When is the ideal time to introduce allergenic foods to infants? Edmond Chan MD FRCPC Becky Blair RD MSc Host: Pediatric Network

Transcription

1 When is the ideal time to introduce allergenic foods to infants? Edmond Chan MD FRCPC Becky Blair RD MSc Host: Pediatric Network

2 The opinions expressed in this presentation are that of the presenter and do not necessarily reflect those of Dietitians of Canada. Further, this presentation should not be reproduced in full or in part without the express written consent of the presenter. Les opinions exprimées dans cette présentation sont celles du présentateur ou de la présentatrice et ne reflètent pas nécessairement celles des Diététistes du Canada. Par ailleurs, cette présentation ne devrait pas être reproduite, que ce soit en partie ou dans son intégralité, sans le consentement écrit exprès du présentateur ou de la présentatrice.

3 Dietary Exposures and Allergy Prevention in High-risk Infants Edmond S. Chan, MD, FRCPC Clinical Associate Professor, University of British Columbia, Canada Head, Division of Allergy & Immunology, Department of Pediatrics June 9, 2018 Dietitians of Canada National Conference Vancouver, BC

4 Faculty/Presenter Disclosure Faculty: Dr. Edmond S. Chan Relationships with commercial interests: Grants/Research Support: DBV Technologies Speakers Bureau/Honoraria: Consulting Fees: Pfizer, Aralez Pharmaceuticals Other: Minor shareholder, Aimmune Therapeutics Relationships without commercial interest: Expert Panel for NIAID (National Institute of Allergy & Infectious Diseases), Early peanut introduction addendum guidelines CSACI, AAAAI, AGA Research support from CIHR, AllerGen, and BCCH Foundation

5 Disclosure of Commercial Support This program has not received financial support. This program has not received in-kind support. Potential for conflict(s) of interest: N/A Mitigating Potential Bias N/A

6 Objectives 1) Review the evidence for introducing non-choking peanut early to prevent peanut allergy 2) Examine new guidelines for preventing peanut allergy 3) Discuss clinical cases of early peanut introduction to illustrate real-world complexities

7 Prevalence of food allergy Canada Australia Most accurate data (oral food challenge proven in 12 month old infants) Peanut 3.0% (95% CI, ) Raw egg allergy, 8.9% (95% CI, ) Sesame allergy, 0.8% (95% CI, ). Soller L et al. J Allergy Clin Immunol Oct;130(4):986-8 Osborne NJ et al. J Allergy Clin Immunol Mar;127(3):668-76

8 Du Toit G. J Allergy Clin Immunol 2016; 137:

9 What not to do

10 February 23, 2015 LEAP study

11 LEAP Trial Design Intervention grp: SPT-Positive Stratum (n=47) 2 g of peanut protein 3 x s/wk Recruitment: n = 640 infants with severe eczema and/or egg allergy n=319 Intervention grp: SPT-Negative Stratum (n=272) Control Grp: SPT-Positive Stratum (n=51) n=321 Age at Control Grp: SPT-Negative Stratum (n=270) clinic visits: 4-11 months 12 months 30 months 60 months Du Toit G et al. NEJM 2015; 372:

12 Primary Outcome. Results Du Toit G et al. N Engl J Med 2015;372: ARR=11.8% ARR=24.7% ARR=14% ARR=13.5% ARR=34% ARR=17% ARR=9.6% ARR=24.7% ARR=12.1%

13 Safety No fatalities No significant between-group difference in the incidence of serious adverse events (AE) AE rate not different based on sensitization At baseline screening: 7 infants failed challenge at first randomized peanut dose All 7 had mild (predominantly cutaneous) reactions, without any need for epinephrine Du Toit G et al. N Engl J Med 2015;372:

14 Meta-analysis of Prevention Trials UK Food Standards sponsored systematic review -16,289 titles screened, 51 studies identified -Included published abstracts of studies in progress/preparation Moderate certainty evidence from 5 trials for protective benefit of early egg introduction (4 raw, 1 cooked) -RR 0.56, P=0.009; ARR 24 cases per 1000 Moderate certainty evidence from 2 trials for protective benefit for early peanut introduction -RR 0.29, P=0.009; ARR 18 cases per 1000 Ierodiakonou D et al. JAMA Sept 20;316(11):

15 Pooled data supports early introduction Ierodiakonou D et al. JAMA Sept 20;316(11):

16 Togias A et al. J Allergy Clin Immunol Jan;139(1):29-44.

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18 HOME HOME The definition of an infant at risk or high-risk is constantly evolving. How does an infant having a first degree relative with an allergic condition compare to the criteria above???

