Related Experiment Video
Updated: Jul 4, 2025
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Early changes in serum interleukin-6 levels in extremely premature newborns for detecting fetal inflammation
Sota Iwatani1, Takao Kobayashi1, Toshihiko Ikuta1
1Department of Neonatology, Hyogo Prefectural Kobe Children's Hospital Perinatal Center, Hyogo, Japan.
Insights
Serum interleukin-6 (IL-6) levels in extremely premature newborns increase after birth and then decrease. Postnatal age-specific cut-off values for IL-6 may help detect fetal inflammation.
Area of Science:
- Neonatalogy
- Perinatal Medicine
- Inflammatory Response
Background:
- Fetal inflammatory response syndrome (FIRS) is linked to elevated fetal inflammatory cytokines and preterm complications.
- Serum interleukin-6 (IL-6) is a key indicator of FIRS, but its postnatal dynamics require clarification.
- Extremely premature newborns (EPNs) are particularly vulnerable to FIRS-related morbidities.
Purpose of the Study:
- To characterize early postnatal changes in serum IL-6 levels in EPNs.
- To establish postnatal age-dependent cut-off values for IL-6 to detect fetal inflammation.
- To correlate IL-6 levels with funisitis, the histological marker of FIRS.
Main Methods:
- Retrospective analysis of 49 EPNs (< 28 weeks gestation).
- Serum IL-6 measurements at delivery, 1-3, 6-12, and 24-36 hours postpartum.
- Receiver operating characteristic (ROC) curve analysis to determine IL-6 cut-off values for funisitis detection.
Main Results:
- Serum IL-6 levels were elevated at 1-3 and 6-12 hours postpartum, returning to delivery levels by 24-36 hours.
- EPNs with funisitis showed significantly higher IL-6 levels at delivery, 1-3, and 6-12 hours.
- ROC analysis yielded IL-6 cut-off values for funisitis detection at different postnatal epochs.
Conclusions:
- Serum IL-6 levels in EPNs exhibit a distinct early postnatal surge and subsequent decline.
- Postnatal age-specific IL-6 cut-off values are crucial for accurately detecting fetal inflammation in EPNs with funisitis.
- These findings aid in the early identification and management of FIRS-related complications in extremely premature infants.
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.
