Keywords
Newborn.
Neonatal sepsis
Interleukin-6
C-reactive protein
Procalcitonin.
Biomarkers.
Neonatal sepsis
Interleukin-6
C-reactive protein
Procalcitonin.
Biomarkers.
How to Cite
Cortés, J. S., Fernández Cruz, L. X., Beltrán Zúñiga, E., Narváez, C. F., & Fonseca-Becerra, C. E. (2019). Neonatal sepsis: physiopathology and biomarkers. Médicas UIS, 32(3), 35–47. https://doi.org/10.18273/revmed.v32n3-2019005
Abstract
Neonatal sepsis is a major cause of morbidity and mortality in newborns worldwide. Its diagnosis remains a challenge due to the nonspecific clinical findings and the lack of efficient diagnostic tools. In the physiopathology of neonatal sepsis, an excessive or suppressed immune response has been described, which can lead to potentially fatal conditions. The prognostic, diagnostic, and follow-up value of several soluble factors altered in neonatal sepsis has been studied. These have been grouped under the term neonatal sepsis biomarkers. Here, aspects of the physiopathology in neonatal sepsis and the characteristics of the most studied biomarkers used for neonatal sepsis diagnosis are described, also, details about other recently studied markers are mentioned. Currently, the use of an early-warning biomarker together with a late-warning biomarker is recommended to get higher diagnostic accuracy. However, a single ideal biomarker for neonatal sepsis has not been found yet. MÉD.UIS.2019;32(3):35-47
References
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22. Pan X, Ji Z, Xue J. Percentage of Peripheral CD19+CD24hiCD38hi Regulatory B Cells in Neonatal Sepsis Patients and Its Functional Implication. Med Sci Monit. 2016 Jul 7;22:2374–2378.
23. Aliefendioglu D, Gürsoy T, Çağlayan O, Aktaş A, Ovalı F. Can Resistin be a New Indicator of Neonatal Sepsis? Pediatr Neonatol. 2014; 55(1):53–7.
24. Ng PC, Ma TP, Lam HS. The use of laboratory biomarkers for surveillance, diagnosis and prediction of clinical outcomes in neonatal sepsis and necrotising enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2015; 100(5):F448–52.
25. Machado JR, Soave DF, da Silva MV, de Menezes LB, Etchebehere RM, Monteiro ML, et al. Neonatal sepsis and inflammatory mediators. Mediators Inflamm. 2014; 2014:1–10.
26. Delanghe JR, Speeckaert MM. Translational research and biomarkers in neonatal sepsis. Clin Chim Acta. 2015; 451(Pt A):46–64.
27. Çelik HT, Portakal O, Yiğit Ş, Hasçelik G, Korkmaz A, Yurdakök M. Efficacy of new leukocyte parameters versus serum C-reactive protein, procalcitonin, and interleukin-6 in the diagnosis of neonatal sepsis. Pediatr Int. 2016; 58(2):119–25.
28. Kara S, Emeksiz Z, Alioğlu B, Dallar Bilge Y. Effects of neonatal sepsis on thrombocyte tests. J Matern Neonatal Med. 2016; 29(9):1406–8.
29. Nguyen DN, Stensballe A, Lai JC, Jiang P, Brunse A, Li Y, et al. Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants. Innate Immun. 2017; 23(6):524–36.
30. Khaertynov KS, Boichuk S V., Khaiboullina SF, Anokhin VA, Andreeva AA, Lombardi VC, et al. Comparative assessment of cytokine pattern in early and late onset of neonatal sepsis. J Immunol Res. 2017; 2017(1):1–8.
31. Dowling DJ, Levy O. Ontogeny of early life immunity. Trends Immunol. 2014;35(7):299–310.
32. Celik IH, Demirel G, Uras N, Oguz ES, Erdeve O, Dilmen U. Función de la concentración sérica de interleucina 6 y proteína C-reactiva para diferenciar la etiología de la septicemia neonatal. Arch Argent Pediatr. 2015;113(6):534–7.
33. Henderson R, Kim S, Lee E. Use of melatonin as adjunctive therapy in neonatal sepsis: A systematic review and metaanalysis. Complement Ther Med. 2018;39(1):131–6.
34. Wang K, Bhandari V, Chepustanova S, Huber G, O′Hara S, O′Hern CS, et al. Which Biomarkers Reveal Neonatal Sepsis?. PLoS One. 2013;8(12): e82700.
35. Pravin-Charles M, Kalaivani R, Venkatesh S, Kali A, Seetha K. Evaluation of procalcitonin as a diagnostic marker in neonatal sepsis. Indian J Pathol Microbiol. 2018;61(1):81.
36. Bell SG. Procalcitonin and Neonatal Sepsis: Is This the Biomarker We Are Looking For? Neonatal Netw. 2017;36(6):380–4.
