Cow's Milk Allergy in Children

Overview

This is a Guidelines summary of NICE's Clinical Knowledge Summary (CKS) on cow's milk allergy in children. This summary only contains recommendations for primary care; for the complete set of recommendations, refer to the full CKS topic. 

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What Is It?

• Food allergy describes an adverse immune-mediated response, which occurs when a person is exposed to specific food allergen(s), usually by ingestion and more rarely by inhalation or skin contact.
• Cow's milk allergy is a reproducible immune-mediated allergic response to one or more proteins in cow's milk.
  • Milk contains casein and whey fractions made up of about 20 potentially sensitizing proteins, which a person can react to.
• Cow's milk allergy can be classified according to the underlying immune mechanism and timing of symptoms.
  • Immunoglobulin (Ig)E-mediated food allergy follows exposure and sensitization to trigger food allergen(s) with the development: of serum-specific IgE antibody. It produces immediate and consistently reproducible symptoms which may affect multiple organs systems. Reactions typically occur up to 2 hours after cow's milk protein ingestion, usually within 20–30 minutes.
  • Non-IgE-mediated food allergy involves a cell-mediated mechanism and reactions are typically delayed. They usually manifest between 2 and 72 hours after cow's milk ingestion.
  • Mixed IgE and non-IgE allergic reactions involve a mixture of both IgE and non-IgE responses and are typically delayed.
• Food sensitization describes the production of serum-specific IgE to food allergens without the clinical symptoms of an allergic reaction on food exposure.
• Food intolerances are non-immune adverse reactions to foods and/or food additives which are distinct from food allergy.
  • They often present non-specifically with gastrointestinal symptoms, headache, fatigue, and musculoskeletal symptoms. Typically, there is a delay in symptom onset and a prolonged symptomatic phase.
  • The exact cause is unknown, but they may be due to enzyme deficiencies or pharmacological reactions to chemicals.

What Are the Complications?

• The possible complications of cow's milk allergy include:
• Stress and anxiety (affecting the child and parents/carers).
  • This may be associated with the need for constant vigilance over food choices,and risk of accidental food exposure and severe reactions.
• Reduced quality of life.
  • Dietary restrictions affecting food shopping and family meal provision, which maybe stressful and time-consuming.
  • The impact on social interactions, such as eating out, playing at friends' houses,attending birthday parties, and participating in school meals.
  • The impact of peer pressure, stigma, and embarrassment about food allergy.
  • Potential social exclusion, such as not being invited to friends' houses, trips, and activities.
• Restricted diet and malnutrition.
  • There is a risk of inadequate nutritional intake, malabsorption, and faltering growth in children if food allergens that contribute essential nutrients are eliminated.
• Development of atopic comorbidities.
  • Cow's milk allergy may be the first stage of the so-called 'allergic march' and maybe associated with the later development of other atopic conditions such as asthma, atopic eczema, and allergic rhinitis.
• Cross-reactivity of other mammalian milks.
  • Potentially cross-reactive milk proteins may include those in goat, ewe, horse, camel, and buffalo milk.
• Severe and life-threatening reactions.
  • Food allergy is the most common trigger of anaphylaxis in the community. There have been rare cases of life-threatening anaphylaxis following cow's milk ingestion in sensitized children.
• Enterocolitis, enteropathy, and proctocolitis
  • Severe non-IgE-mediated allergy may present as food protein-induced enterocolitis syndrome (FPIES) involving the entire gastrointestinal tract with severe vomiting, diarrhoea, hypotension and collapse after milk ingestion; cow's milk-induced enteropathy (which involves the small bowel and may cause secondary lactose intolerance); or proctocolitis (which involves the rectum and colon causing mild rectal bleeding and mucus in stools).
• Eosinophilic oesophagitis.
  • This is a severe form of non-IgE-mediated allergy, typically presenting with a combination of vomiting, food aversion, and faltering growth in an infant.
• Heiner's syndrome.
  • This is a rare milk-induced pulmonary disease. Severe cases may be complicated by pulmonary haemosiderosis, which may present with anaemia or haemoptysis.

When Should I Suspect Cow's Milk Allergy?

Be aware that the clinical features of cow's milk allergy are variable in type and severity and can overlap with other common conditions, so clinical judgement is needed when interpreting symptoms.

