Weaning: The Allergist

1
Weaning The Allergists Point of view
Dal mito alla realtà
Alessandro Fiocchi Melloni Pediatria, Milano
2
Worldwide Temporal Trends in the Prevalence of
Eczema at 6-7 years
ISAAC Phase Three Study Group. Worldwide time
trends in the prevalence of symptoms of asthma,
allergic rhinoconjunctivitis, and eczema in
childhood ISAAC Phases One and Three repeat
multicountry cross-sectional surveys. Lancet.
2006368733-43
3
Prevention of childhood allergy by dietary
manipulation

• Weaning is potentially dangerous for the
  high-risk baby, therefore special care should be
  addressed when new foods are introduced into the
  infant diet, and offending foods such as eggs,
  fish, and peanuts should be further postponed.

Businco L. Clin Exp Allergy, 199020S3, 9-14
4
(No Transcript)
5
Timing of introduction of solid foods

• Kajosaari M. Atopy prophylaxis in high-risk
  infants prospective 5-year follow-up study of
  children with six months exclusive breastfeeding
  and solid food elimination. Adv Exp Med Biol.
  1991310453458
• Fergusson DM. Asthma and infant diet. Arch Dis
  Child. 1983584851
• Fergusson DM. Early solid feeding and recurrent
  childhood eczema a 10-year longitudinal study.
  Pediatrics. 199086541546
• Morgan J. Eczema and early solid feeding in
  preterm infants. Arch Dis Child. 200489309314
• Zutavern A. The introduction of solids in
  relation to asthma and eczema. Arch Dis Child.
  2004 89303308
• Zutavern A. Timing of solid food introduction in
  relation to atopic dermatitis and atopic
  sensitization results from a prospective birth
  cohort study. Pediatrics. 200611740111
• Poole JA. Timing of initial exposure to cereal
  grains and the risk of wheat allergy. Pediatrics.
  2006 11721752182

Greer FR, Sicherer SH, Burks AW AAP Committee on
Nutrition AAP section on Allergy and
Immunology. 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.
2008121183-91
6
AAP review of the literature
Endpoint Finding
Kajosaari M. 1991 Solids 3 vs. 6 months AD ? FA ? at 1 year AD FA at 5 years
Fergusson DM 1983 Solids lt 4 vs. solids gt 4 months AD ? Asthma at 4 years
Fergusson DM 1990 AD ? Asthma at 10 years
Morgan J. 2004 lt 4 vs. gt 4 solids at 4 months AD ? at 1 years
Zutavern A. 2004 Birth cohort No effect
Zutavern A. 2006 Birth cohort No effect
Poole JA. 2006 Early cereals (lt 6 months) ? Cereal-specific IgE
Greer FR, Sicherer SH, Burks AW AAP Committee on
Nutrition AAP section on Allergy and
Immunology. 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.
2008121183-91
7
Timing of introduction of solid foods

• there is no current convincing evidence that
  delaying their introduction beyond 4 to 6 months
  has a significant protective effect on the
  development of atopic disease regardless of
  whether infants are fed cow milk protein formula
  or human milk.
• This includes delaying the introduction of foods
  that are considered to be highly allergic, such
  as fish, eggs, and foods containing peanut
  protein.

