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Acid Suppressant Therapy in Infancy Linked to Increased Risk of Childhood Respiratory Conditions

Key findings

  • This prospective study examined the association between exposure to acid suppressant medications (ASMs) in infancy and the risk of developing childhood respiratory conditions and allergen sensitization
  • The 920 participants were at high risk of recurrent wheeze and subsequent asthma because they were hospitalized for bronchiolitis as infants
  • Infant exposure to ASMs was associated with increased risk of recurrent wheeze by age three years (adjusted HR, 1.58; P=0.001) and increased risk of asthma by age six years (adjusted OR, 1.66; P=0.001)
  • ASM administration was not associated with an increased risk of sensitization to food or aeroallergens in early childhood
  • Clinicians should carefully consider the risks and benefits of ASMs during infancy, and, if they are recommended, the prescriber should discuss the risks and benefits with parents before initiating therapy

Empiric therapy with acid suppressant medications (ASMs) is often given to infants for treatment of gastroesophageal reflux or gastroesophageal reflux disease, despite little evidence of efficacy. Now, Massachusetts General Hospital researchers have documented associations between exposure to ASMs in infancy and the risk of childhood respiratory conditions.

Lacey B. Robinson, MD, MPH, formerly an allergist in the Division of Rheumatology, Allergy and Immunology at Mass General, Carlos A. Camargo, Jr., MD, DrPH, Conn Chair in Emergency Medicine in the Department of Emergency Medicine, and colleagues detail their findings in The Journal of Allergy and Clinical Immunology: In Practice.


The research team analyzed data from the 35th Multicenter Airway Research Collaboration, an ongoing multicenter prospective cohort study of infants (children < 1-year-old) who were hospitalized for bronchiolitis during 2011–2014.

Each participant's parent or guardian completed a detailed in-person interview at enrollment, followed by a structured telephone interview every six months until their child was age six years. In addition, participants were examined once during early childhood at a median age of 3.75 years.

Blood samples and nasopharyngeal aspirates were collected at enrollment, and blood samples were collected again at the early childhood examination.


920 participants in the cohort had data available on ASM exposure during infancy, of whom 202 (22%) were exposed. The median duration of ASM use was 13.7 weeks (interquartile range, 4–31 weeks).

Three outcomes were examined in multivariable analyses:

  • Recurrent wheeze by age 3 years—adjusted HR, 1.58 (95% CI, 1.20–2.08; P=0.001)
  • Food and/or aeroallergen sensitization—adjusted OR (aOR), 1.00 (95% CI, 0.70–1.44; P=0.99)
  • Asthma by age 6 years—aOR, 1.66 (95% CI, 1.22–2.27; P=0.001)

Using a strict definition of ASM exposure:

  • For every 4-week increase in ASM exposure during infancy, participants were 1.14 times more likely to develop asthma by age 6 years (aOR, 1.14; 95% CI, 1.02–1.29; P=0.02)
  • Participants who had >28 weeks of ASM exposure had increased odds of asthma by age 6 years compared with those who had <2 weeks of ASM exposure, suggesting a dose-response relationship (partially adjusted P for trend = 0.01)

Guidance for Prescribers

The American Board of Internal Medicine sponsors a "Choosing Wisely" campaign that calls on medical societies to identify interventions whose necessity should be questioned and discussed with patients. As part of this campaign, the American Academy of Pediatrics advises clinicians not to use acid blockers or motility agents to treat infants for physiologic gastroesophageal reflux that is effortless, painless, and not affecting growth.

This study provides additional reasons for prescribers to avoid ASMs for infants and to discuss the risks and benefits of ASMs with parents before initiating therapy.

greater risk of recurrent wheeze by age three years when infants at high risk of asthma are treated with acid suppressant medications

greater odds of asthma by age six years when infants at high risk of asthma are treated with acid suppressant medications

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