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A Clinicians Role in Cow’s Milk Protein Allergy: Symptom Management vs. Long-Term Outcomes

Cows’ milk protein allergy (CMPA) is defined as “a reproducible adverse reaction of an immunological nature induced by cow’s milk protein”, this most commonly presents by 6 months of age (1). This article will explore the balance between managing symptoms and optimising long-term outcomes for infants with CMPA.  

Depending on the speed of symptom occurrence and the organs involved in this, CMPA is classified as either IgE-mediated or non-IgE-mediated. IgE-mediated CMPA means that antibodies form in response to cows’ milk protein; this is associated with symptoms occurring within a few hours (1, 2). Whereas non-IgE-mediated CMPA is the more common form, and this tends to have a slower onset of up to 72 hours (2). Both forms of CMPA can involve reactions occurring in the skin, gastrointestinal tract and respiratory system; although IgE-mediated CMPA symptoms can be more acute and rare cases can lead to anaphylaxis (1, 2). Non-IgE-mediated CMPA tends to resolve by the age of three, whereas IgE-mediated CMPA more commonly resolves by the age of five (1, 3). Therefore, it is advised to reassess this diagnosis every 6 –12 months from the age of 12 months old (1).

Managing this condition involves medical diagnosis followed by the elimination of cow’s milk protein from the diet (1, 2). Where infants are breastfed, this involves supporting the mother to eliminate cow’s milk protein from her diet, without compromising her nutritional status. Infants of weaning age will also require a nutritious cow’s milk protein-free diet. 

If a baby is formula-fed, clinicians are faced with a few options. Extensively hydrolysed formula (EHF) and amino acid formula (AAF) both meet the criteria for hypoallergenic formula suitable for use in the management of CMPA (1, 2). EHF is produced by reducing cow’s milk proteins into smaller peptides, using heat and enzymes, which are not recognised as harmful by the immune system. AAF contains only non-allergenic amino acids rather than hydrolysed protein peptides. EHF has been found to be effective for the majority of infants with a diagnosis of CMPA, this is also more cost-effective than AAF (4, 5). However, AAF is recommended when symptoms continue while on EHF, or if severe symptoms or anaphylaxis occur (2, 5). 

Another consideration is the use of prebiotics, probiotics and synbiotics. Emerging research suggests that gut bacteria may influence immune and inflammatory responses related to food sensitisation and allergy (6, 7). Furthermore, infants with CMPA have been found to have low levels of Lactobacilli and Bifidobacteria in their gut as compared with healthy infants (8, 9). Although ongoing research is needed in this area, the World Allergy Organization guideline panel reported in 2015 that in relation to allergenic disease prevention “there is a likely net benefit from using probiotics resulting primarily from prevention of eczema”. This panel also suggests using probiotics in infants, and women who breastfeed infants, “at high risk of developing allergy” (6). 

A number of studies have found that the addition of the probiotic Lactobacillus rhamnosus GG (LGG) safely promoted improved tolerance to cow’s milk protein as well as improvements in longer-term outcomes such a reduced risk of atopic dermatitis (i.e. eczema) and asthma (10, 11, 12, 13).

There is less research specifically related to prebiotics and CMPA outcomes. However, infant formula containing long-chain fructo-oligosaccharides (FOS) and short-chain galacto-oligosaccharides (GOS) has been found to promote a similar gut microbiota to that of breastfed infants (14). 

A study from 2017 found that the addition of synbiotics (a mixture of FOS and Bifidobacterium breve M-16 ​V) to AAF that was consumed for eight weeks resulted in improvements in faecal microbiota in infants with CMPA, which was in line with faecal microbiota levels of healthy breastfed infants (15). Similarly, a short study found that feeding infants an EHF containing a mixture of  FOS, GOS and Bifidobacterium breve M-16 ​V led to improvements in the severity of atopic dermatitis; although these improvements only occurred in infants who had raised serum IgE at baseline (16). The lead author of this study, Van der AA, conducted a 1 year follow up using an EHF containing synbiotics with the same group of infants who had atopic dermatitis. They found that asthma-like symptoms such as wheezing and noisy breathing reduced in those taking the synbiotic-containing EHF, and less children in this group had started taking asthma medication by the end of the study (17). 

A study by Browne et al. from 2019 also reported a significant improvement in atopic dermatitis in infants with non-IgE CMPA who were switched from a standard EHF to an EHF containing synbiotics (FOS, GOS and Bifidobacterium breve M-16 ​V) for 4 weeks (18). Importantly, this study identified a significant improvement in parental quality of life as well (18). This finding related to parental quality of life is very relevant, as the management of this condition can have a significant impact on the overall family. For example, a study by Meyer et al. found that parental quality of life and family functioning was worse in families who had a child in the early stages of managing non-IgE mediated food allergies in comparison with families who were taking care of a child with sickle cell disease or intestinal failure (19). Furthermore, roughly half of the parents of children with CMPA surveyed in a study in 2015 reported that having a child with ongoing symptoms led to exhaustion, stress and anxiety and roughly a third stated this negatively impacted their ability to work or enjoy family-time (20). Another study from 2014 found that mothers of children with food allergies displayed higher levels of stress and anxiety (21). 