Greer FR, Sicherer SH, Burks AW AAP Committee on
Nutrition AAP section on Allergy and
Immunology. 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.
2008121183-91
8
Weaning timing in Australia
Foods should be introduced individually Initially
, new foods should be offered no more often than
each five to 10 days Avoid confusion Rule out
the (remote) possibility of food allergy or
sensitivity
Dietary guidelines for
children and adolescents in Australia. Australian
National Health and Medical Research Council,
endorsed 10 April 2003
9
(No Transcript)
10
GINI (German Infant Nutritional Intervention
Study Group)
RCT Level Ib
  2252 newborns enrolled (1995-98) 945
formula-fed vs. 865 breastfed Randomised to four
formulae CMF 16 incidence of atopic
manifestations OR 1 eHF W 14 incidence
of atopic manifestations OR 0.86 pHF W
11 incidence of atopic manifestations OR
0.65 eHF C 9 incidence of atopic
manifestations OR 0.51      
Von Berg A, J Allergy Clin Immunol 2003
111533-40
11
Levels of evidence
Level I a meta-analysis of randomised controlled trials (RCT)
Level I b at least one RCT
Level II a at least one well-designed controlled study without randomisation or systematic review of RCT or cohort studies with high probability of causal relationship
Level II b well-designed case-control or cohort study with confounding bias and/or moderate probability of causal relationship
Level III non-experimental descriptive studies (case reports, case series)
Level IV expert committee reports or opinions or clinical experience of respected authorities
Shekelle PG. Clinical guidelines Developing
guidelines. BMJ, 1999 318 593 -6
12
(No Transcript)
13
Can the early introduction of solid foods
precipitate the development of food allergy?
Cohort study with high probability of causal
relationship Level II a

• 1265 New Zealand neonates
• Prospectively followed-up
• - solid foods introduced to 4 months ? ?
  eczema
• by 2 years
• - solid foods introduced to 4 months ? ?
  recurrent -
• chronic eczema by 10 years

Fergusson DM. Early solid food feeding and
recurrent childhood eczema a 10-year
longitudinal study. Paediatrics 1990 86541-6
14
Can an early introduction of solid foods
anticipate the development of food allergy?
Case-control study Level II b

• A case-control retrospective epidemiological
  study
• early introduction of cereals ? asthma from
  grass allergy (OR 5,95 CI 3,89-9,10)
• early exposure to such foods may not be a
  direct risk factor for asthma, but rather a
  marker of increased risk for developing
  respiratory pathway sensitization to other
  Poaceaes

Armentia A. Early introduction of cereals into
childrens diets as a risk factor for grass
pollen asthma. Clin Exp Allergy 2001311250-5
15
Can an early introduction of solid foods
anticipate the development of food allergy?
Cohort study with high probability of causal
relationship Level II a

• Solid food at an early age (lt 8 weeks or 8-12
  weeks)
• ? ? respiratory illness at 14-26 weeks of age
• ? ? persistent cough at 14-26 and 27-39 weeks of
  age
• ? ? eczema

Forsyth JS. Relation between early introduction
of solid food to infants and their weight and
illnesses during the first two years of life.
BMJ. 19933061572-6.
16
(No Transcript)
17
Eczema and early solid feeding
257 preterm infants Follow-up one year Number
and type of solid foods and risk of eczema
Morgan J. Eczema and early
solid feeding in preterm infants. Arch Dis
Child. 200489309-14
18
Variables not statistically significantfor the
development of eczema by 12 months post-term
Maternal age Single infant vs. twin/triplet Number
of children in the family Maternal/paternal
smoking Pets in home Gestational age - birth
weight Duration of breastfeeding Whether or not
ever breast fed Use of infant cows milk formula
before solid food introduction Use of
hypoallergenic formula before solid food
introduction Week at which were introduced CM,
cheese, eggs, fish, fruit, meat, vegetables,
rice.
Morgan J. Eczema and early solid feeding in
preterm infants. Arch Dis Child. 200489309-14
19
Variables statistically significantfor the
development of eczema by 12 months post-term
Cohort study with high probability of causal
relationship Level II a
Groups OR limits limits
4 foods by 17 weeks post-term 3.49 1.51 8.05
Solids lt 10 weeks or atopic parents 2.94 1.57 5.52
Morgan J. Eczema and early solid feeding in
preterm infants. Arch Dis Child. 200489309-14
20
Food allergy is a matter of geography after all
Cohort study with high probability of causal
relationship Level II a

• prevalence of IgE-mediated food allergy in 9070
  infants and young children (0-2 years)
• 1.2 (104/9070) patients with IgE-mediated food
  allergy
• 0.8 (79/9070) patients with IgE-mediated allergy
  to sesame.
• Sesame seed the single major offender

Dalal I. Food allergy is a matter of geography
after all sesame as a major cause of severe
IgE-mediated food allergic reactions among
infants and young children in Israel. Allergy.
2002 57362-5
21
(No Transcript)
22
Eczema and early solid feeding

• 642 term infants
• Follow-up 5½ years
• Outcome measures
• eczema
• skin prick test inhalants
• preschool wheezing - transient wheezing, at age 5
  years
• Introduction of solids assessed retrospectively
  at age 1 year.

