4,199
Views
121
CrossRef citations to date
0
Altmetric
Review Article

Biomarkers for diagnosis of neonatal sepsis: a literature review

, , &
Pages 1646-1659 | Received 25 Mar 2017, Accepted 19 Apr 2017, Published online: 07 May 2017

References

  • Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am. 2013;60:367–389.
  • Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095–2128.
  • Rajaratnam JK, Marcus JR, Flaxman AD, et al. Neonatal, postneonatal, childhood, and under-5 mortality for 187 countries, 1970-2010: a systematic analysis of progress towards Millennium Development Goal 4. Lancet. 2010;375:1988–2008.
  • Wang H, Liddell CA, Coates MM, et al. Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:957–979.
  • van den Hoogen A, Gerards LJ, Verboon-Maciolek MA, et al. Long-term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of causative agents. Neonatology. 2010;97:22–28.
  • Puopolo KM, Eichenwald EC. No change in the incidence of ampicillin-resistant, neonatal, early-onset sepsis over 18 years. Pediatrics. 2010;125:e1031–e1038.
  • Bailit JL, Gregory KD, Reddy UM, et al. Maternal and neonatal outcomes by labor onset type and gestational age. Am J Obstet Gynecol. 2010;202:245.e1–245.e12.
  • Weston EJ, Pondo T, Lewis MM, et al. The burden of invasive early-onset neonatal sepsis in the United States, 2005-2008. Pediatr Infect Dis J. 2011;30:937–941.
  • Borghesi A, Tzialla C, Decembrino L, et al. New possibilities of prevention of infection in the newborn. J Matern-Fetal Neonatal Med. 2011;24(Suppl 2):28–30.
  • Borghesi A, Stronati M. Strategies for the prevention of hospital-acquired infections in the neonatal intensive care unit. J Hosp Infect. 2008;68:293–300.
  • Brady MT. Health care-associated infections in the neonatal intensive care unit. Am J Infect Control. 2005;33:268–275.
  • Manzoni P, Decembrino L, Gallo E, et al. [Recent advances in prevention of sepsis in the preterm neonate]. Recenti Prog Med. 2010;101:483–489.
  • Kirpal H, Gathwala G, Chaudhary U, et al. Prophylactic fluconazole in very low birth weight infants admitted to neonatal intensive care unit: randomized controlled trial. J Matern-Fetal Neonatal Med. 2016;29:624–628.
  • Cleminson J, Austin N, McGuire W. Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. Cochrane Database Syst Rev. 2015;10:CD003850.
  • Gupta B, Vaswani ND, Sharma D, et al. Evaluation of efficacy of skin cleansing with chlorhexidine in prevention of neonatal nosocomial sepsis: a randomised controlled trial. J Matern-Fetal Neonatal Med. 2016;29:242–247.
  • Sharma D, Gathwala G. Impact of chlorhexidine cleansing of the umbilical cord on cord separation time and neonatal mortality in comparison to dry cord care: a nursery-based randomized controlled trial. J Matern-Fetal Neonatal Med. 2014;27:1262–1265.
  • Gathwala G, Sharma D, Bhakhri B. kiran Effect of topical application of chlorhexidine for umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a randomized controlled trial. J Trop Pediatr. 2013;59:209–213.
  • Sharma DK, Gathwala G, Shastri S. Chlorhexidine- A novel intervention to decrease the nursery stay and antibiotic exposure duration: randomized trial. J Matern-Fetal Neonatal Med. 2016;29:213–217.
  • Darlow BA, Austin NC. Selenium supplementation to prevent short-term morbidity in preterm neonates. Cochrane Database Syst Rev. 2003;CD003312.
  • Kramer MS, Chalmers B, Hodnett ED, et al. Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus. JAMA. 2001;285:413–420.
  • Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Lancet. 2000;355:451–455.
  • Polinski C. The value of the white blood cell count and differential in the prediction of neonatal sepsis. Neonatal Netw. 1996;15:13–23.
