Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 7.
doi: 10.1038/s41390-025-04102-0. Online ahead of print.

Adverse neurodevelopment after multiple sepsis and/or necrotizing enterocolitis in preterm infants: revisiting single-episode paradigm

Jae Hui Ryu  1 , Seung Han Shin  2 , Baek Sup Shin  3 , Ee-Kyung Kim  3 , Han-Suk Kim  3
Affiliations

Adverse neurodevelopment after multiple sepsis and/or necrotizing enterocolitis in preterm infants: revisiting single-episode paradigm

Jae Hui Ryu et al. Pediatr Res. .

Abstract

Background: Systemic inflammation in preterm infants is associated with an increased risk of adverse neurodevelopmental outcomes. This study aimed to investigate the impact of single versus multiple episodes of sepsis and/or necrotizing enterocolitis (NEC) on neurodevelopmental impairment (NDI) in this population.

Methods: This cohort study used data from a nationwide registry, including very low-birth-weight infants born before 32 weeks of gestation from 2013 to 2020. The study population was categorized according to the occurrence of sepsis and/or NEC. Neurodevelopmental assessments at 18-24 months of corrected age were performed using various tools. Any NDI or death was used as the primary outcome.

Results: In the multivariate logistic regression analysis, infants with multiple episodes of sepsis (aOR = 1.43; 95% CI [1.02-2.01]) or both sepsis and NEC (aOR = 1.91; 95% CI [1.26-2.90]) had a significantly higher risk of NDI compared to those without sepsis and NEC. A single sepsis episode without NEC was not associated with an increased risk of NDI.

Conclusion: Multiple episodes of sepsis and/or NEC significantly increased the risk of NDI in VLBW infants, whereas a single episode of sepsis did not. These findings highlight the need to distinguish between single and multiple episodes of systemic inflammation when assessing neurodevelopmental outcomes.

Impact: Multiple episodes of sepsis and/or necrotizing enterocolitis (NEC) significantly increase the risk of neurodevelopmental impairment (NDI) and death in preterm infants. However, a single episode of sepsis alone was not associated with the risk of NDI and NDI or death in the study population. When evaluating the neurodevelopmental outcomes of preterm infants, it is crucial to recognize that a single episode of sepsis may have a lesser impact on NDI compared to recurrent systemic inflammation or NEC episodes.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The KNN registry was approved by the institutional review board of each participating hospital, and informed consent was obtained from the parents of each infant upon enrollment in the NICUs participating in the KNN. All the participants signed an informed consent form. This study was performed in line with the principles of the Declaration of Helsinki. The Institutional Review Board of Seoul National University Hospital exempted this study from review, as the nature of the study involved the use of de-identified registered data (IRB No. 2303-012-1409).

Similar articles

See all similar articles

References

    1. Uccella, S. et al. Influence of Isolated Low-Grade Intracranial Haemorrhages on the Neurodevelopmental Outcome of Infants Born Very Low Birthweight. Dev. Med. Child Neurol. 65, 1366–1378 (2023). - DOI
    1. DeMauro, S. B. Neurodevelopmental Outcomes of Infants with Bronchopulmonary Dysplasia. Pediatr. Pulm. 56, 3509–3517 (2021). - DOI
    1. Bae, S. P., Shin, S. H., Yoon, Y. M., Kim, E. K. & Kim, H. S. Association of Severe Retinopathy of Prematurity and Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes in Preterm Infants without Severe Brain Injury. Brain Sci. 11, 699 (2021). - DOI - PubMed - PMC
    1. Stoll, B. J. et al. Neurodevelopmental and Growth Impairment among Extremely Low-Birth-Weight Infants with Neonatal Infection. JAMA 292, 2357–2365 (2004). - DOI - PubMed
    1. Mitha, A. et al. Neonatal Infection and 5-Year Neurodevelopmental Outcome of Very Preterm Infants. Pediatrics 132, e372–e380 (2013). - DOI - PubMed

LinkOut - more resources