What is the question?

• The question is: What is the relationship between the duration, frequency, and volume of exclusive human milk and/or infant formula consumption and overweight and obesity?

What is the answer to the question?

• Moderate evidence from observational studies indicates that ever, compared with never, consuming human milk is associated with lower risk of overweight and obesity at 2 years of age and older, particularly if the duration of human milk consumption is 6 months or longer. 
• Insufficient evidence is available to determine the relationship between the duration of any human milk consumption, among infants fed human milk, and overweight and obesity at 2 years of age and older; the available evidence was inconsistent.
• Insufficient evidence is available to determine the relationship between the duration of exclusive human milk consumption prior to the introduction of infant formula and overweight and obesity at 2 years of age and older.
• No evidence is available to determine the relationship between the intensity, proportion, or amount of human milk consumed by mixed-fed infants and overweight and obesity at 2 years of age and older.
• No evidence is available to determine the relationship between the intensity, proportion, or amount of human milk consumed at the breast vs by bottle in infants fed human milk as their only source of milk and overweight and obesity at 2 years of age and older. 
• No evidence is available to determine the relationship between consuming human milk or infant formula (i.e., a single substance) vs human milk and infant formula (i.e., both substances, e.g., “topping up”) during a single feeding session and overweight and obesity at 2 years of age and older.

Why was this question asked?

• This important public health question was identified by the U.S. Departments of Agriculture (USDA) and Health and Human Services (HHS) to be examined by the 2020 Dietary Guidelines Advisory Committee.

How was this question answered?

• The 2020 Dietary Guidelines Advisory Committee, Birth to 24 Months Subcommittee conducted a systematic review to answer this question with support from the Nutrition Evidence Systematic Review (NESR) team.

What is the population of interest? 

• The systematic review studied 2 different populations. The first was generally healthy infants and toddlers (birth to 24 months) who were fed human milk and/or infant formula and who had overweight and obesity outcomes examined at 2 years of age or older. The second was generally healthy siblings who were fed differently during infancy or who had different outcomes, or both, and who had rapid weight gain examined between birth and 24 months and/or BMI, body composition, overweight or obesity examined at 2 years of age or older. 

What evidence was found? 

• This review includes 42 articles. 
• The review examined available evidence about:
  • Infants who ever consumed milk (i.e., any amount of human milk) compared with infants who never consumed human milk,
  • Infants who consumed human milk (i.e., any amount of human milk) for different durations, 
  • Infants who consumed human milk exclusively for different durations before infant formula was added to their diets, and 
  • Mixed-fed infants (i.e., consuming both human milk and infant formula, but not complementary foods and beverages) who consumed different amounts of human milk.
  • Infants who consumed human milk as their only source of milk and who consumed different intensities, proportions, or amounts of human milk at the breast versus by bottle, and
  • Mixed-fed infants who consumed a single substance at a single feeding session (i.e., either human milk or infant formula) with mixed-fed infants who consumed both substances at a single feeding session (e.g., “topping up”).
• These articles examined available evidence related to overweight and obesity at 2 years of age and older and, for siblings, about rapid weight gain from birth to 24 months, BMI, and body composition at 2 years of age and older.
• Most evidence examined overweight and obesity in infants who ever consumed human milk compared to infants who never consumed human milk, or in infants who consumed human milk for different durations.
  • Infants who ever consume human milk, and especially infants who consume human milk for 6 months or longer, may have lower risk of overweight and obesity throughout life than infants who never consume human milk. The findings may be due, in part, to factors other than infant feeding that also impact overweight and obesity. 
  • It is not clear whether infants who consume human milk for different durations have different risk of overweight and obesity at 2 years of age and older. The evidence was inconsistent.
• There was not a lot of evidence about infants who consumed human milk exclusively for different durations before infant formula was added to their diets. There was no evidence about infants who consumed human milk at the breast compared to by bottle, or about mixed-fed infants who consumed different amounts of human milk or who consumed human milk and infant formula during the same feeding session compared to during different feeding sessions. 

