore the potential contribution of placental exosomes and maternal inflammatory states to the infants' neurocognitive outcomes.