Nazmul Islam
Derek K. Chu- 1Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, ON, Canada
- 2Department of Medicine, McMaster University, Hamilton, Ontario, ON, Canada
Introduction
Food allergies affect 10% of children globally (1) and are increasingly more common. Anaphylaxis is the most severe form of an allergic reaction and, with foods being the most common trigger, is increasing in incidence in parallel (2). Since there are currently limited treatment options for food allergies, which are frequently lifelong conditions, prevention strategies are needed. Despite the widespread problem and numerous observational studies exploring the allergy epidemic, clear explanations for it, however, remain elusive.
Clinicians, patients and caregivers, and policy makers need to know who is at high risk for developing disease. Terms such as “high risk” should also inform research and the development of evidence-based recommendations for preventing food allergies, but no commonly understood definition exists. Therefore, clinicians, parents, and children are left without the best information to identify children at high risk or potentially modifiable factors that could critically influence food allergy – and healthy child development – trajectories. Knowing the best risk-related evidence could also help clinicians and researchers identify individuals most likely to develop food allergy, enhancing the feasibility and impact of studies.
Current understanding of risk factors for the development of food allergy in children
Several risk factors have been suggested to contribute to food allergy. However, there is a lack of robust evidence addressing the scope, magnitude of effect, and modifiability of factors that promote or protect against its development. We next summarize some exemplars.
To understand genetic factors that might influence the risk of developing food allergy, a genome-wide association study evaluated major histocompatibility II genes in 2,759 United States (US) participants of European ancestry from the Chicago Food Allergy Study with food allergy (defined as a history of an allergic reaction after ingestion of peanut, egg, or milk and food sensitization to the same food [food-specific immunoglobulin E (IgE) ≥ 0.10 kU/L and/or skin prick test mean wheal diameter ≥3 mm]) (3). They reported HLA-DR (odds ratio [OR], 1.7 [95% CI: 1.4–2.1) and HLA-DQ [OR: 1.7 (95% CI: 1.4–2.1)] to be associated with peanut allergy. Using 106 cases and 76 controls, the same team conducted an epigenome-wide association study using the same data addressing cow's milk allergy. They found altered DNA methylation in genes involved in Th1 and Th2 pathways (il1rl1, il5ra, stat4, il4, and ccl18), among others to be associated with disease (4). With food allergy being associated with Th2 dominance (5–7), the relevance of the Th1 pathway epigenetic changes is unclear. But one limitation of the study was that they did not report any relative or absolute measures and only reported summary estimates.
More recently, a systematic review (8) assessed genetic determinants of pediatric food allergy. They included 32 studies, with five of them being genome-wide association studies and the rest being candidate gene studies. Twenty-two of the studies involved a predominantly Caucasian population, with the remaining ten involving Asian-specific populations or people of unknown ethnicity. Furthermore, the sample sizes in the included studies varied, with the smallest study having 30 food allergy cases and 35 nonallergic controls, and the largest study being a genome wide association study with 2,197 European patients (671 with food allergy, 144 non-allergic non-sensitized controls and 1,382 European controls of uncertain phenotype about their food allergy status). They mentioned that flg, hla, il10, il13 were associated with food allergy. Still, the authors made the judgment based on only descriptive results and qualitative judgment, and they did not provide any pooled estimates. To summarize, genetic and epigenetic factors may be associated with food allergy, but the evidence is sparse and their applicability to inform decision making has not reached clinical practice.
