Skip to main content

Dietary exposures and allergy prevention in high-risk infants

Abstract

Infants at high risk for developing a food allergy have either an atopic condition (such as eczema) themselves or an immediate family member with such a condition. Breastfeeding should be promoted and supported regardless of issues pertaining to food allergy prevention, but for infants whose mothers cannot or choose not to breastfeed, using a specific formula (i.e., hydrolyzed formula) is not recommended to prevent food allergies. When cow’s milk protein formula has been introduced in an infant’s diet, make sure that regular ingestion (as little as 10 mL daily) is maintained to prevent loss of tolerance. For high-risk infants, there is compelling evidence that introducing allergenic foods early—at around 6 months, but not before 4 months of age—can prevent common food allergies, and allergies to peanut and egg in particular. Once an allergenic food has been introduced, regular ingestion (e.g., a few times a week) is important to maintain tolerance. Common allergenic foods can be introduced without pausing for days between new foods, and the risk for a severe reaction at first exposure in infancy is extremely low. Pre-emptive in-office screening before introducing allergenic foods is not recommended. No recommendations can be made at this time about the role of maternal dietary modification during pregnancy or lactation, or about supplementing with vitamin D, omega 3, or pre- or probiotics as means to prevent food allergy.

Introduction

The self-reported prevalence of food allergy in Canada is approximately 6% [1], and food allergy has increased over the past few decades [2]. Recent evidence suggests that preventing the development of food allergies in infants is possible. Several studies [3, 4], and one meta-analysis [5], have supported the early introduction of allergenic foods (in particular peanut and cooked egg) as a means of preventing allergies to those foods. This revised statement replaces a previous Canadian Paediatric Society (CPS) document from 2013 [6] and expands on a 2019 CPS practice point on this topic [7]. Recent research supports stronger recommendations than previously, for the active introduction of allergenic foods early in life. Further, there is now compelling evidence that warrants changing other, related recommendations, including the definition of an infant at high risk for developing allergic conditions [3, 8], the role of pre-emptive screening [8,9,10,11,12], the role of hydrolyzed formula [13, 14]] for allergy prevention, and the preventive role of breastfeeding in balance with the early introduction of solid foods [15,16,17].

Defining risk

There is no international consensus on the definition of infants at high risk for food allergy development. The CPS practice point defines an infant at high risk as having either a personal history of atopy or a first-degree relative (at least one parent or sibling) with an atopic condition (such as asthma, allergic rhinitis, food allergy, or eczema) [7]. That definition is used here, too, because it is broader than those based solely on family history [6, 18], and reflects the increasing evidence that the infants most at risk for developing food allergy have a personal history of eczema or other food allergy [19,20,21,22]. This inclusive definition also reflects the definition used by the National Institutes for Allergy and Infectious Diseases (NIAID) for an infant at high-risk of peanut allergy as having severe eczema and/or egg allergy [8]. It is important to remember, however, that food allergy can occur in infants with no specific risk factors [23].

Breastfeeding, and maternal diet during pregnancy and lactation

The available research trials examining the role of maternal allergen ingestion during pregnancy and lactation are observational studies that have demonstrated inconsistent results (Table 1). Systematic reviews of these observational trials have shown no link between maternal dietary intake and food allergy outcomes in children [24, 25]. Some study authors have noted limitations of methods, analysis, and inclusion criteria that have hampered results [26], with one recent systematic review concluding there was “no good evidence to recommend that pregnant or breastfeeding women should change their diet to prevent allergies in infants at high or normal risk” [26, 27]. Specific to peanut allergy, recent studies suggest that mothers ingesting peanut during breastfeeding may decrease the risk of peanut sensitization, provided this is coupled with the early introduction of peanut in the infant’s diet [28, 29]. However, these studies are insufficient to support a recommendation to actively ingest peanut protein during breastfeeding. That there is no benefit to maternal dietary avoidance during pregnancy or lactation has been established, with one Cochrane review not only noting no reduction in atopic disease but possible harms, including a trend toward increased risk for preterm labour or low birth weight [25]. Randomized controlled trials (RCTs) are ongoing that will better inform this issue [30, 31]. Evidence that modifying the maternal diet during pregnancy and breastfeeding is an effective strategy to prevent food allergy is therefore lacking.

Table 1 Exposures and associations with food allergy prevention

The data on breastfeeding itself as a food allergy prevention strategy are also mixed. Some studies have supported breastfeeding as a means to prevent allergy, while others have found no association [32,33,34]. Limitations in the breastfeeding literature include studies that were solely observational, inconsistent breastfeeding durations, and variable diagnostic criteria for food allergy.

For many health promoting reasons other than to prevent food allergy [18], the World Health Organization (WHO) and other leading international bodies [6, 35], support exclusive breastfeeding for an infant’s first 6 months, and continued complementary breastfeeding up to age 2 years and beyond [36, 37].

Choice of formula

There is insufficient evidence at this time to advise on the use of specific formulas, such as hydrolyzed formulas, for allergy prevention. To prevent atopic conditions generally, previous guidelines have recommended the use of hydrolyzed formulas when mothers could not, or chose not to, breastfeed [6, 18]. However, a recent Cochrane review found no evidence to support short-term or prolonged hydrolyzed formula feeding (compared with exclusive breastfeeding) to prevent atopic disease [38]. Also, one recent meta-analysis found no evidence that any hydrolyzed formula, whether partially or extensively hydrolyzed, prevented any atopic conditions, including food allergy [13]. Current evidence does not favour using hydrolyzed formulas rather than intact cow’s milk formula to prevent atopic conditions.

Regarding cow’s milk formula specifically, three observational studies have documented increased risk for developing cow’s milk allergy with delayed or irregular ingestion of cow’s milk early in life [39,40,41]. One recent RCT of 504 infants in Japan found that ingesting a minimum of 10 mL of cow’s milk formula at least once every day (compared with avoiding cow’s milk formula supplementation) at 1–2 months of age significantly reduced cow’s milk allergy at 6 months of age (0.8% versus 6.8%, risk ratio (RR) 0.12, 95% confidence interval (CI) 0.01–0.50; probability (P) < 0.001). Moreover, cow’s milk formula did not ‘compete’ with breastfeeding. Approximately 70% of infants from both groups were still breastfeeding at 6 months of age [42]. Both groups had frequent cow’s milk formula exposure in the first month of life, and the evidence suggested that stopping cow’s milk formula feeds in the second month increased the risk for developing cow’s milk allergy. Therefore, practitioners and families should be aware that irregularly supplementing breastfeeding with cow's milk formula may increase risk for cow's milk allergy. If cow’s milk formula is introduced, regular ingestion (as little as 10 mL daily) should be maintained to prevent loss of tolerance [42].

Introducing solid foods

Several observational studies have found an association between early ingestion (at less than 6 months of age) of a specific food allergen (in particular cow’s milk, egg, and peanut) and lower rates of allergy to that food in childhood [43,44,45]. Studies conducted since 2013, including RCTs, have provided convincing evidence for the early introduction of allergenic foods to prevent food allergy in high-risk infants.

A significant ‘leap’ forward in this field was the Learning Early About Peanut (LEAP) study in infants at high risk for peanut allergy [3], which randomized 640 infants with severe eczema or egg allergy (or both) to either early peanut ingestion (at 4–11 months) or avoidance until 5 years of age. Results demonstrated an 80% reduction in peanut allergy with early peanut ingestion [3]. The LEAP study found a preventative effect in both skin test-negative (13.7% versus 1.9%; P < 0.001) and skin test-positive infants (35.3% versus 10.6%; P = 0.004), which supported early peanut introduction as a means of both primary and secondary prevention. One recent meta-analysis and systematic review confirmed with moderate certainty that introducing peanut early (at 4–11 months) is associated with reducing peanut allergy (RR0.29; 95% CI: 0.11–0.74) [5].

Five RCTs have examined early egg introduction in high-risk infants to prevent egg allergy, with discrepant results, perhaps because egg was ingested in different forms. The only RCT to examine early cooked egg ingestion (the PETIT study) randomized 147 infants with eczema to either egg ingestion at 6 months of age or avoidance until one year of age, and found a significant reduction in egg allergy with earlier ingestion (RR 0.222; 95% CI: 0.081–0.607; P = 0.0012) [4]. By contrast, four RCTs examining early pasteurized raw egg ingestion failed to show a preventative effect against egg allergy, or revealed a high rate of adverse events, or both [46,47,48,49]. One meta-analysis and systematic review reported with moderate certainty that early egg introduction (at 4–6 months) was associated with reduced egg allergy (RR 0.56; 95% CI: 0.36–0.87) [5].

Only one randomized trial, the Enquiring About Tolerance (‘EAT’) study, examined the early introduction of multiple allergenic foods (peanut, cow’s milk, sesame, fish, wheat, egg) [23] in 1303 standard-risk infants. They were randomized to either early (at 3 months) or more typical (at 6 months) ingestion of all six allergens. No significant difference in the rate of food allergy was found between the two groups during the intention to treat analysis (5.6% versus 7.1% respectively; P = 0.32). Adherence was a significant issue in this study, however, at 42.8% overall.

Following the LEAP study, the NIAID released addendum guidelines which recommended that infants with severe eczema, egg allergy, or both have peanut introduced into their diet at 4–6 months of age [8]. For infants with mild to moderate eczema, the recommendation was for at-home introduction at around 6 months of age, and for infants without atopic risk factors, the recommendation was for introduction in accordance with parental preference and cultural norms. The CPS practice point also recommended that infants with either a personal or immediate family history of atopy be introduced to allergenic foods at about 6 (but not before 4) months of age [7, 10], in keeping with other international organizations, such as the Australasian Society of Clinical Immunology and Allergy [10].

There are still several areas of uncertainty. Introducing allergenic solid foods before 6 months of age to prevent food allergy in high-risk infants remains somewhat controversial in some contexts. The optimal amount of allergenic solid per serving is unclear, and evidence concerning other common allergenic foods (e.g., tree nuts, sesame, grains, soy, fish and shellfish) is lacking, although the mechanism of sensitization is believed to be similar. In infants with non-IgE-mediated food allergies (i.e., food protein-induced enterocolitis syndrome [FPIES]), guidelines have recommended delaying introduction of allergenic foods such as egg and peanut to reduce the risk of FPIES in response to those foods [50]. However, because IgE-mediated food allergies are not only more prevalent but generally more difficult to outgrow, the risk for developing an IgE-mediated allergy to peanut or egg from delayed introduction is more concerning than the theoretical benefit of delayed introduction to manage FPIES [51]. Furthermore, the optimal frequency of allergenic solid ingestion remains unknown, although all the RCTs completed to date have required regular ingestion (typically several times a week) as a part of their protocols [3, 39, 40]. As noted above, the cow’s milk formula studies have suggested that irregular exposure could increase the risk for developing cow’s milk allergy [39,40,41]. While the frequency of ingestion of allergenic solids may be unclear, regularity appears to be important, with a few ingestions per week to promote ongoing tolerance being recommended by the CPS in 2019 [7].

There is no hard evidence of benefit for spacing out the introduction of different foods (by a certain number of days, for example), and some allergists may recommend introducing mixtures (e.g., different mixed tree nut butters) on a case-by-case basis, for convenience. A recent survey of paediatricians in the United States found that most did not counsel families to wait 3 days (or longer) between introducing foods, noting that the practice may limit infant food diversity and delay early peanut introduction [52].

Another potential drawback of introducing solid foods before 6 months is the potential impact on the total duration of breastfeeding and the benefits of exclusive breastfeeding. However, neither the LEAP nor EAT studies found that breastfeeding duration differed significantly among their test groups [3, 23], and one recent Canadian survey found that paediatricians and family physicians were largely unconcerned that earlier introduction of solid foods in infant diets would impact breastfeeding negatively [53].

Pre-emptive screening

The NIAID has recommended administering a pre-emptive skin prick test or specific IgE blood tests before introducing peanut to high-risk infants. The American Academy of Pediatrics (AAP) supported this recommendation in their own 2019 statement, but added that testing should “not be a deterrent or generate ‘screening creep’” (e.g., by including lower risk infants with mild to moderate eczema as well as infants in the high-risk category) [8, 14]. However, these screening recommendations have not been adopted in leading British or Australasian guidelines, or in new North American consensus guidance [9, 10, 22]. Significant population-level testing limits, such as high rates of clinically irrelevant positive test results—and the lack of infant oral food challenges to exclude them [53]—make pre-emptive screening impractical [2, 54]. Long waiting lists [53, 55], low cost effectiveness [56, 57], the risk of ‘screening creep’ [58], and low parent stakeholder acceptance of this approach, are further impediments [53, 59, 60] to pre-emptive screening.

One Australian study on feasibility estimated that screening all infants considered to be at high risk for peanut allergy would require testing 16% of the infant population but would still miss 23% of peanut allergy cases [19]. Also, none of the LEAP infants in the early introduction arm experienced anaphylaxis at first ingestion, and no known fatalities following early introduction occurred [3]. Even if anaphylaxis were to occur at the first ingestion, one American study from 2018 showed that only 4% of infants experiencing anaphylaxis had truly severe symptoms, which was lower than in older children, and no fatalities were reported [61]. Another recent American study of food allergy-related emergency room visits found that infants presenting with anaphylaxis tended to do so after the first known ingestion of the offending food, and that children under 2 years of age were less likely to meet anaphylaxis criteria than older children [62]. Data from Australia published in 2019 has similarly shown high uptake of early peanut introduction with no pre-emptive-screening. A threefold increase in early peanut ingestion occurred in 2017/18 based on education alone, with 88.6% (95% CI: 86.1–90.7%) of infants having been introduced to peanut by 12 months of age compared with only 28.4% (95% CI: 27.2–29.7%) in 2007/11 [63]. The risk of having a severe reaction to peanut during at home introduction in infancy is extremely small (0.08%), and increasing awareness of this could assist with implementation of food allergy prevention [64, 65].

