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1、Infant Food AllergiesWhere Are We Now?,Janice Joneja Ph.D.,RD,2,Food Allergy in the Past 7 Years,Nearly 4%of North Americans have food allergies,many more than recorded in the pastIncidence of food allergy much higher in children(8%)than adults(2%)Prevalence of peanut allergy doubled in American chi
2、ldren younger than 5 years of age in the years 2002-2007,3,Food Allergy in the Past 7 Years,Prevalence of food allergy highest in infants and toddlersCows milk allergy incidence:2.5%of infantsUp to 8%of children under 3 years have allergy to a limited number of foods:Cows milk WheatEgg ShellfishSoy
3、FishPeanut Tree nutsFor every child who actually had a food allergy,over three more children were believed wrongly by their parents to suffer from the condition,_Venter et al 2008,4,Age Relationship Between Food Allergy and Atopy,1,2,3,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,Age(in years),0,Relative In
4、cidence,AsthmaRhinitisEczemaFood AllergyAnaphylaxis,Effect of Food Allergens,Effect of Air-borne Allergens,5,Historical Perspective,Sensitization to food allergens was thought to be the start of the“allergic march”Food allergyAtopic dermatitis/eczemaAsthmaRhinitisReducing sensitization to foods was
5、therefore considered the essential first step in allergy prevention,6,Historical Perspective,Measures of prevention were all designed to avoid sensitization to allergens during what were considered the most vulnerable periods:Intra-uterine life From birth to 2-3 yearsThis meant reduction in exposure
6、 to highly allergenic foods:Mothers diet during pregnancy and lactationDelay in introduction of highly allergenic foods during weaningIn spite of these stringent measures to prevent allergy,incidence of all types of allergies have increased significantly,7,Change in Direction During the Past Five Ye
7、ars,Understanding of the importance of immunological sensitization and toleranceRecognition that tolerance not sensitization is the critical step in allergy preventionFinding that exposure to the allergenic food at an optimum stage is probably a critical step in allergy preventionRecognition that to
8、lerance can be induced after allergy has been established leading to important measures for allergy management,8,Allergy is a Response of the Immune System,Our immune systems are designed to protect the body from invasion by foreign materialsAll foods contain proteins derived from plants and animals
9、 all of which are foreign to the human bodyIn order for food to be absorbed,metabolized,and utilized by the body,the immune system needs to be“educated”that the foreign material is safe,_Herz 2008,9,Education of the Immune System,Involves a complex series of immunological reactions controlled by T c
10、ell lymphocytes(T cells)T helper(Th)cells detect foreign proteins(antigens)in any formT cells then trigger a series of immunological reactions,mediated by cytokines(the“control chemicals”of the immune system),_Joneja 2007,10,T-helper Cell Subclasses,There are two subclasses of T-helper cellsTh1Th2Ea
11、ch Th cell type produces its own specific set of cytokinesThe types of cytokines generated determine the resulting immune responseTh1 principally INF-Th2 principally IL-4,11,Role of T-helper Cell Subtypes,Th1 triggers the protective response to a pathogen such as a virus or bacteriumIgM,IgG,IgA anti
12、bodies are producedTh2 is responsible for the allergic(hypersensitivity)reaction IgE antibodies are produced,12,T cells involved in Oral Tolerance,T cell response depends on the type of T helper cell that is activatedLatest research indicates that T cells that produce a cytokine called TGF-are impor
13、tant in inducing oral toleranceSometimes called Th3 cellsT cells that produce IL-10 and IL-13 may also be involved in toleranceThese also regulate immune response to resident microflora,preventing the usual immune inflammatory response to microorganisms,_Strobel and Mowat 2006,13,Oral Tolerance,“Edu
14、cation”of the T cells to not respond to that food protein when it enters via the oral route called oral toleranceContrasts with the active immune responses needed to protect the gut against continual bombardment by invading pathogens and their products(toxins,etc)Also contrasts with the reduced resp
15、onsiveness to the millions of microorganisms that are permanent residents of the large bowelT cells involved in these processes are called regulator T cells(Treg),14,Prevention of Food Allergy in Clinical Practice,Significant change in directives within the past 5 years:Previously:Avoidance of aller
16、gen to prevent sensitization(allergen-specific IgE)Current:Active stimulation of the immature immune system to induce tolerance of the antigens in food,_Rautava et al 2005,15,Factors Predictive of Allergy:High and Low risk Groups,Many factors investigated as possible predictive markers for allergyOn
17、ly significant variable in studies:Family history of allergy(all types)High risk for allergy:One first degree relative with diagnosed allergy(IgE-mediated)of any typeFirst-degree relative:parent or sibling,16,Does Atopic Disease Start in Fetal Life?,Fetal cytokines are skewed to the Th2 type of resp
18、onseSuggested that this may guard against rejection of the“foreign”fetus by the mothers immune systemIgE occurs from as early as 11 weeks gestation and can be detected in cord blood,_Jones et al 2000,17,Does Atopic Disease Start in Fetal Life?(continued),At birth neonates have low INF-and tend to pr
19、oduce the cytokines associated with Th2 response,especially IL-4So why do all neonates not have allergy?,18,Does Atopic Disease Start in Fetal Life?(continued),New research indicates that the immune system of the mother may play a very important role in expression of allergy in the neonate and infan
20、tIgG crosses the placenta;IgE does notCertain sub-types of IgG(IgG1;IgG3)can inhibit IgE response,19,Significance in Practice,Food proteins demonstrated to cross the placenta and can be detected in amniotic fluidExposure to small quantities of food antigens from mothers diet thought to tolerize the
21、fetus,by means of IgG1 and IgG3,within a“protected environment”,20,Immune Response of the Allergic Mother,Atopic mothers immune system may dictate the response of the fetus to antigens in uteroThe allergic mother may be incapable of providing sufficient IgG1 and IgG3 to downregulate(depress)fetal Ig
22、E There is no convincing evidence that sensitization to specific food allergens is initiated prenatally,21,Diet During Pregnancy,Current directive:the atopic mother should strictly avoid her own allergens and replace the foods with nutritionally equivalent substitutesThere are no indications for mot
23、her to avoid other foods during pregnancyA nutritionally complete,well-balanced diet is essentialAuthorities recommend avoidance of excessive intake of highly allergenic foods such as peanuts and nuts to prevent“allergen overload”,but there is no scientific data to support this,_Kramer et al 2006,22
24、,Breast-feeding and Allergy,Studies indicating that breast-feeding is protective against allergy report:A definite improvement in infant eczema and associated gastrointestinal complaints when baby is exclusively breast-fedReduced risk of asthma in the first 24 months of life,_Kirjavainen et al 2002,
25、23,Breast-feeding and Allergy,Other studies are in conflict with these conclusions:Some report no improvement in symptomsSome suggest symptoms get worse with breast-feeding and improve with feeding of hydrolysate formulaeJapanese study suggests that breast-feeding increases the risk of asthma at ado
26、lescence Why the conflicting results?,_Miyake et al 2003,24,Immunological Factors in Human Milk that may be Associated with Allergy:Cytokines and Chemokines,Atopic mothers tend to have a higher level of the cytokines and chemokines associated with allergy in their breast milkThose identified include
27、:IL-4IL-5IL-8IL-13Some chemokines(e.g.RANTES)Atopic infants do not seem to be protected from allergy by the breast milk of atopic mothers,_Snijders et al 2007 KOALA study,25,Immunological Factors in Human Milk that may be Associated with Allergy:TGF-1,Cytokine,transforming growth factor-1(TGF-1)prom
28、otes tolerance to food components in the intestinal immune responseTGF-1 in mothers colostrum may influence the type and intensity of the infants response to food allergensA normal level of TGF-1 is likely to facilitate tolerance to food encountered by the infant in mothers breast milk and later to
29、formulae and solids,_Rigotti et al 2006,26,Implications of Research Data,Exclusive breast-feeding with exclusion of mothers and babys allergens will reduce signs of allergy in the first 1-2 years;specifically:Cows milk allergyEczemaReduction or prevention of early food allergy by breast-feeding does
30、 not seem to have long-term effects on the development of asthma and allergic rhinitisOther benefits of breast-feeding far outweigh any possible negative effects on allergy:exclusive breast-feeding for 4-6 months is strongly encouraged,27,Summary of 2008 AAP Guidelines for Allergy Management Greer e
31、t al 2008,There is no convincing evidence that women who avoid highly allergenic foods,or other foods during pregnancy and breast-feeding lower their childs risk of allergiesFor high-risk for allergy infants(one first-degree relative with established allergy),exclusive breast-feeding for at least 4
32、months prevents or delays the occurrence of atopic dermatitis(eczema),cows milk allergy,and wheezing in early childhood,_Greer et al 2008,_Sicherer and Burks 2008,28,Preventive Effect of Breast-feeding:KOALA Study,Longer duration of breastfeeding is associated with lower risk for eczema in non-atopi
33、c mothersSlightly lower risk for mothers with allergy but no asthmaLonger duration of breastfeeding reduced risk for wheezing in infants:possibly due to reduction in respiratory infectionsThere is a lack of evidence that exclusive or prolonged breast-feeding has any positive effect on the developmen
