Non IgE allergy management: cow's milk, infants

exp date isn't null, but text field is


The aim of the guideline is:

  • To standardise the diagnosis and management of non-IgE mediated CMA
  • To ensure that infants/breast feeding mothers are not on a restricted diet for longer than necessary
  • To ensure that the appropriate formula is prescribed for children with CMA


Patient Group to which the Guideline Applies

The guideline is for infants, up to 1 year old with mild to moderate symptoms of non IgE mediated reactions to cow’s milk without accompanying weight faltering.

Patient Group to which the Guideline does not Apply

The guideline is not appropriate to manage infants showing severe or immediate reactions to milk or milk products and onward referral should be made to the appropriate service.

  • IgE mediated reactions.
    Please note that mothers of infants with IgE mediated CMA should not be advised to exclude cow’s milk from their diet except on the advice of a specialist.
  • Multiple food allergies 
  • Severe symptoms which have failed to respond to medical management such as faltering growth, severe reflux, bloody diarrhoea

Referrals for IgE mediated CMA should be sent to the local Paediatric Allergy Service.


This guideline is for the management of infants with non-IgE mediated cow’s milk allergy (CMA) and is intended for use by all health professionals in the acute and community setting.

1. Introduction

The reported prevalence of CMA varies but it is estimated that it is between 1.8 -7.5% of infants in the first year of life.  The treatment is the complete exclusion of cow’s milk from the infant’s diet.

CMA presents with a variety of clinical symptoms and the reactions may either be non-IgE mediated or IgE mediated.  Non- IgE mediated reactions generally present as delayed, with mild to moderate symptoms.  

IgE mediated reactions result in immediate and potentially severe symptoms e.g. acute angioedema or urticaria (see table 2.1) needing further investigation.

In many infants the diagnosis of cow’s milk allergy has not been confirmed and the infant may remain on the specialist formula and a cow’s milk free diet for longer than necessary, which might have nutritional and social implications.  CMA is confirmed in only one in three children presenting with possible symptoms, using strict, well defined elimination and open challenge criteria.

There are no validated laboratory or skin tests for the diagnosis of non-IgE CMA. The diagnosis can only be confirmed by the planned avoidance of cow’s milk and cow’s milk containing foods followed by re-introduction.

2. Distinguishing IgE from non-IgE mediated Cow’s Milk Allergy

Food allergies may be divided into 2 types – immediate (IgE mediated) and delayed (non-IgE mediated and mixed IgE/non-IgE ). The diagnosis can be differentiated by the signs and symptoms and taking an allergy focused clinical history. 

Signs and symptoms of possible food allergy (NICE 2011) (Table 2.1)

This list is not exhaustive and absence of these does not exclude food allergy

IgE mediated Symptoms & Signs

Non-IgE mediated Symptoms


  • Pruritis
  • Erythema
  • Acute angioedema (lips, face, around the eyes)
  • Acute urticaria – localised or generalised

Gastrointestinal Tract

  • Acute angioedema (lips, tongue and palate)
  • Oral pruritis
  • Acute vomiting/diarrhoea
  • Colicky abdominal pain
  • Nausea

Respiratory Tract

(combination with one of the above symptoms)

  • Upper respiratory tract symptoms (nasal itching, sneezing, rhinorrhoea, or congestion
    (with or without conjunctivitis)
  • Lower respiratory tract symptoms (cough, chest tightness, wheezing, or shortness of breath)


Signs and symptoms of anaphylaxis and other systemic reactions


  • Pruritis
  • Erythema
  • Atopic eczema

Gastrointestinal Tract

  • Constipation
  • Gastro-oesophageal reflux disease
  • Loose frequent stools
  • Blood and/or mucus in stools
  • Abdominal pain
  • Infantile colic
  • Food refusal/aversion
  • Perianal redness
  • Pallor and tiredness
  • Faltering growth and one or more of above gastrointestinal symptoms (with/without serious atopic eczema)

As part of the initial assessment of a reaction to cow’s milk it is important for health care professionals to take an allergy-focused clinical history appropriate for the age of child and presenting symptoms. This history should include the following:

Allergy-focused clinical history (NICE 2011)

Ask about:

History of atopic disease (asthma, eczema or allergic rhinitis) or food allergy in patient, parents or siblings

Details of any foods that are avoided and why

Symptoms that may be associated with food allergy (see section 2.1), including:

  • age at first onset
  • speed of onset
  • duration, severity and frequency
  • setting of reaction (for example, at home or nursery)
  • reproducibility of symptoms on repeated exposure
  • what food and how much exposure to it causes a reaction

Cultural and religious factors that affect the child’s diet

Who has raised the concern and suspects the food allergy

What is the suspected allergen  

The child’s feeding history, including age of weaning if appropriate. Whether the child was breast fed or formula-fed (if the child is breast fed consider the mothers diet) 

Details of previous treatment, including medication, for the presenting symptoms, and the response to this

Any response to the elimination and reintroduction of foods

If allergy history indicates infant likely to have non-IgE reaction to cow’s milk then follow algorithm If IgE then refer to the local Paediatric Allergy Service

3. Algorithm for the management of mild to moderate non-IgE Cows’ Milk Allergy (CMA) in infants

4. Prescribing guidance for milk free formula

All prescriptions for hypoallergenic formulas should be prescribed as an acute prescription; approximately 8 X 400g/450g tin will be required for a 4 week period

P = Preferred formulary   T= Total formulary

Type of Formula


Clinical Indication

Extensively Hydrolysed Formula (eHF) - whey based, containing lactose 

Birth onwards - First choice if no GI symptoms

Milupa Aptamil Pepti® 1(Allergy) Powder (P)

SMA Althera® (T)                     

It is accepted that the majority of children with CMA will improve on an extensively hydrolysed formula and this should be the first choice of formula. ESPGHAN advises that adverse reactions to lactose in children with CMA is not reported in the literature and complete avoidance of lactose is not needed in the majority of cases.