In Canada, there is insufficient evidence to support pre-emptive screening of allergenic foods prior to introducing into children’s diets, and routine testing is not recommended. In-office or virtual [66] introduction of allergenic foods should only be considered for families who are very hesitant, despite education, to try this at home.

Other interventions

Several other interventions, including supplementation with vitamin D [67, 68], omega 3 [69, 70], and pre- or probiotics [71,72,73,74] are being studied as possible food allergy preventive measures, but the data are mixed and no firm conclusions regarding these strategies can be made at this time.

Recommendations for clinicians

  • Consider infants at high risk for food allergy when they have a personal history of atopy or a first-degree relative (at least one parent or sibling) with an atopic condition (such as asthma, allergic rhinitis, food allergy, or eczema).

  • Promote and support breastfeeding for up to 2 years and beyond, regardless of issues pertaining to food allergy prevention.

  • There is still insufficient evidence to recommend modifying the maternal diet to prevent food allergy (i.e., by avoiding or ingesting particular allergenic foods during pregnancy and while breastfeeding).

  • For mothers who cannot or choose not to breastfeed, hydrolyzed formulas should not be recommended to prevent atopic conditions (e.g., eczema, asthma, allergic rhinitis) in either high- or low-risk infants.

  • When cow’s milk protein formula has been introduced in an infant’s diet, make sure that regular ingestion (as little as 10 mL daily) is maintained to prevent loss of tolerance.

  • For high-risk infants, encourage the introduction of allergenic foods (e.g., cooked [not raw] egg, peanut) early, at about 6 months and not before 4 months of age, in a safe and developmentally appropriate way, at home. In infants at low risk for food allergy, allergenic foods can also be introduced at around 6 months of age.

  • New foods, including commonly allergenic foods, can be introduced on successive days, with no evidence of harm to this approach.

  • When allergenic foods have been introduced, make sure that ongoing ingestion of age-appropriate serving sizes is regular (i.e., a few times a week), to maintain tolerance.

  • Pre-emptive screening for infant food allergies is not recommended. Families should be counseled that the risk of a severe reaction on the first exposure to an allergen is extremely low.

  • There is currently insufficient evidence to recommend vitamin D, omega 3, or pre- or probiotic supplements to prevent food allergies in infants.

Availability of data and materials

There is no private material and hence all data and material is publicly available.

Abbreviations

AAP:

American Academy of Pediatrics

CPS:

Canadian Pediatric Society

EAT:

Enquiring About Tolerance

FPIES:

Food Protein Induced Enterocolitis Syndrome

LEAP:

Learning Early About Peanut

RCT:

Randomized controlled trial

References

  1. Clarke AE, Elliott SJ, St Pierre Y, Soller L, La Vieille S, Ben-Shoshan M. Temporal trends in prevalence of food allergy in Canada. J Allergy Clin Immunol Pract. 2020;8(4):1428–30.

    PubMed  Article  Google Scholar 

  2. Sicherer SH, Sampson HA. Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol. 2018;141(1):41–58.

    CAS  PubMed  Article  Google Scholar 

  3. Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803–13.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  4. Natsume O, Kabashima S, Nakazato J, et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;389(10066):276–86.

    PubMed  Article  Google Scholar 

  5. Ierodiakonou D, Garcia-Larsen V, Logan A, et al. Timing of allergenic food introduction to the infant diet and risk of allergic or autoimmune disease: a systematic review and meta-analysis. JAMA. 2016;316(11):1181–92.

    PubMed  Article  Google Scholar 

  6. Chan ES, Cummings C, Atkinson A, et al; Canadian Paediatric Society, Community Paediatrics Committee. Dietary exposures and allergy prevention in high-risk infants: A joint statement with the Canadian Society of Allergy and Clinical Immunology. Paediatr Child Health 2013;18(10):545–54

  7. Abrams EM, Hildebrand KJ, Blair B, Chan ES. Timing of introduction of allergenic solids for infants at high risk. Paediatr Child Health. 2019;24(1):56–7.

    PubMed  PubMed Central  Article  Google Scholar 

  8. Togias A, Cooper SF, Acebal ML, et al. Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. J Allergy Clin Immunol. 2017;139(1):29–44.

