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Can we prevent allergies in children? Michael S. Blaiss, MD
 

Can we prevent allergies in children? Michael S. Blaiss, MD

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Conferencia dictada en el XVII Congreso Latinoamericano de Alergia, Asma e Inmunología, Cartagena, 2012

Conferencia dictada en el XVII Congreso Latinoamericano de Alergia, Asma e Inmunología, Cartagena, 2012

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    Can we prevent allergies in children? Michael S. Blaiss, MD Can we prevent allergies in children? Michael S. Blaiss, MD Presentation Transcript

    • Can we preventallergies in children?Michael S. Blaiss, MDClinical Professor of Pediatrics and MedicineUniversity of Tennessee Health Science CenterMemphis, Tennessee USA
    • Introduction Allergic disorders continue to escalate throughout the world • Asthma-8.2% of US population; 9.4% of children • Up to 30% in some populations, particularly developed countries • Food allergies are becoming most common in infants and children Most present management treats symptoms; none of our treatments cure these conditions Are there things we can do to reduce the risk of allergies developing in our “high risk” population?
    • Who do we target to reducethe risk of the atopic march?
    • Is Parental Atopic History a Reliable Predictor of Allergy? Family history increases the risk of developing allergy, HOWEVER… • Most infants with allergy do not have a family history of atopy. • Most infants with a family history of atopy don’t develop allergies.Parental history is not a reliable predictor of allergyBousquet J. et al. J Allergy Clin Immunol 1986;78: 1019-1022. Halken S et al. Allergy 2000;55: 793-802Bergmann RL, et al. Clin and Exp Allergy.1997;:27:752-760. Exl BM, Nutr Res 2001;21: 355-79
    • Family History 50% to 80% of children will have some form of allergy if both parents have an atopic history… Both Parents (5%) Potential for Childhood Allergy One Parent Correlates Or Sibling To Parents’ (31%) History of AllergyNeither Parent (64%) Percentage of children that developed an allergic manifestation Approximate numbers in developed countries. Adapted from Bousquet J. et al. J Allergy Clin Immunol 1986; Halken S et al. Allergy 2000 Kjellman N. et al. Acta Paediatr Scan 1977 4. Exl BM, Nutr Res 2001;21: 355-79
    • Risk of Allergy Increases with a Positive Family History, But…70% of children with allergy do not have parental history of allergy Neither Parent (70%) One Parent (25%) Parental Atopic History in Infants with Allergy Both Parents (5%) *Approximate numbers in developed countries. Adapted from Bousquet J. et al. J Allergy Clin Immunol 1986;78: 1019-1022; Halken S et al. Allergy 2000;55: 793-802. Bergmann RL, et al. Clin 6 and Exp Allergy.1997;:27:752-760. Exl BM, Nutr Res 2001;21: 355-79
    • Risk ReductionStudies-What’s theData?
    • Maternal Dietary AvoidanceIntervention
    • Maternal Dietary AvoidanceIntervention Faith-Magnusson, K. JACI 1992  The 209 mothers to be, enrolled in a randomized, prospective, allergy-prevention study from allergy- prone families, totally abstained from cows milk and egg from gestational week 28 to delivery.  Looked at the development of allergic disease at 5 years of age in their children, compared with the development of allergic disease in the children of the control mothers  There was NO significant difference in eczema, allergic rhinoconjunctivitis, and asthma
    • Journal Allergy Clinical Immunology 2012
    • Methods Estimated maternal peanut and tree nut intake (n = 61,908) using a validated mid-pregnancy food frequency questionnaire. At 18 months, parental report of childhood asthma diagnosis, wheeze symptoms, and recurrent wheeze (>3 episodes) was collected. Current asthma at 7 years as doctor-diagnosed asthma plus wheeze in the past 12 months and allergic rhinitis as a self-reported doctor’s diagnosis. Odds ratios (ORs) comparing intake of 1 or more times per week versus no intake.
