Chloe A Autran1, Benjamin P Kellman1,2, Jae H Kim1, Elizabeth Asztalos3, Arlin B Blood4, Erin C Hamilton Spence5, Aloka L Patel6, Jiayi Hou7, Nathan E Lewis1,2,8, Lars Bode1. 1. Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA. 2. Bioinformatics and Systems Biology Program, University of California, La Jolla, California, USA. 3. Department of Newborn & Developmental Pediatrics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. 4. Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California, USA. 5. Cook Children's Health Care System, Forth Worth, Texas, USA. 6. Rush University Medical Center, Chicago, Illinois, USA. 7. Clinical & Translational Research Institute, University of California San Diego, La Jolla, California, USA. 8. Novo Nordisk Foundation Center for Biosustainability at the University of California San Diego School of Medicine, La Jolla, California, USA.
Abstract
OBJECTIVE: Necrotising enterocolitis (NEC) is one of the most common and often fatal intestinal disorders in preterm infants. Markers to identify at-risk infants as well as therapies to prevent and treat NEC are limited and urgently needed. NEC incidence is significantly lower in breast-fed compared with formula-fed infants. Infant formula lacks human milk oligosaccharides (HMO), such as disialyllacto-N-tetraose (DSLNT), which prevents NEC in neonatal rats. However, it is unknown if DSLNT also protects human preterm infants. DESIGN: We conducted a multicentre clinical cohort study and recruited 200 mothers and their very low birthweight infants that were predominantly human milk-fed. We analysed HMO composition in breast milk fed to infants over the first 28 days post partum, matched each NEC case with five controls and used logistic regression and generalised estimating equation to test the hypothesis that infants who develop NEC receive milk with less DSLNT than infants who do not develop NEC. RESULTS: Eight infants in the cohort developed NEC (Bell stage 2 or 3). DSLNT concentrations were significantly lower in almost all milk samples in NEC cases compared with controls, and its abundance could identify NEC cases prior to onset. Aggregate assessment of DSLNT over multiple days enhanced the separation of NEC cases and control subjects. CONCLUSIONS: DSLNT content in breast milk is a potential non-invasive marker to identify infants at risk of developing NEC, and screen high-risk donor milk. In addition, DSLNT could serve as a natural template to develop novel therapeutics against this devastating disorder. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
OBJECTIVE: Necrotising enterocolitis (NEC) is one of the most common and often fatal intestinal disorders in preterm infants. Markers to identify at-risk infants as well as therapies to prevent and treat NEC are limited and urgently needed. NEC incidence is significantly lower in breast-fed compared with formula-fed infants. Infant formula lacks human milk oligosaccharides (HMO), such as disialyllacto-N-tetraose (DSLNT), which prevents NEC in neonatal rats. However, it is unknown if DSLNT also protects human preterm infants. DESIGN: We conducted a multicentre clinical cohort study and recruited 200 mothers and their very low birthweight infants that were predominantly human milk-fed. We analysed HMO composition in breast milk fed to infants over the first 28 days post partum, matched each NEC case with five controls and used logistic regression and generalised estimating equation to test the hypothesis that infants who develop NEC receive milk with less DSLNT than infants who do not develop NEC. RESULTS: Eight infants in the cohort developed NEC (Bell stage 2 or 3). DSLNT concentrations were significantly lower in almost all milk samples in NEC cases compared with controls, and its abundance could identify NEC cases prior to onset. Aggregate assessment of DSLNT over multiple days enhanced the separation of NEC cases and control subjects. CONCLUSIONS: DSLNT content in breast milk is a potential non-invasive marker to identify infants at risk of developing NEC, and screen high-risk donor milk. In addition, DSLNT could serve as a natural template to develop novel therapeutics against this devastating disorder. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Entities:
Keywords:
BREAST MILK; INFANT/NEONATAL NUTRITION; NECROTIZING ENTEROCOLITIS; OLIGOSACCHARIDES; PREBIOTIC
Authors: Victor D Torres Roldan; Meritxell Urtecho S; Julia Gupta; Chloe Yonemitsu; Cesar P Cárcamo; Lars Bode; Theresa J Ochoa Journal: Am J Clin Nutr Date: 2020-07-01 Impact factor: 7.045
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