Transcript Primary Prevention of Atopy: Is it possible?

Primary Prevention of Allergies in
Children:
Is it possible?
Adelle R. Atkinson, MD, FRCPC
Consultant Allergist/Immunologist
The Hospital for Sick Children
Toronto, Canada
51st Annual Scientific Assembly
November 2013
Which Way is the Lady Turning?
Conflicts of Interest
 Have been supported by educational grants from
Pfizer, Nestle
Objectives
 By the end of this session, you will be able to:
1. Define primary prevention of atopy.
2. Understand existing guidelines
 Should we believe everything we read?
3. Discuss guidelines for advising your high risk
families
Case
• JG is a 30 year old women who has come to ask your
advice. She is currently 12 weeks pregnant, and has a
healthy but very atopic 2.5 year old (food allergies,
atopic dermatitis, asthma)
• JG would like to know what she can do during and
after her pregnancy to prevent her next child from
having such significant atopy
• JG has environmental allergies and her husband has
asthma
Primary Prevention of AtopyBackground
Allergies
Eczema
Asthma
Primary Prevention of AtopyBackground
 ‘at risk’ children include children with a genetic
predisposition to atopy (usually defined as one first
degree relative affected)
Primary Prevention of AtopyBackground
 Atopic diseases affect a large percentage of
the population (20% in the U.S.)
 Morbidity - discomfort, quality of life, lifethreatening reactions
 Annual direct costs between $7 and $10 billion
per year for allergies and > $18 billion for
asthma
What is Primary Prevention of Atopy?
 Primary prevention is the institution of an
intervention or group of interventions which
prevent the onset of atopy in otherwise at risk
children
 Blocks sensitization and the development of
IgE-mediated responses
Where does Atopy start?
TH1
IFN TNFβ
IL-2
Infection Response
TH2
IL-10
IL-13
IL-4
IL-5
Allergic response
Immune system development
 NORMAL
TH2
TH1
 ALLERGIC
TH2
Allergic
TH1
Deviation
What tips the balance?
 Microbial Stimulation
TH1
TH2
 Modern Living
TH2
Allergic
TH1
Deviation
The Interventions
Maternal modifications
during pregnancy
Maternal modifications
during lactation
Substitution formulas
for cow’s milk
Prevention of atopy
Delayed introduction
of solids
Prolonged Breast
feeding
Further delay of highly
allergenic foods
The literature
>4500 articles found
dealing with this subject
After applying exclusion
criteria = 89
After more detailed
inclusion criteria = 66
Poor studies were
Excluded leaving ≈ 20 for
final analysis
The literature
 Studies very difficult to do:
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randomization
contamination
multiple outcomes
sample sizes
blinding
multiple testing
multiple interventions
no intention to treat
AAP and European Guidelines
for prevention of Atopy – what they “used to say”
AAP (2000)
Breast feeding
Formula
European (2004)
Optimal source of nutrition
for first year
Exclusive BF for 4 to 6
months
Hypoallergenic formulas can
be used to supplement BF
Formula with reduced
allergenicity
Maternal Diet
Should eliminate peanuts and No conclusive evidence for a
treenuts
protective effect of a
maternal exclusion diet
Lactation Diet
Consider eliminating eggs
cow’s milk and fish
Introduction of
Solids
Delayed intro of solids until
Supplementary foods should
6 months
not be introduced until after
5 months
Delay eggs - 2 years
Delay milk - 1 year
Peanuts, tree nuts and fish - 3
years
Controversy as to whether a
lactation exclusion diet is
beneficial in prevention
The Interventions
Maternal modifications
during pregnancy
Maternal modifications
during lactation
Substitution formulas
for cow’s milk
Prevention of atopy
Delayed introduction
of solids
Prolonged Breast
feeding
Further delay of highly
allergenic foods
Modification of maternal diet
 Several papers in our final
analysis dealt with
modifications to the
maternal diet
 No evidence to support
any modification of the
maternal diet as it relates
to primary prevention
 Weight loss 3rd trimester
Modification of maternal diet
Insert Personal anecdote!
