Maternal Risk Factors Associated with Neonatal Necrotizing Enterocolitis: a Meta-Analysis and Systematic Review

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Abstract

Background Neonatal Necrotizing Enterocolitis (NEC) is a multifactorial intestinal disorder that affects 2–5% of premature infants and has a mortality rate of 20–30%. 1 Researchers have identified the impact of maternal factors, such as a negative association of breastmilk feeding and antenatal corticosteroid therapy, on NEC development in infants. 2–5 However, other maternal risk factors have not been analyzed in detail. A better understanding of the role of specific maternal factors in developing NEC can help identify infants at risk and decrease the incidence of NEC. This meta-analysis aims to investigate the independent association between Cesarean section delivery, smoking, preeclampsia, chorioamnionitis, diabetes mellitus, and maternal education on the development of NEC. Methods We systematically searched for journal articles published before April 2025. 6–9 Studies were included if they contained data on incidence rates of NEC for any of the seven risk factors analyzed in this study. Two evaluators independently screened and extracted literature to be used for this meta-analysis. Disagreements were resolved through discussion, and interrater reliability was assessed using Cohen’s Kappa. Results We identified 74 manuscripts that met the inclusion criteria, of which 39 were suitable for our meta-analysis. The pooled risk calculation showed a statistically significant risk of NEC for mothers who smoked during pregnancy (OR: 1.75, 95% CI: 1.26–2.25, n = 10) and for mothers who had preeclampsia (OR: 2.03, 95% CI: 1.43–2.63, n = 8). All other pooled estimates for the maternal factors analyzed showed insignificant evidence of an association with NEC. In addition, the funnel plots and Egger’s regression tests indicated no evidence of publication bias for all maternal factors besides smoking during pregnancy (t = 2.61, p = 0.0313). Conclusions This study highlights a significant association between maternal smoking and preeclampsia during pregnancy and the development of NEC, suggesting a potential causal relationship. This study also identifies chorioamnionitis and Cesarean sections alone as nonsignificant risk factors, despite conflicting claims from other studies. Moreover, this meta-analysis also underscores the need for more research to be conducted to analyze the association between maternal smoking, preeclampsia, Cesarean sections, and chorioamnionitis on the development of NEC.

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