Plasma neuron specific enolase (NSE), tumour necrosis factor-alpha (TNF-) and soluble IL-2 receptor alpha (sIL-2R) levels in children with developmental delay (DD): Use of combined ROC curves to increase their diagnostic value

Background: Developmental delay (DD) occurs when children fail to reach developmental milestones in comparison to peers of the same age range. However, there are no valuable biomarkers for the early diagnosis of DD. Since there is no specific marker for screening the disease, we evaluated plasma NSE, TNF-alpha and sIL2-R alpha as potential markers for this purpose.Methods: In this cross-sectional randomized case-control study, a total of 174 DD patients and 49 matched elderly controls aged between 2 months and 60 months were recruited. A sensitive enzyme-linked immunosorbent assay and an immunoradiometric assay were used to evaluate the levels of plasma IL-1, IL-6, IL-8, IL-10, sIL2-R alpha, TNF-alpha, and NSE. Statistical analyses using t test, chi(2), ANOVA, ROC curves and binary logistic regression models were performed.Results: In comparison to the control group, the DD group had greater levels of NSE, TNF-alpha, and sIL2-R alpha(p < 0.05). In the binary logistic regression analysis of DD, NSE had an odds ratio (OR) of 1.783 (95 % CI 1.297 to 2.451, p = 0.000), indicating that NSE was an independent risk factor for DD. The plasma TNF-alpha level was positively correlated with plasma NSE and sIL2-R alpha levels in the DD group (r = 0.366 and 0.433, respectively), and the DQ score and plasma sIL2-R alpha level in the DD group were positively correlated. The ROC curve revealed that the respective areas under the NSE, TNF-alpha, and sIL2-R alpha ROC curves were 0.9797, 0.9365, and 0.8533, respectively. Moreover, a significant increase in AUC was observed using combined ROC curve analysis.Conclusions: Children with DD have significantly altered plasma concentrations of sIL2-R alpha, NSE, and TNF-alpha. NSE, TNF-alpha and sIL2-R alpha can be used as DD blood biomarkers. This information may be helpful in early diagnosis and intervention.