What is the question?

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

What is the answer to the question?

• Limited evidence suggests that never versus ever being fed human milk is associated with higher blood pressure, within a normal range, at 6 to 7 years of age. 
  
  Evidence about the relationship of never versus ever being fed human milk with blood lipids in childhood was inconclusive, and there was insufficient evidence to determine the relationship of never versus ever being fed human milk with endpoint cardiovascular disease outcomes, blood pressure and blood lipids in adolescence or adulthood, metabolic syndrome, and arterial stiffness. 

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 cardiovascular disease outcomes from childhood through adulthood (ages 2 years and up).

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 available evidence related to cardiovascular disease outcomes in offspring from childhood through adulthood, including blood lipids, blood pressure, arterial stiffness, metabolic syndrome, cardiovascular disease, and cardiovascular disease-related mortality. 
• Most of the evidence examined blood lipids and blood pressure in childhood.
  • Six- to seven-year-old children who were never fed human milk may have higher blood pressure that is still within a normal range than six- to seven-year-old children who were ever fed human milk. 
  • With the evidence that is available, it is not possible to conclude whether children who were never fed human milk have different levels of blood lipids than children who were ever fed human milk.
• There are limitations in the evidence as follows: 
  • There were not a lot of studies examining any one outcome.
  • There was not a lot of evidence about outcomes beyond childhood; therefore, there was no evidence about cardiovascular disease or cardiovascular disease-related mortality, and there was not a lot of evidence about arterial stiffness and metabolic syndrome.
  • None of the studies were from the United States, and people in the United States may have higher cardiovascular disease risk than people in the countries from which the evidence came. 
  • 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 cardiovascular disease 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 cardiovascular disease outcomes in offspring from childhood through adulthood, including blood lipids, blood pressure, arterial stiffness, metabolic syndrome, cardiovascular disease, and cardiovascular disease-related mortality.

Conclusion Statement and Grade

• Limited evidence suggests that never versus ever being fed human milk is associated with higher blood pressure, within a normal range, at 6 to 7 years of age. 
  
  Evidence about the relationship of never versus ever being fed human milk with blood lipids in childhood was inconclusive, and there was insufficient evidence to determine the relationship of never versus ever being fed human milk with endpoint cardiovascular disease outcomes, blood pressure and blood lipids in adolescence or adulthood, metabolic syndrome, and arterial stiffness. 
  
  Grade: Limited – blood pressure at 6 to 7 years of age; Grade Not Assignable – cardiovascular disease, cardiovascular disease-related mortality, blood lipids, arterial stiffness, metabolic syndrome, blood pressure at ages other than at 6 to 7 years

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, including 4 with evidence about blood lipids, 7 with evidence about blood pressure, 2 with evidence about arterial stiffness, and 1 with evidence about metabolic syndrome (1 article presented evidence for both blood pressure and arterial stiffness). None of the included articles presented evidence about cardiovascular disease or cardiovascular disease-related mortality.
• Evidence about the association between never versus ever feeding human milk and higher blood pressure, within a normal range, at 6 to 7 years of age was limited. Across the 5 independent studies (6 articles) that examined blood pressure in children, 3 found statistically significant associations, and all of them showed that never being fed human milk was associated with higher blood pressure within a normal range. The ability to draw stronger conclusions was primarily limited by the small number of studies, the lack of studies from the United States (where cardiovascular disease risk may be higher), and concerns about internal validity such as the potential for confounding.
• Evidence about blood lipids in childhood was inconclusive. Across 3 independent studies, the only significant association was in a subsample of boys, there were no comparable analyses with which to compare the significant finding, and the nonsignificant associations were inconsistent in direction. 
• Evidence related to outcomes beyond childhood was scant, and no studies examined endpoint health outcomes (i.e., cardiovascular disease and cardiovascular disease-related mortality).