    PubMed  PubMed Central  Article  Google Scholar 

  9. British Society for Allergy and Clinical Immunology (BSACI). Preventing food allergy in higher risk infants: guidance for healthcare professionals: https://www.bsaci.org/wp-content/uploads/2020/02/pdf_Early-feeding-guidance-for-HCPs-2.pdf. Accessed 17 Feb 2021.

  10. Netting MJ, Campbell DE, Koplin JJ, et al. An Australian consensus on infant feeding guidelines to prevent food allergy: outcomes from the Australian infant feeding summit. J Allergy Clin Immunol Pract. 2017;5(6):1617–24.

    PubMed  Article  Google Scholar 

  11. Abrams EM, Chan ES, Sicherer SH. Should Younger siblings of peanut allergic children be screened for peanut allergy? J Allergy Clin Immunol Pract. 2018;6(2):414–8.

    PubMed  Article  Google Scholar 

  12. Abrams EM, Singer AG, Chan ES. Pre-emptive screening for peanut allergy before peanut ingestion in infants is not standard of care. CMAJ. 2019;191(42):E1169–70.

    PubMed  PubMed Central  Article  Google Scholar 

  13. Boyle RJ, Ierodiakonou D, Khan T, et al. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis. BMJ. 2016;352:i974.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  14. Greer FR, Sicherer SH, Burks AW, AAP 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.

    PubMed  Article  Google Scholar 

  15. Feeney M, Du Toit G, Roberts G, et al. Impact of peanut consumption in the LEAP Study: feasibility, growth, and nutrition. J Allergy Clin Immunol. 2016;138(4):1108–18.

    PubMed  PubMed Central  Article  Google Scholar 

  16. Perkin MR, Logan K, Marrs T, et al. Enquiring About Tolerance (EAT) study: feasibility of an early allergenic food introduction regimen. J Allergy Clin Immunol. 2016;137(5):1477-86.e8.

    PubMed  PubMed Central  Article  Google Scholar 

  17. Abrams EM, Greenhawt M, Fleischer DM, Chan ES. Early solid food introduction: role in food allergy prevention and implications for breastfeeding. J Pediatr. 2017;184:13–8.

    PubMed  Article  Google Scholar 

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

    PubMed  Article  Google Scholar 

  19. Koplin JJ, Peters RL, Dharmage SC, et al. Understanding the feasibility and implications of implementing early peanut introduction for prevention of peanut allergy. J Allergy Clin Immunol. 2016;138(4):1131-41.e2.

    PubMed  Article  Google Scholar 

  20. Tsakok T, Marrs T, Mohsin M, et al. Does atopic dermatitis cause food allergy? A systematic review. J Allergy Clin Immunol. 2016;137(4):1071–8.

    PubMed  Article  Google Scholar 

  21. Martin PE, Eckert JK, Koplin JJ, et al. Which infants with eczema are at risk of food allergy? Results from a population-based cohort. Clin Exp Allergy. 2015;45(1):255–64.

    CAS  PubMed  Article  Google Scholar 

  22. Fleischer DM, Chan ES, Venter C, et al. A consensus approach to the primary prevention of food allergy through nutrition: guidance from the American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; and the Canadian Society for Allergy and Clinical Immunology. J Allergy Clin Immunol Pract. 2021;9(1):22-43.e4.

    PubMed  Article  Google Scholar 

  23. Perkin MR, Logan K, Tseng A, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374(18):1733–43.

    CAS  PubMed  Article  Google Scholar 

  24. Netting MJ, Middleton PF, Makrides M. Does maternal diet during pregnancy and lactation affect outcomes in offspring? A systematic review of food-based approaches. Nutrition. 2014;30(11–12):1225–41.

    CAS  PubMed  Article  Google Scholar 

  25. Kramer MS, Kakuma R. Cochrane in context: Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Evid Based Child Health. 2014;9(2):484–5.

    PubMed  Article  Google Scholar 

  26. Thompson RL, Miles LM, Lunn J, et al. Peanut sensitisation and allergy: Influence of early life exposure to peanuts. Br J Nutr. 2010;103(9):1278–86.

    CAS  PubMed  Article  Google Scholar 

  27. de Silva D, Geromi M, Halken S, et al. Primary prevention of food allergy in children and adults: systematic review. Allergy. 2014;69(5):581–9.

    PubMed  Article  Google Scholar 

  28. Pitt TJ, Becker AB, Chan-Yeung M, et al. Reduced risk of peanut sensitization following exposure through breast-feeding and early peanut introduction. J Allergy Clin Immunol. 2018;14(2):620-25.e1.

