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 childhood leukemia?
• 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.

• Childhood leukemia includes acute childhood leukemia, generally, as well as acute lymphoblastic leukemia, specifically.

Conclusion statement and grade

• Limited evidence suggests that never versus ever being fed human milk is associated with a slightly higher risk of childhood leukemia. The evidence comparing never being fed human milk with being fed human milk for short durations (i.e., < 6 months) and risk of childhood leukemia is mixed. However, the evidence comparing never being fed human milk with being fed human milk for long durations (i.e., ≥ 6 months) is mostly consistent and 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

• Nineteen articles met the inclusion criteria for this systematic review, which presented evidence from 15 independent case-control studies and 1 retrospective cohort study.
• Five of the 16 studies reported statistically significant associations. The evidence from these 5 studies is consistent and suggests that never versus ever being fed human milk is associated with a higher risk of childhood leukemia. Some of the studies in the body of evidence compared never being fed human milk with being fed human milk for specific durations. The evidence comparing never being fed human milk with being fed human milk for shorter-term durations (i.e., < 6 months) and risk of childhood leukemia is mixed. However, the evidence comparing never being fed human milk with being fed human milk for longer-term durations (i.e., ≥ 6 months) is mostly consistent and is associated with a slightly higher risk of childhood leukemia. Further, the majority of nonsignificant associations are consistent in direction with the significant associations and some of the inconsistency in statistical significance is likely due to inadequate statistical power.
• The ability to draw stronger conclusions was primarily limited by insufficient sample sizes and the retrospective collection of exposure data, which increases the risk of misclassification of the exposure.