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Page 1: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Research on Early Introduction of Hen’s Egg and Cow’s Milk

Johanna Bellach, MD – 31 August 2015

Page 2: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Disclosure

In relation to this presentation, I declare that there are no conflicts of interest.

Johanna Bellach, MD – 31 August 2015

Page 3: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Research on Early Introduction of Hen’s Egg and Cow’s Milk

Johanna Bellach, MD – 31 August 2015

I. Early introduction of hen‘s egg

HealthNuts Study (Australia)

STAR Study (Australia)

HEAP Study (Germany)

II. Early introduction of cow‘s milk

Study by Katz et al. (Israel)

Page 4: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

HealthNuts Study

Koplin JJ et al. JACI 2010Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

Page 5: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Population-based, cross-sectional study

of food allergy in 12-months-old infants

with food challenges used to confirm allergy

→ 2,589 infants participated

→ 231 infants were classified as egg allergic

Koplin JJ et al. JACI 2010Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

Is hen‘s egg allergy associated with duration ofbreastfeeding or ages of introducing hen‘s egg and solids?

HealthNuts Study

Page 6: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Koplin JJ et al. JACI 2010Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

HealthNuts StudyResults

Page 7: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Koplin JJ et al. JACI 2010Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

HealthNuts StudyResults

Page 8: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Koplin JJ et al. JACI 2010Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

HealthNuts StudyResults

Page 9: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Koplin JJ et al. JACI 2010 Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

HealthNuts StudyResults

Page 10: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Lowest risk of egg allergy among infants with first exposure to eggat 4 to 6 months of age in form of cooked egg compared with thoseintroduced later.

Infants with first exposure to egg in form of cooked egg at 4 to 6 months had lower risk of egg allergy than those infants with firstexposure to egg in form of baked egg at the same age. (OR 0.2; 95% CI, 0.06-0.71)

Koplin JJ et al. JACI 2010 Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

HealthNuts StudyResults

Page 11: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Koplin JJ et al. JACI 2010 Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

The data of the HealthNuts study suggestthat early introduction of egg mightprotect against egg allergy.

HealthNuts StudySummary

Introducing cooked egg at 4-6 monthswas associated with a lower risk of egg allergy than later introduction.

Page 12: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

STAR StudySolids Timing for Allergy Research

Palmer DJ et al. JACI 2013 Early regular egg exposure in infants with eczema: A randomized controlled trial

Johanna Bellach, MD – 31 August 2015

Page 13: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

STAR Study

Double-blind randomized controlled trial design

Study population: infants with moderate-to-severe eczema

Sample size: n=86

Aim of the STAR study:

To determine whether early regular oral egg exposurewill reduce IgE-mediated egg allergy

Palmer DJ et al. JACI 2013

Early regular egg exposure in infants with eczema: A randomized controlled trial

Johanna Bellach, MD – 31 August 2015

Page 14: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Palmer DJ et al. JACI 2013

Early regular egg exposure in infants with eczema: A randomized controlled trial

birth 12months

Randomization andstart of STAR study

8 months

Cooked egg exposure Pasteurized rawegg challenge andend of STAR study

Inclusion criteria: SCORAD ≥ 15

4 months

Johanna Bellach, MD – 31 August 2015

STAR Study

Page 15: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Palmer DJ et al. JACI 2013

Early regular egg exposure in infants with eczema: A randomized controlled trial

birth 12months

Randomization andstart of STAR study

8 months

Cooked egg exposure Pasteurized rawegg challenge andend of STAR study

Inclusion criteria: SCORAD ≥ 15

No pretesting and exclusion of childrenon the basis of hen‘s egg specific IgE-levels before intervention!

4 months

Johanna Bellach, MD – 31 August 2015

STAR Study

Page 16: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

86 children wererandomized: 49 in verum group 37 in placebo group

Palmer DJ et al. JACI 2013

Early regular egg exposure in infants with eczema: A randomized controlled trial

birth 4 months 12months

Randomization andstart of STAR study

8 months

Cooked egg exposure Pasteurized rawegg challenge andend of STAR study

Johanna Bellach, MD – 31 August 2015

STAR Study

Page 17: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

86 children wererandomized: 49 in verum group 37 in placebo group

Palmer DJ et al. JACI 2013

Early regular egg exposure in infants with eczema: A randomized controlled trial

birth 4 months 12months

Randomization andstart of STAR study

8 months

Cooked egg exposure Pasteurized rawegg challenge andend of STAR study

Verum group: pasteurized raw whole egg powder (≈ one sixth of an egg per day)

