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Boning Up on Anti-Gastroesophageal Reflux Therapy in Infancy and Associated Fractures in Childhood :
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June 10, 2019

The authors describe a retrospective cohort of 851,631 children born 2001-2013 in the Military Healthcare System followed for at least two years of life, of whom 97,286 were prescribed an acid suppressant in their first year of life, either a PPI (0.9%), an H2RA (8%) or both (2%).

While acid suppression therapy to treat gastroesophageal reflux in infancy has been discouraged per the evidence-based “Choosing Wisely” guidelines that were published in 2013, the practice still occurs. While the evidence for using proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs) to treat infant reflux remains weak, perhaps knowing more about potential risks versus benefits of such therapy can further discourage overuse of these anti-reflux medications.  It is for that reason that we share a new study by Malchodi et al. (10.1542/peds.2018-2625) looking at the risk of fractures in children who were administered a PPI or H2RA during infancy.  The authors describe a retrospective cohort of 851,631 children born 2001-2013 in the Military Healthcare System followed for at least two years of life, of whom 97,286 were prescribed an acid suppressant in their first year of life, either a PPI (0.9%), an H2RA (8%) or both (2%).  The authors found a significant increase in fracture risk in those who received a PPI or both but not in those who got an H2RA agent alone.  In addition, the longer the duration of acid suppression treatment or earlier such treatment was used, the greater the association with fracture.

What are the implications of this study?  We asked Drs. Boruta, Boruta, and Li from Duke to weigh in with an accompanying commentary (10.1542/peds.2019-0909).  They note the adverse effects of PPIs as well as H2RAs and the lack of improvement in clinical trials of infants with reflux on these agents used separately or together. They also note that the association with fractures found in the study by Malchodi et al. has already been reported in adults but not in children until this well-done study came along. As a result of this study, the commentary authors call for longer-term studies like this one to show long-term adverse effects even if the already published short-term effects appear to be benign.  Take a break and read this study and commentary and you will likely want to reassess whether you should be recommending acid suppressant therapy for your infants with reflux, if you haven’t reduced their use already.

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