The Journal of Maternal-Fetal & Neonatal Medicine

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Can Melatonin Be Used as a Marker for Neonatal Sepsis? Abdel-Rahman El-Mashad, Heba Elmahdy, Mohamed El-Dib, Manal Elbatch & Hany Aly To cite this article: Abdel-Rahman El-Mashad, Heba Elmahdy, Mohamed El-Dib, Manal Elbatch & Hany Aly (2015): Can Melatonin Be Used as a Marker for Neonatal Sepsis?, The Journal of Maternal-Fetal & Neonatal Medicine, DOI: 10.3109/14767058.2015.1107898 To link to this article: http://dx.doi.org/10.3109/14767058.2015.1107898

Accepted author version posted online: 16 Oct 2015.

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Just Accepted by The Journal of Maternal-Fetal & Neonatal Medicine Can Melatonin Be Used as a Marker for Neonatal Sepsis? Abdel-Rahman El-Mashad, Heba Elmahdy, Mohamed El-Dib, Manal Elbatch and Hany Aly doi: 10.3109/14767058.2015.1107898 Abstract Background: Melatonin, an indolamine endogenously produced by pineal body, has important role as an anti-oxidant, anti-inflammatory and antiapoptotic. Whether melatonin concentration changes in neonatal sepsis and whether it can be used as a marker of sepsis is unknown.

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Objective: The objective of this study is to evaluate melatonin concentration in the serum as a marker for neonatal sepsis and compare it to standard markers. Study Design: We prospectively studied 40 neonates; 20 diagnosed with late neonatal sepsis and 20 healthy neonates as a control group. Markers of sepsis and melatonin concentration were compared between both groups. Results: The sepsis groups had significantly increased immature to total neutrophils ratio (I/T ratio), and high sensitivity C-reactive protein (HsCRP), and decreased platelet count. Melatonin concentration was increased in sepsis group when compared to control group (27.2 ± 3.3 vs. 11.4 ± 3.2 pg/ml, p=0.001), and positively correlated with HsCRP (r=0.952, P=0.001) and I/T ratio (r= 0.326, p= 0.015). Combining melatonin to HsCRP increased sensitivity and specificity to detect neonatal sepsis to 97.3% and 93.3% respectively. Conclusions: Endogenous melatonin concentration is increased in late neonatal sepsis and can potentially be used as a marker for sepsis especially when combined with CRP.

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Title: Can Melatonin Be Used as a Marker for Neonatal Sepsis? Running title: Melatonin and neonatal sepsis Authors and institutions: Abdel-Rahman El-Mashad1, Heba Elmahdy1, Mohamed El-Dib2, Manal Elbatch3 and Hany Aly2

2

Department of Newborn Services, George Washington University and Children’s National

Health System, Washington, DC

Hany MD,

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Corresponding Author:

900 23rd Street, NW, Suite G-2092, Room G-132 Washington, DC 20037,

E-mail: [email protected], Fax: 202-715-5354, Telephone: 202-715-5236

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Conflict of interest:

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Authors declare no competing financial interests in relation to this work

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Departments of 1 Neonatology, and 2 Biochemistry, Tanta University, Tanta, Egypt

Abstract Background: Melatonin, an indolamine endogenously produced by pineal body, has important role as an anti-oxidant, anti-inflammatory and anti-apoptotic. Whether melatonin concentration changes in neonatal sepsis and whether it can be used as a marker of sepsis is unknown. Objective: The objective of this study is to evaluate melatonin concentration in the serum as

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a marker for neonatal sepsis and compare it to standard markers. Study Design: We prospectively studied 40 neonates; 20 diagnosed with late neonatal sepsis

were compared between both groups.

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Results: The sepsis groups had significantly increased immature to total neutrophils ratio (I/T ratio), and high sensitivity C-reactive protein (HsCRP), and decreased platelet count. Melatonin concentration was increased in sepsis group when compared to control group (27.2 ± 3.3 vs. 11.4 ± 3.2 pg/ml, p=0.001), and positively correlated with HsCRP (r=0.952, P=0.001) and I/T ratio (r= 0.326, p= 0.015). Combining melatonin to HsCRP increased

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sensitivity and specificity to detect neonatal sepsis to 97.3% and 93.3% respectively.

