Maternal risk factors associated with neonatal necrotizing enterocolitis: a meta-analysis and systematic review

Neonatal Necrotizing Enterocolitis (NEC) is a multifactorial intestinal disorder that affects 2-5% of premature infants and has a mortality rate of 20-30%. Maternal factors such as breastmilk feeding and antenatal corticosteroid therapy have been found to influence NEC development in infants, yet other maternal and perinatal contributors have not been analyzed in detail. A better understanding of the role of specific maternal factors in NEC development can help identify infants at risk. This meta-analysis aims to investigate the pooled association between Cesarean section delivery, smoking, preeclampsia, chorioamnionitis, diabetes mellitus, and maternal education on the development of NEC.

We systematically searched for journal articles published before April 2025 in Springer Nature Link, Scopus, PubMed, and Google Scholar. Results were narrowed down using the Boolean search string ("necrotizing enterocolitis" OR "neonatal necrotizing enterocolitis") AND (("maternal risk" OR "maternal factors") OR ("smoking" OR "preeclampsia" OR "chorioamnionitis" OR "diabetes")). Studies were included if they reported NEC incidence rates for any of the examined factors. Two evaluators independently screened and extracted literature, and disagreements were resolved through discussion. Interrater reliability was assessed using Cohen's Kappa.

We identified 74 manuscripts that met the inclusion criteria, of which 26 were suitable for our meta-analysis. We calculated unadjusted ORs from extracted 2 × 2 data, as adjusted estimates were infrequently reported and were not pooled. The unadjusted pooled risk calculation showed a higher odds of NEC for both preeclampsia (OR: 2.11, 95% CI: 1.15-3.06, n = 4) and smoking during pregnancy (OR: 1.97, 95% CI: 1.66-2.28, n = 6). Funnel plots and Egger's regression tests indicated no evidence of publication bias for maternal factors with more than 10 studies.

This study highlights a significant pooled unadjusted association between maternal smoking and preeclampsia during pregnancy and the development of NEC. Chorioamnionitis and Cesarean sections alone were not significantly associated with NEC in this pooled unadjusted analysis, despite conflicting claims from other studies. This meta-analysis underscores the need for more research to be conducted to analyze the association between maternal smoking, preeclampsia, Cesarean sections, chorioamnionitis, and maternal education on the development of NEC.