Am J Perinatol
DOI: 10.1055/s-0042-1748165
Original Article

Assessment of Serum Interleukin-27 and Mean Platelet Volume in Late-Onset Neonatal Sepsis

1   Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
,
Dina M. T. Koptan
2   Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
,
Mohamed Kamal
3   Neonatology Division, Benha Children Hospital, Benha, Egypt
,
Marwa Abd Elhady
1   Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
› Author Affiliations
Funding None.

Abstract

Objectives Late-onset sepsis (LOS) is a substantial contributor to morbidity and mortality among neonates. The use of nonculture-based tools for early diagnosis is an area of active investigation. Therefore, we aimed to evaluate the diagnostic value of serum interleukin-27 (IL-27) and mean platelet volume (MPV) in full-term neonates with LOS.

Study Design In this single-center, cross-sectional study, 90 full-term newborns were assigned to two equal-matched groups as follows: (1) culture-proven sepsis and (2) control groups. Clinical data and laboratory findings as complete blood pictures, including MPV, highly sensitive C-reactive protein, and blood culture results, were recorded. Moreover, IL-27 levels were measured using enzyme-linked immunosorbent assay.

Results IL-27 levels (median = 4,364 pg/mL) and MPV (mean = 12.02 ± 1.54 FL) were significantly higher in the culture-proven sepsis group than in the control group (p < 0.001). For IL-27, the optimum cut-off value for the diagnosis of LOS was 283.8 pg/mL with sensitivity and specificity of 97.8 and 100%, respectively. For MPV, the optimum cut-off value was 11.6 FL, with diagnostic sensitivity and specificity of 77.8 and 97.8%, respectively.

Conclusion IL-27 and MPV are promising markers for the diagnosis of LOS in full-term neonates. The diagnostic performance of IL-27 was superior to MPV.

Key Points

  • Late-onset neonatal sepsis diagnosis is time consuming.

  • Nonculture-based rapid diagnostic tests are much needed.

  • IL-27 is superior in LOS diagnosis to MPV.



