355 - Neurodevelopmental Outcomes in Preterm Infants with Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis

Poster Number: 355
Publication Number: 355.3022

Background: Preterm infants are at high risk for a variety of systemic inflammatory disorders. Their developing brains are susceptible to inflammatory mediators elaborated in these conditions that cross the blood-brain barrier. Necrotizing enterocolitis (NEC), a severe condition of the gut in very low and extremely low birth weight infants, is a prime example of how an inflammatory reaction, perhaps initially localized, becomes generalized. Numerous studies have documented an association between NEC and neurodevelopmental impairment (NDI), but to date, the brain and behavioral deficits associated with neonatal NEC are not fully understood.

Objective: We performed a comprehensive systematic review and meta-analysis of existing literature to characterize the association between NEC and alterations in neurodevelopmental and behavioral outcomes.

Design/Methods: A total of 7,152 manuscripts were returned using our search terms. After title/abstract review and removal of duplicates, 535 were included for full-text extraction, and 140 papers met the criteria for our NEC-focused review. Manuscripts were assessed for high or moderate quality of evidence using GRADE criteria and extracted by two independent reviewers. Cohen’s D effect sizes were used to estimate magnitude of differences between NEC and non-NEC group.

Results: A total of 69 papers were included in the systematic review across all outcome measures; data from 37 papers assessing infant development using Bayley Scales of Infant and Toddler Development were included in the meta-analysis (Fig. 1). Our results describe both short-term (1-3 years) and long-term (up to 13 years) neurodevelopmental outcomes across various domains (Fig. 2). NEC is shown to have consistent associations with cerebral palsy, cognitive delay, and long-term educational difficulties. There is less evidence of increased rates of ADHD or other psychiatric conditions. Infants requiring surgery demonstrate less favorable outcomes compared to infants managed medically. Neuroimaging data is suggestive of white matter microstructure differences between infants with and without NEC. Our meta-analysis also demonstrates that NEC has a moderate effect size on infant development, with consistent impairment across mental, cognitive, language and motor domains (Fig. 3).

Conclusion(s): Our findings suggest that neonatal NEC has deleterious effects on brain and behavioral development, impacting both short-term and long-term outcomes. Further study of risk determination, mechanisms of injury, and interventions to mediate harm are needed.