PAEDIATRIC
WEANING AN INFANT WITH COW’S MILK PROTEIN ALLERGY (CMPA) CMPA is the most common food allergy in babies and young children and the management of CMPA is an ever-evolving landscape. Part 1 of this two-part article takes a look at how CMPA is diagnosed and managed during weaning. CMPA can be defined as a reproducible adverse reaction of an immunological nature induced by cow’s milk protein. CMPA can be classified into IgEmediated immediate-onset, or non-IgEmediated delayed-onset, or a mixed picture, depending on the timing of the onset of symptoms and the organs involved.1 The prevalence of CMPA varies between 1.8% and 7.5% of babies during the first year of life, depending on the type of feeding the infant is receiving: CMPA is more common in formulafed or mixed-fed infants (7%) than in breastfed infants (0.5%).2,3 CMPA most often presents with symptoms within the first three to six months of life and rarely presents after 12 months of age. The focus of CMPA management has shifted over the past 10 years from one of strict avoidance of the known food allergens and provision of suitable alternatives, to a balancing act between avoiding allergens and at the same time promoting the acquisition of oral tolerance.4 WHEN SHOULD COW’S MILK PROTEIN ALLERGY (CMPA) BE SUSPECTED?
CMPA should be suspected in infants or children who have one or more of the signs and symptoms described in Table 1 opposite.3 PROGNOSIS
The outlook for children with CMPA is very positive, with most children growing out of their CMPA, although the age at which this occurs is highly variable. Approximately 75% of children
with CMPA will grow out of their allergy by three years of age and 90% will have outgrown it by six years of age. CMPA will persist until adulthood in a small percentage of individuals. The ESPGHAN guidelines5 recommend that children be re-evaluated every 6-12 months to assess tolerance to cow’s milk protein. In 2015, Lifschitz et al2 reported that, overall, children with non-IgEmediated CMPA have a better chance of outgrowing their allergy, whereas children with IgE-mediated CMPA with high levels of milk-specific IgE antibodies, multiple food allergies and/ or concomitant asthma and allergic rhinitis, had a higher risk of CMPA persisting for longer.2,5
Paula Hallam RD, PG Cert (Paed Diet) Specialist Paediatric Dietitian Paula is a Specialist Paediatric Dietitian and owner of Tiny Tots Nutrition Ltd. She helps families of babies and children with many nutritional concerns, such as fussy eating, iron deficiency anaemia, constipation, growth faltering and food allergies. She also facilitates weaning workshops for new mums.
HOW IS CMPA DIAGNOSED?
Early and reliable diagnosis of CMPA is very important, so that the appropriate dietary restrictions can be initiated where CMPA is confirmed, or avoided where the diagnosis has been refuted.1 When there is a suspicion of CMPA in an infant, an allergy-focused clinical history, tailored to the presenting symptoms, is the first step in assessing the child.3 An ‘allergy-focused diet history’ tool has been developed by Isabel Skypala and Carina Venter to help guide the correct and accurate diagnosis of CMPA.6 The European Academy of Allergy and Clinical Immunology (EAACI) guidelines on food allergy suggest that the allergy-focused history is fundamental to the establishment of a diagnosis and the mechanisms and food triggers involved.7
REFERENCES Please visit the Subscriber zone at NHDmag.com
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This information is intended for Healthcare Professionals only. Neocate Syneo is a Food for Special Medical Purposes for the dietary management of Cow’s Milk Allergy, Multiple Food Protein Allergies and other conditions where an amino acid based formula is recommended. It must be used under medical supervision after consideration of all feeding options, including breastfeeding. †Product can be provided to patients upon the request of a Healthcare Professional. They are intended for the purpose of professional evaluation only. *Accurate at time of publication, October 2019 Probiotic Bifidobacterium breve M-16V and prebiotic scFOS/lcFOS blend CMA: Cow’s Milk Allergy AAF: Amino Acid-based Formula References: 1. Candy et al. Pediatr Research. 2018;83(3):677-686 2. Burks W. et al. Pediatr Allergy Immunol 2015;26:316-322 3. De Boissieu D. et al. J Pediatr 1997; 131(5):744-747 4. Vanderhoof JA. et al. J Pediatr 1997; 131 (5):741-744 5. Fox et al. Clin Tranl Allergy. 2019;9:5 Nutricia Advanced Medical Nutrition, White Horse Business Park, Trowbridge, Wiltshire, BA14 0XQ
www.neocate.co.uk If you would like to order a product sample to be delivered directly to a patient†, please visit www.nutriciaproducts.com/samples
PAEDIATRIC Table 1: Signs and symptoms of CMPA IgE-mediated CMPA
Non-IgE-mediated CMPA Speed of onset of symptoms
Acute and a rapid onset (up to two hours after ingestion) Skin reactions Pruritus (itching) Erythema (redness) Acute urticarial – localised or generalised Acute angioedema – most commonly of the lips, face and around the eyes
Non-acute and generally delayed (manifest up to 48 hours after ingestion) Pruritus Erythema Atopic eczema
Gastrointestinal symptoms Angioedema of the lips, tongue and palate Oral pruritus Nausea Colicky abdominal pain Vomiting Diarrhoea
Gastro-oesophageal reflux disease Loose or frequent stools Blood and/or mucus in stools Abdominal pain Infantile colic Food refusal or aversion Constipation Perianal redness Pallor and tiredness Faltering growth in conjunction with at least one or more gastrointestinal symptoms above (with or without significant atopic eczema)
