Gestational Age Dependency of Umbilical Cord Serum IL-6 Levels for Detecting Fetal Inflammation

Am J Perinatol. 2022 Jul;39(9):987-994. doi: 10.1055/s-0040-1721373. Epub 2020 Nov 26.

Abstract

Objective: The fetal inflammatory response syndrome (FIRS) is characterized by elevated concentrations of inflammatory cytokines in fetal blood, with preterm delivery and morbidity. Umbilical cord serum interleukin-6 (UC-s-IL-6) is an ideal marker for detecting FIRS. However, the effect of gestational age (GA) on UC-s-IL-6 levels has not been reported. This study aimed to determine the relationship between GA and UC-s-IL-6 levels, and GA-dependent cutoff values of UC-s-IL-6 levels for detecting fetal inflammation.

Study design: UC-s-IL-6 concentrations were measured in 194 newborns (44 extremely preterm newborns (EPNs) at 22-27 weeks' GA, 68 very preterm newborns (VPNs) at 28-31 weeks' GA, and 82 preterm newborns (PNs) at 32-34 weeks' GA). Linear regression analyses were used to correlate GA and UC-s-IL-6 levels. Receiver operating characteristic (ROC) curves analyses were performed for detecting the presence of funisitis, as the histopathological counterpart of FIRS.

Results: A significant negative correlation between GA and UC-s-IL-6 levels was found in newborns with severe funisitis (r s = - 0.427, p = 0.004) and those with mild funisitis (r s = - 0.396, p = 0.025). ROC curve analyses revealed the area under the curve for detecting funisitis were 0.856, 0.837, and 0.622 in EPNs, VPNs, and PNs, respectively. The UC-s-IL-6 cutoff value in EPNs (28.1 pg/mL) exceeded those in VPNs and PNs (3.7 and 3.0 pg/mL, respectively).

Conclusion: UC-s-IL-6 levels were inversely correlated with GA especially in newborns with funisitis. Such GA dependency of UC-s-IL-6 should be considered for detecting fetal inflammation.

Key points: · IL-6 levels inversely correlate with GA.. · Higher IL-6 levels strongly indicate funisitis.. · Detecting cutoff values differ depending on GA..

MeSH terms

  • Chorioamnionitis* / diagnosis
  • Female
  • Fetal Blood
  • Fetal Diseases
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Inflammation
  • Interleukin-6
  • Systemic Inflammatory Response Syndrome
  • Umbilical Cord

Substances

  • Interleukin-6

Supplementary concepts

  • fetal inflammatory response syndrome