Intrauterine inflammation has been associated with preterm birth and poor neonatal outcomes, with some evidence of immunomodulation in exposed fetuses. In this study we sought to test the hypothesis that fetal immune maturation and sensitivity is likely to be altered in pregnancies with evidence of feto-placental inflammation.
Mixed umbilical cord blood was collected from Caesarean section deliveries delivered 34-42 weeks’ gestation (n=44). Placentas were classified by histopathology as having inflammation in the fetal tissue (n=13), inflammation in the maternal tissue (n=10), or no inflammation (n=23). None of the pregnancies had histological chronic chorioamnionitis, clinical evidence of intrauterine infection, or received antenatal glucocorticoids.
Cord blood was exposed shortly after delivery (< 2 hours) to a panel of immune stimuli [R848, LPS, PGN, poly (I:C), cGAMP, and 5’ppp-dsDNA] and incubated for 24 h at 37oC. Plasma was harvested and subsequently concentrations of G-CSF, IFN-γ, IL-1β, IL-6, IL-8, IL-10, and TNF-α were determined by multiplex assay to generate immune response profiles. Multivariate comparisons were made between fetal inflammation, maternal inflammation, and no inflammation groups using the Kruskal-Wallis test, then further analysed by univariate comparisons between each individual group using the Mann-Whitney test.
Fetuses with inflammation in the fetal regions of the placenta (funisitis, FIRS or acute chorioamnionitis) had a significantly increased IL-6 responses to cGAMP and 5'ppp-dsRNA (ligands for STING and RIG-I, respectively) compared to fetuses with maternal inflammation (chronic or acute villitis or deciduitis) or no inflammation (P<0.05). On the other hand, IL-8, IL-10, and G-CSF responses to poly (I:C) (a TLR3 agonist) were significantly suppressed in the fetal inflammation group (P<0.05).
Our study suggests that fetal immune responsivity is altered in pregnancies with sub-clinical feto-placental inflammation. This may be associated with perturbations in fetal immune development and altered infection risk. Further long-term studies are required to explore this possibility.