Zutavern A. The introduction of solids in
relation to asthma and eczema.
Arch Dis Child 2004 89303-8
23
Eczema and early solid feeding
Food lt 3 months gt 3 months P lt

Solid foods 34.4 35.0 0.88
Fish 35.2 35.7 0.90
Milk 32.3 41.2 0.032
Egg 30.5 39.3 0.025
Zutavern A. The introduction of solids in
relation to asthma and eczema.
Arch Dis Child 2004 89303-8
24
Eczema and early solid feeding
Cohort study with confounding bias Level II b
results do not support the guidelines for the
prevention of asthma and allergy in general
populations stating that the introduction of
solids should be delayed for at least 46 months.

Zutavern A. The introduction of solids in
relation to asthma and eczema.
Arch Dis Child 2004 89303-8
25
Reverse causality a Chinese shadow question?
26
Reverse causality a Chinese shadow question?
27
Reverse causality a Chinese shadow question?
28
AD, sensitization and early solid feeding

• LISA
• 3097 healthy fullterm infants
• 4 German cities (Munich, Leipzig, Wesel, Bad
  Honnef)
• Self-completion questionnaires (0, 6, 12,
  18, 24 months)
• Clinical evaluation at 2 years
• CAP with CM, wheat, peanut, soybean, codfish,
  HDM, cockroach, cat, grass, birch, molds
• questionnaires doctors diagnosis of AD, age of
  introduction of solid foods, vegetables, cereal,
  fruit, meat, dairy products, egg, fish, others
  (soybean, nuts, cacao, chocolate)

Zutavern A. Timing of solid food introduction in
relation to atopic dermatitis and atopic
sensitization results from a prospective birth
cohort study. Pediatrics 2006 117 401-11
29
OR for AD by introduction of foods lt 6 months in
2612 children
All
Any solids 1.07 (0.831.39)
gt 5 foods 0.80 (0.571.12)
Vegetables 1.02 (0.781.34)
Fruits 1.02 (0.781.35)
Cereals 0.94 (0.681.29)
Meat 1.08 (0.721.62)
Dairy products 1.39 (0.782.50)
No early AD Early AD
0.67 (0.441.02) 1.08 (0.731.59)
1.06 (0.611.83) 0.61 (0.370.99)
0.66 (0.431.01) 1.03 (0.691.54)
0.65 (0.420.99) 0.98 (0.651.50)
0.44 (0.270.72) 1.16 (0.711.90)
0.83 (0.441.59) 1.17 (0.642.13)
0.54 (0.251.14) 1.39 (0.782.50)
Zutavern A. Timing of solid food introduction in
relation to atopic dermatitis and atopic
sensitization results from a prospective birth
cohort study. Pediatrics 2006 117 401-11
30
OR for AD by introduction of foods lt 6 months in
2612 children
Cohort study with confounding bias Level II b

• no evidence for a protective effect of a delayed
  introduction of solids on AD and sensitization at
  2 years of age
• no evidence for a protective effect of a delayed
  introduction of solids on AD and sensitization in
  children of atopic parents
• strata of children without early skin or
  allergic symptoms were interpreted as undistorted
  from reverse causality

Zutavern A. Timing of solid food introduction in
relation to atopic dermatitis and atopic
sensitization results from a prospective birth
cohort study. Pediatrics 2006 117 401-11
31
Fish consumption during the first year of life
and development of allergic diseases during
childhood.
Cohort study with high probability of causal
relationship Level II a