In terms of family history, a study used the Chicago Family Cohort Food Allergy database to assess the likelihood that siblings of a person with a food allergy will also develop food sensitization and allergies (9). They defined food allergy status of the children based on the data collected from questionnaire-based interviews with each parent performed by the study staff, results of allergen specific IgE measurements (≥0.35 kUA/L considered as children having food allergy) and skin prick testing (mean wheal diameter >3 mm). They defined clinical reaction if children had a history of reaction within 2 h of ingestion and skin or blood sensitization (IgE ≥ 0.35 kUA/L). Of the 1,120 children meeting their case definition of food allergies and at least one sibling, 67% of the siblings had sensitization, and 14% had clinical reactions. However, their adjusted multinomial regression model showed no clear association for food allergy among siblings (relative risk reduction [RRR], 1.27 [95% CI: 0.94–1.60). On the other hand, another study assessed the impact of a family history of allergic disease on the risk of developing food allergy in the first year by using the HealthNuts population-based cohort (10). They defined food allergy if the children had positive oral food challenge (hives, vomiting, angioedema or anaphylaxis) within 2 h of a dose of the challenge food (egg, peanut or sesame). After multivariable logistic regression, they found that having one immediate family member with a history of any allergic disease [adjusted OR: 1.4 (95% CI: 1.1–1.7)] and two or more allergic family members [adjusted OR: 1.8 (95% CI: 1.5–2.3)] are associated with food allergy in children when compared to those with no family history of allergic disease. These studies show that the limited data addressing genetic factors suggests they could play a minor role in promoting food allergy.
The National Academies of Sciences, Engineering, and Medicine (NAS) described other factors, including non-genetic factors (often environmental), in their 2017 systematic review (11). For example, they concluded weak but consistent evidence that a compromised skin barrier plays a role in sensitization as a precursor to food allergy. The greater likelihood of food allergy in people with mutations in filaggrin, a protein involved in maintaining the skin barrier, favoured the concept (OR: 31 [95% CI: 3 to >100) (12). The result used to support this concept, however, is unreliable and at risk of sparse data bias because of having an estimate far away from the null with extreme confidence intervals (13). A number of recent randomized trials, however, have attempted to improve skin barrier function early in life with the aim of preventing food allergy and they failed to do so (14–16). The relationship between skin barrier impairment and risk for developing food allergy remains to be clarified.
Regarding environmental exposures, a recent review (17) summarized the evidence on risk factors for food allergy with a focus on the outdoor physical environment. They reported that vitamin D insufficiency (<50 nmol/L) (18) at age 12 months [adjusted OR: 11.51 (95% CI: 2.01–65.79)], air pollution- PM2.5 (19) [adjusted OR: 1.75 (95% CI: 1.23–2.47)], environmental greenness (20) [adjusted OR: 1.59 (95% CI: 1.05–2.42)], and pollen exposure (21) [adjusted OR: 1.21 (95% CI: 1.01–1.44)] are associated with higher risk in the development of food allergy. They also reported that children reared on farms and near animals [adjusted OR: 0.6 (95% CI: 0.5–0.8)] and children with older siblings and those who attend childcare by six months of age [adjusted OR: 0.5 (95% CI: 0.3–0.8)] are associated with lower risk in the development of food allergy (22). However, we cannot rely entirely on these results as they have a few limitations, i.e., selection bias and high loss to follow-up, which may weaken inferences. Future robust studies are required to address causality.
In summary, evidence to date is conflicting or insufficient as few studies have examined these environmental factors with objective measures of IgE-mediated food allergy. A future systematic and comprehensive research needs to consider the interrelationships between multiple environmental factors.
In terms of modifiable exposures, risks associated with childhood vaccination have been raised, and one argument is that switching to acellular pertussis may have skewed immune responses toward food allergies (23). A cohort of 819 children who received the cellular or acellular vaccine at roughly the same time based on availability found no clear changes in food allergy (adjusted risk ratio [RR], 0.70 [95% CI: 0.26–1.84]) (24).
Another modifiable exposure could be food allergen in the home environment. In a study of infants participating in a study by the United States Consortium for Food Allergy Research (CoFAR) assessed whether environmental peanut exposure is a risk for food allergy or not. They defined food allergy if children had serum IgE ≥ 5 kUA/mL. They found that the amount of peanut in the infants' house dust was associated with an increased risk of developing peanut allergy [OR: 2.10 (95% CI: 1.20–3.67)] (25). Systematic evaluation is required to establish whether this association is reliable.