  • Bizzarro MJ, Raskind C, Baltimore RS, et al. Seventy-five years of neonatal sepsis at Yale: 1928-2003. Pediatrics. 2005;116:595–602.
  • Shane AL, Stoll BJ. Neonatal sepsis: progress towards improved outcomes. J Infect. 2014;68(Suppl 1):S24–S32.
  • Zea-Vera A, Ochoa TJ. Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr. 2015;61:1–13.
  • Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110:285–291.
  • Wattal C, Oberoi JK. Neonatal sepsis. Indian J Pediatr. 2011;78:473–474.
  • Gerdes JS. Clinicopathologic approach to the diagnosis of neonatal sepsis. Isr J Med Sci. 1994;30:430–441.
  • Gerdes JS. Clinicopathologic approach to the diagnosis of neonatal sepsis. Clin Perinatol. 1991;18:361–381.
  • Gerdes JS. Diagnosis and management of bacterial infections in the neonate. Pediatr Clin North Am. 2004;51:939–959. (viii–ix).
  • Tosson AMS, Speer CP. Microbial pathogens causative of neonatal sepsis in Arabic countries. J Matern Fetal Neonatal Med. 2011;24:990–994.
  • Sharma D, Patel A, Soni P, et al. Empedobacter brevis meningitis in a neonate: a very rare case of neonatal meningitis and literature review. Case Rep Pediatr. 2016;2016:7609602.
  • Sharma D, Sharma P, Soni P, et al. Ralstonia picketti neonatal sepsis: a case report. BMC Res Notes. 2017;10:28.
  • Sharma D, Patel A, Soni P, et al. Leminorella sepsis in very low birth weight neonate as cause of neonatal mortality. J Matern-Fetal Neonatal Med. 2017;30:1057–1059.
  • Sharma D, Dasi T, Murki S, et al. Kluyvera ascorbata sepsis in an extremely low birth weight infant. Indian J Med Microbiol. 2015;33:437–439.
  • Goldstein B, Giroir B, Randolph A. International Consensus Conference on Pediatric Sepsis International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2–8.
  • Kellogg JA, Ferrentino FL, Goodstein MH, et al. Frequency of low level bacteremia in infants from birth to two months of age. Pediatr Infect Dis J. 1997;16:381–385.
  • Hedegaard SS, Wisborg K, Hvas A-M. Diagnostic utility of biomarkers for neonatal sepsis-a systematic review. Infect Dis (Lond). 2015;47:117–124.
  • Hendricks-Munoz K, Xu J, Mally P. Biomarkers for neonatal sepsis: recent developments [Internet]. Res Rep Neonatol. 2014;2014:157–168.
  • Murphy K, Weiner J. Use of leukocyte counts in evaluation of early-onset neonatal sepsis. Pediatr Infect Dis J. 2012;31:16–19.
  • Rozycki HJ, Stahl GE, Baumgart S. Impaired sensitivity of a single early leukocyte count in screening for neonatal sepsis. Pediatr Infect Dis J. 1987;6:440–442.
  • Christensen RD, Rothstein G, Hill HR, et al. Fatal early onset group B streptococcal sepsis with normal leukocyte counts. Pediatr Infect Dis. 1985;4:242–245.
  • Hornik CP, Fort P, Clark RH, et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev. 2012;88(Suppl 2):S69–S74.
  • Schmutz N, Henry E, Jopling J, et al. Expected ranges for blood neutrophil concentrations of neonates: the Manroe and Mouzinho charts revisited. J Perinatol. 2008;28:275–281.
  • Polin RA. Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129:1006–1015.
  • Manroe BL, Weinberg AG, Rosenfeld CR, et al. The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J Pediatr. 1979;95:89–98.
  • Da Silva O, Ohlsson A, Kenyon C. Accuracy of leukocyte indices and C-reactive protein for diagnosis of neonatal sepsis: a critical review. Pediatr Infect Dis J. 1995;14:362–366.
  • Hornik CP, Benjamin DK, Becker KC, et al. Use of the complete blood cell count in early-onset neonatal sepsis. Pediatr Infect Dis J. 2012;31:799–802.
