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CONTEXT: Necrotizing enterocolitis (NEC) is a devastating intestinal disease affecting preterm infants. Studies implicate viral infections in etiopathogenesis.

OBJECTIVE: To summarize the association of viral infections with NEC by systematic review and meta-analysis.

DATA SOURCES: We searched Ovid-Medline, Embase, Web of Science, and Cochrane databases in November 2022.

STUDY SELECTION: We included observational studies that examined the association between viral infections and NEC in newborn infants.

DATA EXTRACTION: We extracted data regarding the methodology, participant characteristics, and outcome measures.

RESULTS: We included 29 and 24 studies in the qualitative review and meta-analysis, respectively. The meta-analysis demonstrated a significant association between viral infections and NEC (odds ratio [OR], 3.81, 95% confidence interval: 1.99-7.30, 24 studies). The association remained significant after excluding the outliers (OR, 2.89 [1.56-5.36], 22 studies) and studies with poor methodology (OR, 3.33 [1.73-6.43], 22 studies). In subgroup analysis based on participants' birth weight, studies including very low birth weight infants only (OR, 3.62 [1.63-8.03], 8 studies) and non-very low birth weight infants only (OR, 5.28 [1.69-16.54], 6 studies) showed a significant association. In subgroup analysis based on specific viruses, infection with rotavirus (OR, 3.96 [1.12-13.95], 10 studies), cytomegalovirus (OR, 3.50 [1.60-7.65], 5 studies), norovirus (OR, 11.95 [2.05-69.84], 2 studies), and astrovirus (OR, 6.32 [2.49-16.02], 2 studies) was significantly associated with NEC.

LIMITATIONS: Heterogeneity of the included studies.

CONCLUSIONS: Viral infection is associated with an increased risk of NEC in newborn infants. We need methodologically sound prospective studies to assess the effect of preventing or treating viral infections on NEC incidence.


Humans, Infant, Infant, Newborn, Enterocolitis, Necrotizing, Infant, Newborn, Diseases, Infant, Premature, Infant, Very Low Birth Weight, Prospective Studies, Virus Diseases

Published Open-Access