Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation.
BACKGROUND
Neonatal sepsis is a common and life-threatening disorder, particularly among preterm infants. Early initiation of antibiotic therapy is frequently delayed because the first clinical signs of sepsis are non-specific and there are no reliable early laboratory indicators. We investigated the time course of expression and the prognostic power of the early inflammatory mediators interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), and circulating intercellular adhesion molecule-1 (cICAM-1) before clinical diagnosis of sepsis.


METHODS
In a prospective multicentre study, we monitored 182 very-low-birthweight infants in six intensive-care units for occurrence of sepsis. During routine or clinically indicated blood sampling, an additional sample was collected for measurement of IL-1ra, IL-6, cICAM-1, and C-reactive protein (CRP). Infants were grouped into those with proven sepsis, no infection, or unclassified. The mean study duration was 34 days. Whenever sepsis occurred, a study period of 10 days was defined: day 0 was the day of clinical diagnosis of sepsis; days -4 to -1 were the 4 days before diagnosis; days +1 to +5 were the 5 days after. We compared the concentrations of the immune mediators during the 10-day study period with group-specific baseline values from before day -4.


RESULTS
101 infants were included in the analysis: 21 with proven sepsis, 20 with no infection, and 60 unclassified. We excluded 57 because of incomplete datasets and 24 who had early-onset sepsis. IL-1ra and IL-6 increased significantly 2 days before diagnosis of sepsis; maximum median increases within the study period were 15-fold for IL-1ra and 12-fold for IL-6. The diagnostic sensitivities of IL-1ra, IL-6, and CRP concentrations on day 0 of diagnosis were 93%, 86%, and 43%, respectively; corresponding values on day -1 were 64%, 57%, and 18%. The specificities of IL-1ra, IL-6, and CRP concentrations were 92%, 83%, and 93%. cICAM-1 had a specificity of only 64%.


CONCLUSIONS
IL-1ra and IL-6 are superior to cICAM-1 and CRP as predictors of sepsis 1 or more days before clinical diagnosis. Ad-hoc measurement of these cytokines could allow earlier initiation of antibiotic therapy with corresponding improvement in outcome in very-low-birthweight infants with sepsis.
Küster
H
H
Children's Hospital, Kinderpoliklinik, University of Munich, Germany.
Weiss
M
M
Willeitner
A E
AE
Detlefsen
S
S
Jeremias
I
I
Zbojan
J
J
Geiger
R
R
Lipowsky
G
G
Simbruner
G
G
D001317:Austria; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D005858:Germany; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000097:blood / Q000175:diagnosis*; D012795:Sialoglycoproteins / Q000097:blood*; D018154:Slovakia; D013997:Time Factors
D015415:Biomarkers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D012795:Sialoglycoproteins; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein