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Enteral diet and necrotizing enterocolitis in neonates: a scoping review and parent outcome prioritization project Open Access


Other title
Enteral nutrition
Necrotizing enterocolitis
Type of item
Degree grantor
University of Alberta
Author or creator
Shulhan, Jocelyn R
Supervisor and department
Hartling, Lisa (Paediatrics)
Examining committee member and department
Larsen, Bodil (Paediatrics; Agricultural, Food & Nutritional Science)
Kumar, Manoj (Paediatrics)
Jones, Allyson (Physical Therapy; School of Public Health)
Fenton, Tanis (Community Health Sciences)
Medical Sciences-Paediatrics

Date accepted
Graduation date
2017-11:Fall 2017
Master of Science
Degree level
Necrotizing enterocolitis (NEC) is a potentially life-threatening inflammatory disease of the gut affecting newborns, especially preterm infants. This complex disease is affected by numerous risk factors including genetics, intestinal microbiota, immune system responses, cardiac or respiratory conditions, and diet. Several studies have investigated the effect of diet on NEC, and many have found that bovine milk-based products are linked to more NEC cases than an exclusive human milk diet. Reasons for this effect are unclear. Further, the effect of other nutrition products like protein-hydrosylated formulas and fortifiers is largely unknown. Obtaining reliable evidence on diet and NEC is difficult, given the rarity of the disease, confounding in observational studies, and the costs of nutrition products and coordinating large studies. In order to advance the field of NEC and nutrition, a comprehensive evaluation of the literature, and development of sufficiently powered, high-quality studies relevant to researchers, clinicians and families are needed. This thesis includes three studies: 1) a narrative review providing background on NEC, preterm nutrition and an overview of the association between diet and NEC in infants; 2) a scoping review mapping clinical research on different enteral diets and NEC, and systematic review of hydrolyzed nutrition products; and 3) a parent cross sectional survey on outcome prioritization that identified outcomes most important to parents, as well as compared parent priorities to commonly reported outcomes in the literature. The scoping review identified 76 studies, mostly observational studies comparing a predominantly or exclusively human milk diet with an exclusive or partial bovine milk-based formula diet. The majority of these studies suggest that human milk may be protective against NEC, but sample size was often inadequate to detect significant differences between feeding groups. Only 1/5 RCTs, 6/21 cohort studies and 11/16 case control studies found that an exclusive or predominantly human milk diet resulted in significantly fewer NEC cases than a diet containing a higher proportion of bovine milk-based products. Two randomized controlled trials comparing protein-hydrosylated fortifiers to intact-protein bovine milk-based fortifiers found no significant difference between the fortifiers and the development of NEC; however, the small sample size and imprecision of the effect estimates identified a low grade of evidence. The parent outcome prioritization study included 15 participants from across Canada and found that infant death and NEC were the most important outcomes to parents. Parents prioritized outcomes involving parents (e.g. quality of life) more than the reflected quantitative literature; whereas, nutrition-related outcomes (e.g. duration of parenteral nutrition) were considered lower parent priorities but were often reported as primary outcomes in the literature. In order to understand the true effect of protein-hydrosylated products compared to human milk and bovine milk-based products on NEC, a large clinical trial is needed. We recommend collaborating with a parent advisory committee during the planning stages of future trials to ensure family-relevant outcomes are included when evaluating NEC and treatment interventions.
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication
Shulhan J, Hartling L, Dicken B, Larsen B.(2017). Current knowledge of necrotizing enterocolitis in preterm infants and the impact of different types of enteral nutrition products. Adv Nutr, 8(1):80-91. doi: 10.3945/an.116.013193

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