Usefulness of estimation of cord blood lipopolysaccharide binding protein and neutrophilic elastase concentration versus C-reactive protein concentration in the prediction of early-onset neonatal infections
DOI:
https://doi.org/10.12775/JEHS.2025.80.57632Keywords
C-reactive protein, early-onset bacterial infection, lipopolysaccharide-binding protein, eutrophil elastase, newbornAbstract
Introduction. Congenital infection in a newborn is an infection caused by pathogens passed on to the child by the mother intrauterine or perinatally. Sepsis is the most common form of early-onset infection in newborns. The diagnosis in the newborn is difficult due to the absence of characteristic clinical signs as well as specific and infection-specific laboratory deviations.
Objective. The study was conducted to estimate the predictive value of cord blood plasma concentration of lipopolysaccharide-binding protein, and neutrophil elastase in the prediction of early onset sepsis in preterm and full-term neonates. Correlation with C-reactive protein was assessed.
Materials and methods. Patients enrolled in the study (n=153) were divided in 4 groups: B-I- 39 infected preterm; B-II- 24 infected full-term; K-I- 45 non-infected preterm and K-II- 45 full-term neonates without signs of infection. The research material was umbilical cord taken immediately after delivery in the presence of risk factors for infection and without risk factors for obtaining a control group. The concentration of lipopolysaccharide binding protein, activity of neutrophilic elastase and CRP concentration were determined in the collected samples.
Results. The cord blood plasma LBP and neutrophil elastase concentration was higher in infected preterm and term neonates. Cord blood LBP is a highly specific and sensitive biomarker of sepsis immediately after birth. High levels of LBP and neutrophil elastase in cord blood correlate with CRP.
Conclusions. Measuring the concentration of LBP and neutrophil elastase in cord blood plasma may help in the detection of early onset sepsis in newborns with prenatal risk factors.
References
1. Gibbs RS, Duff P. Progres in pathogenesis and management of clinical intraamniotic infection. Am J Obstet Gynecol 1991, 164,1317-1326. DOI: 10.1016/0002-9378(91)90707-x.
2. Volante E, Moretti S, Pisani F, Bevilacqua G. Early diagnosis of bacterial infection in the neonate. J Maternal Fetal Neonatal Med 2004; 16, 13-16.
DOI: 10.1080/14767050410001727116
3. Stoll BJ, Puopolo KM, Hansen NI, Sánchez PJ, Bell EF, Carlo WA, Cotten CM, D'Angio CT, Kazzi SN, Poindexter BB, Van Meurs KP, Hale EC, Collins MV, Das A, Baker CJ, Wyckoff MH, Yoder BA, Watterberg KL, Walsh MC, Devaskar U, Laptook AR, Sokol GM, Schrag SJ, Higgins RD. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies. JAMA Pediatr 2020, 174, e200593. doi: 10.1001/jamapediatrics.2020.0593.
4. Bedford Russel AR, Kumar R. Early onset neonatal sepsis: diagnostic dilemmas and practical meagement. Arch Dis Child Fetal Neonatal 2015, 100, 350-354. DOI: 10.1136/archdischild-2014-306193
5. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definition Conference. Intensive Care Med 2003, 29, 530-538. DOI: 10.1007/s00134-003-1662-x.
6. Chiesa C, Pacifico L, Natale F., Hofer N, Osborn JF, Resch B. Fetal and early neonatal interleukin-6 response. Cytokine 2015, 76, 1-12. DOI: 10.1016/j.cyto.2015.03.015
7. Sakha K, Husseini MB, Seyyedsadri N. The role of the procalcitonin in diagnosis of neonatal sepsis and correlation between procalcitonin and C-reactive protein in these patients. Pak J Bio Sci 2008, 11, 1785-1790. DOI: 10.3923/pjbs.2008.1785.1790
8. Haque KN. Definitions of bloodstream infection in the newborn. Pediatr Crit Care Med 2005, 6, 45-49. DOI: 10.1097/01.PCC.0000161946.73305.0A
9. Meena J, Charles MV, Ali A, Ramakrishnan S, Gosh S, Seetha K. Utility of cord blood culture in early onset neonatal sepsis. Australas Med J 2015, 8, 263-267.
DOI: 10.4066/AMJ.2015.2460
10. Puopolo KM, Benitz WE, Zaoutis TE. Committee on fetus and newborn; Committee on infectious diseases. Management of Neonates Born at ≥35 0/7 Weeks' Gestation With Suspected or Proven Early-Onset Bacterial Sepsis. Pediatrics 2018, 142, e20182894.