Conclusions: Endogenous melatonin concentration is increased in late neonatal sepsis and

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can potentially be used as a marker for sepsis especially when combined with CRP. Keywords: late onset sepsis – marker – infants – anti-oxidant

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and 20 healthy neonates as a control group. Markers of sepsis and melatonin concentration

Introduction Neonatal sepsis is a serious medical condition contributing to 15% of neonatal deaths worldwide.1 Neonatal Sepsis is characterized by systemic signs of infection frequently associated with bacteremia. Late onset sepsis is classically defined as sepsis with an onset > 7 days of life but more recently defined as onset > 3 days of life. 2 In addition to short term morbidities and mortality, it is associated with neurodevelopmental impairment and cerebral

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palsy. 3 Early identification of sepsis is needed to provide proper and timely treatment to improve

outcome. On the other hand, empirical treatment of babies is associated with emergence of

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development of asthma, obesity and other immune related illnesses. 5,6

Microbiological cultures requires days to grow, and relying on clinical findings can be misleading. Many of the signs and symptoms of sepsis are non-specific and can be attributed to a non- infectious process. 7,8 Neonatal sepsis induces significant inflammatory process, and oxidative stress. 9,10 This reflects on conventional laboratory tests, for example complete blood count (CBC) including white cell count, immature/ total neutrophil ratio and platelet count in addition to C-reactive protein (CRP). However, changes in CBC and CRP occur over

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time after onset of sepsis and have low specificity and positive predictive values.11,12 Melatonin is an indolamine endogenously produced by pineal body. It has many

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physiological functions in circadian rhythm, sleep, neuroendocrine, and cerebrovascular systems. 13-15 Melatonin also has important role as an anti-oxidant, anti-inflammatory and anti-apoptotic agent.16 When studied as a therapeutic agent in sepsis, it was associated with decreased inflammatory markers and improved outcome.17,18 The status of melatonin

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resistant organisms. 4 In addition, early exposure to antibiotics has been associated with later

concentration in the serum of infants with and without sepsis is not known. Furthermore, we are not aware of any study that utilized endogenous melatonin as marker for neonatal sepsis. In this prospective study, we aim to evaluate melatonin concentration in the serum as a marker for neonatal sepsis and compare it to standard markers such as CBC and CRP.

Patients and Methods Patients We prospectively studied 40 neonates; 20 diagnosed with late neonatal sepsis by clinical and laboratory investigations and 20 healthy neonates as a control group. All patients were admitted or evaluated at follow up in the Tanta University Hospital during the period from May 2012 to April 2013. Patients were included in the sepsis group if (1) born at term (≥ 37

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weeks GA), (2) more than 3 days of life, and (3) fulfilled clinical signs of sepsis (See below). Infants were excluded if they were (1) premature ( 72 hours of life were evaluated by blood culture before starting antibiotics. Both sepsis group and control group were evaluated by the following labs: a) complete blood count with differential count: Venous blood was collected on EDTA solution and differential count was done on Leishman stained peripheral blood

smear. The evaluation was done using Coulter T660 Cell Counter (Coulter, Miami, FL, USA). Immature/ Total Neutrophil ratio (I/T ratio) was determined by dividing number of bands on number of total neutrophils; b) high sensitivity C- Reactive Protein (HsCRP); 19 c) serum melatonin: Samples were analyzed for melatonin concentration using an enzyme immunoassay method (Melatonin ELISA, IBL, Germany) based on the competition principle and microtiter plate separation. The lowest detectable concentration that could be distinguished from the zero standards was 3.0 pg/mL (defined as mean of the odds of the zero

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calibration minus two SDs) as read from the standard curve. The extraction procedure yielded approximately 90% to 100% recovery of added melatonin in samples. Intra-assay and interassay variation coefficients were less than 10%.

Data were analyzed using SPSS (Statistical Package for the Social Science, Chicago, IL,

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USA) version 18. Data were summarized using mean, standard deviation (SD) for continuous variables and percent for categorical variables. Comparisons between groups were done using t-test for continuous variables and chi square/Fisher’s exact test for categorical variables. Correlation between HsCRP and melatonin was measured using Spearman's rank correlation

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coefficient. Differences were considered significant when P values were < 0.05.