Modification of maternal diet
2007
Modification of Lactation diet
 Many studies looking at a
variety of avoidance diets
during lactation
 Specific food antigens are
detectable in breast milk
within hours
 There is a trend towards
modification of eczema
with the avoidance of
certain foods but the
effect appears to be
short-lived
Prolonged and Exclusive Breastfeeding
 Is Exclusive breastfeeding for at least 4
to 6 months
protective?
 Studies very difficult
to do
 For many reasons,
breast-feeding is
encouraged
Introduction of solids ? delayed
 Some evidence to
suggest the modification
of eczema and food
allergies with delayed
introduction of solids
until 4 to 6 months of age
 Significant delays may
increase allergic
tendencies as a
“window” of tolerance
may be missed
 Insert interesting
anecdote here!
Further delay of highly allergenic
foods?
 No good evidence to
support this delay
 Previous “delay”
recommendations
(AAP) not based on
good evidence
 New
recommendations NO
DELAY
Choice of formula
 Majority of studies focus on
this issue
 Extensively hydrolyzed:
Nutramigen (eHF-C),
Pregestimil and Alimentum
(eHF-C)
 Partially hydrolyzed:
Goodstart (whey)
 Evidence supports a
preventative effect in the
appearance of eczema as
far out as 10 years in some
prospective studies for pHF
(whey)
Choice of Formula
 GINI Study (German Infant Nutritional Intervention)
 Prospective study looking at the longer-term effect of
nutritional intervention with hydrolysate infant formulas
on allergic manifestations in high-risk children
 2252 children randomized at birth to 4 groups to receive
(if not breastfeeding):
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partially hydrolyzed whey (pHF-W)
extensively hydrolyzed casein (eHF-C)
extensively hydrolyzed whey (eHF-W)
standard cow’s milk formula
Choice of Formula
 Outcomes:
 Parent-reported, physician diagnosed allergic diseases
 Intention to treat was used
 Outcomes reported at:
 1 year
 6 years
 10 years
Choice of Formula
 10 year results (published in 2013):
 Significant preventive effect on the cumulative
incidence of Atopic Dermatitis with pHF-W and eHF-C
 No protective effect in any group on asthma, wheeze,
sensitization to foods and allergic rhinitis
 pHF-W more cost-effective than eHF-C
AAP and European Guidelines for
prevention of Atopy
AAP (2000)
Breast
feeding
Formula
Optimal source of nutrition for
first year
YES
European (2004)
Exclusive BF for 4 to 6 months
Yes
Hypoallergenic formulas can be
Formula with reduced
used to supplement BF YES
allergenicity YES
Maternal
Diet
Lactation
Diet
Should eliminate peanuts and
No conclusive evidence for a
protective effect of a maternal
Introduction
of Solids
Delayed intro of solids until 6
treenuts NO
Consider eliminating eggs cow’s
milk and fish NO
exclusion diet YES
Controversy as to whether a
lactation exclusion diet is
beneficial in prevention
YES
months YES
Further delay of highly allergenic
foods NO
Supplementary foods should
not be introduced until after 5
months YES
AAP (2008)
European (2004)
Breast
feeding
For infants at high risk of developing atopic disease,
there is evidence that exclusive breastfeeding for at
least 4 months compared with feeding intact cow
milk protein formula decreases the cumulative
incidence
of atopic dermatitis and cow milk allergy in the
first 2 years of life.
The most effective dietary regimen is
exclusively
breast-feeding for at least 4–6 months
Formula
there is evidence that atopic dermatitis may be
delayed or prevented by the use of extensively or
partially hydrolyzed formulas,
Formulas with documented reduced
allergenicity for at least 4 months,
combined with avoidance of solid food and
cows milk for the same period may be
considered.
