Early changes in serum interleukin-6 levels in extremely premature newborns for detecting fetal inflammation

Cytokine. 2024 Apr:176:156528. doi: 10.1016/j.cyto.2024.156528. Epub 2024 Feb 2.

Abstract

Background: Fetal inflammatory response syndrome (FIRS) is defined by elevated levels of inflammatory cytokines circulating in fetal blood, which may result in preterm morbidities. Serum interleukin-6 (IL-6) level has been reported to be a good indicator of FIRS; however, changes in IL-6 levels after birth remain to be elucidated. Herein, we characterized early changes in serum IL-6 levels in extremely premature newborns (EPNs, < 28 wks gestation), and then determined the cut-off values for detecting fetal inflammation at each postnatal epoch.

Methods: In this single-center study, 49 EPNs were retrospectively studied. Serum IL-6 measurements are routinely performed at delivery, 1-3, 6-12, and 24-36 h of life. Receiver operating characteristic (ROC) curve analyses were performed for detecting the presence of funisitis, the histologic counterpart of FIRS.

Results: Overall, serum IL-6 levels were significantly elevated at 1-3 (298 [31-4719] pg/mL) and 6-12 (29 [2-12,635] pg/mL) hours of life, then returned to at-delivery levels at 24-36 h of life. When comparing serum IL-6 levels at each postnatal epoch, the levels at delivery, 1-3, and 6-12 h of life were significantly higher in the EPNs with funisitis. Serum IL-6 cut-off values at delivery, 1-3, 6-12, and 24-36 h of life for the presence of funisitis were 20, 572, 290, and 13 pg/mL with area under ROCs of 0.75, 0.71, 0.68, and 0.53, respectively.

Conclusions: Serum IL-6 levels in EPNs significantly increase early after birth, then decrease to at-delivery levels by 24-36 h of life. Therefore, postnatal age-dependent cut-off values of serum IL-6 might be considered for detecting fetal inflammation with confirmed funisitis.

Keywords: Chorioamnionitis; Fetal inflammatory response syndrome; Funisitis; Interleukin-6 (IL-6); Morbidities.

MeSH terms

  • Chorioamnionitis*
  • Female
  • Fetus
  • Humans
  • Infant, Newborn
  • Inflammation
  • Interleukin-6*
  • Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester
  • Retrospective Studies

Substances

  • Interleukin-6
  • Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester
  • IL6 protein, human