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Statistical Analyses

Results A total of 40 patients were enrolled, 20 in the sepsis group and 20 controls. There was no difference in the demographic characteristics between both study groups.(Table1) Clinical presentations in the sepsis group are demonstrated in Table 2. Seventeen out of twenty blood cultures were positive. A list of microorganisms revealed are presented in Table 2. On laboratory evaluation, the sepsis groups had significantly less Hb concentration and platelet count while had significantly increased I/T ratio, and HsCRP concentrations when

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compared to the control group.(Table 3) Melatonin concentration was significantly increased in sepsis group when compared to control group ( 27.2 ± 3.3 vs 11.4 ± 3.2, p=0.001). (Figure 1) In the sepsis group, melatonin concentration positively correlated with CRP (r=0.952,

When evaluating the sensitivity and specificity of melatonin concentration as a marker of

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sepsis, it has a sensitivity of 93.5% and specificity 85.6%. (Figure 2) Sensitivity and specificity were increased by combining melatonin concentration with HsCRP to 97.3% and

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93.3% respectively

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P=0.001) and I/T ratio (r= 0.326, p= 0.015); however did not correlate with total WBC count.

Discussion: To our knowledge, this is the first study to evaluate endogenous melatonin concentration in neonates with and without neonatal sepsis. Its concentration was increased in the sepsis group when compared to normal controls. Melatonin is an endogenous antioxidant and anti-inflammatory indolamine, that likely to be secreted in systemic inflammatory process as sepsis. Bacterial infection induces sepsis via the production of endotoxins (bacterial wall lipopolyscharides (LPS). LPS triggers the activation

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of cellar and humoral immune responses. This is associated with significant increase in inflammatory cytokines which are a major determinant of clinical features of sepsis. Also infection is associated with tissue infiltration with phagocytic cells and production of reactive

killing by neutrophils and macrophages. However when ROS and RNS are in excess, are

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associated with microvascular dysfunction and organ failure.20 Numerous studies have documented increased inflammatory cytokines, oxidative radicals and anti-oxidant enzymes in neonatal sepsis.

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Melatonin acts as an anti-oxidant directly by neutralizing ROS and

NOS, and indirectly by stimulating antioxidant enzyme activity e.g. superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase.23,24 metabolites also have anti-inflammatory properties.

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Both melatonin and its

It acts on B cells leading to reduction

in production of proinflammatory cytokines,26 reduces the inflammatory-derived activation

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of phospholipase A2, lipoxygenase, and cyclooxygenases,27 and reduces recruitment of polymorphonuclear leukocytes to inflammatory site.

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Although never used as an

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endogenous marker for neonatal sepsis, exogenous melatonin was studied as a therapeutic agent. In one study, melatonin supplementation was associated with decreased level of lipid peroxidation products and improved clinical outcome. 18 We have further studied our study population for the typical markers used clinically for

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oxygen species (ROS) and reactive nitrogen species (RNS), which are important for bacterial

detection of sepsis, namely CBC and HsCRP. There was significant difference in these markers in patients with and without sepsis. Although the total WBC count did not differ between groups, the I/T ratio was increased in the sepsis group. Also, although the mean platelet count was above the conventional normal range of 150,000, platelet count has been significantly less in the sepsis group. It is well known that the value of total WBCs is limited in neonatal sepsis.29 A recent study showed association between late onset sepsis and high and low white blood cell counts, high absolute neutrophil counts, high I/T ratio and low platelet counts, however all had low sensitivity. 30

HsCRP level was increased in patients with sepsis. CRP is a non-specific acute phase reactant which can increase in a variety of different conditions and is affected by getational age and age. 29. CRP is synthesized within six to eight hours of infection and can increase up to 1000 fold with a long half life (19 hours). That is reflected on the low sensitivity if checked at onset of infection (60%) which gradual incraes in 24 hours (82%) and 48 hours (84%).31 Numerous studies have shown low sensitivity when tested once with significant improvement in its negative predictive value if used serially. 32,33.

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When comparing the predictive value of melatonin with HsCRP, they had comparable predictive values. However combining HsCRP and melatonin was associated with increased sensitivity and specificity.

patients. Limitations of this study include measurement of melatonin concentration only

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once. Further studies are needed to explore the value of melatonin in neonatal sepsis in early

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onset sepsis. Also more studies are needed to test its utility in premature infants.

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The results of this study should be utilized cautiously because of the small number of study

Conclusions Endogenous melatonin concentration is increased in late neonatal sepsis and can be used as a marker especially when combined with CRP. Further studies are needed to correlate melatonin concentration with neonatal outcomes after sepsis. Also, studies are needed to

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follow melatonin concentration/ behavior during the course of treatment.

References 1.

2. 3.

7. 8.

9.

10.

ST

11.

A

6.

12. 13.

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5.

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4.

