Viral Infections and Neonatal Necrotizing Enterocolitis: A Meta-analysis

Abstract

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.

Association between viral infection and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis

“…The quality of each included study was assessed according to the Newcastle-Ottawa Scale (NOS), and the results are detailed in Supplemental Table 2 . Based on past experience, literature rated 0 to 3 is considered high risk of bias, 4 to 6 is considered moderate risk of bias, and 7 to 9 is considered low risk of bias [ 35 ]. Agreement between the two independent reviewers (X.G.…”

The emerging role of the gut virome in necrotizing enterocolitis

“…Other viruses such as human astrovirus, adenovirus, torovirus, and cytomegalovirus have been detected in sporadic NEC [ 14 , [41] , [42] , [43] , [44] ]. A meta-analysis of 24 studies with 4356 infants demonstrated that viral infection is linked to increased risk of NEC in newborns, especially infection with rotavirus, cytomegalovirus, norovirus, and astrovirus [ 7 ]. However, different viruses have been found in different studies, and even no specific viral pathogens have been detected in some studies [ 45 , 46 ].…”

“…The expansion of Caudovirales and the reduction of Microviridae are the most consistently observed change of gut virome in IBD [ [4] , [5] , [6] ]. Although gut bacteria are likely involved in NEC pathogenesis, recent studies suggest a connection between the gut virome and NEC etiology [ 7 , 8 ]. This review explores the development of the gut virome in newborns, summarizes recent evidence on its role in NEC, and discusses its promising therapeutic applications.…”

Congenital cytomegalovirus in Sub-Saharan Africa—a narrative review with practice recommendations

“…In South Africa, 2% of term infants have acquired pCMV by 3 weeks and 21% by 3 months of age (45). In term infants pCMV is usually asymptomatic, but in preterm infants up to 15% of infants with pCMV have symptomatic disease which may include sepsis-like syndrome with respiratory distress, feed intolerance and potentially necrotising enterocolitis, jaundice, hepatitis, thrombocytopenia and neutropenia (45)(46)(47).…”