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

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.