Cow’s Milk Protein Allergy (CMPA) in Children: A Guide for Healthcare Professionals

Summary: Cow’s milk protein allergy (CMPA) or cow’s milk allergy (CMA) is an autoimmune reaction to the proteins in milk namely whey and casein. There can be a number of risk factors and detailed assessment is important to identify if IgE-mediated or non-IgE-mediated allergy for appropriate management. In both cases, initial management would require the elimination of dairy-based formula milk and other dairy products from the baby’s diet.

Navigating the world of paediatric food allergies is no easy feat for healthcare professionals and one of them is cow’s milk protein allergy (CMPA). This post will equip you with an in-depth understanding of what cow’s milk protein allergy is and how to manage it.

Let’s dive deeper into the world of CMPA!

What is Cow’s milk protein allergy (CMPA)? 

Definition

Cow’s milk protein allergy (CMPA) or Cow’s milk allergy (CMA) is an allergy to one or more proteins present in cow’s milk. These can be broadly classified as casein and whey proteins. The body’s immune response to the presence of these proteins can either be IgE-mediated, non-IgE mediated or mixed. (1) 

Prevalence

The prevalence of food allergy has increased in the past 20-30 years worldwide, with the highest disease burden in infants and young children. (2) The prevalence of CMPA in children living in the developed world is approximately 2% to 3%. This percentage is likely for the IgE-mediated cow’s milk protein allergy as the non-IgE-mediated milk allergy’s prevalence is not well known. (3)

According to a study, infants under one year of age are likely to be affected with mild to moderate non-IgE mediated milk allergy. (4)  

After egg allergy, cow’s milk protein allergy is found to be the most common food allergy in infants and young children. (5) 

CMPA Risk Factors

• During early childhood, boys have a higher risk of developing cow’s milk allergy than girls
• A family history of atopy increases the chance of developing food allergies
• A family history of confirmed food allergies increases the chance of food allergy 
• Confirmed food allergy to another food increases the likelihood of developing a milk allergy
• Comorbid atopic conditions like eczema or asthma can increase the chances of severe allergic reactions. (6)

Symptoms of CMPA

Symptoms of cow’s milk protein allergy (CMPA) can occur within days to weeks after birth and vary in degree of severity. And they can be divided into 3 classes depending on the type and severity of the reaction:

• IgE mediated 
• Non-IgE mediated
• Or both

IgE-mediated CMPA symptoms

These reactions typically develop within seconds to 2 hours of ingestion of cow’s milk and are treatment resistant, they can present as follows:

SKIN

• Localised or generalised acute urticaria
• Acute angioedema, most commonly of the face, lips and around the eyes
• Erythema
• Pruritis
• Atopic eczema or an acute flare-up of pre-existing eczema

GASTROINTESTINAL

• Nausea
• Vomiting 
• Oral pruritis
• Angio-oedema of the lips, palate and tongue
• Colicky abdominal pain or discomfort
• Diarrhoea

RESPIRATORY (usually in combination with one or more of the above)

• Upper respiratory tract- Congestion (with or without conjunctivitis), sneezing, nasal itching or rhinorrhoea
• Lower respiratory tract- Cough, wheezing, shortness of breath or chest tightness

OTHER

• Anaphylaxis or
• Systemic allergic reactions

*This list of symptoms and signs is not exhaustive and their absence does not exclude food allergy diagnosis.   

Non-IgE-mediated CMPA symptoms

These symptoms typically develop between 2-72 hours of having cow’s milk and can be one or more of the following:

SKIN

• Erythema or flushing
• Pruritis
• Atopic eczema

GASTROINTESTINAL (GIT)

• Food refusal or aversion
• GORD
• Vomiting
• Irritability
• Infantile colic
• Abdominal discomfort or pain
• Pallor and tiredness
• Frequent and/or loose stools
• Constipation
• Mucous and/or blood in stools
• Perianal redness
• Faltering growth with at least one or more GIT symptoms

RESPIRATORY (usually in combination with one or more of the above) 

• Lower respiratory tract- Cough, wheezing, shortness of breath or chest tightness 

It is important to remember that the above-mentioned symptoms can occur independently in babies and young children. Therefore, it is essential to do a thorough assessment before confirming a diagnosis of cow’s milk allergy. (7)

