Cow’s milk alternatives for children with cow’s milk allergy and beyond

Abstract

Cow’s milk allergy (CMA) is one of the most common food allergies in the first years of life, with worldwide prevalence estimated to range from 2% to 5%. While the majority of children with CMA will eventually develop tolerance to cow’s milk proteins (it is estimated that >75% of children with CMA develop tolerance to cow’s milk proteins by the age of 3 years, and >90% develop tolerance by the age of 6 years), the selection of an appropriate cow’s milk (CM) alternative for those with CMA is vital to ensure adequate growth and development during childhood. The increasing number of CM alternative products on the commercial market with markedly different nutritional content and micronutrient fortification adds a layer of complexity that can be challenging for both families and clinicians to navigate. This article aims to provide guidance and clarity to Canadian paediatricians and primary care clinicians on recommending the most appropriate, safe, and nutritionally optimal CM alternatives for individuals with CMA, and beyond.

Cow’s milk allergy (CMA) is one of the most common food allergies in the first years of life, with worldwide prevalence estimated to range from 2% to 5% (1–3). While the majority of children with CMA will eventually develop tolerance to cow’s milk proteins (it is estimated that >75% of children with CMA develop tolerance to cow’s milk proteins by the age of 3 years, and >90% develop tolerance by the age of 6 years) (4), the selection of an appropriate cow’s milk (CM) alternative for those with CMA is vital to ensure adequate growth and development during childhood. The increasing number of CM alternative products on the commercial market with markedly different nutritional content and micronutrient fortification adds a layer of complexity that can be challenging for both families and clinicians to navigate. This article aims to provide guidance and clarity to Canadian paediatricians and primary care clinicians on recommending the most appropriate, safe, and nutritionally optimal CM alternatives for individuals with CMA, and beyond.

DIFFERENTIATION OF COW’S MILK ALLERGY (CMA) SUBTYPES

The nomenclature of CMA can lead to confusion, as ‘cow’s milk protein allergy’ is commonly used by clinicians and families to describe both immunoglobulin E (IgE)-mediated and non-IgE-mediated CMA. This leads to confusion as the disease process, natural history, and subsequent management of these conditions is very different. The classification of CMA has been widely published (5,6), and will not be reviewed in detail.

In brief, IgE-mediated CMA occurs within minutes to 2 hours from the time of ingestion and can affect many body systems. The most common symptoms are cutaneous, including urticaria (1). IgE-mediated CMA typically occurs in CM formula-fed infants or when introducing complementary foods in breastfed infants. Concentrations of CM protein in breast milk are low enough that they typically do not trigger an IgE-mediated reaction (5).

Non-IgE-mediated allergy typically presents as delayed, isolated gastrointestinal symptoms. The spectrum of non-IgE-mediated allergy is broad, with symptoms ranging in severity from mild bloody stools in an otherwise thriving infant (as seen in food protein induced allergic proctocolitis; FPIAP) to acute severe vomiting resulting in dehydration (as seen in food protein-induced enterocolitis syndrome; FPIES) (6).

RECOMMENDATIONS FOR INFANT FEEDING IN THE FIRST 2 YEARS OF LIFE

For healthy, term infants, the Canadian Paediatric Society (CPS) recommends exclusive breastfeeding for the first 6 months of life and supports breastfeeding for up to 2 years and beyond (7). Further, the CPS recently reaffirmed the recommendation of promoting and supporting breastfeeding regardless of issues related to food allergy prevention (i.e., the early introduction of allergens for the prevention of food allergy among infants at high risk) (8). For infants in whom exclusive breastfeeding is not possible, commercial CM-based infant formula is typically recommended until 9 to 12 months of age, after which pasteurized homogenized CM may be introduced (9). Recommendations for the management of CMA at any age requires eliminating CM protein from the diet while continuing to provide foods that are nutritionally balanced. Between the ages of 0 and 9 months, providing an appropriate CM protein alternative is of major significance as the child receives all, or almost all, of their nutrition from either breastmilk or infant formula. Until 2 years of age, children may remain dependent on breastmilk or formula as their main source of nutrition.

