الفهرس 
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Abstract
Neonatal sepsis is a major health issue, particularly in the preterm neonatal population, where low birth weight, an immature immune system and other compromising factors make it a primary cause of morbidity, mortality and antibiotics use.
Neonatal sepsis is a systemic condition involving hemodynamic changes and clinical manifestations caused by bacterial, viral, or fungal infection that occurs within the first 28 days of life. It is classified as early onset sepsis (EOS;≤72 hours after birth), and late onset sepsis (LOS;≥72 hours after birth) .
Neonatal septic shock, a severe clinical evolution of sepsis and it is a common cause of death in critically ill newborns. The incidence of septic shock in the NICU is 1.3- 5.6%, while the mortality of septic shock is 36-40% .
The accurate diagnosis of sepsis in the neonatal population is challenging and problematic because of nonspecific clinical presentation and it can rapidly progress into septic shock, multisystem organ failure and death.
Blood culture remains the gold standard for the diagnosis of neonatal sepsis, but roughly 48-72 hours are needed to obtain a reliable response, thus isolation of a pathogen is not always successful (false negative) .
Because neonatal sepsis is a life-threatening condition that continues to be a worldwide cause of neonatal death, there is a need to investigate the potential clinical role of novel biomarkers with high sensitivity and specificity in predicting the onset of systemic inflammation and sepsis. C-Reactive Protein (CRP) is a nonspecific marker for the diagnosis of neonatal sepsis. In fact, a raised CRP is not necessarily diagnostic for Neonatal Sepsis and may occur due to a physiologic rise after birth, infection, autoimmune disease and meconium aspiration. Also, the CRP levels do not increase significantly until almost 14-48 hours after the start of infection.
Presepsin (PSEP), which is a fraction of the soluble CD14 and also named CD14 subtype (sCD14-ST), has received increasing attention over the past 10 years as a possible early marker of sepsis and it seems to ensure a high sensitivity and specificity for the diagnosis of neonatal sepsis.
Presepsin (PSEP) is the cleaved truncated form of the soluble CD 14 (sCD14), which is a multifunctional cell surface glycoprotein expressed on the cell-surface of different immune cell lines and represents a specific high-affinity receptor for complexes of lipopolysaccharides. In addition, it is implicated in the recognition of a wide variety of bacterial products, including peptidoglycans and the major cell wall component of Gram-positive bacteria.
After its stimulation by pathogens, the CD14 complex is released by shedding from the cell surface, yielding sCD14, which is then cleaved by the plasma protease activity, generating sCD14 fragments. The 64-amino acid N-terminal fragments constitute the PSEP.
Therefore, the aim of the study was to assess the accuracy of Presepsin for diagnosis and early detection of sepsis and septic shock among preterm neonates.
This prospective diagnostic cohort study was carried out on 75 preterm neonates with symptoms suspicious of sepsis admitted to the NICU. The enrolled neonates were followed from the time of diagnosis of neonatal sepsis and start of antibiotic therapy, throughout the length of stay in NICU who were classified into 3 groups according to Wynn et al.’s definitions.
• group 1: Infection (suspected infection not meeting the criteria for sepsis).
• group 2: Sepsis (neonatal systemic inflammatory response syndrome, SIRS, plus suspected or proven infection).
• group 3: Septic shock (sepsis plus cardiovascular organ dysfunction).
Summary of our results:
There was an insignificant difference among the studied groups regarding the maternal history (DM, fever, PROM > 18 h, UTI, preeclampsia, antibiotics and previous sibling death/ NICU.
APGAR at 5 min was significantly lower in group 2 (Proven Sepsis) and group 3 (Septic shock) compared to group 1 (Infection) (P=0.036, 0.001 respectively) and was significantly lower in group 3 (Septic shock) compared to group 2 (Proven Sepsis) (P=0.042).
Concerning the clinical presentations, cyanosis, hypotonia, oliguria, mottling and hepatosplenomegaly were significantly different among the studied groups (P<0.05). Other clinical presentations (prolonged resuscitation, fever, poor reflexes, lethargy, respiratory distress, pallor, jaundice, feeding intolerance and apnea) were insignificantly different among the studied groups.
Regarding the vital signs, HR, CRT, SBP and DBP were significantly different among the studied groups (P<0.05). Temperature and RR were insignificantly different among the studied groups.
Regarding the laboratory investigations, TLC, absolute neutrophil count, PLT count, and CRP were significantly different among the studied groups (P<0.001), whereas Hb level was insignificantly different among the studied groups.
