A little more than 5 years ago I wrote about gastroesophageal reflux in infants, focusing on bogus treatment claims made by some chiropractors. But pediatric medical professionals are far from perfect in our management of this common and almost always benign condition, as I explained in 2014:

Too many of us begin to alter our approach because of the influence of practicing in the real world and of common hardwired errors in how we interpret reality. Overuse of prescription medications, unnecessary formula hopping and potentially unsafe recommendations on sleep positioning are unfortunately widespread. Our pharmaceutical interventions carry significant risk with little evidence of benefit for most patients…

Sadly not much has changed since then, despite the inclusion of a recommendation to avoid acid blocking medications when treating physiologic infant reflux in the Choosing Wisely campaign.

What do I mean by “physiologic reflux”? I use that term to differentiate the common occurrence of the passage of stomach contents into the esophagus, and often into the oral cavity and onto the infant’s clothing, blanket, or caregiver’s face, from reflux disease associated with pathology such as severe pain and/or poor weight gain. Virtually all young infants have episodes of reflux upwards of 30 times every day, with more than half spitting daily up at the typical peak around 4 months of life. By one year, almost none do.

Reflux is commonly blamed by parents and pediatricians for general fussiness, something which is not supported by evidence. The assumption is that acid from the stomach causes damage to the esophagus and subsequent pain, resulting in excessive crying but this is actually rare. Reflux to the point of feeding difficulty and poor weight gain is also very uncommon.

I go into far greater detail in my previous post on the subject, which I encourage you to read. The bottom line, though, is that medications aimed at treating subjective symptoms attributed to reflux are generally no better than placebo. In this post, I want to focus on the inappropriate use of these acid blocking drugs and a recent study further demonstrating that the risk outweighs benefit in most cases.

In 2014, I listed pneumonia and gut infections, such as the infamous Clostridium difficile, as the primary risks associated with popular proton pump inhibiting (PPI) medications. Since then, there have been increasing concerns regarding the risk of bone fractures. A study published in Pediatrics this month adds more fuel to that fire.

In this retrospective cohort study, researchers collected data from the Military Healthcare System on children born between October 1, 2001 and September 30, 2013, focusing on those who received care for at least their first 2 years of life and as long as 14 years. After excluding children with conditions that might predispose to fractures, such as bone disease, prematurity, or abuse, they were left with nearly 852,000 low-risk children. Of these, roughly 97,000 had been started on acid suppressing medications in the first year of life. The remaining 754,345 children served as a control for comparison.

The researchers looked at whether children receiving acid suppression were prescribed a histamine blocker such as Zantac, a PPI, or both, and for how long. They followed the subjects out through five years looking for any diagnoses of bone fractures. After analysis and adjustment for time and the occurrence of previous fractures, they found a clear signal in the data.

Compared to controls, children prescribed a PPI in the first year of life were roughly 20% more likely to suffer a fracture before age 5 years. Those on both a PPI and a histamine blocker had an increased risk of more than 30% if initiated in the first 6 months of life. Children only prescribed a histamine blocker were not found to be at increased risk of fracture. Risk of fracture was generally higher the earlier that children were placed on a PPI or PPI and histamine blocker, and the longer that they were on them.

The mechanism for the increased risk of fracture with PPIs isn’t known, but it appears to be a direct inhibitory effect on the function of osteoclasts. These are cells that play a role in the repair and maintenance of bone. There is even less known about why histamine blocking acid suppressing drugs might increase fracture risk when combined with PPIs but not when used alone.

It’s important to point out that while this study adds to our understanding of potential risks in young children taking acid suppressing medications, we can’t say that they are a cause of fractures. Non-accidental trauma is unfortunately a common cause of injury in infants and young children. Regardless of what medications a child may be on, we should not be distracted from consideration of the possibility of physical abuse in the setting of fractures.

Conclusion: Judicious use of acid suppression in infants is warranted

Though overprescribed, there are circumstances where medications that suppress gastric acid are appropriate in infants. The take home shouldn’t be to never use them, but to be cautious. In most cases of reflux, and sometimes even reflux disease, non-pharmaceutical interventions (not chiropractic) do the trick. If these fail, or if a child has severe reflux disease, PPIs in particular should be used for as short an amount of time as possible.


Posted by Clay Jones

Clay Jones, M.D. is a pediatrician and a regular contributor to the Science-Based Medicine blog. He primarily cares for healthy newborns and hospitalized children, and devotes his full time to educating pediatric residents and medical students. Dr. Jones first became aware of and interested in the incursion of pseudoscience into his chosen profession while completing his pediatric residency at Vanderbilt Children’s Hospital a decade ago. He has since focused his efforts on teaching the application of critical thinking and scientific skepticism to the practice of pediatric medicine. Dr. Jones has no conflicts of interest to disclose and no ties to the pharmaceutical industry. He can be found on Twitter as @SBMPediatrics and is the co-host of The Prism Podcast with fellow SBM contributor Grant Ritchey. The comments expressed by Dr. Jones are his own and do not represent the views or opinions of Newton-Wellesley Hospital or its administration.