What is the question?

• The question is: What is the relationship between shorter versus longer durations of any human milk feeding and childhood leukemia?

What is the answer to the question?

• Limited but consistent evidence suggests that, among infants fed some amount of human milk, a shorter versus longer duration of any human milk feeding is associated with a slightly higher risk of childhood leukemia. 

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 leukemia in childhood (ages 2-12 years).

What evidence was found? 

• This review includes 8 articles. 
• These articles compared infants fed human milk for shorter durations with infants fed human milk for longer durations. The infants could be fed any amount of human milk.
• These articles examined acute childhood leukemia or acute lymphoblastic leukemia, which is the most common type of acute childhood leukemia.
• Children who were fed human milk for shorter durations may have a slightly higher risk of childhood leukemia than children who were fed human milk for longer durations.
• There are limitations in the evidence as follows: 
  • There were not a lot of articles that studied this relationship, and some of the articles studied groups of children that may have been too small to detect whether there is a relationship between shorter versus longer durations of any human milk feeding and childhood leukemia.
  • Most of the studies asked mothers to remember how long they had fed their children human milk when they were infants, and if mothers of children with leukemia remembered or reported differently from mothers of children without leukemia, 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 shorter versus longer durations of any human milk feeding and childhood leukemia?
• This systematic review examines comparisons of infants who were fed human milk for shorter durations with infants who were fed human milk for longer durations. 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.  
• Childhood leukemia includes acute childhood leukemia, generally, as well as acute lymphoblastic leukemia, specifically.

Conclusion Statement and Grade

• Limited but consistent evidence suggests that, among infants fed some amount of human milk, a shorter versus longer duration of any human milk feeding is associated with a slightly higher risk of childhood leukemia. 
  
  Grade: Limited

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 

• Eight articles met the inclusion criteria for this systematic review, which presented evidence from 8 case-control studies. 
• The notable feature of this body of evidence was its consistency in the direction of the associations across most of the studies. Two of the 8 studies reported statistically significant associations that suggested that shorter versus longer durations of any human milk feeding are associated with higher risk of childhood leukemia. Further, the majority of non-significant associations, some of which had wide confidence intervals indicative of suboptimal statistical power, were consistent in direction with the significant associations.  
• The ability to draw stronger conclusions was primarily limited by the small number of studies, insufficient sample sizes, and the retrospective collection of exposure data, which increases the risk of misclassification of the exposure.