An Elevated Fetal Interleukin-6 Concentration Can Be Observed in Fetuses with Anemia Due to Rh Alloimmunization: Implications for the Understanding of the Fetal Inflammatory Response Syndrome

Overview

Journal J Matern Fetal Neonatal Med

Publisher Informa Healthcare

Specialty Gynecology & Obstetrics

Date 2010 Aug 13

PMID 20701435

Citations 17

Authors

Edi Vaisbuch

Roberto Romero

Ricardo Gomez

Juan Pedro Kusanovic

Shali Mazaki-Tovi

Tinnakorn Chaiworapongsa

Sonia S Hassan

Affiliations

Soon will be listed here.

Abstract

Objective: The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm prelabor rupture of the membranes and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia.

Methods: Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/ml. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis.

Results: (1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); (2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration -- the lower the hematocrit, the higher the fetal IL-6 (r=-0.68, p=0.004); (3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18-2.63 vs. 1.46 pg/ml, IQR 1.76-14.7; p=0.02); (4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6.

Conclusions: An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization.

Citing Articles

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Contribution of Fetal Inflammatory Response Syndrome (FIRS) with or without Maternal-Fetal Inflammation in The Placenta to Increased Risk of Respiratory and Other Complications in Preterm Neonates.

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Greenfield K, Badovinac V, Griffith T, Knoop K Immunohorizons. 2021; 5(6):512-522.

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Kabyemela E, Fried M, Kurtis J, Moses G, Gorres J, Muehlenbachs A Front Immunol. 2021; 12:624136.

PMID: 33995348 PMC: 8120033. DOI: 10.3389/fimmu.2021.624136.

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