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No cashew allergy in infants introduced to cashew by age 1 year

2020; Elsevier BV; Volume: 147; Issue: 1 Linguagem: Inglês

10.1016/j.jaci.2020.07.003

1097-6825

Rachel L. Peters, Danny Ye Barret, Victoria X. Soriano, Vicki McWilliam, Adrian J. Lowe, Anne–Louise Ponsonby, Mimi L.K. Tang, Shyamali C. Dharmage, Lyle C. Gurrin, Jennifer J. Koplin, Kirsten P. Perrett,

Contact Dermatitis and Allergies

Similar to peanut allergy, tree nut allergy is common, can be severe, and seldom resolves.1McWilliam V. Peters R. Tang M.L.K. Dharmage S. Ponsonby A.L. Gurrin L. et al.Patterns of tree nut sensitization and allergy in the first 6 years of life in a population-based cohort.J Allergy Clin Immunol. 2019; 143: 644-650.e5Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar,2Mullins R.J. Wainstein B.K. Barnes E.H. Liew W.K. Campbell D.E. Increases in anaphylaxis fatalities in Australia from 1997 to 2013.Clin Exp Allergy. 2016; 46: 1099-1110Crossref PubMed Scopus (132) Google Scholar Evidence that early introduction of peanut and egg before age 12 months reduces the prevalence of IgE-mediated food allergy has led to a paradigm shift in infant feeding advice for allergenic solid foods, from avoidance to timely introduction.3Ierodiakonou 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: 1181-1192Crossref PubMed Scopus (204) Google Scholar In recent years, infant feeding guidelines internationally recommend introduction of allergenic foods such as peanut in the first year of life; however, because of lack of evidence, there was no specific recommendation for tree nut introduction.4Australasian Society of Clinical Immunology and AllergyInfant feeding and allergy prevention. Brookvale, NSW: ASCIA; 2016.https://www.allergy.org.au/patients/allergy-prevention/ascia-guidelines-for-infant-feeding-and-allergy-preventionDate accessed: March 20, 2019Google Scholar,5Togias A. Cooper S.F. Acebal M.L. Assa'ad A. Baker Jr., J.R. Beck L.A. 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: 29-44Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar We aimed to determine whether the introduction of cashew in the infant diet in the first year of life was associated with the risk of cashew allergy. HealthNuts is a population-based longitudinal study of 5276 infants recruited from council-run immunization sessions in metropolitan Melbourne, Australia, at age 11 to 15 months from 2007 to 2011. Parents completed a questionnaire collecting demographic information as well as data on the timing of food introduction in the infant's diet; specifically, parents were asked whether they had introduced any nuts into the infant's diet, to specify which nut and the age in months that the nut had been introduced. Skin prick testing (SPT) at recruitment was performed to 4 foods (milk, egg, peanut, and sesame), and infants with a detectable wheal (≥1 mm) were invited for oral food challenge (OFC) at the Royal Children's Hospital, Melbourne, Australia. OFCs were deemed positive if they met 1 of the following criteria, 3 or more noncontact urticaria lasting for 5 minutes or more, angioedema, vomiting, or evidence of anaphylaxis. The cohort was followed up at age 4 years with a questionnaire and those who reported any new food reactions or who were food allergic at age 1 year were invited for an allergy assessment that included a panel of SPT (including cashew) and OFC. Cashew OFCs were first performed at age 4 years among those with detectable cashew wheal but no known tolerance. The first comprehensive assessment of cashew allergy prevalence was undertaken at age 6 years, where all participants were invited to complete a questionnaire and comprehensive health assessment that included SPT to 8 foods including cashew. Those with a detectable SPT wheal (≥1 mm) were offered OFC.6Koplin J.J. Wake M. Dharmage S.C. Matheson M. Tang M.L. Gurrin L.C. et al.Cohort profile: the HealthNuts study: population prevalence and environmental/genetic predictors of food allergy.Int J Epidemiol. 2015; 44: 1161-1171Crossref PubMed Scopus (52) Google Scholar Cashew sensitization at age 6 years was defined as SPT wheal size greater than or equal to 3 mm. Cashew allergy at age 6 years was defined as previously described and was informed by OFC, SPT, and questionnaire responses (see footnote Table I).1McWilliam V. Peters R. Tang M.L.K. Dharmage S. Ponsonby A.L. Gurrin L. et al.Patterns of tree nut sensitization and allergy in the first 6 years of life in a population-based cohort.J Allergy Clin Immunol. 2019; 143: 644-650.e5Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Timing of cashew introduction was dichotomized as early (age ≤12 months) or delayed (age >12 months or not yet introduced).Table IAssociation between age of cashew ingestion and cashew allergy outcomes at age 6 yOutcomeN∗Only participants with complete data on exposure, outcomes, and potential confounders contributed data to this table. The sample size for cashew allergy is greater than that for cashew sensitization, because cashew tolerance was informed by questionnaire data for those who did participate in SPT.