Mixed IgE and non-IgE mediated CMPA Symptoms and signs

Mixed clinical features may present with eczema, GORD, constipation and/or diarrhoea. (8, 9)

Distinguishing CMPA from Lactose Intolerance

Lactose intolerance is an intolerance to the sugar lactose in cow’s milk. Whereas the cow’s milk allergy is due to the proteins present in cow’s milk. Lactose intolerance is classified into 2 classes:

• Primary lactose intolerance: Congenital lactase deficiency which does not manifest till 5 years of age and affects a very small percentage of populations.
• Secondary lactose intolerance: Acquired lactose intolerance that is transient and can occur due to gut damage from infections like gastroenteritis. 

Symptoms of lactose intolerance may be similar to that of non-IgE mediated cow’s milk allergy like abdominal pain, bloating and explosive diarrhoea within 30-60 minutes of cow’s milk or lactose-containing foods intake. 

Assessment of Cow’s Milk Protein Allergy (CMPA)

If signs or symptoms suggest the possibility of a cow’s milk protein allergy (CMPA) in a child, conduct an assessment to determine whether the allergy is IgE- or non-IgE-mediated. Based on the findings, proceed with the appropriate management plan.

A- Anthropometry: Weight history from birth along with length and head circumference helps establish whether any faltering growth concerns are present as they would need addressing.

B- Biochemical: Check if any tests have been performed prior to referral like skin prick or blood or other intolerance tests. Ask if the patient is on any medication or multivitamin supplement. If mum is breastfeeding exclusively, ask if she is taking any multivitamins and mineral supplements.

C-Clinical: Ask about

• Symptoms and their 
  • Onset- within seconds to 2 hours or later in 2-72 hours, 
  • Severity- mild, moderate or severe, 
  • Duration- how long do they last and how they resolve

• If develops symptoms with inhalation, contact or ingestion of cow’s milk or other dairy-based products
• If previously fine with dairy intake or developed reaction upon initial introduction
• Any family history of food allergies, atopic eczema or asthma
• Any other food or environmental allergies
• Any other comorbidities  

 D-Dietary Recall: Ask

• Initial milk tried with since birth, and if any improvement with any of the milk 
• If exclusively breastfed, has mum tried a dairy-free diet and reintroduced back
• If over 6 months, weaning age, foods introduced so far, especially common food allergens like egg, soya, sesame, fish, peanuts
• Milk currently on, quantity and frequency of intake in 24 hours
• If > 6 months old, take 24 hour food history

Diagnosis

Diagnosis of IgE-mediated CMPA 

• If symptoms are suggestive of IgE-mediated reaction to cow’s milk, the patient must be referred to the allergy specialist and dietitians for dairy-free dietary advice till seen by the allergy specialist. 
• If a baby is under 1 year old and formula fed, would require a specialist formula prescription. The first line treatment is extensively hydrolysed formula milk, if these are not well tolerated then amino acid-based formulas can be offered. If a baby is <6 months old, can be offered soya-based formula milk provided they are able to tolerate soya-based products.
• If a baby is exclusively breastfed, the mother will need to exclude dairy products from her diet completely but can have dairy alternatives. 
• Diagnosis of Ige-mediated allergy can be confirmed with a skin prick test, immunoglobulin-specific blood test or food challenge within the hospital for safety purposes.

Confirming the diagnosis of non-IgE-mediated CMPA

If a baby is having mild to moderate symptoms, they would need a trial of cow’s milk-free formula and diet if weaned, for 4 weeks followed by reintroduction of cow’s milk back in the diet. If symptoms improve or resolve upon elimination and come back upon reintroduction, that confirms the diagnosis. But if there is no change in symptoms upon exclusion of cow’s milk from the diet then continue to offer cow’s milk and refer to local paediatric service for further investigation. 

• If there is a delayed onset of symptoms, confirm the diagnosis with milk challenge in babies under 1-year-old. 
• If formula fed, trial on hypoallergenic formula milk for 4 weeks followed by milk challenge, provided symptoms settle on specialist milk.
• If baby is exclusively breastfed, the maternal diet is to be free of all dairy products. 
• If baby is >1 year old, offer them plant-based, fortified, over the counter alternatives in place of dairy products. 

