In this study, we investigated the diagnostic value of NLR and PLR to detect SI and SBI. Although we found significantly higher NLR values in infants with SI and SBI, our results indicate that CRP level show more accuracy to detect SI and SBI. PLR did not show statistical significance in differentiating SI or SBI from non-SI or non-SBI group.
The need to clinically distinguish SI and SBI from more benign causes of fever in young infants remains clinically challenging. Patient outcomes are determined not only by virulence of invading pathogens, but also by host response. Neonates and infants are the most immunocompromised because of their poorly developed innate and adaptive immunity system responses. [24–26] This has resulted them in increased susceptibility to develop severe infections from various pathogens.[27, 28] Therefore, early recognition and detection of sepsis is of high importance in neonates and infants because it improves the outcome of the patients.
Multiple biomarkers have been proposed but improvement is still needed for clinical management. To date, most biomarkers are discussed in terms of sepsis prognosis and duration of antibiotics. [29–31] Early in the course of sepsis, most biomarkers fail to predict ongoing bacterial infection when fever is the only symptom.[32] Some studies advise to use a combination of biomarkers to improve the sensitivity and specificity.[33] However, these employ biomarkers that are costly and require a turnaround time. We need a biological marker that must be easily accessible, cheap, rapid, sensitive, and specific as much as possible. Nevertheless, WBC and CRP remain the most widely used biomarkers for bacterial infection diagnosis.
Many clinical studies suggested NLR in addition to CRP, WBC and neutrophil count as an important marker in early bacteremia diagnosis and evaluation of sepsis outcomes. [34–37] Also NLR was observed in some studies to be more efficient than regular inflammation biomarkers among adults. [34, 38] A study of adults with suspected bacteremia and sepsis, which grouped the patients according to procalcitonin levels, showed procalcitonin and NLR has the highest correlation value. [34] Thus, NLR was shown to be significant in adult population in early sepsis prediction compared to standard diagnostic biomarkers. [34, 36, 38] However, there were very few neonatal or paediatric studies conducted to evaluate the use of NLR for prediction of sepsis and the optimal cut-off values are still under debate. In the study by Alkan et al, NLR values were much higher in septic newborn babies. Using NLR cut-off value at 1.77, the sensitivity and specificity were 78% and 78%, respectively. [17] In our study using similar NLR cut-off point of 1.77, the sensitivity and specificity for SI was 25.3% and 82.8%, respectively, and sensitivity and specificity for SBI, 26.5% and 81.9%, respectively. This lower performance could be due to the different patient spectrum included in the studies, as the two previous studies were performed in NICU in which the prevalence of neonatal sepsis was higher, compared to infants presented to emergency department. This might affect the SI or SBI diagnosis and its prevalence. We found that NLR with cut-off at 0.97 proposed by Sun Y et al. has better sensitivity and specificity especially for SBI, 62.2% and 56.8% respectively. However, this cut-off point was used to predict bronchopulmonary dysplasia in premature babies < 32 weeks with congenital pneumonia and therefore the result is not generalizable. [39]
For our cohort, we found that CRP 20 or more had the highest positive likelihood for both SI and SBI (5.68 and 7.97 respectively) and positive predictive value (73.44% and 65.62% for SI and SBI respectively). (Tables 2a and 2b). ANC 1.5K or less had the highest sensitivity for SI (95.78%, 95% CI 91.5-98.29%) and SBI (96.94%, 95% CI 91.31–99.36%) and negative predictive value for SI 76.67% (95% CI 58.98–88.25%) and SBI (90%, 95% CI 73.58–96.68%). ANC 10K or more has the highest specificity for SI (96.2%, CI 93.81–97.86%) and SBI (96.54%, CI 94.45–98.01%). While we found a correlation between NLR with SI and SBI, as a blood count index, it did not fare better than using specific neutrophil cut-offs. However, NLR is a simple and easy to calculate biomarker using routine laboratory data without additional technique or cost. Our study provided initial evidence for NLR in the evaluation of young febrile infants less than 90 days old. It is unknown, however, if when combined with other biomarkers, there might be of synergistic value when evaluating serious infection and serious bacterial infection in young febrile infants, especially in resource limited settings.
PLR is a blood ratio that is largely used in chronic diseases and malignancies in adults. [40–42] Arcagok et al. evaluated the role of PLT in early onset neonatal sepsis and identified that PLR levels of suspected and definite early onset sepsis were significantly higher than that of control group, with 91.3% sensitivity & 97.6% specificity using a cut off level of 57.7. [43] In contrast to our study, we did not find any significant association between PLR and serious infection or serious bacterial infection.
The present study had several limitations. First, the study was designed as a retrospective study lacking longitudinal observation. Therefore, we could not measure the biomarkers in the following hours or days after sepsis diagnosis. While the baseline NLR is undoubtedly of prognostic value, increase or decrease in the NLR during the course of illness may also be importance. Second, there is lack of consensus regarding the most appropriate cut-off value for NLR. This was variably reported in the literature and for the NLR to be useful as a screening tool for clinicians, there needs to be consensus on the definitions of “high” versus “low” NLR. Third, though all infants have complete blood count performed, CRP were not performed in all presenting infants. Only 89.5% of the infants included in the study had CRP done. This could have led to a certain selection of children.