37. Chiesa C, Pacifico L, Osborn JF, Bonci E, Hofer N, Resch B. Early-Onset Neonatal Sepsis: Still Room for Improvement in Procalcitonin Diagnostic Accuracy Studies. Medicine (Baltimore). 2015;94(30):e1230.
38. Hahn W-H, Song J-H, Kim H, Park S. Is procalcitonin to C-reactive protein ratio useful for the detection of late onset neonatal sepsis? J Matern Neonatal Med. 2018;31(6):822–6.
39. Hu J, DU P, Bei D. [Diagnostic value of interleukin 6 for neonatal sepsis: a Meta analysis]. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17(11):1176–82.
40. Zhao F, Liu G, Zhang J. [Value of IL-6 and IL-8 in the diagnosis of neonatal sepsis]. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17(12):1311–5.
2. Wynn JL, Wong HR. Pathophysiology and Treatment of Septic Shock in Neonates. Clin Perinatol. 2010 Jun;37(2):439–79.
3. Ho J, Zhang L, Liu X, Wong SH, Wang MHT, Lau BWM, et al. Pathological Role and Diagnostic Value of Endogenous Host Defense Peptides in Adult and Neonatal Sepsis: a systematic review. Shock. 2017 Jun;47(6):673–9.
4. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.
5. Sharma D, Farahbakhsh N, Shastri S, Sharma P. Biomarkers for diagnosis of neonatal sepsis: a literature review. J. Matern.-Fetal Neonatal Med. 2018 Jun 18;31(12):1646–59.
6. Badr HS, El-Gendy FM, Helwa MA. Serum stromal-derivedfactor- 1 (CXCL12) and its alpha chemokine receptor (CXCR4) as biomarkers in neonatal sepsis. J. Matern.-Fetal Neonatal Med. 2018 Aug 18;31(16):2209–15.
7. Chauhan N, Tiwari S, Jain U. Potential biomarkers for effective screening of neonatal sepsis infections: an overview. Microb pathog. 2017; 107(Jun):234-242.
8. Jeon JH, Namgung R, Park MS, Park KI, Lee C. Positive maternal c-reactive protein predicts neonatal sepsis. Yonsei Med J. 2014; 55(1):113-7.
9. Cetin O, Aydın ZD, Verit FF, Zebitay AG, Karaman E, Elasan S, et al. Is maternal blood procalcitonin level a reliable predictor for early onset neonatal sepsis in preterm premature rupture of membranes? Gynecol Obstet Invest. 2017; 82(2):163–9.
10. Ayazi P, Mahyar A, Daneshi MM, Jahanihashemi H, Esmailzadehha N, Mosaferirad N. Comparison of serum il-1beta and c reactive protein levels in early diagnosis and management of neonatal sepsis. Infez Med. 2014; 22(4):296–301.
11. Kan B, Razzaghian HR, Lavoie PM. An immunological perspective on neonatal sepsis. Trends Mol Med. 201; 22(4):290–302.
12. Ceballos CA, Loaiza N, Romero J, Ospina M, Vásquez EM. Caracterización de las gestantes tamizadas para streptococcus agalactiae y su relación con sepsis neonatal temprana, en la clínica del prado de Medellín (Colombia), año 2010. Infectio. 2014; 18(2):66–71.
13. Alvarado-Gamarra G, Alcalá-Marcos KM, Abarca-Alfaro DM, Bao-Castro V. Microbiological and therapeutic characteristics of confirmed neonatal sepsis at a hospital in Lima, Peru. Rev Peru Med Exp Salud Publica. 2016, 33(1): 74–82.
14. Mkony MF, Mizinduko MM, Massawe A, Matee M. Management of neonatal sepsis at Muhimbili National Hospital in Dar es Salaam: diagnostic accuracy of C – reactive protein and newborn scale of sepsis and antimicrobial resistance pattern of etiological bacteria. BMC Pediatr. 2014, 14(1): 293.
15. Freitas FT de M, Romero GAS. Early-onset neonatal sepsis and the implementation of group B streptococcus prophylaxis in a Brazilian maternity hospital: a descriptive study. Brazilian J Infect Dis. 2017, 21(1): 92–7.
16. Gilfillan M, Bhandari V. Biomarkers for the diagnosis of neonatal sepsis and necrotizing enterocolitis: Clinical practice guidelines. Early Hum Dev. 2017, 105:25–33.
17. Bedford Russell AR, Kumar R. Early onset neonatal sepsis: diagnostic dilemmas and practical management. Arch Dis Child - Fetal Neonatal Ed. 2014, 100(4): F1- F5.
18. Hedegaard SS, Wisborg K, Hvas AM. Diagnostic utility of biomarkers for neonatal sepsis – a systematic review. Infect Dis (Auckl). 2015 Mar 4;47(3):117–24.
