What is the question?

• The question is: What is the relationship between iron from supplements consumed during infancy and toddlerhood and growth, size, and body composition? 

What is the answer to the question?

• Moderate evidence indicates that human milk-fed infants who are supplemented with iron do not have greater growth, and may have slower growth, than human milk-fed infants not supplemented with iron.
• Insufficient evidence is available to determine the relationship between iron from supplements consumed during infancy and body composition during infancy.
• Insufficient evidence is available to determine the relationship between iron from supplements consumed during infancy and growth, size, and body composition beyond age 12 months. 
• Insufficient evidence is available to determine the relationship between iron from supplements consumed after age 12 months and growth, size, and body composition.

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? 

• Iron supplementation was examined in healthy infants and toddlers (birth to 24 months) with outcomes measured at any age.

What evidence was found? 

• This review includes 10 articles.
• The articles examined infants and toddlers who consumed iron from supplements. Most studies compared infants who consumed iron from supplements with infants who did not consume iron from supplements. Fewer studies compared infants who consumed iron from supplements with infants who consumed different dosages of iron from supplements or iron from fortified foods. 
• The outcomes of interest were growth, size, and body composition at any age, however the articles only examined growth and size and almost all of the outcomes were measured during infancy.
• The evidence indicated that infants fed human milk who are supplemented with iron do not have greater growth, and may have slower growth, than infants not supplemented with iron.
• There are limitations in the evidence as follows:
  • There were not a lot of articles, and some of the articles studied groups of infants and toddlers that may have been too small to detect a relationship between iron supplementation and growth or size.
  • The studies differed from one another in some important ways, such as the timing of iron supplementation, infants’ consumption of iron-fortified infant formula or iron-rich foods, and the study populations examined, which may have had differences in risk. 

How up-to-date is this systematic review?

• This review searched for studies from January 2000 to January 2020 

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 iron from supplements consumed during infancy and toddlerhood and growth, size, and body composition?

Conclusion statements and grades

• Moderate evidence indicates that human milk-fed infants who are supplemented with iron do not have greater growth, and may have slower growth, than human milk-fed infants not supplemented with iron. (Grade: Moderate)
• Insufficient evidence is available to determine the relationship between iron from supplements consumed during infancy and body composition during infancy. (Grade: Grade not assignable)
• Insufficient evidence is available to determine the relationship between iron from supplements consumed during infancy and growth, size, and body composition beyond age 12 months. (Grade: Grade not assignable)
• Insufficient evidence is available to determine the relationship between iron from supplements consumed after age 12 months and growth, size, and body composition. (Grade: Grade not assignable)

Methods

• A literature search was conducted using 4 databases (PubMed, Embase, CINAHL, and Cochrane) to identify articles that evaluated the intervention or exposure of iron from supplements consumed during infancy and toddlerhood and growth, size, and body composition outcomes. A manual search was conducted to identify articles that may not have been included in the electronic databases searched. Articles were screened by two 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

• Ten articles met the inclusion criteria for this systematic review, which presented evidence from 8 randomized controlled trials, 1 non-randomized controlled trial, and 1 study that did not clearly describe its prospective study design. 
• The intervention or exposure of interest was iron from supplements consumed during infancy and toddlerhood. Dietary supplements are products that contain one or more dietary ingredients (in this case, iron) intended to be taken by mouth to supplement the diet. Nine studies examined iron supplementation during infancy, and only 1 study examined iron supplementation during toddlerhood.
• The comparators of interest were different dosages of iron from supplements and iron from fortified foods. 
• The outcomes of interest were measures of growth, size, and body composition at any age. However, no articles were identified that examined outcomes beyond 24 months. The articles presented evidence about growth (i.e., change in size between birth or baseline and follow-up) and size (i.e., attained size at follow-up). However, no articles presented evidence about body composition (e.g., percent fat mass, skinfold thickness). 
• Moderate evidence, from 5 studies that compared iron from supplements with no iron from supplements, indicated that human milk-fed infants who are supplemented with iron do not have greater growth, and may have slower growth, than human milk-fed infants not supplemented with iron. Inconsistencies in the evidence may be explained by differences in the risk of iron deficiency between the populations studied, differences in participants’ consumption of iron-fortified formula or iron-rich foods, and differences in the timing of iron supplementation. This heterogeneity, the small number of studies, and the small sample sizes, were the primary factors limiting the ability to draw stronger conclusions. 
• Evidence available from 3 studies was insufficient to determine whether a relationship exists between iron from supplements, compared with a different dosage or duration of iron from supplements, and growth or size, because the studies used heterogeneous interventions that could not be compared.
• Evidence available from 2 studies was insufficient to determine whether a relationship exists between iron from supplements, compared with iron from fortified foods, and growth or size, because the studies used heterogeneous interventions that could not be compared.