These are just a few examples that the National Academies and others have identified as possible risk factors. Other examples include inherent risks, such as male sex, genetics (HLA, and specific genes as described above) (26, 27), and potentially modifiable risk factors, such as improved hygiene, the microbiome (28, 29), vitamin D deficiency (18), reduced intake of omega-3-polyunsaturated fatty acids (30), lower consumption of antioxidants (31), increased use of antacids (32), obesity (33), and the timing and method of ingestion of foods (34). Credible evidence proving whether these risk factors are genuinely causal or not, and precise estimates of effect are required in order for them to be actionable. Further, guidance addressing how to apply these numerous potential associations, and deciphering which are spurious or trustworthy, to improve health outcomes is needed.
Changing recommendations on the timing of food introduction as an intervenable risk factor for the development of food allergy in children
The primary intervenable risk factor identified to date is avoiding common allergens early in life. There is a hypothesis that changing recommendations about food allergy over time is responsible for the higher incidence of food allergy.
In the year 2000, the American Academy of Pediatrics (AAP) committee on nutrition recommended that “breastfeeding mothers should continue breastfeeding for the first year of life or longer: for infants at risk for developing food allergy, hypoallergenic formulas can be used to supplement breastfeeding, and mothers should eliminate peanuts and tree nuts [e.g., almonds, walnuts, etc. (sic)] and consider eliminating eggs, cow's milk and fish from their diets while nursing.” Solid foods should not be introduced into the diet of infants (defined by elevated levels of cord blood IgE and serum IgE in infancy and an atopic family history) 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 (35). Soon after these recommendations, food allergy specialists became concerned about increasing trends in food allergy among young children (36). The AAP revised the recommendation in 2008, stating insufficient data to support the delayed introduction of allergenic foods (37). In the next few years, the idea of primary prevention and using an early introduction to help prevent food allergy came to the front with the publication of the LEAP trial (38). In this trial, they randomly assigned 530 infants with severe eczema, egg allergy, or both between 2006 and 2009 to consume or avoid peanuts until 60 months of age. They reported that introduction of peanuts decreased the frequency (1.9% [n = 10] in the consumption group vs. 13.7% [n = 73] in the avoidance group; absolute risk difference (ARR), 11.8% [95% CI: 3.4–20.3]) of development of peanut allergy among children. One limitation of the study is that the study excluded 76 children had large wheals after the skin-prick test. The safety and effectiveness of early peanut consumption in that population remain unknown, and the study results' generalizability is questionable as well. In the wake of this report, United States guidelines addressing the prevention of peanut allergy reversed their previous advice to delay the introduction of allergic foods (39, 40). These data show the importance of addressing uncertainty with randomized trials.
