Download Management of Pediatric Food Allergy

Prevention of Allergy
Janice M. Joneja, Ph.D., RD
2006
Approach to Infant Allergy
• Prediction
– Identification of the atopic baby before initial
allergen exposure may allow prevention of allergy
• Prevention
– Measures to prevent initial allergic sensitization of
potentially atopic infant
• Identification
– Methods for identification of an established food
allergy
• Management
– Strategies for avoiding the allergenic food and
providing complete balanced nutrition from
alternative sources to ensure optimum growth and
development
2
Prevention of Food Allergy in
Clinical Practice
Requirement:
• Practice guidelines for:
– Prevention of sensitization to food allergens
– Prevention of expression of allergy
• Consensus for practice guidelines using
evidence-based research
Current status:
• Lack of consensus
3
Possible Confounding Variables in Studies
and Subjects
• Variability in genetic predisposition of infant
to allergy
• Mother’s allergic history
• Role of in utero environment
• Exposure to allergens
– Exclusivity of breast-feeding
– Inclusion of infant’s allergens in mother’s diet
– Dietary exposure not recognized in infant or
mother
– Exposure to inhalant and contact allergens
4
Does Atopic Disease Start in Fetal Life?
• Fetal cytokines are skewed to the Th2 type
of response
• Suggested that this may guard against
rejection of the “foreign” fetus by the
mother’s immune system
• IgE occurs from as early as 11 weeks
gestation and can be detected in cord blood
_____________
Jones et al 2000
5
Does Atopic Disease Start in Fetal Life?
(continued)
• At birth neonates have low INF- and
tend to produce the cytokines associated
with Th2 response, especially IL-4
• So why do all neonates not have allergy?
6
Does Atopic Disease Start in Fetal Life?
(continued)
• New research indicates that the immune
system of the mother may play a very
important role in expression of allergy in the
neonate and infant
• IgG crosses the placenta; IgE does not
• Certain sub-types of IgG (IgG1; IgG3) can
inhibit IgE response
7
Does Atopic Disease Start in Fetal Life?
(continued)
• IgG1 and IgG3 are the more “protective” subtypes
of IgG
• IgG1 and IgG3 tend to be lower than normal in
allergic mothers
• In allergic mothers, IgE and IgG4 are abundant
• In mothers with allergy and asthma, IgE is high at
the fetal/maternal interface
• Fetus of allergic mother may thus be primed to
respond to antigen with IgE production
8
Significance in Practice
• Food proteins demonstrated to cross the placenta
and can be detected in amniotic fluid
• Allergen-specific T cells in fetal blood
demonstrated to:
– Ovalbumin
– Alpha-lactalbumin
– Beta-lactoglobulin
• Exposure to small quantities of food antigens from
mother’s diet thought to tolerize the fetus, by
means of IgG1 and IgG3, within a “protected
environment”
9
Immune Response of the Allergic Mother
• Atopic mother’s immune system may
dictate the response of the fetus to antigens
in utero
• The allergic mother may be incapable of
providing sufficient IgG1 and IgG3 to
downregulate fetal IgE
• However – there is no convincing evidence
that sensitization to specific food allergens
is initiated prenatally
10
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
11
Pregnancy Diet and Fish Intake
2006 study
• Frequent maternal intake (2–3 times/wk or more)
of fish reduced the risk of food sensitizations by
over a third
• A similar trend (not significant) was found for
inhalant allergies
• In the whole study population, i.e. allergic group
plus non-allergic group: correlation between
increased consumption of fish and decreased
prevalence of SPT positivity for foods
• Reduced incidence of allergic sensitization
thought to be due to the omega-3 content of fish
_______________
Calvani et al 2006
12
The Neonate:
Conditions That Predispose to Th2 Response
• Inherited allergic potential (maternal and paternal)
• Intrauterine environment
• Immaturity of the infant’s immune system
– Major elements of the immune system are in place, but
do not function at a level to provide adequate protection
against infection
– The level of immunoglobulins (except maternal IgG) is
a fraction of that of the adult
– Secretory IgA (sIgA) absent at birth: provided by
maternal colostrum and breast milk throughout lactation
13
The Neonate:
Conditions That Predispose to Th2 Response
• Increased uptake of antigens:
– Hyperpermeablilty of the immature digestive
mucosa
– Immaturity of the gut-associated lymphoid
tissue (GALT) means reduced effectiveness of
antigen processing at the luminal interface
– Inflammatory conditions in the infant gut
(infection or allergy) that interfere with the
normal antigen processing pathway
14
Breast-feeding and Allergy
Studies indicating that breast-feeding is
protective against allergy report:
– A definite improvement in infant eczema and
associated gastrointestinal complaints when:
• Baby is exclusively breast-fed
• Mother eliminates highly allergenic foods
from her diet
– Reduced risk of asthma in the first 24 months
of life
15
Breast-feeding and Allergy
• Other studies are in conflict with these
conclusions:
– Some report no improvement in symptoms
– Some suggest symptoms get worse with breastfeeding and improve with feeding of
hydrolysate formulae
– Japanese study suggests that breast-feeding
increases the risk of asthma at adolescence
• Why the conflicting results?