    • Delayed introduction of“allergenic” foods
    • Is the Low Prevalence of Peanut Allergy in Israel Due to Hypoallergenic Peanut Products? S. J. Maleki, S. L. Hefle, et al. JACI 2005 San Antonio. RATIONALE: In Israel the majority of infants less than 12 months old regularly consume peanut products in contrast to the UK where infants avoid peanut products Are the peanut protein allergens different in Israel than UK and USA?
    • Peanut Allergy in Israel RESULTS: Peanut protein levels from Israeli and U.K. products were found to be between 68-100%. The Ara h 1, Ara h 2 and Ara h 3 proteins in each peanut product were intact and the levels were comparable as seen in US and UK CONCLUSIONS: The contents of peanut protein, individual major allergens and IgE binding capacity of the popular snacks from Israel CANNOT explain the large discrepancies in the prevalence of peanut allergy among the two countries. IS PROTECTION DUE TO EARLY INTRODUCTION OF PEANUT??
    • Egg Introduction and Egg Allergy“HealthNuts”  study,  2589  infants  population-based, cross-sectional study 4-6 mo 7-9 mo 10-12 mo >12 mo 0 0.1 0.5 1 2 5 10 RR (95% CI) Effects seen in high-risk and low-risk infants with cooked eggintroduction Adjusted for confounding factors Confirmed egg allergy Koplin et al JACI 2010
    • Introduction of milk/milk products and atopy outcomes• KOALA Birth cohort (n=2558, Netherlands)• Followed to age 2: Delayed milk/milk products associated with eczema; delayed “other  foods”  with  atopy,  prolonged  BFing- protective. Adjusted Odds Ratio EczemaSnijders et alPediatrics2008;122:e115-22 Age at introduction of milk protein (mo)
    • What’s the Bottom-Line?What does it all mean?
    • Should all children have allfoods continuously in the firstfew months of life? No! No! No! A one-time ingestion of a small amount of cow’s milk, egg, peanut, etc. MAY lead to oral tolerance Studies are going on—We may see an oral vaccine of these foods given once in infancy in the physician’s office.
    • Breast Feeding
    • Friedman and Zeiger JACI 2005
    • J Allergy Clin Immunol 2010;125:1013-9
    • Soy and Hydrolysate Formulas
    • Relative Risk of Atopic Dermatitis Meta Analysis- Infants with a Family History of Atopy Does breast feeding reduce the risk allergy? Formula Feeding, Risk = 1 1.00 0.5831 Gdalevich M, et al. J Am Acad Derm. 2001;45:520-527.
    • Relative Risk of Atopic Dermatitis Meta Analysis - Infants with a Family History of Atopy Same data: But Converting Breast feeding risk to “1” Breast feeding does not “decrease” risk. Formulas “increase” risk. 1.72 Breast Feeding is THE Standard 1.0032Adapted. OR with BF= .58 vs CMF Gdalevich M, et al. J Am Acad Derm. 2001;45:520-527.
    • Today’s “modern formula” for Non-breastfed Infants Intact (allergenic) cow milkprotein formula in a sterile form. Any alternatives?
    • Protein size and AllergenicityHigh Molecular Weight Low Molecular Weight Immune System Potential for Hypersensitivity (Allergic Reaction)
    • Hydrolysis Can Reduce Allergenicity of Cow Milk Proteins* 14,000 ~12,000 12,000 10,000 Daltons 8,000 6,000 4,000 2,000 ~ 450 ~1,220 0 Extensively Partially Whole Protein Hydrolyzed Casein Hydrolyzed Whey Casein/Whey Median Molecular Weight of Infant Formulas***It must be noted that, unlike extensively hydrolyzed casein formulas, partially hydrolyzed whey formulas are routine infant formulas and not 36intended for therapeutic use in infants who have already presented with allergic disease.**Approximate values as reported by major manufacturers.