Evaluating the impact of the revised guidelines on food allergy incidence, however, is complex. Using the Rochester Epidemiology Project, a retrospective cohort study (41) examined the epidemiology of food allergies among inhabitants of all ages in Olmsted County, Minnesota, over a 10-year period from January 2, 2002, through December 31, 2011, to determine the incidence and temporal trends of food allergies. They defined food allergy based on the following criteria: if participants had IgE ≥ 0.35 kU/L, positive skin prick testing (mean wheal diameter >3 mm), or positive findings on an open food challenge. They found 578 new cases of food allergies and the average annual incidence rate was higher among males compared with females (4.1 [95% CI: 3.6–4.5] vs. 3.0 [95% CI: 2.7–3.4] per 10,000 person-years; 3.6 per 10,000 person-years overall) during the study period. They also reported that between 2002 and 2009, when the AAP released recommendations and withdrew them, there was a significant rise on the incidence of food allergies, followed by stabilization. Between the calendar years 2002–2003 and 2006–2007, the pediatric incidence rate of food allergy increased from 7.0 (95% CI 6.2–8.9) to 13.3 (95% CI 10.9–15.7) per 10,000 before stabilizing at 12.5 and 12.1 in the next two calendar years. Similarly, an Australian study (42) measured the change in population prevalence of peanut allergy in infants after introducing guidelines to feed peanut early in life to try to prevent peanut allergy using two population-based cross-sectional samples (2007–2011 and 2018–2019) of 7,209 infants aged 12 months in Australia. Their main outcome was a change in prevalence estimates over time. To measure the outcome, all infants underwent skin prick tests for peanut and those with positive results underwent oral food challenges. The study revealed no clear decrease in food allergy after publishing guidelines recommending early peanut introduction (prevalence of peanut allergy across the population (2.6% [95% CI: 1.8%–3.4%] in 2018–2019 cohort vs. 3.1% [95% CI: 2.3%–4.1%] in 2007–2011 cohort [difference, −0.5% (95% CI, −1.4% to 0.4%)]. One interpretation of these data hypothesize that no apparent decrease in allergy prevalence could be consistent with the introduction of guidelines averting a continued rise in food allergy. Regardless, these two studies show that translating evidence from randomized trials to population level impact in food allergy is complex and strategies addressing prevention require further study.
Discussion and insights for future research
Due to advancements in understanding risk factors and possible biomarkers, as well as their integrative, immunological, microbiological, and epigenetic variables, food allergy research is currently in an exciting new phase. The volume of publications is similarly increasing. For instance, The Tolerance induction through Early Feeding to prevent Food Allergy (TEFFA) trial evaluating the effectiveness of introducing egg, cows milk, peanut, and hazelnut via a rusk-like feeding powder on food allergy development in the first year of life (43). The Start Eating Early Diet (SEED) trial will experiment to see the role of several common allergens (milk, egg, peanut, cashew, walnut, sesame, soy, and almond) consumed in the first year of life on food allergy outcomes by two years of age (44). From 23 weeks of gestation until the breastfed newborn is four months old, the Australian PrEggNut multicenter trial compares a high peanut and egg diet to a conventional diet, with results for peanut and egg allergy outcomes determined at 12 months of age (45). Furthermore, The Pebbles trial in Australia testing to determine whether applying a ceramide-dominant emollient cream as a skin barrier strategy to high-risk infants from birth is more effective at preventing eczema, food sensitization, and challenge-confirmed food allergy at 12 months of age than using standard skin care (46).
Lack of consensus, however, among patients, clinicians and policymakers regarding food allergy risk factors and recommendations causes uncertainty in clinicians and parents regarding who is at elevated risk. One approach that might prove useful to address potential research waste is to do fewer individual epidemiological studies and instead more robust large-scale studies, including a complete systematic assessment of the current evidence.
Understanding the factors that promote or protect against the increasing allergy outbreak is essential to addressing it. With only one intervention identified to be able to prevent food allergy – early introduction of food allergens – the systematic identification of factors that credibly increase or decrease the risk for food allergy will be crucial to ending the rise in food allergy.
Author contributions
The authors’ responsibilities were as follows – NI and DC: wrote and revised the manuscript. All authors contributed to the article and approved the submitted version.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Abbreviations
IgE, immunoglobulin E; NAS, National academies of sciences, engineering, and medicine; CoFAR, consortium of food allergy research; AAP, American academy of pediatrics.
References
1. Chafen JJS, Newberry SJ, Riedl MA, Bravata DM, Maglione M, Suttorp MJ, et al. Diagnosing and managing common food allergies: a systematic review. JAMA. (2010) 303(18):1848–56. doi: 10.1001/jama.2010.582
