Diagnostic utility of the systemic immune-inflammatory index in preterm neonates with late-onset sepsis

Abstract

Objective: To assess if systemic immune-inflammatory index (SII) has a diagnostic role for late-onset sepsis (LOS) in premature neonates. Patients and Methods: A single-center retrospective observational study including preterm infants with culture-proven LOS and controls was conducted between January 2017 and December 2022. SII was derived using complete blood count values acquired at the beginning of and three to five days before LOS. SII was compared between the LOS group and controls. Results: A total of 144 infants were included in the study. The SII values of the LOS group were found to be significantly increased in comparison to the control group [376.74 (11.11 – 15170) vs. 235.24 (46.83 – 1214.38) (median, min-max), P =0.018]. The SII values significantly increased when pre-sepsis and LOS values were compared [200.6 (0 – 1295.78) vs. 328.28 (0 – 14678, P<0.001]. As determined using the receiver operating characteristic analysis, the area under the curve for SII was 0.621 (44.4% sensitivity, 83.3% specificity, 72.7% positive predictive value, and 60% negative predictive value) for predicting LOS. Conclusion: Although, further research is required, SII may be used with other biomarkers to identify LOS in preterm infants and may constitute a readily accessible additional diagnostic parameter.

Keywords

• Late-onset sepsis
• Systemic immune-inflammatory index
• Neonate
• Biomarker

References

1. Sands K, Spiller OB, Thomson K, Portal EAR, Iregbu KC, Walsh TR. Early-onset neonatal sepsis in low – and middle-income countries: Current Challenges and Future Opportunities. Infect Drug Resist 2022 ;15:933-46. doi: 10.2147/IDR.S294156.
2. Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet 2017;390 :1770-80. doi: 10.1016/S0140-6736(17)31002-4.
3. Shane AL, Stoll BJ. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis. Am J Perinatol 2013;30:131-41. doi:10.1055/s-0032.133.3413.
4. Ran NC, van den Hoogen A, Hemels MAC. Gram-negative Late-onset Sepsis in Extremely Low Birth Weight Infants Is Emerging in The Netherlands Despite Quality Improvement Programs and Antibiotic Stewardship!Pediatr Infect Dis J 2019;38:952-7.
5. Cantey JB, Lee JH. Biomarkers for the diagnosis of neonatal sepsis. Clin Perinatol 2021;48:215-27. doi: 10.1016/j. clp.2021.03.012.
6. Panda SK, Nayak MK, Rath S, Das P. The utility of the neutrophil-lymphocyte ratio as an early diagnostic marker in neonatal sepsis. Cureus 2021;13:e12891.doi: 10.7759/ cureus.12891.
7. Kurul Ş, Simons SHP, Ramakers RH, et al. Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates. Crit Care 2021;25:12. doi: 10.1186/s13054.020.03423-2.
8. Goldberg O, Amitai N, Chodick G, et al. Can we improve early identification of neonatal late-onset sepsis? A validated prediction model. J Perinatol 2020; 40:1315-22.