Respiratory symptoms (usually combined with one or more of the above signs and 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)
Asthma
Other Signs or symptoms of anaphylaxis or other systemic allergic reactions
The ‘Management of Allergy in Primary Care’, or MAP guideline has been developed to help clinicians and dietitians with the diagnosis of infants with suspected CMPA.8 This guideline was developed predominantly to help diagnose infants with suspected non-IgE-mediated CMPA, but also talks about IgE-mediated CMPA. This has recently been updated to the new international iMAP guidelines.9 There has also been an recent update to the Milk Allergy in Primary Care guideline for the diagnosis and management of CMPA.13 CONFIRMATORY ALLERGY TESTS
The diagnosis of IgE-mediated food allergy is based on a combination of the clinical history and examination, allergy tests such as skin prick tests (SPTs) and/or serum IgE blood tests (sIgE), as well as oral food challenges where 40
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indicated.1,5 It is important to remember that SPTs and sIgE are tests that detect the presence of immunoglobulin E antibodies, but they cannot differentiate between sensitisation alone and clinical allergy.1 It is an unequivocal clinical history of a reaction after cow’s milk exposure, coupled with evidence of sensitisation that will help make a near certain diagnosis of CMPA in an infant.1 Oral food challenges can help resolve diagnostic uncertainty if there is an equivocal clinical history and negative tests, or if the allergy tests are positive but there is an unconvincing clinical history after exposure to cow’s milk.1 UNPROVEN TESTS
Determination of IgG antibodies or IgG subclass antibodies against cow’s milk protein has no role in diagnosing CMPA.5 In addition, hair analysis,
PAEDIATRIC applied kinesiology, provocation neutralisation, cytotoxicity assay and electrodermal testing, should not be used for diagnosing CMPA, as they have no validity and/or evidence to support their use.1 HOW IS CMPA MANAGED?
Management of CMPA involves the complete avoidance of all foods containing cow’s milk protein for a period of time – usually at least six months from diagnosis or until 12 months of age. The proteins in cow’s milk are called whey and casein. Other mammalian milk proteins, such as goat or sheep milks should also be avoided, as proteins are up to 90% similar to cow’s milk proteins.2,5 BREASTFEEDING AND CMPA
Breastfeeding provides the best source of nutrition for babies and mums of infants with CMPA should be supported and encouraged to continue breastfeeding for as long as they would like to, preferably up to two years as recommended by the World Health Organisation (WHO), alongside the introduction of solid foods from around six months.10 Research has shown many benefits of breastfeeding, such as decreased prevalence of overweight/obesity in children who have been breastfed,11 decreased incidence of gastrointestinal and respiratory infections, improved neurological outcomes and favourable gastrointestinal microbiome.12 Occasionally, breastfed babies may react to the milk proteins in breast milk and, in this case, the mum will need to avoid all dairy products from her diet whilst breastfeeding. This is usually done as a trial for between two and six weeks to see if an infant’s symptoms improve and then reintroduce to confirm if the symptoms return. If they do not return, then the mum should be advised to return to a normal diet.8,9 The decision as to whether a breastfeeding mum should also avoid soya products is very
individual and should be discussed with a dietitian or doctor. Ideally, a dietitian should assess the calcium intake of the breastfeeding mum, as her calcium requirement is high at 1250mg/day. A calcium supplement should be suggested if her intake is inadequate, as well as a vitamin D supplement of 10 micrograms per day. Calcium phosphate supplements are better absorbed than calcium carbonate or lactate.1 A breastfeeding mum avoiding dairy products may also need an iodine supplement, as dairy products are one of the main sources of iodine in the UK diet, along with white fish. APPROPRIATE FORMULAS
Extensively hydrolysed formula If an infant is on an infant formula with or without any breast milk, this will need to change to a hypoallergenic infant formula. These formulas are by prescription only. For a list of different brands available, please see Part 2 of this article in the next issue of NHD. PLEASE NOTE: Partially hydrolysed formulas available online or over the counter are not suitable for the treatment of CMPA. What about soya formula? Soya formula is not recommended for babies under six months of age. For babies over six months, this may be a suitable option, but at least 50% of infants with non-IgE-mediated or delayed CMPA also react to soya protein and, therefore, soya formula (or soya milk used in foods) is not a suitable alternative in this group of children. Extensively hydrolysed formulas are the first-line formula choice for infants with CMPA who are not breastfed.1,2,5 Conversely, in infants with IgE-mediated or immediate onset CMPA, most will tolerate soya. It has been reported that approximately 10-15% of children with IgE-mediated CMPA do not tolerate soya.1,2,5 Calcium fortified soya products can be a useful addition to the weaning diet of an infant with CMPA.
