Prenatal exposure to acid-suppressant medications and the risk of recurrent wheeze at 3 years of age in children with a history of severe bronchiolitis

Robinson, Lacey B.; Arroyo, Anna Chen; Dantas, Marina A.S.; Espinola, Janice A.; Sullivan, Ashley F.; Camargo, Carlos A.

doi:10.1016/j.jaip.2019.02.039

Cited by 7 publications

(3 citation statements)

References 11 publications

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“…[14][15][16][17] In support, a growing number of epidemiological studies have reported positive associations of allergic diseases in offspring with ASM use during pregnancy and infancy (eTable 1 in the Supplement). [4][5][6][7][8][18][19][20][21][22][23][24][25] However, these studies did not fully address confounding by indication and within-family shared factors. [26][27][28] Given that asthma and GERD are often concomitant (up to 80% of patients with asthma have GERD) and asthma may induce GERD or vice versa, 29 prior findings could have been confounded by GERD rather than showing a true association between allergic diseases and ASM use.…”

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confidence: 99%

Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children

et al. 2023

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ImportanceExisting observational data have indicated positive associations of acid-suppressive medication (ASM) use in prenatal and early life with allergic diseases in children; however, no study to date has accounted for confounding by indication or within-familial factors.ObjectiveTo evaluate the association of prenatal or infant exposure to ASMs with risk of allergic diseases in children.Design, Setting, and ParticipantsThis nationwide, cohort study included data from South Korea’s National Health Insurance Service mother-child–linked database from January 1, 2007, to December 31, 2020. Participants included mother-child pairs of neonates born from April 1, 2008, to December 31, 2019.ExposuresPrenatal and infant exposure to ASMs (histamine 2 receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]).Main Outcomes and MeasuresComposite and individual outcomes of allergic diseases (asthma, allergic rhinitis, atopic dermatitis, and food allergy) in children (followed up to 13 years of age) were assessed. The ASM-exposed individuals were compared with unexposed individuals in propensity score (PS)–matched and sibling-matched analyses to control for various potential confounders and within-familial factors. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazards regression models.ResultsThe study included 4 149 257 mother-child pairs. Prenatal exposure analyses included 808 067 PS-matched pairs (763 755 received H2RAs, 36 529 received PPIs) among women with a mean (SD) age of 31.8 (4.2) years. The PS-matched HR was 1.01 (95% CI, 1.01-1.02) for allergic diseases overall (asthma: HR, 1.02 [95% CI, 1.01-1.03]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.02]; atopic dermatitis: HR, 1.02 [95% CI, 1.01-1.02]; food allergy: HR, 1.03 [95% CI, 0.98-1.07]); in sibling-matched analyses, the HRs were similar to those of PS-matched analyses but were not significant (allergic diseases: HR, 1.01; 95% CI, 0.997-1.01). Infant exposure analyses included 84 263 PS-matched pairs (74 188 received H2RAs, 7496 received PPIs). The PS-matched HR was 1.06 (95% CI, 1.05-1.07) for allergic diseases overall (asthma: HR, 1.16 [95% CI, 1.14-1.18]; allergic rhinitis: HR, 1.02 [95% CI, 1.01-1.03]; atopic dermatitis: HR, 1.05 [95% CI, 1.02-1.08]; food allergy: HR, 1.28 [95% CI, 1.10-1.49]); asthma risk (HR, 1.13; 95% CI, 1.09-1.17) remained significantly higher among children exposed to ASMs during infancy in sibling-matched analyses. The findings were similar for H2RAs and PPIs analyzed separately and were robust across all sensitivity analyses.Conclusions and RelevanceThe findings of this cohort study suggest that there is no association between prenatal exposure to ASMs and allergic diseases in offspring. However, infant exposure to ASMs was associated with a higher risk of developing asthma, although the magnitude was more modest than previously reported. Clinicians should carefully weigh the benefits of prescribing ASMs to children, accompanied by subsequent close monitoring for any clinically relevant safety signals.

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Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children

et al. 2023

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“…Previous work in this cohort found that prenatal ASM exposure was associated with increased risk of recurrent wheezing. 1 Taken together, these findings suggest that allergen sensitization may not be the sole mechanism by which prenatal ASM exposure increases risk of childhood respiratory and allergic disease.…”

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confidence: 92%

“…Prenatal exposure to ASMs is associated with increased risk of atopic disease in childhood including recurrent wheeze and asthma. [1][2][3] The mechanism by which exposure to these medications increase risk is unknown. Increased risk of allergen sensitization has been proposed as a possible mechanism.…”

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Prenatal exposure to acid suppressant medications and risk of allergen sensitization

Robinson

Arroyo

Geller

et al. 2022

Pediatric Allergy Immunology

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To the editor, Acid suppressant medications (ASMs), such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), are commonly used during pregnancy to treat symptoms of reflux or gastroesophageal reflux disease (GERD). Prenatal exposure to ASMs is associated with increased risk of atopic disease in childhood including recurrent wheeze and asthma. [1][2][3] The mechanism by which exposure to these medications increase risk is unknown. Increased risk of allergen sensitization has been proposed as a possible mechanism. 4,5 The objective of this study was to estimate the association between prenatal exposure to ASMs and risk of allergen sensitization in early childhood.We used data from the 35th Multicenter Airway Research Collaboration (MARC-35), an ongoing multicenter prospective cohort study comprised of children with a history of severe bronchiolitis during infancy (n = 921). Study design and participants have been previously described. 6 Briefly, infants (age < 1 year) were enrolled during hospitalization for bronchiolitis at 17 US hospitals during the 2011-2014 winter seasons.Prenatal exposure to ASMs was defined as maternal use of either PPI or H2RA during pregnancy, which was obtained from parent/ guardian reports by questionnaire at enrollment. Parents/guardians were asked, "When pregnant with your child, did you/the biological mother take H2 blockers or proton pump inhibitors for gastroesophageal reflux (heartburn, GERD) or ulcers?" Examples were provided.

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Emerging Insights into the Impact of Air Pollution on Immune-Mediated Asthma Pathogenesis

Tuazon

Kilburg-Basnyat

Oldfield

et al. 2022

Curr Allergy Asthma Rep

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Prenatal exposure to acid-suppressant medications and the risk of recurrent wheeze at 3 years of age in children with a history of severe bronchiolitis

Cited by 7 publications

References 11 publications

Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children

Prenatal and Infant Exposure to Acid-Suppressive Medications and Risk of Allergic Diseases in Children

Prenatal exposure to acid suppressant medications and risk of allergen sensitization

Emerging Insights into the Impact of Air Pollution on Immune-Mediated Asthma Pathogenesis

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