Childhood Acid Suppressants May Increase Allergy Risk—A Systematic Review and Meta-Analysis

Song, Harris Jun Jie Muhammad Danial; Lee, Charlotte Tze Min; Ng, Faye Yu Ci; Tan, Benjamin Kye Jyn; Siah, Kewin Tien Ho; Tham, Elizabeth Huiwen

doi:10.1016/j.jaip.2022.09.042

Cited by 4 publications

(11 citation statements)

References 40 publications

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“…25 Acid suppressants have also been demonstrated to increase sensitization to orally digested proteins. 26 In a recent meta-analysis, 10 childhood acid suppressant use has been associated with elevated risk of asthma, atopic dermatitis, and allergic rhinitis. A meta-analysis 27 has also reported associations between maternal acid suppressant use and asthma, and both PPIs and histamine H2receptor antagonists have been found to increase risk in offspring.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 Early life use of antibiotics contributes to dysbiosis of the gut microbiome. [6][7][8][9] Acid suppressants have been demonstrated to alter gut permeability, thus increasing antigen sensitization, 10,11 yet also have anti-inflammatory properties and are often the first-line treatment for newly diagnosed EoE. 12 Early life has been demonstrated to be the period for colonization of the gut, where perturbations may have lasting consequences to diversity and relative abundance features of the microbiome.…”

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confidence: 99%

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Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Esophagitis

Jensen,

Svane,

Erichsen

et al. 2023

JAMA Pediatr

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ImportanceEosinophilic esophagitis (EoE), a chronic disease with significant patient and health care burden, has increased rapidly in incidence across many countries. Elucidating risk factors for disease development is a priority for health care practitioners and patients.ObjectiveTo evaluate the association of maternal and infant use of antibiotics and acid suppressants with the development of EoE.Design, Setting, and ParticipantsThis was a population-based, case-control study of pediatric EoE (1996-2019) in Denmark using pathology, prescription, birth, inpatient, and outpatient health registry data and with complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. Study data were analyzed from September 2020 to August 2023.ExposuresMaternal and infant use of antibiotics and acid suppressants, examining medication class, timing, and frequency of use.Main Outcome and MeasureDevelopment of EoE.ResultsIncluded in the study was a total of 392 cases and 3637 sex- and year of birth–matched controls with a median (IQR) age of 11.0 (6.0-15.0) years, 2772 male individuals (68.8%), and 1257 female individuals (31.2%). Compared with children with no antibiotic prescriptions filled during infancy, those with any use of an antibiotic had an associated 40% increase in risk of EoE (adjusted odds ratio [aOR], 1.4; 95% CI, 1.1-1.7). Those with 3 or more prescriptions had an associated 80% increase in risk of EoE (aOR, 1.8; 95% CI, 1.3-2.5). Frequency of maternal antibiotic use was associated with an increased risk (1 prescription: aOR, 1.4; 95% CI, 1.0-1.8; 3≤ prescriptions: aOR, 2.1; 95% CI, 1.4-3.2). Risk was highest for use in the third trimester and in the first 6 months from birth. Any acid suppressant use in infancy was associated with increased risk of EoE (aOR, 15.9; 95% CI, 9.1-27.7). Restriction of cases to those diagnosed at 5 years or older yielded similar results (aOR, 11.6; 95% CI, 5.5-24.8). For maternal use, 3 or more prescriptions were associated with an increased risk of EoE for her offspring (aOR, 5.1; 95% CI, 1.8-14.8).Conclusions and RelevanceMaternal and infant antibiotic use were associated with increased risk of developing EoE, in a dose-response manner, and the magnitude of association was highest for exposure near the time of delivery. Increased risk was also observed with maternal and infant acid suppressant use. Exposure during early life, a period of known developmental susceptibility, may confer the greatest risk and opportunity for risk mitigation.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Esophagitis

Jensen,

Svane,

Erichsen

et al. 2023

JAMA Pediatr

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“…The meta-analysis of pediatric ASM exposure and asthma yielded pooled HRs of 1.52 for PPIs and 1.40 for H2RAs. 57 Noh et al also observed null associations for pediatric exposure to both drugs for most allergic disease outcomes in sibling-matched analyses, reporting only small associations for asthma (aHR 1.16, 95% CI 1.14-1.18). 42 Another cohort study based on prospective parental reporting exposure data and clinician-confirmed diagnosis of allergic disease showed negative associations for PPIs (aOR 0.21, 95% CI 0.03-1.56) and H2RAs (aOR 0.15, 95% CI 0.04-0.64) in relation to food allergy, albeit in a small sample (n = 797).…”