_______________
Miyake et al 2003
16
Immunological Factors in Human Milk that
may be Associated with Allergy:
Cytokines and Chemokines
• Atopic mothers tend to have a higher level of the
cytokines and chemokines associated with allergy
in their breast milk
• Those identified include:
IL-4
IL-5
IL-8
IL-13
Some chemokines (e.g. RANTES)
• Atopic infants do not seem to be protected from
allergy by the breast milk of atopic mothers
17
Immunological Factors in Human Milk that
may be Associated with Allergy: TGF-1
• Cytokine, transforming growth factor-1 (TGF1) promotes tolerance to food components in the
intestinal immune response
• TGF-1 in mother’s colostrum may influence the
type and intensity of the infant’s response to food
allergens
• A normal level of TGF-1 is likely to facilitate
tolerance to food encountered by the infant in
mother’s breast milk and later to formulae and
solids
______________
Rigotti et al 2006
18
Immunological Factors in Human Milk that may be
Associated with Allergy: TGF-1 (continued)
• TGF-1 in mothers of infants who developed IgEmediated CMA
(+challenge; + SPT) lower than in:
– Mothers of infants with non-IgE CMA
(+ challenge; - SPT)
– Mothers of infants without CMA
(- challenge; - SPT)
__________________
Saarinen et al 1999
19
Implications of Research Data
• Exclusive breast-feeding with exclusion of infant’s known
allergens will protect the child against allergy if it is
inherited from the father
• 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 breastfeeding does not seem to have long-term effects on the
development of asthma and allergic rhinitis
• Other benefits of breast-feeding far outweigh any possible
negative effects on allergy: exclusive breast-feeding for 46 months is strongly encouraged
20
Current Recommendations for Practice
Preventive Measures
Mother is atopic:
– Mother eliminates all sources of her own
allergens prior to and during pregnancy to
reduce IgE and IgG4 in the uterine environment
– Continues to avoid her own allergens during
lactation
– Exclusive breast-feeding without exposure of
infant to external sources of food allergens for 6
months
21
Current Recommendations for Practice
(continued)
Father and or siblings atopic; mother is nonatopic:
– No recommendations for mother to restrict her
diet during pregnancy
– No recommendations for mother to restrict her
diet during lactation unless the baby shows
signs of allergy
– Exclusive breast-feeding for 4-6 months
22
Current Recommendations for Practice
(continued)
• Some studies suggest that maternal avoidance of
the most highly allergenic foods during lactation
may reduce sensitization of infant with family
history of allergy
• Foods to be avoided:
– Peanuts
– Tree nuts
- Shellfish
- Fish
- Eggs
- Milk
• Benefits of this remain to be proven; the strategy
is recommended by some authorities
• Hypoallergenic infant formulae if breast-feeding
not possible
23
Current Recommendations for Practice
(continued)
• No family history of allergy:
– Good nutrition practices for mother from
preconception onwards
– Good nutrition practices for early infant feeding
– Breast-feeding is the best possible source of
nutrition and protection
– Allergen avoidance is unnecessary unless the
infant demonstrates signs of allergy
24
Current Recommendations for Practice
(continued)
• If infant demonstrates overt signs of allergy
(eczema; gastrointestinal complaints; rhinitis;
wheeze)
– Identify specific food trigger by elimination and
challenge
– Exclusive breast-feeding with mother excluding her
own and baby’s food allergens
– If breast-feeding is not possible, extensively hydrolyzed
casein formula
• Careful monitoring of mother’s diet during
lactation for nutritional adequacy, especially of
vitamins and trace elements
25
Foods Most Frequently Causing Allergy
in Babies and Children
1. Egg
6. Fin fish
» white
7. Wheat
»yolk
8. Soy
2. Cow’s milk
9. Beef
3. Peanut
10. Chicken
4. Nuts
11. Citrus fruits
5. Shellfish
12. Tomato
26
Suggested Sources of Sensitizing Food
Allergens
• Present thinking is that sensitization occurs
predominantly from external sources
• The antigens in mother’s milk then elicit