Johanna Bellach, MD – 31 August 2015

STAR Study

Page 18: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

86 children wererandomized: 49 in verum group 37 in placebo group

Palmer DJ et al. JACI 2013

Early regular egg exposure in infants with eczema: A randomized controlled trial

birth 4 months 12months

Randomization andstart of STAR study

8 months

Cooked egg exposure Pasteurized rawegg challenge andend of STAR study

Verum group: pasteurized raw whole egg powder (≈ one sixth of an egg per day)

Control group: rice flour powder

Johanna Bellach, MD – 31 August 2015

STAR Study

Page 19: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Johanna Bellach – EAACI 07/06/2015

Palmer DJ et al. JACI 2013

Early regular egg exposure in infants with eczema: A randomized controlled trial

Primary outcome:IgE-mediated egg allergy at 12 months of age

Allergic reaction to the pasteurized raw egg challengeand sensitization to egg

OR

Independent medical decision against egg challenge due to previous allergic reaction to egg

and sensitization to egg

STAR Study

Page 20: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Palmer DJ et al. JACI 2013

Early regular egg exposure in infants with eczema: A randomized controlled trial

Allergic reactions to study powder

31% (15/49) children of the verum group had an allergicreaction to the study powder.

67% (10/15) reacted at the first dose of study powder, one with an anaphylactic reaction!

All except one child reacted at the first to seventh dose (during the first week?).

Johanna Bellach, MD – 31 August 2015

STAR StudyResults

Page 21: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Palmer DJ et al. JACI 2013

Early regular egg exposure in infants with eczema: A randomized controlled trial

Allergic reactions to study powder

31% (15/49) children of the verum group had an allergicreaction to the study powder.

67% (10/15) reacted at the first dose of study powder, one with an anaphylactic reaction!

All except one child reacted at the first to seventh dose (during the first week?).

Johanna Bellach, MD – 31 August 2015

STAR StudyResults

→ Pause of study recruitment at the request of the Human

Research Ethics Committee to examine the rate of allergic reactionsto the study powder and cases of anaphylaxis

Page 22: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Palmer DJ et al. JACI 2013 Early regular egg exposure in infants with eczema: A randomized controlled trial

Primary Outcome:Diagnosis of IgE-mediated egg allergy at 12 months of age

Verum group: 14/42 (33%) Control group: 18/35 (51%)

RR, 0.65; 95% CI, 0.38-1.11

Lower proportion of infants with diagnosis of IgE-mediated hen‘s egg allergy in verum group, but nostatistical significance.

Johanna Bellach, MD – 31 August 2015

STAR StudyResults

Page 23: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Koplin JJ et al. JACI 2010 Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

The Results of the STAR study suggest thatearlier introduction of hen‘s egg does not increase the risk of hen‘s egg allergy in children with moderate to severe eczema.

Many infants were already allergic to hen‘segg by 4 months of age and showedallergic reactions on first exposures tohen‘s egg.

STAR StudySummary

Page 24: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

HEAP StudyHen’s Egg Allergy Prevention

Unpublished data by the research group of Prof. Kirsten Beyer at Jaffe Satellite Institute of Food Allergy at Charité Universitätsmedizin Berlin

Johanna Bellach, MD – 31 August 2015

Page 25: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Research on early introduction of cow’s milk

Johanna Bellach, MD – 31 August 2015

Katz Y et al. JACI 2010. Early exposure to cow‘s milk protein is protectiveagainst IgE-mediated cow‘s milk protein allergy

Page 26: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Prospective observational study of 13,019 infants that were born at the Assaf-Harofeh Hospital in Zerifin, Israel

Feeding history was obtained by telephone interview and questionnaire:

• Demographic details• Breastfeeding behavior• Age of introduction of CMP-based formula on a regular basis• Adverse responses to cow’s milk protein

Infants with probable adverse reactions to cow‘s milk were examined, skin prick tested and challenged orally.

Katz Y et al. JACI 2010 Early exposure to cow‘s milk protein is protective against IgE-mediated cow‘s milk protein allergy

Study by Katz et al.

Johanna Bellach, MD – 31 August 2015

Page 27: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Cumulative incidence of IgE-mediated cow‘smilk allergy in study cohort: 0.5% (66/13,109)

Mean age of onset of IgE-mediated cow‘s milk allergy was 3.9 months

82.8% showed reactions on the first day ofconsumption of cow‘s milk protein, the remaining17.2% within 7 days.

