Neurodevelopmental Outcome after Late-Onset Bacterial Sepsis in Infants Born before 29 Weeks' Gestation

Abstract

Objective

Neonatal late-onset sepsis is associated with increased mortality and morbidity, adversely impacting long-term outcome. The objective of this study was to examine neurodevelopmental (ND) outcomes at 18 to 24 months' corrected age (CA) in infants with late-onset bacterial sepsis (LOS) and to categorize outcomes based on type of bacterial pathogen in a cohort of preterm infants born less than 29 weeks gestation in Canada.

Study Design

We conducted a retrospective cohort study of all non-anomalous infants born at <29 weeks gestational age (GA) who were admitted to Canadian NICUs, from January 1, 2010, to December 31, 2017, who had an ND assessment at 18 to 24 months' CA at Canadian Neonatal Follow-Up Network clinics. The primary outcome was the composite outcome of death or ND impairment (NDI). Secondary outcomes included significant NDI, and each component of primary outcome. We compared ND outcomes among infants with Gram-positive (GP) sepsis, Gram-negative (GN) sepsis, mixed sepsis, and no sepsis using bivariate and multivariate analyses after adjusting for potential confounders.

Results

Of the 3,640 infants included, 823 (22.6%) developed LOS. Of the 823 infants, 569 (69.1%) had GP sepsis, 172 (20.9%) had GN sepsis, and 82 (10%) had mixed sepsis. Infants with LOS had significantly lower birth weight, GA, younger mothers, and significantly higher rates of major neonatal morbidities compared with the no-sepsis group. In multivariable logistic regression, infants with GN sepsis and mixed sepsis had significantly higher odds of death/NDI (GN sepsis, adjusted odds ratio [aOR] = 1.80; 95% CI: 1.27, 2.54; mixed LOS, aOR = 2.38, 95% CI: 1.41, 4.01) as compared with no sepsis.

Conclusion

Late-onset bacterial sepsis, particularly Gram-negative and mixed sepsis, was associated with an increased risk of adverse outcomes including death or NDI at 18 to 24 months CA in infants born <29 weeks' GA in Canada.

Key Points

• Late-onset sepsis is an important risk factor for morbidity and mortality in preterm infants.

• The clinical presentations vary depending on the causative bacteria.

• There is limited data on neurodevelopmental outcomes based on type of bacterial pathogen.

Keywords

bacteria - cognitive score - death - late-onset sepsis - neurodevelopmental outcome - pathogen

^‡ Network details are available in the [Supplementary Material] (available in the online version only).

Publication History

Received: 01 April 2025

Accepted: 22 December 2025

Article published online:
29 January 2026

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