Document 6429084

Prevention of allergy through
dietary interventions:
What is the evidence?
Hania Szajewska
The Medical University of Warsaw
Department of Paediatrics
Dietary interventions
to prevent allergy
• Maternal pregnancy/lactation diet
• Exclusive breastfeeding
• Use
se of dietary products with reduced
allergenicity
• Timing of introduction of complementary
foods
ESPGHAN Committee on Nutrition
AAP Committee on Nutrition and
Section of Allergy and Immunology
Replaces the AAP 2000 policy statement on hypoallergenic formulas
EAACI, Section of Pediatrics
Maternal pregnancy
and/or lactation diet
Is it effective?
Maternal pregnancy diet
Outcome measure
RR (95% CI)
Atopic eczema in first 12-18
months (2 RCTs, n=334)
1.01 (0.6-1.8)
Asthma in first 18 months
(2 RCTs, n=334)
2.2 (0.4-13)
Allergic urticaria in first 18
months (1 RCT, n=163)
1.01 (0.20-5.15)
Any atopic condition in first
18 months (1 RCT, n=163)
0.71 (0.34-1.49)
Favours elimination diet
1
Favours regular diet
Kramer, Kakuma. Cochrane Review 2006
Maternal pregnancy diet
• Unlikely to reduce substantially her child’s
risk of atopic diseases
• Such diet may have an adverse effect on
maternal and/or fetal nutrition
– Lower mean gestational weight gain
– Higher risk of preterm birth
– Reduction in mean birthweight
Kramer, Kakuma. Cochrane Review 2006
Maternal lactation diet
Outcome measure
RR (95% CI)
Atopic eczema in first 18
mo (1 RCT, n=26)
0.7 (0.3-1.7)
1
Outcome measure
WMD (95% CI)
Eczema area score
(1 RCT, n=34)
-0.8 (-4.4 to 2.8)
Eczema activity score
(1 RCT, n=34)
-1.4 (-7 to 4.4)
Favours elimination diet
0
Favours regular diet
Maternal pregnancy/lactation diet
Recommendations
• AAP 2008
– Not recommended
• EAACI 2008
– No conclusive evidence for protective effect
• ESPGHAN
– Not recommended
Studies with methodological shortcomings,
shortcomings many non-RCTs
Breastfeeding
• What is already known on this topic?
– Reduction in the risk of atopic dermatitis in
children with a family history of atopy and
exclusivey breast fed for at least 3 months
AHRQ April 2007
Breastfeeding
• What is already known on this topic?
– Evidence is conflicting as to whether prolonged
and exclusive BF increases, decreases, or has no
effect on the risks of athma and allergy
– Virtually all evidence is based on observational
studies
• What is new on this topic?
Kramer et al. BMJ 2007;335:815
Breastfeeding
PROBIT Study
• Setting
– Belarussian maternity hospitals & polyclinics
• Participants
– 17 046 mother-infant
infant pairs
– 13 889 (81.5%) followed up at age 6.5 years
• Intervention
– BF promotion intervention modeled on the
WHO/UNICEF baby-friendly
friendly hospital initiative
Kramer et al. BMJ 2007;335:815
PROBIT Study
• Main outcome measures
– Asthma and allergies in childhood
questionnaire
– Skin prick tests of five inhalant antigens
Kramer et al. BMJ 2007;335:815
What the study adds?
• Prolonged and exclusive BF had no protective
effect on allergic symptoms and diagnoses or
on positive skin prick tests
Kramer et al. BMJ 2007;335:815
Limitations
• Cluster randomised trials have not always
been well designed and analysed
• Lack of blinding in the identification and
randomisation of individual participants can
be a problem
Eldridge S et al. BMJ 2008;336:876-80
Limitations
• Highly selected sample
– those intending to breast-feed
feed
• True prevalence of asthma/allergy
– may not have been measured by either history of asthma
symptoms or positive SPT for airborne allergens
• Reported asthma prevalence low compared to
many countries
• Low positive predictive value of SPT
• Still, the best evidence to date
Recommendations
• AAP 2008
– For infants at high risk of atopy, exclusive BF for
at least 4 mo vs intact CMP formula decreases
AD and CMA in the first 2 years of life
– Exclusive
xclusive BF for at least 3 months protects
against wheezing in early life
– No conclusive effect beyond 6 yrs
y of age
Recommendations
• EAACI 2008
– BF for at least 4-6
6 months all infants irrespective
of atopic heredity
• ESPGHAN 2008
– Exclusive or full BF [in all infants] for about 6
months is a desirable goal.
Hydrolysed formulas
• Partially hydrolysed (PH) formula
– Contains reduced oligopeptides that have a
molecular weight of generally less than 5000 d
• Extensively hydrolysed (EH) formula
– Contains only peptides that have a molecular
weight of less than 3000 d
Greer et al. Pediatrics 2008;121:183-191
Cochrane Review 2006
Formulas containing hydrolysed protein
• Objective
– To determine whether use of HF prevents allergy
and food intolerance.