19. Omran A, Maaroof A, Saleh MH, Abdelwahab A. Salivary C-reactive protein, mean platelet volume and neutrophil lymphocyte ratio as diagnostic markers for neonatal sepsis. J Pediatr (Rio J). 2018 an;94(1):82–7.
20. Vivas MC, Rengifo ES, Mendieta LMG. Caracterización epidemiológica de pacientes con Sepsis Neonatal en un hospital de la ciudad de Cali (Colombia), 2014. Arch Med. 2017 Dec 6;17(2):225–33.
21. Jaramillo-Bustamante JC, Marín-Agudelo A, Fernández-Laverde M, Bareño-Silva J. Epidemiología de la sepsis en pediatría: primer estudio colombiano multicéntrico. CES Medicina.2019;1(23) :85– 92.
22. Pan X, Ji Z, Xue J. Percentage of Peripheral CD19+CD24hiCD38hi Regulatory B Cells in Neonatal Sepsis Patients and Its Functional Implication. Med Sci Monit. 2016 Jul 7;22:2374–2378.
23. Aliefendioglu D, Gürsoy T, Çağlayan O, Aktaş A, Ovalı F. Can Resistin be a New Indicator of Neonatal Sepsis? Pediatr Neonatol. 2014; 55(1):53–7.
24. Ng PC, Ma TP, Lam HS. The use of laboratory biomarkers for surveillance, diagnosis and prediction of clinical outcomes in neonatal sepsis and necrotising enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2015; 100(5):F448–52.
25. Machado JR, Soave DF, da Silva MV, de Menezes LB, Etchebehere RM, Monteiro ML, et al. Neonatal sepsis and inflammatory mediators. Mediators Inflamm. 2014; 2014:1–10.
26. Delanghe JR, Speeckaert MM. Translational research and biomarkers in neonatal sepsis. Clin Chim Acta. 2015; 451(Pt A):46–64.
27. Çelik HT, Portakal O, Yiğit Ş, Hasçelik G, Korkmaz A, Yurdakök M. Efficacy of new leukocyte parameters versus serum C-reactive protein, procalcitonin, and interleukin-6 in the diagnosis of neonatal sepsis. Pediatr Int. 2016; 58(2):119–25.
28. Kara S, Emeksiz Z, Alioğlu B, Dallar Bilge Y. Effects of neonatal sepsis on thrombocyte tests. J Matern Neonatal Med. 2016; 29(9):1406–8.
29. Nguyen DN, Stensballe A, Lai JC, Jiang P, Brunse A, Li Y, et al. Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants. Innate Immun. 2017; 23(6):524–36.
30. Khaertynov KS, Boichuk S V., Khaiboullina SF, Anokhin VA, Andreeva AA, Lombardi VC, et al. Comparative assessment of cytokine pattern in early and late onset of neonatal sepsis. J Immunol Res. 2017; 2017(1):1–8.
31. Dowling DJ, Levy O. Ontogeny of early life immunity. Trends Immunol. 2014;35(7):299–310.
32. Celik IH, Demirel G, Uras N, Oguz ES, Erdeve O, Dilmen U. Función de la concentración sérica de interleucina 6 y proteína C-reactiva para diferenciar la etiología de la septicemia neonatal. Arch Argent Pediatr. 2015;113(6):534–7.
33. Henderson R, Kim S, Lee E. Use of melatonin as adjunctive therapy in neonatal sepsis: A systematic review and metaanalysis. Complement Ther Med. 2018;39(1):131–6.
34. Wang K, Bhandari V, Chepustanova S, Huber G, O′Hara S, O′Hern CS, et al. Which Biomarkers Reveal Neonatal Sepsis?. PLoS One. 2013;8(12): e82700.
35. Pravin-Charles M, Kalaivani R, Venkatesh S, Kali A, Seetha K. Evaluation of procalcitonin as a diagnostic marker in neonatal sepsis. Indian J Pathol Microbiol. 2018;61(1):81.
36. Bell SG. Procalcitonin and Neonatal Sepsis: Is This the Biomarker We Are Looking For? Neonatal Netw. 2017;36(6):380–4.
37. Chiesa C, Pacifico L, Osborn JF, Bonci E, Hofer N, Resch B. Early-Onset Neonatal Sepsis: Still Room for Improvement in Procalcitonin Diagnostic Accuracy Studies. Medicine (Baltimore). 2015;94(30):e1230.
38. Hahn W-H, Song J-H, Kim H, Park S. Is procalcitonin to C-reactive protein ratio useful for the detection of late onset neonatal sepsis? J Matern Neonatal Med. 2018;31(6):822–6.
39. Hu J, DU P, Bei D. [Diagnostic value of interleukin 6 for neonatal sepsis: a Meta analysis]. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17(11):1176–82.
40. Zhao F, Liu G, Zhang J. [Value of IL-6 and IL-8 in the diagnosis of neonatal sepsis]. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17(12):1311–5.
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