Nutritional strategies and gut microbiota composition as risk factors for necrotizing enterocolitis in very-preterm infants

Abstract

The pathophysiology of necrotizing enterocolitis (NEC) remains poorly understood. We assessed the relation between feeding strategies, intestinal microbiota composition, and the development of NEC. We performed a prospective nationwide population-based study, EPIPAGE 2 (Etude Epidémiologique sur les Petits Ages Gestationnels), including preterm infants born at <32 wk of gestation in France in 2011. From individual characteristics observed during the first week of life, we calculated a propensity score for the risk of NEC (Bell's stage 2 or 3) after day 7 of life. We analyzed the relation between neonatal intensive care unit (NICU) strategies concerning the rate of progression of enteral feeding, the direct-breastfeeding policy, and the onset of NEC using general linear mixed models to account for clustering by the NICU. An ancillary propensity-matched case-control study, EPIFLORE (Etude Epidémiologique de la flore), in 20 of the 64 NICUs, analyzed the intestinal microbiota by culture and 16S ribosomal RNA gene sequencing. Among the 3161 enrolled preterm infants, 106 (3.4%; 95% CI: 2.8%, 4.0%) developed NEC. Individual characteristics were significantly associated with NEC. Slower and intermediate rates of progression of enteral feeding strategies were associated with a higher risk of NEC, with an adjusted OR of 2.3 (95% CI: 1.2, 4.5; = 0.01) and 2.0 (95% CI: 1.1, 3.5; = 0.02), respectively. Less favorable and intermediate direct-breastfeeding policies were associated with higher NEC risk as well, with an adjusted OR of 2.5 (95% CI: 1.1, 5.8; = 0.03) and 2.3 (95% CI: 1.1, 4.8; = 0.02), respectively. Microbiota analysis performed in 16 cases and 78 controls showed an association between and with NEC ( = 0.001 and = 0.002). A slow rate of progression of enteral feeding and a less favorable direct-breastfeeding policy are associated with an increased risk of developing NEC. For a given level of risk assessed by propensity score, colonization by and/or is significantly associated with NEC. This trial (EPIFLORE study) was registered at clinicaltrials.gov as NCT01127698.

Preterm infants with necrotising enterocolitis demonstrate an unbalanced gut microbiota

“…A higher diversity in Clostridium species was found in the control group with various clostridial species, that is C. clostridioforme , C. butyricum , Clostridium paraputrificum and C. tertium . Of note, we did not find significant differences neither in C. butyricum colonisation between infants with and without NEC, as described by Cassir et al., although we used the same technique , nor in Clostridium neonatale as recently reported .…”

Variability of Very Low Birth Weight Infant Outcome and Practice in Swiss and US Neonatal Units

“…35 The higher ratio of partial human milk feeding at discharge in SNN will have had no immediate impact on the outcome at discharge of primary hospitalization but may indicate a higher breastfeeding proportion during hospital stay, which is known to be beneficial. 36,37 The strength of this study lies in the size of the population, the high cohort representation, the homogeneity of the data collection, and the combination of patient and unit-level data. Limitations are given by the type of study; a cohort study can never rule out all confounding and the ability of risk adjustment to isolate relevant outcome differences is limited.…”

Evolution of Gut Microbiome and Metabolome during Stage 1 Necrotizing Enterocolitis: a Case-Control Study

“…From a clinical and microbiological point of view, studies of NEC were focused only on established and severe phenotypes such as NEC-2 and NEC-3. Based on the French study EPIPAGE 2, the incidence of proved NEC-2 and NEC-3 is 1-5% in preterm infants born at less than 32 weeks of gestation [13].…”