Extensively Hydrolysed Formula (eHF)  – casein based & lactose free

Birth onwards - First  choice if present with GI symptoms

Nutramigen® 1 with LGG (Mead Johnson) (P)

Similac® Alimentum Powder (Abbott (T)

These are the recommended formulae for infants with non IgE mediated CMA presenting with Gastrointestinal symptoms

Nutramigen 1 with LGG  is prepared with cooled boiled water and is contraindicated for premature infants or immunocompromised infants.  

Amino Acid Formula


Birth onwards -First choice if exclusively breast fed & need top up Neocate® LCP Powder (SHS) (P)         

Nutramigen® Puramino (Mead Johnson (T)

SMA Alfamino® (T)

AAF is recommended for infants presenting with symptoms of CMA whilst exclusively breast fed who need a top up formula.  It may also be used for more severe presentations such as a history of anaphylaxis, or severe gastrointestinal and /or skin presentations, usually in association with faltering growth. 

It should only be prescribed for other presentations on the advice of a paediatric dietitian or paediatrician.  

 Soya Formula


Soya infant formula is readily available for parents to buy in retail outlets.


Infants < 6months
Soya infant formula should not be used as first line treatment as reaction to soya is reported in small number of infants. The Committee on Toxicology has advised that they not be used in infants under 6 months as they contain phytoestrogens, which may adversely affects reproductive health. 

Soya based infant formulas may be used on specialist advice in infants 0-6 months of age for other reasons, e.g.  galactosaemia, 

Infants > 6 months of age
Soya infant formula can be considered for use where extensively hydrolysed formula (eHF) has been refused by the infant or if the infant is already taking soya in the diet without any adverse reaction. 

Other formula and milk substitutes


Goat’s milk Formula  - Given the high risk of cross reactivity between cows’ and goats’ milk proteins, the Government advises that goats’ milk infant and follow-on formula are not suitable for infants with a cows’ milk allergy.

Supermarket soya milks, oat or rice milks are nutritionally incomplete and should not be used as a milk substitute for infants under 12months

5. Confirmation of the diagnosis of non IgE mediated Cow's Milk Allergy

There are no validated laboratory or skin tests for the diagnosis of non IgE CMA. Diagnosis can only be confirmed by the planned avoidance of cow’s milk and cow’s milk containing foods followed by re-introduction. This should be done after 2-4 weeks on the cow’s milk free formula 

If the diagnosis is confirmed refer to Paediatric Dietetics for advice. The Dietitian will assess the nutritionally adequacy of the infant’s diet and the diet of breast feeding mothers and advise on calcium and vitamin supplements if appropriate.

A further challenge and reintroduction of milk will be discussed with the family at around one year of age.

6. Patient Information Leaflets to be used with this guideline

The following information leaflets should be given to parents/carers and are available on the Clinical Guidelines page on Staffnet. 

7. Further information and onward referral

Referrals to Paediatric Dietetics should be made through SCI Gateway. 

For further information please contact the local Paediatric Dietitian:  

RHC 0141 451 6443 or
RAH 0141 314 6808
IRH 01475 524058
VOL 01389 817413





  1. Agostoni C, Axelsson I, Goulet O. Medical Position Paper: Soy Protein Infant Formulae and Follow On Formulae: A Commentary by the ESPGHAN Committee on Nutrition. Journal of Pediatric Gastroenterology and Nutrition 2006;42:352-361.
  1. Du Toit G., Meyer R, Shah N et al. Identifying and Managing cows’ milk protein allergy Arch Dis Child Educ Pract Ed 2010;95:134-144
  1. Fiocchi A, Brozek J et al. World Allergy Organisation (WAO) Diagnosis and rationale for action against cows milk allergy (DRACMA) guidelines. Pedatr Allergy Immunol 2010;21;1-125
  1. Koletzko S, Niggemann B, Arato A et al. Diagnostic approach and management of cow’s-milk protein allergy in infants and children: ESPGHAN GI Committee Practical Guidelines. JPGN;55;2;August 2012.
  1. Ludman S, Shah N, Fox AT. Managing cows’ milk allergy in children. BMJ 2013;347:f5424
  1. Luyt D, Ball H, Makwana N et al. BSACI guidelines for the diagnosis and management of cow’s milk allergy. Clinical & Experimental Allergy 2014 44, 642-672
  1. National Institute for Health and Clinical Excellence (NICE): Food allergy in children and young people. Diagnosis and assessment of food allergy in children and young people in primary care and community settings. Clinical guideline 116. February 2011. NICE. London.
  1. Venter C, Brown T, Shah N et al. Diagnosis and management of non-IgE-medicated cow’s milk allergy in infancy – a UK primary care practical guide. Clinical and Translational Allergy 2013;3:23.
Editorial Information

Last reviewed: 02 August 2016

Next review: 31 October 2018

Author(s): Anne Maclean

Approved By: Area Drug and Therapeutic Committee