2. Branum AM, Lukacs SL. Food allergy among US children: trends in prevalence and hospitalizations. (2008).
3. Hong X, Hao K, Ladd-Acosta C, Hansen KD, Tsai H-J, Liu X, et al. Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children. Nat Commun. (2015) 6(1):1–12. doi: 10.1038/ncomms7304
4. Hong X, Ladd-Acosta C, Hao K, Sherwood B, Ji H, Keet CA, et al. Epigenome-wide association study links site-specific DNA methylation changes with cow's milk allergy. J Allergy Clin Immunol. (2016) 138(3):908–11. doi: 10.1016/j.jaci.2016.01.056
5. Chu DK, Llop-Guevara A, Walker TD, Flader K, Goncharova S, Boudreau JE, et al. IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization. J Allergy Clin Immunol. (2013) 131(1):187–200.e1–8. doi: 10.1016/j.jaci.2012.08.002
6. Chu DK, Mohammed-Ali Z, Jiménez-Saiz R, Walker TD, Goncharova S, Llop-Guevara A, et al. T helper cell IL-4 drives intestinal Th2 priming to oral peanut antigen, under the control of OX40L and independent of innate-like lymphocytes. Mucosal Immunol. (2014) 7(6):1395–404. doi: 10.1038/mi.2014.29
7. Chu DK, Jimenez-Saiz R, Verschoor CP, Walker TD, Goncharova S, Llop-Guevara A, et al. Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo. J Exp Med. (2014) 211(8):1657–72. doi: 10.1084/jem.20131800
8. Suaini NHA, Wang Y, Soriano VX, Martino DJ, Allen KJ, Ellis JA, et al. Genetic determinants of paediatric food allergy: a systematic review. Allergy. (2019) 74(9):1631–48. doi: 10.1111/all.13767
9. Gupta RS, Walkner MM, Greenhawt M, Lau CH, Caruso D, Wang X, et al. Food allergy sensitization and presentation in siblings of food allergic children. J Allergy Clin Immunol. (2016) 4(5):956–62. doi: 10.1016/j.jaip.2016.04.009
10. Koplin JJ, Allen KJ, Gurrin LC, Peters RL, Lowe AJ, Tang MLK, et al. The impact of family history of allergy on risk of food allergy: a population-based study of infants. Int J Environ Res Public Health. (2013) 10(11):5364–77. doi: 10.3390/ijerph10115364
11. National Academies of Sciences E, Medicine. Finding a path to safety in food allergy: assessment of the global burden, causes, prevention, management, and public policy. (2017).
12. Venkataraman D, Soto-Ramírez N, Kurukulaaratchy RJ, Holloway JW, Karmaus W, Ewart SL, et al. Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence. J Allergy Clin Immunol. (2014) 134(4):876–82. doi: 10.1016/j.jaci.2014.07.033
13. Greenland S, Mansournia MA, Altman DG. Sparse data bias: a problem hiding in plain sight. Br Med J. (2016) 353:1–6. doi: 10.1136/bmj.i1981
14. Chalmers JR, Haines RH, Bradshaw LE, Montgomery AA, Thomas KS, Brown SJ, et al. Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial. Lancet. (2020) 395(10228):962–72. doi: 10.1016/S0140-6736(19)32984-8
15. Skjerven HO, Lie A, Vettukattil R, Rehbinder EM, LeBlanc M, Asarnoj A, et al. Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicentre, cluster-randomised trial. Lancet. (2022) 399(10344):2398–411. doi: 10.1016/S0140-6736(22)00687-0
16. Kelleher MM, Cro S, Van Vogt EV, Cornelius V, Lodrup Carlsen KC, Skjerven HO, et al. Skincare interventions in infants for preventing eczema and food allergy: a cochrane systematic review and individual participant data meta-analysis. Clin Exp Allergy. (2021) 51(3):402–18. doi: 10.1111/cea.13847
17. Peters RL, Mavoa S, Koplin JJ. An overview of environmental risk factors for food allergy. Int J Environ Res Public Health. (2022) 19(2):722. doi: 10.3390/ijerph19020722