Oza S, Lawn JE, Hogan DR, Mathers C, Cousens SN. Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000-2013. Bull World Health Organ 2015;93(1):19-28. Bentlin MR, de Souza Rugolo LMS. Late-onset sepsis: Epidemiology, evaluation, and outcome. NeoReviews 2010;11(8):e426-e435. Bakhuizen SE, de Haan TR, Teune MJ, van Wassenaer-Leemhuis AG, van der Heyden JL, van der Ham DP, Mol BW. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications. Acta Paediatr 2014;103(12):1211-8. Le J, Nguyen T, Okamoto M, McKamy S, Lieberman JM. Impact of empiric antibiotic use on development of infections caused by extended-spectrum betalactamase bacteria in a neonatal intensive care unit. Pediatr Infect Dis J 2008;27(4):314-8. Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr 2014;168(11):1063-9. Marra F, Marra CA, Richardson K, Lynd LD, Kozyrskyj A, Patrick DM, Bowie WR, Fitzgerald JM. Antibiotic use in children is associated with increased risk of asthma. Pediatrics 2009;123(3):1003-10. Guerti K, Devos H, Ieven MM, Mahieu LM. Time to positivity of neonatal blood cultures: fast and furious? J Med Microbiol 2011;60(Pt 4):446-53. Piantino JH, Schreiber MD, Alexander K, Hageman J. Culture negative sepsis and systemic inflammatory response syndrome in neonates. NeoReviews 2013;14(6):e294-e305. Machado JR, Soave DF, da Silva MV, de Menezes LB, Etchebehere RM, Monteiro ML, dos Reis MA, Correa RR, Celes MR. Neonatal sepsis and inflammatory mediators. Mediators Inflamm 2014;2014:269681. Cancelier AC, Petronilho F, Reinke A, Constantino L, Machado R, Ritter C, DalPizzol F. Inflammatory and oxidative parameters in cord blood as diagnostic of earlyonset neonatal sepsis: a case-control study. Pediatr Crit Care Med 2009;10(4):467-71. Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a hematologic scoring system. The Journal of Pediatrics 1988;112(5):761-767. Volante E, Moretti S, Pisani F, Bevilacqua G. Early diagnosis of bacterial infection in the neonate. J Matern Fetal Neonatal Med 2004;16 Suppl 2:13-6. Brzezinski A. Melatonin in humans. New England Journal of Medicine 1997;336(3):186-195. Gitto E, Marseglia L, Manti S, D'Angelo G, Barberi I, Salpietro C, Reiter RJ. Protective Role of Melatonin in Neonatal Diseases. Oxid Med Cell Longev 2013;2013:980374. Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR. Melatonin-A pleiotropic, orchestrating regulator molecule. Progress in Neurobiology 2011;93(3):350-384. Alonso-Alconada D, Alvarez A, Arteaga O, Martinez-Ibarguen A, Hilario E. Neuroprotective Effect of Melatonin: A Novel Therapy against Perinatal HypoxiaIschemia. Int J Mol Sci 2013;14(5):9379-95. Srinivasan V, Pandi-Perumal SR, Spence DW, Kato H, Cardinali DP. Melatonin in septic shock: some recent concepts. J Crit Care 2010;25(4):656.e1-6.

14.

15.

16.

17.

21. 22.

24.

25.

26.

27. 28.

ST

29.

30.

31.

JU

Downloaded by [University of Otago] at 23:44 24 October 2015

23.

TE D

20.

CC EP

19.

