Is pro-adrenomedullin a more useful marker in hospitalized infants with sepsis?

Abstract

Dear Editor, We read with great interest the recent article by Benito et al. [1] whose objective was to assess the usefulness of two biomarkers, midregional pro-adrenomedullin (pro-ADM) and C-proendothelin-1 (CT-pro-ET-1), in predicting bacterial infection and, especially, invasive bacterial infection (IBI) in wellappearing infants with fever without source. They found that plasma levels of both endothelium-derived precursor peptides were higher in well-appearing febrile infants with focal and IBI than in patients with viral or self-limited infection. CT-pro-ET-1 showed a significant difference between patients with no bacterial infection and those with focal bacterial infection (p<0.05), but not between patients with focal bacterial infection and IBI. Levels of midregional pro-ADM showed no statistically significant differences among the three groups. These markers had a lower diagnostic accuracy for assessing the severity of bacterial infection than other biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). In the initial univariate analysis, they found that PCT of ≥0.5 ng/mL, midregional pro-ADM of ≥0.7 nmol/L, andCRPof≥40mg/Lwere significantly associated with IBI. The only independent risk factor identified in the final multivariate model was a higher PCT level (≥0.5 ng/mL). In a recent similar study, we sought to compare sequential measurements of white blood cell count, CRP, interleukin-6 (IL-6), and pro-ADM in proven sepsis and clinical sepsis and the control group in newborns. A total of 76 patients with neonatal sepsis (31 with proven sepsis and 45 with clinical sepsis) and 52 healthy controls were enrolled. Mean baseline serum levels of CRP, IL-6, and pro-ADM were significantly higher in both proven and clinical sepsis groups compared to those in healthy controls (p <0.001 for both). Although mean baseline CRP and IL-6 levels were similar between groups, mean baseline pro-ADM level was higher in the proven sepsis group than that in clinical sepsis group (p <0.001). The calculated cutoff values for CRP, IL-6, and pro-ADM in distinguishing patients with sepsis group were 4.87 mg/L, 26 pg/mL, and 3.9 nmol/L, respectively. Area under the curve analysis for comparing patients with proven sepsis and healthy controls once again revealed the set cutoff values for CRP, IL-6, and pro-ADM to have specificities and positive predictive values of 100 %, with respective sensitivities of 96.7, 93.5, and 93.5 %. Negative predictive values for the three markers were 98.1, 96.2, and 96.2 %, respectively. Our study demonstrated that pro-ADM is a novel marker that may be used especially for the early diagnosis of neonatal sepsis. The fact that pro-ADM levels showed more rapid decreases compared to CRP in our study, we suggested that rather than being used alone, the use of pro-ADM in combination with conventional acute phase reactants may be more useful in the diagnosis and follow-up of patients with neonatal sepsis [2]. In conclusion, in relation to our study, we think that the result by Benito et al. [1] which showed pro-ADM as a weak marker in diagnosis of IBI might be both due to short half-life of the marker and the time of the obtaining the blood (whether early or late in emergency room). In contrast, we found proADM to be useful in the early detection of neonatal sepsis. Results of both studies suggest that pro-ADMmay be a useful marker in closely followed up hospitalized patients rather than outpatient infants and children. M. Y. Oncel (*) :N. Uras :U. Dilmen Division of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara 06230, Turkey e-mail: dryekta@gmail.com