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Original article
Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants
  1. Chloe A Autran1,
  2. Benjamin P Kellman1,2,
  3. Jae H Kim1,
  4. Elizabeth Asztalos3,
  5. Arlin B Blood4,
  6. Erin C Hamilton Spence5,
  7. Aloka L Patel6,
  8. Jiayi Hou7,
  9. Nathan E Lewis1,2,8,
  10. Lars Bode1
  1. 1Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA
  2. 2Bioinformatics and Systems Biology Program, University of California, La Jolla, California, USA
  3. 3Department of Newborn & Developmental Pediatrics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  4. 4Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California, USA
  5. 5Cook Children's Health Care System, Forth Worth, Texas, USA
  6. 6Rush University Medical Center, Chicago, Illinois, USA
  7. 7Clinical & Translational Research Institute, University of California San Diego, La Jolla, California, USA
  8. 8Novo Nordisk Foundation Center for Biosustainability at the University of California San Diego School of Medicine, La Jolla, California, USA
  1. Correspondence to Dr Lars Bode, Department of Pediatrics, University of California San Diego School of Medicine, 9500 Gilman Dr., Mail code 0715, San Diego, CA 92093, USA; lbode{at}ucsd.edu

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.

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Footnotes

  • CAA and BPK contributed equally.

  • Twitter Follow Benjamin Kellman @bkell1123

  • Contributors LB and JHK designed research; CAA, LB, EA, ABB, ECHS, ALP and JHK recruited patients, collected samples and conducted research; CAA, BPK, NEL, JH and LB analysed data and performed statistical analysis; BPK, JH, JHK, NEL and LB wrote the manuscript; LB had primary responsibility for final content. All authors read and approved the final version of the manuscript.

  • Funding The project was supported by a grant from Abbott Nutrition, a division of Abbott Laboratories, and the National Institutes of Health, Grant R00DK078668 (LB) and UL1TR000100 (Clinical and Translational Research Institute), and support from the Novo Nordisk Foundation that had been provided to the Center for Biosustainability at the Technical University of Denmark (NEL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • Competing interests None declared.

  • Ethics approval University of California San Diego Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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