World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum...

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World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices Scott H. Sicherer, MD Clinical Professor of Pediatrics Jaffe Food Allergy Institute Mount Sinai School of Medicine New York AAAAI Orlando 2012: Session 3307

Transcript of World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum...

Page 1: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

World Allergy ForumFood Allergy: Pathogenesis

and Prevention

Early Dietary Exposures and Feeding Practices

Scott H. Sicherer, MDClinical Professor of Pediatrics

Jaffe Food Allergy InstituteMount Sinai School of Medicine

New York

AAAAI Orlando 2012: Session 3307

Page 2: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Disclosures

• NIH-NIAID Funding for studies• Food Allergy Initiative Consultant

and funding for studies• Food Allergy & Anaphylaxis Network

Medical Advisor

Page 3: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Learning Objectives

• Understand the current data on atopy prevention through infant diet

• Advise families on dietary approaches with regard to food allergy prevention

Suggested References : 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. Greer F, Sicherer S, Burks AW. Pediatrics. 2008;121(1):183-91 and Guidelines for the Diagnosis and Management of Food Allergy in the US Boyce et al. J Allergy Clin Immunol 2010; 126(6 Suppl):S1-58.

Page 4: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Prevention Through Diet• Prevention of… • Through “ingestion”…

Sensitization

Choice of breast milk substitution

Breast feeding-with Maternal diet alteration

Pregnancy

Breast feeding

Disease

Complementary foodsWhen/what

Inflammation

Page 5: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

What are “normal” feeding practices?

• Breast feed• Weaning• Solids that are easily managed by an infant• Progression as teeth erupt

Page 6: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Breast Feeding (focus on eczema) • 18 prospective studies ( Gdalevich JAAD 2001; 45:520-

7)– Atopic (OR 0.58; 95% CI, 0.41-0.92)– Non-atopic (OR 0.84; 95% CI, 0.59-1.19)

•Recent studies suggest genetic differences affect risk(Hong et al JACI 2011;128:374-81)

• 21 studies ( Yang YW BJD 2009;161:373-383)• Overall : OR 0.89 (95% CI 0.76-1.04)• vs. formula OR 0.7 (95% CI 0.50-0.99)

•(but p=NS removing Chandra)

• ISAAC Study (Flohr C BJD 2011;165:1280-9)• 51,119 children. No evidence of overall protection.

Recent studies trend to

less protection

Page 7: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Meta-Analysis: Maternal Diet Restriction While Breast Feeding• Insufficient evidence that maternal

allergen avoidance prevents atopic disease

• Possible exception for atopic dermatitis • 2 studies

• 2010 Food Allergy Guidelines: Not recommended to reduce FA

Kramer Kakuma Cochrane database 2006

Page 8: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

The German Infant Nutritional Intervention Study

• “At risk” for atopy (one 1 st degree)• Randomized to study formula (within context of

instruction to breast-feed)

– Cow’s milk formula (CMF)– Extensively hydrolyzed casein (eHF-C)– Extensively hydrolyzed whey (eHF-W)– Partially hydrolyzed whey (pHF-W)

Von Berg A JACI 2003; 111:533

0

2

4

6

8

10

12

14

16

%

AtopicDerm

FoodAllergy

Any Atopy

CMFeHF-CeHF-WpHF-W

** *Von Berg JACI 2007Von Berg JACI 2008

Page 9: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

• Lesson #1: Cannot assume a formula’s effect (e.g., eHF-W)

• Lesson #2: Impact on subtypes of risk*

The German Infant Nutritional Intervention Study

0

0.2

0.4

0.6

0.8

1

1.2

Odds Ratio

No AD in FH AD in FH

CMFeHF-CeHF-WpHF-W

*Trends

Page 10: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Randomized Trial of 3 Formulas if Weaning

• 620 infants positive family history atopy• Cow’s milk vs. soy vs partially hydrolyzed

whey at weaning• Followed age 2 years (93%) and age 7

(80%)• 50% exposed ~5 months, ~75% 1 year• No differences in AD, food skin tests,

asthma, rhinitis Lowe et al JACI 2011;128:360-5

Page 11: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Prevention Formulas• Soy not recommended for “prevention”

(AAP, NIAID)• “Hydrolyzed infant formulas”

recommended over whole cow’s milk protein for “at risk” (NIAID Guideline) and some evidence for reduced atopic dermatitis (slight advantage of extensive casein hydrolysate versus partial whey hydrolysate weighed by cost (AAP)

