This document discusses cows' milk protein allergy (CMPA). It notes that CMPA is more common than lactose intolerance and can cause infant distress and impaired growth. Diagnosis is difficult as there is no single diagnostic test, and it is often missed leading to delayed treatment. Management involves dietary avoidance of cows' milk protein and using extensively hydrolyzed formula for bottle-fed infants. Delayed diagnosis can negatively impact growth and development. Guidelines are needed to shorten time to diagnosis and treatment to reduce burden on healthcare systems.

1. Dr.Khalid Hama Salih,
Pediatrics specialist
M.B.Ch.; D. C.H
F.I.B.M.S.ped

3. Cows milk protein allergy;Cows milk protein allergy;
CMPACMPA
 CMPA is;CMPA is;
 Much more common than lactose intoleranceMuch more common than lactose intolerance
 Easily missed, can be difficult to diagnoseEasily missed, can be difficult to diagnose
 Causes infant distress, impaired growth & a wideCauses infant distress, impaired growth & a wide
variety of clinical symptomsvariety of clinical symptoms
 Spectrum of disease; no one pathognomonicSpectrum of disease; no one pathognomonic
symptomsymptom
 There is no diagnostic testThere is no diagnostic test

4. Effective management of CMPA within the NHS couldEffective management of CMPA within the NHS could
lead to quicker improvement in symptoms and reduce the burdenlead to quicker improvement in symptoms and reduce the burden
on NHS resourceson NHS resources
Management of cows’ milk allergy in the UKManagement of cows’ milk allergy in the UK
Sladkevicius & Guest, 2008Sladkevicius & Guest, 2008
1,000 infants with CMPA analysed for treatment patterns and outcomes1,000 infants with CMPA analysed for treatment patterns and outcomes
over first 12 months following initial presentation to a GPover first 12 months following initial presentation to a GP
Mean age to be put on a diet after initially seeing a GP was 2.2 monthsMean age to be put on a diet after initially seeing a GP was 2.2 months
Mean time to diagnosis = 3.6 monthsMean time to diagnosis = 3.6 months
Time to symptom resolution = 2.9 monthsTime to symptom resolution = 2.9 months
Average 18.2 GP visits over 12 monthsAverage 18.2 GP visits over 12 months
42% of patients referred to a specialist physician42% of patients referred to a specialist physician
Waiting time for referral = approx 3.7 monthsWaiting time for referral = approx 3.7 months
Mean 7.6 GP visits before referralMean 7.6 GP visits before referral
ConclusionConclusion
 Consensus guidelines are required for the management of CMPA in order toConsensus guidelines are required for the management of CMPA in order to
shorten the time to treatment, diagnosis and symptom resolution and to decreaseshorten the time to treatment, diagnosis and symptom resolution and to decrease
the consumption of healthcare resourcesthe consumption of healthcare resources
Sladkevicius E & Guest J. Abstract presented at WCPGHAN, Brazil, August 2008: WCP-307.

5. Effective management of CMPA within the NHS couldEffective management of CMPA within the NHS could
lead to quicker improvement in symptoms and reduce the burden on NHSlead to quicker improvement in symptoms and reduce the burden on NHS
resourcesresources
Budget impact of managing cows’ milkBudget impact of managing cows’ milk
allergy in theallergy in the UKUK
Sladkevicius & Guest, 2008Sladkevicius & Guest, 2008
 Each infant with CMPA costs an estimated £1,289 to the NHS over the firstEach infant with CMPA costs an estimated £1,289 to the NHS over the first
12 months after initial diagnosis12 months after initial diagnosis
 For managing 18,350 infants in the UK this equate to an estimated annual costFor managing 18,350 infants in the UK this equate to an estimated annual cost
of £23.6 millionof £23.6 million
ConclusionConclusion
 Any strategy that can improve healthcare delivery and thereby shorten the timeAny strategy that can improve healthcare delivery and thereby shorten the time
to diagnosis, treatment and symptom resolution should potentially decrease the burden CMPAto diagnosis, treatment and symptom resolution should potentially decrease the burden CMPA
imposes on the UK’s NHSimposes on the UK’s NHS
Guest J & Sladkevicius E. Abstract presented at WCPGHAN, Brazil, August 2008: WCP-309.