18. Allen KJ, Koplin JJ, Ponsonby A-L, Gurrin LC, Wake M, Vuillermin P, et al. Vitamin D insufficiency is associated with challenge-proven food allergy in infants. J Allergy Clin Immunol. (2013) 131(4):1109–16. doi: 10.1016/j.jaci.2013.01.017
19. Brauer M, Hoek G, Smit HA, De Jongste JC, Gerritsen J, Postma DS, et al. Air pollution and development of asthma, allergy and infections in a birth cohort. Eur Respir J. (2007) 29(5):879–88. doi: 10.1183/09031936.00083406
20. Markevych I, Ludwig R, Baumbach C, Standl M, Heinrich J, Herberth G, et al. Residing near allergenic trees can increase risk of allergies later in life: LISA Leipzig study. Environ Res. (2020) 191:110132. doi: 10.1016/j.envres.2020.110132
21. Susanto NH, Lowe AJ, Salim A, Koplin JJ, Tang MLK, Suaini NHA, et al. Associations between grass pollen exposures in utero and in early life with food allergy in 12-month-old infants. Int J Environ Health Res. (2022) 32(4):712–22. doi: 10.1080/09603123.2020.1793920
22. Koplin JJ, Martin PE, Tang MLK, Gurrin LC, Lowe AJ, Osborne NJ, et al. Do factors known to alter infant microbial exposures alter the risk of food allergy and eczema in a population-based infant study? J Allergy Clin Immunol. (2012) 129(2):AB231. doi: 10.1016/j.jaci.2011.12.150
23. Estcourt MJ, Campbell DE, Gold MS, Richmond P, Allen KJ, Quinn HE, et al. Whole-cell pertussis vaccination and decreased risk of IgE-mediated food allergy: a nested case-control study. J Allergy Clin Immunol. (2020) 8(6):2004–14. doi: 10.1016/j.jaip.2019.12.020
24. Venter C, Stowe J, Andrews NJ, Miller E, Turner PJ. No association between atopic outcomes and type of pertussis vaccine given in children born on the isle of wight 2001–2002. J Allergy Clin Immunol. (2016) 4(6):1248–50. doi: 10.1016/j.jaip.2016.06.005
25. Brough HA, Liu AH, Sicherer S, Makinson K, Douiri A, Brown SJ, et al. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy. J Allergy Clin Immunol. (2015) 135(1):164–70. doi: 10.1016/j.jaci.2014.10.007
26. Lack G. Update on risk factors for food allergy. J Allergy Clin Immunol. (2012) 129(5):1187–97. doi: 10.1016/j.jaci.2012.02.036
27. Fleischer DM, Chan ES, Venter C, Spergel JM, Abrams EM, Stukus D, 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. (2021) 9(1):22–43. doi: 10.1016/j.jaip.2020.11.002
28. Savage JH, Lee-Sarwar KA, Sordillo J, Bunyavanich S, Zhou Y, O'Connor G, et al. A prospective microbiome-wide association study of food sensitization and food allergy in early childhood. Allergy. (2018) 73(1):145–52. doi: 10.1111/all.13232
29. Huang YJ, Marsland BJ, Bunyavanich S, O'Mahony L, Leung DYM, Muraro A, et al. The microbiome in allergic disease: current understanding and future opportunities—2017 PRACTALL document of the American academy of allergy, asthma & immunology and the European academy of allergy and clinical immunology. J Allergy Clin Immunol. (2017) 139(4):1099–110. doi: 10.1016/j.jaci.2017.02.007
30. Furuhjelm C, Warstedt K, Larsson J, Fredriksson M, Böttcher MF, Fälth-Magnusson K, et al. Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy. Acta Paediatr. (2009) 98(9):1461–7. doi: 10.1111/j.1651-2227.2009.01355.x
31. Tuokkola J, Lamminsalo A, Metsälä J, Takkinen H-M, Tapanainen H, Åkerlund M, et al. Maternal antioxidant intake during pregnancy and the development of cows’ milk allergy in the offspring. Br J Nutr. (2021) 125(12):1386–93. doi: 10.1017/S0007114520003633
32. Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM. Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood. JAMA Pediatr. (2018) 172(6):e180315. -e. doi: 10.1001/jamapediatrics.2018.0315