%Unadjusted OR (95% CI)P valueAdjusted OR†The cashew sensitization model was adjusted for patient sex, parental country of birth, pet dogs, siblings, family history of any allergy, sibling history of allergy, eczema diagnosis, and parent-reported reaction to foods. Because of computational limitations of running exact logistic regression models, only a limited number of confounders could be adjusted for simultaneously. Separate models were run adjusting for each potential confounder individually, with the final model adjusted for the only 2 variables that altered the magnitude of association from the unadjusted OR: parent-reported reaction to common allergens and parent-reported eczema diagnosis. (95% CI)P valueCashew sensitization Delayed24274.94Reference group—Reference group— Early1120.890.17 (0.02-1.25).080.22 (0.03-1.61).14Cashew allergy‡Cashew allergy was defined as any of the following in the context of cashew sensitization: (1) positive OFC (n = 21), (2) recent reaction consistent with OFC stopping criteria in the past 12 mo (n = 5) or (3) positive OFC at age 4 y with SPT ≥8 mm at age 6 y (n = 32), or (4) SPT response of ≥8 mm but no age 4 y OFC (n = 42). Cashew tolerance was defined as any of the following: (1) negative OFC; (2) SPT response of 0-2 mm; (3) SPT response of 3-7 mm or no SPT, and parent-reported ingestion history (eaten >1 time since age 4 y) and no reaction since age 4 y and no parental report of food avoidance.1 Delayed27853.59Reference group—Reference group— Early1400.000.13 (0.00-0.73).010.19 (0.00-1.09).07OR, Odds ratio.∗ Only participants with complete data on exposure, outcomes, and potential confounders contributed data to this table. The sample size for cashew allergy is greater than that for cashew sensitization, because cashew tolerance was informed by questionnaire data for those who did participate in SPT.† The cashew sensitization model was adjusted for patient sex, parental country of birth, pet dogs, siblings, family history of any allergy, sibling history of allergy, eczema diagnosis, and parent-reported reaction to foods. Because of computational limitations of running exact logistic regression models, only a limited number of confounders could be adjusted for simultaneously. Separate models were run adjusting for each potential confounder individually, with the final model adjusted for the only 2 variables that altered the magnitude of association from the unadjusted OR: parent-reported reaction to common allergens and parent-reported eczema diagnosis.‡ Cashew allergy was defined as any of the following in the context of cashew sensitization: (1) positive OFC (n = 21), (2) recent reaction consistent with OFC stopping criteria in the past 12 mo (n = 5) or (3) positive OFC at age 4 y with SPT ≥8 mm at age 6 y (n = 32), or (4) SPT response of ≥8 mm but no age 4 y OFC (n = 42). Cashew tolerance was defined as any of the following: (1) negative OFC; (2) SPT response of 0-2 mm; (3) SPT response of 3-7 mm or no SPT, and parent-reported ingestion history (eaten >1 time since age 4 y) and no reaction since age 4 y and no parental report of food avoidance.1McWilliam V. Peters R. Tang M.L.K. Dharmage S. Ponsonby A.L. Gurrin L. et al.Patterns of tree nut sensitization and allergy in the first 6 years of life in a population-based cohort.J Allergy Clin Immunol. 2019; 143: 644-650.e5Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Open table in a new tab OR, Odds ratio. The association between introduction of cashew and cashew sensitization was modeled using logistic regression; exact logistic regression was used for cashew allergy because 1 of the cells formed by the outcome and categorical predictor variable had no observations.7Hirji K.F. Mehta C.R. Patel N.R. Computing distributions for exact logistic regression.J Am Stat Assoc. 1987; 82: 1110-1117Crossref Scopus (211) Google Scholar Potential confounders considered were sex, parental country of birth (both Australia, 1 or both Asian and other), presence of siblings, pet dogs (none, allowed inside the house, outside only), parent report of a doctor diagnosis of eczema, parent-reported reactions to common food allergens, sibling history of allergy (no siblings, siblings without allergy, siblings with allergy), and family history of allergy, all reported in the age 1 year questionnaire. All statistical analysis was performed using Stata (Release 15.1; StataCorp LLC, College Station, Tex). Ethics approval was obtained from the Royal Children's Hospital Human Research Ethics Committee (27047 and 32294) and from the Victorian State Government Office for Children (CDF/07/492) and the Department of Human Services (10/07). As described previously,1McWilliam V. Peters R. Tang M.L.K. Dharmage S. Ponsonby A.L. Gurrin L. et al.Patterns of tree nut sensitization and allergy in the first 6 years of life in a population-based cohort.J Allergy Clin Immunol. 2019; 143: 644-650.e5Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar,6Koplin J.J. Wake M. Dharmage S.C. Matheson M. Tang M.L. Gurrin L.C. et al.Cohort profile: the HealthNuts study: population prevalence and environmental/genetic predictors of food allergy.Int J Epidemiol. 