Biomarkers in Diagnosing Late-onset Neonatal Sepsis

Adem POLAT1, Turan TUNÇ1, Buket KILIÇASLAN2 , Hacer ERGİN3, Dilek DİLLİ4, Ramazan ÖZDEMİR5, Emrah CAN6, Sinan USLU7 Turkish Neonatal Sepsis Study Group: Emel OKULU8, Özge AYDEMİR9, Bahri ERMİŞ10, Sara EROL11, Nazlı GÜLTEKİN12, Merih ÇETÌNKAYA13, Nilüfer GÜZOĞLU14, Deniz HANTA15, Beyza ÖZCAN16, Fatma NARTER17, H. Tolga ÇELİK18 Article History: Received: March 11, 2021; Accepted: March 22, 2021; Published: March 31, 2021. Research Article ISSN 2572-4355 Citation Adem POLAT et al. (2021), Biomarkers in Diagnosing Late-onset Neonatal Sepsis. Int J Ped & Neo Heal. 5:3, 23-32 Background Late onset bacterial sepsis of neonates (LOS) is a highly mortal disease, although it is still a diagnostic challenge. Unfortunately a gold standard diagnostic test has yet to be described. In the current study it was aimed to investigate the diagnostic value of sTREM-1, PTX-3 and Pro-ADM in LOS and compare with currently used biomarkers. Methods In this multi-centric prospective study, patients were recruited from different NICUs among Turkey. Neonates, hospitalized with a suspicion of LOS were included. Patients were divided into three groups as; proven sepsis, clinical sepsis and control group regarding clinical and laboratory findings. The primary outcome was to evaluate any difference between groups regarding the diagnostic value of the biomarkers. Results The study consisted of 192 patients; proven sepsis (n=86), clinical sepsis (n=60) and control (n=46) groups. Mean CRP (P<0.001), mean WBC (P=0.015) and mean procalcitonin (PCT) (P=0.004) levels were significantly higher and mean platelet level was significantly lower (P<0.001) in clinical sepsis and proven sepsis groups. No statistical difference was present between groups regarding mean PTX-3 (P = 0.189), Pro-ADM (P = 0.536) and sTREM-1 (P = 0.091) levels. Conclusion Serum PTX-3, Pro-ADM and sTREM-1 levels did not indicate LOS diagnosis. Regarding previous studies Volume 5 Issue 3, March 2021 Published by Biocore Group | www.biocoreopen.org/ijpn/archive.php 23 1Gülhane Military Medical Academy, School of Medicine, Department of Pediatrics, Division of Neonatology, Turkey 2Special Adana Metro Hospital, Division of Neonatology, Turkey 3Pamukkale University School of Medicine, Department of Pediatrics, Division of Neonatology, Turkey 4Dr Sami Ulus Children’s Hospital, Turkey 5Inonu University School of Medicine, Department of Pediatrics, Division of Neonatology, Turkey 6Bagcılar Training and Research Hospital, Division of Neonatology, Turkey 7Sisli Hamidiye Etfal Educational and Research Hospital, Division of Neonatology, Turkey 8Ankara University School of Medicine Department of Pediatrics Division of Neonatology, Turkey 9Osman Gazi University School of Medicine, Department of Pediatrics Division of Neonatology, Turkey 10SakaryaUniversity School of Medicine, Department of Pediatrics Division of Neonatology, Turkey 11Etlik Zubeyde Hanim Maternity and Research Hospital Division of Neonatology, Turkey 12Meram School of Medicine, Department of Pediatrics Division of Neonatology, Turkey 13Kanuni Educational and Research Hospital Division of Neonatology, Turkey 14Kırıkkale School of Medicine, Department of Pediatrics Division of Neonatology, Turkey 15 Adana Maternity and Children’s Hospital, Turkey 16Konya Training and Research Hospital, Turkey 17Dr Lutfi Kırdar Kartal Education and Research Hospital, Turkey 18Hacettepe University Faculty of Medicine Department of Pediatrics Division of Neonatology, Turkey

[1]  J. Montaner,et al.  Inflammatory and stress markers predicting pneumonia, outcome, and etiology in patients with stroke , 2020, Neurology: Neuroimmunology & Neuroinflammation.

[2]  C. Launes,et al.  Diagnostic and prognostic value of procalcitonin and mid-regional pro-adrenomedullin in septic paediatric patients , 2020, European Journal of Pediatrics.

[3]  N. Mostafa,et al.  Pentraxin 3 as a novel diagnostic marker in neonatal sepsis. , 2020, Journal of neonatal-perinatal medicine.

[4]  F. Battal,et al.  Serum Pentraxin 3 Concentration in Neonatal Sepsis , 2019, Journal of Pediatric Infectious Diseases.

[5]  V. Bhandari,et al.  Neonatal sepsis biomarkers: where are we now? , 2019, Research and Reports in Neonatology.

[6]  Amal Ahmed,et al.  Utility of presepsin, soluble triggering receptor expressed on myeloid cells-1, and neutrophil CD64 for early detection of neonatal sepsis , 2019, Infection and drug resistance.