Page 12: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Dietary Prevention Program, US

• Randomized, prospective, 288 subjects, one parent with atopy and sensitization

• Program:– Pregnancy, 3 rd trimester-no milk, egg, peanut,

reduced soy/wheat– Lactation, avoid same, supplement casein

hydrolysate– Solids at 6 mo, 12 mo-CM, wheat, soy, 24 mo-

egg, 36 mo-peanut, fish

• Followed to age 7 years

Zeiger JACI 1989;Zeiger PAI 1992;Zeiger JACI 1995

Page 13: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Dietary Prevention Program, USPeriod Prevalence of Disorders

Zeiger JACI 1989;Zeiger PAI 1992;Zeiger JACI 1995

0

5

10

15

20

25

30

35

%

Age 1 Age 2 Age 4 Age 7

Asthma

0

5

10

15

20

25

30

35

%

Age 1 Age 2 Age 4 Age 7

Atopic dermatitis

0

5

10

15

20

25

30

35

%

Age 1 Age 2 Age 4 Age 7

Food Allergy

ProphylaxisNo diet

*

*

Page 14: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

“Prevention”

• Breast feed 1 year• If supplement, “hypoallergenic

formula”• Solids delay to age 6 mo • Should eliminate Peanut, Tree nuts,

and consider eliminate egg, milk, fish “others” while nursing

• No Cow’s milk to 12 mo• No Egg to age 2 yr• No Peanut, Tree Nuts, fish to 3 yr• Pregnancy: consider peanut

exclusion

AAP Committee on Nutrition, 2000

Suggestions aimed at “high risk”

Page 15: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Solid Foods*

Rat

e of

Ecz

ema

0

5

10

15

20

25

30

35

No Solids 1-2 Solids 3-4 Solids 5+ Solids

Fergusson et al Clin Allergy 1981

Atopic Dermatitis OR (95% CI)

Veg (>4 mo)

Egg (>8 mo)

Zutavern et al ADC 20040.1 0.2 0.5 1 2 4

05

10152025303540

AD (%)

Age 1 Age 5

3 months6 months

Age of Solid food Introduction

Kajosaari & SaarinenActa Ped Scand 1983

Page 16: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Solid Food Post 2000

• Germany (Filipiak J Pediatr 2007;151:352)

– 4753 infants (birth cohort): Among “at risk” atopy if waited on giving egg (RR 1.8, 95% CI: 1.2-2.6)

• Belgium (Sariachvili PAI 2010;21:74)

– Case Control: Solids before 4 months, less eczema (OR 0.49; 95% CI 0.3-0.7)

• Finland (Nwaru Pediatrics 2010;125:50)

– Cohort 994: Later introduction of solid foods associated with higher food sensitization

• Netherlands (Tromp Arch Pediatr Adolesc Med 2011;165:933)

– Cohort 6905: No relationship of eczema/wheeze to receiving milk, egg, soy, nut, wheat prior to age 6 months

Page 17: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Complementary feeding and food sensitization: Detroit

• Enrolled 1258 women, 44.9% parental atopy

• Dietary inclusion of complementary foods at < 4 months versus food sensitization at age 2-3 years

• 74.2% with data for this analysisFamily Atopy

IgE > 0.7 kUA/L E/M, >0.35 peanut

Adjusted odds ratio

P-value

Yes Egg/milk 0.5 (0.3-0.9) 0.023

Yes Peanut 0.2 (0.1-0.7) 0.007

No Egg/milk 1.0 (0.6-2.0) 0.894

No Peanut 1.3 (0.6-2.7) 0.544

Joseph et al JACI 2011;127:1203-10

Page 18: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Egg Introduction and Egg AllergyEgg Introduction and Egg Allergy

Koplin et al JACI 2010

RR (95% CI)

0 0.1 0.5 1 2 5 10

4-6 mo

7-9 mo

>12 mo

10-12 mo

“HealthNuts” study, 2589 infants population-based, cross-sectional study

� Effects seen in high-risk and low-risk infants with cooked egg introduction� Adjusted for confounding factors� Confirmed egg allergy

Page 19: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Cereal Grain Introduction and Wheat Cereal Grain Introduction and Wheat

