New Insight into the Effects of Proton-Pump Inhibitors in Children

Proton-pump inhibitors (PPIs) are frequently prescribed to suppress stomach acid in patients with gastroesophageal reflux disease (GERD). Prescribing rates of PPIs in children have risen more than 500% in the past two decades, despite growing concerns about their risks: Previous research has linked their use to an increased risk of various pulmonary and gastrointestinal infections in both adults and children.

The Aerodigestive Center at Boston Children's Hospital has been at the forefront of research into PPIs and children. Two recent studies from the center offer more insight into their effects.

No increased risk of COVID-19 from PPIs

Several studies in adults have examined the association between the use of PPIs and COVID-19 infection. Although results have varied across individual studies, meta-analyses have generally found little to no increased risk of COVID-19 infection in adults taking PPIs and a possible increased risk of more severe infection in COVID-19 positive adults taking PPIs. However, little is known about the effects of PPIs on the risk of COVID-19 in children.

To learn more about this relationship, Suzanna Hirsch, MD, and her colleagues in the Aerodigestive Center reviewed data from the medical records of 116,209 children who were tested for COVID-19 between March 2020 and January 2023 at Boston Children's. They also searched the records to identify which of these patients also took PPIs prior to COVID-19 testing.

The team found no association between PPI use and a higher risk of positive COVID-19 tests in children, nor did PPIs appear to affect the risk of hospitalization from COVID-19 in this population. The study is published in The Journal of Pediatrics.

"Though we always recommend using PPIs only when medically indicated, these results provide reassuring evidence that children who require PPIs likely do not need to worry about these medications worsening the risk of getting COVID-19 or of becoming particularly sick from a COVID-19 infection," says Hirsch.

PPIs do appear to alter the gut microbiome

While Hirsch's study found no relationship between PPIs and COVID-19 infection in children, research has linked these drugs to increased rates of other infections, including upper respiratory infections. Yet few pediatric studies have examined the effects of PPIs on the microbiome. Research in adults suggests that PPI use may result in the migration of oropharyngeal and upper gastrointestinal microbes (such as Streptococcus and Prevotella) to the lower GI tract.

A team of Boston Children's researchers, including the Center's director, Rachel Rosen, MD, MPH, and Jason Zhang, MD, Ph.D., sought to determine whether PPIs have similar results in children. They used 16S RNA sequencing to analyze oropharyngeal and stool samples taken from 24 children both before and eight weeks after starting PPI therapy.

Although they didn't find any shifts in microbiome diversity, they did identify significant changes in certain types of bacteria. Specifically, "PPI use was associated with increased amounts of Streptococcus and lower levels of Bifidobacterium, Peptostreptococcus, and Turicibacter in the stool."

In line with research in adults, this study, published in Clinical and Translational Gastroenterology, also found an increase in oropharyngeal microbes in the stool—particularly in younger children.

"When it comes to the developing microbiomes of children, we need to remember: 'First, do no harm,'" says Zhang. "We've known for a while now that overusing antibiotics is detrimental to the gut microbiome, and our study proposes similar caution when it comes to PPIs.

"PPIs are useful for a narrow list of pediatric indications, but outside of that, a 'trial of PPI' might harm the microbiome enough to outweigh the potential benefits."