[7]  T. Tunç,et al.  Assessment of novel biomarkers: sTREM-1, pentraxin-3 and pro-adrenomedullin in the early diagnosis of neonatal early onset sepsis. , 2019, Journal of neonatal-perinatal medicine.

[8]  F. Younis,et al.  Clinical study of Presepsin and Pentraxin3 in critically ill children , 2018, Journal of critical care.

[9]  S. Fahmey,et al.  Diagnostic and prognostic value of proadrenomedullin in neonatal sepsis , 2018, Korean Journal of Pediatrics.

[10]  S. Wong,et al.  Pentraxin-3 as a marker of sepsis severity and predictor of mortality outcomes: A systematic review and meta-analysis. , 2018, The Journal of infection.

[11]  S. Abdelhamid,et al.  Time to Positivity and Antibiotic Sensitivity of Neonatal Blood Cultures , 2017, Journal of global infectious diseases.

[12]  R. Farhadi,et al.  Pentraxin 3 in neonates with and without diagnosis of pulmonary hypertension. , 2017, Clinical biochemistry.

[13]  Jong-seo Yoon,et al.  Pentraxin 3 as a clinical marker in children with lower respiratory tract infection , 2015, Pediatric pulmonology.

[14]  S. Kurtoğlu,et al.  Pentraxin 3 concentrations of the mothers with preterm premature rupture of membranes and their neonates, and early neonatal outcome , 2015, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[15]  F. Castorena-Torres,et al.  Can sTREM-1 predict septic shock & death in late-onset neonatal sepsis? A pilot study. , 2015, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[16]  C. Giaquinto,et al.  Current management of late onset neonatal bacterial sepsis in five European countries , 2014, European Journal of Pediatrics.

[17]  N. Andrawes,et al.  Circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as diagnostic and prognostic marker in neonatal sepsis. , 2014, Cytokine.

[18]  J. García-García,et al.  Lack of value of midregional pro-adrenomedullin and C-terminal pro-endothelin-1 for prediction of severe bacterial infections in infants with fever without a source , 2013, European Journal of Pediatrics.

[19]  M. Landini,et al.  How Can the Microbiologist Help in Diagnosing Neonatal Sepsis? , 2012, International journal of pediatrics.

[20]  E. Molloy,et al.  Soluble Triggering Receptor Expressed on Myeloid Cells-1 (Strem-1) in Neonatal Sepsis , 2011, Pediatric Research.

[21]  A. Hagag,et al.  Prognostic value of plasma pro-adrenomedullin and antithrombin levels in neonatal sepsis , 2011, Indian pediatrics.

[22]  A. Breathnach,et al.  Risk factors for late onset gram-negative infections: a case–control study , 2010, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[23]  W. Benitz.  Adjunct laboratory tests in the diagnosis of early-onset neonatal sepsis. , 2010, Clinics in perinatology.

[24]  G. Li Volti,et al.  Pentraxin-3 in late-preterm newborns with hypoxic respiratory failure. , 2010, Frontiers in bioscience.

[25]  A. Mantovani,et al.  PENTRAXIN 3 AND C-REACTIVE PROTEIN IN SEVERE MENINGOCOCCAL DISEASE , 2009, Shock.

[26]  A. Lapillonne,et al.  Outcome and prognostic factors in neonates with septic shock* , 2008, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[27]  Barbara Bottazzi,et al.  Pentraxins in Innate Immunity: From C-Reactive Protein to the Long Pentraxin PTX3 , 2007, Journal of Clinical Immunology.

[28]  J. Andrejaitienė.  [The diagnostic value of procalcitonin in severe sepsis]. , 2006, Medicina.

[29]  C. Roussos,et al.  Soluble triggering receptor expressed on myeloid cells 1 as an anti-inflammatory mediator in sepsis. , 2006, Intensive care medicine.

[30]  S. Zakynthinos,et al.  Does soluble triggering receptor expressed on myeloid cells‐1 play any role in the pathogenesis of septic shock? , 2005, Clinical and experimental immunology.

[31]  A. Randolph,et al.  International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics* , 2005, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[32]  F. Huang,et al.  Neonatal sepsis in the neonatal intensive care unit: characteristics of early versus late onset. , 2004, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[33]  J. Struck,et al.  Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients , 2004, Peptides.

[34]  M. Colonna,et al.  TREM-1 amplifies inflammation and is a crucial mediator of septic shock , 2001, Nature.

[35]  M. Colonna,et al.  Cutting Edge: Inflammatory Responses Can Be Triggered by TREM-1, a Novel Receptor Expressed on Neutrophils and Monocytes1 , 2000, The Journal of Immunology.

[36]  C R Bauer,et al.  Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network. , 1998, The Pediatric infectious disease journal.

[37]  F. Marumo,et al.  Characterization of immunoreactive adrenomedullin in human plasma and urine. , 1995, Life sciences.

[38]  T. Ishimitsu,et al.  Clinical studies on the sites of production and clearance of circulating adrenomedullin in human subjects. , 1994, Hypertension.