  • Philip AG, Hewitt JR. Early diagnosis of neonatal sepsis. Pediatrics. 1980;65:1036–1041.
  • Ismail AQT, Gandhi A. Using CRP in neonatal practice. J Matern Fetal Neonatal Med. 2015;28:3–6.
  • Clyne B, Olshaker JS. The C-reactive protein. J Emerg Med. 1999;17:1019–1025.
  • Jaye DL, Waites KB. Clinical applications of C-reactive protein in pediatrics. Pediatr Infect Dis J. 1997;16:735–747.
  • Kolb-Bachofen V. A review on the biological properties of C-reactive protein. Immunobiology. 1991;183:133–145.
  • Hofer N, Zacharias E, Müller W, et al. An update on the use of C-reactive protein in early-onset neonatal sepsis: current insights and new tasks. Neonatology. 2012;102:25–36.
  • Pourcyrous M, Bada HS, Korones SB, et al. Significance of serial C-reactive protein responses in neonatal infection and other disorders. Pediatrics. 1993;92:431–435.
  • Franz AR, Steinbach G, Kron M, et al. Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections. Pediatrics. 1999;104:447–453.
  • Kawamura M, Nishida H. The usefulness of serial C-reactive protein measurement in managing neonatal infection. Acta Paediatr. 1995;84:10–13.
  • Benitz WE. Adjunct laboratory tests in the diagnosis of early-onset neonatal sepsis. Clin Perinatol. 2010;37:421–438.
  • Mussap M. Laboratory medicine in neonatal sepsis and inflammation. J Matern Fetal Neonatal Med. 2012;25(Suppl 4):24–26.
  • Wasunna A, Whitelaw A, Gallimore R, et al. C-reactive protein and bacterial infection in preterm infants. Eur J Pediatr. 1990;149:424–427.
  • Edgar JDM, Gabriel V, Gallimore JR, et al. A prospective study of the sensitivity, specificity and diagnostic performance of soluble intercellular adhesion molecule 1, highly sensitive C-reactive protein, soluble E-selectin and serum amyloid A in the diagnosis of neonatal infection. BMC Pediatr. 2010;10:22.
  • Abdollahi A, Shoar S, Nayyeri F, et al. Diagnostic value of simultaneous measurement of procalcitonin, interleukin-6 and hs-CRP in prediction of early-onset neonatal sepsis. Mediterr J Hematol Infect Dis. 2012;4:e2012028.
  • Ganesan P, Shanmugam P, Sattar SBA, et al. Evaluation of IL-6, CRP and hs-CRP as Early Markers of Neonatal Sepsis. J Clin Diagn Res. 2016;10:DC13–DC17.
  • Whicher J, Bienvenu J, Monneret G. Procalcitonin as an acute phase marker. Ann Clin Biochem. 2001;38:483–493.
  • Russwurm S, Wiederhold M, Oberhoffer M, et al. Molecular aspects and natural source of procalcitonin. Clin Chem Lab Med. 1999;37:789–797.
  • Dandona P, Nix D, Wilson MF, et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab. 1994;79:1605–1608.
  • Hahn W-H, Song J-H, Park I-S, et al. Reference intervals of serum procalcitonin are affected by postnatal age in very low birth weight infants during the first 60 days after birth. Neonatology. 2015;108:60–64.
  • Chiesa C, Panero A, Rossi N, et al. Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis. 1998;26:664–672.
  • Chiesa C, Pellegrini G, Panero A, et al. C-reactive protein, interleukin-6, and procalcitonin in the immediate postnatal period: influence of illness severity, risk status, antenatal and perinatal complications, and infection. Clin Chem. 2003;49:60–68.
  • Assumma M, Signore F, Pacifico L, et al. Serum procalcitonin concentrations in term delivering mothers and their healthy offspring: a longitudinal study. Clin Chem. 2000;46:1583–1587.
  • Lee J, Bang YH, Lee EH, et al. The influencing factors on procalcitonin values in newborns with noninfectious conditions during the first week of life. Korean J Pediatr. 2017;60:10–16.
