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

Can we prevent

allergies in children?

Michael S. Blaiss, MD Clinical Professor of Pediatrics and Medicine

University of Tennessee Health Science Center

Memphis, 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 reduce

the risk of the atopic march?

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 and Exp Allergy.1997;:27:752-760. Exl BM, Nutr Res 2001;21: 355-79

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.

Is Parental Atopic History a

Reliable Predictor of Allergy?

Parental history is not a reliable predictor of allergy

Family History

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

50% to 80% of children will have some form of

allergy if both parents have an atopic history…

Potential for

Childhood

Allergy

Correlates

To Parents’

History of

Allergy

Both Parents

(5%)

One Parent

Or Sibling

(31%)

Neither Parent

(64%)

Percentage of children that developed an

allergic manifestation

6

Risk of Allergy Increases with a

Positive Family History, But…

Parental Atopic

History in Infants

with Allergy

Both Parents

(5%)

One Parent (25%) Neither Parent (70%)

70% of children with allergy do not have parental history of allergy

*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

and Exp Allergy.1997;:27:752-760. Exl BM, Nutr Res 2001;21: 355-79

Risk Reduction

Studies-What’s the

Data?

Maternal Dietary Avoidance

Intervention

Maternal Dietary Avoidance

Intervention

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 cow's 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

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

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

Eczema

Age at introduction of milk protein (mo)

Snijders et al

Pediatrics

2008;122:e115-22

What’s the Bottom-Line?

What does it all mean?

Should all children have all

foods continuously in the first

few 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

31

Relative Risk of Atopic Dermatitis Meta Analysis- Infants with a Family History of Atopy

Does breast feeding reduce the risk allergy?

Gdalevich M, et al. J Am Acad Derm. 2001;45:520-527.

0.58

1.00

Formula Feeding, Risk = 1

32

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.

Gdalevich M, et al. J Am Acad Derm. 2001;45:520-527. Adapted. OR with BF= .58 vs CMF

1.72

1.00

Breast Feeding is THE Standard

Today’s “modern formula” for

Non-breastfed Infants

Intact (allergenic) cow milk

protein formula in a sterile form.

Any alternatives?

High Molecular Weight

Potential for Hypersensitivity (Allergic Reaction)

Low Molecular Weight

Immune System

Protein size and Allergenicity

36

Hydrolysis Can Reduce Allergenicity

of Cow Milk Proteins*

4501,220

12,000

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

Extensively

Hydrolyzed Casein

Partially

Hydrolyzed Whey

Whole Protein

Casein/Whey

Dal

tons

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

intended for therapeutic use in infants who have already presented with allergic disease.

**Approximate values as reported by major manufacturers.

37

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

0

20

40

60

80

Von Berg 2008 Oldaeus 1997 Zeiger 1995 Mallet 1992

Cum

ulat

ive

Inci

denc

e of

AD

(%)

Extensively Hydrolyzed CaseinIntact Cow Milk

p=0.006

p<0.05

p=NS

p=0.059

* 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

*****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.

38

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

*Graph depicts only published, peer-reviewed, prospective trials with data collection at timepoints >12 months. **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.

p<0.002

p=NS

p=NS p<0.01

0

10

20

30

40

50

60

Von Berg 2008 Oldaeus 1997 Zeiger 1995 Mallet 1992

Cu

mu

lati

ve

In

cid

en

ce

(%

AD

)

Extensively Hydrolyzed

Casein

Intact Cow Milk

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.

40

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

*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

****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.

0.0

20.0

40.0

60.0

Von Berg

2008

Chan 2002 Exl 2000 Marini 1996 Vandenplas

1995

Tsai 1991 Vandenplas

1988

Cum

ula

tive Incid

ence o

f A

D (%

)

Partially Hydrolyzed WheyIntact Cow Milk

p<0.05

p=0.004

p<0.05

p=NS p<0.05

p>0.05

p>0.05

41

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

*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

***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.

P<0.021

P=0.09

NS NS

NS

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.

43

The German Infant Nutritional

Intervention (GINI) Study

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%

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

Effect of Hydrolyzed Cow Milk Formula

for Allergy Prevention

44

GINI Study - Risk of AD at 12 months: Adjusted Odds Ratio

0 0.2 0.4 0.6 0.8 1


Casein

Partially Hydrolyzed Whey


Whey

Intact Cow Milk 1.0

0.56

0.42

44% risk reduction vs. CMF



0.81 CI (0.48-1.4)


CI (0.32-0.99)

CI (0.22-0.79)

*

*

*p < 0.05 vs Intact Cow Milk

45

GINI Study - Risk of AD at 6 years: Adjusted Odds Ratio


*p < 0.05 vs Intact Cow Milk

*

0 0.2 0.4 0.6 0.8 1


Casein

Partially Hydrolyzed Whey


Whey

Intact Cow Milk 1.0

0.64

0.55

36% risk reduction vs CMF

45% risk reduction vs CMF

0.74 26% risk reduction vs CMF CI (0.56-0.98)

CI (0.48-0.86)

CI (0..39-0.76)

*

*

Guidelines for the Diagnosis and Management of Food

Allergy in the United States: Summary of the NIAID

Sponsored 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

Thank you!!

Follow me on Twitter at

wheezemd

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

Health & Medicine

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