From Gram-Negative Neonatal Sepsis to Neurodevelopmental Impairment: A Retrospective Cohort Study in Preterm Infants

Gram-negative neonatal sepsis remains a cause of morbidity and mortality in preterm infants, yet the relationship between early clinical severity and long-term neurodevelopmental outcomes is incompletely defined. This study aimed to characterize Gram-negative sepsis in preterm infants and to evaluate its short-term and 18-24-month neurodevelopmental consequences.

We conducted a retrospective observational cohort study of preterm infants admitted to a tertiary neonatal intensive care unit between 1 January 2022 and 31 December 2023. Infants with culture-proven Gram-negative neonatal sepsis, including both early-onset sepsis (EOS) and late-onset sepsis (LOS), were included. Clinical, microbiological, therapeutic, and laboratory data were collected, and survivors were assessed at 18-24 months' corrected age using the Bayley Scales of Infant and Toddler Development.

Among infants with culture-proven Gram-negative sepsis, late-onset cases were more frequent than early-onset cases, and Klebsiella pneumoniae was the most common pathogen (38.0%). Multidrug-resistant organisms were associated with 52.0% of infections. In-hospital mortality was 26.0%. Major short-term complications included intraventricular hemorrhage (24.0%), severe intraventricular hemorrhage (20.0%), necrotizing enterocolitis (12.0%), bronchopulmonary dysplasia (20.0%), and meningitis (10.0%). Among survivors who underwent neurodevelopmental assessment, neurodevelopmental impairment was observed in 38.0%, most frequently affecting the language (22.5%) and cognitive (20.0%) domains. Infants with neurodevelopmental impairment had significantly lower gestational age and birth weight and higher inflammatory biomarker levels. In multivariable analyses, lower gestational age emerged as the strongest independent predictor of both mortality (adjusted OR 0.19, 95% CI 0.04-0.99) and neurodevelopmental impairment (adjusted OR 0.12, 95% CI 0.02-0.71).

Gram-negative neonatal sepsis in preterm infants was associated with substantial mortality, severe neonatal complications, and a high burden of later neurodevelopmental impairment. Lower gestational age was independently associated with adverse short- and long-term outcomes. These findings support early recognition, targeted antimicrobial therapy, and structured neurodevelopmental follow-up in this high-risk population.