What is the question?

• The question is: What is the relationship between never versus ever feeding human milk and inflammatory bowel disease?

What is the answer to the question?

• Evidence about the relationship between never versus ever being fed human milk and inflammatory bowel disease in offspring is inconclusive. 

Why was this question asked? 

• This important public health question was identified and prioritized as part of the U.S. Department of Agriculture and Department of Health and Human Services Pregnancy and Birth to 24 Months Project.

How was this question answered? 

• A team of Nutrition Evidence Systematic Review staff conducted a systematic review in collaboration with a group of experts called a Technical Expert Collaborative.

What is the population of interest? 

• The population of interest was generally healthy infants and toddlers (ages 0-24 months) who were in studies examining inflammatory bowel disease throughout the lifespan.

What evidence was found? 

• This review includes 13 articles. 
• These articles compared infants who were never fed human milk with infants who were ever fed human milk (i.e., any amount of human milk).
• These articles examined diagnosed inflammatory bowel disease, including Crohn’s disease and ulcerative colitis. 
• With the evidence that is available, it is not possible to conclude whether individuals who were never fed human milk have a different risk of inflammatory bowel disease than individuals who were ever fed human milk.
• There are limitations in the evidence as follows: 
  • The findings are inconsistent.
  • Some of the articles studied groups of people that may have been too small to detect whether there is a relationship between never versus ever feeding human milk and inflammatory bowel disease.
  • It is possible for factors other than infant feeding to impact the outcomes, and these factors were addressed differently by different studies.
  • Most of the studies asked participants and their parents to remember whether or not they had been fed human milk when they were infants, and if participants with inflammatory bowel disease or their parents remembered or reported differently from those without inflammatory bowel disease, it could impact the findings. 

How up-to-date is this systematic review? 

• This review includes literature from 01/1980 to 03/2016.

Background

• This systematic review was conducted as part of the U.S. Department of Agriculture and Department of Health and Human Services Pregnancy and Birth to 24 Months Project.
• The goal of this systematic review was to examine the following question: What is the relationship between never versus ever feeding human milk and inflammatory bowel disease?
• This systematic review examines comparisons of infants who were never fed human milk with infants who were ever fed human milk (i.e., any amount of human milk feeding).  Human milk feeding was defined as feeding human milk alone or in combination with infant formula and/or complementary foods or beverages such as cow’s milk.  Human milk was defined as mother’s own milk provided at the breast (i.e., nursing) or expressed and fed fresh or after refrigeration or freezing.  Donor milk (e.g., banked milk) was not examined in this review. Infant formula was defined as commercially-prepared infant formula meeting FDA and/or Codex Alimentarius international food standards.
• This systematic review examines diagnosed inflammatory bowel disease (including Crohn’s disease and ulcerative colitis), only, to ensure that it addresses the relationship of never versus ever feeding human milk with inflammatory bowel disease and not the relationship of never versus ever feeding human milk with the many other diseases and conditions with similar symptoms

Conclusion Statement and Grade

• Evidence about the relationship between never versus ever being fed human milk and inflammatory bowel disease in offspring is inconclusive. 
  
  Grade: Grade Not Assignable

Methods  

• The systematic review was conducted by a team of staff from the Nutrition Evidence Systematic Review in collaboration with a Technical Expert Collaborative.
• A single literature search was conducted to identify literature for several related systematic reviews that examined infant milk-feeding practices and different outcomes. The search was conducted in CINAHL, Cochrane, Embase, and PubMed, and used a search date range of January 1980 to March 2016. A manual search was done to identify articles that may not have been included in the electronic databases searched. 
• Articles were screened independently by 2 NESR analysts to determine which articles met predetermined criteria for inclusion.
• Data from each included article were extracted, risks of bias were assessed, and both were checked for accuracy. 
• The body of evidence was qualitatively synthesized, a conclusion statement was developed, and the strength of the evidence (grade) was assessed using pre-established criteria including evaluation of the internal validity/risk of bias, adequacy, consistency, impact, and generalizability of available evidence.

Summary of Evidence 

• Thirteen articles met the inclusion criteria for this systematic review, which presented evidence from 1 nested case-control study and 11 independent case-control studies (1 research group presented evidence about Crohn’s disease and ulcerative colitis in the same population in separate articles). 
• The evidence was inconclusive. Three case-control studies found never versus ever feeding human milk is associated with higher risk of Crohn’s disease and of ulcerative colitis, 1 case-control study found that never versus ever feeding human milk is associated with a lower risk of Crohn’s disease. Among the remaining studies, there were some nonsignificant associations with wide confidence intervals (indicative of suboptimal statistical power), most of which were in the direction of never versus ever feeding human milk being associated with higher risk of IBD outcomes, and there were some nonsignificant associations with reasonably narrow confidence intervals (indicative of sufficient statistical power). 
• The evidence had several limitations, including the inconsistency of the findings, insufficient sample sizes for some studies, the potential for confounding, and the retrospective collection of exposure data, which increases the risk of misclassification of the exposure.