33. Visness CM, London SJ, Daniels JL, Kaufman JS, Yeatts KB, Siega-Riz A-M, et al. Association of obesity with IgE levels and allergy symptoms in children and adolescents: results from the national health and nutrition examination survey 2005–2006. J Allergy Clin Immunol. (2009) 123(5):1163–9. doi: 10.1016/j.jaci.2008.12.1126
34. 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. doi: 10.1016/j.jaci.2017.11.003
35. Committee on N. Hypoallergenic infant formulas. Pediatrics. (2000) 106(2):346–9. doi: 10.1542/peds.106.2.346
36. Branum AM, Lukacs SL. Food allergy among children in the United States. Pediatrics. (2009) 124(6):1549–55. doi: 10.1542/peds.2009-1210
37. Greer FR, Sicherer SH, Burks AW. American academy of pediatrics 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):183–91. doi: 10.1542/peds.2007-3022
38. Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. (2015) 372:803–13. doi: 10.1056/NEJMoa1414850
39. Togias A, Cooper SF, Acebal ML, Assa’ad A, Baker JR, Beck LA, 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. World Allergy Organ J. (2017) 10(1):1–18. doi: 10.1186/s40413-016-0137-9
40. Ierodiakonou D, Garcia-Larsen V, Logan A, Groome A, Cunha S, Chivinge J, 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. doi: 10.1001/jama.2016.12623
41. Willits EK, Park MA, Hartz MF, Schleck CD, Weaver AL, Joshi AY. Food allergy: A comprehensive population-based cohort study. Minnesota: Elsevier (2018).
42. Soriano VX, Peters RL, Moreno-Betancur M, Ponsonby A-L, Gell G, Odoi A, et al. Association between earlier introduction of peanut and prevalence of peanut allergy in infants in Australia. JAMA. (2022) 328(1):48–56. doi: 10.1001/jama.2022.9224
43. Kalb B, Meixner L, Trendelenburg V, Unterleider N, Dobbertin-Welsch J, Heller S, et al. Tolerance induction through early feeding to prevent food allergy in infants with eczema (TEFFA): rationale, study design, and methods of a randomized controlled trial. Trials. (2022) 23(1):1–11. doi: 10.1186/s13063-022-06126-x
44. FARE. The Start Eating Early Diet (SEED) Study (2022). Available at: https://www.foodallergy.org/resources/start-eating-early-diet-seed-initiative (Accessed October 2022).
45. Council N. Pregnant women eating eggs and peanuts to reduce baby food allergies (PrEggNut Study) (2022). Available at: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12618000937213 (Accessed October 2022).
46. Lowe A, Su J, Tang M, Lodge CJ, Matheson M, Allen KJ, et al. PEBBLES Study protocol: a randomised controlled trial to prevent atopic dermatitis, food allergy and sensitisation in infants with a family history of allergic disease using a skin barrier improvement strategy. BMJ Open. (2019) 9(3):e024594. doi: 10.1136/bmjopen-2018-024594
Keywords: food allergy, risk factors, infants and children, developmental origins and life-course theories, IgE mediated food alergy
Citation: Islam N and Chu DK (2022) What is causing the rise in food allergy? A narrative review of risk factors for the development of food allergy in infants and children. Front. Allergy 3:1037596. doi: 10.3389/falgy.2022.1037596
Received: 6 September 2022; Accepted: 31 October 2022;
Published: 24 November 2022.
Edited by:
Linda Cox, Consultant, United StatesReviewed by:
Kirsten P. Perrett, Murdoch Children's Research Institute, Australia© 2022 Islam and Chu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Derek K. Chu Y2h1ZGtAbWNtYXN0ZXIuY2E=
Specialty Section: This article was submitted to Food Allergy, a section of the journal Frontiers in Allergy