• Suspect a diagnosis of cow's milk allergy in children who have:
  • One or more of the symptoms and signs listed in Table 1 of the full guideline.
  • Multiple, persistent, severe, or treatment-resistant symptoms (such as gastro-oesophageal reflux disease [GORD], atopic eczema, or chronic constipation).
  • Note: if there is a suspected severe IgE-mediated allergy, severe systemic reaction, and/or anaphylaxis, see the CKS topic on Angio-oedema and anaphylaxis for information on emergency management.

How Should I Assess a Child With Suspected Cow's Milk Allergy?

If a diagnosis of cow's milk allergy is suspected on the basis of reported or observed clinical features, assess the child to help distinguish between IgE- and non-IgE-mediated allergy, and manage appropriately.

• Take an allergy-focused history by asking about:
  • The symptoms, severity, frequency, speed of onset, duration, and the timing of the reaction in relation to cow's milk exposure. A food and symptom diary may be helpful.
    • Symptoms usually develop within a week of cow's milk introduction, although they may be delayed for several weeks.
    • Reactions may be triggered by food ingestion, inhalation, or skin contact (rare).
  • The form in which milk has been ingested (fresh, processed, cooked, or baked), and the quantity.
    • The trigger is usually cow's milk, however, it may be cow's milk protein in maternal breast milk in infants who are exclusively breastfed (rare in IgE-mediated allergy).
    • IgE-mediated reactions usually occur following a small amount of milk, whereas non-IgE-mediated reactions usually occur after ingestion of larger volumes of milk.
  • Any uneventful exposures to cow's milk before or after the reaction.
  • The setting of reactions (such as school or home).
  • The reproducibility of symptoms on repeated cow's milk exposure.
  • The age when symptoms started, the child's feeding history (age of complementary feeding [weaning], breast- or formula-fed), weight gain, and nutritional status.
    • Most affected children present by six months of age; onset is rare after 12 months of age.
    • If the child is currently being breastfed, ask about the mother's diet.
  • Any comorbid atopic conditions such as asthma, eczema, or allergic rhinitis; any history of other food allergies.
  • Any family history of food allergy or atopic conditions, particularly in parents and siblings.
  • Any symptom response to dietary restrictions or reintroduction of cow's milk, and/or medications tried, such as oral antihistamines.
• Examine the child for:
  • Nutritional status and growth, including weight, length/height, and calculation of body mass index (BMI).
  • Any signs of a clinical reaction.
  • Any signs of comorbid conditions such as atopic eczema, asthma, and/or allergic rhinitis.
  • Any signs suggesting an alternative diagnosis.
• Consider arranging skin prick testing and/or serum-specific IgE allergy testing if there is suspected IgE-mediated cow's milk allergy, depending on local referral pathways and availability.
  • 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.

What Else Might It Be?

• Alternative diagnoses which may present similarly to cow's milk allergy include:
  • Food intolerance (a non-immune adverse reaction), for example lactose intolerance caused by an inability to digest and absorb dietary lactose.
    • Symptoms of lactose intolerance may overlap with those of non-IgE-mediated cow's milk allergy if there is cow's milk-induced enteropathy, and may present with abdominal pain, bloating, and explosive diarrhoea typically 30–60 minutes following ingestion of lactose-containing foods.
    • Congenital lactase deficiency is very rare, does not usually manifest before 5 years of age, and is seen in small populations in Finland and Russia, for example.
    • Acquired or secondary lactose intolerance is usually transient and may occur with mucosal damage due to underlying gut conditions, such as following gastroenteritis.
  • Other food allergies (such as egg, soya protein, or wheat allergy) or allergies to other substances (such as animal dander, moulds, and dust).
  • Colic.
  • Gastro-oesophageal reflux disease (GORD).
  • Crohn's disease.
  • Coeliac disease.
  • Constipation.
  • Ulcerative colitis.
  • Pancreatic insufficiency (such as in cystic fibrosis).
  • Infection (for example urinary tract infection).
  • Anatomical abnormalities, such as Meckel's diverticulum, intussusception, malrotation of the gut.

Scenario: Suspected Cow's Milk Allergy

From birth to 5 years.

How Should I Manage Suspected IgE-mediated Cow's Milk Allergy?