DOI: 10.1542/peds.2018-2894
11. Mussap M. New diagnostic tools for neonatal sepsis: the role of a real-time polymerase chain reaction for the early detection and identification of bacterial and fungal species in blood samples. J Chemother 2007, 19, 31–34. DOI: 10.1080/1120009x.2007.11782441
12. Tröger B, Härtel C, Buer J, Dördelmann M, Felderhoff-Müser U, Höhn T, Hepping N, Hillebrand G, Kribs A, Marissen J, Olbertz D, Rath PM, Schmidtke S, Siegel J, Herting E, Göpel W, Steinmann J, Stein A. Clinical Relevance of Pathogens Detected by Multiplex PCR in Blood of Very-Low-Birth Weight Infants with Suspected Sepsis - Multicentre Study of the German Neonatal Network. PLoS One 2016, 11, e0159821.
doi: 10.1371/journal.pone.0159821.
13. Chen K-F, Chaou C-H, Jiang J-Y, Yu H-W, Meng Y-H, Tang W-C, Wu C-C. Diagnostic Accuracy of Lipopolysaccharide-Binding Protein as Biomarker for Sepsis in Adult Patients: A Systematic Review and Meta-Analysis.
PlosONE 2016, 11, e0153188.doi:10.1371/journal.pone.0153188 2016
14. Sugitharini V, Prema A, Berla Thangam E. Inflammatory mediators of systemic inflammation in neonatal sepsis. Inflamm Res 2013, 62, 1025-1034. doi: 10.1007/s00011-013-0661-9.
15. Tita ATN, Andrews WA. Diagnosis and Management of Clinical Chorioamnionitis. Clin Perinatol 2010, 37, 339-354. DOI: 10.1016/j.clp.2010.02.003
16. Töllner U. Early diagnosis of septicemia in the newborn. Clinical studies and sepsis score. Eur J Pediatr 1982, 138, 331-337. DOI: 10.1007/BF00442511
17. Goldstein B, Giroir B, Randolph A.: International Pediatric SepsisConsensus Conference: Definitions for sepsis and organ dysfunctionin pediatrics. Pediatr Crit Care Med 2005, 6, 2-8.
18. Wynn JL. Defining neonatal sepsis. Curr Opin Pediatr 2016, 28, 135-140.
DOI: 10.1097/01.PCC.0000149131.72248.E6
19. Gomella TL, Eyal FG, Bany-Mohammed F. Neonatology. The McGraw-Hill Companies, Inc., Lange Medical Books/McGraw-Hill International, New York, 2020.
20. Murgas Torrazza R, Neu J. The developing intestinal microbiome and its relationship to health and disease in the neonate. J Perinatol 2011, 31, 29-34. DOI: 10.1038/jp.2010.172
21. Chen FC, Sarioglu N, Büscher U, Dudenhausen JW. Lipopolysaccharide binding protein in the early diagnosis of intraamniotic infection of pregnant women with premature rupture of the membranes. J Perinat Med 2009, 37, 135-139. DOI: 10.1515/JPM.2009.004
22. Espinoza J, Romero R, Chaiworapongsa T, Kim JC, Yoshimatsu J, Edwin S, Rathnasabapathy C, Tolosa J, Donnenfeld A, Craparo F, Gomez R, Bujold E. Lipoplysaccharide- binding protein in microbial invasion of the amniotic cavity and human parturition. J Maternal Fetal Neonatal Med 2002, 12, 313-321. DOI: 10.1080/jmf.12.5.313.321
23. Roos T, Martin TR, Ruzinski JT, Leturcq DJ, Hillier S, Patton DL, Eschenbach DA. Lipopolysaccharide binding protein and soluble CD14 receptor protein in amniotic fluid and cord blood in patients at term. Am J Obstet Gynecol 1997, 177, 1230-1237.
DOI: 10.1016/s0002-9378(97)70044-9
24. Berner R, Fürll B, Stelter F, Dröse J, Müller HP, Schütt C. Elevated levels of lipopolysaccharide –binding protein and Soluble CD14 in plasma in neonatal early- onset sepsis. Clin Diagn Lab Immunol 2002, 9 , 440-445. DOI: 10.1128/cdli.9.2.440-445.2002
25. Lequier LL, Nikaidoh H, Leonard SR, Bokovoy JL, White ML, Scannon PJ, Giroir BP. Preoperative and postoperative endotoxemia in children with congenital heart disease. Chest 2000, 117, 1706-1712. DOI: 10.1378/chest.117.6.1706
26. Proulx F, Seldman E, Mariscalco MM, Lee K, Caroll S. Increased circulating levels of lipopolysaccharide binding protein in children with Eschericha coli O157:H7 hemorrhagic colitis and hemolytic uremic syndrome. Clin Diagn Lab Immunol 1999, 6, 773.
