Early introduction of the “Big Eight” allergenic foods

Analysis of the risk of early food introduction

Although accounts of food allergy date back to at least 400 BCE,¹ significant concern in the medical literature can be traced back to the late 1980s. In May 1990, the British Medical Journal(BMJ) published a report of 4 deaths due to peanut allergy, noting, “All 4 were aware of their allergies, but could not avoid the allergen.”² In 1992, Pediatric Annals stated that the most worrisome food allergy problem for pediatricians was peanut allergy because peanut appeared to be the most dangerous of the allergenic foods.³

Practicing physicians were anxious to offer parents a way to reduce their infants’ risk of developing food allergy and researchers were anxious to provide guidance. With a lack of robust evidence, they would have done well to follow the dictum, “Don’t just do something, stand there,” but that is not what occurred. In August 2000, the American Academy of Pediatrics (AAP) Committee on Nutrition established infant feeding guidelines that it described as reasonable, although it was acknowledged that there were no conclusive studies on which to base definitive recommendations.⁴ The guidelines stated “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.” Despite the lack of supporting evidence, by the late 1990s this advice had become gospel.

Although it may still feel somewhat surprising that guidelines were promulgated without good evidence, it is worth remembering that the concept of evidence-based medicine was not yet firmly established, the term only having been introduced in the 1990s.^5,6

Concurrent with the new feeding guidelines, the prevalence of food allergy increased, and it became clear that the strategy of withholding these foods from infants to reduce the risk of developing food allergy had failed. In January 2008, an AAP Clinical Report acknowledged that there was no support for restricting the diet of infants beyond 4 to 6 months of age as a way to protect against the development of allergic disease such as eczema, asthma, or food allergy.⁷

New insight into peanut allergy

In November 2008, Gideon Lack, MD, and George Du Toit, MD, published a paper noting that despite guidelines recommending avoidance of peanut during infancy in the United States, United Kingdom, and Australia, peanut allergy had increased in these countries.⁸ They observed in particular that peanut allergy (PA) prevalence appeared to be much lower in Israel, where infants freely ate a peanut-containing snack during infancy. Their study confirmed not only their observation, but also that it was difficult to attribute this to something other than the early introduction of peanut to infants. (The study controlled for other factors, such as differences in social class, genetic background, and the particular variety of peanuts consumed.)

Lack and Du Toit concluded: “These findings raise the question of whether early introduction of peanut during infancy, rather than avoidance, will prevent the development of PA.” To answer this question, they conducted the Learning Early About Peanut (LEAP) study, which demonstrated unequivocally that infants at high risk of developing peanut allergy who ate peanut early and continuously had an at least 80% lower risk of developing peanut allergy than high-risk infants for whom the introduction of peanut was intentionally delayed.⁹

Over the years there have been other studies that lacked the definitive evidence of LEAP but provided compelling evidence that the early introduction of allergenic foods to infants might very well prevent the development of food allergy.

As far back as 2006, a study published in Pediatrics concluded that delayed initial exposure to cereal grains until after age 6 months may increase the risk of developing wheat allergy and that delayed introduction as a guideline could not be recommended.¹⁰

In August 2008, just 7 months after the AAP established that delaying the Big Eight (peanut, milk, shellfish, tree nut, egg, fish, wheat, and soy) was of no benefit, a paper in Pediatric Allergy and Immunology explored the relationship between starting solids and food intolerance, noting that concern about the practice of delaying foods until age 6 months was increasing. The authors concluded: “Tolerance to food allergens appears to be driven by regular, early exposure to these proteins during a ‘critical early window’ of development.”¹¹

In June 2009, Göran Wennergren, MD, PhD, from the Department of Pediatrics, University of Gothenburg, Queen Silvia Children’s Hospital, Gothenburg, Sweden, wrote a paper with the provocative title “What if it is the other way around? Early introduction of peanut and fish seems to be better than avoidance.” Wennergren proposed that the early introduction of foods during infancy might induce tolerance, thereby preventing the development of allergy.¹²

In January 2013, the inaugural issue of the Journal of Allergy and Clinical Immunology: In Practice did a review of the current literature and expert opinion and published recommendations for the prevention of allergic disease through dietary intervention, stating that new information suggests that delaying the introduction of foods to infants might increase the risk of food allergy, and “the early introduction of allergenic foods may prevent food allergy in infants/children.”¹³

In December 2013, the Canadian Pediatric Society in a joint statement with the Canadian Society of Allergy and Clinical Immunology stated that although research in this area was not complete, parents should not delay the introduction of any specific foods beyond age 6 months because this would not prevent, and might even increase, the risk of developing food allergy. It was noted that the strength of evidence for this was in the middle range.¹⁴

LEAP changes everything

The publication of LEAP in February 2015 was met with great acclaim. Anthony S. Fauci, MD, director of the National Institute of Health and Infectious Diseases, stated, “For a study to show a benefit of this magnitude in the prevention of peanut allergy is without precedent. The results have the potential to transform how we approach food allergy prevention.”¹⁵

In April 2019, the AAP published “The effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, hydrolyzed formulas, and timing of introduction of allergenic complementary foods,” a review and summary of current feeding guidelines stating that Infants at high risk should be fed peanut food at age 4 to 6 months after considering testing first for peanut allergy. For moderate-risk infants, the introduction of peanut-containing food is recommended at 6 months, and for low-risk infants it is recommended that families follow their own preferences and cultural practices. Regarding the other Big Eight allergenic foods, it is only reiterated that there is no evidence that delayed introduction is of benefit.¹⁶

The current guidelines are no doubt consistent with the strength of the evidence, and the guidelines established in 2000 are nothing if not a cautionary tale about making recommendations based on insufficient evidence. However, implementing guidelines based solely on the strength of evidence may not lead to best practices. An article in the Journal of Medical Ethics in 2004 described epistemological evidence-based medicine (EBM) as “setting the hierarchy and the gold standard of medical knowledge” and practical EBM as “a term describing the optimal way to practice medicine.”¹⁷ Analyzing the costs and benefits of early introduction results in a powerful argument that the guidelines ought to strongly recommend the early introduction of the Big Eight to all infants as a best practice.