If a diagnosis of IgE-mediated cow's milk allergy is suspected following initial assessment:

• Arrange immediate ambulance transfer to Accident and Emergency if:
  • There are systemic symptoms or suspected anaphylaxis with or without angio-oedema. 
• Arrange referral to a specialist allergy clinic for allergy testing to confirm the diagnosis and guide management, the urgency depending on clinical judgement, if:
  • There is a history of one or more severe systemic reactions.
  • There is a history of concurrent asthma; or a severe reaction to a trace amount of food allergen (airborne, or contact through skin only).
  • There is significant atopic eczema, where multiple or cross-reactive food allergies are suspected.
  • The diagnosis is uncertain.
  • There are multiple suspected food allergies.
  • Allergy testing to confirm the diagnosis is not available in primary care.
  • Allergy testing is needed to assess whether tolerance has developed, depending on local referral pathways and availability.
  • There is persistent parental or carer suspicion of food allergy (particularly if there are difficult or perplexing symptoms) despite a lack of supporting history, or persistent anxiety about the diagnosis of food allergy.
• Whilst awaiting specialist assessment, consider arranging referral to a paediatric dietitian.
  • The GP Infant Feeding Network hosts the Milk Allergy in Primary Care (MAP) Guideline 2019 which has useful algorithms on suspected and confirmed cow's milk allergy.
  • If the child is symptomatic while exclusively breastfed (rare), actively support continued breastfeeding. Advise the mother to exclude all cow's milk protein from her diet, and advise on the need for dietary supplementation with calcium and vitamin D according to local protocols.
  • Note: if the infant is asymptomatic on exclusive breastfeeding, do not exclude cow's milk from the maternal diet.
  • If the infant is formula-fed or mixed feeding and the mother is unable to return to exclusive breastfeeding, advise a trial of extensively hydrolysed formula (eHF).
• Advise parents/carers on sources of information and support (see full guideline).
• If a diagnosis of IgE-mediated allergy is confirmed, follow-up is usually arranged by the specialist allergy service.
  • Follow-up may include serial allergy testing and subsequent oral food challenge to test for acquired tolerance.
  • Parents/carers should be given written advice on prompt recognition and management of acute symptoms following accidental or new exposures.
  • Advise parents/carers to have oral antihistamines available at home, in case there is a return of symptoms on reintroduction or any accidental exposure.

For information on allergy testing, refer to the full guideline.

How Should I Manage Suspected Non-IgE-mediated Allergy? 

If a diagnosis of non-immunoglobulin (Ig)E-mediated cow's milk allergy is suspected following initial assessment:

• Consider referral to a specialist allergy clinic, the urgency depending on clinical judgement, if:
  • There is a history of faltering growth in combination with one or more gastrointestinal symptoms.
  • There is a history of one or more severe delayed reactions. Note: arrange an urgent referral to a paediatric dietitian whilst awaiting specialist assessment if there is suspected severe non-IgE-mediated allergy.
  • The diagnosis is uncertain.
  • There is a history of less severe reaction to a trace amount of food allergen (airborne, or contact through skin only).
  • There are multiple suspected food allergies.
  • There is a history of persistent or poorly controlled asthma.
  • There is significant atopic eczema, where multiple or cross-reactive food allergies are suspected.
  • There is persistent parental or carer suspicion of food allergy (particularly if there are difficult or perplexing symptoms) despite a lack of supporting history, or persistent anxiety about the diagnosis of food allergy.
  • Parents/carers are unable to perform a home reintroduction of cow's milk.
• Consider arranging referral to a paediatric dietitian, the urgency depending on clinical judgement, who can provide:
  • Regular monitoring of growth and nutritional status (including faltering growth or excessive weight gain).
  • Advice on a cow's milk-free diet including hypoallergenic infant formulas and suitable substitute foods if complementary feeding (weaning).
  • Advice on performing a cow's milk elimination trial and home reintroduction, and follow-up.
  • Advice on inappropriate dietary restriction; vitamin and calcium supplementation; and any feeding problems.
  • Advice if the child is already on a restricted diet for other reasons, which may be cultural or religious.
• If referral to a specialist allergy clinic is not needed, advise a trial elimination of all cow's milk from the mother's/infant's diet for 2–4 weeks.
  • The GP Infant Feeding Network hosts the Milk Allergy in Primary Care (MAP) Guideline 2019 which has useful algorithms on suspected and confirmed cow's milk allergy.
    • note: it is important to explain and agree on the need for planned early reintroduction of cow's milk when the trial elimination is started.
  • In exclusively breastfed babies, actively support continued breastfeeding where possible. Advise the mother to exclude all cow's milk protein from her diet, and advise on the need for dietary supplementation with calcium and vitamin D according to local protocols.
  • In formula-fed or mixed-fed infants, actively support continued breastfeeding where possible. If the mother is unable to return to exclusive breastfeeding, advise the parents or carers to replace cow's milk-based formula with a hypoallergenic infant formula.
    • If an infant is asymptomatic on exclusive breastfeeding and symptoms only occur with cow's milk-based 'top-up' feeds, advise the mother to continue breastfeeding and to continue to consume cow's milk in her diet. No further action may be needed while the infant remains asymptomatic on exclusive breastfeeding. If 'top-up' feeds are needed, advise the parents or carers to replace cow's milk-based formula with a hypoallergenic infant formula.
    • Note: if there is suspected severe non-IgE-mediated allergy, advise that an amino acid formula (AAF) should be used.
    • Note: if there is suspected severe non-IgE-mediated allergy and/or severe concomitant atopic eczema, consider seeking specialist advice on the need to avoid other foods such as soya protein and egg from the diet as well.
  • In infants who are complementary feeding (weaning) and older children, advise the parents or carers to exclude cow's milk protein from the child's diet and ensure referral to a paediatric dietitian has been arranged, for ongoing nutritional guidance and follow-up.
• Following strict adherence to a trial elimination of all cow's milk for 2–4 weeks:
  • If there is a clear improvement in symptoms, arrange a home reintroduction of cow's milk into the mother's or infant's diet to confirm the diagnosis of non-IgE-mediated cow's milk allergy.
    • Note: in exclusively breastfed babies, cow's milk should be reintroduced into the maternal diet in previously consumed amounts, over a one-week period.
    • If there is no return of symptoms, a diagnosis of cow's milk allergy is not confirmed and the mother/infant may resume normal feeding.
    • If there is a return of symptoms, the mother/infant should continue to exclude all cow's milk from the diet. If formula-fed or mixed feeding, a hypoallergenic infant formula should be advised. If symptoms clearly improve, a diagnosis of cow's milk allergy is confirmed.
  • If there is no clear improvement in symptoms:
    • If cow's milk allergy is still suspected, arrange referral to a specialist allergy clinic and consider seeking specialist advice on the need to avoid other foods such as soya protein and egg from the diet as well. If formula-fed or mixed feeding and a trial of extensively hydrolysed formula (eHF) has already been done, consider starting a trial of amino acid formula (AAF) whilst awaiting specialist assessment.
    • If cow's milk allergy is no longer suspected, the mother/infant may resume normal feeding and consider referral to a local paediatric service for further assessment if symptoms persist.
    • The iMAP Milk Allergy Guideline Home reintroduction protocol leaflet may be helpful for parents/carers.
• Advise parents/carers on sources of information and support:
• The iMAP Milk Allergy Guideline Home reintroduction protocol leaflet may be helpful for parents/carers.
• Advise that allergy testing with skin prick tests or serum-specific IgE antibody tests are not needed to confirm the diagnosis of non-IgE mediated allergy.

For information and support sources, refer to the full CKS topic.

Hypoallergenic Infant Formulas

The choice of cow's milk substitute should take into account the child's age, growth, severity of symptoms, and nutritional composition needed. A paediatric dietitian may advise on the appropriate infant milk formula to prescribe.