How up-to-date is this systematic review?

• This review searched for studies published between January 2011 and September 2019 and additional sibling studies published between January 1980 and September 2019. 

Background

• This important public health question was identified by the U.S. Departments of Agriculture (USDA) and Health and Human Services (HHS) to be examined by the 2020 Dietary Guidelines Advisory Committee.
• The 2020 Dietary Guidelines Advisory Committee, Birth to 24 Months Subcommittee, conducted a systematic review to answer this question with support from the Nutrition Evidence Systematic Review (NESR) team.
• The goal of this systematic review was to examine the following question: What is the relationship between the duration, frequency, and volume of exclusive human milk and/or infant formula consumption and overweight and obesity? 

Conclusion statements and grades

• Ever vs never consuming human milk
  • Moderate evidence from observational studies indicates that ever, compared with never, consuming human milk is associated with lower risk of overweight and obesity at ages 2 years and older, particularly if the duration of human milk consumption is 6 months or longer. (Grade: Moderate)
• Duration of any human milk consumption among infants fed human milk
  • Insufficient evidence is available to determine the relationship between the duration of any human milk consumption, among infants fed human milk, and overweight and obesity at ages 2 years and older; the available evidence was inconsistent. (Grade: Grade not assignable)
• Duration of exclusive human milk consumption before the introduction of infant formula
  • Insufficient evidence is available to determine the relationship between the duration of exclusive human milk consumption before the introduction of infant formula and overweight and obesity at ages 2 years and older. (Grade: Grade not assignable)
• Intensity, proportion, or amount of human milk consumed by mixed-fed infants
  • No evidence is available to determine the relationship between the intensity, proportion, or amount of human milk consumed by mixed-fed infants and overweight and obesity at ages 2 years and older. (Grade: Grade not assignable)
• Intensity, proportion, or amount of human milk consumed at the breast vs by bottle in infants fed human milk as their only source of milk
  • No evidence is available to determine the relationship between the intensity, proportion, or amount of human milk consumed at the breast vs by bottle in infants fed human milk as their only source of milk and overweight and obesity at ages 2 years and older. (Grade: Grade not assignable)
• Consuming human milk or infant formula (i.e., a single substance) vs human milk and infant formula (i.e., both substances) during a single feeding session
  • No evidence is available to determine the relationship between consuming human milk or infant formula (i.e., a single substance) vs human milk and infant formula (i.e., both substances, e.g., “topping up”) during a single feeding session and overweight and obesity at ages 2 years and older. (Grade: Grade not assignable)

Methods

• Two literature searches were conducted to identify articles published from January 1980 to March 2016, and from March 2016 to September 2019. The searches used 4 databases (PubMed, Embase, CINAHL, and Cochrane).  A manual search was conducted to identify articles that may not have been included in the electronic databases searched. 
• Articles were screened by 2 NESR analysts independently for inclusion based on pre-determined criteria. Articles published between 2011 and 2019 were included if they met the pre-determined criteria and examined human milk and infant formula exposures from birth to 24 months and the outcomes of overweight and obesity at 2 years of age and older. Additional articles, published between 1980 and 2011, were included if they met the pre-determined criteria and compared siblings within the same family. Sibling studies are unique because they reduce the risk of bias from confounding from genetic and environmental factors that siblings share. 
• Data extraction and risk of bias assessment were conducted for each included study, and both were checked for accuracy. 
• The Committee qualitatively synthesized the body of evidence to inform development of a conclusion statement, and graded the strength of evidence using pre-established criteria for risk of bias, consistency, directness, precision, and generalizability.

