Non-IgE Cows' Milk Protein Allergy Guidance (Paediatric Guidelines)

Between 1 to 17.5% ^{1, 2} of all infants show symptoms suggesting adverse reactions to cows' milk.  However evidence also indicates that following a food challenge, confirmed milk reaction is less than 1%³ .  CMPA in exclusively breast-fed babies is lower (0.5%) compared to formula-fed or mixed fed infants. 

The guidelines published by  ESPGHAN ⁴  Ludman et al⁵ and Venter et al  ^6,  on the diagnosis and management of cow’s milk protein allergy in infants (The MAP guideline) have been used as the basis for these guidelines on the management in primary care. Allergy UK

Children with the following conditions should be excluded from following this pathway and onward referral made to the appropriate service such as general paediatrics or paediatric dermatology.

Exclusions are infants with:

• IgE mediated reactions
• Multiple allergies
• Severe symptoms which have failed to respond to medical management such as faltering growth, bloody diarrhoea, severe reflux*

For Argyll and Bute - Referrals should be sent to the relevant Paediatrician and dietitian - nhsh.dietitiansdirect@nhs.scot

* In North Highland patients with severe reflux should be referred directly to the infant feeding clinic via the Paediatric Dietitians: paediatricdietitians@highland.gov.uk. Referral pathway can be found at: http://intranet.nhsh.scot.nhs.uk/Org/DHS/ChildrensServices/HospitalPaediatrics/Documents/Nutrition/infant feeding clinic/Pathway_for_referral_to_IFDC and IFAC DRAFT2 2018.doc

Note that the list in this table is not exhaustive and the absence of these symptoms does not exclude food allergy

Consider food allergy in children whose symptoms do not respond adequately to treatment for: Atopic eczema, Gastro-oesophageal reflux disease and chronic gastrointestinal symptoms including constipation

Adapted from: National Institute for Health and Clinical Excellence (NICE): Food allergy in children and young people. ⁸

Allergy-focused clinical history (NICE 2011⁷)

As part of the initial assessment of a non-IgE reaction to cows' milk protein 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:

Assessment of severity of symptoms of Non–IgE mediated CMPA

The majority of presentations of Non-IgE CMA are likely to be mild to moderate and most formula fed infants will be successfully treated using EHF. Those with more severe symptoms warrant use of AAF. AAF is significantly more expensive than EHF and should only be used when clinically indicated. Symptoms are shown in the table below.

Primary lactose intolerance:

This is not an allergic reaction and can arise as a result of an inherited deficiency in lactase, the enzyme needed to digest lactose, which is the carbohydrate found in all mammalian milk.  This is extremely uncommon in the UK.

Secondary lactose intolerance:

May occur post gastroenteritis as a result of severe diarrhoea, this is usually transient and should resolve without action within a few weeks.  It may also occur secondary to the ongoing gastrointestinal symptoms resulting from undiagnosed CMPA. Symptoms should resolve following appropriate treatment of cows' milk protein allergy.

Symptoms:

Like all carbohydrate intolerance, lactose intolerance causes osmotic diarrhoea. 

*Nutramigen LGG 1+2 contain the probiotic Lactobicillus GG and therefore should not be fed to premature infants (until they have reached their estimated date of delivery) or infants who might have immune problems.

Gastrointestinal symptoms associated with CMPA can cause secondary lactose intolerance. To reduce the risk of misdiagnosis during the exclusion and challenge process an alternative formula which is also lactose free should be prescribed in those infants presenting with gastrointestinal symptoms.  Lactose containing formula can be used for the treatment of cows' milk allergy, following confirmation of diagnosis or if there is poor palatability of initially prescribed formula.

Soya formula should not be used in infants under 6 months but can be used in an infant over 6 months if EHF are not accepted due to poor palatability. Soya infant formula is available for purchase from a retail outlet therefore, if soya formula is required, it does not require prescription.

All prescriptions for alternative formulas should be prescribed as an acute prescription. Approximately 10 tins will be required per 4 weeks. Prescription should continue until 12 months of age minimum and ongoing if deemed necessary under dietetic review.

Soya infant formula

This is no longer on the Formulary and should not be prescribed.

Soya infant formula should not be used first line in the diagnosis and treatment of cows' milk protein allergy as, dependent on presenting symptoms, there may be up to a 50% chance that infants will also react to soya formula. ¹⁰  

Soya formula should not be used routinely in infants aged 0 to 6 months as it contains phytoestrogens that could pose a risk to long term reproductive health. ^{11, 12} A recent systematic review and meta-analysis found no significant effect on reproduction function ¹³ however currently, recommendations remain unchanged in that it is not suitable for under 6 months of age except for:

Exceptions:

• Vegan mothers who do not exclusively breastfeed, may choose to use soya infant formula
• Under the advice of special paediatric services may use soya infant formula e.g. galactosaemia
• Infants who are at nutritional risk as refusing alternative formula.

Other formula and milk substitutes

Goat or other mammalian milk formulas are not suitable for the treatment of Non-IgE CMPA as protein structures are similar to cow’s milk and there is a high risk of cross reaction.

Supermarket soya, oat or nut milks are not nutritionally complete and should not be used as a milk substitute for infants under 12 months. In most cases, following dietetic review, they can be used as the main drink after 12 months.

