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Abstract Neonatal early-onset sepsis (EOS) refers to sepsis occurring within 72 hours of delivery in infants. EOS can be caused by organisms transmitted from the mother. Without prompt antibiotic therapy, EOS can rapidly progress, leading to neurological issues and infant mortality. There is an urgent need for novel, accurate indicators to facilitate early detection of EOS. Progranulin (PGRN) is a protein consisting of 593 amino acids. PGRN is involved in various cell types, including astrocytes, microglia, neurons, and endothelial cells. Its roles in immunology, infection, and inflammation have been documented. This study aimed to measure Progranulin in umbilical cord blood to determine whether it can predict EONS in preterm labor with premature rupture of membranes (PROM). This study included 50 cases of preterm infants born to pregnant women with PROM and admitted for delivery in Benha University Hospital during the period from June 2021 to December 2021. Statistical analysis showed that: • Neonates in the EOS group exhibited a significantly lower mean gestational age (31 ± 3 weeks) compared to those in the non-EOS group (33 ± 3 weeks) (P = 0.007). • A higher prevalence of consanguinity was observed in the EOS group (75%) in contrast to the non-EOS group (40.9%) (P = 0.015). Notably, 100% of neonates in the EOS group experienced premature rupture of membranes (PROM), a stark contrast to the 31.8% in the non-EOS group, indicating a strong association (P < 0.001). • The EOS group exhibited a higher occurrence of fetal risk factors (75%) compared to the non-EOS group (45.5%) (P = 0.033). Moreover, neonates affected by EOS had significantly lower weight (1534 ± 636 grams) compared to their non-EOS counterparts (2030 ± 475 grams) (P = 0.003). • The presence of any symptoms of early-onset neonatal sepsis (EONS) was significantly higher in the EOS group (82.1%) compared to the non-EOS group (31.8%), with a P-value of <0.001. • Neonates with EOS had notably lower mean hemoglobin levels (11.2 ± 2.1 g/dL) compared to those without EOS (15.4 ± 1.9 g/dL, P < 0.001). There was also a significant difference in the Total Leukocyte Count (TLC), with neonates in the EOS group having higher levels (21.55 ± 8.81 x 10^9/L) than those in the non-EOS group (14.77 ± 3.12 x 10^9/L, P < 0.001). The median neonatal C-reactive protein (CRP) levels were significantly higher in EOS cases (54, range 12 - 156) compared to non-EOS cases (6, range 0 - 54, P < 0.001). A significant difference was observed in the levels of progranulin in the umbilical cord, with higher levels observed in neonates with EOS (mean 55.7 ± 12.5 ng/mL) compared to those without EOS (mean 36.9 ± 9.4 ng/mL, P < 0.001). • The mortality rate was significantly higher in the EOS group (50%) compared to the non-EOS group (4.5%), with a P-value of <0.001. However, the length of hospital stay did not significantly differ between the two groups (P = 0.883). • The ROC curve analysis demonstrates the performance of the Umbilical cord progranulin in predicting early onset sepsis, with an AUC of 0.883 (95% CI: 0.793 - 0.973), suggesting a very good ability to distinguish between neonates with and without early-onset sepsis (EOS). The best cutoff was >51.9, at which sensitivity, specificity, PPV, and NPV were 71.4%, 95.5%, 95.2%, and 72.4 |