symptoms in the previously sensitized infant
• Exposure to food antigens in breast milk normally
tolerizes infant to foods
• However, recent research suggests that
sensitization via breast milk may occur in the
atopic mother and baby pair: this remains to be
proven
27
Suggested Sources of Sensitizing Allergens
(continued)
• Food sources of allergens
– Via placenta prenatally (unproven)
– Mother’s diet via breast milk during lactation
– Infant formulae, especially in the new-born nursery
before first feeding of colostrum
– Solid foods
– Covertly by caretakers
– Accidentally
28
Introduction of Solid Foods
• Disagreement among authorities about:
– At what age to introduce solids
– Which solids to introduce
– Which foods should be delayed until
later age
29
Introduction of Solid Foods
• Results of studies are confounded by:
– Genetic factors may influence development of
tolerance or sensitization
– Th1 or Th2 response may be influenced by
environmental exposure
– Some initial evidence that “window of
opportunity” in maturation of systems may play
a role
30
Recommendations for Introduction of Solids
to High Risk for Allergy Infants
• Most recent US consensus document
recommends for infant at risk for allergy:
– Optimal age for introduction of solids is six
months
– Dairy products introduced at 12 months
– Eggs at 24 months
– Peanut, tree nuts, fish, seafood delayed until at
least 36 months
• Supplemental formula feeding no earlier
than 6 months
__________________
Fiocchi et al July 2006
31
Recommendations for Introduction of Solids
to High Risk for Allergy Infants
• Introduction of solid foods should be
individualized
• Foods should be introduced one at a time in small
amounts
• Mixed foods containing various potential food
allergens should not be given unless tolerance to
each ingredient has been assessed
32
Recent Evidence for Early Introduction of
Solids?
• “Delaying initial exposure to cereal grains until after 6
months may increase the risk of wheat allergy”1
• Based on questionnaires and parental report of wheat
allergy
• Excluded children with celiac disease
• 16 children reported to have wheat allergy by parents
• Four had wheat-specific IgE
• These four were reported to have been first exposed to
wheat grains after 6 months of age
Previous studies:
• “The possibility of cereal allergy after the
introduction of cereal formula during the lactation
period should not be underestimated”2
_________________
1Poole et al June 2006
________________
2Armentia et al 2002
33
Introduction of Solid Foods in Relationship to
Diabetes and Celiac Disease
• DAISY1 and BABYDIAB2 studies suggest that
the age at which an at-risk for diabetes infant is
fed cereal is important in determining his or her
risk of type 1 diabetes mellitus (DM)
– Autoantibody directed against pancreatic islet cells used
for detecting DM, not onset of the disease
• Both studies indicate that early introduction of
gluten-containing cereals is a risk factor in DM
• DAISY shows similar risk from early introduction
of rice-based (non-gluten) cereals
______________
1Norris et al 2003
______________
2Zeigler et al 2003
34
Introduction of Solid Foods in Relationship to
Diabetes and Celiac Disease
• Previous studies had implicated early introduction
of cow’s milk as a precipitating factor
• BABYDIAB actually suggested early exposure to
cow’s milk may be protective
• DAISY results suggest that high risk for celiac
disease occurs if gluten-containing grains are
introduced before 3 months or after 7 months
• Final conclusions:
– “Current infant feeding practices should not be
changed”
_______________
Norris et al 2005
35
Measures to Reduce Food Allergy in Infants
with Symptoms of Allergy or at High Risk
Because of Genetic Background
1. Exclusive breast-feeding for the first 6 months
2. Total maternal avoidance of:
– any food inducing allergy symptoms in the infant
– any food inducing allergy symptoms in mother
–
–
–
–
–
Eggs
Cow’s milk and milk products
Peanuts
Nuts
Shellfish
_________________
Zeiger S. 2003
Muraro et al 2004
As a preventive
measure initially if
not avoided in
above categories
{clinicians
disagree about
this}
36
Measures to Reduce Food Allergy in Infants