Section: Study Findingsmentioning

confidence: 96%

“…56 observational studies, of which 11 were eligible and independently included in our review. 39,40,57 The ineligible study from each systematic review did not investigate the ASMs required for inclusion. Most studies (23, including the systematic reviews) reported on effects of both PPIs and H2RAs; three focused only on PPIs, and none included only H2RAs.…”

Section: Study Characteristicsmentioning

confidence: 99%

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Acid‐suppressive medication and incidence of chronic childhood immune‐mediated diseases: A scoping review

Madej,

Atanassova,

McGuire

et al. 2023

Pediatric Allergy Immunology

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BackgroundUse of acid‐suppressive medications (ASMs), for example, proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs), has been rising along with the incidence of pediatric immune‐mediated diseases (IMDs). We conducted a scoping review to characterize the literature about prenatal or pediatric exposure to ASMs in relation to incident pediatric IMDs.MethodsElectronic searches were conducted to identify studies from 2001 to 2023 on (a) prenatal or pediatric exposure to PPIs and/or H2RAs and (b) the risk of developing chronic IMDs during childhood. Eligible studies after title/abstract and full‐text screening underwent data abstraction.ResultsOf 26 eligible studies, 11 focused on prenatal ASM exposure and 16 on pediatric exposure. Asthma was the most commonly investigated outcome (16 studies), followed by other allergic diseases (8), eosinophilic esophagitis (3), inflammatory bowel disease (2), and other autoimmune diseases (2). Positive associations between ASM exposure and pediatric IMD outcomes emerged in all but two recent studies, which reported null or negative associations with allergic diseases. The strength of associations was similar across exposure times (prenatal/pediatric), medications (PPIs/H2RAs), and outcomes. Dose–response relationships were often present (7/11 studies). Reported effects by trimester and age of exposure varied. Commonly reported limitations were residual confounding, exposure misclassification, and outcome misclassification.ConclusionIn summary, prenatal or pediatric exposure to PPIs and/or H2RAs has frequently, but not exclusively, been associated with the development of asthma, other allergic diseases, and chronic gastrointestinal IMDs. However, concerns remain about confounding and other sources of bias. Prescribers and families should be aware of these possible risks of ASMs.

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Environmental Risk Factors, Protective Factors, and Biomarkers for Allergic Rhinitis: A Systematic Umbrella Review of the Evidence

Xu,

Liu,

et al. 2023

Clinic Rev Allerg Immunol

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Many potential environmental risk factors, protective factors, and biomarkers of AR have been published, but so far, the strength and consistency of their evidence are unclear. We conducted a comprehensive review of environmental risk, protective factors, and biomarkers for AR to establish the evidence hierarchy. We systematically searched Embase, PubMed, Cochrane Library, and Web of Science electronic database from inception to December 31, 2022. We calculated summary effect estimate (odds ratio (OR), relative risk (RR), hazard ratio (HR), and standardized mean difference (SMD)), 95% confidence interval, random effects p value, I2 statistic, 95% prediction interval, small study effects, and excess significance biases, and stratification of the level of evidence. Methodological quality was assessed by AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). We retrieved 4478 articles, of which 43 met the inclusion criteria. The 43 eligible articles identified 31 potential environmental risk factors (10,806,206 total population, two study not reported), 11 potential environmental protective factors (823,883 total population), and 34 potential biomarkers (158,716 total population) for meta-analyses. The credibility of evidence was convincing (class I) for tic disorders (OR = 2.89, 95% CI 2.11–3.95); and highly suggestive (class II) for early-life antibiotic use (OR = 3.73, 95% CI 3.06–4.55), exposure to indoor dampness (OR = 1.49, 95% CI 1.27–1.75), acetaminophen exposure (OR = 1.54, 95% CI 1.41–1.69), childhood acid suppressant use (OR = 1.40, 95% CI 1.23–1.59), exposure to indoor mold (OR = 1.66, 95% CI 1.26–2.18), coronavirus disease 2019 (OR = 0.11, 95% CI 0.06–0.22), and prolonged breastfeeding (OR = 0.72, 95% CI 0.65–0.79). This study is registered in PROSPERO (CRD42022384320).

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Childhood Acid Suppressants May Increase Allergy Risk—A Systematic Review and Meta-Analysis

Cited by 4 publications

References 40 publications

Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Esophagitis

Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Esophagitis

Acid‐suppressive medication and incidence of chronic childhood immune‐mediated diseases: A scoping review

Environmental Risk Factors, Protective Factors, and Biomarkers for Allergic Rhinitis: A Systematic Umbrella Review of the Evidence

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