2015; 44: 1161-1171Crossref PubMed Scopus (52) Google Scholar the participation rate in the HealthNuts study was 74% (n = 5276) at age 1 year, whereas at age 6 years, 84% (n = 4441) of the original cohort completed a questionnaire and 61% (n = 3232) completed a health assessment. The present analysis includes participants with complete data on age of introduction of cashew reported at age 1 year, potential confounders considered, and cashew allergy outcomes (n = 2925 for cashew allergy and n = 2539 for cashew sensitization). By age 12 months, 4.8% (N = 140 of 2925; 95% CI, 4.0%-5.6%) of infants had consumed cashew. At age 6 years, the prevalence of cashew sensitization was 4.8% (95% CI, 4.0%-5.7%) and that of cashew allergy was 3.4% (95% CI, 2.8%-4.1%). These estimates differ from the estimates from previous reports from our cohort because it is restricted to those who had complete data for this analysis. No child who ate cashew by age 12 months developed cashew allergy (0%; 95% CI, 0%-2.6%), compared with 3.6% (95% CI, 2.9%-4.4%) of those who had not consumed cashew by age 12 months. After adjustment for confounding variables, there was weak evidence that early introduction of cashew was associated with reduced odds of cashew allergy (adjusted odd ratio, 0.19; 95% CI, 0.00-1.09; P = .07). The magnitude of association was similar for cashew sensitization, but CIs were wider (adjusted odds ratio, 0.22; 95% CI, 0.03-1.61; P = .14). This is the first report of a possible protective association between the ingestion of cashew in the first year of life and cashew allergy. In 2015, the Learning Early About Peanut randomized controlled trial showed that in a cohort with severe eczema or egg allergy (n = 628), regular ingestion of peanut up to age 60 months reduced peanut allergy by 81%, compared with the control group who avoided peanut for this time (17.2% to 3.2%; P < .01).8Du Toit G. Roberts G. Sayre P.H. Bahnson H.T. Radulovic S. Santos A.F. et al.Randomized trial of peanut consumption in infants at risk for peanut allergy.N Engl J Med. 2015; 372: 803-813Crossref PubMed Scopus (1074) Google Scholar It has been postulated that the high-risk cohort of Learning Early About Peanut and the extended length of allergen avoidance in the control group may overstate the true population effect of early peanut introduction, although interestingly, our observational population-based study has found a similar reduction in risk for early cashew introduction. The dual allergen exposure hypothesis described by Lack9Lack G. Epidemiologic risks for food allergy.J Allergy Clin Immunol. 2008; 121: 1331-1336Abstract Full Text Full Text PDF PubMed Scopus (423) Google Scholar is a plausible explanation for these results. Strengths of our study include the population-based rather than high-risk cohort, with findings generalizable to the wider population. Furthermore, the HealthNuts study uses definitive allergy outcomes, including OFCs to define food allergy prevalence. Limitations include the possibility of recall error for early life exposures that were reported at age 1 year; however, because these were completed at age 12 months, information on whether or not food allergens had been introduced is likely to be reliable. Selective attrition may have increased the prevalence of cashew allergy at age 6 years, due to higher rates of participation by those with a family or personal history of allergy, but this is unlikely to have biased the association between age of introduction and cashew allergy.1McWilliam V. Peters R. Tang M.L.K. Dharmage S. Ponsonby A.L. Gurrin L. et al.Patterns of tree nut sensitization and allergy in the first 6 years of life in a population-based cohort.J Allergy Clin Immunol. 2019; 143: 644-650.e5Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar We present the first evidence that the early introduction of cashew may decrease the frequency of cashew allergy in a population-based cohort; however, cashew allergy and introduction was uncommon and the risk reduction could not be quantified precisely. Future clinical trials are required to assess the frequency, dose, and timing of cashew ingestion for cashew allergy prevention, and how cashew can be safely and effectively introduced with other allergenic solid foods into the infant's diet, which may be key to reversing the food allergy epidemic. We thank the parents and children who participated in the HealthNuts study as well as the staff of Melbourne's Local Government Areas for access to community immunization clinics. We also thank the HealthNuts Safety Committee: Associate Professor Noel Cranswick (Australian Paediatric Pharmacology Research Unit, Murdoch Children's Research Institute), Dr Joanne Smart (Department of Allergy and Immunology, Royal Children's Hospital, Melbourne, Australia), and Professor Jo Douglass (Director, Department of Allergy and Immunology, Royal Melbourne Hospital, Melbourne, Australia). We thank ALK Abello, S.A. Madrid, España, for providing the allergens for the skin prick tests. We also thank the HealthNuts study research staff: Nicholas Osborne, Megan Mathers, Dean Tey, Marnie Robinson, Giovanni Zurzolo, Leone Thiele, Helen Czech, Deborah Anderson, Carley Garner, and John Molloy.