Preterm infants are at high risk for systemic inflammatory disorders, including sepsis, meningitis, bronchopulmonary dysplasia, and necrotizing enterocolitis (NEC). The developing brain of the premature newborn is especially susceptible to the cascade of inflammatory mediators elaborated in these conditions that cross the blood-brain barrier. NEC, a severe and potentially fatal condition of the gut that occurs in premature newborns, is a prime example of how an inflammatory reaction, perhaps initially localized, can become generalized and cause systemic harm. One such result is brain injury, especially to the cerebral white matter, which may lead to neurodevelopmental abnormality and dysregulated behavior. Numerous studies have documented an association between necrotizing enterocolitis and neurodevelopmental impairment (NDI), but to date, the brain and behavioral deficits associated with neonatal NEC are not fully understood. We performed a comprehensive systematic review and meta-analysis of existing literature to characterize brain injury and behavioral alterations associated with NEC. 7153 peer-reviewed published manuscripts were screened by two independent reviewers and evidence quality was assessed using GRADE criteria. Of these papers, 62 satisfied the criteria for our review (i.e., no case reports, meta-analyses, systematic reviews, or animal studies). Data from 32 papers using Bayley Scales of Infant and Toddler Development to assess infant outcomes were included in the meta-analysis. Our findings support neonatal necrotizing enterocolitis having deleterious effects on brain and behavioral development and impact on cognitive function, risk of cerebral palsy and motor impairment, educational achievement, behavior, and neuroanatomy. We discuss herein findings of both short-term outcomes (1-3 years) and long-term outcomes (until 13 years). Our meta-analysis also indicates that NEC has a moderate effect size on infant development, with consistent impairment across mental, cognitive, language and motor domains.

The authors have declared no competing interest.

The study did not receive any funding

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All data in this systematic review and meta-analysis are from published manuscripts.