Evaluation of Traditional Biomarkers and Novel Inflammatory Indices in the Diagnosis of Late-Onset Neonatal Sepsis: A Case-Control Study

Early diagnosis and detection of LOS are challenging due to its often nonspecific symptoms and the limited diagnostic efficacy of commonly used biomarkers. Therefore, a combined evaluation of clinical and laboratory findings is necessary. While initial assessment often includes nonspecific tests such as complete blood count and inflammatory markers, the most important test is a blood culture of at least 1 mL of blood before antibiotic administration.Although acute phase reactants such as C-reactive protein (CRP), procalcitonin (PCT), and various interleukins are used to support the diagnosis of sepsis in newborns, they are also elevated by other non-infectious inflammatory causes (fetal hypoxia, birth stress, RDS, MAS, IVH, surgery, and pneumothorax). Serum CRP could be a useful biomarker for LOS in newborn infants if it can be demonstrated to have acceptable levels of accuracy. Currently, the role of serum CRP in diagnostic algorithms for late-onset infection is largely varied in the absence of robust evidence to inform the development of guidelines or protocols. Further studies have shown that the immature/total neutrophil ratio and absolute neutrophil values are poor predictors of LOS. Due to age-specific, gestational age-dependent, and neonatal physiological changes in the early postpartum period, there is no consensus on the threshold value of serum PCT levels in bacterial infection.Common laboratory markers of infection, such as white blood cell count (WBC), immature neutrophil/total neutrophil ratio (IT ratio), hematological tests (thrombocytopenia), and acute phase reactants (CRP, PCT), do not have sufficient specificity and sensitivity to detect all infected newborns.Literature analysis has shown that, despite extensive research, the diagnosis and antibiotic treatment of neonatal sepsis cannot currently be determined based on a single biomarker. However, instead of searching for new biomarkers, testing combinations of two or more of the currently available biomarkers seems easier and more productive. The literature has focused primarily on the diagnosis of LOS in preterm neonates. Our current study differs from previous studies in that it evaluates the systemic inflammation aggregate index (SIAI) and systemic inflammation index (SII) values serially, in addition to classical biomarkers. Our aim is to identify a practical combination of commonly used laboratory tests that can evaluate the diagnosis and monitoring of term LOS when suspected.