Neutrophil CD11b expression, soluble tumor necrosis factor receptors and plasma interleukin 6 as markers of early neonatal sepsis

ABSTRACT

The value of neutrophil CD11b expression, soluble tumor necrosis factor receptors [sTNF-R] 55 and 75 and plasma interleukin-6 [IL-6] in early detection of neonatal infection was studied in 288 neonates. The studied newborns were classified into 4 group group 0 [not infected], group 1 [possibly infected], group 2a [probably infected, culture-ve] and group 2b [culture +ve infection]. We looked for the optimal cutoff points of these parameters using the receiver operating characteristics [ROC] curve. The neutrophil CD11b expression by flowcytometry [FCM] was >100 median FU in all neonates with confirmed infection, >60 in all but one neonate of those with suspected infection, and <60 FU in non-infected group. A cutoff value of 60 FU or greater a 96% sensitivity, and a negative value of 99%. The sTNF-R 55 levels were significantly higher in the culture +ve group; 2a [median 7ng/ml], 2b [median 12ng/ml], and 1 [median 7ng/ml] than group 0 [median 3.9 ng/ml]. The sensitivity and specificity of a cutoff level of 6 ng/ml were 75% and 69% respectively. Similarly, sTNF-R 75 levels in groups 2a [median 11.2ng/ml], 2b [median 7 ng/ml], and 1 [median 10.6 ng/ml] than group 0 [median 7 ng/ml]. With a cutoff value of 9 ng/ml, sensitivity and specificity were 80% and 67% respectively The median levels of plasma IL-6 in groups 2a, 2b, 1, and 0 were 700 pg/ml, 260 pg/ml, 160 pg/ml, and 0 pg/ml respectively. A cutoff value of 100 pg/ml was 83.3% sensitive and 90.3% specific in diagnosing neonatal infection. For newborns sampled at birth or within the 1st postnatal hour, sensitivity was 100% and specificity 92.3%. This high sensitivity persisted until the 12th hour of life. On the other hand sensitivity of C- reactive protein [CRP] was low initially but improved with progress of infection. It is concluded that neutrophil CD11b is a promising test for ruling out early onset neonatal sepsis. If validated prospectively, such assay may reduce hospital stay and antibiotic use in newborns at risk of sepsis. High plasma IL-6 alone before 12th hour of life, and combined with high CRP thereafter, provides a useful maker for identifying the majority infected neonates. The sTNF-R seem less useful in this context because of their smaller magnitude of variation