  • Kordek A, Łoniewska B, Podraza W, et al. Usefulness of estimation of blood procalcitonin concentration versus C-reactive protein concentration and white blood cell count for therapeutic monitoring of sepsis in neonates. Postepy Hig Med Dosw. 2014;68:1516–1523.
  • Luzzani A, Polati E, Dorizzi R, et al. Comparison of procalcitonin and C-reactive protein as markers of sepsis. Crit Care Med. 2003;31:1737–1741.
  • Hahn W-H, Song J-H, Kim H, et al. Is procalcitonin to C-reactive protein ratio useful for the detection of late onset neonatal sepsis? J Matern Fetal Neonatal Med. 2017;0:1–5.
  • Wacker C, Prkno A, Brunkhorst FM, et al. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013;13:426–435.
  • Yuan H, Huang J, Lv B, et al. Diagnosis value of the serum amyloid A test in neonatal sepsis: a meta-analysis. Biomed Res Int. 2013;2013:520294.
  • Lannergård A, Friman G, Ewald U, et al. Serum amyloid A (SAA) protein and high-sensitivity C-reactive protein (hsCRP) in healthy newborn infants and healthy young through elderly adults. Acta Paediatr (Oslo Nor 1992). 2005;94:1198–1202.
  • Arnon S, Litmanovitz I, Regev R, et al. The prognostic virtue of inflammatory markers during late-onset sepsis in preterm infants. J Perinat Med. 2004;32:176–180.
  • Arnon S, Litmanovitz I, Regev R, et al. Serum amyloid A protein is a useful inflammatory marker during late-onset sepsis in preterm infants. Biol Neonate. 2005;87:105–110.
  • Arnon S, Litmanovitz I, Regev RH, et al. Serum amyloid A: an early and accurate marker of neonatal early-onset sepsis. J Perinatol. 2007;27:297–302.
  • Cetinkaya M, Ozkan H, Köksal N, et al. Comparison of serum amyloid A concentrations with those of C-reactive protein and procalcitonin in diagnosis and follow-up of neonatal sepsis in premature infants. J Perinatol. 2009;29:225–231.
  • Behrendt D, Dembinski J, Heep A, et al. Lipopolysaccharide binding protein in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2004;89:F551–F554.
  • Delsesto D, Opal SM. Future perspectives on regulating pro-and anti-inflammatory responses in sepsis. Contrib Microbiol. 2011;17:137–156.
  • Pavcnik-Arnol M, Hojker S, Derganc M. Lipopolysaccharide-binding protein in critically ill neonates and children with suspected infection: comparison with procalcitonin, interleukin-6, and C-reactive protein. Intensive Care Med. 2004;30:1454–1460.
  • Turner D, Hammerman C, Rudensky B, et al. Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram. Arch Dis Child Fetal Neonatal Ed. 2006;91:F283–F286.
  • D’Alquen D, Kramer BW, Seidenspinner S, et al. Activation of umbilical cord endothelial cells and fetal inflammatory response in preterm infants with chorioamnionitis and funisitis. Pediatr Res. 2005;57:263–269.
  • Berner R, Fürll B, Stelter F, et al. Elevated levels of lipopolysaccharide-binding protein and soluble CD14 in plasma in neonatal early-onset sepsis. Clin Diagn Lab Immunol. 2002;9:440–445.
  • Kishimoto T. The biology of interleukin-6. Blood. 1989;74:1–10.
  • Hodge G, Hodge S, Han P, et al. Multiple leucocyte activation markers to detect neonatal infection. Clin Exp Immunol. 2004;135:125–129.
  • Hirano T, Yasukawa K, Harada H, et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986;324:73–76.
  • Raynor LL, Saucerman JJ, Akinola MO, et al. Cytokine screening identifies NICU patients with Gram-negative bacteremia. Pediatr Res. 2012;71:261–266.
  • Küster H, Weiss M, Willeitner AE, et al. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet (Lond Engl). 1998;352:1271–1277.
