Risk Factors and Clinical Outcomes of Early-Onset Versus Late-Onset Neonatal Sepsis in Intensive Care Settings: A Comparative Study

Background: Neonatal sepsis is a leading cause of morbidity and mortality in low-resource settings, with early-onset (EOS) and late-onset sepsis (LOS) exhibiting distinct risk factors and clinical trajectories. In Pakistan, where antimicrobial resistance is an escalating threat, robust local data are urgently needed to inform effective management. To compare the risk factors, microbiological profiles, and clinical outcomes associated with EOS and LOS among neonates admitted to the NICU at Hayatabad Medical Complex, Peshawar. Methods: A prospective observational cohort study was conducted Study duration 8 April 2024 to 7 may 2025...setting NICU Paeds Department Hayatabad Medical Complex Peshawa. All neonates (≤28 days) with culture-confirmed or clinically defined sepsis were enrolled and categorized as EOS (onset ≤72 hours) or LOS (>72 hours). Data on maternal and neonatal risk factors, microbiology, antimicrobial resistance, and outcomes were systematically collected. Statistical analyses included chi-square, t-tests, and multivariable logistic regression; all analyses used R and SPSS software. Ethical approval and parental informed consent were obtained. Results: Of 314 enrolled neonates, 152 (48.4%) had EOS and 162 (51.6%) had LOS. Maternal factors such as prolonged rupture of membranes (26.3% vs. 8.0%, p<0.001), maternal fever (21.1% vs. 8.0%, p=0.001), and chorioamnionitis (7.9% vs. 1.9%, p=0.02) were significantly more common in EOS. LOS was strongly associated with central line use (44.4% vs. 21.7%, p<0.001) and parenteral nutrition (37.7% vs. 18.4%, p<0.001). Multi-drug resistant organisms were isolated more frequently in LOS (51% vs. 36%, p=0.009). NICU mortality was 15.1% in EOS and 19.8% in LOS (p=0.24), with LOS associated with longer hospital stays (median 16 vs. 11 days, p=0.002). On multivariable analysis, low birth weight and MDR infection were independent predictors of mortality. Conclusions: Distinct perinatal and nosocomial risk patterns characterize EOS and LOS in this high-burden NICU, with LOS presenting greater challenges due to antimicrobial resistance and prolonged hospitalization. Integrated perinatal infection control, device management, and antimicrobial stewardship are critical to improving neonatal outcomes in Pakistan and similar settings.