ALTERNATIVES TO CM FOR CHILDREN WITH CMA

Human milk

CMA in exclusively breastfed children, usually presenting as food protein-induced allergic proctocolitis (FPIAP) (6), can usually be managed with an extensive CM elimination diet in the lactating parent and continued exclusive breastfeeding (5).

A lactating parent pursuing a CM elimination diet should receive support to ensure adequate protein, calcium and vitamin D intake, and education on appropriate meal planning, label reading, and avoidance of CM. In Canada, CM is a priority allergen and, as of December 2021, must be specified in plain language on all food labels, including in a ‘contains’ or ‘may contain’ statement, if it is an ingredient in a packaged food product (10).

The results of CM elimination from the diet are not immediate, as CM allergens (such as β-lactoglobulin) have been detected in breast milk for at least 7 days after ingestion of CM (11). The international interpretation of the Milk Allergy in Primary Care (iMAP) guideline recommends a 2- to 4-week trial of an elimination diet to test its efficacy as a treatment (12). If at any point the child’s growth falters or clinical symptoms do not resolve, a trial of extensively hydrolyzed or amino acid-based formula may be indicated (12).

Therapeutic infant formulas

For the vast majority of infants with CMA (>90%), an extensively hydrolyzed formula (>90% of peptides with a molecular weight <3 kDa) (13) is sufficient for symptom resolution (14). In the small subset of patients who have persistent symptoms with an extensively hydrolyzed formula, an amino acid-based formula can be considered (14). Barriers to the use of these specialized formulas include expense, accessibility, and palatability (14).

Of note, partially hydrolyzed formulas (peptides which range from 3 to 10 kD molecular weight) (13) are not considered suitable for the treatment of CMA because the protein remains large enough to be recognized by the immune system. Lactose-free formulas contain intact CM protein and are not appropriate for the treatment of CMA.

Soy-based formulas

Infant soy-based formulas are Health Canada-approved and a commercially available alternative to CM-based, extensively hydrolyzed, or amino acid-based formulas in Canada. The CPS only recommends soy-based formula for term infants who cannot have CM-based formulas because of health, cultural, or religious reasons, such as a vegan lifestyle or galactosemia (9). The European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) and the American Academy of Pediatrics (AAP) have also recommended that extensively hydrolyzed or amino acid-based formulas are the preferred option in the treatment of CMA over the use of soy-based formula. This recommendation is due to studies that have shown higher reported adverse events (atopic eczema, urticaria, erythema, and gastrointestinal symptoms) and potential association with increased peanut allergy incidence among infants with CMA <6 months of age fed soy-based formula (15,16). These associations have not been demonstrated in infants >6 months of age.

Other hesitations around the use of soy-based formula in infants <6 months of age include the presence of phytoestrogens, aluminum, and phytates (plant-based compounds which can impair absorption of minerals and trace elements) (15). It has been suggested that these concerns have been addressed in modern soy-based formula due to higher phosphorus and calcium content, and fortification with iron and zinc (17). Evidence remains inconclusive on the effect of phytoestrogen intake during infancy on long-term human development, reproduction, and endocrine function, although presently, there is no clear indication of harm (17).

In IgE-mediated CMA, most infants (~85%) can tolerate soy, even if they are cosensitized (16,18,19). Similarly, in non-IgE-mediated CMA, most infants (at least 80%) can tolerate soy (6). In addition, it is important to ask parents whether their child has already tried soy-based products at the time of diagnosis, particularly those eating complementary foods. Soy beans form the basis of many foods, such as tofu, soy sauce, miso, tempeh, and soy proteins from soy flour, soy concentrates/isolates, and texturized soy are commonly incorporated into baked goods (e.g., breads, cakes, cookies, etc.), meat products (e.g., luncheon meats, hotdogs/sausages, ground meat patties, etc.), and meat alternatives (20). If the child has already tried and tolerated soy at the time of diagnosis of CMA, a soy-based formula may be a reasonable alternative. Soy-based formula can be considered in cases where an extensively hydrolyzed or amino acid-based formula are not tolerated due to issues with palatability, or in cases where cost is a significant barrier.