    Article  Google Scholar 

  29. Azad MB, Dharma C, Simons E, et al. Reduced peanut sensitization with maternal peanut consumption and early peanut introduction while breastfeeding. J Dev Orig Health Dis. 2020. https://doi.org/10.1017/S2040174420001129 (Online ahead of print).

    Article  PubMed  Google Scholar 

  30. Telethon Kids Institute. The origins project. The PrEggNut and BENEFIT studies. https://originsproject.telethonkids.org.au/sub-projects/the-preggnut-and-benefit-studies/. Accessed 17 Feb 2021.

  31. Australian New Zealand Clinical Trials Registry. PrEggNut study. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375199. Accessed 15 Jan 2021.

  32. van Odijk J, Kull I, Borres MP, et al. Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966–2001) on the mode of early feeding in infancy and its impact on later atopic manifestations. Allergy. 2003;58(9):833–43.

    PubMed  Article  Google Scholar 

  33. Saarinen UM, Kajosaari M. Breastfeeding as prophylaxis against atopic disease: prospective follow-up study until 17 years old. Lancet. 1995;346(8982):1065–9.

    CAS  PubMed  Article  Google Scholar 

  34. Jelding-Dannemand E, Malby Schoos A-M, Bisgaard H. Breast-feeding does not protect against allergic sensitization in early childhood and allergy-associated disease at age 7 years. J Allergy Clin Immunol. 2015;136(5):1302-8.e1-13.

    PubMed  Article  Google Scholar 

  35. World Health Organization. Health topics/breastfeeeding. www.who.int/health-topics/breastfeeding#tab=tab_1. Accessed 17 Feb 2021.

  36. Grueger B; Canadian Paediatric Society, Community Paediatrics Committee. Weaning from the breast. https://www.cps.ca/en/documents/position/weaning-from-the-breast.

  37. Health Canada, Canadian Paediatric Society, Dietitians of Canada, and Breastfeeding Committee for Canada. Nutrition for Healthy Term Infants: Recommendations from 6 to 24 Months: https://www.canada.ca/en/health-canada/services/canada-food-guide/resources/infant-feeding/nutrition-healthy-term-infants-recommendations-birth-six-months/6-24-months.html. Accessed 15 Jan 2021.

  38. Osborn DA, Sinn JK, Jones LJ. Infant formulas containing hydrolysed protein for prevention of allergic disease. Cochrane Database Syst Rev. 2018;10(10):CD003664.

    PubMed  Google Scholar 

  39. Onizawa Y, Noguchi E, Okada M, Sumazaki R, Hayashi D. The association of the delayed introduction of cow’s milk with IgE-mediated cow’s milk allergies. J Allergy Clin Immunol Pract. 2016;4(3):481-88.e2.

    PubMed  Article  Google Scholar 

  40. Katz Y, Rajuan N, Goldberg MR, et al. Early exposure to cow’s milk protein is protective against IgE-mediated cow’s milk protein allergy. J Allergy Clin Immunol. 2010;126(1):77-82.e1.

    CAS  PubMed  Article  Google Scholar 

  41. Peters RL, Koplin JJ, Dharmage SC, et al. Early exposure to cow’s milk protein is associated with a reduced risk of cow’s milk allergic outcomes. J Allergy Clin Immunol Pract. 2019;7(2):462-70.e1.

    PubMed  Article  Google Scholar 

  42. Sakihara T, Otsuji K, Arakaki Y, Hamada K, Sugiura S, Ito K. Randomized trial of early infant formula introduction to prevent cow’s milk allergy. J Allergy Clin Immunol. 2021;147(1):224–32.

    CAS  PubMed  Article  Google Scholar 

  43. Katz Y, Goldberg MR, Rajuan N, Cohen A, Leshno M. The prevalence and natural course of food protein-induced enterocolitis syndrome to cow’s milk: a large-scale, prospective population-based study. J Allergy Clin Immunol. 2011;127(3):647-53.e1-3.

    CAS  PubMed  Article  Google Scholar 

  44. Koplin JJ, Osborne NJ, Wake M, et al. Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol. 2010;126(4):807–13.

    PubMed  Article  Google Scholar 

  45. Du Toit G, Katz Y, Sasieni P, et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol. 2008;122(5):984–91.

    PubMed  Article  CAS  Google Scholar 

  46. Wei-Liang Tan J, Valerio C, Barnes EH, et al. A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy. J Allergy Clin Immunol. 2017;139(5):1621-28.e8.

    PubMed  Article  Google Scholar 

  47. Palmer DJ, Metcalfe J, Makrides M, et al. Early regular egg exposure in infants with eczema: a randomized controlled trial. J Allergy Clin Immunol. 2013;132(2):387-92.e1.