Rice milk should not be used in children under 4.5 years due to unacceptable levels of naturally occurring arsenic, relative to body weight.

Alternative formula smell and taste significantly differently from breast milk or standard infant formula. To ensure acceptability, infants should transition from their existing formula to the alternative formula following the guidance below, altering total volume to mirror usual intake:

• Day 1: 5oz Cows' milk formula & 1oz Alternative formula
• Day 2: 4oz Cows' milk formula & 2oz Alternative formula
• Day 3: 3oz Cows' milk formula & 3oz Alternative formula
• Day 4: 2oz Cows' milk formula & 4oz Alternative formula
• Day 5: 1oz Cows' milk formula & 5oz Alternative formula
• Day 6: 6oz Alternative formula

Breast fed/Mixed feeding Infants:

Breast fed infants need not transition to an alternative formula if mum is following a milk free diet. They can continue to breast feed as long as acceptable to the family. However, if mixed feeding or if planning to stop breast feeding, to ensure acceptability of the alternative formula, infants should, if possible, transition to the alternative formula following the guidance above or by mixing alternative formula with expressed breast milk, if available.

Stool Alterations:

Stool colour may change to green following transition to Extensively Hydrolysed Formula or Amino Acid Formula

This advice is for infants with Non-IgE mediated food allergy only (i.e. delayed reaction with mild to moderate symptoms which occur 2 hours to 2 days after ingestion of cows' milk).

• If your child has had a severe reaction to food consult your doctor before challenging with cow’s milk.  
• If your child is unwell do not progress with the challenge, continue avoiding milk and using the alternative formula. Start the challenge when your child is better.
• If your child is weaning, do not introduce any additional new foods during the challenge period.

Cows' milk must be reintroduced in order to confirm diagnosis. This should be done gradually over several days using the steps below. If your baby shows any sign of return of their symptoms of cows' milk allergy at any time during challengedo not proceed with the next step. Return to using the alternative formula and milk free diet. Inform your GP or Health Visitor and they will refer you to a Dietitian. The Dietitian will arrange to see you and your child to monitor your child’s growth and ensure your child’s diet is adequate for their needs while they are excluding cows' milk.

Formula feeding:

• Day 1: 5oz Alternative formula & 1oz Cows' milk formula
• Day 2: 4oz Alternative formula & 2oz Cows' milk formula
• Day 3: 3oz Alternative formula & 3oz Cows' milk formula
• Day 4: 2oz Alternative formula & 4oz Cows' milk formula
• Day 5: 1oz Alternative formula & 5oz Cows' milk formula
• Day 6: 6oz Cows' milk formula

The volumes above are just an example but are useful to show the correct ratio of cows' milk to alternative formula for the challenge period.  Allow your baby to feed to appetite, if they are having 7oz, start with 1oz cows' milk formula added to 6oz alternative, the challenge will take a little longer to complete.

Breast feeding:

Cows' milk should be gradually reintroduced to mother's diet over a period of 1 week.

Hydrolysed formula and soya-based formulas contain alternative sugars, which can cause tooth decay. Once the deciduous teeth start to erupt, they should be brushed twice daily with a small, soft toothbrush and a smear of fluoride toothpaste

The National Children and Young peoples allergy Network CYANS has produced a number of useful patient resources that can be accessed and printed for use via the link below:

CYANS patient information leaflets

1. Host A. Frequency of cows’ milk allergy in childhood ANN Allergy Immuno. 2002:89 (suppl 1) 33-7
2. Rona RJ, Keil T, Summers C et al.The prevalence of food allergy: A Meta analysis The Journal of Allergy and Clinical Immunology 2010;Vol120:3:638-646
3. Schoemaket A.A. et al. Incidence and natural history of challenge proven cows milk allergy in European children – EuroPrevall birth cohort: European Journal of Allergy and Clinical Immunology 2015; 70(8):963-72 https://doi.org/10.1111/all.12630
4. Koletzko S, Niggemann B, Arato A et al. Diagnostic approach and management of cow’s-milk protein allergy in infants and children: ESPHAN GI committee Practical Guidelines. JPGN;55;2;August 2012.
5. Ludman S, Shah N, Fox AT. Managing cows’ milk allergy in children. BMJ 2013;347:f5424
6. 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.
7. Fiocchi A, Brozek J et al. World Allergy Organisation (WAO) Diagnosis and rationale for action against cow’s milk allergy (DRACMA) guidelines. Paediatric Allergy Immunology 2010;21;1-125
8. 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.
9. 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
10. 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.
11. COT (2003): Phytoestrogens and health. FSA. Accessed 29 July 2019. foodstandards.gov.uk/multimedia/pdfs/phytoreport0503
12. BDA Paediatric Group Position Statement on use of soya formula 
13. Vandenplas Y, Castrellon PG, Rivas R et al. Safety of soya-based infant formulas in children. Br J Nutr 2014 (Febr 10);1-21.
14. SACN (2018). Feeding in the First Year of Life. Accessed 24 April 2019. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/725530/SACN_report_on_Feeding_in_the_First_Year_of_Life.pdf

Written by Jan Chapple, Lead Paediatric Dietitian, NHS Highland (Argyll and Bute) and Julie Johnson, Lead Paediatric Dietitian, NHS Highland (North Highland)