title: Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
authors.forename: Chloe A
authors.initials: CA
authors.lastname: Autran
authors.affiliation: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.|Bioinformatics and Systems Biology Program, University of California, La Jolla, California, USA.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Kellman
authors.affiliation: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Newborn & Developmental Pediatrics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Asztalos
authors.affiliation: Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California, USA.
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Blood
authors.affiliation: Cook Children's Health Care System, Forth Worth, Texas, USA.
authors.forename: Erin C Hamilton
authors.initials: ECH
authors.lastname: Spence
authors.affiliation: Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Aloka L
authors.initials: AL
authors.lastname: Patel
authors.affiliation: Clinical & Translational Research Institute, University of California San Diego, La Jolla, California, USA.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.|Bioinformatics and Systems Biology Program, University of California, La Jolla, California, USA.|Novo Nordisk Foundation Center for Biosustainability at the University of California San Diego School of Medicine, La Jolla, California, USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Lewis
authors.affiliation: Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Bode
mesh_terms: D001942:Breast Feeding; D016022:Case-Control Studies; D015331:Cohort Studies; D020345:Enterocolitis, Necrotizing / Q000209:etiology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D008297:Male; D008895:Milk, Human / Q000737:chemistry*; D009844:Oligosaccharides / Q000032:analysis*; D011446:Prospective Studies; D012306:Risk; D018570:Risk Assessment
chemical_list: D009844:Oligosaccharides
keywords: BREAST MILK; INFANT/NEONATAL NUTRITION; NECROTIZING ENTEROCOLITIS; OLIGOSACCHARIDES; PREBIOTIC