Pediatric Allergy
Prevention and Management
Change in Direction During the Past
Three Years
Understanding of the importance of immunological
sensitization and tolerance
Recognition that tolerance not sensitization is the critical
step in allergy prevention
Finding that exposure to the allergenic food at the
optimum age is probably a critical step in allergy
Recognition that tolerance can be induced after allergy
has been established – leading to important measures
for allergy management
Prevention of Food Allergy in Clinical
Significant change in directives within the past 3
 Previously:
Avoidance of allergen to prevent
sensitization (allergen-specific IgE)
 Current:
Active stimulation of the immature
immune system to induce tolerance of the
antigens in food
Rautava et al 2005
Diet During Pregnancy
Current directive: the atopic mother should strictly
avoid her own allergens and replace the foods with
nutritionally equivalent substitutes
There are no indications for mother to avoid other
foods during pregnancy
A nutritionally complete, well-balanced diet is essential
Authorities recommend avoidance of excessive intake of
highly allergenic foods such as peanuts and nuts to
prevent “allergen overload”, but there is no scientific
data to support this
Kramer et al 2006
Implications of Research Data
Exclusive breast-feeding with exclusion of mother’s
and baby’s allergens will reduce signs of allergy in
the first 1-2 years
Reduction or prevention of early food allergy by
breast-feeding does not seem to have long-term
effects on the development of asthma and allergic
Other benefits of breast-feeding far outweigh any
possible negative effects on allergy: exclusive breastfeeding for 4-6 months is strongly encouraged
Summary of 2008 AAP Guidelines for Allergy
Management [Greer et al 2008]
There is no convincing evidence that women who
avoid highly allergenic foods, or other foods during
pregnancy and breast-feeding lower their child’s risk of
For high-risk for allergy infants (one first-degree
relative with established allergy), exclusive breastfeeding for at least 4 months prevents or delays the
occurrence of atopic dermatitis (eczema), cow’s milk
allergy, and wheezing in early childhood
There is a lack of evidence that exclusive breast-feeding
has any positive effect on the development of asthma in
older children
Greer et al 2008
Sicherer and Burks 2008
Summary of 2008 AAP Guidelines
In infants at high risk for allergy who are not
exclusively breast-fed for 4-6 months there is
modest evidence that the onset of atopic disease
(allergy), especially eczema, may be delayed or
prevented by the use of hydrolyzed formulas
Extensively hydrolyzed formulas have a greater
protective effect than partially hydrolyzed
Summary of 2008 AAP Guidelines
There is no good evidence that soy-based infant
formulas have any preventive effect on the
development of allergy
There is little evidence that delaying the timing
of the introduction of solid foods beyond 4-6
months of age prevents the occurrence of allergy
Thygaran and Burks 2008
Infant Formulae for the Allergic Baby
Current Recommendations
Modest evidence that allergy may be delayed or
prevented by the use of hydrolyzed formulas compared
with formula of intact cow’s milk proteins
Cow’s milk based formula if there are no signs of milk
Partially hydrolysed (phf) whey-based formula if there
are no signs of milk allergy
Extensively hydrolysed (ehf) casein based formula if
milk allergy is proven
Greer et al AAP 2008
Von Berg et al 2007
Recommendations for Introduction of Solids
to High Risk for Allergy Infants
Little evidence that delaying the introduction of
complementary foods beyond 4-6 months of age
prevents allergy
Introduction of solid foods should be individualized
Foods should be introduced one at a time in small
Mixed foods containing various potential food allergens
should not be given unless tolerance to each ingredient
has been assessed
Greer et al AAP 2008
European Food Safety Authority EFSA 2009
Introduction of Solid Foods in
Relationship to Celiac Disease
Results suggest that in high risk for celiac disease
infants introduction of gluten-containing grains before
3 months or after 7 months increases incidences of
development of CD1
Introduction of gluten while breast-feeding offers
protection or delays onset of celiac disease in at-risk
Introduce gluten grains in small amounts between 4 and 6
months while infant is breastfed
Continue breast-feeding for a further 2-3 months
1Norris et al 2005
2Guandalini 2007
Introduction of Peanuts
Directives from pediatric societies (1998 - 2007)
recommended avoidance of peanuts by mothers during
pregnancy and lactation, and delaying introduction of
peanuts until after 2 or even 3 years of age
Research indicates that incidence of peanut allergy in
children rose dramatically in the years following release
of these directives
Recent research suggests:
Avoidance of peanuts reduced development of tolerance
Early exposure leads to reduced incidence of peanut allergy
Hourihane et al 2007
Introduction of Peanuts
Study (n=10,786) among primary school age Jewish
children in UK and Israel
 Prevalence of peanut allergy (PA):
Median monthly consumption of peanut in infants aged
8 – 14 months:
In UK:
In Israel:
In UK:
In Israel:
7.1 g
Difference not due to atopy, genetic background, social
class, or peanut allergenicity
Israeli infants consume peanuts in high quantities
during the first year of life
Du Toit et al 2008
Introduction of Fish
Historically, fish consumption during infancy was
considered to be a risk factor for allergy
