Diagnostic Value of Progranulin in Neonatal Sepsis

__________________________________________________ Background: The symptoms of neonatal sepsis are often hard to identify, which can lead to misdiagnosis. Because of the shortcomings of relying solely on blood cultures for diagnosis, surrogate biomarkers of sepsis are frequently employed. Progranulin is a secreted protein that acts as


Aim of the Work:
Evaluating the diagnostic value of serum progranulin in neonatal sepsis could potentially lead to earlier detection and improved prognosis for affected neonates.The determination of the sample size was performed by a two-tailed t-test to evaluate the difference between two independent means (two groups).The parameters for this calculation were as follows:

Patients & Methods:
 The effect size (d) was set at 0.82.
 The probability of a Type I error (α err prob) was set at 0.05.
 The power of the test (1-β err prob) was set at 0.97.
As a result of these parameters, the calculated sample sizes were 45 for both group 1 and group 2, leading to a total sample size of 90.*; significant, U; Mann-Whitney U test, X 2 ; Chi-square test CRP levels were notably higher in neonatal sepsis cases than in controls, with a median and interquartile range of 48 (24 -96) in neonatal sepsis patients and 3 (2 -4) in controls (Table 2).There was no significant association among serum progranulin levels and any of the personal data of neonatal sepsis patients (Table 5).There was no significant distinction in serum progranulin levels among different types of sepsis, between preterm and full-term, or between improved and deceased patients (Table 8).

Discussion
Sepsis is a critical condition that poses a threat to life.because they fail to distinguish between infection and sepsis [12].Therefore, there's a critical need for new diagnostic tools for sepsis.
Progranulin is a multifunctional factor that is broadly exhibited.and involved in numerous physiological and pathological processes [5].
Anti-inflammatory effects are attributed to its ability to increase interleukin-10 production and decrease TNF1 signaling [13,14].
In this research, it was observed that the levels of CRP were significantly elevated in the case group compared to the control group.
Conversely, both Hb and platelet levels were significantly reduced in the case group in comparison to the controls.
Numerous studies align with these findings.
For instance, a study by Tam & Bendel found that CRP was an independent predictor of a positive blood culture upon adjusted analysis [22].In another study by Benitz et al., which involved serial CRP measurements in neonates, both sensitivity and specificity were initially poor but showed significant improvement with multiple measurements.
This study also reported a nonspecific physiological increase over a 3-day period, influenced by non-infectious perinatal and maternal factors [22].According to Hornik et al., low platelet counts were also linked to late-onset sepsis [23].Contrary to our results, Shoukry et al. stated that anemia is not a consistent characteristic in neonates with a positive blood culture [24].
In their systematic review of fifteen studies involving 11,009 records, Murthy et al. also found that a gestational age below 37 weeks and a premature rupture of membranes were the most commonly documented risk factors for sepsis [25].
In this research, Klebsiella pneumoniae was the predominant gram-negative bacterium, shown to be the most common pathogen that was isolated [21].
According to the findings of this research, the levels of serum progranulin among newborn people with sepsis were found to be significantly higher than those found in the control group.Infection and progranulin have been the subject of a great number of investigations that have been conducted.The relatively small sample size in this singlecenter study and just a single measurement of progranulin levels are the main study's limitations, but its key strength is that we only included neonates with sepsis that were confirmed by blood culture.

Conclusions:
The levels of progranulin in the serum could potentially act as a promising diagnostic indicator for neonatal sepsis.There is a significant positive association among serum progranulin & CRP levels.No link was observed between progranulin levels and the prognosis of neonatal sepsis.