– If HF are effective, to determine what type of HF
is most effective
HF, hydrolysed formula
Osborn DA, Sinn J. Cochrane Review 2006
Cochrane Review 2006
Formulas containing hydrolysed protein
• Search Strategy
– Cochrane Library, MEDLINE, EMBASE, CINAHL
– All up to March 2006
– RCTs, with ≥80% follow-up
up
• Updates a previous version (2003)
• Major differences
– Inclusion of GINI Study (1 y)
– Exclusion of RCTs, if original data unable to be verified
Osborn DA, Sinn J. Cochrane Review 2006
Comparisons to be discussed
•
•
•
•
•
HF
vs
PHF
vs
EHF (whey) vs
EHF (casein) vs
EHF
vs
CMF
CMF
CMF
CMF
PHF
HF, hydrolysed formula; PHF, partially hydrolysed; EHF, extensively hydrolysed; CMF, cow’s milk formula
Hydrolysed formula
vs cow’s milk formula
Outcome
RR (95% CI)
Any allergy
7 RCTs (n=2514)
Cow’s milk allergy
1 RCT (n=67)
0.8 (0.7 to 0.9)
Favours hydrolysed formula
0.4 (0.2 to 0.9)
1
Favours cow’s milk formula
Osborn DA, Sinn J. Cochrane Review 2006
Hydrolysed formula
vs cow’s milk formula
Any allergy
NNT 12
(95% CI 9 to 20)
Osborn DA, Sinn J. Cochrane Review 2006
Hydrolysed formula
vs cow’s milk formula
• No significant difference
– Incidence of childhood allergy
– Infant eczema
– Childhood eczema incidence
– Childhood eczema prevalence
– Infant asthma
– Childhood asthma
– Rhinitis
– Food allergy
Osborn DA, Sinn J. Cochrane Review 2006
Partially hydrolysed whey formula
vs cow’s milk formula
Outcome
RR (95% CI)
Any allergy
7 RCTs (n=1482)
Cow’s milk allergy
1 RCT (n=67)
0.8 (0.7 to 0.97)
Favours hydrolysed formula
0.4 (0.2 to 0.9)
1
Favours cow’s milk formula
Osborn DA, Sinn J. Cochrane Review 2006
Partially hydrolysed whey formula
vs cow’s milk formula
Any allergy
NNT 19
(95% CI 11 to 71)
Osborn DA, Sinn J. Cochrane Review 2006
Partially hydrolysed whey formula
vs cow’s milk formula
• No significant difference
– Childhood allergy
– Infant or childhood asthma
– Eczema
– Rhinitis
– Food allergy
Osborn DA, Sinn J. Cochrane Review 2006
Extensively hydrolysed whey
formula vs cow’s milk formula
• No significant difference
– Any allergy infancy & childhood
– Asthma childhood
– Eczema infancy & childhood
Osborn DA, Sinn J. Cochrane Review 2006
Extensively hydrolysed casein
formula vs cow’s milk formula
Outcome
RR (95% CI)
Any allergy childhood
1 RCT (n=431)
Eczema infancy
3 RCTs (n=1237)
0.7 (0.5 to 0.97)
Favours hydrolysed formula
0.7 (0.5 to 0.97)
1
Favours cow’s milk formula
Osborn DA, Sinn J. Cochrane Review 2006
Extensively hydrolysed casein
formula vs cow’s milk formula
Any allergy childhood
NNT 11
(95% CI 6 to 103
Osborn DA, Sinn J. Cochrane Review 2006
Extensively hydrolysed casein
formula vs cow’s milk formula
Eczema in infancy
NNT 27
(95% CI 14 to 322)
Osborn DA, Sinn J. Cochrane Review 2006
Extensively hydrolysed casein
formula vs cow’s milk formula
• No significant difference
– Any allergy infancy
– Eczema childhood
– Asthma infancy
– Asthma childhood
Osborn DA, Sinn J. Cochrane Review 2006
Extensively hydrolysed formula
vs partially hydrolysed formula
• ↓ Food allergy
• No significant difference
– All allergy
– Any other specific allergy (e.g. eczema, asthma)
Osborn DA, Sinn J. Cochrane Review 2006
Cochrane Review 2006
Summary (positive results)
Comparison
Outcome
HF vs CMF
PH vs CMF
EH casein vs CMF
EH vs PH
NNT
95% CI
Any allergy
12
9 to 20
Cow’s milk allergy
4
3 to 19
Any allergy
19
11 to 71
Cow’s milk allergy
4
3 to 19
Any allergy
11
6 to 103
Eczema
27
14 to 322
Food allergy
15
8 to 64
CMF, cow’s milk formula; EH, extensively hydrolysed; HF, hydrolysed formula; PH, partially hydrolysed
Methodological problems
Would you
recommend HF
to prevent allergy?
If yes,
what type of HF?
Protein hydrolysates
Recommendations
• AAP 2008
– Not
ot all HF provide the same degree of benefit
– eHF
HF may be more effective than pHF
p
• EAACI 2008
– Formula
rmula with documented reduced allergenicity
for at least 4 months
• ESPGHAN/ESPACI (1999)
– Formula with confirmed reduced allergenicty
Complementary feeding
• What is already known on this topic?