Be aware that there are no reliable allergy tests to confirm the diagnosis of non-IgE-mediated allergy. Advise the parents/carers that the following diagnostic tools are not recommended for the diagnosis of cow’s milk allergy:

• Serum-specific immunoglobulin (Ig)G testing,
• Vega testing (electroacupuncture devices),
• Applied kinesiology (muscle strength testing),
• Hair analysis (assessing mineral content),
• Atopy patch testing

Differential Diagnosis

It is very important to thoroughly investigate the symptoms before concluding a diagnosis of cow’s milk protein allergy (CMPA) as they might be present due to some other health condition. 

Food Intolerance: For example, lactose intolerance, where the body struggles to digest lactose, a component found in milk. This often manifests as abdominal discomfort, bloating, and diarrhea around 30-60 minutes after consuming lactose.

Other Food Allergies: Some individuals may have allergies to other food items such as eggs, soy protein, or wheat, or to environmental factors like animal dander, moulds, or dust.

Colic: It is quite common among infants and can sometimes mimic symptoms of cow’s milk allergy.

Gastroesophageal Reflux Disease (GORD): This condition can lead to symptoms that are quite similar to a milk allergy.

Inflammatory Bowel Diseases (Crohn’s Disease or Ulcerative Colitis): They can present with gastrointestinal symptoms similar to a milk allergy.

Coeliac Disease: It is an immune reaction to eating gluten and can sometimes present with symptoms similar to cow’s milk allergy.

Constipation: Although typically identified by its signature symptom, it can sometimes be confused with a milk allergy due to associated abdominal discomfort.

Pancreatic Insufficiency: Conditions such as cystic fibrosis can lead to pancreatic insufficiency, resulting in symptoms that might be mistaken for a milk allergy.

Infections: Certain infections, like urinary tract infections, can sometimes present with symptoms similar to a milk allergy.

Anatomical Abnormalities: Conditions like Meckel’s diverticulum, intussusception, and gut malrotation can all present with gastrointestinal symptoms that might be mistaken for a cow’s milk allergy. (10)

Management 

IgE-mediated CMPA Management

• If symptoms are life-threatening due to anaphylaxis or other systemic reaction, the patient should be immediately transferred to the emergency department.
• Patients should be referred to an allergy specialist for allergy testing to confirm diagnosis and advice on management. The urgency of referral would depend on several factors:

  –  History of severe reaction on trace amount of food allergen (through skin contact or airborne), or concurrent asthma

  – Significant atopic eczema where cross-reactive or multiple food allergies are suspected

  – History of one or more systemic reactions

  – Suspected multiple food allergies

 – Unavailability of allergy testing in primary care 

  – Diagnosis is uncertain

  – Parental/carer persistent anxiety around the diagnosis of food allergy

• Patient should also be referred to a local paediatric dietitian to offer parents support with a cow’s milk-free diet for their child. 

If <6 months old:

• If a baby is symptomatic and exclusively breastfed, advise the mother to exclude all sources of cow’s milk and dairy from her diet and have vitamin D and calcium supplements.
• If a baby is asymptomatic and exclusively breastfed, the mother can continue to have dairy products in her diet.
• If a baby is formula fed or combined fed and the mother cannot exclusively breastfeed then extensively hydrolysed formula milk is the first line treatment that can be advised to trial. 

    If >6 months old baby:

• Parents should be advised to continue offering either extensively hydrolysed formula milk till the first birthday or if breastfed, maternal diet to be free of cow’s milk protein and other dairy products.
• If a diagnosis is confirmed, milk-free weaning advice is to be given to parents along with information on the use of fortified dairy-free alternatives to meet nutritional requirements.
• Once the baby is 12 months old, advise to wean off the formula and on to a fortified over-the-counter dairy alternative milk.
• Advise parents on how to check the food labels and look for specific food allergens and avoid “may contain dairy” products. For open-market foods, advise parents to either ask the vendor or avoid offering these to children with a confirmed diagnosis.
• Some free-from-product finder applications might come in handy.

• Once the diagnosis of IgE-mediated allergy is confirmed, the patient is followed up at an allergy clinic either for repeat testing or food challenge at the hospital. Parents are advised about management using an allergy action plan like one offered by the British Society for Allergy and Clinical Immunology (BSACI). For accidental exposure, parents are advised to keep oral antihistamines.  