19 Only ~0.9% of all infants have severe eczema

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21 How is regularity of ingestion ensured in Israel? Mother of infant brought to me for in-office peanut introduction: Mom had previously lived in Israel, and said the regularity of ingestion is addressed by Bamba being in every pre-school, school, social environment imaginable. Kids there eat it at least weekly because they re surrounded by it everywhere they go... Here in N. America, peanut bans at schools are very controversial?bans might perpetuate culture of avoidance, even for infants Wang J, Fleischer DM. J Allergy Clin Immunol Pract Mar - Apr;5(2):

22 Controversies with NIAID guideline Confusing to have different ages of introduction (4-6 vs ~6 months) Screening skin tests/sige frequently falsely positive: No reported fatalities from exposure in 1 st year of life Israel has no screening, peanut introduced early, and essentially no peanut allergy Lack of access to testing and oral challenges, resource limitations Screening creep : Delayed introduction due to over-diagnosis of severe eczema, egg allergy (plausibility at <6 months), and over-testing Turner PJ, Campbell DE. JAMA Feb 13

23 Early solids vs Exclusive breastfeeding 6 mo Proposed COMPROMISE: Balancing amount of evidence for allergy prevention if solids introduced <6 mo vs. amount of evidence for harm Use phrase: introduce solids at around 6 months but not before 4 months Oct 2016 Australasian guidelines on infant feeding and allergy prevention CPS Practice Point just accepted for publication May 17, 2018 at around 6 months but not before 4 months Abrams EM, Greenhawt M, Fleischer DM, Chan ES. J Pediatr Mar 3

24 Studying early food introduction in the real world FAKT-GAPS study (Food Allergy Knowledge Translation Gaps) 2016 survey of Canadian allergists, pediatricians, and family physicians on early peanut introduction 2018 repeat survey for comparison OEUF study (Oral food challenge barrier) Study of barriers and solutions to improving access to oral food challenges in Canada

25 Allergist data, FAKT-GAPS study 79/196 CSACI allergist respondents 64.4%(95%CI: ) of allergist respondents were pediatric trained Preliminary data

26 How many infants have severe eczema? Silverberg JI, Simpson EL. Associations of childhood eczema severity: a US population-based study. Dermatitis May- Jun;25(3): Eczema prevalence 12.97%, of which 67% mild, 26% moderate, and 7% severe Rough calculation: 8.7% of all infants have mild eczema 3.4% of all infants have moderate eczema 0.9% of all infants have severe eczema

27 Continued confusion amongst parents and providers about the cause of eczema It is essentially impossible to prove that eating specific food(s) causes eczema Much of the perceived improvement is coincidental & anecdotal The literature is very weak for this perceived effect The LEAP study proves the opposite, i.e.) that eczema causes food allergy The cause of eczema is a genetic skin barrier defect E.g. Filaggrin gene defect

28 What is Filaggrin? Cork MJ et al. J Invest Dermatol Aug; 129(8):

29 AD = Atopic Dermatitis Early/regular emollient to Prevent AD U.S./U.K. study 124 neonates at high risk (1 st degree relative with atopy), randomized, assessor blinded: daily emollient within 3 weeks of birth vs. controls asked to use none RR 0.5 (95% CI, ) for intervention group s cumulative incidence of atopic dermatitis at 6 months (22%) vs control (43%) Japan study similar outcomes (next slide) Simpson EL et al. J Allergy Clin Immunol 2014 Oct;134: neonates (1 st degree relative with AD, (?) not enough subjects to show reduction in egg sensitization with moisturizer Horimukai K et al. J Allergy Clin Immunol 2014 Oct;134:

30 ~32% fewer neonates using moisturizer (starting week 1) had AD at week 32 compared with controls (p=0.012) Horimukai K et al. J Allergy Clin Immunol 2014 Oct;134:

31 Harms of avoiding foods to treat eczema Children who stop eating food(s) to treat eczema are at risk for future anaphylaxis due to loss of tolerance 2015 study: 19% of children developed immediate reactions (30% of those anaphylactic) within 1.4 years (range= years) of stopping the food(s) Chang A et al. J Allergy Clin Immunol Pract Mar-Apr;4(2): Restrictive diets place infants at risk of poor growth and nutrition Due to the above reasons, much better to treat eczema with topical medications, moisturization, etc rather than dietary restriction

32 Some recent clinical cases of mine Can be tricky to interpret infant histories, skin tests, sige blood tests, and oral challenges

33 Case 1: Contradicting WHO may be necessary 15 month old older sibling with peanut allergy Hx of immediate widespread hives with peanut at 6 months SPT peanut 13x15mm. Both parents are dermatologists. Mother is currently pregnant. What advice should be given to the mother regarding peanut introduction for the soon to be born infant? Given the older sister reacted at the young age of 6 months, when should peanut be introduced for the next child? Abrams EM, Chan ES, Sicherer SH. J Allergy Clin Immunol Pract Mar - Apr;6(2):

34 Case 2: Mild eczema, afraid, false positive 11 mo. old, hx of very mild eczema, wheeze once 6 yo brother w. anaphylaxis to milk, egg, tree nuts, persistent asthma. Tolerates peanut. Family counseled to introduce peanut early Family ultimately afraid, and skin tests requested at 11 mo. Peanut 9x4mm (sige 1.8 ku/l), Cashew 8x5mm (sige 5.48 ku/l) What should be the next step? Peanut oral challenge: Passed Cashew challenge: Failed Greenhawt M, Fleischer DM, Atkins D, Chan ES. Complexities of early peanut introduction. J Allergy Clin Immunol Pract. 2016;4:221-5

35 Case 3: Even more false positives History of dry skin (no eczema), lives in Calgary Peanut butter (PB) at home at 6 mo after mom heard about NIAID guidelines on TV. On 5 th day some redness on face, saw family MD, peanut sige 2 ku/l, referred to internist, skin test results: peanut 4, almond 3, cashew 3, sesame 3, macadamia 4, egg white 4 Referred to me as second opinion, seen at 8 months All skin tests repeated & negative, PB challenge (observed ingestion) same day passed. Diagnosis of contact irritation around mouth. Why are skin prick/specific IgE tests so inaccurate and difficult to interpret for most MD s? Why do so few MD s offer oral food challenges, esp to infants?

36 Case 4: Is it possible to prevent peanut allergy in an infant with uncontrolled eczema? Family hx: 3yo sister with severe (untreated) eczema and 8mm positive SPT peanut (were afraid to introduce it) 8 mo old sib, widespread eczema, afraid of topical medications (untreated despite Peds Derm), afraid to try allergenic foods Mom chose observed ingestion without testing, after 3 rd dose crying ++, scratching before/after ingestion; subsequent SPT 5x6mm; >3 hrs after swelling ears, scattered hives. Mom curious about re-trying at home. Possible to accurately diagnose peanut allergy here? Avoid peanut? Abrams EM, Chan ES. J Pediatr Apr;195:

37 Practical take home messages 1. Almost all infants should be introduced to non-choking peanut at ~ 6 months at home 2. The relatively few infants who have severe eczema or egg allergy should vs may need to see an MD at ~ 6 months for testing (ideally observed ingestion/oral challenge) Once introduced, give regularly/several times per week/indefinitely 4. For family of any infant afraid to introduce at home, beware of potential for false positive skin/blood tests!

38 When is the ideal time to introduce allergenic foods to infants? Edmond Chan MD FRCPC Becky Blair RD MSc Host: Pediatric Network

39 Financial Interest Disclosure (over the past 24 months) No relevant financial relationships with any commercial interests

40 The importance of prevention Anaphylaxis Serious reaction and may cause death (CSACI, 2016) Impact of pediatric elimination diets on: Growth (Christie et al., 2002; Flammarion et al., 2011; Robbins et al., 2014; Meyer et al., 2016) Nutritional status (Berni Canani et al., 2014; Maslin et al., 2016, Meyer et al., 2016; Kvammen et al., 2018) risk as # of food allergies increases No apparent risk with dietitian intervention & counselling Impact on food acceptance & aversion?