• Extensively hydrolysed formulas (eHFs) are usually used first-line.
  • They are whey or casein-based and are generally well tolerated by infants and children with cow's milk allergy.
• Amino acid formulas (AAFs) should be reserved for children:
  • With severe symptoms of IgE- or non-IgE-mediated allergy or a history of anaphylaxis.
  • Who cannot tolerate or have ongoing symptoms with eHFs.
  • Whose symptoms do not respond to maternal avoidance of cow's milk, or have symptoms while exclusively breastfeeding
• Partially hydrolysed formulas are not recommended in the management of cow's milk allergy.
• Soya protein-based formulas should not be used first-line.
  • They may be used in some children over 6 months of age who do not have soya allergy.
  • They should not be used in infants less than six months of age or in those with suspected soya allergy.
• The absorption of minerals and trace elements may be lower because of their phytate content.
• They contain appreciable amounts of isoflavones with a weak oestrogenic action that can lead to high serum concentrations in infants, with a theorized hormonal effect on the reproductive system, however there is no consensus in the literature.
• Be aware that up to 60% of people with non-IgE-mediated cow's milk allergy and up to 14% with IgE-mediated allergy also react to soya.
• Other milk substitutes
  • Alternative 'milk' beverages such as almond, oat, coconut, or rice milks have poor nutritional value compared with cow's milk, and are not suitable for use as an infant's main drink under 1 year of age.
    • Rice milk is not advised before the age of 4.5 years due to its natural inorganic arsenic content.
  • Lactose-free formulas contain intact cow's milk protein, and should not be used in suspected or confirmed cow's milk allergy.
  • Other mammalian milk proteins (including unmodified cow, sheep, buffalo, horse, or goat's milk) are not recommended for infants with cow's milk allergy.
    • They are not adequately nutritious to provide the sole food source for infants.
    • There is a risk of possible allergenic cross-reactivity with milk or formulas based on other mammalian milk proteins.
  • The Milk Allergy in Primary Care (MAP) guideline advises when prescribing hypoallergenic infant formula, until complementary feeding (weaning), a fully formula-fed infant will normally need around 2–3 tins of formula per week. It has a different taste and smell to cow's milk-based formula, and can be gradually introduced into a child's feeds over several days before replacing cow's milk-based formula completely.
  • The First Steps Nutrition Trust (firststepsnutrition.org) is an independent public health nutrition charity that provides information on the range and composition of infant milks and breastmilk substitutes.
    • Its publication Specialised infant milks in the UK: infants 0–6 months. Information for health professionals contains detailed information on extensively hydrolysed formulas (eHFs), amino acid formulas (AAFs), and soya protein-based infant formulas which are available in the UK.
  • The British Dietetic Association (www.bda.uk.com) has a Food Fact Sheet Suitable milks for children with cows milk allergy which may also be helpful.

Scenario: Confirmed Non-IgE-mediated Cow's Milk Allergy

From birth to 5 years.

How Should I Manage Confirmed Mild-to-Moderate Non-IgE-mediated Allergy?

If a diagnosis of mild-to-moderate non-IgE-mediated cow's milk allergy has been confirmed following a cow's milk elimination trial and subsequent home reintroduction:

• Check whether referral to a specialist allergy clinic is needed, for example if a child develops clinical features of severe non-IgE-mediated cow's milk allergy.
• Ensure referral to a paediatric dietitian has been arranged.
• Advise strict adherence to a cow's milk-free diet for the mother/infant until the child is 9–12 months old and for at least 6 months. If symptoms do not improve over this time:
  • If cow's milk allergy is no longer suspected, the mother/infant may resume normal feeding and consider referral to a local paediatric service for further assessment if symptoms persist.
  • If cow's milk allergy is still suspected, arrange referral to a specialist allergy clinic and consider seeking specialist advice on the need to avoid soya protein and egg from the diet as well.
  • Note: The iMAP guidance notes that in exclusively breastfed infants, the likelihood of sufficient cow's milk protein passing into breast milk to trigger reactions is low, so complete cow's milk exclusion may not be needed.
• Following a cow's milk-free diet, advise a planned home reintroduction of cow's milk into the mother's or infant's diet, to assess if tolerance has been acquired.
  • Note: if the child has signs of current atopic eczema or there is any history at any time of immediate-onset symptoms, do not advise a home reintroduction and instead arrange referral to an allergy specialist for allergy testing and ongoing management.
  • Tolerance to cow's milk protein should be assessed using a 'milk ladder' and monitoring for the return of symptoms.
    • A milk ladder reintroduces baked milk products first as heating reduces allergenicity. Once tolerance is established, greater exposure of less processed milk should be gradually encouraged, ending in the reintroduction of fresh cow's milk.
    • Advise parents/carers to have oral antihistamines available at home, in case there is a return of symptoms on reintroduction.
    • If symptoms return on reintroduction of cow's milk, a cow's milk-free diet should be continued, and the child should be re-evaluated after a further 6 to 12 months.
• Provide parents/carers with information on sources of advice and support.
• Provide parents/carers with advice on food allergen avoidance, including prompt recognition of symptoms, the risks of accidental exposure, and tips when travelling.