Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection.
OBJECTIVE
To evaluate plasma levels of interleukin-6 (IL-6) and soluble tumor necrosis factor receptors (sTNF-R) 55 and 75 in neonates as a contribution to the early diagnosis of infection.


METHODS
We prospectively measured IL-6 and sTNF-R 55 and sTNF-R 75 plasma levels in 157 newborn infants admitted to our regional neonatal center in a 3-month period and in cord blood of 131 newborn infants delivered in our obstetrics unit. C-reactive protein was sequentially determined after admission. Newborn infants were classified into four groups: group 0, not infected; group 1, possibly infected; group 2a, infected (culture positive), and group 2b, probably infected (culture negative). We looked for the optimal cutoff point of these parameters, using the receiver operating characteristics (ROC) curve.


RESULTS
IL-6 levels were significantly higher in group 2 (n = 11; median level, 250 pg/ml; range, 0 to 81,000), group 2b (n = 25; median level, 750 pg/ml; range, 0 to 180,000), and group 1 (n = 35; median level, 160 pg/ml; range 0 to 10,000), in comparison with group 0 (n = 217; median level, 0 pg/ml; range, 0 to 3400). A cutoff value of 100 pg/ml or greater obtained by the ROC method gives a sensitivity of 83.3% and a specificity of 90.3%. For inborn infants (n = 220) sampled at birth, sensitivity is 100% and specificity 92.3%. This high sensitivity persists until the twelfth hour of life. The sTNF-R 55 levels are significantly higher in group 2a (median, 12.0 ng/ml; range, 3.2 to 24.4). In group 2b (median, 7.0 ng/ml; range, 3.0 to 25.2), and in group 1 (median, 7.0 ng/ml; range, 2.5 to 18.9) than in group 0 (median, 3.9 ng/ml; range, 1.5 to 15.0), and with a cutoff value of 6 ng/ml, sensitivity is 75% and specificity 69%. The sTNF-R 75 levels are significantly higher in group 2a (median, 17.0 ng/ml; range, 7.2 to 48.8). In group 2b (median, 11.2 ng/ ml; range, (2.0 to 31.3), and in group 1 (median, 10.6 ng/ml; range, 2.0 to 33.0); than in group 0 (median, 7.0 ng/ml; range, 1 to 23.0). With a cutoff value of 9 ng/ ml, sensitivity is 80% and specificity 67%. Sensitivity of C-reactive protein is low initially but improves with time. Combining IL-6 with C-reactive protein provides the possibility of identifying the majority of infected infants in the postnatal period.


CONCLUSIONS
A plasma IL-6 level of 100 pg/ml or greater, obtained before the twelfth hour of life, appears to be an ideal marker for detecting early-onset neonatal infection with a high degree of sensitivity and specificity. After the twelfth hour, the combined determination of IL-6 and C-reactive protein may be equally useful. The sTNF-R levels appear to be less useful in the early diagnosis of infection because of their smaller magnitude of variation.
Messer
J
J
Neonatal Unit, University Hospital of Strasbourg, Hopital de Hautepierre, France.
Eyer
D
D
Donato
L
L
Gallati
H
H
Matis
J
J
Simeoni
U
U
D015703:Antigens, CD / Q000097:blood*; D001424:Bacterial Infections / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000097:blood*; D011446:Prospective Studies; D012372:ROC Curve; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012680:Sensitivity and Specificity
D015703:Antigens, CD; D015415:Biomarkers; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D002097:C-Reactive Protein