Alternative mammalian milks

Alternative mammalian milks are generally considered inappropriate for children with CMA. CM protein is structurally similar to phylogenically related mammals (e.g., goat, sheep, buffalo) (21,22). Children with CMA are therefore likely to experience adverse reactions to these other mammalian milks as well (21,22). Although children are less likely to react to the milk of less closely related mammals (e.g., donkeys, horses, camels) (22), there are key differences in the nutritional content of these milks in comparison with CM or comparable alternatives (such as low folate content of goat milk); thus, they are generally not recommended for children (23).

Plant-based beverages

There are increasing plant-based beverages (PBB) available in Canada. Between 2018 and 2021, it is estimated that 161 cow’s milk alternative beverages were launched in the Canadian consumer market (24). The most common PBB for sale in Canada are derived from soy, almond, cashew, coconut, rice, and more recently oat and pea. PBB are often called plant-based ‘milks’ because of their white colour and consistency (23), however, Canadian regulations specify that the term ‘milk’ should only be used in reference to a product from the normal lacteal secretion obtained from the mammary gland of an animal (25).

Nationally representative data highlights an increase in PBB consumption among the general Canadian population. Using data from the Canadian Community Health Survey, Islam et al. (2021) observed that the number of Canadians (≥2 years of age) reporting consumption of PBB increased from 1.8% in 2004 to 3.0% in 2015 (26). While there is a paucity of nationally representative data on consumption of PBB in Canada from 2015 onward, data from families with pre-school aged children (n=51) in Ontario suggested that up to 35% of families purchased both cow’s milk and PBB (27).

Although PBB may be tolerated in patients with CMA, some of these drinks have important nutritional limitations. Besides soy-fortified beverage, PBB are not nutritional substitutes for CM, as many have inadequate protein and other nutrient content to meet the nutritional needs of young children. A recent Canadian review comparing commercially available milk and PBB illustrated that some PBB provided as low as 5% of the protein content of cow’s milk (28). Further, in an analysis of 30 case reports, it was observed that the exclusive or near exclusive consumption of PBB among infants and toddlers was associated with failure-to-thrive, protein-energy malnutrition, metabolic disturbances, iron-deficiency anemia, and rickets (29). Therefore, PBB are generally not recommended for children under 2 years of age (30,31), and should not be used as the sole source of nutrition in young children.

Despite the recommendation that PBB be avoided for children under 2 years, there are increasing reports of consumption of PBB among children over 1 year of age (29,30). There is also a growing interest in pursuing a CM-free diet for adults and children, stemming from concerns such as the treatment of animals, environmental impacts of animal husbandry, and health benefits of a CM-free diet touted in popular culture yet largely unsupported by evidence (32). Although further data on the environmental impact of CM products are required, a recent study from Oxford University based on a multi-indicator global database from 119 different countries estimated that CM has a much higher environmental impact than PBB, creating ~3× the carbon emissions and requiring ~9× and ~3× the land and water, respectively (33). However, the environmental impact of plant-based beverages is estimated to vary by type (e.g., almond beverage requires ~5× more water than the production of oat beverage, despite almond beverage only containing about 4 almonds per cup) (33,34). To make informed choices, consumers using environmental impact estimates to make food and beverage choices need to be aware of the low nutrient content of some of these PBB.

Families and health practitioners should refer to the Canadian Nutrition Facts Table on beverages of interest, as there are differences in PBB nutrient content and fortification. Currently, Canadian regulations do not have set requirements for manufacturers regarding the caloric density, macronutrient distribution, or fortification of calcium or vitamin D for these products (35). There continues to be both calcium and vitamin D-fortified and unfortified PBB for sale in Canada (35), so care should be taken to ensure adequate intake of micronutrients for children.

We have developed the Milk and Milk Alternatives infographic (Figure 1) to guide clinicians in selecting appropriate PBB available in Canada. To obtain nutrient values, we searched the Canadian Nutrient File for cow’s milk and plant-based beverages. Unsweetened versions were selected when available (soy, coconut, and cashew), as sweetened PBB are considered sugar-sweetened beverages which should be limited in children (36). However, only sweetened almond beverage was available in the Canadian Nutrient File, and rice beverage did not specify whether it was unsweetened or sweetened. For PBB not available in the Canadian Nutrient File (oat, pea, and macadamia nut), nutrient values were obtained from food labels of commonly accessible brands in community grocery stores (Whole Foods and Costco) in Vancouver, BC, Canada.

