Cytokine profiling of maternal peripheral and umbilical cord blood in term and preterm labor

Immune dysregulation is increasingly implicated in the initiation of labor and the pathogenesis of preterm birth (PTB), yet the relative immune signatures of maternal and fetal compartments remain poorly defined. We performed multiplex profiling of 48 cytokines, chemokines and growth factors in paired maternal peripheral blood (PB) and umbilical cord blood (CB) collected from 78 pregnancies, including term births, spontaneous PTB (S-PTB), and PTB associated with premature rupture of membranes (PROM-PTB). Our data showed that PB and CB displayed clearly distinct immune landscapes, with CB enriched for immune-regulatory mediators and exhibiting more coordinated cytokine correlation networks, indicative of a highly structured fetal immune milieu. Principal component analysis revealed substantial overlap in global cytokine profiles among term and PTB subtypes in both compartments, consistent with largely conserved immune architecture. Accordingly, cytokine levels in maternal PB remained largely comparable across labor types, with no significant differences observed among term, S-PTB, and PROM-PTB pregnancies. In contrast, CB exhibited pronounced PTB-associated immune remodeling relative to term delivery, characterized by increased expression of growth factors M-CSF and SCF. Beyond these shared changes, S-PTB was further marked by upregulation of IFN-γ, IL-2Rα, MIP-1α, SDF-1α, G-CSF and SCGF-β, whereas PROM-PTB showed broader reductions in eotaxin and HGF. Together, these findings indicate that immune alterations associated with PTB are predominantly reflected in the fetal circulation and may involve distinct immunological mechanisms across PTB subtypes.