  • Smulian JC, Vintzileos AM, Lai YL, et al. Maternal chorioamnionitis and umbilical vein interleukin-6 levels for identifying early neonatal sepsis. J Matern Fetal Med. 1999;8:88–94.
  • Smulian JC, Bhandari V, Campbell WA, et al. Value of umbilical artery and vein levels of interleukin-6 and soluble intracellular adhesion molecule-1 as predictors of neonatal hematologic indices and suspected early sepsis. J Matern Fetal Neonatal Med. 1997;6:254–259.
  • Mehr S, Doyle LW. Cytokines as markers of bacterial sepsis in newborn infants: a review. Pediatr Infect Dis J. 2000;19:879–887.
  • Cernada M, Badía N, Modesto V, et al. Cord blood interleukin-6 as a predictor of early-onset neonatal sepsis. Acta Paediatr. 2012;101:e203–e207.
  • Ng PC, Lam HS. Diagnostic markers for neonatal sepsis. Curr Opin Pediatr. 2006;18:125–131.
  • Silveira RC, Procianoy RS. Evaluation of interleukin-6, tumour necrosis factor-alpha and interleukin-1beta for early diagnosis of neonatal sepsis. SPAE. 1999;88:647–650.
  • Hou T, Huang D, Zeng R, et al. Accuracy of serum interleukin (IL)-6 in sepsis diagnosis: a systematic review and meta-analysis. Int J Clin Exp Med. 2015;8:15238–15245.
  • Reinsberg J, Dembinski J, Dorn C, et al. Determination of total interleukin-8 in whole blood after cell lysis. Clin Chem. 2000;46:1387–1394.
  • Franz AR, Sieber S, Pohlandt F, M K, G S. Whole blood interleukin 8 and plasma interleukin 8 levels in newborn infants with suspected bacterial infection. Acta Paediatr (Oslo Nor 1992). 2004;93:648–653.
  • Resch B, Gusenleitner W, Müller WD. Procalcitonin and interleukin-6 in the diagnosis of early-onset sepsis of the neonate. Acta Paediatr. 2003;92:243–245.
  • Mishra UK, Jacobs SE, Doyle LW, et al. Newer approaches to the diagnosis of early onset neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2006;91:F208–F212.
  • Boskabadi H, Maamouri G, Afshari JT, et al. Serum interleukin 8 level as a diagnostic marker in late neonatal sepsis. Iran J Pediatr. 2010;20:41–47.
  • Boskabadi H, Maamouri G, Tavakol Afshari J, et al. Evaluation of serum interleukins-6, 8 and 10 levels as diagnostic markers of neonatal infection and possibility of mortality. Iran J Basic Med Sci 2013;16:1232–1237.
  • Kocabaş E, Sarikçioğlu A, Aksaray N, et al. Role of procalcitonin, C-reactive protein, interleukin-6, interleukin-8 and tumor necrosis factor-alpha in the diagnosis of neonatal sepsis. Turk J Pediatr. 2007;49:7–20.
  • Zhou M, Cheng S, Yu J, et al. Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis. PloS One. 2015;10:e0127170.
  • Berner R, Niemeyer CM, Leititis JU, et al. Plasma levels and gene expression of granulocyte colony-stimulating factor, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 in neonatal early onset sepsis. Pediatr Res. 1998;44:469–477.
  • Ng PC, Cheng SH, Chui KM, et al. Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 1997;77:F221–F227.
  • de Bont ES, Martens A, van Raan J, et al. Diagnostic value of plasma levels of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in newborns with sepsis. Acta Paediatr. 1994;83:696–699.
  • Lv B, Huang J, Yuan H, et al. Tumor necrosis factor-α as a diagnostic marker for neonatal sepsis: a meta-analysis. Scientific World J. 2014;2014:471463.
  • Weirich E, Rabin RL, Maldonado Y, et al. Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection. J Pediatr. 1998;132:445–451.
