Long-term neurodevelopment in preterm neonates with necrotizing enterocolitis: systematic review and meta-analysis

Introduction Necrotizing enterocolitis (NEC) is a common complication in preterm infants and is associated with significant mortality and long-term morbidity, including gastrointestinal sequelae, brain injury, and developmental delays. This systematic review and meta-analysis examines long-term neurodevelopmental outcomes in infants born at less than 34 weeks’ gestation who survive NEC and identifies specific developmental domains most vulnerable to neurodevelopmental impairment. Methods The systematic review was performed according to the PRISMA guidelines. We systematically searched Pubmed (including MEDLINE), Embase and Web of Science for relevant articles. Studies were graded for quality using the GRADE system and bias was assessed using the ROBINS-E Risk of Bias tool. We performed gestational-age stratified subgroup analyses (22–28 weeks versus 29–34 weeks) and evaluated the risk of impairment in different neurodevelopmental domains. Results Survivors of NEC are at increased risk of neurodevelopmental impairment (RR 1.42, 95% CI 1.32–1.53). Several neurodevelopmental domains are negatively impacted, such as motor skills (RR 2.08, 95% CI 1.86–2.32), cognition (RR 1.75, 95% CI 1.57–1.96), vision (RR 4.36, 95% CI 2.91–6.55), hearing (RR 4.09, 95% CI 2.91–5.77) and cerebral palsy (RR 2.48, 95% CI 2.15–2.86). The risk of epilepsy and behavioral problems does not differ between NEC survivors and age-matched controls. This increased risk of impairment after NEC persists after stratification for gestational age and extends into school-age. Conclusion NEC Survivors face an elevated risk of neurodevelopmental impairment, irrespective of gestational age, with deficits spanning multiple developmental domains. These findings highlight the need for targeted, long-term follow-up to enable timely detection and individualized interventions for developmental delays throughout childhood. Systematic review registration http://www.crd.york.ac.uk/PROSPERO , identifier CRD42022322564.