6. What is CMPA?
 "...an adverse reaction to cows' milk resulting from an
immunologic hypersensitivity to one or more milk
proteins“
How many infants are affected?
 challenge-confirmed CMPA ranges between 5–8%
 worldwide.while 5–15% of infants suffer from
symptoms suggestive of adverse reactions to cow’s
milk protein Generally resolves by 1-3 years of age2
 self-reported CMPA has been documented to be
between 1.0–17.5% in preschoolers and 1.0–13.5% in
children aged 5–16 years old.
COWS’ MILK PROTEIN ALLERGY
– DEFINITION AND INCIDENCE
1 Hill DJ et al. J Pediatr 1986; 109; 270-276.
2. Høst A. Ann Allergy Asthma Immunol 2002; 89 (6 Suppl 1): 33-37.

7. CMPA can develop from the neonatal period, peak by 1 year
of age and remit in childhood. Onset of symptoms is related to
antigen exposure and generally occurs within the first 2
months of life. Referral studies suggest that CMPA usually
resolves in about 3–4 years. However, a recent study involving
807 children with CMPA found that CMPA can persist into
adolescence. The condition persists beyond 12 years of age in
approximately one third of these children, while 12% of them
remained allergic to cow’s milk until the age of 18 years
Sicherer SH & Leung DY. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in
2009. J Allergy Clin Immunol 2010;125:85–97.

8. Risk factors for persistent CMPA may include:
• A clinical diagnosis of asthma, rhinitis, eczema, early respiratory
symptoms with skin and/or gastrointestinal symptoms, and a
positive family history of atopic disease 9,12
• Severe symptoms at the time of diagnosis9,18–20
• Larger wheal diameter at SPT with fresh milk – each 1 mm
increment in wheal diameter is associated with longer duration of
disease9
• Clinical type of CMPA – several studies found that 15% of
children with IgE-mediated CMPA remained allergic after 8.6
years while all children with non-IgE-mediated CMPA outgrew
their allergy after 5 years2,21,22

10. milkHypersensitivity
IgE mediated allergy
Non-IgE mediated allergy
CMPA
(allergic hypersensitivity(
Milk intolerance
(non-allergic hypersensitivity(
Involving the
immune system
Not involving the
immune system
Adapted from Johansson SGO et al. 2004.
ALLERGY OR INTOLERANCE?
Go to symptoms

11. PhysiologyPhysiology
 IgE mediatedIgE mediated ::Immediate (minute to hr)Immediate (minute to hr)
Urticaria, swelling, wheezing, vomiting,Urticaria, swelling, wheezing, vomiting,
anaphylactic symptomsanaphylactic symptoms
Can be life threateningCan be life threatening
 Non IgE mediated – at least 50% (no tests available)Non IgE mediated – at least 50% (no tests available)
Gut or skin symptoms more likelyDelayed ,colicGut or skin symptoms more likelyDelayed ,colic
,constipatio,heiner syndrome,constipatio,heiner syndrome
Mixed type: eczemz,asthma,eosinophylic enteropathyMixed type: eczemz,asthma,eosinophylic enteropathy

12. Symptoms of CMPASymptoms of CMPA
Gastrointestinal
50-60% pts
Vomiting/regurgitation Colic*
Gastro-oesophageal reflux* Diarrhoea
Abdominal discomfort Constipation*
Blood in stools
Skin
50-60% pts
Rash Urticaria
Eczema* Angio-oedema
Swollen lips
Respiratory
20-30% pts
Rhinitis
Chronic cough
Wheezing
General Food refusal
Poor growth
Iron-deficient anaemia
Irritability/poor sleep (cying/irritable for >3hr/day for 3
days/week over a 3 week period)
Source: Vandenplas et al., 2007.1

13. ::DiagnosisDiagnosis
 DBPCFCDBPCFC
 OFCOFC
 SPTSPT
 serum cow’s milk-specific IgE testserum cow’s milk-specific IgE test

14. . The double-blind placebo-controlled food challenge
(DBPCFC) is considered
However, an open oral food challenge (OFC) represents a
more practical approach. A negative DBPCFC should always
be followed by an open OFC. When dealing with IgE-
mediated acute reactions with objective signs, a positive open
OFC may be sufficient. Open OFCs are done in the annual
assessment of tolerance onset of CMPA
In the workup of CMPA, a skin prick test (SPT) should be
considered, particularly when it is impractical or impossible to
conduct an OFC. A wheal diameter cut-off of ≥ 6 mm (≤ 2
years of age) and ≥ 8 mm (> 2 years of age) generally defines
CMPA.
When an OFC and an SPT are not possible, serum cow’s
milk-specific IgE test may be considered..

15. Diagnosing CMPADiagnosing CMPA
 Red flags? Red flags include – falteringRed flags? Red flags include – faltering
growth, blood in stools, anaphylactoidgrowth, blood in stools, anaphylactoid
reactions – these warrant urgentreactions – these warrant urgent
referral/discussion with paedsreferral/discussion with paeds
 Positive historyPositive history
 Exclusion diet for 2 – 4 weeksExclusion diet for 2 – 4 weeks
 Bottle-fed : extensively hydrolysed formulaBottle-fed : extensively hydrolysed formula
 Breast fed : maternal diary free diet (with calciumBreast fed : maternal diary free diet (with calcium
supps)supps)
 Rechallenge with CMPA after 4 weekRechallenge with CMPA after 4 week

17. Delayed diagnosis: Effects of CMPADelayed diagnosis: Effects of CMPA
delay in diagnosis of CMPA, continued exposure to CMP can lead to
increasing enteric inflammation resulting in bloody diarrhea, anemia,
dehydration, and failure to follow normal patterns of growth and weight
gain. Intestinal inflammation may be limited to mild proctitis or true
enterocolitis with esophagitis, gastritis and colitis.
There is higher risk of growth restriction when CMPA develops in the very
young infant, therefore early diagnosis and treatment via a change to the
infant’s diet can decrease risks associated with CMPA, including impaired
growth.1
Vandenplas Y et al. Guidelines for the diagnosis and management of cow’s milk protein allergy
in infants. Arch Dis Child 2007;92:902–8.

18. MANAGEMENTMANAGEMENT
 Dietary recommendationsDietary recommendations
AvoidanceAvoidance
Cross-contact and hidden ingredients — Patients must beCross-contact and hidden ingredients — Patients must be
counseled about accidental exposure to food allergens viacounseled about accidental exposure to food allergens via
cross-contactcross-contact
 Food labels — Patients must read all food labelsFood labels — Patients must read all food labels
 Extensively heated milk — Many individuals with CMA canExtensively heated milk — Many individuals with CMA can
tolerate extensively heated or baked forms of milk. However,tolerate extensively heated or baked forms of milk. However,
the only available diagnostic test to determine whichthe only available diagnostic test to determine which
individuals can tolerate extensively heated milk (unless it isindividuals can tolerate extensively heated milk (unless it is
currently in their diet) is an oral food challengecurrently in their diet) is an oral food challenge

19.  In breastfed infants, this includes a maternalIn breastfed infants, this includes a maternal
exclusion diet avoiding cow's milk proteinexclusion diet avoiding cow's milk protein
 In formula-fed infants, use of eitherIn formula-fed infants, use of either
extensively hydrolyzed or amino acid-basedextensively hydrolyzed or amino acid-based
infant formulaeinfant formulae
•Vandenplas Y, Koletzko S, Isolauri E, et al. Guidelines for the diagnosis and management of
cow's milk protein allergy in infants. Arch Dis Child 2007; 92:902.

20. CROSS-REACTIVITYCROSS-REACTIVITY
Allergy to other mammalian milk
In vitro studies have shown extensive cross-reactivity between
milk from cows, sheep, and goats, but only weak cross-
reactivity with proteins from donkeys and mares [1].
A randomized, crossover study showed that donkey's milk was
better tolerated and more effective than goat's milk in reducing
symptoms of atopic dermatitis in children with CMA [2].
Nearly 90 percent (23/26) of these children reacted to goat's
milk when challenged, but only one reacted to donkey's milk
•1.Schrander JJ, van den Bogart JP, Forget PP, et al. Cow's milk protein intolerance in infants under 1 year of
•age: a prospective epidemiological study. Eur J Pediatr 1993; 152:640.
•2.Osterballe M, Hansen TK, Mortz CG, et al. The prevalence of food hypersensitivity in an unselected
population of children and adults. Pediatr Allergy Immunol 2005; 16:567.

21. Co-sensitization (by skin testing) to soy is common inCo-sensitization (by skin testing) to soy is common in
patients with CMA, but clinical co-allergy due to cross-patients with CMA, but clinical co-allergy due to cross-
sensitization based upon cross-reactive proteins betweensensitization based upon cross-reactive proteins between
soy and milk is not. In one study, co-sensitization to soysoy and milk is not. In one study, co-sensitization to soy
milk was noted in 17 percent of patients with CMA, butmilk was noted in 17 percent of patients with CMA, but
all of these patients tolerated ingestion of soy [all of these patients tolerated ingestion of soy [11].].
Another small study reported a 10 percent incidence ofAnother small study reported a 10 percent incidence of
clinical soy allergy, mostly non-IgE-mediated, in infantsclinical soy allergy, mostly non-IgE-mediated, in infants
with CMA fed soy formula [with CMA fed soy formula [22]. These limited data]. These limited data
suggest that soy is a safe alternative for many childrensuggest that soy is a safe alternative for many children
with CMA, especially those with IgE-mediated CMA.with CMA, especially those with IgE-mediated CMA.
11.. Jansen JJ, Kardinaal AF, Huijbers G, et al. Prevalence of food allergy and intolerance in the adult Dutch population. J AllergyJansen JJ, Kardinaal AF, Huijbers G, et al. Prevalence of food allergy and intolerance in the adult Dutch population. J Allergy
Clin Immunol 1994; 93:446.Clin Immunol 1994; 93:446.
Cross-reactivity to other protein sources
•2.Natale M, Bisson C, Monti G, et al. Cow's milk allergens identification by two-dimensional immunoblotting and mass spectrometry. Mol Nutr
Food Res 2004; 48:363.

23.  Proven when symptoms resolve on CMP-freeProven when symptoms resolve on CMP-free
diet and recur on challenge.diet and recur on challenge.
 Restart CMP-free diet for 6 months or untilRestart CMP-free diet for 6 months or until
aged 1 yearaged 1 year....
 Rechallenge with CMP at 12 months of ageRechallenge with CMP at 12 months of age
and every 6 months until passes or aged 3and every 6 months until passes or aged 3

24.  Extensively-hydrolysed or amino acid based?Extensively-hydrolysed or amino acid based?
 Evidence is that 10% pts will not tolerate EHF andEvidence is that 10% pts will not tolerate EHF and
will need amino acid feedwill need amino acid feed
 If severe symptoms this rises to 50%If severe symptoms this rises to 50%
 Agreed that EHF appropriate (& cheaper) for thoseAgreed that EHF appropriate (& cheaper) for those
managed in primary care, amino acid feeds formanaged in primary care, amino acid feeds for
those requiring secondary carethose requiring secondary care
 Any role for partially hydrolysed formula?Any role for partially hydrolysed formula?

31.  SUMMARY AND RECOMMENDATIONSSUMMARY AND RECOMMENDATIONS
 Cow's milk allergy is the most common food allergy in young children affectingCow's milk allergy is the most common food allergy in young children affecting
about 2.5 percent of infants. Milk is a less common allergen in adults, affectingabout 2.5 percent of infants. Milk is a less common allergen in adults, affecting
about 0.2 percent of the adult population.about 0.2 percent of the adult population.
 Tolerance is achieved by the majority of children with CMA. Non-IgE mediatedTolerance is achieved by the majority of children with CMA. Non-IgE mediated
CMA tends to resolve by early childhood, whereas IgE-mediated CMA may persistCMA tends to resolve by early childhood, whereas IgE-mediated CMA may persist
into adolescence and beyondinto adolescence and beyond
 Casein and whey proteins are the milk proteins responsible for the majority of IgE-Casein and whey proteins are the milk proteins responsible for the majority of IgE-
mediated milk allergies.mediated milk allergies.
 Manifestations of milk allergy include IgE mediated reactions, such asManifestations of milk allergy include IgE mediated reactions, such as
urticaria/angioedema and anaphylaxis, mixed IgE and non-IgE mediated reactionsurticaria/angioedema and anaphylaxis, mixed IgE and non-IgE mediated reactions
such as atopic dermatitis (eczema) and eosinophilic esophagitis, and non-IgEsuch as atopic dermatitis (eczema) and eosinophilic esophagitis, and non-IgE
mediated forms of allergy that present with delayed gastrointestinal manifestations.mediated forms of allergy that present with delayed gastrointestinal manifestations.
 Diagnosis of IgE-mediated milk allergy is based upon careful history supported byDiagnosis of IgE-mediated milk allergy is based upon careful history supported by
skin prick tests and in vitro tests for specific IgE. An oral food challenge isskin prick tests and in vitro tests for specific IgE. An oral food challenge is
warranted if the diagnosis of milk allergy is uncertain. Diagnostic testing for non-warranted if the diagnosis of milk allergy is uncertain. Diagnostic testing for non-
IgE mediated manifestations is limited.IgE mediated manifestations is limited.

33. Management of CMPAManagement of CMPA

Infants at high risk of atopy:Infants at high risk of atopy: For infants at high risk of developing atopy,For infants at high risk of developing atopy,
evidence has shown that exclusive breastfeeding for at least 4 months orevidence has shown that exclusive breastfeeding for at least 4 months or
supplementing breastfeeding with an infant formula containing partiallysupplementing breastfeeding with an infant formula containing partially
hydrolyzed or extensively hydrolyzed protein decreases the risk of atopichydrolyzed or extensively hydrolyzed protein decreases the risk of atopic
dermatitis compared with breastfeeding supplemented with standard cow’sdermatitis compared with breastfeeding supplemented with standard cow’s
milk protein infant formula.milk protein infant formula.55
For infants who are exclusively formula-fed,For infants who are exclusively formula-fed,
the German Infant Nutritional Intervention (GINI) Study, which comparedthe German Infant Nutritional Intervention (GINI) Study, which compared
3 hydrolyzed formulas (partially hydrolyzed whey, extensively hydrolyzed3 hydrolyzed formulas (partially hydrolyzed whey, extensively hydrolyzed
whey and extensively hydrolyzed casein), reported reduced incidence ofwhey and extensively hydrolyzed casein), reported reduced incidence of
atopic dermatitis with the partially hydrolyzed whey formula and theatopic dermatitis with the partially hydrolyzed whey formula and the
extensively hydrolyzed casein formula compared with standard cow’s milkextensively hydrolyzed casein formula compared with standard cow’s milk
formula or extensively hydrolyzed whey formula.formula or extensively hydrolyzed whey formula.5,65,6

34. nfants with confirmed CMPA:nfants with confirmed CMPA: For exclusively breastfed infants with confirmed CMPA, it hasFor exclusively breastfed infants with confirmed CMPA, it has
traditionally been recommended that the mother avoid cow’s milk for the duration oftraditionally been recommended that the mother avoid cow’s milk for the duration of
breastfeeding; a clinical report released by the AAP in January 2008 now points to a lack ofbreastfeeding; a clinical report released by the AAP in January 2008 now points to a lack of
evidence for dietary restrictions during breastfeeding to prevent atopic disease with theevidence for dietary restrictions during breastfeeding to prevent atopic disease with the
possible exception of atopic eczema.5 For formula-fed infants, whether exclusive or inpossible exception of atopic eczema.5 For formula-fed infants, whether exclusive or in
combination with some breastfeeding, formula options include those with specific indicationcombination with some breastfeeding, formula options include those with specific indication
for allergic infants. Extensively hydrolyzed casein formulas are well tolerated by most infantsfor allergic infants. Extensively hydrolyzed casein formulas are well tolerated by most infants
with CMPA, but in some cases, they may still cause an allergic reaction. Amino acid-basedwith CMPA, but in some cases, they may still cause an allergic reaction. Amino acid-based
formulas contain protein in its simplest form, and may be recommended if the infant’sformulas contain protein in its simplest form, and may be recommended if the infant’s
condition doesn't improve with a hydrolyzed formulacondition doesn't improve with a hydrolyzed formula..
Soy protein-based formulas are frequently recommended as an alternative formula. However,Soy protein-based formulas are frequently recommended as an alternative formula. However,
soybean protein ranks second as an antigen in the first months of life, particularly in infantssoybean protein ranks second as an antigen in the first months of life, particularly in infants
with primary cow's milk intolerance who are placed on a soy formula.5 The recent AAP reportwith primary cow's milk intolerance who are placed on a soy formula.5 The recent AAP report
states that there is no conclusive evidence for allergy prevention with soy-based formula.states that there is no conclusive evidence for allergy prevention with soy-based formula.55
It is important to note that only extensively hydrolyzed casein or amino acid-based formulasIt is important to note that only extensively hydrolyzed casein or amino acid-based formulas
have official indication for the treatment of known allergic disorders. Partially hydrolyzedhave official indication for the treatment of known allergic disorders. Partially hydrolyzed
formula is not recommended for the treatment of allergy.formula is not recommended for the treatment of allergy.88

35. MPA: Is there potential forMPA: Is there potential for
primary preventionprimary prevention??
 rotein composition:rotein composition: A 2003 meta-analysis conducted by the CochraneA 2003 meta-analysis conducted by the Cochrane
Collaboration indicated that reducing the risk of common allergic manifestations inCollaboration indicated that reducing the risk of common allergic manifestations in
infancy is possible by feeding either 100% whey protein, partially hydrolyzedinfancy is possible by feeding either 100% whey protein, partially hydrolyzed
formula or extensively hydrolyzed casein formula instead of intact cow's milkformula or extensively hydrolyzed casein formula instead of intact cow's milk
protein formula.8 As noted earlier in this article, the GINI study found that feedingprotein formula.8 As noted earlier in this article, the GINI study found that feeding
a hydrolyzed formula – partially hydrolyzed whey or extensively hydrolyzeda hydrolyzed formula – partially hydrolyzed whey or extensively hydrolyzed
casein – vs. intact cow's milk formula or extensively hydrolyzed whey formulacasein – vs. intact cow's milk formula or extensively hydrolyzed whey formula
during the first 4 months of life reduced the risk of allergic manifestations duringduring the first 4 months of life reduced the risk of allergic manifestations during
the first year of life.the first year of life.5,65,6
 Timing for introduction of solids:Timing for introduction of solids: In contrast to long-held beliefs regardingIn contrast to long-held beliefs regarding
introduction of solids, in the recent clinical report, the AAP reversed its stance onintroduction of solids, in the recent clinical report, the AAP reversed its stance on
delaying the introduction of common allergens including dairy, eggs, and nuts,delaying the introduction of common allergens including dairy, eggs, and nuts,
citing a lack of evidence that delaying introduction beyond age 4-6 months has aciting a lack of evidence that delaying introduction beyond age 4-6 months has a
significant protective effect on the development of atopic disease.significant protective effect on the development of atopic disease.55
 Probiotic supplementation:Probiotic supplementation: Evidence shows that the intestinal flora in formula-Evidence shows that the intestinal flora in formula-
fed infants is influenced by the protein composition of the formula used. A higherfed infants is influenced by the protein composition of the formula used. A higher
proportion of bifidobacteria and lactobacilli has been found in infants fed withproportion of bifidobacteria and lactobacilli has been found in infants fed with
whey formula vs. casein formula. Since it is known that oral probioticwhey formula vs. casein formula. Since it is known that oral probiotic

