الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Neonatal sepsis is the main cause of morbidity and mortality in neonate. Neonatal sepsis is a diagnosis made in infants less than 28 days of life and consists of a clinical syndrome that may include systemic signs of infection, circulatory shock, and multisystem organ failure. Neonatal sepsis may be divided into two types: early-onset neonatal sepsis and late-onset neonatal sepsis. EOS is typically described as infection and sepsis occurring within the first 24 hours to first week of life. LOS has been labeled as after the first week of life, up to 28 days. Early onset sepsis can progress rapidly with neurological complications and lead to neonatal death. group B Streptococcus is the most common etiologic agent, while E coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rate of group B streptococcus disease but have been associated with increased rates of Gram negative infections, especially among very low birth weight infants. The incidence of sepsis is higher in preterm 26/1000 born preterm neonates. When neonatal sepsis is diagnosed early, with early treatment that will decrease risk of complication. The identification of neonates at risk for early onset sepsis is frequently based on a constellation of perinatal risk factors that are neither sensitive nor specific. Furthermore, diagnostic tests for neonatal sepsis has poor positive predictive accuracy. As a result, clinicians often treat well appearing infants for extended periods of time even when bacterial culture are negative. Blood culture is the gold standard test for definitive diagnosis of early onset sepsis but this method take 2 to 3 days before the result become available too long for early diagnosis. High risk neonate are often treated empirically selected broad spectrum antibiotics but this may encourage the development of resistant strain. Progranulin (PGRN) is a 593 amino acid that is the precursor for granulin. PGRN is expressed in a variety of cell types including neurons, microglia, astrocytes and endothelial cells functionally implicated in immunity. Progranulin is widely expressed in mammalian tissues, has been identified as a multifaceted immunoregulatory molecule through regulating the critical TNF/TNFR signaling. Recently, several studies reported that PGRN play an important role in immunity against bacterial infection. Progranulin levels were highly elevated in pediatric sepsis patients compared with healthy controls. PGRN may serve as a potential biomarker for the early diagnosis of early onset sepsis in newborn. We aimed to study serum level of progranulin as a diagnostic marker in early onset sepsis in neonate and compare its effectiveness with other commonly used biomarker such as procalcitonin (PCT) and C-reactive protein (CRP). we compared the diagnostic performance of progranulin in early onset neonatal sepsis and evaluate whether PGR combined with clinical commonly used biomarker could better distinguish neonatal sepsis. This case control study was conducted at Benha university hospitals on 80 neonates who were admitted to neonatal ICU (NICU) of Benha university hospitals of both sexes from July 2022 to May 2023 and were divided in to two groups. Infected group (Cases): included 40 neonates (with proven and probable infection). Non-infected group (Controls): included 40 neonates (with possible infection and unlikely infection). All subjects were examined and Prenatal history, Natal history, Postnatal and present history were taken. Complete blood counts (CBC), Blood culture, C–Reactive Protein (CRP), Procalcitonin (PCT), and Progranulin (PGRN) were measured. The summary of our results: There was significant difference between two groups regarding delivery method normal vaginal delivery incidence was higher in infected group than non-infected group. There was no significant difference between the two groups regarding gestational age, sex. Regarding maternal risk factors, the infected group had a history of maternal chorioamnitis, PROM>18h & birth trauma at significantly higher rates than the non-infected group, while there were non-significant differences between the two groups regarding the history of maternal skin rash or maternal UTI. The infected group had a significant higher frequency of maternal fever, while there was no significant difference between groups regarding gestational diabetes mellitus Regarding anthropometric measures there was no significant difference between two groups regarding weight, length and head circumference. Regarding Apgar Score at 1 min was significantly lower in the infected group compared to the non-infected group, while there was no significant differences between two groups regarding heart rate, respiratory rate & temperature. Regarding clinical signs, the most common presentation was vomiting and feeding intolerance. Clinical signs of infected group including apnea, bradycardia, hepatomegaly, hypoglycaemia neurological signs were significantly higher at time of diagnosis compared to non-infected group, while signs as Hypotonia and Jaundice were not significantly difference between two groups. Regarding the laboratory parameters the infected group had significant higher levels of white blood cells, I/T ratio, and significant lower level of platelet count compared to the non-infected group. While there was no significant difference between two groups regarding hemoglobin level. Infection biomarkers (CRP, PCT & PGRN) were significantly higher in infected group than non infected group. Regarding the primary outcome at the infected group had a significantly higher for duration of NICU admission & duration of oxygenation. Regarding the secondary outcome, the death was significantly higher in infected group compared to non infected group. Inflammatory biomarkers were significantly correlated with complication of sepsis regarding meningitis, convulsion, DIC, NEC, septic arthritis, organ failure except PGRN that was not correlated with hydrocephalous. The infectious biomarkers PGRN, PCT and CRP were correlated with the duration of NICU admission. PGRN and PCT correlated with mortality while CRP not correlated with mortality. Two biomarkers, PGRN and PCT, were found to be significant predictors for neonatal Sepsis, while CRP was not when considering its effect alongside PGRN and PCT. The combination of PGRN and PCT together had a strong association with Sepsis. The results showed that the addition of PGRN to PCT resulted in an increased AUC values (from 0.836 to 0.987, p <0.001), with a specificity of 91% and a PPV of 87.7%. For CRP, PCT, and PGRN together, the AUC value increased to 0.996, which was also higher than that for CRP together with PCT with AUC of 0.763 (p = 0.00053).