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 nutrient status?

What is the answer to the question?

• Moderate evidence indicates that ever, compared with never, consuming human milk may be associated with fatty acid status from birth to 24 months. However, the difference in fatty acid status between infants fed human milk and infants fed infant formula is likely to depend on the composition of the human milk and infant formula consumed. Insufficient evidence is available to determine the relationship between ever, compared with never, consuming human milk and iron and zinc status from birth to 24 months. No evidence is available to determine the relationship between ever, compared with never, consuming human milk and iodine, vitamin B12, and vitamin D status from birth to 24 months.
• Insufficient evidence is available to determine the relationship between the duration of any human milk consumption, among infants fed human milk, and iron, zinc, vitamin D, and fatty acid status from birth to 24 months. No evidence is available to determine the relationship between the duration of any human milk consumption, among infants fed human milk, and iodine or vitamin B12 status from birth to 24 months.
• Insufficient evidence is available to determine the relationship between the duration of exclusive human milk consumption before the introduction of infant formula and fatty acid status. No evidence is available to determine the relationship between the duration of exclusive human milk consumption before the introduction of infant formula and iron, zinc, iodine, vitamin B12, or vitamin D status from birth to 24 months. 
• No evidence is available to determine the relationship between the intensity, proportion, or amount of human milk consumed by mixed-fed infants and iron, zinc, iodine, vitamin B12, vitamin D, or fatty acid status from birth to 24 months.

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 population of interest was generally health infants and toddlers (birth to 24 months).

What evidence was found? 

• This review includes 23 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.
• These articles examined available evidence related to iron, zinc, iodine, vitamin D, vitamin B12, and fatty acid status.
• Most evidence compared fatty acid status between infants who ever and never consumed human milk. Infants who ever consume human milk and infants who never consume human milk (i.e., formula-fed infants) may have differences in fatty acid status. The difference in fatty acid status probably depends on infant formula ingredients and human milk composition.
• There are limitations in the evidence as follows:
  • There was not a lot of evidence about infants who consumed human milk for different durations, infants who consumed human milk exclusively for different durations before infant formula was added to their diets, iron status, zinc status, and vitamin D status. There was no evidence about mixed-fed infants who consumed different amounts of human milk, iodine status, and vitamin B12 status.
  • Most studies were designed to examine the effect of new infant formula ingredients and not the systematic review question.
  • Some of the infant formulas used in the studies may be different from infant formulas currently sold in the United States. 
  • 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 searched for studies from January, 1980 to 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 nutrient status? 

Conclusion statements and grades

Ever vs never consuming human milk

• Moderate evidence indicates that ever, compared with never, consuming human milk may be associated with fatty acid status from birth to 24 months. However, the difference in fatty acid status between infants fed human milk and infants fed infant formula is likely to depend on the composition of the human milk and infant formula consumed. (Grade: Moderate)
• Insufficient evidence is available to determine the relationship between ever, compared with never, consuming human milk and iron and zinc status from birth to 24 months. No evidence is available to determine the relationship between ever, compared with never, consuming human milk and iodine, vitamin B12, and vitamin D status from birth to 24 months. (Grade: Grade not assignable)

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 iron, zinc, vitamin D, and fatty acid status from birth to 24 months. No evidence is available to determine the relationship between the duration of any human milk consumption, among infants fed human milk, and iodine or vitamin B12 status from birth to 24 months. (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 fatty acid status. No evidence is available to determine the relationship between the duration of exclusive human milk consumption before the introduction of infant formula and iron, zinc, iodine, vitamin B12, or vitamin D status from birth to 24 months. (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 iron, zinc, iodine, vitamin B12, vitamin D, or fatty acid status from birth to 24 months. (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, respectively. The searches used 4 databases (PubMed, Cochrane, Embase, and CINAHL) to identify articles that evaluated the intervention or exposure of the duration, frequency, and volume of exclusive human milk and/or infant formula consumption and the outcomes of iron, zinc, iodine, vitamin B12, vitamin D, and fatty acid status. 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. 
• 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 conclusion statements, 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 examines the relationship between the duration, frequency, and volume of exclusive human milk and/or infant formula consumption and nutrient status. Specifically, this systematic review examines available evidence that compares:

  • 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, and 
  • 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. 
• 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 iron status (including iron deficiency and anemia), zinc status, iodine status, vitamin B12 status, vitamin D status, and fatty acid status. 
• This review identified 23 articles. 
  • Iron status: Ten articles, published between 1990 and 2019, examined the relationships of (a) ever, compared with never, consuming human milk, and (b) different durations of any human milk consumption, among infants fed human milk, with iron status from birth to 24 months. 
    • (a) The evidence available from 2 studies did not show a consistent association between ever, compared with never, consuming human milk and anemia. The evidence available from 5 studies did not show consistent associations between ever, compared with never, consuming human milk and hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, red cell distribution width, serum ferritin, or serum iron.
    • (b) The evidence available from 3 studies did not show a consistent association between the duration of any human milk consumption, among infants fed human milk, and iron deficiency or anemia. The evidence available from 4 studies did not show consistent associations between the duration of any human milk consumption, among infants fed human milk, and hemoglobin, hematocrit, serum ferritin, serum iron, mean corpuscular volume, transferrin receptor, or transferrin saturation.
  • Zinc status: Five articles, published between 1986 and 1994, examined the relationships of (a) ever, compared with never, consuming human milk, and (b) different durations of any human milk consumption, among infants fed human milk, with zinc status from birth to 24 months. 
    • (a) The evidence available from 4 studies did not show a consistent association between ever, compared with never, consuming human milk and zinc status.
    • (b) The evidence available from 2 studies was insufficient to determine whether there is an association between the duration of any human milk consumption, among infants fed human milk, and zinc status.
  • Vitamin D status: One article, published in 2014, examined the relationship between the duration of any human milk consumption, among infants fed human milk, and vitamin D status from birth to 24 months. This evidence was insufficient to determine whether there is an association between the duration of any human milk consumption, among infants fed human milk, and vitamin D status.
  • Fatty acid status: Nine articles, published between 1986 and 2016, examined the relationships of (a) ever, compared with never, consuming human milk, (b) different durations of any human milk consumption, among infants fed human milk, and (c) different durations of exclusive human milk consumption before the introduction of infant formula with fatty acid status from birth to 24 months.
    • (a) The evidence available from 7 studies was moderately consistent in showing that ever, compared with never, consuming human milk is related to fatty acid status, but the direction and strength of associations can vary depending on the composition of the infant formula fed to participants who never consumed human milk (and also likely due to the composition of human milk, although this could not be assessed), as well as the specific types of fatty acids examined in the blood.
    • (b) The evidence available from 1 study was insufficient to determine whether an association exists between the duration of any human milk consumption, among infants fed human milk, and fatty acid status.
    • (c) The evidence available from 1 study was insufficient to determine whether an association exists between the duration of exclusive human milk consumption before the introduction of infant formula and fatty acid status.
  • No studies met the inclusion criteria that examined iodine status or vitamin B12 status.
• The ability to draw stronger conclusions was primarily limited by:
  • The small number of studies that presented evidence on each topic, 
  • The study designs, as most studies were designed to examine the effect of novel infant formula compositions rather than differences in outcomes between infants ever and never fed human milk,
  • Concerns about the generalizability of the evidence to U.S. infants consuming infant formulas currently on the market, and 
  • Concerns about the potential for bias, especially bias due to confounding.