9. Zhang S, Luan X, Zhang W, Jin Z. Platelet-to-lymphocyte and neutrophil-to-lymphocyte ratio as predictive biomarkers for early-onset neonatal sepsis. J Coll Physicians Surg Pak 2021;30:821-4. doi: 10.29271/jcpsp.2021.07.821.
10. Aydogan S, Dilli D, Soysal C, et al. Role of systemic immuneinflammatory index in early diagnosis of sepsis in newborns with CHD. Cardiol Young 2022;32:1826-32. doi: 10.1017/ S104.795.1122001202.
11. Inder TE Perlman JM, Volpe JJ. Preterm intraventricular hemorrhage/posthemorrhagic hydrocephalus. In: Volpe JJ, Ed. Volpe’s Neurology of the Newborn 6th edn. Philadelphia: Elsevier, 2018:637-98.
12. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163:1723-9. doi: 10.1164/ ajrccm.163.7.2011060.
13. International Committee for the Classification of Retinopathy of Prematurity, The international classification of retinopathy of prematurity revisited. Arch Ophthalmol 2005;123:991-9. doi: 10.1001/archopht.123.7.991.
14. Pergialiotis V, Konstantopoulos P, Karampetsou N, et al. Calprotectin levels in necrotizing enterocolitis: a systematic review of the literature. Inflamm Res 2016; 65:847-52. doi: 10.1007/s00011.016.0963-9.
15. Bakhuizen SE, de Haan TR, Teune MJ, et al. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications. Acta Paediatr 2014;103:1211-8. doi: 10.1111/apa.12764.
16. Manandhar SR, Basnet R. Micro-erythrocyte sedimentation rate in neonatal sepsis of a tertiary hospital: A descriptive cross-sectional study. J Nepal Med Assoc 2020;58:377-82. doi: 10.31729/jnma.4984.
17. Eichberger J, Resch E, Resch B. Diagnosis of neonatal sepsis: The role of inflammatory markers. Front Pediatr 2022;10:840288. doi: 10.3389/fped.2022.840288.
18. Carbone F, Montecucco F, Sahebkar A. Current and emerging treatments for neonatal sepsis. Expert Opin Pharmacother 2020;21:549-56. doi: 10.1080/14656.566.2020.1721464.
19. Manouni El Hassani S, Berkhout DJC, Niemarkt HJ, et al. Risk factors for late-onset sepsis in preterm infants: A multicenter case-control study. Neonatology 2019;116:42-51. doi: 10.1159/000497781.
20. Glaser MA, Hughes LM, Jnah A, Newberry D. Neonatal sepsis: A review of pathophysiology and current management strategies. Adv Neonatal Care 2021;21:49-60. doi: 10.1097/ ANC.000.000.0000000769.
21. Wynn JL. Defining neonatal sepsis. Curr Opin Pediatr 2016;28:135-40. doi: 10.1097/MOP.000.000.0000000315.
22. Labenne M, Lizard G, Ferdynus C, et al. A clinic-biological score for diagnosing early-onset neonatal infection in critically ill preterm infants. Pediatr Crit Care Med 2011;12:203-9. doi: 10.1097/PCC.0b013e3181e2a53b.
23. Liu Y, Zhao L, Wu Z. Accuracy of C-Reactive Protein Test for neonatal septicemia: A diagnostic meta-analysis. Med Sci Monit 2019; 25:4076-81. doi: 10.12659/MSM.916968.
24. Vouloumanou EK, Plessa E, Karageorgopoulos DE, Mantadakis E, Falagas ME. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis. Intensive Care Med 2011;37:747-62.doi: 10.1007/s00134.011.2174-8.
25. Reinhart K, Meisner M, Brunkhorst FM. Markers for sepsis diagnosis: what is useful? Crit Care Clin 2006;22:503-19, ix-x. doi: 10.1016/j.ccc.2006.03.003.
26. Pontrelli G, De Crescenzo F, Buzzetti R, et al. Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a metaanalysis. BMC Infect Dis 2017; 17:302.
27. Arcagok BC, Karabulut B. Platelet to lymphocyte ratio in neonates: A predictor of early onset neonatal sepsis. Mediterr J Hematol Infect Dis 2019;11:e2019055. doi: 10.4084/ MJHID.2019.055.
28. Russell CD, Parajuli A, Gale HJ, et al. The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: A systematic review and meta-analysis. J Infect 2019;78:339- 48. doi: 10.1016/j.jinf.2019.02.006.
29. Yang YL, Wu CH, Hsu PF, et al. Systemic immuneinflammation index (SII) predicted clinical outcome in patients with coronary artery disease. Eur J Clin Invest 2020;50:e13230. doi: 10.1111/eci.13230.
30. Fest J, Ruiter R, Mulder M, et al. The systemic immuneinflammation index is associated with an increased risk of incident cancer-A population-based cohort study. Int J Cancer 2020 ;146:692-8. doi: 10.1002/ijc.32303.
31. Ceran B, Alyamaç Dizdar E, Beşer E, Karaçağlar NB, Sarı FN. Diagnostic role of systemic inflammatory indices in infants with moderate-to-severe hypoxic ischemic encephalopathy. Am J Perinatol. 2021 Dec 2. doi: 10.1055/a-1673-1616.
32. Kocaaslan R, Dilli D, Çitli R. Diagnostic Value of the Systemic Immune-Inflammation Index in Newborns with Urinary Tract Infection. Am J Perinatol 2022 Oct 1. doi: 10.1055/s- 0042.175.7353.
33. Sun Y, Chen C, Zhang X, et al. Neutrophil-to-lymphocyte ratio is an early predictor of bronchopulmonary dysplasia. Front Pediatr 2019; 7:464. doi: 10.3389/fped.2019.00464.
34. Holzfurtner L, Shahzad T, Dong Y, et al. When inflammation meets lung development-an update on the pathogenesis of bronchopulmonary dysplasia. Mol Cell Pediatr 2022;9:7. doi: 10.1186/s40348.022.00137-z.