Proton Pump Inhibitors Increase Risk of Infections in Children

Based on new research findings, scientists say proton pump inhibitors should not be given to young children unless there's a clear indication to do so.

Proton pump inhibitors (PPIs) are medications used to treat heartburn, acid reflux, and gastroesophageal reflux disease (GERD). They are available over the counter and work by reducing acid production in the stomach.

Although generally considered safe and effective, recent research found that in adults, long-term use of PPIs may increase the risk of dementia. In addition, scientists have found evidence that PPI use may disrupt the gut microbiota, leading to an increased risk of infections.

While adults are more likely to use proton pump inhibitors, these medications are also used to treat GERD and other digestive tract conditions in children. However, in very young children, the symptoms of GERD are similar to uncomplicated gastroesophageal reflux — AKA "spitting up." Infants with this type of reflux typically stop spitting up once they can stand and walk.

Still, healthcare providers may prescribe PPIs to help manage this type of uncomplicated reflux. Because of this, PPI use among young children is on the rise. For example, data from a 2022 study shows an eight-fold increase in PPI use among children in Denmark, with similar trends in other countries, including the United States.

Yet not much is known about the safety of PPI use in this population.

In a new study published on August 14 in JAMA Pediatrics, researchers examined one possible safety concern regarding PPI use in children. Specifically, if these acid reflux drugs could lead to infections.

The scientists looked at data from all children born between 2010 and 2018 who received PPIs, histamine 2 receptor antagonists, or antacids/alginate to treat GERD or other gastrointestinal conditions. The data came from the Mother-Child EPI-MERES Register build by the French Health Data System (SNDS).

Among the 1,262,424 children treated for gastrointestinal conditions, 606,645 received PPIs, and 655,779 were not given the drugs.

After assessing the data, the researchers found that children exposed to proton pump inhibitors had a 30% higher risk of viral infections and a 56% higher risk of bacterial infections compared to those who did not receive the reflux drugs.

In addition, PPIs increased the risks of bacterial and viral infections in the digestive tract, ear, nose, and throat, lower respiratory tract, kidneys or urinary tract, and nervous system.

Because of these findings, the scientists suggest that PPIs should not be used without a clear indication in this population.

Why would proton pump inhibitors cause infections?

Although the study authors aren’t sure why PPI use in young children might lead to infections, they suggest that the drug may alter the gut biome by changing its composition and function.

"The composition of the microbiota undergoes major changes during infancy, especially in preterm infants. Therefore, PPI exposure during this period could have a notable impact," the authors wrote.

They also say that PPI use may reduce the stomach's pH levels — which hampers the body's ability to destroy pathogens.

In addition, the authors suggest that PPIs may also directly affect multiple functions of the immune system.

In an accompanying editorial, Jay Berry, M.D., MPH, and Jonathan Mansbach, M.D., MPH, of Boston Children's Hospital conclude, "Given the results of the compelling analysis […] it is time to limit PPI use in infants and children, especially when they are otherwise healthy and until further investigation distinguishes who has the most favorable risk-benefit ratio."