Maternal
Diet
restrictions
Lack of evidence that maternal dietary restrictions play
a significant role in prevention
No conclusive evidence for a protective
effect of a maternal exclusion diet
Lactation
Diet
Antigen avoidance during lactation does not prevent
atopic disease (? Exception eczema-need more data)
No conclusive evidence for protective
effect of maternal exclusion diet during
lactation
Introduction
of Solids
Although solid foods should not be introduced before
4 to 6 months of age, there is no current convincing
evidence that delaying their introduction beyond this
period has a significant protective effect on the
development of atopic disease
No protective effect of dietary intervention after 4 to 6
months
Supplementary foods should not be
introduced until after 5 months
There is no evidence for preventive effect
of dietary restrictions after the age of 4–6
months.
Practical Guidelines - How to advise
your patients
> Breast-feeding is the treatment of choice for all
high risk infants for as long as possible (minimum
4 months)
> In high risk infants who cannot be exclusively
breast-fed there is evidence that use of an
extensively or partially hydrolysed formula
reduces the risk of eczema
> To date, there is insufficient evidence to support
antigen avoidance during pregnancy
> There is insufficient evidence to support antigen
avoidance during lactation
Practical Guidelines - How to advise
your patients
> There is no evidence that delayed
introduction of solids beyond 4 to 6 months
has a protective effect
> There is insufficient evidence to support
further delay of particularly antigenic foods
(such as cow’s milk, egg, peanut/treenut)
Summary
 Here is what we said we would do:
1. Define primary prevention of atopy.
2. Understand existing guidelines
 Should we believe everything we read?
3. Discuss guidelines for advising your high risk
families
References
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Arshad SH Allergen avoidance and prevention of atopy. Curr Opin Allergy Clin Immunol 2004;4:119-123.
Greer FR et. Al. Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: the
Role of maternal Dietary Restriction, Breastfeeding, Timing of Introduction of complementary Foods, and Hydrolyzed Formulas.
Pediatrics 2008:121;183-191.
Halken S Prevention of allergic disease in childhood: clinical and epidemiological aspects of primary and secondary allergy
prevention. Pediatric Allergy and Immunology 2004;15(suppl. 16):9-32.
Host A, Koletzko B, Dreborg S, et al. Joint Statement of the European Society for Paediatric Allergology and Clinical Immunology
(ESPACI) Committee on Hypoallergenic Formulas and the European Socient for Paediatric Gastroenterology, Hepatology and
Nutrition (ESPGHAN) Committee on Nutrition. Dietary products used in infants for treatment and prevention of food allergy.
Arch Dis Child. 1999;81:80-84.
Kramer MS, Kakuma R Maternal dietary antigen avoidance during pregnancy and/or lactation for preventing or treating atopic
disease in the child (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd.
Muraro, A et. Al. Dietary prevention of allergy diseases in infants and small children Part III: Critical review of published peerreviewed observational and inteventional studies and final recommendations. Pediatric Allergy and Immunology 2004: 15;291-307.
Osborn DA, Sinn J Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants (Cochrane
Review). In: The Cochrane Library, Issue2, 2004. Chichester, UK: John Wiley & Sons, Ltd.
Ram FSF, Ducharme FM, Scarlett J Cow’s milk protein avoidance and development of childhood wheeze in children with a family
history of atopy (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd.
vonBerg A, et. Al. Allergies in high-risk schoolchildren after early intervention with cow’s milk protein hydrolysates: 10-year
results from the German Infant Nutritional Intervention (GINI) study. Journal of Allergy and Clinical Immunology. 2013
June;131(6):1565-73.
Zeiger RS Food Allergen Avoidance in the Prevention of Food Allergy in Infants and Children. Pediatrics 2003;111(6):1662-1671.
“There should be no teaching without the patient for a text,
and the best teaching is often that taught by the patient
himself”
Sir William Osler
Remarkable teacher known for his clarity, precision and economy of words
Thank you