• A birth cohort of 4089 new-born infants
• Parental questionnaires at 2 months, 1, 2 and 4
  years
• Parental allergic disease associated with
  delayed introduction of fish
• in the childs diet ? exclusion of such
  children
• Onset of eczema or wheeze during the first year
  of life associated
• with delayed introduction of fish in the
  childs diet ? exclusion of
• such children
• Fish during the first year of life ? reduced
  risk for allergic disease
  ? reduced risk of sensitization
• IgE-sensitization to fish in 18 of the 2614
  children

Kull I. Fish consumption during the first year of
life and development of allergic diseases during
childhood. Allergy 2006 61 1009-15
32
Introduction of solids and atopic conditions at 6
years of age (multivariate)
Ealrly vs late introduction of solids 4-6 months Ealrly vs late introduction of solids 4-6 months Ealrly vs late introduction of solids 4-6 months
aOR 95CI
Doctor diagnosis of eczema 0.71 0.39-1.33
Symptoms of eczema 0.60 0.24-1.51
Doctor diagnosis of asthma 1.10 0.36-3.32
Asthma symptoms 0.76 0.46-1.27
Diagnosis of allergic rhinitis 1.12 0.42-2.99
Allergic rhinitis symptoms 1.01 0.63-1.60
Food sensitisation 3.13 1.45-6.74
Inhalant sensitisation 0.92 0.57-1.49
Zutavern A, LISA Study Group. Timing of solid
food introduction in relation to eczema, asthma,
allergic rhinitis, and food and inhalant
sensitization at the age of 6 years results from
the prospective birth cohort study LISA.
Pediatrics. 2008121e44-52
33
Introduction of solids and atopic conditions at 6
years of age (multivariate)
Ealrly vs late introduction of solids gt6 months Ealrly vs late introduction of solids gt6 months Ealrly vs late introduction of solids gt6 months
aOR 95CI
Doctor diagnosis of eczema 0.44 0.18-1.08
Symptoms of eczema 0.51 0.15-1.70
Doctor diagnosis of asthma 1.20 0.31-4.70
Asthma symptoms 0.77 0.40-1.46
Diagnosis of allergic rhinitis 1.45 0.45-4.63
Allergic rhinitis symptoms 0.63 0.33-1.21
Food sensitisation 3.01 1.19-7.61
Inhalant sensitisation 1.01 0.54-1.87
Zutavern A, LISA Study Group. Timing of solid
food introduction in relation to eczema, asthma,
allergic rhinitis, and food and inhalant
sensitization at the age of 6 years results from
the prospective birth cohort study LISA.
Pediatrics. 2008121e44-52
34
One-year prevalences of doctor diagnoses of
eczema, asthma, and allergic rhinitis (n 2073)
Zutavern A, LISA Study Group. Timing of solid
food introduction in relation to eczema, asthma,
allergic rhinitis, and food and inhalant
sensitization at the age of 6 years results from
the prospective birth cohort study LISA.
Pediatrics. 2008121e44-52
35
Eczema vs. age of first introduction of solids
Zutavern A, LISA Study Group. Timing of solid
food introduction in relation to eczema, asthma,
allergic rhinitis, and food and inhalant
sensitization at the age of 6 years results from
the prospective birth cohort study LISA.
Pediatrics. 2008121e44-52
36
Asthma vs. age of first introduction of solids
Zutavern A, LISA Study Group. Timing of solid
food introduction in relation to eczema, asthma,
allergic rhinitis, and food and inhalant
sensitization at the age of 6 years results from
the prospective birth cohort study LISA.
Pediatrics. 2008121e44-52
37
Allergic rhinitis vs. age of first introduction
of solids
Zutavern A, LISA Study Group. Timing of solid
food introduction in relation to eczema, asthma,
allergic rhinitis, and food and inhalant
sensitization at the age of 6 years results from
the prospective birth cohort study LISA.
Pediatrics. 2008121e44-52
38
Conclusions

• Delayed introduction of solids not associated
  with decreased asthma, allergic rhinitis, or
  sensitization against food or inhalant allergens
  at 6 years of age
• Food sensitization more frequent in late
  introduction
• Relationship between the timing of solid
  introduction and eczema not clear.
• Eczema more frequent in children who received a
  more diverse diet within the first 4 months.

