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Alimentation for primary and secondary prevention of food allergy

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Primary and secondary prevention of atopy through alimentation (feeding /diet / food)
Feeding pattern and timing of food introduction

Overview

  • Maternal diet
  • Breast-feeding
  • Complementary foods during infancy
  • Allergenic foods during infancy
  • Dietary nutrient intake during pregnancy and infancy

Maternal diet 

  • No evidence that avoidance of cow’s milk or egg during pregnancy reduces allergic disease
  • Inconclusive data for peanut ingestion during pregnancy
  • No evidence for maternal avoidance of allergenic foods during lactation

The development and prediction of atopy in high-risk children: Follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance

  • 1981 – 1984 study
  • Prophylaxis group
    Last trimester – avoid milk, egg and peanuts
    Breast feeding – avoid milk, egg and peanuts
  • Solids – 6 mo
    CM – 12 mo
    Egg – 24 mo
    Peanuts – 36 mo

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Breast-feeding

  • Exclusive breastfeeding for 3-4 months reduces:
  • Infantile eczema in high-risk infants
    Gdalevich M et al. Breastfeeding and the onset of AD in childhood: a systematic review and meta-analysis of prospective studies J. Am Acad Dermatol 2001; 45:520-7
  • Wheezing under 4 years
    Kull I et al. JACI 2004;114:755-60, Giwercman C et al. JACI 2010; 125:806-71, Elliott L et al. JACI 2008;122:49-54
  • Cow’s milk allergy until 18 months (not food allergy in general)
    Muraro A. et al. PAI 2004; 15:291-307, Kramer MS et al. Cochrane review 2002
  • Allergic rhinitis (borderline significance)

Early complementary foods

Introduction before 17 weeks increases risk of:

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Late complementary foods

  • Introduction > 4-6 months
  • Not protective for AD, asthma, AR
    Zutavern A et al. Timing of solid food introduction
    in relation to eczema, AR, food and inhalant
    sensitization: a prospective birth cohort.
    Pediatrics 2006;117:401-11
  • Later food sensitization
    Nwaru BI et al. Age at introduction of solid foods
    during the first year and allergic sensitization at
    age 5 years. Pediatrics 2010;125:50-59
  • Joseph CLM et al. Early complementary
    feeding and risk of food sensitization
    in a birth cohort. JACI 2011;127:1203-10

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Diversity of complementary foods

  • Low food diversity at 6 months (<4 foods) associated with food and inhalant sensitization age 5 years
  • Stronger effect in children with AD or parental atopy

Complementary foods and breastfeeding

  • Concomitant breastfeeding with cow’s milk protein associated with reduction in food allergy (DBPCFC)
  • Breastmilk contains:
  • Allergenic proteins (oral exposure)
    Immunologic factors (TGF-β, IL-12 (Th1), soluble CD14)
    Prebiotics

Allergenic foods during infancy

  • Observational studies
  • Timing of introduction of egg, fish, wheat, cow’s milk
  • Although adjusted still possibility of bias
  • Prospective randomised controlled studies
  • Primary prevention
  • Secondary prevention

Introduction of cooked egg at 4-6 months is associated with reduction in egg allergy

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Wheat introduction by 6 months is associated with a lower rate of wheat allergy

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Early cow’s milk introduction associated with reduced incidence of cow’s milk protein allergy

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Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy 

Methods

5171 Jewish school children in UK and 5615 Jewish school children in Israel were compared for food allergies and atopy.

Questionnaire based assessment of peanut allergy validated by challenges.

Infant weaning for peanut and other foods was determined in infants using a validated FFQ.

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Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy

 

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Peanut allergy as a function of household peanut consumption and whether child ate peanut by 12 months 

High Household Peanut Consumption in subgroup of High-Risk Controls

If sensitisation occurs through environmental exposure in atopic individuals, one would not expect to find children in the high-risk control group (EA but not PA) with substantial environmental exposure to peanut. Surprisingly, although the median environmental peanut exposure in this group was very low, 11% had a household consumption of over 20g/week and in 1.9% it was over 50g/week.
One possible explanation is that these children had milder eczema, and peanut was unable to penetrate the skin barrier. However, there was no difference in eczema severity or age of onset between this sub-group (>20g/week) and the other high-risk controls.
Another explanation is that early introduction of peanut into the diet may have tolerised these infants, protecting them from PA, despite high environmental exposure. Figure 4 illustrates how the strong relationship between PA (in high-risk children) and environmental exposure breaks down in the subgroup of children who themselves ate peanuts by 12 months. It is noteworthy that 5 of the 15 EA children who ate peanuts by 1 year had environmental exposure of over 20g/week. 29%(2/7) of children who ate peanuts by 1 year and whose environmental exposure was over 20g/week were peanut allergic compared to 82%(60/73) of those who did not eat peanuts by 1 year(p=0.0012).