    PubMed  Article  Google Scholar 

  48. Palmer DJ, Sullivan TR, Gold MS, Prescott SL, Makrides M. Randomized controlled trial of early regular egg intake to prevent egg allergy. J Allergy Clin Immunol. 2017;139(5):1600-07.e2.

    CAS  PubMed  Article  Google Scholar 

  49. Bellach J, Schwarz V, Ahrens B, et al. Randomized placebo-controlled trial of hen’s egg consumption for primary prevention in infants. J Allergy Clin Immunol. 2017;139(5):1591-99.e2.

    CAS  PubMed  Article  Google Scholar 

  50. Nowak-Węgrzyn A, Chehade M, Groetch ME, et al. International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: executive summary—Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. 2017;139(4):1111-26.e4.

    PubMed  Article  Google Scholar 

  51. Abrams EM, Hildebrand KJ, Chan ES, Canadian Paediatric Society, Allergy Section. Non-IgE-mediated food allergy: evaluation and management. Paediatr Child Health. 2021;26(3):173–81.

    PubMed  PubMed Central  Article  Google Scholar 

  52. Samady W, Campbell E, Aktas ON, et al. Recommendations on complementary food introduction among pediatric practitioners. JAMA Netw Open. 2020;3(8):e2013070.

    PubMed  PubMed Central  Article  Google Scholar 

  53. Abrams EM, Singer AG, Soller L, Chan ES. Knowledge Gaps and barriers to early peanut introduction among allergists, pediatricians, and family physicians. J Allergy Clin Immunol Pract. 2019;7(2):681–4.

    PubMed  Article  Google Scholar 

  54. Abrams EM, Sicherer SH. Diagnosis and management of food allergy. CMAJ. 2016;188(15):1087–93.

    PubMed  PubMed Central  Article  Google Scholar 

  55. Abrams EM, Chan ES. Potential pitfalls in applying screening criteria in infants at risk of peanut allergy. J Pediatr. 2018;195:269–74.

    PubMed  Article  Google Scholar 

  56. Shaker M, Stukus D, Chan ES, Fleischer DM, Spergel JM, Greenhawt M. “To screen or not to screen”: comparing the health and economic benefits of early peanut introduction strategies in five countries. Allergy. 2018;73(8):1707–14.

    CAS  PubMed  Article  Google Scholar 

  57. Greenhawt M, Shaker M. Determining levers of cost-effectiveness for screening infants at high risk for peanut sensitization before early peanut introduction. JAMA Netw Open. 2019;2(12):e1918041.

    PubMed  PubMed Central  Article  Google Scholar 

  58. Turner PJ, Campbell DE. Implementing primary prevention for peanut allergy at a population level. JAMA. 2017;317(11):1111–2.

    PubMed  Article  Google Scholar 

  59. Abrams EM, Soller L, Singer AG, Fleischer DM, Greenhawt M, Chan ES. Comparison of practice patterns among Canadian allergists before and after NIAID guideline recommendations. J Allergy Clin Immunol Pract. 2019;7(8):2901-03.e3.

    PubMed  Article  Google Scholar 

  60. Hsu E, Soller L, Abrams EM, Protudjer JLP, Mill C, Chan ES. Oral food challenge implementation: the first mixed-methods study exploring barriers and solutions. J Allergy Clin Immunol Pract. 2020;8(1):149-56.e1.

    PubMed  Article  Google Scholar 

  61. Samady W, Trainor J, Smith B, Gupta R. Food-induced anaphylaxis in infants and children. Ann Allergy Asthma Immunol. 2018;121(3):360–5.

    PubMed  Article  Google Scholar 

  62. Ko J, Zhu S, Alabaster A, Wang J, Sax DR. Prehospital treatment and emergency department outcomes in young children with food allergy. J Allergy Clin Immunol Pract. 2020;8(7):2302-09.e2.

    PubMed  Article  Google Scholar 

  63. Soriano VX, Peters RL, Ponsonby A-L, et al. Earlier ingestion of peanut after changes to infant feeding guidelines: the EarlyNuts study. J Allergy Clin Immunol. 2019;144(5):1327-35.e5.

    PubMed  Article  Google Scholar 

  64. Abrams EM, Primeau M-N, Kim H, Gerdts J, Chan ES. Increasing awareness of the low risk of severe reaction at infant peanut introduction: Implications during COVID-19 and beyond. J Allergy Clin Immunol Pract. 2020;8(10):3259–60.

    PubMed  PubMed Central  Article  Google Scholar 

  65. Tsuang A, Chan ES, Wang J. Food-induced anaphylaxis in infants: can new evidence assist with implementation of food allergy prevention and treatment? J Allergy Clin Immunol Pract. 2021;9(1):57–69.