  • Nupponen I, Andersson S, Järvenpää AL, et al. Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis. Pediatrics. 2001;108:E12
  • Adib M, Ostadi V, Navaei F, et al. Evaluation of CD11b expression on peripheral blood neutrophils for early detection of neonatal sepsis. Iran J Allergy Asthma Immunol. 2007;6:93–96.
  • Graversen JH, Madsen M, Moestrup SK. CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. Int J Biochem Cell Biol. 2002;34:309–314.
  • Fabriek BO, Dijkstra CD, van den Berg TK. The macrophage scavenger receptor CD163. Immunobiology. 2005;210:153–160.
  • Prashant A, Vishwanath P, Kulkarni P, et al. Comparative assessment of cytokines and other inflammatory markers for the early diagnosis of neonatal sepsis-a case control study. PLoS One. 2013;8:e68426.
  • Garlanda C, Bottazzi B, Bastone A, et al. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu Rev Immunol. 2005;23:337–366.
  • Mantovani A, Garlanda C, Doni A, et al. Pentraxins in innate immunity: from C-reactive protein to the long pentraxin PTX3. J Clin Immunol. 2008;28:1–13.
  • Sprong T, Peri G, Neeleman C, et al. Pentraxin 3 and C-reactive protein in severe meningococcal disease. Shock. 2009;31:28–32.
  • Fiedler U, Augustin HG. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol. 2006;27:552–558.
  • Fiedler U, Reiss Y, Scharpfenecker M, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med. 2006;12:235–239.
  • Mussap M, Cibecchini F, Noto A, et al. In search of biomarkers for diagnosing and managing neonatal sepsis: the role of angiopoietins. J Matern Fetal Neonatal Med. 2013;26(Suppl 2):24–26.
  • Mankhambo LA, Banda DL, Study Group IPD, Jeffers G, et al. The role of angiogenic factors in predicting clinical outcome in severe bacterial infection in Malawian children. Crit Care (Lond Engl). 2010;14:R91.
  • Ni W, Han Y, Zhao J, et al. Serum soluble urokinase-type plasminogen activator receptor as a biological marker of bacterial infection in adults: a systematic review and meta-analysis. Sci Rep. 2016;6:39481.
  • Huttunen R, Syrjänen J, Vuento R, et al. Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study. J Intern Med. 2011;270:32–40.
  • Siahanidou T, Margeli A, Tsirogianni C, et al. Clinical value of plasma soluble urokinase-type plasminogen activator receptor levels in term neonates with infection or sepsis: a prospective study. Mediators Inflamm. 2014;2014:375702.
  • Okulu E, Arsan S, Akin IM, et al. Serum levels of soluble urokinase plasminogen activator receptor in infants with late-onset sepsis. J Clin Lab Anal. 2015;29:347–352.
  • Wu Y, Wang F, Fan X, et al. Accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients: a systematic review and meta-analysis. Crit Care. 2012;16:R229.
  • Adly AAM, Ismail EA, Andrawes NG, et al. Circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as diagnostic and prognostic marker in neonatal sepsis. Cytokine. 2014;65:184–191.
  • Saldir M, Tunc T, Cekmez F, et al. Endocan and soluble triggering receptor expressed on myeloid cells-1 as novel markers for neonatal sepsis. Pediatr Neonatol. 2015;56:415–421.
  • Pontrelli G, De Crescenzo F, Buzzetti R, et al. Diagnostic value of soluble triggering receptor expressed on myeloid cells in paediatric sepsis: a systematic review. Ital J Pediatr. 2016;42:44.
  • Lim Y-P, Bendelja K, Opal SM, et al. Correlation between mortality and the levels of inter-alpha inhibitors in the plasma of patients with severe sepsis. J Infect Dis. 2003;188:919–926.
  • Fries E, Kaczmarczyk A. Inter-alpha-inhibitor, hyaluronan and inflammation. Acta Biochim Pol. 2003;50:735–742.
  • Baek YW, Brokat S, Padbury JF, et al. Inter-alpha inhibitor proteins in infants and decreased levels in neonatal sepsis. J Pediatr. 2003;143:11–15.