41 How & when to prevent food allergy? Shown to be ineffective or lacks evidence: Pregnancy and lactation Dietary antigen avoidance (Kramer & Kakuma, 2012), LCPUFA supplementation (Gunaratne et al., 2015) Infancy Soy formula, prebiotics, probiotics, LCPUFA, exclusive breastfeeding vs. early intro of infant formula (Osborn & Sinn, 2006; Osborn & Sinn, 2007; Osborn & Sinn 2013; Schindler et al., 2016; Smith & Becker, 2016)

42 Food Allergy Prevention- Position Statements Recommendations (in brief): -breastfeed exclusively for the first six months of life -do not delay the intro of any specific solid food beyond 6 months -inducing tolerance by introducing solid foods at 4 to 6 months of age is currently under investigation and cannot be recommended at this time

43 Practice Resources

44 J Allergy Clin Immunol 2017; 139: 29-44

45 For the first time, this guideline defines at risk as the presence of severe eczema or egg allergy. J Allergy Clin Immunol 2017; 139: p. 32

46 Practice Resource

47 DC Interim statement Interim advice: For infants with severe eczema or egg allergy: Apply at about six months practice advice (NHTI 6-24 months) LEAP inclusion criteria was 4-11 months of age lack of sub-analysis done that compared 4-6 months vs months for primary outcome Infant with severe eczema key message: avoid delaying the introduction of peanut physician or allergist peanut allergy testing + supervised feeding before peanut is introduced do not routinely screen and direct families to health care providers before 6 months of age

48 DC Interim statement Infant with suspected egg allergy infant reacts to egg protein in breastmilk key message: avoid delaying the introduction of peanut Hard to implement in practice must be IgE egg protein allergic may take time for mother to identify egg vs. other potentially allergenic foods in her diet diagnostic accuracy of egg allergy in infants < 4 months of age? unknown whether existence of other food allergy is equally relevant (e.g. CPMA)

49 DC Interim statement Enquiring About Tolerance (EAT): RCT of general population of exclusively breastfed infants (UK) Intervention: early introduction (3+ months of age) of peanut, cooked hen s egg, cow s milk, sesame, whitefish and wheat Comparison: WHO guidelines for solid food intro after 6 months of age Food allergy to 1+ foods measured between 1-3 years Results: Low compliance by intervention parents No statistically significant difference between intervention and control in the prevalence of food allergy measured at 3 years Fewer food allergy cases amongst parents who adhered to the intervention compared to parents following WHO guidelines Perkin et al., 2016

50 DC Interim statement Interim advice: For mild to moderate eczema and no eczema: Apply at about six months practice advice (NHTI 6-24 months) When first offered, avoid offering more than one of the common food allergens per day, Wait 2 days before another common food allergy is introduced, As new foods are introduced, encourage parents to watch for signs of allergy, Ensure texture and size of the food is age appropriate, and Continue to offer the commonly allergenic food regularly to maintain tolerance.

51 Practice Guidance If a low risk family has been advised by their primary care practitioner to introduce solids and allergenic foods between 4-6 months: be supportive no evidence introduce solids prior to 6 months (4-6 months) increases food allergy risk, impacts breastfeeding duration or growth may benefit iron stores? decrease food allergy risk? reinforce signs of developmental readiness ensure foods are texture appropriate for age

52 National policy recommendation Is there justification for a more flexible national policy re: exclusive breastfeeding to ensure all infants are exposed to food proteins before six months?

53 National policy recommendation

54 National policy recommendation The Great Outcome Debate Exclusive breastfeeding recommendation (NHTI, 2013): Recommend exclusive breastfeeding for the first six months. Outcomes: Gastrointestinal tract infections, possibly respiratory tract infections infant, developed world (Kramer & Kakuma, 2012) VS Introduction of common food allergens before six months could prevent the development of pediatric food allergy potentially severe and lifelong

55 Thank-you for listening!