Summary of the evidence

• This systematic review examined the relationship between the duration, frequency, and volume of exclusive human milk and/or infant formula consumption and overweight and obesity. Specifically, this systematic review examined available evidence that compared:
  • Infants who ever consumed milk (i.e., any amount of human milk) with infants who never consumed human milk,
  • Infants who consumed human milk (i.e., any amount of human milk) for different durations, 
  • Infants who consumed human milk exclusively for different durations before the introduction of infant formula, 
  • Mixed-fed infants (i.e., consuming both human milk and infant formula, but not complementary foods and beverages) who consumed different intensities, proportions, or amounts of human milk,
  • Infants who consumed human milk as their only source of milk and who consumed different intensities, proportions, or amounts of human milk at the breast versus by bottle, and
  • Mixed-fed infants who consumed a single substance at a single feeding session (i.e., either human milk or infant formula) with mixed-fed infants who consumed both substances at a single feeding session (e.g., “topping up”).
• Human milk refers to mother’s own milk provided at the breast (i.e., nursing) or expressed and fed fresh or after refrigeration or freezing. Examinations of donor milk are not included in this review. Exclusive human milk consumption refers to consuming human milk alone and not in combination with infant formula or complementary foods and beverages. Infant formula refers to commercially prepared infant formula meeting the FDA and/or Codex Alimentarius international food standards. Complementary foods and beverages are foods and beverages other than human milk or infant formula (liquids, semisolids, and solids) provided to an infant or young child to provide nutrients and energy.
• The outcomes of interest were overweight and obesity at ages 2 years and older. Available evidence about rapid weight gain from birth to 24 months and BMI and body composition at ages 2 years and older were also examined from studies that conducted within-family analyses of discordant siblings (i.e., siblings fed differently during infancy, siblings with differences in outcome status, or both).
• This review identified 42 articles that met the inclusion criteria. Thirty of the 42 articles presented evidence about ever, compared with never, consuming human milk, and 21 of the 42 articles presented evidence about different durations of any human milk consumption (i.e. some articles presented evidence about both exposures).
• The 30 articles that examined the relationship between ever, compared with never, consuming human milk, and overweight and/or obesity at ages 2 years and older presented evidence from 21 independent cohorts. 
  • The evidence had strong consistency. Fourteen of the 21 studies found significant associations and all of them showed that ever, compared with never, consuming human milk is associated with lower risk of overweight and/or obesity at ages 2 years and older. One study showed a marginal association in the same direction, and some of the remaining studies were underpowered. 
  • The evidence available from 5 of 7 studies that compared infants who consumed human milk for different durations with infants who never consumed human milk suggested that a longer duration of human milk consumption (e.g., ≥6 months) is most likely to be associated with reduced risk of overweight or obesity, compared to never consuming human milk.
  • In 4 studies, the investigators conducted within-family analyses of siblings, which are designed to reduce bias due to confounding from genetic and environmental factors (factors that siblings share). Some of these analyses showed an attenuation of the significant associations found in full-sample analyses, suggesting that confounding may explain some of the association between ever, compared with never, consuming human milk and overweight and/or obesity at ages 2 years and older. 
  • The ability to draw stronger conclusions was primarily limited by the potential for confounding in a body of evidence made up of observational studies, and some concerns about the generalizability of the evidence from the studies conducted outside the United States (because U.S. populations may have higher risk of overweight and obesity than do the populations sampled for the non-U.S. studies). 
• The 21 articles that examined the relationship between the duration of any human milk consumption, among infants fed human milk, and overweight and/or obesity at ages 2 years and older presented evidence from 1 cluster randomized controlled trial and 18 independent cohorts. 
  • The evidence was inconclusive. Nine of the 19 studies reported significant associations, but they were inconsistent in direction. In addition, potential bias from confounding and the limited generalizability of the evidence from the non-U.S. studies raised concerns (in particular because the prevalence of obesity among the participants of the cluster randomized controlled trial, conducted in Belarus, was much lower than the prevalence among youth in the United States).
• Evidence available from 2 studies was insufficient to determine the relationship between the duration of exclusive human milk consumption before the introduction of infant formula and overweight and/or obesity at ages 2 years and older.
• No studies were identified that examined the intensity, proportion, or amount of human milk consumed by mixed-fed infants, the intensity, proportion, or amount of human milk consumed at the breast versus by bottle, or consuming a single substance (i.e., either human milk or infant formula) versus both human milk and infant formula during a single feeding session.