Inflammatory mediators in umbilical plasma from neonates who develop early-onset sepsis.
OBJECTIVE
To study whether early-onset neonatal sepsis is associated with a prenatal immune response with elevated umbilical plasma levels of inflammatory mediators, and to study whether mediator levels may be helpful in identifying infected neonates.


METHODS
Nested case-control study.


METHODS
Cord blood was sampled from 7,073 consecutively delivered neonates. After review of the medical records, neonates suspected to suffer from infection were classified as infected (n = 52) or noninfected but sick controls (n = 33). We also included a group of healthy controls (n = 99). Umbilical plasma levels of tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1beta, IL-6, IL-8, soluble TNF receptors (p55 and p75), IL-1 receptor antagonist (IL-1RA) and C-reactive protein were measured by immunoassays.


RESULTS
Infected neonates had higher levels of TNFalpha, IL-1beta, IL-6, IL-8, p55, p75 and IL-1RA than healthy controls (all p < 0.01). Among preterm infants (GA <37 weeks), those with infection (n = 11) had higher levels of IL-1beta, IL-6, IL-8, p55 and p75 than noninfected sick controls (n = 13) (all p < 0.05), but among term infants, the infected did not differ from the noninfected sick controls. Receiver operator characteristic plots showed that IL-1beta, IL-6 and IL-8 identified preterm infected neonates accurately.


CONCLUSIONS
Early-onset neonatal sepsis is associated with a prenatal immune response with increased TNFalpha, IL-1beta, IL-6, IL-8, p55, p75 and IL-1RA levels in umbilical plasma. Among neonates who present symptoms suggestive of infection, cytokine levels may be helpful in identifying preterm, but not term infected individuals.
Døllner
H
H
Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, University Medical Center, Trondheim, Norway. henrik.dollner@medisin.ntnu.no
Vatten
L
L
Linnebo
I
I
Zanussi
G F
GF
Laerdal A
Austgulen
R
R
D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000097:blood*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D012372:ROC Curve; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000097:blood*; D012795:Sialoglycoproteins / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C507763:IL1RN protein, human; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein