Transcript Cows’ milk protein allergy

COWS’ MILK PROTEIN ALLERGY
& LACTOSE INTOLERANCE:
THE USE & ABUSE OF SPECIALISED INFANT FORMULAE
2011
Aim
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To outline the differences between cows’ milk
protein allergy (CMPA) and lactose intolerance
To give guidance on how to suspect lactose
intolerance & CMPA
To show the algorithm for CMPA in bottle fed
babies; Vandenplas 2007, including the use of
specialised infant formulae
To discuss the role of soya, rice & goat’s milks etc
To show some illustrative cases
CMPA and lactose intolerance
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Allergy is a reaction to a foreign protein (allergen)
Allergy involves the immune system
Intolerance does not
Lactose is a sugar, therefore not an allergen
Lactose is present in all animal milks including breast milk
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Cows’ milk protein allergy (CMPA) & lactose
intolerance are two very different things
Lactose intolerance
Allergy
Lactose; “milk sugar”
Lactase
Glucose
Lactose
Galactose
Lactase; brush border of duodenum
Lactase levels highest
at birth, tend
reduce thereafter
Lactose intolerance; 3 types
Congenital
Primary
Acquired
Congenital lactose intolerance
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Extremely rare autosomal
recessive disorder
associated with a
complete absence of
lactase expression.
Finns & Russians
Primary lactose intolerance;
childhood/teenage & adult onset
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Lactase deficiency:
extremely common in this
age group
Lactase levels genetically
programmed to decline
steadily after 2 years of
age, but rarely become
symptomatic until after 7
years of age
Acquired lactose intolerance
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Transient by nature
After gastroenteritis, bowel surgery etc
Takes about 3 months to resolve
Who gets it?
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Prevalence
Northern Europeans (ie most of UK!) have the lowest
prevalence of primary lactose intolerance; usually only
manifest over the age of 5 years
Central & Southern Europeans have higher rates
Hispanic, African and Indians have much higher
prevalence, maybe apparent over the age of 2+ years
Premature babies; < 34 weeks gestation (70% term
lactase levels at 34 weeks)
So what happens to the lactose?
Reaches large bowel undigested
 Creates abnormal osmotic load to bowel
This causes;
 Bacterial fermentation of lactose to hydrogen gas,
 Increased faecal water,
 Increased gut transit time,
 Explosive acid stools with
 Excoriated bottom
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Lactose intolerance; clinical
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Mainly relating to (bacterial fermentation of lactose
in) the large bowel
 Bloating
 Pain
& discomfort
 “Gassy”
 Diarrhoea
 Explosive stools; no blood except from
 Sore bottom
Lactose intolerance; investigation
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Making the diagnosis;
History is the key
Stool pH & reducing substances (hot fresh sample,
within the hour!)
Normal stool pH ~6
< 5.3 is acidic and diagnostic of carbohydrate
(sugar) malabsorption
Breath hydrogen test; rarely done in children
Lactose intolerance; management
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Lactose intolerance; suitable milks;
Enfamil O Lac
SMA LF
Soya over 6 months of age
Colief is lactase drops
CMPA
Cows milk protein allergy; CMPA
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CMPA is;
 Much
more common than lactose intolerance
 Easily missed, can be difficult to diagnose
 Causes
infant distress, impaired growth & a wide variety
of clinical symptoms
 Spectrum of disease; no one pathognomonic
symptom
 There is no diagnostic test
CMPA; how big is the problem?
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5-15% of infants show symptoms suggestive of
adverse reaction to cows’ milk protein
Symptoms of CMPA
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Often, but not always occur within first few weeks after
introduction of CMP, e.g. after period of breast feeding
Median onset of symptoms from exposure =24 hrs
Many develop symptoms in at least 2 systems;
Gastro intestinal tract:
Skin :
Respiratory tract:
Mild, moderate or severe
50-60%
50-60%
20-30%
Most frequent symptoms of CMPA
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Irritability, distress, colic, arching,
regurgitation, vomiting, difficulty feeding
Loose stools, bloody stools
Iron deficiency anaemia
Atopic dermatitis/eczema
Swelling of lips & tongue
Runny nose, otitis media, chronic cough & wheeze
Alarm symptoms; refer when
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Failure to thrive
Macroscopic blood loss; colitis
Hypoalbuminaemia (Protein Losing Enteropathy)
Severe, difficult to manage eczema
Acute laryngeal oedema or bronchospasm
Anaphylaxis
Management of cows milk allergy in
the UK
Guest et al 2008
1000 infants with CMPA
Study period =12 month period following initial visit to GP
Mean age at presentation to GP; 3 months
Time to be put on a diet;
Time to symptom resolution;
Time to diagnosis;
2.2 months
2.9 months
3.6 months
Average of 18.2 visits to GP in 12 month period, 4.2 visits before
appropriate milk introduced
42% referred to a specialist
Average of 7.6 visits before specialist referral
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How did they initially present?
 Combination
of GI & atopic/skin symptoms = 55%
 GI symptoms alone = 22%
 Atopic/skin symptoms alone = 9%
 Acute IgE symptoms in less than 10%
What other milks were they put on initially?
 60%
soya formula
 18% with extensively hydrolysed formula
 3% with an amino acid formula
Diagnosis and management of
CMPA in formula-fed infants*
*Adapted from Vandenplas Y et al. Arch Dis Child. 2007; 92 (10): 902-908.
What is a suitable alternative to cows’
milk?
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Any extensively hydrolysed protein formula (EHF) will be
suitable for ~80-90%
Extensively hydrolysed protein With added MCT (55%)
Aptamil Pepti
(whey)
Aptamil Pepti Junior
Nutramigen
(casein)
Pregestimil
For the other 10-20%:
Single amino acid (“elemental”) formula
Neocate LCP
Nutramigen AA
Danone
Nutricia/Cow &
Gate/Milupa
Standard
infant
formula
Extensively
hydrolysed
formula
EHF + MCT
Cow and Gate 1 & 2
Aptamil products
SMA products
Cost
Taste
Allergen
-icity
Aptamil Pepti
Mead Johnson
Nutramigen
Low
Good
High
High
Poor
Low
Whey formula
Contains LCPs (omega 3&6)
80-85% short peptide chains
15-20% single amino acids
63% protein chains < 1000 daltons
Calcium & iron enriched
34% residual lactose
Per 400g tin £8.62
Pepti Junior (+50%
MCT)
Appropriate for malabsorption
disorders
63% protein chains < 1000 daltons
Lactose free
Per 400 g tin £10.68
Single amino
acid
formulae
Casein formula
Lactose free
95% protein chains < 1000 daltons
Per 400 g tin £8.95
Pregestimil (+55% MCT)
Appropriate for malabsorption disorders
Per 400 g tin £9.81
Neocate LCP
Nutramigen AA with LIPIL* (blend
100% amino acid formula
Calcium enriched
Produced in a milk free
environment
Lactose free
Per 400g tin £23.83
of Omega 3 (DHA and Omega 6 ARA fatty acids
present in breast milk)
Lactose free
Per 400 g tin £22.05
Formula fed infants with mild –
moderate CMPA
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Diagnostic elimination diet (DED)
>80% will respond to an EHF (extensively
hydrolysed formula)
Some casein based (Nutramigen, Pregestimil)
Some whey based – taste better! (Aptamil Pepti)
Allow at least 2 weeks, up to 4 weeks for some symptoms to
resolve.
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But many improve in 48-72 hours
~10-20% will not respond and will need single amino acid
formula (Neocate LCP, Nutramigen AA)
Infants < 6 months of age
Stop all supplementary feeds/weaning during DED
Prescribable indications
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Aptamil Pepti
Extensively hydrolysed protein formula
Whey based (improved palatability)
>97% of infants with CMPA will respond clinically
Low levels of lactose (not lactose free)
May be some clinical benefits to small amounts of
residual lactose (improves calcium absorption &
lactase is an inducible enzyme)
What about breast fed babies?
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Continue to breast feed
CMP elimination diet in mum, exclude egg too
Supplement with calcium
Vandenplas guidelines
Prognosis
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Cows’ milk protein allergy persists in only a minority
Most outgrow by teenage years (~75%)
20% by 4 years of age
Those with positive IgE based tests more likely to
have persistent allergy
Risk factors for persistent allergy: Co existent asthma
& rhinitis
FAQs-1
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Why not soya milk?
