Interleukin-6 as a Biomarker of Early-Onset Neonatal Sepsis

Abstract

Objective The aim of this study is to determine the utility of C reactive protein (CRP) and interleukin (IL)-6 in the diagnosis of neonatal sepsis (NS) in a neonatal intensive care unit (NICU) in the south of Colombia. Study Design A nonmatched case–control study was conducted. Convenience sampling was performed. Data were obtained from clinical records. IL-6 levels were determined using enzyme-linked immunosorbent assay. Receiver operator characteristic (ROC) curve analysis and Youden's index were used to determine the optimal cutoffs for CRP and IL-6 levels in diagnosing NS, early-onset NS (EONS), and late-onset NS (LONS). Results Data from 31 cases and 62 controls were included. History of chorioamnionitis (infinite odds ratio [OR] [3.07-infinity]), and the presence of meconium-stained amniotic fluid during birth (OR: 9.04 [1.35–112]) were identified as risk factors for NS. Differences in CRP (p < 0.0001) and IL-6 (p < 0.0485) levels were also found, more significantly for LONS and EONS patients, respectively. In the diagnosis of LONS using CRP levels, the area under the ROC curve (AUC) was 0.8371 (p < 0.0001). The optimal cutoff was 0.53 mg/dL. For EONS diagnosis using IL-6, the AUC was 0.6869 (p = 0.0315) and the optimal cutoff was 17.75 pg/mL. Conclusion Differences between CRP and IL-6 levels were found between control and NS groups. Furthermore, CRP showed greater potential diagnostic utility in the LONS group, whereas IL-6 showed greater potential utility in the EONS group. Key Points

The Value of Perinatal Factors, Blood Biomarkers and Microbiological Colonization Screening in Predicting Neonatal Sepsis

“…The analysis of IL-6 concentrations showed a strong predictive value for neonatal sepsis (both EOS and LOS). Our data favor a cut-off value at 100 ng/L, while different cut-off values have been suggested by others [ 25 , 26 , 27 , 28 , 29 , 30 ]. The sensitivity and specificity at this cut-off value showed similar results to those published in 2018 by the Association of the Scientific Medical Societies in Germany (AWMF) [ 6 , 26 , 31 , 32 ].…”

Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis

“…First clinical studies using CRP as biomarker to detect bacterial infections were performed in the late 1980s, and CRP was used in the 1990s for detection of septic neonates showing promising clinical usage of CRP for diagnosis of neonatal sepsis [ 36 , 37 , 38 , 39 ]. The most recent study correlating neonatal sepsis with elevated levels of CRP and IL-6 was published by Cortes et al and demonstrated that CRP could be a useful biomarker in combination with other inflammatory biomarkers, especially for late-onset neonatal sepsis [ 40 ]. Recently, 14 clinical studies were summarized by Pay and Shaw [ 41 ] ) showing a correlation of salivary CRP and serum CRP levels with R 2 of 0.53 ± 0.23, comparable to the result of our study with a R 2 value of 0.52 ( Figure 1 A).…”

“…Even though clinical studies linked salivary CRP positively as a marker for metabolic syndrome [ 42 ], detection of obesity in children [ 43 ], or pneumonia in neonates [ 17 ], a study published in 2019 with 37 healthy young males showed no clear correlation between salivary and serum concentrations of CRP [ 44 ]. Additionally, even though CRP is commonly used as a marker for neonatal sepsis, recent clinical studies claimed the need of other salivary markers for diagnosis due to unreliable screening validity of salivary CRP [ 18 , 19 , 40 ].…”

Diagnosis of neonatal sepsis: the past, present and future

“…Cortes et al evaluated diagnostic accuracy of IL-6 and CRP in EOS and LOS 104 . Authors concluded that IL-6 (>17.75 pg/mL) showed greater accuracy in EOS while CRP (>0.53 mg/dL) was more accurate in LOS.…”