Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection,☆☆,

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Abstract

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. STUDY DESIGN: 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. CONCLUSION: 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. (J PEDIATR 1996;129:574-80)

Section snippets

Study population

In a prospective study, we included all newborn infants admitted to the neonatal unit between March and May 1994 and measured IL-6, sTNF-R, and CRP. During the same period, IL-6 and sTNF-R were systematically determined in cord blood of the newborn infants delivered in the obstetrics unit and in the blood of some of their mothers.

In all cases the parents were informed and their written consent was obtained.

Methods of determination

Interleukin-6. Blood (100 μl, allowing a double determination) was collected in

Study population

The study population comprised 131 newborn infants systematically sampled in the obstetrics unit and 157 newborn infants admitted to the NICU. In all newborn infants the IL-6 and soluble TNF-α receptors were determined. In 58 of these infants, sampled at delivery, the same determinations were made in their mothers. The 157 neonates referred to the NICU also had a leukocyte count with differential count, sequential CRP determinations, and blood and local cultures according to clinical

DISCUSSION

For the efficient care of any infants at risk of infection, there is a requirement for a marker that responds early, is sensitive (identifying all patients with true sepsis), and is specific (to reduce unnecessary antibiotic treatment or to shorten it). Indeed, bacteriologic results need time and, even if negative, do not exclude sepsis. Such a marker would therefore be useful in reducing antibiotic treatment. In this study, we evaluated for the first time TNF-α receptors plasma levels for this

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From the Neonatal Unit, University Hospital of Strasbourg, Hopital de Hautepierre, Strasbourg, France, and F. Hoffmann-LaRoche, Ltd., Basel, Switzerland

☆☆

Reprint requests: Jean Messer, MD, Pédiatrie II, Hôpital de Hautepierre, 67098 Strasbourg-Cedex, France.

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