AllergyAllergy

OR (95% CI)

0 0.1 0.5 1 2 5 10

0-6 mo

≥7 mo

“Daisy” study (US), 1612 infants, birth cohort obser vational study

Poole et al Pediatrics 2006

� Parent reported wheat allergy in 1%, 4 with positive wheat-IgE � Adjusted for parental allergic diseases and any food allergy < 6mo of age� Designed to investigate natural hx of diabetes and celiac disease in a HLA-

predisposed population

Page 20: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Cow’s Milk Introduction and Milk Allergy

Katz et al JACI 2010

Prospective feeding study of 13019 infants in Israel, telephone interview, encourage to breast feed

� Low prevalence of IgE-mediate allergy 0.5%, which confirmed milk allergy� Regards parental atopy as a potential confounding factor� Nursery milk exposures not considered

Page 21: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

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.

AdjustedOdds RatioEczema

Age at introduction of milk protein (mo)

Snijders et al Pediatrics 2008;122:e115-22

Page 22: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Government and Pediatric Society Response To Peanut

Allergy “Epidemic”• Avoid peanut during

pregnancy, lactation and wait to age 3 years to feed it

• American Academy of Pediatrics 2000

• Committee on Toxicology (UK) 1999

Page 23: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Ingestion is bad…Uh oh…?

Maybe if you don’t eat it, you touch it, have accidental periodic ingestions that are all sensitizing?

Sicherer et al JACI 2003, 2010 Grundy et al JACI 2002; Du Toit JACI 2008;Fox JACI 2009

Before Advice to avoid

After Advice to avoid

Percentpeanut allergy in children

Page 24: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Source: Sicherer SH and Sampson HA. “Peanut allergy : Emerging concepts and approaches for an apparent epidemic.” J Allergy Clin Immunol 120(3): 491-503.

Peanut

Allergy

Genetic predispositionto peanut allergy

Geneticpredisposition Atopic

Dermatitis

Dietary &Environmental

Exposures

Use ofAntacids

Ingestion of cross-reactiveproteins (soy)

Topicalexposure

Pollenproteins

Manner of processing

Frequencyof ingestion

Timing

Dose

Maternal ingestionduring pregnancy

Maternal ingestionduring breast feeding

Page 25: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

What are “normal” feeding practices?

• Breast feed• Weaning• Solids that are easily managed by an infant• Progression as teeth erupt

Page 26: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Weaning Foods

• Thailand-coconut, chilis, tamarind, lemon grass

• Africa-meats• China-rice, fish, vegetables, meat• India-wheat, rice, milk, egg, fish,

legumes• Japan-rice, soy, fish

Source: Wikipedia

Page 27: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

What are “normal” feeding practices?

• Breast feed• Weaning• Solids that are easily managed by an infant via pre -mastication• Progression as teeth erupt

Page 28: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Hafeez, S. et al. Arch Pediatr Adolesc Med 2011;165 :92-93.

Characteristics Mothers Completing the Questionnaire Asking Whether They Have Ever Given Pre-masticated Food to Their

Children• Anonymous

survey• 90, HIV

infected mothers

• Brooklyn, NY• Overall, 18%

pre-masticated

N=90 Yes, Premasticates

Born US 18%

Born Carribean or Central America

13%

Born Africa 29%

Hispanic 7%

African American 38%

African 29%

Mother Pre-masticated 42%

Mother did not Pre-masticate 12%

Page 29: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

ENDS: MEANS• Prevention of… • Through ingestion…

Breast feeding-with Maternal diet alteration

Pregnancy

Breast feeding

Choice of breast milk substitution

Complementary foodsWhen/what

Sensitization

Disease

Inflammation

Page 30: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

ENDS: MEANS• Prevention of… • Through ingestion…

Breast feeding-with Maternal diet alteration

Pregnancy

Breast feeding

Choice of breast milk substitution

Complementary foodsWhen/what

No obviousEffect (?)

Good foreveryone,exclusive to4-6 mo No, but for

high risk maybe (AD)

Certain Hydrolyzedformulas, notsoy, not cow’smilk

Nothingspecial(exceptions?)

Page 31: World Allergy Forum Food Allergy: Pathogenesis and Prevention slides.pdf · World Allergy Forum Food Allergy: Pathogenesis and Prevention Early Dietary Exposures and Feeding Practices

Thank You!