Publication History

Received: 11 December 2021

Accepted: 17 March 2022

Article published online:
17 May 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Nighat A, Nasrul H. Disease burden of NICU at a tertiary care hospital, Karachi, Pakistan. J Dow Univ Health Sci 2012; 6: 32-35
  • 2 Stoll BJ. Infections of the neonatal infant. In: Berhman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 17th ed. Philadelphia, PA:: WB Saunders Company;; 2004: 623-639
  • 3 Ibe BC. Neonatal infections. In: Azubuike JC, Nkanginieme KEO, eds. Paediatrics and Child Health in a Tropical Region. 2nd ed. Owerri, Nigeria:: African Educational services;; 2007: 197-203
  • 4 Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am 2013; 60 (02) 367-389
  • 5 Beutz M, Sherman G, Mayfield J, Fraser VJ, Kollef MH. Clinical utility of blood cultures drawn from central vein catheters and peripheral venipuncture in critically ill medical patients. Chest 2003; 123 (03) 854-861
  • 6 Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet 2017; 390 (10104): 1770-1780
  • 7 Deleon C, Shattuck K, Jain SK. Biomarkers of neonatal sepsis. Neoreviews 2015; 16: e297-e308
  • 8 Sharma D, Farahbakhsh N, Shastri S, Sharma P. Biomarkers for diagnosis of neonatal sepsis: a literature review. J Matern Fetal Neonatal Med 2018; 31 (12) 1646-1659
  • 9 Zong M, Bruton JD, Grundtman C. et al. TLR4 as receptor for HMGB1 induced muscle dysfunction in myositis. Ann Rheum Dis 2013; 72 (08) 1390-1399
  • 10 Tosson AMS, Glaser K, Weinhage T. et al. Evaluation of the S100 protein A12 as a biomarker of neonatal sepsis. J Matern Fetal Neonatal Med 2020; 33 (16) 2768-2774
  • 11 Şen C, Volpe N, Villain C. et al. Study to evaluate the role of TNFα, IL1β, IL6 in diagnosis and severity assessment of neonatal sepsis among term, appropriate for gestational age newborns. Perinatal J 2021; 29: 179-185
  • 12 Aparicio-Siegmund S, Garbers C. The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions in immunity. Cytokine Growth Factor Rev 2015; 26 (05) 579-586
  • 13 Wong HR, Cvijanovich NZ, Hall M. et al. Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children. Crit Care 2012; 16 (05) R213
  • 14 Wong HR, Liu KD, Kangelaris KN, Lahni P, Calfee CS. Performance of interleukin-27 as a sepsis diagnostic biomarker in critically ill adults. J Crit Care 2014; 29 (05) 718-722
  • 15 He Y, Du WX, Jiang HY. et al. Multiplex cytokine profiling identifies interleukin-27 as a novel biomarker for neonatal early onset sepsis. Shock 2017; 47 (02) 140-147
  • 16 Jacobs L, Berrens Z, Stenson EK. et al. Interleukin-27 as a candidate diagnostic biomarker for bacterial infection in immunocompromised pediatric patients. PLoS One 2018; 13 (11) e0207620
  • 17 Yan J, Mitra A, Hu J. et al. Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells. J Hepatol 2016; 64 (05) 1128-1136
  • 18 Seman BG, Vance JK, Rawson TW. et al. Elevated levels of interleukin-27 in early life compromise protective immunity in a mouse model of gram-negative neonatal sepsis. Infect Immun 2020; 88 (03) e00828-e19
  • 19 Wang J, Wang Z, Zhang M, Lou Z, Deng J, Li Q. Diagnostic value of mean platelet volume for neonatal sepsis: a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99 (32) e21649
  • 20 Ramesh Bhat Y. Platelet indices in neonatal sepsis: a review. World J Clin Infect Dis 2017; 7: 6-10
  • 21 Blencowe H, Vos T, Lee AC. et al. Estimates of neonatal morbidities and disabilities at regional and global levels for 2010: introduction, methods overview, and relevant findings from the Global Burden of Disease study. Pediatr Res 2013; 74 (Suppl. 01) 4-16
  • 22 Hedegaard SS, Wisborg K, Hvas AM. Diagnostic utility of biomarkers for neonatal sepsis–a systematic review. Infect Dis (Lond) 2015; 47 (03) 117-124
  • 23 Mwesigye P, Rizwan F, Alassaf N, Khan R. The role and validity of diagnostic biomarkers in late-onset neonatal sepsis. Cureus 2021; 13 (08) e17065
  • 24 Wojno ED, Hunter CA. New directions in the basic and translational biology of interleukin-27. Trends Immunol 2012; 33 (02) 91-97
  • 25 Zhang J, Qian X, Ning H, Yang J, Xiong H, Liu J. Activation of IL-27 p28 gene transcription by interferon regulatory factor 8 in cooperation with interferon regulatory factor 1. J Biol Chem 2010; 285 (28) 21269-21281
  • 26 Li J, Gran B, Zhang GX, Rostami A, Kamoun M. IL-27 subunits and its receptor (WSX-1) mRNAs are markedly up-regulated in inflammatory cells in the CNS during experimental autoimmune encephalomyelitis. J Neurol Sci 2005; 232 (1-2): 3-9
  • 27 Fahmy EM, Kamel NM, Abdelsadik A. et al. Assessment of interleukin-27 and chemokine RANTES as biomarkers for early onset neonatal sepsis. Egypt J Immunol 2020; 27 (01) 9-18
  • 28 Abo El Magd NM, Abdel Salam SA, Aly YAF, Fahim NA. The role of serum interleukin-27 as a diagnostic biomarker for diagnosis of neonatal sepsis. Egypt J Immunol 2018; 25 (02) 87-95
  • 29 Morita Y, Masters EA, Schwarz EM, Muthukrishnan G. Interleukin-27 and its diverse effects on bacterial infections. Front Immunol 2021; 12: 678515
  • 30 Milas GP, Karageorgiou V, Bellos I. Mean platelet volume and neonatal sepsis: a systematic review and meta-analysis of diagnostic accuracy. J Matern Fetal Neonatal Med 2021; (e-pub ahead of print). DOI: 10.1080/14767058.2021.1879039.
  • 31 Sharma B, Sharma M, Majumder M, Steier W, Sangal A, Kalawar M. Thrombocytopenia in septic shock patients–a prospective observational study of incidence, risk factors and correlation with clinical outcome. Anaesth Intensive Care 2007; 35 (06) 874-880
  • 32 Budak YU, Polat M, Huysal K. The use of platelet indices, plateletcrit, mean platelet volume and platelet distribution width in emergency non-traumatic abdominal surgery: a systematic review. Biochem Med (Zagreb) 2016; 26 (02) 178-193
  • 33 Kokacya MH, Copoglu US, Kivrak Y, Ari M, Sahpolat M, Ulutas KT. Increased mean platelet volume in patients with panic disorder. Neuropsychiatr Dis Treat 2015; 11: 2629-2633
  • 34 Dong Y, Speer CP. Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed 2015; 100 (03) F257-F263
  • 35 Pammi M, Weisman LE. Late-onset sepsis in preterm infants: update on strategies for therapy and prevention. Expert Rev Anti Infect Ther 2015; 13 (04) 487-504
  • 36 Kumar R, Musoke R, Macharia WM, Revathi G. Validation of c-reactive protein in the early diagnosis of neonatal sepsis in a tertiary care hospital in Kenya. East Afr Med J 2010; 87 (06) 255-261
  • 37 Loni R, Sengupta A, Jaganathan G, Singh PK. The evaluation of C-reactive protein as a screening tool for neonatal sepsis. Int J Contemp Pediatr 2016; 3: 1329-1333
  • 38 Tosson AMS, Koptan D, Abdel Aal R, Abd Elhady M. Evaluation of serum and salivary C-reactive protein for diagnosis of late-onset neonatal sepsis: a single center cross-sectional study. J Pediatr (Rio J) 2021; 97 (06) 623-628
  • 39 Aldayel A, Alshammari AH, Hakami MT. et al. C-reactive protein in early diagnosis of neonatal late-onset sepsis: systematic review and meta-analysis. Ann Med Health Sci Res 2020; 10: 1013-1017
  • 40 Brown JVE, Meader N, Cleminson J, McGuire W. C-reactive protein for diagnosing late-onset infection in newborn infants. Cochrane Database Syst Rev 2019; 1: CD012126