  • Chaaban H, Singh K, Huang J, et al. The role of inter-alpha inhibitor proteins in the diagnosis of neonatal sepsis. J Pediatr. 2009;154:620–622.e1.
  • Degraeuwe PLJ, Nieman FHM. The diagnostic value of inter-alpha inhibitor proteins for neonatal sepsis. J Pediatr. 2010;156:341. (author reply 341).
  • Tunc T, Cekmez F, Cetinkaya M, et al. Diagnostic value of elevated CXCR4 and CXCL12 in neonatal sepsis. J Matern Fetal Neonatal Med. 2015;28:356–361.
  • Mussap M, Noto A, Fravega M, et al. Soluble CD14 subtype presepsin (sCD14-ST) and lipopolysaccharide binding protein (LBP) in neonatal sepsis: new clinical and analytical perspectives for two old biomarkers. J Matern-Fetal Neonatal Med. 2011;24(Suppl 2):12–14.
  • Topcuoglu S, Arslanbuga C, Gursoy T, et al. Role of presepsin in the diagnosis of late-onset neonatal sepsis in preterm infants. J Matern Fetal Neonatal Med. 2016;29:1834–1839.
  • Aydemir O, Ozcan B, Yucel H, et al. Asymmetric dimethylarginine and l-arginine levels in neonatal sepsis and septic shock. J Matern Fetal Neonatal Med. 2015;28:977–982.
  • Mohamed WAW, Saeed MA. Mannose-binding lectin serum levels in neonatal sepsis and septic shock. J Matern Fetal Neonatal Med. 2012;25:411–414.
  • Ozdemir O, Dinleyici EC, Tekin N, et al. Low-mannose-binding lectin levels in susceptibility to neonatal sepsis in preterm neonates with fetal inflammatory response syndrome. J Matern Fetal Neonatal Med. 2010;23:1009–1013.
  • El-Mashad A-R, Elmahdy H, El-Dib M, et al. Can melatonin be used as a marker for neonatal sepsis? J Matern Fetal Neonatal Med. 2016;29:2870–2873.
  • İpek İÖ, Saracoglu M, Bozaykut A. α1-Acid glycoprotein for the early diagnosis of neonatal sepsis. J Matern Fetal Neonatal Med. 2010;23:617–621.
  • Stranieri I, Kanunfre KA, Rodrigues JC, et al. Usefulness of a 16S rDNA real-time PCR to monitor neonatal sepsis and to assist in medical decision to discontinue antibiotics. J Matern Fetal Neonatal Med. 2016;29:2141–2144.
  • Yerlikaya FH, Kurban S, Mehmetoglu I, et al. Serum ischemia-modified albumin levels at diagnosis and during treatment of late-onset neonatal sepsis. J Matern Fetal Neonatal Med. 2014;27:1723–1727.
  • Decembrino L, DeAmici M, Silvestri AD, et al. Plasma lactoferrin levels in newborn preterm infants with sepsis. J Matern Fetal Neonatal Med. 2016;0:1–4.
  • Fanos V, Van den Anker J, Noto A, et al. Metabolomics in neonatology: fact or fiction? Semin Fetal Neonatal Med. 2013;18:3–12.
  • Petrakou E, Mouchtouri A, Levi E, et al. Interleukin-8 and monocyte chemotactic protein-1 mRNA expression in perinatally infected and asphyxiated preterm neonates. Neonatology. 2007;91:107–113.
  • Dessì A, Liori B, Caboni P, et al. Monitoring neonatal fungal infection with metabolomics. J Matern Fetal Neonatal Med. 2014;27(Suppl 2):34–38.
  • Dessì A, Corsello G, Stronati M, et al. New diagnostic possibilities in systemic neonatal infections: metabolomics. Early Hum Dev. 2014;90(Suppl 1):S19–S21.
  • Fanos V, Antonucci R, Barberini L, et al. Clinical application of metabolomics in neonatology. J Matern-Fetal Neonatal Med. 2012;25(Suppl 1):104–109.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.