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Weaning: The Allergists Point of view Dal mito alla realtà Alessandro Fiocchi Melloni Pediatria, Milano.

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Presentation on theme: "Weaning: The Allergists Point of view Dal mito alla realtà Alessandro Fiocchi Melloni Pediatria, Milano."— Presentation transcript:

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. 2006;368:733-43

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, 1990;20:S3, 9-14

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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. 1991;310:453–458 Fergusson DM. Asthma and infant diet. Arch Dis Child. 1983;58:48–51 Fergusson DM. Early solid feeding and recurrent childhood eczema: a 10-year longitudinal study. Pediatrics. 1990;86:541–546 Morgan J. Eczema and early solid feeding in preterm infants. Arch Dis Child. 2004;89:309–314 Zutavern A. The introduction of solids in relation to asthma and eczema. Arch Dis Child. 2004; 89:303–308 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 Poole JA. Timing of initial exposure to cereal grains and the risk of wheat allergy. Pediatrics. 2006; 117:2175–2182 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. 2008;121:183-91

6 AAP review of the literature 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. 2008;121: EndpointFinding Kajosaari M Solids 3 vs. 6 monthsAD FA at 1 year AD = FA = at 5 years Fergusson DM 1983 Solids < 4 vs. solids > 4 months AD Asthma = at 4 years Fergusson DM 1990 AD Asthma = at 10 years Morgan J solids at 4 months AD at 1 years Zutavern A Birth cohortNo effect Zutavern A Birth cohortNo effect Poole JA Early cereals (< 6 months) Cereal-specific IgE

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. 2008;121:183-91

8 Weaning timing in Australia Dietary guidelines for children and adolescents in Australia. Australian National Health and Medical Research Council, endorsed 10 April 2003 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

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10 2252 newborns enrolled ( ) 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 GINI (German Infant Nutritional Intervention Study Group) Von Berg A, J Allergy Clin Immunol 2003; 111: RCT Level Ib RCT Level Ib

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:

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13 Can the early introduction of solid foods precipitate the development of food allergy? 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; 86:541-6 Cohort study with high probability of causal relationship Level II a Cohort study with high probability of causal relationship Level II a

14 Can an early introduction of solid foods anticipate the development of food allergy? 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 2001;31: Case-control study Level II b Case-control study Level II b

15 Solid food at an early age (< 8 weeks or 8-12 weeks) respiratory illness at weeks of age persistent cough at and 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. 1993;306: Can an early introduction of solid foods anticipate the development of food allergy? Cohort study with high probability of causal relationship Level II a Cohort study with high probability of causal relationship Level II a

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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. 2004;89:309-14

18 Morgan J. Eczema and early solid feeding in preterm infants. Arch Dis Child. 2004;89: Variables not statistically significant for 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.

19 Variables statistically significant for the development of eczema by 12 months post-term Morgan J. Eczema and early solid feeding in preterm infants. Arch Dis Child. 2004;89: GroupsORlimits 4+ foods by 17 weeks post-term Solids < 10 weeks or atopic parents Cohort study with high probability of causal relationship Level II a Cohort study with high probability of causal relationship Level II a

20 Food allergy is a matter of geography after all 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; 57:362-5 Cohort study with high probability of causal relationship Level II a Cohort study with high probability of causal relationship Level II a

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22 Zutavern A. The introduction of solids in relation to asthma and eczema. Arch Dis Child 2004: 89: term infants Follow-up 5½ years Outcome measures: 1.eczema 2.skin prick test inhalants 3.preschool wheezing - transient wheezing, at age 5 years 4.Introduction of solids assessed retrospectively at age 1 year. Eczema and early solid feeding

23 Zutavern A. The introduction of solids in relation to asthma and eczema. Arch Dis Child 2004: 89:303-8 Eczema and early solid feeding Food< 3 months> 3 monthsP < Solid foods Fish Milk Egg

24 Zutavern A. The introduction of solids in relation to asthma and eczema. Arch Dis Child 2004: 89:303-8 …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 4–6 months. Eczema and early solid feeding Cohort study with confounding bias Level II b Cohort study with confounding bias Level II b

25 Reverse causality: a Chinese shadow question?

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28 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: a.CAP with CM, wheat, peanut, soybean, codfish, HDM, cockroach, cat, grass, birch, molds b.questionnaires: doctors diagnosis of AD, age of introduction of solid foods, [vegetables, cereal, fruit, meat, dairy products, egg, fish, others (soybean, nuts, cacao, chocolate)] AD, sensitization and early solid feeding 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:

29 OR for AD by introduction of foods < 6 months in 2612 children All Any solids1.07 (0.83–1.39) > 5 foods0.80 (0.57–1.12) Vegetables1.02 (0.78–1.34) Fruits1.02 (0.78–1.35) Cereals0.94 (0.68–1.29) Meat1.08 (0.72–1.62) Dairy products1.39 (0.78–2.50) No early ADEarly AD 0.67 (0.44–1.02)1.08 (0.73–1.59) 1.06 (0.61–1.83)0.61 (0.37–0.99) 0.66 (0.43–1.01)1.03 (0.69–1.54) 0.65 (0.42–0.99)0.98 (0.65–1.50) 0.44 (0.27–0.72)1.16 (0.71–1.90) 0.83 (0.44–1.59)1.17 (0.64–2.13) 0.54 (0.25–1.14)1.39 (0.78–2.50)

30 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: OR for AD by introduction of foods < 6 months in 2612 children 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 Cohort study with confounding bias Level II b Cohort study with confounding bias Level II b

31 Kull I. Fish consumption during the first year of life and development of allergic diseases during childhood. Allergy 2006: 61: Fish consumption during the first year of life and development of allergic diseases during childhood. 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 Cohort study with high probability of causal relationship Level II a Cohort study with high probability of causal relationship Level II a

32 Introduction of solids and atopic conditions at 6 years of age (multivariate) 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. 2008;121:e44-52 Ealrly vs late introduction of solids: 4-6 months aOR95%CI Doctor diagnosis of eczema Symptoms of eczema Doctor diagnosis of asthma Asthma symptoms Diagnosis of allergic rhinitis Allergic rhinitis symptoms Food sensitisation Inhalant sensitisation

33 Introduction of solids and atopic conditions at 6 years of age (multivariate) 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. 2008;121:e44-52 Ealrly vs late introduction of solids: >6 months aOR95%CI Doctor diagnosis of eczema Symptoms of eczema Doctor diagnosis of asthma Asthma symptoms Diagnosis of allergic rhinitis Allergic rhinitis symptoms Food sensitisation Inhalant sensitisation

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. 2008;121:e44-52

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. 2008;121:e44-52

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. 2008;121:e44-52

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. 2008;121:e44-52

38 Conclusions 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. 2008;121:e44-52 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.

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. 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 Exposure ascertainment was another important source of bias Most studies failed to systematically define the quality and quantity of solid foods that were introduced Some study results may have been influenced by outcome misclassification Lack of blinding to feeding history during study examinations may have led to a biased evaluation of outcome status.

40 To eat or not to eat…

41 Can avoidance of solid foods prevent the development of food allergy? Saarinen UM, Kajosaari M Prophylaxis of atopic disease: role of infant feeding. Lancet i: , 1980 Kajosaari M, Saarinen UM Prophylaxis of atopic disease by six months' total solid foods elimination. Acta Paed Scand 72:411, 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 < b food allergy a < b RCT Level Ib RCT Level Ib

42 2252 newborns enrolled ( ) 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 GINI (German Infant Nutritional Intervention Study Group) Von Berg A, J Allergy Clin Immunol 2003; 111: RCT Level Ib RCT Level Ib

43 Age 4-8 months 1 yr* 2.5 yr* 5 yr * Randomisation/ Stratification 4-8 month old children eczema and/or egg allergy Recruitment Intervention group – Peanut consumed 3 times per week(n240) Control Group (n240) peanut avoidance LEAP Study – Immune Tolerance Network WAO Meeting Bangkok Courtesy of Stephen Durham,

44 LEAP Study (Learning Early About Peanut Allergy): Induction of oral tolerance to peanut Patients: 480 Age: 4-11 months Criteria: Severe eczema Egg allergy SCORAD>40 Exclusion: Peanut allergy Assessment: 1, 2.5 and 5 years WAO Meeting Bangkok Courtesy of Stephen Durham, Primary endpoint: peanut allergy at 5 years of age by DBPCFC

45 WAO Meeting Bangkok Courtesy of Stephen Durham,

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48 1.Breastfeeding is indicated during the first 6 months 2.Complementary feeding from the sixth month of life 3.Delay exposure to solid foods for prevention of food allergies 4.Introduce foods individually and gradually 5.Mixed foods containing various food allergens should not be given as starting foods 6.Cooked, homogenised foods preferred to their fresh counterparts when processing reduces allergenicity Final recommendations ACAAI ARFC. Weaning and food allergy. Ann Allergy Asthma Immunol 2006; 97:10-21

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