Management of non-IgE mediated CMPA

• If a child develops severe non-IgE mediated symptoms, refer to an allergy specialist.
• Ensure referral to a paediatric dietitian has been made who can:
  • Provide advice on cow’s milk-free diet including hypoallergenic formulas and suitable dairy-free foods and drinks if a baby is at weaning age.
  • Provide guidance and support for elimination diet trial and reintroduction of cow’s milk in diet to confirm a diagnosis
  • Monitor nutritional status and growth for any signs of faltering growth.
  • Advise on mineral and vitamin supplements if needed
  • Offer support with a restricted diet due to cultural or religious factors.

Babies with a confirmed diagnosis of non-IgE mediated CMPA would need to follow a strict dairy-free diet for 6 months and until 9-12 months old. 

Dairy-free Diet Advice in the first year of Life

• If exclusively breastfed, the maternal diet should be dairy free with alternative plant-based substitutes and vitamin D and calcium supplementation. 
• If a breastfed baby only showed symptoms when exposed to standard formula milk then the mother to continue to have dairy in her diet. The iMAP guidance states that in exclusively breastfed infants, not enough cow’s milk protein passes into breastmilk to trigger a reaction in the infant therefore, cow’s milk exclusion from the maternal diet may not be needed.
• If combined or formula fed, switch to hypoallergenic formula milk till the first birthday and then to over-the-counter fortified plant-based alternatives. 
• Educate parents on milk-free weaning, how to check labels on pre-packaged products, what terms to lookout for and avoid “may contain dairy” products. Further information on label checking can be found on Allergy UK website. Advise parens to ensure product is dairy free when buying from open market or bakeries. Equip parents with ideas regarding how to cope with their baby’s allergy at social events.
• Advise on appropriate use of fortified dairy alternatives like plant based yoghurts, cheese, spreads, creams and milks. Emphasize on not to offer the plant based milk as a drink before baby is 12 months old but to use it to cook their food. Signpost parents to dairy free recipes online or offer them some resources on it. 
• Give parents advice about the most important nutrients food sources like calcium, iodine and iron. If baby is having >500 ml of formula milk in the first year of life, they do not need supplements but if breastfed, would require vitamin D supplement. 

Milk Reintroduction Advice

• Once the 6-month dairy-free period is over and the baby is between 9-12 months old, offer them advice on reintroducing dairy back in their baby’s diet gradually using Milk Allergy in primary care  (iMAP) milk ladder. Some recipes for the first few steps can be given to parents if they wish to offer homemade products to their baby.  
• Recommend appropriate nutrient supplements from age 1 onwards as per your national guidelines.
• Advise parents to gradually wean their baby off the hypoallergenic formula milk and onto a fortified plant-based dairy alternative milk. 

When giving milk reintroduction advice, inform parents that sometimes it can take a while for a baby or a child to grow out of the allergy and therefore to continue trying on the ladder steps after a gap period of 4-6 weeks. Give parents supporting resources and offer ongoing support via email or telephone call if you have the capacity.

Cross-reactivity between soya and dairy proteins

Cross-reactivity between soya and dairy proteins refers to a situation where a child allergic to cow’s milk protein may also react to soya proteins. This happens because the immune system confuses the proteins in soya with those in cow’s milk due to their similar structures. 

According to Primary Care Notebook, approximately 10-14% of infants with CMPA will also react to soya proteins. This cross-reactivity is especially prevalent in cases of non-IgE-mediated CMPA, with up to 50% of these infants reacting to soya proteins. However, soya-based formulas are not recommended for babies under 6 months of age due to the presence of isoflavones, which may exert a weak estrogenic effect. There’s also a risk of cross-reactivity between mammalian milk.

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*Disclaimer: The information provided in these blog posts is intended to support and assist healthcare professionals in expanding their knowledge base and staying informed about the latest advancements in paediatric nutrition. However, this information should not be used as a substitute for your professional clinical judgement. While every effort is made to ensure the accuracy of the information, healthcare professionals should continue to use their discretion in diagnosing and treating health conditions. Always adhere to your local and national clinical guidelines and protocols when providing care. The author is not responsible for any actions taken based on the content of these blog posts