What is the question?

• The question is: What is the relationship between never versus ever feeding human milk and diabetes outcomes in offspring?

What is the answer to the question?

• Limited evidence from observational studies suggests that never versus ever being fed human milk is associated with higher risk of type 1 diabetes. 
  
  There is insufficient evidence to determine whether or not there is a relationship between never versus ever feeding human milk and type 2 diabetes, prediabetes, fasting glucose, HbA1C, insulin resistance, and glucose tolerance throughout the lifespan.

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 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 diabetes outcomes throughout the lifespan.

What evidence was found? 

• This review includes 21 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 available evidence related to diabetes outcomes in offspring, including fasting glucose, HbA1C, glucose tolerance/insulin resistance, and the incidence and prevalence of prediabetes, type 1 diabetes, and type 2 diabetes. 
• Most of the evidence examined type 1 diabetes.
  • Individuals who were never fed human milk may have higher type 1 diabetes risk than individuals who were ever fed human milk. 
• There are limitations in the evidence as follows: 
  • There were not a lot of studies examining type 2 diabetes or intermediate diabetes outcomes such as fasting glucose, HbA1C, and insulin resistance.
  • 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 type 1 diabetes in offspring.
  • Most of the studies asked mothers to remember whether or not they had fed their offspring human milk when they were infants, and if mothers of individuals with type 1 diabetes remembered or reported differently from mothers of individuals without type 1 diabetes, it could impact the findings.
  • It is possible for factors other than infant feeding to impact the outcomes, and these factors were addressed differently by different studies.

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 diabetes outcomes in offspring?
• 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 available evidence related to diabetes outcomes in offspring, including fasting glucose, HbA1C, glucose tolerance/insulin resistance, and the incidence and prevalence of prediabetes, type 1 diabetes, and type 2 diabetes.

Conclusion Statement and Grade

• Limited evidence from observational studies suggests that never versus ever being fed human milk is associated with higher risk of type 1 diabetes. 
  
  There is insufficient evidence to determine whether or not there is a relationship between never versus ever feeding human milk and type 2 diabetes, prediabetes, fasting glucose, HbA1C, insulin resistance, and glucose tolerance throughout the lifespan.
  
  Grade: Limited – type 1 diabetes; Grade Not Assignable – type 2 diabetes, prediabetes, fasting glucose, HbA1C, insulin resistance, glucose tolerance

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 

• Twenty-one articles met the inclusion criteria for this systematic review, including 16 with evidence about type 1 diabetes, 2 with evidence about type 2 diabetes, and 3 with evidence about the intermediate diabetes outcomes fasting glucose, HbA1C, and insulin resistance.  
• Evidence about the association between never versus ever feeding human milk and higher risk of type 1 diabetes was limited. Across the 15 independent studies (16 articles) that examined type 1 diabetes, 6 found statistically significant associations. The primary difference between the studies that did and did not report significant associations was statistical power. With 1 exception, the statistically significant associations suggested that never versus ever being fed human milk is associated with higher risk of type 1 diabetes. The ability to draw stronger conclusions was primarily limited by insufficient sample sizes, concerns about internal validity such as the potential for confounding, and the retrospective collection of exposure data, which increases the risk of misclassification of the exposure. 
• Evidence related to type 2 diabetes and intermediate diabetes outcomes (e.g., fasting glucose, HbA1C, and insulin resistance) was scant.