What is the question?

• The question is: What is the relationship between shorter versus longer durations of exclusive human milk feeding and diabetes outcomes in offspring?

What is the answer to the question?

• Limited evidence from observational studies suggests that shorter versus longer durations of exclusive human milk feeding are associated with higher risk of type 1 diabetes. Limited evidence, from a single study that used a strong design, also suggests that the duration of exclusive human milk feeding is not associated with fasting glucose or insulin resistance at 11.5 years of age.
  
  There is insufficient evidence to determine whether or not there is a relationship between shorter versus longer durations of exclusive human milk feeding and type 2 diabetes, prediabetes, and HbA1c throughout the lifespan, and fasting glucose and insulin resistance at ages other than 11.5 years

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 diabetes outcomes throughout the lifespan.

What evidence was found? 

• This review includes 18 articles. 
• These articles compared infants fed human milk exclusively for shorter durations with infants fed human milk exclusively for longer durations. 
• 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. 
• Almost all of the evidence examined type 1 diabetes. One study that used a strong design examined fasting glucose and insulin resistance at 11.5 years of age.
  • Individuals who were fed human milk exclusively for shorter durations may have higher type 1 diabetes risk than individuals who were fed human milk exclusively for longer durations. 
  • Individuals who were fed human milk exclusively for shorter durations and individuals who were fed human milk exclusively for longer durations do not seem to have differences in fasting glucose or insulin resistance at 11.5 years of age.
• There are limitations in the evidence as follows: 
  • No studies examined type 2 diabetes and only one study examined intermediate diabetes outcomes.
  • Some of the articles studied groups of people that may have been too small to detect whether there is a relationship between shorter versus longer durations of exclusive human milk feeding and type 1 diabetes in offspring. 
  • Most of the studies asked mothers to remember how long they had fed their offspring human milk exclusively 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.
  • There was no evidence from the U.S. about fasting glucose or insulin resistance, and metabolic risk in the U.S. may be higher than it is in the population with available evidence.

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 shorter versus longer durations of exclusive human milk feeding and diabetes outcomes in offspring?
• This systematic review examines comparisons of infants who were fed human milk exclusively for shorter durations with infants who were fed human milk exclusively for longer durations. Exclusive human milk feeding was defined as feeding human milk alone and not in combination with infant formula and/or complementary foods or beverages such as cow’s milk. This definition is inclusive of the World Health Organization definitions of exclusive and predominant breastfeeding, which permit limited quantities of (a) drops or syrups containing vitamins, minerals, or medicines, (b) water and water-based drinks such as sweetened water and teas, (c) fruit juice, (d) oral rehydration salts solution, and (e) ritual fluids . 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. 
• 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 shorter versus longer durations of exclusive human milk feeding are associated with higher risk of type 1 diabetes. Limited evidence, from a single study that used a strong design, also suggests that the duration of exclusive human milk feeding is not associated with fasting glucose or insulin resistance at 11.5 years of age.
  
  There is insufficient evidence to determine whether or not there is a relationship between shorter versus longer durations of exclusive human milk feeding and type 2 diabetes, prediabetes, and HbA1c throughout the lifespan, and fasting glucose and insulin resistance at ages other than 11.5 years
  
  Grade: Limited –fasting glucose and insulin resistance at age 11.5 years, type 1 diabetes; Grade Not Assignable – fasting glucose and insulin resistance at ages other than 11.5 years, type 2 diabetes, prediabetes, HbA1C

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 

• Eighteen articles met the inclusion criteria for this systematic review, including 17 with evidence about type 1 diabetes, and 1 with evidence about fasting glucose and insulin resistance. 
• Evidence about the association between shorter versus longer durations of exclusive human milk feeding and higher risk of type 1 diabetes was limited. Seven studies found significant associations, all of which were inverse associations between the duration of exclusive human milk feeding and type 1 diabetes risk. However, some of the studies most likely to have sufficient statistical power found nonsignificant associations. The ability to draw stronger conclusions was primarily limited by this inconsistency, insufficient sample sizes for some of the studies, 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 about the lack of an association between the duration of exclusive human milk feeding and fasting glucose and insulin resistance at 11.5 years of age was also limited. One cluster randomized controlled trial provided strong evidence. The ability to draw stronger conclusions was limited by only having 1 study and because the study was not conducted in the United States where metabolic risk may be higher.
• There was no evidence related to type 2 diabetes, prediabetes, and HbA1C, or about fasting glucose and insulin resistance outside of age 11.5 years.