Cord blood biomarkers of the fetal inflammatory response

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 23-42 weeks), IL-1 beta increased with FIR among preterm subgroups (P = 0.0001 for <32 weeks; P = 0.0009 for 33-36 weeks). 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-1 beta, 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.