The full benefits of a broad recommendation to eat the Big Eight cannot be fully quantified, but the potential is vast:

·      A universal recommendation of early introduction of peanut would benefit high-risk infants who are not recognized as such.

·      Many new cases of peanut allergy annually are in the low-risk group, and although LEAP categorized infants as high-, medium-, and low-risk, risk falls on a continuum. It seems quite likely, then, that some number of these low-risk infants would benefit from early introduction.

·      Based on current prevalence, 320,000 of the children born this year can be expected to develop food allergy and, as already noted, there is significant, if not conclusive, evidence of benefit in a number of studies. My own review of common illnesses and their treatments shines a light on the (perhaps obvious) reality that medical interventions are often broadly accepted in the absence of definitive evidence, if for no other reason than the simple fact that definitive evidence can be so difficult to obtain.²⁴

The diet of many children is suboptimal. Adding the Big Eight to an infant’s diet makes it more varied and nutritious, and studies show this increases the chance that the child will remain a healthy eater.²⁵

In other words, Eat the Eight-early and often. 

References:

1. Sampson HA. Food allergy: past, present and future. Allergol Int. 2016;65(4):363-369.

2. Donovan K, Peters J. Vegetable burger allergy: all was nut as it appeared. BMJ. 1990;300(6736):1378.

3. Waggoner M. Parsing the peanut panic: the social life of a contested food allergy epidemic. Soc Sci Med. 2013;90:49-55.

4. American Academy of Pediatrics. Committee on Nutrition. Hypoallergenic infant formulas. Pediatrics. 2000;106(2 pt 1);346-349.

5. Claridge JA, Fabian TC. History and development of evidence-based medicine. World J Surg. 2005;29(5):547-553.

6. Sur RL, Dahm P. History of evidence-based medicine. Indian J Urol. 2011;27(4):487-489.

7. Greer FR, Sicherer SH, Burks AW; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Allergy and Immunology. The 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. Pediatrics. 2008;121(1):183-191.

8. Du Toit G, Katz Y, Sasieni P, et al. Lack early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008;122(5):984-991.

9. Du Toit G, Roberts G, Sayre, et al; LEAP Study Team. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803-813.

10. Poole JA, Barriga K, Leung DY, et al. Timing of initial exposure to cereal grains and the risk of wheat allergy. Pediatrics. 2006;117(6):2175-2182.

11. Prescott SL, Smith P, Tang M, et al. The importance of early complementary feeding in the development of oral tolerance: concerns and controversies. Pediatr Allergy Immunol. 2008;19(5):375-380.

12. Wennergren G. What if it is the other way around? Early introduction of peanut and fish seems to be better than avoidance. Acta Paediatr. 2009;98(7):1085-1087.

13. Fleischer DM, Spergel JM, Assa’ad AJ. Pongracic JA. Primary prevention of allergic disease through nutritional interventions. J Allergy Clin Immunol Pract. 2013;1(1):29-36.

14. Abrams EM, Hildebrand K, Blair B, Chan ES; Canadian Paediatric Society. Timing of introduction of allergenic solids for infants at high risk. Canadian Paediatric Society website. Available at: https://www.cps.ca/en/documents/position/allergenic-solids. Published January 24, 2019. Accessed August 14, 2019.

15. National Institutes of Health. Peanut consumption in infancy lowers peanut allergy [press release]. Available at: https://www.nih.gov/news-events/nih-researchmatters/peanut-consumption-infancy-lowers-peanut-allergy. Published February 23, 2015. Accessed August 14, 2019.

16. Greer FR, Sicherer SH, Burks AW: Committee on Nutrition; Section on Allergy and Immunology. The effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, hydrolyzed formulas, and timing of introduction of allergenic complementary foods. Pediatrics. 2019;143(4):e20190281.

17. Saarni S, Gylling HA. Evidence based medicine guidelines: a solution to rationing or politics disguised as science. J Med Ethics. 2004;30(2):171-175.

18. Feeney M, Du Toit G, Roberts G; et al; Immune Tolerance Network LEAP Study Team. Impact of peanut consumption in the LEAP study: feasibility, growth, and nutrition. J Allergy Clin Immunol. 2016;138(4):1108-1118.

19. Bock SA, Munoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001;107(1);191-193.

20. Rudders SA, Banerji A, Clark S, Camargo CA Jr. Age-related differences in the clinical presentation of food-induced anaphylaxis. J Pediatr. 2011:158(2):326-328.

21. Topal E, Bakirtas A, Yilmaz O, et al. Anaphylaxis in infancy compared with older children. Allergy Asthma Proc. 2013;34(3):233-238.

22. Koplin JJ Peters RL, Dharmage SC, et al; HealthNuts study investigators. Understanding the feasibility and implications of implementing early peanut introduction for prevention of peanut allergy. J Allergy Clin Immunol. 2016;138(4):1131.e2-1141.e2.

23. Turner PJ, Campbell DE. Implementing primary prevention for peanut allergy at a population level. JAMA. 2017;317(11):1111-1112.

24. Sunog R, Eat the Eight: Preventing Food Allergy with Food and the Imperfect Art of Medicine. The Nasiona; 2019.

25. Birch L, Savage JS, Ventura A. Influences on the development of children’s eating behaviours: from infancy to adolescence. Can J Diet Pract Res. 2007;68(1):s1-s56.