(continued)
3. Colostrum as soon after birth as possible: provides
sIgA which is absent in newborn
4. Avoid infant formulae in the newborn nursery: NO
exposure to formulae in the hospital
5. Avoid small supplemental feedings of infant formulae
at widely spaced intervals
6. If formula is unavoidable introduce in incremental
doses over a 3-4 week period
37
Measures to Reduce Food Allergy in Infants
(continued)
7. Introduce solid foods after 6 months starting with the least
allergenic. Use incremental dose introduction to promote
oral tolerance
8. Delay the most allergenic foods until after 12 months:
– Cow’s milk
 Eggs
– Shellfish
 Fish
9. Delay peanuts and nuts until after 2-3 years
10. Other foods are not specified, but it may be beneficial to
delay introducing the following foods if the child shows
signs of allergy:
– Citrus Fruits
 Tomatoes
– Beef
 Chicken
– Soy
 Wheat
38
Infant Formulae for the Allergic Baby
Current Recommendations
• Cow’s milk based formula if there are no
signs of milk allergy
• 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
39
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 have become intolerant to other
foods in the meantime
• Tolerance of specific foods :
After 1 year:
– 26% decrease in allergy to:
• Milk  Soy
• Egg  Wheat

Peanut
– 2% decrease in allergy to other foods
________________
Bishop et al 1990
40
Prognosis
Age at which milk was tolerated by milk-allergic
children:
– 28% by 2 years of age
– 56% by 4 years of age
– 78% by 6 years of age
• About 25% of allergic children develop
respiratory allergies
• Allergy to some foods more often than others
persists into adulthood:
– Peanut
 Tree nuts
– Shellfish
 Fish
41
Progression of Peanut Allergy
• Peanut allergy, like many early food allergies, can be
outgrown
• 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
42
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
43
Probiotics
Microorganisms in the Bowel
• The healthy large bowel sustains a resident
microbiota of bacteria, fungi, and other harmless
microorganisms
• Beneficial effects include:
– Synthesis of vitamins:
•
•
•
•
•
Vitamin K
Biotin
Thiamin
Folic acid
Vitamin B12
– Interaction with immune cells to maintain a healthy
epithelium
– Positive competition with invading pathogens to resist
disease
44
Resident Microbiota
• An individual’s bowel microflora is established after
weaning
• Remains stable throughout life unless events
intervene
• Individuals in the same household, eating the same
diet, may have a vastly different bowel microflora
• After oral antibiotics several microbial species will be
killed, but after about 6 months the previous strains
become re-established and microflora returns to its
pre-antibiotic state
• Probiotics may alter the gut microenvironment by
changing the types of microorganisms present and
the cytokines produced by the local immune cells
45
Bowel Microflora and Allergy
• The type of gut colonization during the first weeks of
life may predispose an individual to atopic disease
• Microflora of the bowel of a breastfed infant is
different from that of a formula-fed baby
• The gut microflora influences:
– Resistance to infection
– Immunological environment for subsequent
challenges, including food allergens
– May influence predominance of Th1 or Th2
response
_________________
Kirjavainen et al 1999
46
Probiotic
• Living micro-organisms within a food that is
designed to provide health benefits beyond the
food’s inherent nutritional value
• The types of micro-organisms used have certain
characteristics to be of any value:
– Must be capable of living within the human bowel
without causing any harm to the host
– Produce metabolites to improve the health of the body
– Have a beneficial interaction with the local immune
cells
______________
Thompson 2001
47
Probiotic Characteristics
• Probiotic micro-organisms alter the gut
microflora by competitively interacting with
the existing flora by:
– Production of antimicrobial metabolites
– Modulating the local immune response to the
indigenous micro-organisms
_____________
Shanahan 2000
48
Forms of Probiotic Agents
• Examples of food supplements containing