    • Extensively hydrolyzed casein formula can reduce the incidence of AD in infancy Cumulative Incidence of Atopic Dermatitis ≤ 12 Months: ExtensivelyHydrolyzed Casein Formula vs Cow Milk Formula in Risk Reduction Studies 80 Extensively Hydrolyzed Casein Intact Cow Milk Cumulative Incidence of AD (%) p=0.006 60 40 p=0.059 p<0.05 20 p=NS 0 V Berg 2008 on Oldaeus 1997 Zeiger 1995 Mallet 1992 * Graph depicts only published, peer-reviewed, prospective trials. ** 9 months: Oldaeus 1997; 12 months: Von Berg 2008, Zeiger 1995, Mallet 1992; **** p-values in italics indicate that no p-value is reported in publication; p-value is based on calculated OR and CI 37 *****Because questions and controversy have arisen regarding the clinical trials carried out by Dr. R Chandra (1989, 1991, 1997), the information is not presented here.
    • Extensively hydrolyzed casein formula can reduce the incidence of AD in infancy Cumulative Incidence of Atopic Dermatitis > 12 Months: Extensively Hydrolyzed Casein Formula vs Cow Milk Formula in Risk Reduction Studies Extensively Hydrolyzed Casein Cumulative Incidence (%AD) 60 p=NS Intact Cow Milk 50 40 p<0.002 30 p=NS p<0.01 20 10 0 Von Berg 2008 Oldaeus 1997 Zeiger 1995 Mallet 1992*Graph depicts only published, peer-reviewed, prospective trials with data collection at timepoints >12 months. 38**18 months: Oldaeus 1997, Chandra 1989; 4 years: Mallet 1992; 7 years: Zeiger 1995; 6 years: Von Berg 2008.***Because questions and controversy have arisen regarding the clinical trials carried out by Dr. R Chandra (1989, 1991, 1997), the information is not presented here.
    • Extensively Hydrolyzed Casein Formulas and Allergy Risk Reduction Extensively hydrolyzed casein formulas are effective in reducing the risk of atopic dermatitis. These formulas have increased osmolality, usually less palatable. Approved by the FDA as exempt (therapeutic) formulas. Designed to treat symptoms of cow’s milk allergy.
    • Partially hydrolyzed whey formula can reduce the risk of AD in infancy Cumulative Incidence of Atopic Dermatitis ≤ 12 Months Partially Hydrolyzed Whey Formula vs Cow Milk Formula in Risk Reduction Studies 60.0 Partially Hydrolyzed Whey Intact Cow MilkCumulative Incidence of AD (%) p<0.05 p=0.004 p=NS 40.0 p<0.05 p>0.05 p<0.05 20.0 p>0.05 0.0 Von Berg Chan 2002 Exl 2000 Marini 1996 Vandenplas Tsai 1991 Vandenplas 2008 1995 1988 *Graph depicts only published, peer-reviewed, prospective trials with data collection at time points ≤12 months. **4 months: Vandenplas 1988; 6 months: Exl 2000; 12 months: Von Berg 2008, Marini 1996, Vandenplas 1995, Tsai 1991 ***p-values in italics indicate that no p-value is reported in publication; p-value is based on calculated OR and CI 40 ****Because questions and controversy have arisen regarding the clinical trials carried out by Dr. R Chandra (1989, 1991, 1997), the information is not presented here.
    • Partially hydrolyzed whey formula can reduce the risk of AD in infancy Cumulative Incidence of Atopic Dermatitis > 12 Months Partially Hydrolyzed Whey Formula vs Cow Milk Formula in Risk Reduction Studies P=0.09 P<0.021 NS NS NS*Graph depicts only published, peer-reviewed, prospective trials with data collection at timepoints >12 months.**30 months: Chan 2002; 3 years: Marini 1996; 4 years: D’Agata 1996; 5 years: Chandra 1997, Vandenplas 1995; 6 years: Von Berg 2008 41***p-values in italics indicate that no p-value is reported in publication; p-value is based on calculated OR and CI****Because questions and controversy have arisen regarding the clinical trials carried out by Dr. R Chandra (1989, 1991, 1997), the information is not presented here.