36. diagnostic procedure may include elimination of the suspected
food, challenge, and re-elimination. In breastfed infants, this
includes a maternal exclusion diet avoiding cow's milk
protein, and in formula-fed infants, use of either extensively
hydrolyzed or amino acid-based infant formulae [47]. If
minimal to no improvement is noted on a milk avoidance diet,
the food in question is not responsible for symptoms, the diet
has not been restricted enough

37. . The double-blind placebo-controlled food challenge
(DBPCFC) is considered the ‘gold standard’ for diagnosing
food allergies. However, an open oral food challenge (OFC)
represents a more practical approach. A negative DBPCFC
should always be followed by an open OFC. When dealing
with IgE-mediated acute reactions with objective signs, a
positive open OFC may be sufficient. Open OFCs are done in
the annual assessment of tolerance onset of CMPA
In the workup of CMPA, a skin prick test (SPT) should be
considered, particularly when it is impractical or impossible to
conduct an OFC. A wheal diameter cut-off of ≥ 6 mm (≤ 2
years of age) and ≥ 8 mm (> 2 years of age) generally defines
CMPA.
When an OFC and an SPT are not possible, serum cow’s
milk-specific IgE test may be considered..

38.  Diagnosis of CMPADiagnosis of CMPA
In the breastfed infant: To distinguish CMPA from other possibleIn the breastfed infant: To distinguish CMPA from other possible
sensitivities derived from breastmilk, the mother should exclude cow'ssensitivities derived from breastmilk, the mother should exclude cow's
milk, peanuts, and hen's eggs from her diet for 2-4 weeks. If the infant’smilk, peanuts, and hen's eggs from her diet for 2-4 weeks. If the infant’s
symptoms improve over this time, the mother should introduce one foodsymptoms improve over this time, the mother should introduce one food
back into her diet per week. If there is no improvement after an eliminationback into her diet per week. If there is no improvement after an elimination
diet, a specialist in pediatric allergy should be consulted.diet, a specialist in pediatric allergy should be consulted.
 In the formula-fed infant: Where CMPA is suspected, elimination of CMPIn the formula-fed infant: Where CMPA is suspected, elimination of CMP
from the infant’s diet is accomplished by switching to a therapeuticfrom the infant’s diet is accomplished by switching to a therapeutic
formula that is indicated for allergy prevention; this could be anformula that is indicated for allergy prevention; this could be an
extensively hydrolyzed formula or an amino acid-based formula. It hasextensively hydrolyzed formula or an amino acid-based formula. It has
been found that up to 10% of infants with CMPA will have an allergicbeen found that up to 10% of infants with CMPA will have an allergic
reaction to an extensively hydrolyzed formula. Again, a specialist inreaction to an extensively hydrolyzed formula. Again, a specialist in
pediatric allergy should be consulted if neither of these formula typespediatric allergy should be consulted if neither of these formula types
improves symptoms.improves symptoms.11
 VandenplasVandenplas Y et al. Guidelines for the diagnosis and management of cow’s milk protein allergy inY et al. Guidelines for the diagnosis and management of cow’s milk protein allergy in

40. Algorithm for the diagnosis and management of cow’s milk protein allergy (CMPA) in
exclusively breast-fed infants. eHF, extensively hydrolysed formula.
Vandenplas Y et al. Arch Dis Child 2007;92:902-908
Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.

42. Algorithm for the diagnosis and management of cow’s milk protein allergy (CMPA) in
formula-fed infants.
Vandenplas Y et al. Arch Dis Child 2007;92:902-908
Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.

