Neurodevelopmental outcomes of preterm with necrotizing enterocolitis: a systematic review and meta-analysis

While neonatal necrotising enterocolitis (NEC) is associated with high mortality rates in newborns, survivors can face long-term sequelae. However, the relationship between NEC and neurodevelopmental impairment (NDI) in preterm infants remains unclear. To explore the relationship between neonatal NEC and neurodevelopmental outcomes in preterm infants, we searched PubMed, EMBASE, and the Cochrane Library from their inception to February 2024 for relevant studies. Studies included were cohort or case-control studies reporting neurodevelopmental outcomes of NEC in preterm infants. Two independent investigators extracted data regarding brain damage and neurodevelopmental outcomes in these infants at a corrected age exceeding 12 months. Odds ratios (ORs) were pooled using a random effects model. We included 15 cohort studies and 18 case-control studies, encompassing 60,346 infants. Meta-analysis of unadjusted and adjusted ORs demonstrated a significant association between NEC and increased odds of NDI (OR 2.15, 95% CI 1.9-2.44; aOR 1.89, 95% CI 1.46-2.46). Regarding brain injury, pooled crude ORs indicated an association of NEC with severe intraventricular haemorrhage (IVH) (OR 1.42, 95% CI 1.06-1.92) and periventricular leucomalacia (PVL) (OR 2.55, 95% CI 1.76-3.69). When compared with conservatively treated NEC, surgical NEC potentially carries a higher risk of NDI (OR 1.78, 95% CI 1.09-2.93) and severe IVH (OR 1.57, 95% CI 1.20-2.06). However, the risk of PVL did not show a significant difference (OR 1.60, 95% CI 0.47-5.40).

Our meta-analysis provides evidence suggesting an association between NEC and NDI. Additionally, the severity of intestinal lesions appears to correlate with a higher risk of NDI. Further high-quality studies with comprehensive adjustments for potential confounding factors are required to definitively establish whether the association with NDI is causal.

• NEC is a serious intestinal disease in the neonatal period with a high mortality rate, and surviving children may have digestive system sequelae. • Compared with non-NEC preterm infants, the reported incidences of brain injury and neurodevelopmental disorders in NEC preterm infants are not the same.

• The risk of neonatal brain injury and neurodevelopmental disorders in preterm infants with NEC is higher than that in non-NEC infants, and the risk of NDI in surgical NEC infants is higher than that in the conservative treatment group. • NEC may increase the risk of motor, cognitive, language development delays, and attention deficits in children.