    • Partially Hydrolyzed Whey Formulas and Allergy Risk Reduction Partially hydrolyzed whey formulas may be effective in reducing the risk of atopic dermatitis. They are designed for routine use to reduce the risk of cow’s milk allergy symptoms. Unlike extensively hydrolyzed casein formulas, partially hydrolyzed whey formulas are routine infant formulas and not intended for therapeutic use in infants who have already presented with allergic disease.
    • The German Infant Nutritional Intervention (GINI) Study Effect of Hydrolyzed Cow Milk Formula for Allergy Prevention Largest, longest, independent study assessing the risk of AD with hydrolyzed infant formula 2,252 infants enrolled in the study:  889 exclusively breastfed to 4 mo  945 infants included in per protocol  418 infants either non-compliant or drop-outs  Extensively hydrolyzed casein had significantly higher number of non-compliant subjects than other formula groups (p=0.02) Incidence of allergic manifestation at 12 months was 13% and by 6 years it was 39%43 Von Berg et al., 2003 J Allergy Clin Immunol 111(3): 533-40 Von Berg et al. 2008 J Allergy Clin Immunol 121(6): 1442-1447
    • GINI Study - Risk of AD at 12 months: Adjusted Odds Ratio Intact Cow Milk 1.0 Extensively Hydrolyzed Whey 0.81 CI (0.48-1.4) 19% risk reduction vs. CMFPartially Hydrolyzed Whey 0.56 CI (0.32-0.99) * 44% risk reduction vs. CMF * 58% risk reduction vs. CMF Extensively Hydrolyzed Casein 0.42 CI (0.22-0.79) 0 0.2 0.4 0.6 0.8 1 *p < 0.05 vs Intact Cow Milk 44 Von Berg et al., 2003 J Allergy Clin Immunol 111(3): 533-40
    • GINI Study - Risk of AD at 6 years: Adjusted Odds Ratio Intact Cow Milk 1.0 Extensively Hydrolyzed 0.74 CI (0.56-0.98) Whey * 26% risk reduction vs CMFPartially Hydrolyzed Whey 0.64 CI (0.48-0.86) * 36% risk reduction vs CMF Extensively Hydrolyzed Casein 0.55 CI (0..39-0.76) * 45% risk reduction vs CMF 0 0.2 0.4 0.6 0.8 1 *p < 0.05 vs Intact Cow Milk 45 Von Berg et al., 2008 J Allergy Clin Immunol 121(6): 1442-47
    • Guidelines for the Diagnosis and Management of FoodAllergy in the United States: Summary of the NIAIDSponsored Expert Panel Report; JACI 2010 Guideline 39: The EP suggests that the use of hydrolyzed infant formulas, as opposed to cow’s milk formula, may be considered as a strategy for preventing the development of FA in at-risk infants who are not exclusively breast-fed (‘‘at risk’’ is defined in Guideline 32) Cost and availability of extensively hydrolyzed infant formulas may be weighed as prohibitive factors
    • Recommendation Maternal dietary restrictions during pregnancy and breastfeeding are not recommended. 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.
    • Recommendations (cont.) There is evidence that breastfeeding for at least 4 months protects against wheezing in early life and decreased risk of asthma Breastfeeding should be recommended because of other beneficial effects, BUT if breast feeding is not possible, an extensively hydrolyzed casein or partially hydrolyzed whey formula is recommended (rather than conventional cow’s milk formulas) Soy formulas and other formulas (eg, goat’s milk) are not recommended for reducing food allergy risk
    • Recommendation (cont.) Solid foods should not be introduced before 4 to 6 months, though studies are needed for a one time introduction of allergenic foods during this time frame for oral tolerance Delaying the introduction of solids past 6 months shows no evidence of a protective benefit— regardless of type of formula used or breastfeeding. This includes solids that are thought to be highly allergenic
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