34、t of asthma in older children,_Snijders et al 2007 KOALA study,29,Summary of 2008 AAP Guidelines continued,In infants at high risk for allergy who are not exclusively breast-fed for 4-6 months there is modest evidence that the onset of atopic disease(allergy),especially eczema,may be delayed or prev
35、ented by the use of hydrolyzed formulasThere is no good evidence that soy-based infant formulas have any preventive effect on the development of allergy,30,Preventive Effect of Hydrolyzed Infant Formulae,No evidence of any reduction in allergy with hydrolyzed formula compared to breastfeedingLimited
36、 evidence that prolonged feeding with hydrolyzed formula compared to cows milk reduces incidence of CMA and eczemaNo evidence that hydrolyzed formulas have any effect on the development of rhinitis and asthma laterExtensively hydrolyzed cows milk(Ehf)formulas marginally better than partially hydroly
37、zed whey(Phf)in prevention,_Osborn and Sinn 2009 Cochrane Review,_Von Berg et al GINI Study 2009,31,Infant Formulae for the Allergic BabyCurrent Recommendations,Cows milk based formula if there are no signs of milk allergyPartially hydrolysed(phf)whey-based formula if there are no signs of milk alle
38、rgy in high risk for allergy groupExtensively hydrolysed(ehf)casein based formula if milk allergy is proven,_Greer et al AAP 2008Von Berg et al 2007,32,Recommendations for Introduction of Solids to High Risk for Allergy Infants,Little evidence that delaying the introduction of complementary foods be
39、yond 4-6 months of age prevents allergyIntroduction of solid foods should be individualizedFoods should be introduced one at a time in small amountsMixed foods containing various potential food allergens should not be given unless tolerance to each ingredient has been assessed,_Greer et al AAP 2008,
40、_Thygaran and Burks 2008,33,Introduction of Solid Foods in Relationship to Celiac Disease,Results suggest that in high risk for celiac disease infants introduction of gluten-containing grains before 3 months or after 7 months increases incidences of development of CD1Introduction of gluten while bre
41、ast-feeding offers protection or delays onset of celiac disease in at-risk infants2Recommendations:Introduce gluten grains in small amounts between 4 and 6 months while infant is breastfedContinue breast-feeding for a further 2-3 monthsSimilar results for wheat allergy3,_1Norris et al 2005,_2Guandal
42、ini 2007,_3Poole et al 2006,34,Introduction of Peanuts,Directives from pediatric societies(1998-2007)recommended avoidance of peanuts by mothers during pregnancy and lactation,and delaying introduction of peanuts until after 2 or even 3 years of ageResearch indicates that incidence of peanut allergy
43、 in children rose dramatically in the years following release of these directivesRecent research suggests:Avoidance of peanuts reduced development of toleranceEarly exposure leads to reduced incidence of peanut allergy,_Hourihane et al 2007,35,Introduction of Peanuts,Study(n=10,786)among primary sch
44、ool age Jewish children in UK and IsraelPrevalence of peanut allergy(PA):In UK:1.85%In Israel:0.17%Median monthly consumption of peanut in infants aged 8 14 months:In UK:0In Israel:7.1 gDifference not due to atopy,genetic background,social class,or peanut allergenicityIsraeli infants consume peanuts
45、 in high quantities during the first year of life,_Du Toit et al 2008,36,Introduction of Fish,Historically,fish consumption during infancy was considered to be a risk factor for allergyRecent research indicates otherwise:Regular fish consumption during the first year of life associated with a reduce
46、d risk for allergic disease by age 4 years(n=4089)1Babies of mothers who frequently consumed fish(2-3 times per week or more)during pregnancy had one third less food sensitivities than those whose mothers did not consume fish during pregnancy2,_1Kull et al 2006,_2Calvani et al 2006,37,Introduction o
47、f Fish,Study(n=5,000);20.9%developed eczema by 1 year:Babies who were fed fish before nine months of age were 24%less likely to develop eczema by age 1 yearOmega-3 content of fish did not seem to influence the outcomeThe age at which egg and milk were introduced did not affect development of eczemaB
48、reast-feeding did not have any significant impact on development of eczema,_Alm et al 2009,_Hibbeln et al 2007 ALSPAC study,38,The Natural History of Food Allergy,Food allergy most often begins in the first 1 to 2 years of lifeChild is sensitized to the food protein by the immune system developing a
49、llergen-specific IgE to that proteinSensitization does not necessarily mean that the child will develop symptoms when that food is eatenOver time most food allergy is lost,_Wood 2003,39,Prognosis,Most children outgrow early food allergyJohns Hopkins Childrens Center USAMilk allergy outgrown:20%by 4
50、years42%by 8 years79%by 16 yearsEgg allergy outgrown:4%by 4 years37%by 10 years68%by 16 yearsAllergy to some foods more often than others persists into adulthood:Peanut Tree nuts Seeds Shellfish Fish,_Skripak et al 2007,40,Induction of Oral Tolerance,Tolerance to a specific food can be induced by or
