Diagnostic Role of Systemic Inflammatory Indices in Infants with Moderate-to-Severe Hypoxic Ischemic Encephalopathy

Abstract

Background When the newborn brain is exposed to hypoxia, as in hypoxic ischemic encephalopathy (HIE), it causes an inflammatory response. A wide variety of inflammatory markers are therefore used in the diagnosis of HIE.

Objective We aimed to determine the diagnostic role of systemic inflammatory indices in infants with moderate-to-severe HIE. We have also investigated the effect of hypothermia treatment over those indices.

Study Design A retrospective cohort study of infants suffering from moderate-to-severe HIE was conducted in a tertiary-level neonatal intensive care unit between September 2019 and March 2021. Systemic inflammatory indices including systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated for infants with HIE and controls at baseline, and after therapeutic hypothermia in those with HIE.

Results A total of 103 infants (53 in the HIE group and 50 in the control group) were included in the study. Median gestational ages (GA) were 39 (37–40) and 38 (37–39) weeks, and median birth weights (BW) were 3,165 (2,890–3,440) and 3,045 (2,850–3,460) g in the HIE and control groups, respectively. GA, BW, mode of delivery, and gender of infants were similar between the groups. Infants in the HIE group had significantly higher NLR (p = 0.001), SII (p = 0.001), PIV (p = 0.001), and SIRI (p = 0.004) values when compared with the control group. Those indices decreased significantly after hypothermia treatment in the HIE group. Areas under curve for NLR, PLR, MLR, SII, SIRI, and PIV to predict HIE were found to be 0.808, 0.597, 0.653, 0.763, 0.686, and 0.663, respectively. Cutoff values having a good ability to predict HIE for SII and NLR were 410 and 1.12. Elevated NLR level above 1.12 was found to be an independent predictor for HIE, as revealed by multivariate analyses. No associations were found between systemic inflammatory indices and amplitude-integrated electroencephalography (aEEG) patterns, presence of seizures, and death.

Conclusion Systemic inflammatory indices may represent reliable and readily available predictors of HIE risk. NLR seems to be an independent factor in diagnosing moderate-to-severe HIE.

Key Points

• Systemic inflammatory incides are readily calculated from the peripheral blood count.

• NLR is an independent and valuable factor in diagnosing moderate-to-severe hypoxic-ischemic encephalopathy.

• Systemic inflammatory incides might be feasible for diagnosing hypoxic-ischemic encephalopathy.

Keywords

asphyxia - hypoxic ischemic encephalopathy - neutrophil-to-lymphocyte ratio - newborn - systemic inflammatory indices

Publikationsverlauf

Eingereicht: 12. August 2021

Angenommen: 04. Oktober 2021

Accepted Manuscript online:
19. Oktober 2021

Artikel online veröffentlicht:
02. Dezember 2021

• References

• 1 Cowan F, Rutherford M, Groenendaal F. et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003; 361 (9359): 736-742
• 2 Hagberg H, Mallard C, Ferriero DM. et al. The role of inflammation in perinatal brain injury. Nat Rev Neurol 2015; 11 (04) 192-208
• 3 Mallard C, Tremblay ME, Vexler ZS. Microglia and neonatal brain injury. Neuroscience 2019; 405: 68-76
• 4 Takemiya T, Fumizawa K, Yamagata K, Iwakura Y, Kawakami M. Brain interleukin-1 facilitates learning of a water maze spatial memory task in young mice. Front Behav Neurosci 2017; 11: 202
• 5 Peng F, Hu D, Lin X. et al. The monocyte to red blood cell count ratio is a strong predictor of postoperative survival in colorectal cancer patients: the Fujian prospective investigation of cancer (FIESTA) study. J Cancer 2017; 8 (06) 967-975
• 6 Fest J, Ruiter R, Ikram MA, Voortman T, van Eijck CHJ, Stricker BH. Reference values for white blood-cell-based inflammatory markers in the Rotterdam study: a population-based prospective cohort study. Sci Rep 2018; 8 (01) 10566
• 7 Akisu M, Kumral A, Canpolat FE. Turkish Neonatal Society Guideline on neonatal encephalopathy. Turk Pediatri Ars 2018; 53 (1, suppl 1): S32-S44
• 8 Zahorec R. Ratio of neutrophil to lymphocyte counts–rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001; 102 (01) 5-14
• 9 Templeton AJ, Ace O, McNamara MG. et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 2014; 23 (07) 1204-1212
• 10 Cananzi FCM, Minerva EM, Samà L. et al. Preoperative monocyte-to-lymphocyte ratio predicts recurrence in gastrointestinal stromal tumors. J Surg Oncol 2019; 119 (01) 12-20
• 11 Hu B, Yang XR, Xu Y. et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res 2014; 20 (23) 6212-6222
• 12 Xu L, Yu S, Zhuang L. et al. Systemic inflammation response index (SIRI) predicts prognosis in hepatocellular carcinoma patients. Oncotarget 2017; 8 (21) 34954-34960
• 13 Fucà G, Guarini V, Antoniotti C. et al. The pan-immune-inflammation value is a new prognostic biomarker in metastatic colorectal cancer: results from a pooled-analysis of the Valentino and TRIBE first-line trials. Br J Cancer 2020; 123 (03) 403-409
• 14 Alsulaimani AA, Abuelsaad AS, Mohamed NM. Inflammatory cytokines in neonatal hypoxic ischemic encephalopathy and their correlation with brain marker S100 protein: a case control study in Saudi Arabia. J Clin Cell Immunol 2015; 6: 1-8
• 15 Yilmaz G, Arumugam TV, Stokes KY, Granger DN. Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation 2006; 113 (17) 2105-2112
• 16 Djordjevic D, Rondovic G, Surbatovic M. et al. Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume-to-platelet count ratio as biomarkers in critically ill and injured patients: which ratio to choose to predict outcome and nature of bacteremia?. Mediators Inflamm 2018; 2018: 3758068
• 17 Zhao C, Wei Y, Chen D, Jin J, Chen H. Prognostic value of an inflammatory biomarker-based clinical algorithm in septic patients in the emergency department: an observational study. Int Immunopharmacol 2020; 80: 106145
• 18 Çakir E, Özkoçak Turan I. Which hemogram-derived indices might be useful in predicting the clinical outcomes of sepsis patients in the intensive care unit?. Cukurova Med J 2021; 46 (02) 532-539
• 19 Wang L, Song Q, Wang C. et al. Neutrophil to lymphocyte ratio predicts poor outcomes after acute ischemic stroke: a cohort study and systematic review. J Neurol Sci 2019; 406: 116445
• 20 Huang G, Chen H, Wang Q. et al. High platelet-to-lymphocyte ratio are associated with post-stroke depression. J Affect Disord 2019; 246: 105-111
• 21 Pin TW, Eldridge B, Galea MP. A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy. Eur J Paediatr Neurol 2009; 13 (03) 224-234
• 22 Fest J, Ruiter R, Mulder M. et al. The systemic immune-inflammation index is associated with an increased risk of incident cancer-a population-based cohort study. Int J Cancer 2020; 146 (03) 692-698
• 23 Yang YL, Wu CH, Hsu PF. et al. Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease. Eur J Clin Invest 2020; 50 (05) e13230
• 24 Asmussen A, Busch HJ, Helbing T. et al. Monocyte subset distribution and surface expression of HLA-DR and CD14 in patients after cardiopulmonary resuscitation. Sci Rep 2021; 11 (01) 12403