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Am J Clin Nutr. 2017 Sep;106(3):821-830. doi: 10.3945/ajcn.117.152967. Epub 2017 Jun 28.

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

Author information

1
Department of Neonatal Medicine, jcroze@chu-nantes.fr.
2
Epidémiologie Clinique, Clinical Investigation Center - Clinical Epidemiology (CIC004), and.
3
INRA, UMR 1280 Physiology of Nutritional Adaptations, Nantes University Hospital, Nantes, France.
4
INSERM, U1153, Obstetrical, Perinatal and Pediatric Epidemiology Team, Epidemiology and Statistics Sorbonne Paris Cité Research Center.
5
Risks in Pregnancy Department, and.
6
Clinical investigation center CIC P1419, Cochin Hotel-Dieu Hospital, AP-HP, Paris, France.
7
Micalis Institute, INRA, AgroParisTech, University Paris-Saclay, Paris, France.
8
EA 4065 Intestinal Ecosystem, Probiotics, Antibiotics, Faculty of Pharmacy, Paris Descartes University, Paris, France.
9
Department of Neonatal Medicine, Croix Rousse Hospital, Lyon Hospitals, Lyon, France.
10
Department of Neonatal Medicine, AP-HP, Necker Enfants Malades Hospital, Paris, France; and.
11
Department of Pediatrics, University of Florida, Gainesville, FL.

Abstract

Background: The pathophysiology of necrotizing enterocolitis (NEC) remains poorly understood.Objective: We assessed the relation between feeding strategies, intestinal microbiota composition, and the development of NEC.Design: 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.Results: 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; P = 0.01) and 2.0 (95% CI: 1.1, 3.5; P = 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; P = 0.03) and 2.3 (95% CI: 1.1, 4.8; P = 0.02), respectively. Microbiota analysis performed in 16 cases and 78 controls showed an association between Clostridium neonatale and Staphylococcus aureus with NEC (P = 0.001 and P = 0.002).Conclusions: 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 C. neonatale and/or S. aureus is significantly associated with NEC. This trial (EPIFLORE study) was registered at clinicaltrials.gov as NCT01127698.

KEYWORDS:

breastfeeding; clostridia; necrotizing enterocolitis; preterm infant; speed of increasing enteral nutrition

PMID:
28659297
PMCID:
PMC5573022
DOI:
10.3945/ajcn.117.152967
[Indexed for MEDLINE]
Free PMC Article

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