Recommendations:
https://ejmr.journals.ekb.eg/levels.Furthermore, serum progranulin was the most effective laboratory parameter in diagnosing neonatal sepsis, with the highest area under the ROC curve following CRP.No link was found between progranulin levels and the outcome of Sepsis in neonates.The most prevalent risk factors for sepsis were premature rupture of membranes and prematurity.In terms of prevalence among gram-negative organisms, Klebsiella pneumoniae was found to be the most common., MRSA and CoNS were identified as the most frequently isolated grampositive organisms.Conclusions: Progranulin levels in the serum could serve as a promising diagnostic biomarker for neonatal sepsis._______________________________________________________________________________ 1. Introduction: Neonatal sepsis is a medical illness defined as changes in blood flow and other general symptoms, caused by the existence of hazardous microorganisms like viruses, bacteria, or fungus in usually sterile fluids such as blood or cerebrospinal fluid within the 1st 28 days of life [1].Neonatal sepsis is a prominent factor contributing to morbidity and illness in newborn infants [2].It's estimated that out of every 100,000 live births, 2,202 newborns develop neonatal sepsis, with a mortality rate of 11individuals of neonatal sepsis each year [3].The identification of new biomarkers for diagnosing neonatal sepsis is crucial, as early diagnosis improves the prognosis [4].Progranulin, a secretory protein consisting of 593 amino acids and rich in cysteine, is expressed in macrophages, neurons, adipose tissues, epithelial cells, fibroblasts, and chondrocytes.It acts as an anti-inflammatory agent and plays a protective role in sepsis and endotoxic shock [5].Studies have found that progranulin levels in the bloodstream are significantly higher in adult and pediatric cases with sepsis than in healthy individuals [6], also in newborns with early-onset sepsis compared to uninfected newborns [4].
It's defined by the sudden failure of organs [8].Globally, it's estimated that over 31.5 million people are affected by sepsis, leading to almost 5.3 million deaths due to ongoing or repeated organ failure [9].Survivors of sepsis often face long-term negative impacts, including severe & lasting functional disabilities, and a diminished quality of life related to health [10].Sepsis frequently results in hospital admissions and high rates of readmission [11].Diagnosing sepsis is a challenge due to the absence of a definitive standard.Additionally, the lack of standardized definitions hinders the comparison of findings from clinical and epidemiological investigations [5].The existing sepsis criteria are being revised whilst MRSA and coagulase-negative staph (CoNS) were the most frequent gram-positive bacteria.This is consistent with research conducted at Al Demerdash and Ain Shams University Specialized Hospital, where Klebsiella was shown to be the most commonly seen gram-negative bacteria, whereas CoNS was most often encountered gram-positive organism [26].Nevertheless, in separate research carried out at the Neonatal https://ejmr.journals.ekb.eg/Intensive Care Units (NICUs) of the Children's Hospital of Ain Shams University as well as El-Hussein Hospital, Al-Azhar University, Egypt, Escherichia coli was

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Following approval from the Local Ethical Committee (FMBSUREC/07022021/Ahmed), the parents of those participating in the research provided written informed consent.

Table 1 :
Personal data among neonatal sepsis patients and controls.
This research involved 90 participants from the NICU of Beni-Suef University Hospital, separated into two groups: Group A (45 individuals diagnosed with neonatal sepsis) and Group B (45 healthy controls).The delivery method for 84.4% of neonatal sepsis individuals and 93.3% of controls was cesarean section, with no significant variation among the two groups (Table1).https://ejmr.journals.ekb.eg/

Table 2 :
Laboratory data among neonatal sepsis patients and controls.

Table 2 :
Serum progranulin among neonatal sepsis patients and controls.

Table 4 :
Correlation of serum progranulin and personal data among neonatal sepsis patients:

Table 5 :
Correlation of serum progranulin and laboratory data among neonatal sepsis patients:Serum progranulin levels were significantly and positively associated with CRP levels of earlyonset neonatal sepsis patients (Table7).

Table 6 :
Correlation of serum progranulin and CRP among early-onset neonatal sepsis patients:

Table 7 :
Serum progranulin levels in early and late-onset sepsis, preterm and full-term, improved and dead neonates.Serum progranulin level was the most effective laboratory parameter after CRP in diagnosing neonatal sepsis, with an Area under the ROC curve (AUC) of 0.883 (Table9). https://ejmr.journals.ekb.eg/

Table 8 :
Cutoff value of serum progranulin that can discriminate between patients with neonatal sepsis and sepsis-free neonates.