 

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German Infant Nutritional Intervention

  • Multicentre randomised controlled trial
  • Efficacy of 3 infant formulas vs. CMF in infancy
  • 2252 high risk infants received 1 of 4 formulas for first 4 months if mothers unable to breast-feed
  • Main outcomes were patient reported, physician diagnosed allergic disease

Largest study of its kind – Multicentre RCT to assess efficacy of 3 infant formulas vs CM in infancy. Recruited 1995-1998 in 2 regions of germany 2252 high risk infants randomised to receive 1 of 4 formulas for first 4/12 as a BM substitute – high risk defined as a first degree relative with allergy. Formulas were cow’s milk formula, partial whey hydrosylate (no longer available in UK), casein based eHF (nutramigen), whey based eHF (nutramigen) Only had it if they needed a BM substitute so some didn’t use their formula as they stuck to BM. Also some deviated from the prescribed formula  so again will have per protocol and ITT analyses. Main outcomes were patient reported, physician diagnosed allergic disease

Reported at 1yr, 3yr & 6yr

Headline showed persistent effect on AD thru all 3 ages but no effect on asthma

German Infant Nutrition Study

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Study shows us the change from age 7-10yrs.
Graph shows point prevalence of eczema and whilst the results look impressive there actually wasn’t really an additional effect of decreased eczema during the 7-10yr period – the overall 10 yr difference- which still stands – is driven by the effect in earlier life. Only exception is EHF-C in the per protocol group where there is an additional effect.

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Cochrane systematic review

  • No evidence to support feeding with hydrolysed formula compared to exclusive breast feeding
  • High risk infants unable to breastfeed, hydrolysed formula vs. cow’s milk formula reduces infant and childhood allergy and infant cow’s milk allergy
  • Further RCTs comparing partially hydrolysed whey, or extensively hydrolysed casein to cow’s milk formulas

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Dietary nutrient intake

  • Fruit and vegetables
  • Mediterranean diet
  • Vitamin A, D and E and zinc
  • Omega 3 and 6

Maternal recommendations

Maternal diet during pregnancy and lactation

  • No recommendation to avoid any allergenic foods
  • Diet rich in fruit and vegetables / Mediterranean diet
  • Studies ongoing regarding Vitamin D supplementation

Breastfeeding

  • Exclusive breast-feeding for 4 months
  • Continued breast-feeding during introduction of complementary foods
  • If unable to breastfeed consider hydrolysed formula

Weaning recommendations

  • Do not commence weaning before 17 weeks
  • Commence weaning between 17 weeks to 26 weeks
  • Introduce >4 weaning foods by 26 weeks
  • One new food every 3 days
  • Diet rich in fruits and vegetables

Allergenic foods

Introduce all allergenic foods from 6 months

  • Introduce cow’s milk whilst breastfeeding (4-6 months)
  • Introduce wheat and egg around 6 months
  • Introduce fish by 9 months
  • Introduce peanut between 6-12 months
  • If child has moderate eczema or family history of peanut allergy may consider testing prior to introduction

Acknowledgements

  • Gideon Lack
  • Adam Fox
  • Sophie Flammarion
  • Kerry Makinson
  • Martin Penagos
  • Allergy Team GSTT

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Oral Route

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Endoscopic and biopsy findings in patients with and without celiac disease. (A) High-definition endoscopic photo of normal small intestine. The villi are clearly visible with no evidence of atrophy or scalloping of the folds. (B) Biopsy specimen of normal small intestine (hematoxylin-eosin; original magnification, × 100). (C) PillCam image of small intestine in a patient with celiac disease, showing scalloping of the mucosal folds (arrows) characteristic of a malabsorption pattern. There is also evidence of villous atrophy compared with normal. (D) Biopsy specimen of small intestine in a patient with celiac disease (hematoxylin-eosin; original magnification, × 100). Note the loss of villous architecture.

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Cohort analysis for egg allergy

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Cohort analysis for cow’s milk allergy

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Actual vs target enrolment
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Identifying infants at high risk of peanut allergy: LEAP screening study

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Primary Endpoint

  • The proportion of participants with peanut allergy at 60 months of age.
  • Peanut allergy is defined by the Double Blind Placebo Controlled Food Challenge

Secondary Endpoints

  • The proportion of participants with allergic sensitisation to food allergens (30 and 60 months)
  • The proportion of participants with allergic rhinoconjunctivitis and asthma (30 and 60 months)
  • The proportion of participants with food allergy at 60 months
  • Incidence of adverse events, laboratory anomalies, and nutritional evaluations
  • Results of cellular and humoral immune response to peanut and other specific allergens

Can you avoid…

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Food antigen exposure is a necessary but not a sufficient condition for oral tolerance

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In high-risk infants [….] the following recommendations seem reasonable at this time:

Breastfeeding mothers should continue breastfeeding for the first year of life or longer. During this time, for infants at risk, hypoallergenic formulas can be used to supplement breastfeeding.

Mothers should eliminate peanuts and tree nuts (eg, almonds, walnuts, etc) and consider eliminating eggs, cow’s milk, fish, and perhaps other foods from their diets while nursing. Solid foods should not be introduced into the diet of high-risk infants until 6 months of age, with dairy products delayed until 1 year, eggs until 2 years, and peanuts, nuts, and fish until 3 years of age.

b) No maternal dietary restrictions during pregnancy are necessary with the possible exception of excluding peanuts;

 

AMERICAN ACADEMY OF PEDIATRICS
Committee on Nutrition 2008

Section on Allergy and Immunology

Although solid foods should not be introduced before 4 to 6 months of age, there is no current convincing evidence that delaying their introduction beyond this period has a significant protective effect on the development of atopic disease regardless of whether infants are fed cow milk protein formula or human milk. This includes delaying the introduction of foods that are considered to be highly allergic, such as fish, eggs, and foods containing peanut protein.

6. For infants after 4 to 6 months of age, there are insufficient data to support a protective effect of any dietary intervention for the development of atopic disease.

 

Avoidance Studies

Avoidance studies have failed to reduce the rate of food allergies. This is because:

  • They were not sufficiently rigorous
  • The concept of avoidance is wrong

 

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