Early-life antibiotic exposure and childhood food allergy: A systematic review

• Published in: Journal of allergy and clinical immunology Vol. 144; no. 5; pp. 1445 - 1448
• Main Authors: Netea, Stejara A., Messina, Nicole L., Curtis, Nigel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2019; Elsevier Limited
• Subjects: Age; Allergic diseases; Antibiotics; Asthma; Bias; Blood; Children; Codes; Dermatitis; Diagnosis; Disease; Eczema; Emergency medical services; Exposure; Food allergies; Food intolerance; Immune system; Immunoglobulin E; Infants; Microbiomes; Milk; Rhinitis; Skin diseases; Skin tests; Studies; Systematic review; Australia; United States > US; Norway
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2019.08.001

Of the 4 studies that found a significant association, in 3 studies food allergy was defined by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, which do not distinguish between food intolerance and food allergy.6-8 The fourth study that found a significant association defined food allergy by using a more robust definition, namely self-reported allergic reaction (using a standardized interview) plus a positive IgE test or skin prick test result.4 One of the 2 studies that did not find a significant association also used ICD-9-CM codes but included the results of IgE or skin prick tests to define food allergy.5 The other study that did not find an association used parent-reported allergic reaction (interview) plus a report of a positive blood IgE test or positive skin prick test result.3 Among the 4 studies that found an association, the extent to which protopathic bias was considered, and the adjustment models used differed, which affects the interpretation of their results. Because IgE-mediated food allergies have been associated with concomitant IgE-mediated allergic diseases,9 3 studies6-8 adjusted for other allergic diseases. The association between antibiotics and food allergies is likely to be multifactorial. Because the microbiome plays a critical role in development of the immune system, antibiotic-induced changes in the microbiome are likely to be the predominant mechanism by which antibiotic exposure influences the risk of food allergy.1 As a result of their stronger influence on the microbiome, broad-spectrum (in contrast to narrow-spectrum) antibiotics are likely to have a greater influence on the development of the immune system and allergic disease. First author, year of publication Study design/country No. of participants/age group Antibiotic exposure Outcome definition Results Relevant allergic factors included in adjusted results Linear association observed Antibiotic class specified Eggesbo et al,3 2003 Prospective cohort/ Norway 2803/ 0-2.5 y First 6 mo of life Parent-reported immediate reaction to egg plus positive IgE test result or positive OFC result∗ OR, 1.4 (95% CI, 0.6-3.3); aOR, 1.5 (95% CI, 0.6-3.7) None No No Risnes et al,4 2011 Prospective cohort/ United States 1401/ 0-6 y First 6 mo of life Parent-reported allergic reaction (interview) plus report of a positive blood IgE test or positive SPT result OR, 1.93 (95% CI, 1.38-2.71); aOR, 1.59 (95% CI, 1.10-2.28) LRI, parental asthma No No Dowhower Karpa et al,5 2012 Retrospective case-control/ United States 99 cases and 192 control subjects/ 0-18 y First 18 y of age ICD-9-CM codes plus positive IgE test or positive SPT result or pediatrician-diagnosed food allergy OR, 1.35 (95% CI, 0.680-2.68) None No No Love et al,6 2016 Retrospective case-control/ United States 1504 cases and 5995 control subjects/ 0-3 y First year of life Physician's diagnosis with matching ICD-9-CM code ≥1 AB course vs none: OR, 1.22 (95% CI, 1.08-1.37); ≥1 AB course vs none: aOR, 1.21 (95% CI, 1.06-1.39); >5 AB courses vs none: aOR, 1.64 (95% CI, 1.31-2.05) Asthma, eczema, wheeze Yes; increase in aOR Yes Hirsch et al,7 2017 Retrospective case-control/United States 484 cases and 598 control subjects/2 mo-7 y Milk allergy: up to 30 d before diagnosis†Non-milk food allergy: 0-12 mo† Outpatient, inpatient, or emergency department encounter or medication order plus ICD-9-CM codes Milk allergy diagnosed up to 300 d†1-2 AB courses vs none: OR, 1.43 (95% CI, 0.97-2.09); ≥3 AB courses vs none: OR, 2.39 (95% CI, 1.25-4.59); 1-2 AB courses vs none: aOR, 1.35 (95% CI, 0.84-2.17); ≥3 AB courses vs none: aOR, 3.65 (95% CI, 1.75-7.60)Non-milk food allergy diagnosed up to 700 d†1-2 AB courses vs none: OR, 1.27 (95% CI, 0.96-1.69); ≥3 AB courses vs none: OR, 1.95 (95% CI, 1.38-2.75); 1-2 AB courses vs none: aOR, 1.01 (95% CI, 0.66-1.55); ≥3 AB courses vs none: aOR, 1.40 (95% CI, 0.85-2.33) Infants with other allergic diseases Yes; increase in OR Yes Li et al,8 2019 Retrospective case-control/United States 500,647 antibiotic users and 500,647 antibiotic non-users/0-4 y First year of life ICD-9-CM code ≥1 vs none: HR, 1.40 (95% CI, 1.34-1.45)1 vs none: HR, 1.49 (95% CI, 1.41-1.58); ≥2 vs none: HR, 1.31 (95% CI, 1.24-1.39)≥1 vs none: aHR, 1.46 (95% CI, 1.38-1.55) Rhinitis, dermatitis, toxic effect, and other adverse food reactions Yes; no increase in HR No Table I Summary of studies that have investigated the association between early-life exposure to antibiotics and childhood food allergy