Zutavern A, LISA Study Group. Timing of solid
food introduction in relation to eczema, asthma,
allergic rhinitis, and food and inhalant
sensitization at the age of 6 years results from
the prospective birth cohort study LISA.
Pediatrics. 2008121e44-52
39
Insufficient evidence to suggest that, on its
own, the early introduction of solids to infants
is associated with an increased risk of asthma,
food allergy,allergic rhinitis, or animal
allergies.

• Some study results may have been influenced by
  outcome
• misclassification

• Many studies lacked a rigorous design and so were
  susceptible to multiple biases.

• Some failed to adjust for important known
  confounders, such as milk type used or parental
  history of atopy

• Lack of blinding to feeding history during study
  examinations may have led to a biased evaluation
  of outcome status.

• Exposure ascertainment was another important
  source of bias

• Most studies failed to systematically define the
  quality and quantity of solid foods that were
  introduced

40
To eat or not to eat
41
Can avoidance of solid foods prevent the
development of food allergy?
RCT Level Ib

• 135 children with allergic parents breastfed
  until 6 months
• Group A (70) - 6 months cooked vegetables,
  apple, pear, cereals
• 8 months beef,
  fish
• 10 months egg
• Group B (65) - 3 months potato, carrot,
  cereals, beef
• 4 months egg, fish
• 5 months fruits, commercial
  foods
• 6 months free diet
• eczema a lt b
• food allergy a lt b

Saarinen UM, Kajosaari M Prophylaxis of atopic
disease role of infant feeding. Lancet i
166-167, 1980 Kajosaari M, Saarinen UM
Prophylaxis of atopic disease by six months'
total solid foods elimination. Acta Paed Scand
72411, 1983
42
GINI (German Infant Nutritional Intervention
Study Group)
RCT Level Ib
  2252 newborns enrolled (1995-98) 945
formula-fed vs. 865 breastfed Randomised to four
formulae CMF 16 incidence of atopic
manifestations OR 1 eHF W 14 incidence
of atopic manifestations OR 0.86 pHF W
11 incidence of atopic manifestations OR
0.65 eHF C 9 incidence of atopic
manifestations OR 0.51      
Von Berg A, J Allergy Clin Immunol 2003
111533-40
43
LEAP Study Immune Tolerance Network
WAO Meeting Bangkok 2007 - Courtesy of Stephen
Durham,
44
LEAP Study (Learning Early About Peanut
Allergy)Induction of oral tolerance to peanut
Primary endpoint peanut allergy at 5 years of
age by DBPCFC

• Patients 480
• Age 4-11 months
• Criteria Severe eczema
• Egg allergy
• SCORADgt40
• Exclusion Peanut allergy
• Assessment 1, 2.5 and 5 years

WAO Meeting Bangkok 2007 - Courtesy of Stephen
Durham,
45
WAO Meeting Bangkok 2007 - Courtesy of Stephen
Durham,
46
WAO Meeting Bangkok 2007 - Courtesy of Stephen
Durham,
47
WAO Meeting Bangkok 2007 - Courtesy of Stephen
Durham,
48
Final recommendations

• Breastfeeding is indicated during the first
  6 months
• Complementary feeding from the sixth month of
  life
• Delay exposure to solid foods for prevention of
  food allergies
• Introduce foods individually and gradually
• Mixed foods containing various food allergens
  should not be given as starting foods
• Cooked, homogenised foods preferred to their
  fresh counterparts when processing reduces
  allergenicity

ACAAI ARFC. Weaning and food allergy. Ann Allergy
Asthma Immunol 2006 9710-21
49
(No Transcript)