    PubMed  Article  Google Scholar 

  66. Latrous M, Zhu R, Mack DP, et al. Web-based Infant Food Introduction (WIFI): Feasibility and satisfaction of virtual allergist-supervised food introduction. J Allergy Clin Immunol Pract 2021;S2213-2198(21)00598-5. Online ahead of print.

  67. Allen KJ, Koplin JJ, Ponsonby A-L, et al. Vitamin D insufficiency is associated with challenge-proven food allergy in infants. J Allergy Clin Immunol 2013;131(4):1109–16, 1116.e1–6.

  68. Molloy J, Koplin JJ, Allen KJ, et al. Vitamin D insufficiency in the first 6 months of infancy and challenge-proven IgE-mediated food allergy at 1 year of age: a case-cohort study. Allergy. 2017;72(8):1222–31.

    CAS  PubMed  Article  Google Scholar 

  69. Anandan C, Nurmatov U, Sheikh A. Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis. Allergy. 2009;64(6):840–8.

    CAS  PubMed  Article  Google Scholar 

  70. Garcia-Larsen V, Ierodiakonou D, Jarrold K, et al. Diet during pregnancy and infancy and risk of allergic or autoimmune disease: a systematic review and meta-analysis. PLoS Med. 2018;15(2):e1002507.

    PubMed  PubMed Central  Article  Google Scholar 

  71. Dotterud CK, Storrø O, Johnsen R, Oien T. Probiotics in pregnant women to prevent allergic disease: a randomized, double-blind trial. Br J Dermatol. 2010;163(3):616–23.

    CAS  PubMed  Article  Google Scholar 

  72. Kukkonen K, Savilahti E, Haahtela T, et al. Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic diseases: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2007;119(1):192–8.

    CAS  PubMed  Article  Google Scholar 

  73. Osborn DA, Sinn JK. Probiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst Rev. 2007;4:CD006475.

    Google Scholar 

  74. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group 2007 1 (modified by the EBM Guidelines Editorial Team): https://www.gradeworkinggroup.org/. Accessed 15 Jan 2021.

  75. Abrams EM, Chan ES. It’s not mom’s fault: Prenatal and early life exposures that do and do not contribute to food allergy development. Immunol Allergy Clin. 2019;39(4):447–57.

    Article  Google Scholar 

Download references

Acknowledgements

This position statement has been reviewed by the Canadian Paediatric Society’s Nutrition and Gastroenterology Committee. Special thanks are due to Maude Perreault, RD PhD and Brock Williams RD MSc PhD (candidate), who reviewed this document on behalf of the Dietitians of Canada.

Canadian Paediatric Society Community Paediatrics Committee (2020–2021) members: Tara Chobotuk MD, Carl Cummings MD (past Chair), Michael Hill MD, Audrey Lafontaine MD, Alisa Lipson MD, Marianne McKenna MD (Board Representative), Julia Orkin MD (Chair), Larry Pancer (past Member). Liaisons: Peter Wong MD, CPS Community Paediatrics Section. Canadian Paediatric Society Allergy Section (2020–2021) Executive members: Elissa M. Abrams MD MPH (President), Edmond S. Chan MD (Secretary-treasurer). Principal authors: Elissa M. Abrams MD MPH, Julia Orkin MD, Carl Cummings MD, Becky Blair MSc RD, Edmond S. Chan MD. Canadian Society of Allergy and Clinical Immunology: Elissa M Abrams MD MPH, Wade Watson MD MEd, Tim Vander Leek MD, Adelle Atkinson MD, Marie-Noel Primeau MD, Marie-Josee Francoeur MD, Mary McHenry MD, Elana Lavine MD, Edmond S. Chan MD. Dietitians of Canada: Maude Perreault RD PhD, Brock Williams MSc RD, Jen Yates RD. This position statement is being co-published by the Canadian Society of Allergy and Clinical Immunology and by the Canadian Paediatric Society.

Funding

No funding was received.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the drafting and revision of this manuscript.

Corresponding author

Correspondence to Elissa M. Abrams.

Ethics declarations

Ethics approval and consent to participate

This involved no research subjects and hence no ethics approval was required nor was consent to participate required.

Consent for publications

We give consent for publication.

Competing interests

The authors have no relevant competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Abrams, E.M., Watson, W., Vander Leek, T.K. et al. Dietary exposures and allergy prevention in high-risk infants. Allergy Asthma Clin Immunol 18, 36 (2022). https://doi.org/10.1186/s13223-021-00638-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13223-021-00638-y

Keywords

  • Breastfeeding
  • Food allergy
  • Infants