live culture:
–
–
–
–
–
–
–
Yogurts
Fermented milks
Fortified fruit juice
Powders
Capsules
Tablets
Sprays
49
Prebiotics
• Non-digestible food ingredients that selectively
stimulate a limited number of bacteria, to
improve health
• Examples:
– Fructo-oligosaccharides (FOS)
– Lactulose
– Galacto-oligosaccharides (GOS)
• Provided in:
–
–
–
–
Beverages and fermented milks
Health drinks and spreads
Cereals, confectionery, cakes
Food supplements
50
Synbiotics
• Combine prebiotics and probiotics
• Prebiotic substrate should enhance survival
of probiotic bacteria
• Example:
– Bifidobacteria + fructo-oligosaccharide (FOS)
• In order to establish the new species, need
to continue to provide live culture, and
appropriate substrate
51
Probiotics and Lactose Intolerance
• Lactobacilli, bifidobacteria and Streptococcus
thermophilus, assist in reducing the symptoms of
lactose intolerance
• Produce the enzyme beta-galactosidase (lactase) in
yogurt
• Microbial lactase breaks down lactose
• The fermented milk itself delays gastrointestinal
transit, thus allowing a longer period of time in
which both the human and microbial lactase
enzyme can act on the milk lactose.
52
Microflora and Lactose Intolerance
• Lactose tolerance in people who are deficient in
lactase may be improved by continued ingestion of
small quantities of milk
• Does not improve or affect the production of lactase
in the brush border cells of the small intestine
• Continued presence of lactose in the colon contributes
to the establishment and multiplication of bacteria
capable of synthesizing the beta-galactosidase
enzyme over time
• Resident micro-organisms will break down the
undigested lactose in the colon
• Reduces the osmotic imbalance within the colon that
is the cause of much of the distress of lactose
intolerance
_________________53
de Vrese et al 2001
Clinical Trials of Probiotics
• Not all probiotics have been tested in clinical
studies with regard to allergy prevention or
treatment
• L. bulgaricus seemed to have no effect on
immune parameters, whereas it was associated
with lower frequency of allergies
• L. acidophilus consumption accelerated
recovery from food allergy symptoms
• These effects have also been observed in
infants with eczema and cow's milk allergy
using infant formulas supplemented with
L. rhamnosus.
54
Trials on Probiotics and Eczema Prevention
•
•
•
•
•
•
Pregnant women took capsules containing Lactobacillus
rhamnosus GG (LGG) during the last two to four weeks of
pregnancy
The newborn infants were given the same microorganism
from birth to six months
Breast-feeding mothers continued to take the capsules
during lactation
The babies were given the bacteria mixed with water by
spoon
Subjects taking the probiotic had a reduced risk of
developing atopic dermatitis (eczema) compared to controls
up to 4 years of age
Other studies found no reduced incidence of eczema in
babies treated with probiotics
_________________
Kalliomaki et al 2003
55
Prebiotics and Eczema
•
•
A few preliminary studies suggested increased
bifidobacteria may be associated with a decreased
incidence of atopic dermatitis
Stool of infants fed formula containing
oligosaccharides (FOS and GOS) in comparison to
infants not fed the test formula had:
–
–
–
–
–
•
Increased numbers of bifidobacteria and lactobacilli
Increased amount of short chain fatty acids
Increased proportion of acetate
Decreased proportion of propionate
Lower stool mean pH
This is closer to that seen in breast-fed babies
compared to those fed usual infant formulae
_______________
Ben XM et al 2004
56
____________
Knol et al 2005
Status of Probiotics as Therapy
• Great care must be taken in transferring data from
laboratory and experimental animal studies into
human use
• Applies also to the use of known probiotics, some
of which are already present in human nutrition,
such as yoghurt
• Not all strains of bacteria in use as probiotics are
completely harmless
• Their immune-modifying effects and possible
antiallergic and anti-cancer actions require large
clinical studies
57
Detailed Schedule for Introducing
Solids to the Allergic Baby
• Factsheets and FAQs:
• www.allergynutrition.com
58