Gitto E, Karbownik M, Reiter RJ, Xian Tan D, Cuzzocrea S, Chiurazzi P, Cordaro S, Corona G, Trimarchi G, Barberi I. Effects of melatonin treatment in septic newborns. Pediatric Research 2001;50(6):756-760. Ishibashi M, Takemura Y, Ishida H, Watanabe K, Kawai T. C-reactive protein kinetics in newborns: application of a high-sensitivity analytic method in its determination. Clin Chem 2002;48(7):1103-6. Gitto E, Pellegrino S, Gitto P, Barberi I, Reiter RJ. Oxidative stress of the newborn in the pre- and postnatal period and the clinical utility of melatonin. Journal of Pineal Research 2009;46(2):128-139. Batra S, Kumar R, Seema, Kapoor AK, Ray G. Alterations in antioxidant status during neonatal sepsis. Annals of Tropical Paediatrics 2000;20(1):27-33. Seema, Kumar R, Mandal RN, Tandon A, Randhawa VS, Mehta G, Batra S, Ray GN, Kapoor AK. Serum TNF-alpha and free radical scavengers in neonatal septicemia. Indian Journal of Pediatrics 1999;66(4):511-516. Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress: A review. Journal of Biomedical Science 2000;7(6):444-458. Rodriguez C, Mayo JC, Sainz RM, AntolÃ-n I, Herrera F, MartÃ-n V, Reiter RJ. Regulation of antioxidant enzymes: A significant role for melatonin. Journal of Pineal Research 2004;36(1):1-9. Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX. Melatonin and its relation to the immune system and inflammation. Annals of the New York Academy of Sciences 2000;917:376-386. Mohan N, Sadeghi K, Reiter RJ, Meltz ML. The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-κB. Biochemistry and Molecular Biology International 1995;37(6):1063-1070. Radogna F, Diederich M, Ghibelli L. Melatonin: A pleiotropic molecule regulating inflammation. Biochemical Pharmacology 2010;80(12):1844-1852. Mayo JC, Sainz RM, Tan DX, Hardeland R, Leon J, Rodriguez C, Reiter RJ. Antiinflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. Journal of Neuroimmunology 2005;165(1-2):139-149. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal Infectious Diseases. Evaluation of Neonatal Sepsis. Pediatric Clinics of North America 2013;60(2):367389. Hornik CP, Benjamin DK, Becker KC, Benjamin DK, Jr., Li J, Clark RH, CohenWolkowiez M, Smith PB. Use of the complete blood cell count in late-onset neonatal sepsis. Pediatr Infect Dis J 2012;31(8):803-7. Ng PC. Diagnostic markers of infection in neonates. Arch Dis Child Fetal Neonatal Ed 2004;89(3):F229-35. Benitz WE, Han MY, Madan A, Ramachandra P. Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics 1998;102(4):E41. Pourcyrous M, Bada HS, Korones SB, Baselski V, Wong SP. Significance of serial Creactive protein responses in neonatal infection and other disorders. Pediatrics 1993;92(3):431-5.

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32. 33.

Figure legend: Figure 1: Comparison of melatonin concentration (pg/ml) in sepsis group and control

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group.

Figure 2: Receiver Operating Curve (ROC) for melatonin as marker for neonatal

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sepsis.

Table 1: Demographic data of studied groups: Control group

(n=20)

(n=20)

16.1 ±5.3

13.4 ± 3.5

0.241

38.1± 2

38.3±0.6

0.76

3.02±0.23

3.01±0.33

0.927

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8 (40%)

9 (45%)

0.45

Cesarean section a

11(55%)

Post-natal age (days) Gestational age (weeks) Weight (g)

10(50%)

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Data are presented as mean ± SD except a presented as number (percentage) Downloaded by [University of Otago] at 23:44 24 October 2015

P value

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Sepsis group

0.736

Table 2: Clinical presentation and blood culture results of patients in the sepsis group (n=20):

3 (15%) 4 (20%)

6 (30%) 4 (20%) 3 (15%) 2 (10%) 2 (10%) 3 (15%)

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Klebsiella Pseudomonas aeruginosa E coli Staph aureus Acinatobacter No growth

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Blood culture results (Microorganism)

N (%) 13 (65%) 16 (80%) 7 (35%) 5 (25%) 11 (55%) 3 (15%)

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Clinical presentation Lethargy Poor feeding Pallor Jaundice Hypothermia Gastrointestinal problems (vomiting, intolerance, distension) Respiratory distress Hypotonia

Table 3: Laboratory tests in both sepsis and control groups: Control group

(n=20)

(n=20)

Hb (gm/dl)

10.92±1.27

14.11±0.94

0.018

WBCs (c/cmm3)

10.71±5.01

8.50±1.06

0.076

Platelets (c/mm3)

150.1±33.6

258.6±41.6

0.017

I/T Ratio

0.20±0.12

0.12±0.01

0.006

HsCRP (mg/dl)

33.83±15.34

Data are presented as mean ± SD

P value

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Sepsis group

0.17±7.11

0.001

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ratio, HsCRP: high sensitivity C-reactive protein.

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Hb: hemoglobin concentration, WBCs: White Blood Cells, I/T: immature to total neutrophils

Can melatonin be used as a marker for neonatal sepsis?

Melatonin, an indolamine endogenously produced by pineal body, has important role as an anti-oxidant, anti-inflammatory and anti-apoptotic. Whether me...
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