Background:

1. Complementary feeding is the process that starts when human milk or infant formula is complemented by other foods and beverages, beginning during infancy and typically continuing to 24 months of age.

2. This systematic review was conducted by a team of Nutrition Evidence Systematic Review (NESR) staff as part of the U.S. Department of Agriculture and Department of Health and Human Services Pregnancy and Birth to 24 Months Project.

3. The goal of this systematic review was to answer the following research question: What is the relationship between types and amounts of complementary foods/beverages and food allergy, atopic dermatitis/eczema, asthma, and allergic rhinitis?

Conclusion Statement and Grade:

1. Peanut, tree nuts, seeds:

   1. ○

      Strong evidence suggests that introducing peanut in the first year of life (after 4 months of age) may reduce risk of food allergy to peanuts. This evidence is strongest for introducing peanut in infants at the highest risk (with severe atopic dermatitis and/or egg allergy) to prevent peanut allergy, but is also applicable to infants at lower risk. However, the evidence for tree nuts and sesame seeds is limited.

   2. ○

      Limited evidence also suggests that there is no relationship between consumption of peanut, tree nuts, or sesame seeds during the complementary feeding period and risk of atopic dermatitis/eczema and asthma.

   3. ○

      There is not enough evidence to determine if there is a relationship between consuming peanut, tree nuts, or seeds as complementary foods and allergic rhinitis.

2. Egg:

   1. ○

      Moderate evidence suggests that introducing egg in the first year of life (after 4 months of age) may reduce risk of food allergy to egg.

   2. ○

      Limited evidence suggests that there is no relationship between the age of introduction to egg and risk of atopic dermatitis/eczema and asthma.

   3. ○

      There is not enough evidence to determine if there is a relationship between consuming egg as a complementary food and allergic rhinitis.

3. Fish:

   1. ○

      Limited evidence suggests that introducing fish in the first year of life (after 4 months of age) may reduce risk of atopic dermatitis/eczema.

   2. ○

      There is not enough evidence to determine if there is a relationship between consuming fish as a complementary food and risk of allergy to fish or other foods, asthma, or allergic rhinitis. There is also not enough evidence to determine if there is a relationship between consuming shellfish as a complementary food and risk of food allergy, atopic dermatitis/eczema, asthma, or allergic rhinitis.

4. Cow’s milk products:

   1. ○

      Limited evidence suggests there is no relationship between age of introduction of cow’s milk products, such as cheese and yogurt, and risk of food allergy and atopic dermatitis/eczema.

   2. ○

      There is not enough evidence to determine if there is a relationship between consuming milk products during the complementary feeding period and risk of asthma or allergic rhinitis.

5. Wheat:

   1. ○

      There is not enough evidence to determine if there is a relationship between wheat consumption during the complementary feeding period and risk of food allergy, atopic dermatitis/eczema, asthma, or allergic rhinitis.

6. Soy:

   1. ○

      There is not enough evidence to determine if there is a relationship between soybean consumption during the complementary feeding period and risk of food allergy, atopic dermatitis/eczema, asthma, or allergic rhinitis.

7. Foods and beverages that are not common allergens:

   1. ○

      Limited evidence from observational studies suggests that introducing foods not commonly considered to be allergens, such as fruits, vegetables, and meat, in the first year of life (after 4 months of age) is not associated with risk of food allergy, atopic dermatitis/eczema, asthma, or allergic rhinitis.

8. Diet diversity and dietary patterns:

   1. ○

      There is not enough evidence to determine a relationship between diet diversity or dietary patterns and risk of food allergy, atopic dermatitis/eczema, asthma, or allergic rhinitis.

Grade: Strong – Peanut; Moderate - Egg; Limited – Fish, cow’s milk products, tree nuts or seeds, foods and beverages that are not common allergens; Grade Not Assignable – Wheat, soy, diet diversity, dietary patterns

Methods:

1. This systematic review was conducted by a team of NESR staff in collaboration with a Technical Expert Collaborative.

2. A literature search was conducted using 4 databases (CINAHL, Cochrane, Embase, and PubMed) to identify articles published from January 1980 to February 2017 that examined the types and/or amounts of complementary foods and beverages (CFB) consumed and food allergy, atopic dermatitis/eczema, asthma, and allergic rhinitis. CFB were defined as foods and beverages other than human milk or infant formula provided to an infant or young child. Outcomes included incidence and prevalence of food allergy, atopic dermatitis/eczema, asthma, and allergic rhinitis. A manual search was done to identify articles that may not have been included in the electronic databases searched. Articles were screened in a dual manner, independently by 2 NESR analysts, to determine which articles met predetermined criteria for inclusion.