Recent research indicates otherwise:
Regular fish consumption during the first year of life
associated with a reduced risk for allergic disease by age 4
years (n=4089)1
Babies of mothers who frequently consumed fish (2-3 times
per week or more) during pregnancy had one third less food
sensitivities than those whose mothers did not consume fish
during pregnancy2
1Kull et al 2006
2Calvani et al 2006
Introduction of Fish
Study (n= 5,000); 20.9% developed eczema by 1 year:
 Babies who were fed fish before nine months of age
were 24% less likely to develop eczema by age 1 year
 Omega-3 content of fish did not seem to influence the
 The age at which egg and milk were introduced did not
affect development of eczema
 Breast-feeding did not have any significant impact on
development of eczema
Alm et al 2009
The Natural History of Food Allergy
Food allergy most often begins in the first 1 to 2
years of life
Child is sensitized to the food protein by the
immune system developing allergen-specific IgE
to that protein
Sensitization does not necessarily mean that the
child will develop symptoms when that food is
Over time most food allergy is lost
Wood 2003
Development of Tolerance
25% of infants lost all food allergy symptoms after 1
year of age
Most infants will outgrow milk allergy by 3 years of
age, but may become intolerant to other foods
Tolerance of specific foods :
After 1 year:
 26% decrease in allergy to:
2% decrease in allergy to other foods
Age at which milk was tolerated by milk-allergic
 28% by 2 years of age
 56% by 4 years of age
 78% by 6 years of age
 About 25% of food allergic children develop
respiratory allergies
 Allergy to some foods more often than others
persists into adulthood:
Tree nuts
University of Portsmouth UK
Milk allergy outgrown:
Egg allergy outgrown:
½ by 3 years
Of 272 allergic babies, only 60 (22%) were allergic at age 3 years
In these the most common allergies were:
¾ by 3 years
Peanuts (11)
Eggs (9)
Milk (4)
Wheat, Brazil nut; Almond (2 each)
Hazelnut, Cashew, Corn (1 each)
None were allergic to tomato or fish at age 3 years
Savage et al 2007
Induction of Oral Tolerance
Tolerance to a specific food can be induced by
oral administration of the offending food by
process of “low dose continuous exposure”
Designated (SOTI: specific oral tolerance
Starting with very low dosages
Gradually increasing daily dosage up to the
equivalent of the usual daily intake
Followed by daily maintenance dose
Niggemann et al 2006
Desensitization to
Cow’s Milk
18 children with confirmed CMA >4 years of age
underwent SOTI
Starting dose 0.05 ml cow’s milk
Increased to 1 ml on first day
Increasing dosage weekly up to a daily dose of 200-250
Results: 16/18 tolerated 200-250 ml milk
Length of process median 14 weeks (range 11-17
Tolerance has been maintained for >1 year
Zapatero et al 2008
Oral Tolerance Induction to
Milk, Egg, and Peanut
36% of children with IgE-mediated allergy to cow’s
milk and hen’s egg developed permanent tolerance of
the foods after a median 21 months specific oral
tolerance induction (SOTI)1
4 peanut-allergic children underwent SOTI:
Daily doses of peanut flour starting at 5 mg peanut protein
2-weekly dosage increase up to 800 mg protein
All subjects tolerated at least 10 whole peanuts (2.38 g
protein) on post-intervention challenge2
1Staden et al 2007
2Clark et al 2009
Progression of Peanut Allergy
Peanut allergy, like many early food allergies, can be
In 2001 pediatric allergists in the U.S. reported that
about 21.5 per cent of children will eventually outgrow
their peanut allergy1
Those with a mild peanut allergy, as determined by the
level of peanut-specific IgE in their blood, have a 50%
chance of outgrowing the allergy2
Only about 9% of patients are reported to outgrow
their allergy to tree nuts3
1Skolnick et al 2001
2Fleischer et al 2003
3Fleischer et al 2005
Maintaining Tolerance of Peanut
When there is no longer any evidence of
symptoms developing after a child has
consumed peanuts, it is preferable for that child
to eat peanuts regularly, rather than avoid them,
in order to maintain tolerance to the peanut
Children who outgrow peanut allergy are at risk
for recurrence, but the risk has been shown to
be significantly higher for those who continue to
avoid peanuts after resolution of their symptoms
Fleischer et al 2004
Take Home Message
Allergy prevention emphasizes inducing
tolerance rather than avoiding sensitization
Beginning of tolerance to foods may occur in
utero or during breast-feeding
Restriction of maternal diet to avoid highly
allergenic foods during pregnancy or lactation is
Unless either mother or baby is allergic to them
Take Home Message
Exclusive breast-feeding should continue to 4-6
months of age
Complementary foods (solids) should be
introduced no later than 6 months of age
Gluten-containing foods should be introduced
not later than 6 months of age while breastfeeding continues
Take Home Message
Management of established food allergy
Accurate identification of the allergenic
 Careful avoidance of the food allergens –
especially if there is any risk of anaphylaxis
 Avoidance of unnecessary food restrictions
Take Home Message
 Provision
of complete balanced
nutrition by substituting foods of equal
nutritional value
 Monitoring the child’s response at
intervals to determine when the food
allergy has been outgrown
 Maintenance of tolerance by feeding
tolerated foods regularly
Invitation to Further Information
Joneja, J.M.Vickerstaff Dealing with Food Allergies in Babies
and Children Bull Publishing Company, Boulder, Colorado.
October 2007