CMO update 37 January 2004
“Soya should not be used as first line management
of CMPA, lactose intolerance or galactokinase deficiency”
Soya milks have high phyto-oestrogen content; long term
risk to reproductive health of infants (COT 2003)
Significant risk of cross reactivity of ~30% (-50%); soy is
a potential allergen
SACN advises no unique clinical condition which
particularly requires the use of soya based formulae
www.sacn.gov.uk
www.foodstandards.gov.uk
FAQs-2
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Is soya ever ok?
Child over 6 months of age
Refusing to drink EHF or AA formula
Vegans
FAQs-3
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Why not goat’s milk?
2006 DoH advice;
Goat’s milk protein formulae not suitable for
infants under 12 months of age
High chance of cross reaction, ~30%; proteins are
very similar
Low in folate
Similar levels of lactose to cows’ milk
(all animal milks contain lactose)
Rice milk
High levels of arsenic
Not recommended under 4 years of age
FAQs-4
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What about investigations?
GOLD standard is history + improvement on DED
Other tests not usually necessary, unless history of
anaphylaxis
Problems with IgE based tests eg RAST & Skin Prick Tests:
 Only
about 50% of CMPA is IgE mediated
 50% of healthy newborns have circulating IgE to cow’s milk
 IgE antibodies may appear & be present with no clinical
history of CMPA
 Negative tests do NOT exclude allergy
FAQs-5
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CMPA and associations
Significant overlap between CMPA and Gastrooesophageal reflux disease of infancy
(~40% of those with GORDI have CMPA)
Associated with other food allergies (eg soya up to
50%)
Associated with atopic dermatitis
Associated with positive family history of food
allergy and atopy
FAQs -6
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What about the lactose?
Theoretical reasons to suggest that a lactose-free
formula may not be beneficial in the longer term.
Lactase is an inducible enzyme and requires the
presence of some lactose in the intestine for optimal
development (Shulman et al, 2005)
Removing lactose unnecessarily from diet risks
lactase levels permanently declining
Illustrative case 1
Corey aged 3 months
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Presented to children’s ward with bloody stool for 2 months
Began when mum stopped breast feeding and changed to
formula @ 4 weeks of age
No vomiting, irritability or colic
Mother has allergy to cats, dogs, peanuts, and has asthma
Dad’s sister had problems tolerating cows milk as a baby
Clinical diagnosis of CMPA; start EHF (Aptamil Pepti in this
case)
No tests necessary
Clinic 4 weeks later, 4 months old
Thriving
Well
No blood in stools since 36 hours after EHF introduced
Referral to dietitian for weaning advice
Corey
Illustrative case 2
Oliver aged 2 months
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Admitted at 2 months of age with vomiting, loose stools & colic
Formula fed (“hungry baby” formula as not settling with feeds)
Taking Colief with little effect
Mum allergic to cows milk (diagnosed at 3 years of age)
Clinical diagnosis of CMPA
Changed to EHF
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Seen 3 weeks later: “much better”
Diarrhoea stopped
Less irritable, much happier, sleeping longer
No longer on Colief
Still some vomiting and regurgitation
Started on anti reflux treatment
Best Practice: Identifying and managing cow's
milk protein allergy
 George du Toit et al Archives of Disease in
Childhood; 2010;95:134-144
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References and resources
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http://www.cks.nhs.uk/colic_infantile/evidence/references
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Vandenplas et al Archives of Disease in Childhood October 2007: 92; 10; 902
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Lactose Intolerance in Infants, Children, and Adolescents Pediatrics 2006;118;12791286 Melvin B. Heyman and for the Committee on Nutrition
Influence of changes in lactase activity and small intestinal mucosel growth on lactose
digestion and absorption in preterm infants, Robert J. Shulman, William W. Wong, and E.
O’Brian Smith, Am J Clin Nutr 2005; 81: 472-9
Early feeding, feeding tolerance, and lactase activity in preterm infants, Robert J.
Shulman, Richard J. Schanler, Chantal Lau, Margaret Heitkemper, Ching-Nan Ou, and E.
O’Brian Smith,, J Pediatr 1998; 133: 645-9
NICE guidelines April 2011
Any questions?