3. Data from each included article were extracted, risk of bias was assessed. 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. Research recommendations were identified.

Summary of Evidence:

1. Thirty-nine studies included in this systematic review examined the relationship between consuming specific types of CFB (including amounts, and the age at which the specific CFB were introduced) and risk of food allergies, atopic dermatitis/eczema, asthma, and allergic rhinitis occurring during childhood through 18 years of age. An additional 12 studies examined diet diversity and two studies examined dietary patterns during the complementary feeding period in relation to these outcomes.

2. A number of studies examined consumption of the most common allergenic foods during the complementary feeding period and risk of atopic disease.

   1. ○

      Fourteen studies examined the consumption of peanuts, tree nuts, or seeds during the complementary feeding period in relation to risk of developing atopic disease, including two RCTs. Nine studies (two RCTs) examined food allergy, five studies examined atopic dermatitis/eczema, and two studies examined asthma; no studies were identified that examined risk of allergic rhinitis.

   2. ○

      Twenty-eight studies examined the consumption of eggs as a complementary food in relation to risk of developing any atopic disease, including six RCTs. Thirteen studies (six RCTs) examined food allergies, fifteen studies (one RCT) examined atopic dermatitis/eczema, four studies examined asthma, and five studies examined allergic rhinitis.

   3. ○

      Twenty-four studies examined the consumption of fish as a complementary food in relation to risk of developing atopic disease, including one RCT. Six studies (one RCT) examined food allergies, fifteen studies examined atopic dermatitis/eczema, seven studies examined asthma, and seven studies examined allergic rhinitis.

   4. ○

      Sixteen studies examined the consumption of cow’s milk products, such as cheese and yogurt, during the complementary feeding period in relation to risk of developing atopic disease, including one RCT. Four studies (one RCT) examined food allergies, nine studies examined atopic dermatitis/eczema, three studies examined asthma, and three studies examined allergic rhinitis.

   5. ○

      Eighteen studies, including 1 RCT, 11 PCSs, 5 nested case-control studies, and 1 case-control study, examined the consumption of wheat or cereals (including, but not limited to, wheat cereal) during the complementary feeding period in relation to risk of developing atopic disease. Eight studies examined food allergies, 9 studies examined atopic dermatitis/eczema, 3 studies examined asthma, and 2 studies examined allergic rhinitis.

   6. ○

      Four prospective cohort studies examined the relationship between age of introduction to soy and risk of developing atopic disease. One study examined food allergies, three studies examined atopic dermatitis/eczema, and one study examined asthma.

3. A number of observational studies also examined the relationship between other types of CFB, not considered to be major allergens (e.g., fruit, vegetables, meat), and atopic diseases.

4. The studies that examined diet diversity or dietary patterns were all observational, including 11 prospective cohort studies (from six cohorts) and three case-control studies.

5. Many of the studies included in this review exclusively enrolled or primarily enrolled subjects who were at greater risk of allergies and/or atopic disease than the general population on the basis of family history. However, despite the inclusion of higher risk populations in this body of evidence, the results are probably generalizable to infants and toddlers who are lower risk for atopic disease but the benefit of early introduction on preventing allergy may not be as great.

6. In order to better understand how specific types of foods consumed during infancy and toddlerhood impact risk of developing atopic disease, more research is needed that a) uses randomized, controlled study designs, b) uses valid and reliable measures, c) uses consistent definitions of diet diversity and/or dietary patterns, and assesses these exposures at multiple time points across the complementary feeding period, d)adjusts for key confounders, e) takes into consideration the mechanisms by which specific types of foods may affect risk of developing atopic disease when determining which diet-health relationships to investigate, and what analyses are appropriate, and f) accounts for potential for reverse causality exists due to baseline atopic disease risk status impacting both complementary feeding behaviors and risk of developing atopic disease