44. Symptoms of CMASymptoms of CMA
ss

45. Management of CMPA in secondaryManagement of CMPA in secondary
carecare
 Likely to be more severe cases – eg falteringLikely to be more severe cases – eg faltering
growth, blood in stools, severe refluxgrowth, blood in stools, severe reflux
 Includes those not responding to primary careIncludes those not responding to primary care
managementmanagement
 SPT/RAST?SPT/RAST?
 Go straight for amino-acid based formula (egGo straight for amino-acid based formula (eg
neocate).neocate).
 Do not re-challenge after 4 weeksDo not re-challenge after 4 weeks
 Consider alternative diagnosis if notConsider alternative diagnosis if not
improvingimproving

46. Controversies in developingControversies in developing
guidelineguideline
 Re-challenge at 4 weeks or not?Re-challenge at 4 weeks or not?
 Some suggest re-challenge, others say not, others say trySome suggest re-challenge, others say not, others say try
EHF rather than amino acid feedEHF rather than amino acid feed
 Agreed to re-challenge in primary care where more likelyAgreed to re-challenge in primary care where more likely
to be “temporary” feed issues which resolve with timeto be “temporary” feed issues which resolve with time
rather than treatment.rather than treatment.
 Not to re-challenge in secondary care as more likely toNot to re-challenge in secondary care as more likely to
have significant symptoms and re-challenge more harmfulhave significant symptoms and re-challenge more harmful
(& harder to sell to parents)(& harder to sell to parents)
 Role of SPT/RAST?Role of SPT/RAST?

47. Body system affected Symptoms
Oral tract
• Itching and redness
of mouth and lips
Respiratory tract
• Rhinitis
• Asthma
• Wheezing
Skin
• Urticaria
• Angiodema
• Atopic dermatitis
Gastrointestinal tract
• Vomiting
• Abdominal pain
• Diarrhoea
Allergic symptomsAllergic symptoms

48. Breastfeeding is the gold standardBreastfeeding is the gold standard
in infant nutrition to 6 monthsin infant nutrition to 6 months
Breastmilk content per 100ml1
Less
eczema
Less
smelly
nappies
Protection
against
diarrhoea and
upset
stomach
Lower risk of
diabetes
Protection
against
chest
infections
and
wheezing
Protectio
n against
ear
infections
Better
mental
development
1.Jensen RG (ed) Handbook of Milk Composition. New York: Academic Press, 1995. 2. Vandenplas Y et al.
Arch Dis Child. 2007; 92 (10): 902-908.
Fat 3.4g
Vits & mins 0.173g
Carbohydrates
6.7g
Prebiotic
OS 1.0g
Other 0.2g
Protein
1.2g

49. Diagnosis and management ofDiagnosis and management of CMPA in formula-fed infants*CMPA in formula-fed infants*
*Adapted from Vandenplas Y et al. Arch Dis Child. 2007; 92 (10): 902-908.

50. Diagnosis and management of CMPA in formula-fed Infants*Diagnosis and management of CMPA in formula-fed Infants*
*Adapted from Vandenplas Y et al. Arch Dis Child. 2007; 92 (10): 902-908.

51. Table 1. Medical history in a workup for CMPA
1. Is this CMPA? What is the nature of the symptoms? •
– Gastrointestinal, respiratory, cutaneous or generalised
2. Has the child been
exposed to CMP? What is the timing of the reaction post-exposure? •
– IgE-mediated reactions usually occur within 20 minutes to 2 hours
following ingestion of cow’s milk
– Non-IgE-mediated reactions are usually more delayed in onset
– In a minority of infants who are exclusively breastfed, CMP may
be transmitted via human milk, and thus maternal diet should be
investigated7
3. Consider other differential diagnoses
4. Consider other food protein allergy
5. Consider family history
6. Are there any other
concomitant atopic
condition? The majority of children with CMPA also have eczema, while 25% of
them • will go on to develop other food allergies. These children are at risk of developing
asthma. Additionally, asthma is a risk factor for more severe food-induced reactions