Part 2 of Paula’s CMPA and weaning article will focus on the reintroduction of allergenic and dairy-free foods and micronutrient management. Look out for this in the November issue of NHD.
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Advertorial
The importance of palatability when choosing an extensively hydrolysed formula for the management of cow’s milk allergy in formula fed infants Cow’s milk allergy (CMA) is the most common food allergy in infants, affecting an estimated 1.3–2.9% of children in the UK.2,3 Expert consensus4 recommends extensively hydrolysed formulas (EHFs) as first line for formula-fed infants presenting with suspected mild-to-moderate IgE-mediated or non-IgEmediated CMA. Cow’s milk substitutes need to be both nutritionally adequate and well tolerated. In addition, the British Society for Allergy and Clinical Immunology (BSACI) recognise that palatability may be an important factor in formula choice, particularly in older infants, when managing CMA.5–7
Aptamil Pepti is the UK’s most palatable EHF20 In recently published research, the relative palatability of EHFs marketed in the UK was tested head-to-head by 100 healthcare professionals (51 dieticians and 49 General Practitioners). Overall, Aptamil Pepti was ranked as the most liked EHF on the UK market (Figure 1).20 Figure 1. Overall liking results (% of participants placing each sample in each rank position) Percentage participants
The prevalence of food allergy is on the rise1
100 80 60 40 20 0 2
1
Palatability is important because by the time infants are prescribed EHF their taste preferences may have already developed8
Poor palatability can sometimes be an issue for infants as research exploring the development of flavour preference in infancy seems to point to a ‘window of plasticity’ which begins to close at around 3.5 months of age.8 Unfamiliar flavours introduced following its closure may be at a heightened risk of rejection.12,15 Further, an audit of Primary Care data has shown that the mean age of presentation for infants with CMA is 3.2 months, with infants receiving a first prescription for a nutritional intervention at an average age of 5.4 months.16 Cow’s milk is a rich source of nutrients and optimal growth is particularly important in the early years when CMA occurs.17 Therefore, rejection of a cow’s milk substitute may become an issue clinically if infants first receive an EHF during a period in which the relative risk of rejection is high; inadequate intake potentially translating to a nutritional deficit. For this reason, adequate consumption of a hypoallergenic formula, like EHF, is paramount to achieve nutritional requirements,18,19 and should continue until two years of age where CMA persists.5,6,9 For formula-fed infants with CMA, selecting the most suitable and acceptable EHF is crucial, and consideration should be given to palatability in order to ensure acceptability, and hence intake.
4 (Least liked)
Rank (1–4) Aptamil Pepti
Similac Alimentum
SMA Althera
Nutramigen LGG
Adapted from: Maslin K, et al. 2018.20
The superior palatability of Aptamil Pepti is likely due to the fact that it is a whey-based, lactose containing formula. Wheybased hydrolysates have been shown to have superior palatability compared with casein based hydrolysates.21 In addition, lactose, the primary carbohydrate in breastmilk, is believed to improve palatability, as well as helping to increase calcium absorption22 and positively affecting gut microbiota.23 The study also explored healthcare professionals’ beliefs around how palatability may impact infants and their families. The vast majority of participants agreed that better palatability would result in an increased chance of non-rejection (96%), more content families (92%) and infants (81%), and decreased wastage and healthcare costs (90%; Figure 2).20 Figure 2. HCP (n=100) perception of the impact of palatability, expressed as percentage agreement 100 Percentage agreement
In EHFs, the protein is broken down by hydrolysis in order to reduce its allergenicity.9 However, as a consequence, EHFs may be bitter in taste.10–14
3
(Most liked)
80 60 40
96
92
Increase the chance of nonrejection
Result in more content families
90
89
83
81
Decrease switch to other formula
Result in more content infants
20 0
Adapted from: Maslin K, et al. 2018.20
Decrease Increase wastage and compliance healthcare costs
Advertorial This information is intended for healthcare professional use only Breastfeeding is best for babies
Sensory attributes of Aptamil Pepti24
SUMMARY OF KEY POINTS
Knowledge of the attributes that affect palatability may aid in the understanding of which EHFs are relatively less likely to be rejected.
• CMA is the most common food allergy in infants2,3
Further work was undertaken to study the specific sensory aspects of Aptamil Pepti in comparison to the other available EHFs to help understand what made it the most palatable.