– Systematic review: search date March 2005
– Early feeding may increase the risk of eczema
– Little data supporting an association between
early solid feeding and other allergic conditions
• What is new on this topic?
Tarinii BA et al. Arch Pediatr Adolesc Med 2006;160:502-7
Allergic diseases &
Potentially allergenic foods
• What is already known on this topic?
– Only little information about timing of
complementary food introduction and its association
with the development of allergic diseases in
available
Potentially allergenic foods
Previous recommendations
AAP 2000
ASCIA 2006
ACAAI 2006
Solid
foods
Cow’s milk
Eggs
Peanuts
Fish
>4 mo
>12 mo
>24 mo
>36 mo
>36 mo
Option
Option
>36 mo
>36 mo
>4-6 mo
>12 mo
>24 mo
Potentially allergenic foods
• What is new on this topic?
GINI Study
Prospective birth cohort study
• Aim
– To assess the association between the
introdution of solids in the first 12 m and the
occurence of eczema during the first 4 y of life
• Prospective birth cohort study
• N=4753
– Intervention group (family history of atopy)
– Non-intervention
intervention group (no history of atopy)
Filipiak et al. J Pediatr 2007;151:352-8
GINI Study
Prospective birth cohort study
• Outcomes
– Doctor-diagnosed
diagnosed and symptomatic eczema
• Results
– No association between the time of introduction
of solids or the diversity of solids and eczema
– Non-intervention
intervention group – risk for doctor
diagnosed eczema
• ↓ avoidance of soybean/nuts
• ↑ avoidance of egg in the first year
Filipiak et al. J Pediatr 2007;151:352-8
GINI Study
What the study adds?
• No evidence supporting a delayed
introduction of solids >4 m or a delayed
introduction of most potentially allergenic
solids >6 m for the prevention of eczema
Filipiak et al. J Pediatr 2007;151:352-8
LISA Study
Prospective birth cohort study
• Aim
– To investigate whether a delayed introduction of
solids (past 4 or 6 m) is protective against the
development of eczema, asthma, allergic rhinitis,
and food or inhalant sensitisation at the age of 6 y
• Prospective birth cohort study
• N=2073
Zutavern et al. Pediatrics 2008;121:e44-e52
LISA Study
Eczema
• A - In relation to first
introduction of solids
• B - In relation to first
introduction of any
solids in children
without early
symptoms
Zutavern et al. Pediatrics 2008;121:e44-e52
LISA Study
Eczema
Eczema more frequent in children
who received a more diverse
diet within the first 4 months
• A - In relation to first
introduction of solids
• B - In relation to first
introduction of any
solids in children
without early
symptoms
Zutavern et al. Pediatrics 2008;121:e44-e52
LISA Study
Asthma
• C - In relation to first
introduction of solids
• D - In relation to first
introduction of any
solids in children
without early
symptoms
Zutavern et al. Pediatrics 2008;121:e44-e52
LISA Study
Allergic rhinitis
•
E - In relation to first
introduction of solids
• F - In relation to first
introduction of any
solids in children
without early
symptoms
Zutavern et al. Pediatrics 2008;121:e44-e52
LISA Study
What the study adds?
• No evidence supporting a delayed
introduction of solids beyond 4 or 6 months
for the prevention of asthma, allergic rhinitis,
and food or inhalant sensitisation at the age
of 6 y
• For eczema, conflicting results
Zutavern et al. Pediatrics 2008;121:e44-e52
KOALA Birth Cohort Study
• Aim
– To evalaute any associations between the
introduction of cow milk products/other solid
food products and infant atopic manifestations in
the second year of life
• Birth cohort study, n=2558, The Netherlands
Snijders et al. Pediatrics 2008;122:e115-122
KOALA Birth Cohort Study
Delayed introduction of both cow milk products and other food products
was associated with a higher risk for eczema
Snijders et al. Pediatrics 2008;122:e115-122
KOALA Birth Cohort Study
• Conclusion
– Delaying the introduction of cow milk or other
products may not be favourable in preventing
the development of atopy
Snijders et al. Pediatrics 2008;122:e115-122
What would be your
recommendations for complementary
foods for the prevention of allergic
diseases?
Potentially allergenic foods
Recommendations
• ESPGHAN 2008
– Avoidance or delayed introduction of potentially
allergenic foods, such as fish and eggs, has not
been convincingly shown to reduce allergies
ESPGHAN Committee on Nutrition. JPGN 2008; 46: 99–110
99
Potentially allergenic foods
Recommendations
• AAP 2008
– Solid foods not before 4 to 6 mo
– Delayed introduction
• No evidence that prevents atopy
• Also
lso applies to foods thought to be highly allergic,
such as fish, eggs, and foods containing peanut
protein
• EAACI 2008
– Avoidance
voidance of solid food and cow’s milk for at least 4 mo
Potentially allergenic foods
• In summary, what’s new
– New guidelines downplay role of diet in
preventing pediatric allergies
Dietary interventions
to prevent allergy
• Maternal pregnancy/lactation diet
• Exclusive breastfeeding
• Use
se of dietary products with reduced
allergenicity
• Delayed introduction of solid foods
Thank you
for your attention