Katz Y et al. JACI 2010 Early exposure to cow‘s milk protein is protective against IgE-mediated cow‘s milk protein allergy

Johanna Bellach, MD – 31 August 2015

Study by Katz et al.Results

Page 28: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Group I: 0 to 14 days; Group II: 15 to 104 days; Group III: 105 to 194 days; Group IV: 195 to 374 days

Katz Y et al. JACI 2010 Early exposure to cow‘s milk protein is protective against IgE-mediated cow‘s milk protein allergy

Johanna Bellach, MD – 31 August 2015

Study by Katz et al.Results

Page 29: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Group I: 0 to 14 days; Group II: 15 to 104 days; Group III: 105 to 194 days; Group IV: 195 to 374 days

Katz Y et al. JACI 2010 Early exposure to cow‘s milk protein is protective against IgE-mediated cow‘s milk protein allergy

Johanna Bellach, MD – 31 August 2015

Study by Katz et al.Results

Half of the newborns(49,6%) of the wholecohort were exposed tocow‘s milk protein in thefirst 2 weeks

Page 30: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Group I: 0 to 14 days; Group II: 15 to 104 days; Group III: 105 to 194 days; Group IV: 195 to 374 days

Katz Y et al. JACI 2010 Early exposure to cow‘s milk protein is protective against IgE-mediated cow‘s milk protein allergy

Johanna Bellach, MD – 31 August 2015

Study by Katz et al.Results

Half of the newborns(49,6%) of the wholecohort were exposed tocow‘s milk protein in thefirst 2 weeks

But: neonatal exposureto small quantities ofcow‘s milk proteinformula in the newbornnursery cannot beexcluded for all groups!

Page 31: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Katz Y et al. JACI 2010 Early exposure to cow‘s milk protein is protective against IgE-mediated cow‘s milk protein allergy

Johanna Bellach, MD – 31 August 2015

Study by Katz et al.Results

Introduction at 4-6 months!

Infants whose regular exposure to cow‘s milk protein was withheld untilthe age of 4 to 6 months were at the highest risk for IgE-mediated cow‘smilk allergy.

Page 32: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Koplin JJ et al. JACI 2010 Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

The study data suggest that earlycomplementary feeding of cow‘s milk proteinalong with breast-feeding on a regular basisstarting before the age of 4 months promotesoral tolerance.

Study by Katz et al.Summary

Page 33: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Koplin JJ et al. JACI 2010 Can early introduction of egg prevent egg allergy in infants? A population-based study.

Johanna Bellach, MD – 31 August 2015

The study data suggest that earlycomplementary feeding of cow‘s milk proteinalong with breast-feeding on a regular basisstarting before the age of 4 months promotesoral tolerance.

There is still the need of interventional trials tovalidate whether the early introduction ofcow‘s milk protein can prevent cow‘s milk allergy!

Study by Katz et al.Summary

Page 34: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Johanna Bellach, MD – 31 August 2015

There is no clear evidence yet that theearly introduction of hen‘s egg or cow‘smilk can prevent hen‘s egg allergy andcow‘s milk allergy, respectively.

The current findings suggest that primarypreventive interventions would have tostart earlier than 4-6 months of age.

Early Introduction of Hen’s Egg and Cow’s Milk

Conclusions

Page 35: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Early Introduction of Hen’s Egg and Cow’s Milk

Ongoing Research

Australia

STEP Study: Starting time for Egg Protein

BEAT Study: Beating Egg Allergy

United Kingdom

EAT Study: Enquiring About Tolerance

Japan

Prevention of egg allergy in infants with atopic dermatitis

Johanna Bellach, MD – 31 August 2015

Page 36: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Early Introduction of Hen’s Egg and Cow’s Milk

Ongoing Research

Australia

STEP Study: Starting time for Egg Protein

BEAT Study: Beating Egg Allergy

United Kingdom

EAT Study: Enquiring About Tolerance

Japan

Prevention of egg allergy in infants with atopic dermatitis

Johanna Bellach, MD – 31 August 2015

Within the European iFAAM* Project a metaanalysis andpooled analysis of 7 interventional trialson food allergyprevention is planned.

Page 37: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Johanna Bellach – EAACI 07/06/2015

Thanks to…

Page 38: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Johanna Bellach – EAACI 07/06/2015

…our funding partners…

Page 39: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

Johanna Bellach – EAACI 07/06/2015

…all participating families…

Page 40: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

…and the whole research group at the Jaffe Satellite Institute of Food Allergy Research

led by Prof. Kirsten Beyer…

Johanna Bellach – EAACI 07/06/2015

Page 41: Research on Early Introduction of/media/Files/Activity...Research on Early Introduction of Hen’s Egg and Cow’s Milk Johanna Bellach, MD –31 August 2015I. Early introduction of

…and to you for listening!

Johanna Bellach – EAACI 07/06/2015


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