In conclusion, clinicians play a vital role in supporting patients and their families with the management of CMPA. There is emerging exciting research related to improving both the symptom management and longer-term allergenic outcomes of infants with CMPA; including the use of prebiotics, probiotics and synbiotics. 

References:

  1. Luyt et al. (2014) “BSACI guideline for the diagnosis and management of cow’s milk allergy”. Clinical & Experimental Allergy, 44:642–672 [accessed January 2021 via: https://www.bsaci.org/wp-content/uploads/2020/09/Milk-guideline-pdf.pdf]  
  2. NICE (2019) ‘Cow's milk allergy in children” [accessed January 2021 via: https://cks.nice.org.uk/topics/cows-milk-allergy-in-children/]
  3. Skypala et al. (2015) “The development of a standardised diet history tool to support the diagnosis of food allergy”. Clinical and Translational Allergy, 5:7 [accessed January 2021 via: https://ctajournal.biomedcentral.com/articles/10.1186/s13601-015-0050-2]
  4. Host et al. (1999) “Dietary products used in infants for treatment and prevention of food allergy. Joint Statement of the European Society for Paediatric Allergology and Clinical Immunology (ESPACI) Committee on Hypoallergenic Formulas and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition”. Arch Dis Child, 81:80-4
  5. Meyer et al. (2017) ‘When Should Infants with Cow’s Milk Protein Allergy Use an Amino Acid Formula? A Practical Guide”
  6. Fiocchi et al. (2015) “World allergy organization-McMaster university guidelines for allergic disease prevention (GLAD-P): probiotics”. World Allergy Organization Journal, 8:4. 
  7. Fox et al. (2019) “The potential for pre-, pro- and synbiotics in the management of infants at risk of cow's milk allergy or with cow's milk allergy: An exploration of the rationale, available evidence and remaining questions”. World Allergy Organ J, 12:5 [accessed January 2021 via: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555906/]
  8. Thompson-Chagoyan et al. (2011) “Faecal microbiota and short-chain fatty acid level in faeces from infants with cow's milk protein allergy”. Int Arch Allergy Immunol, 156:325–332. 
  9. Kirjavainen et al. (2002) “Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning?” Gut, 51:51–55.
  10. Canani et al. (2012) “Effect of Lactobacillus GG on tolerance acquisition in infants with cow's milk allergy: a randomized trial”. J Allergy Clin Immunol, 129(2):580–582.
  11. Canani et al. (2013) “Formula selection for the management of children with cow's milk allergy influences the rate of acquisition of tolerance: a prospective multicenter study”. J Pediatr, 163(3):771–777.
  12. Canani et al. (2013) “Extensively hydrolysed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial”. J Allergy Clin Immunol, 139(6):1906–1913. 
  13. Canani et al. (2016) “Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants”. ISME J, 10:742–750.
  14. Oozeer et al. (2013) “Intestinal microbiology in early life: specific prebiotics can have similar functionalities as human-milk oligosaccharides”. Am J Clin Nutr, 98:561–571.
  15. Candy et al. (2017) “A synbiotic containing amino acid-based formula improves gut microbiota in non-IgE mediated allergic infants”. Pediatr Res.
  16. Van der AA et al. (2010) “Effect of a new synbiotic mixture on atopic dermatitis in infants: a randomized-controlled trial”. Clin Exp Allergy, 40:795–804.
  17. Van der AA et al. (2011) “Synbiotics prevent asthma-like symptoms in infants with atopic dermatitis”. Allergy, 66: 170–177.
  18. Browne et al. (2019) Poster Discussion D31: European Academy of Allergy and Clinical Immunology Paediatric Allergy and Anaphylaxis meeting “A synbiotic EHF may help improve atopic dermatitis-like symptoms and parental QOL in infants with non-IgE mediated cow’s milk allergy”. 
  19. Meyer et al. (2017) “The impact on quality of life on families of children on an elimination diet for Non-immunoglobulin E mediated gastrointestinal food allergies”. World Allergy Organization Journal, 10:8.
  20. Lozinsky et al. (2015) “Cow’s Milk Protein Allergy from Diagnosis to Management: A Very Different Journey for General Practitioners and Parents”. Children (Basel), 2(3): 317–329. [accessed January 2021 via: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928770/]
  21. Lau et al. (2014) “Anxiety and stress in mothers of food-allergic children”. Pediatric Allergy and Immunology, 25:3. [accessed January 2021 via: https://www.researchgate.net/publication/261768867_Anxiety_and_stress_in_mothers_of_food-allergic_children

 

This article was kindly supported by Nutricia