DOI: 10.1128/CDLI.6.5.773-773.1999
27. Takeshita S, Tsujimoto H, Kawase H, Kawamura Y, Sekine I. Increased levels of lipopolisaccharide binding protein in plasma in children with Kawasaki disease. Clin Diagn Lab Immunol 2002, 9, 205-206. DOI: 10.1128/cdli.9.1.205-206.2002
28. Behrendt D, Dembinski J, Heep A, Bartmann P. Lipopolysaccharide binding protein in preterm infants. Arch Dis Fetal Neonatal 2004;89:551-4. DOI: 10.1136/adc.2003.030049
29. Pavcnik-Arnol M, Hojker S, Derganc M. Lipopolysaccharide-binding protein, lipopolysaccharide, and soluble CD14 in sepsis of critically ill neonates and children. Intensive Care Med 2007;33:1025-32. DOI: 10.1007/s00134-007-0626-y
30. Tsaka T, Herkner KR. Infectious diseases in the neonate: Diagnosis and monitoring by quantitative plasma polymorphonuclear leucocyte- elastase determination. J Pediatr 1990; 117: 968-70. DOI: 10.1016/s0022-3476(05)80147-7
31. Tegtmeyer FK, Horn C, Richter A, van Wees J. Elastase-alpha-1-proteinase inhibitor complex, granulocyte count, ratio of immature to total granulocyte count and C-reactive protein in neonatal septicemia. Eur J Pediatr 1992;151:53-6. DOI: 10.1007/BF02113257
32. Jensen JG, Madsen P, Rix M, Rosthøj S, Ebbesen F. Capillary plasma neuthrophil elastase alpha-1- proteonase inhibitor complex as infection parameter in neonates. Scand J Clin Lab Invest 1996;56:37- 40. DOI: 10.3109/00365519609088585
33. Kidokoro K, Furuhashi M, Kuno N, Ishikawa K. Amniotic fluid neutrophil elastase and lactate dehydrogenase: association with histologic chorioamnionitis. Acta Obstet. Gynecol Scand 2006;85: 669-74. DOI: 10.1080/01443610600604432
34. Hata T, Kawamura T, Inada K, Fujiwaki R, Ariyuki Y, Hata K, Kitao M. Interleukin-6, interleukin-8, and granulocyte elastase in newborns with fetal distress. Gynecol Obstet Invest 1996;42:174-7. DOI: 10.1159/000291944
35. Speer CP, Ninjo A, Gahr M. Elastase-alpha-1-proteinase inhibitor in early diagnosis of neonatal septicemia. J. Pediatr 1986;108:987-90. DOI: 10.1016/s0022-3476(86)80945-3
36. Bakakos P, Messaritaki A, Mandyla H, Nicolaidou P, Anagnostakis D. Plasma and urine elastase alpha-1-proteinase inhibitor levels in neonatal urinary tract infection. Biol Neonate 2002;81:109-12. DOI: 10.1159/000047194
37. Laskowska-Klita T, Czerwińska B, Maj-Pucek M. Neutrophil elastase level in cord blood and diagnosis of infection in mature and premature neonates. Developmental Period Medicine 2002;6:13-21. PMID: 12177509
38. Henneke P, Osmers I, Bauer K, Lamping N, Versmold HT, Schumann RR. Impaired CD14- dependent and independent response of polymorphonuclear leukocytes in preterm infants. J Perinat Med 2003;31:176-83. DOI: 10.1515/JPM.2003.024
39. Rodwell RL, Taylor KM, Tudehope DI, Gray PH. Capillary plasma elastase α1 proteinase inhibitor in infected and non-infected neonates. Arch Dis Child 1992;67:436-9.
DOI: 10.1136/adc.67.4_spec_no.436
40. Sampériz S, Millet V, Lacroze V, Unal D. Valeur diagnostique du dosage de l'élastase granulocytaire au sang du cordon ombilical chez des nouveau-nés en situation de risque d'infection maternofœtale. Arch Pediatr 1997;4:406-10. DOI:10.1016/s0929-693x(97)86661-4.
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