Figure 1.

Summary of recommendations for cow’s milk alternatives in children with cow’s milk allergy and comparison of nutritional content of cow’s milk and common cow’s milk alternatives available in Canada.

KEY NUTRITIONAL CONSIDERATIONS OF A COW’S MILK-FREE DIET FOR CHILDREN

While the 2019 Canada’s Food Guide no longer specifies a recommended number of dairy or CM servings per day (37), CM products can be important sources of protein, fat, calories, calcium, phosphorus, and vitamin D in children (30). It is possible for children to have a balanced diet without consuming CM (38). An observational study by Weder et al. compared diets of vegetarian and vegan children aged 1 to 3 years in Germany (n=430). They found no difference in anthropometric measurements or caloric intake between the groups, and that all children had adequate protein and fat intake from their diets (39). This finding highlights that well-planned vegan and CM-free diets can meet the macronutrient needs of young children.

In terms of micronutrients, it is unlikely a child will meet their Recommended Dietary Allowance of calcium without regularly consuming either dairy products or a fortified PBB alternative. Calcium intake could be addressed by a combination of other food choices (e.g. beans, leafy green vegetables, cereal grains, etc.) (40) and/or supplementation. Most children, even with the consumption of CM or fortified alternatives, do not consume sufficient vitamin D without supplementation. Using data from the Canadian Community Health Survey 2015, Vatanparast et al. (2020) observed that 99.0 ± 0.4% of children aged 1 to 8 years not consuming a vitamin D supplement did not meet the Estimated Average Requirement (the amount estimated to meet the needs of ~50% of healthy individuals within the population) for vitamin D intake from diet alone, while only 19.0 ± 1.3% of those who consumed a vitamin D supplement did not meet the EAR (41). Vitamin D intake can be addressed by recommending ongoing supplementation to meet requirements. PBB may also have lower B vitamin content, such as folate and vitamin B12 (42), but these nutrients can be compensated for in a well-balanced diet. Consultation with a Registered Dietitian can aid in the assessment of dietary intake and provision of dietary recommendations to ensure appropriate growth and development in children fed CM alternatives.

CONCLUSIONS

An increasing number of CM alternative products are available to Canadian families. Canadian paediatricians and primary care clinicians may refer to our summary of recommendations and developed infographic (Figure 1) to aid in selecting the most appropriate, safe, and nutritionally optimal CM alternatives for children with CMA, and beyond.

WHAT’S NEW.

• The number of plant-based beverages available in Canada continues to expand and national trends indicate that intake is increasing among Canadians

• Plant-based beverages continue to not be recommended for children <2 years of age

• Key considerations for the selection of a plant-based beverage in children >2 years of age include macronutrient content (protein and fat), calcium and vitamin D fortification, and addition of sugar/sweeteners

• Our Milk and Milk Alternatives infographic (see Figure 1) has been developed to guide Canadian clinicians in recommending an appropriate plant-based beverage for children >2 years of age

Author Contributions

Conceptualization—BAW, SCE, KW, KJH; writing—original draft preparation, BAW, SCE, KW; writing—infographic development, KMC; writing—critical review and editing, KMC, KJH; guarantor of the clinical content of this submission, KJH. All authors have read and agreed to the published version of the manuscript.

Creative Commons

The developed infographic, Milk & Milk Alternatives: Nutrition Facts, was adapted with permission from a previous version submitted to the Canadian Nutrition Society Annual Infographic Competition (43).

Funding

No funding was secured for this report. BAW and KMC are supported by Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Awards.

Potential Conflicts of Interest

KJH reports honoraria from the Canadian Society of Allergy and Clinical Immunology and the BC Society of Allergy and Immunology. KJH is also a voting member of the National Advisory Committee on Immunizations, a member of the Medical Advisory Board, Canadian Immunodeficiency Patient Organization – Member, Medical Advisory Board, and member of the Board of Directors, Canadian Society of Allergy and Clinical Immunology. All three are volunteer positions. There are no other disclosures. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.