Cord blood biomarkers of the fetal inflammatory response

Abstract

In current neonatal practice, clinical signs of intrauterine infection (IUI) are often non-specific. From a large panel of immune biomarkers, we seek to identify cord blood markers that are most strongly associated with the fetal inflammatory response (FIR), a specific placental lesion associated with serious neonatal complications. We used multiplex immunoassay to measure 27 biomarkers, selected as part of an NIH-funded study of preterm birth, according to gestational age(GA) and extent of placental inflammation: involvement of chorion, amnion, decidua (maternal inflammatory response, MIR); extension to umbilical cord or chorionic plate (FIR). We used false-discovery rate (FDR<5%, P<0.001) to account for multiple comparisons. Among 506 births (GA 23-42wks), IL-1β increased with FIR among preterm subgroups (P=0.0001 for <32wks; P=0.0009 for 33-36wks). IL-6 and IL-8 increased with FIR among preterm and full-term infants (P<0.0001). P-trend for IL-6 and IL-8 with MIR versus FIR was <0.0001. Comparison with respect to clinical IUI yielded persistent elevation with FIR even when clinical signs were absent. The remaining 24 markers were not significantly associated. We conclude that among 27 cord blood biomarkers, IL-1β, IL-6 and IL-8 are selectively associated with FIR. These markers may be clinically useful indicators of extensive IUI associated with poor neonatal outcome.

Clinical chorioamnionitis at term V: umbilical cord plasma cytokine profile in the context of a systemic maternal inflammatory response

“…Umbilical cord plasma IL-8, IL-10, and MCP-1 concentrations were significantly associated with FIRS. Our findings are consistent with those of Mestan et al, who used multiplex immunoassays and reported that, among the 27 cord blood biomarkers examined, the concentrations of IL-1β, IL-6, and IL-8 were associated with the presence of funisitis (the magnitude of association was stronger for IL-6 and IL-8 than for IL-1β) [268]. …”

“…Several studies have demonstrated the potential value of umbilical cord plasma concentrations of IL-6 [105, 250–277] and IL-8 [257, 260–262, 267, 268, 276, 278, 279] for the identification of intra-amniotic infection and early-onset neonatal sepsis. Our findings are consistent with those of Lencki et al, who reported that neonates born to mothers with clinical chorioamnionitis had higher umbilical cord plasma concentrations of IL-6, but not IL-1β and soluble IL-2 receptor, than those without this condition [280].…”

Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants

“…Placental inflammation is associated with early onset neonatal infection [23–25], although only a fraction of infants with histologic chorioamnionitis develop EOS [22]. Some cord blood biomarker levels are associated with placental inflammation representing a neonatal response to a perinatal insult [26, 27]. Although the role of placental histopathology in the diagnosis of neonatal sepsis and treatment decisions remains unclear [28], placental inflammation may be a useful tool to identify infants exposed to intraamniotic infection.…”

Inflammation-related proteins in the blood of extremely low gestational age newborns. The contribution of inflammation to the appearance of developmental regulation

“…Thus, the protein concentration differences between the preterm and the full term might reflect environmental, obstetrical and neonatal influences, just as readily as developmental regulation [15]. …”