Presepsin level was significantly different among the studied groups at all measurements (D1, D3 and D5) (P<0.001).
At D1 and D3, Presepsin level was significantly higher in group 3 (Septic shock) compared to group 1 (Infection) and group 2 (Proven Sepsis) (P<0.05) and was significantly higher in group 2 (Proven Sepsis) compared to group 1 (Infection) (P<0.05). At D5, Presepsin level was significantly higher in group 3 (Septic shock) compared to group 1 (Infection) and group 2 (Proven Sepsis) (P<0.05) and was insignificantly different between group 1 (Infection) and group 2 (Proven Sepsis).
Within group 1 (Infection) and group 2 (Proven Sepsis), Presepsin level was significantly lower at D3 and D5 compared to D1 (P<0.001). whereas in group 3 (Septic shock), Presepsin level was significantly lower at D5 compared to D1 (P=0.007) and was insignificantly different between D1 and D3.
As shown in the previous table, in all neanates included in group 1 (Infection) showed no growth on the blood culture, whereas there blood culture was positive in both group 2 (Proven Sepsis) and group 3 (Septic shock), with no significant difference between both groups regarding the culture results.
Regarding the fate of the studied groups, antibiotic therapy, inotropic drugs, and hydrocortisone were significantly different among the studied groups (P=0.010, <0.001, 0.004 respectively), whereas length of stay in NICU and the outcome were insignificantly different among the studied groups.
there were insignificant correlations between Presepsin at D1and gender, GA at delivery, birth weight and mode of delivery.
There was a significant positive correlation between Presepsin at D1 and CRP level (r=0.264, P=0.022).
There was a significant positive correlation between Presepsin at D5 and CRP level (r=0.495, P<0.001).
CRP is a significant factor in the early diagnosis of infection in group 1 (Infection) with AUC= 0.845, P value <0.001, at cut off ≤5 mg/dl, 92% sensitivity, 72% specificity, 62.2% PPV and 94.7 % NPV.
CRP is an insignificant factor in the early diagnosis of neonatal sepsis in group 2 (Proven Sepsis).
CRP is a significant factor in the early diagnosis of septic shock in group 3 (Septic shock) with AUC= 0.926, P value <0.001, at cut off >6 mg/dl, 96% sensitivity, 80% specificity, 70.6% PPV and 97.6 % NPV.
In group 1 (Infection), Presepsin level at D1 is a significant factor in the early diagnosis of infection with AUC= 0.869, P value <0.001, at cut off ≤1120 ng/L, 80% sensitivity, 70% specificity, 57.1% PPV and 87.5% NPV.
Presepsin level at D3 is a significant factor in the early diagnosis of neonatal sepsis with AUC= 0.838, P value <0.001, at cut off ≤989 ng/L, 80% sensitivity, 68% specificity, 55.6% PPV and 87.2% NPV.
Additionally, Presepsin level at D5 is a significant factor in the early diagnosis of neonatal sepsis with AUC= 0.758, P value <0.001, at cut off ≤685 ng/L, 84% sensitivity, 64% specificity, 53.8% PPV and 88.9% NPV.
In group 2 (Proven Sepsis), Presepsin level only at D5 is a significant factor in the early diagnosis of neonatal sepsis with AUC= 0.549, P value =0.027, at cut off =685 ng/L, 64% sensitivity, 52% specificity, 40% PPV and 74.3% NPV. Presepsin level at D1 and D3 is an insignificant factor in the early diagnosis of neonatal sepsis.
In group 3 (septic shock), Presepsin level at D1 is a significant factor in the early diagnosis of septic shock with AUC= 0.817, P value <0.001, at cut off >1065 ng/L, 96% sensitivity, 70% specificity, 54.5% PPV and 96.8% NPV.
Presepsin level at D3 is a significant factor in the early diagnosis of neonatal sepsis with AUC= 0.840, P value <0.001, at cut off >785 ng/L, 96% sensitivity, 60% specificity, 49% PPV and 96.2% NPV.
Additionally, Presepsin level at D5 is a significant factor in the early diagnosis of neonatal sepsis with AUC= 0.758, P value <0.001, at cut off >677 ng/L, 92% sensitivity, 70% specificity, 60.5% PPV and 94.6% NPV.
On multiple regression analysis, we found that only PLT count, CRP, Presepsin at D1, Presepsin at D3 and Presepsin at D5 were significant predictors of neonatal sepsis.
On multiple regression analysis, we found that only APGAR at 5 min, PLT count, CRP, Presepsin at D1, Presepsin at D