• EHFs are first-line formulas in most formula fed infants with CMA5–8,15,16
Sensory attributes including odour, flavour, basic tastes, texture, as well as mouthfeel and aftertaste, were studied.
• Bitter EHFs may be strongly rejected after 4 months of age12,15
Sensory notes such as ‘malty’ odour and flavour, ‘milky’ flavour, and ‘sweet’ were found to have a positive correlation with ‘liking’. Less desirable sensory characteristics include ‘saltiness’, ‘sourness’, ‘bitterness’, and ‘astringency’.24
• The mean age at first prescription of an EHF is 5.4 months16
The sensory attributes of Aptamil Pepti, scored the highest for all desirable notes (sweet, malty odour and flavour, and milky flavour), whilst also scoring the lowest for less desirable basic tastes (sour flavour, and bitter flavour and aftertaste; Figure 3).24
0–100 Assessment Scale
Casein-based
Casein-based
60 40
Whey-based
• BSACI guidelines recognise palatability as a key factor in EHF choice5–7 • A head-to-head study has shown Aptamil Pepti to be the UK’s most palatable EHF20
Figure 3. Key sample differences (mean scores)
80
• Poor palatability can lead to rejection, which could impact growth17,25
For further information, downloadable resources and e-learning, visit www.eln.nutricia.co.uk or contact our healthcare professional helpline on 0800 996 1234.
Whey-based
20 0 Milky
Malty
Veggy
Burnt cheese
Yeasty
Sweet
Salty
Sour
Bitter Astringent Fatty
Aptamil Pepti
Similac Alimentum
SMA Althera
Nutramigen LGG
Adapted from: Campden BRI. 2017.
24
IMPORTANT NOTICE: Aptamil Pepti 1 & 2 are foods for special medical purposes for the dietary management of cow’s milk allergy. They should only be used under medical supervision, after full consideration of the feeding options available including breastfeeding. Aptamil Pepti 1 is suitable for use as the sole source of nutrition for infants from birth, and/or as part of a balanced diet from 6-12 months. Aptamil Pepti 2 is only suitable for babies over 6 months as part of a mixed diet.
References 1. Parrish CP, Kim H. CurrAllergyAsthma Rep 2018;18(8):41. 2.VenterC, et al. Allergy2008;63(3):354–359. 3. SchoemakerAA, et al. Allergy2015;70(8):963–972. 4.VenterC, et al. Clin Transl Allergy 2017;7(1):26. 5.VenterC, et al. Clin Transl Allergy 2013;3(1):23. 6. Luyt D, et al. Clin Exp Allergy 2014;44(5):642–672. 7. Walsh J, et al. BrJ Gen Pract 2014;64(618):48–49. 8. Mennella JA, et al. Am J Clin Nutr 2011;93(5):1019–1024. 9. Fiocchi A, et al. World Allergy Organ J 2010;3(4):57–161. 10. Pedrosa M, et al. J Investig Allergol Clin Immunol 2006;16(6):351–356. 11. Sausenthaler S, et al. Clin Nutr 2010;29(3):304–306. 12. Mennella JA, et al. Pediatrics 2004;113(4):840–845. 13. Miraglia Del Giudice M, et al. Ital J Pediatr 2015;41(1):42.14. de Jong NW, et al. Ann Allergy Asthma Immunol 2014;113:227–238. 15. Mennella JA, Castor SM. Clin Nutr 2012;31(6):1022–1025. 16. Sladkevicius E, et al. J Med Econ 2010;13(1):119–128. 17. Meyer R, et al. Clin Transl Allergy 2014;4(1):31. 18. Maslin K, et al. Clin Transl Allergy 2016;6:20. 19. Flammarion S, et al. Pediatr Allergy Immunol 2011;22(2):161–165. 20. Maslin K, et al. Pediatr Allergy Immunol 2018;29(8):857–862. 21. Venter C. Cow’s milk protein allergy and other food hypersensitivities in infants [Online]. https://www.jfhc.co.uk/cows-milk-protein-allergy-and-other-food-hypersensitivities-in-infants. Published: 24 November 2010. Accessed: 16 August 2019. 22. Abrams SA, Griffin IJ, Davila PM. Am J Clin Nutr 2002;76(2):442–446. 23. Francavilla R, Calasso M, Calace L, et al. Pediatr Allergy Immunol 2012;23(5):420–427. 24. Campden BRI. Sensory Evaluation of EHFs following the Quantitative Descriptive Analysis (QDA®) approach. [S/REP/142065/1B]. 14th August 2017. 25. Vandenplas Y, et al. Eur J Pediatr 2014;173(9):1209–1216. 19-066. Date of prep: September 2019. © Danone Nutricia Early Life Nutrition 2019