PPIs Linked to Long-Term Infection in Kids

Marcus A. Banks

August 29, 2023

Researchers in France are warning against the overzealous use of acid-suppressing drugs in infants after finding that the medications are associated with an increase in risk of serious infections later in life.

The focus on the use of proton-pump inhibitors (PPIs) during infancy comes as use of the drugs in young children is rising in France, New Zealand, Scandinavia, and the United States. Much of this use is not to manage confirmed cases of gastroesophageal reflux but rather to soothe the jangled nerves of parents of babies in discomfort, according to the researchers, who have studied national prescribing patterns. In addition to concerns about infection, inappropriate or prolonged use of the acid suppressants is also associated with an increase in the risk of such conditions as hospital-acquired acute kidney injury and inflammatory bowel diseases in children.

PPIs such as omeprazole are effective at reducing gastric acid in babies with gastroesophageal reflux disease. But the researchers warn against using the drugs to manage normal spitting up and dribbling that would have resolved of itself anyway.

"In this study, increased risk of serious infections was associated with PPI use in young children, overall and for various sites and pathogens. In this population, PPIs should not be used without a clear indication," epidemiologist Marion Lassalle, PharmD, PhD, of EPI-PHARE, in Saint-Denis, who led the study, and her colleagues reported in JAMA Pediatrics.

Drawing on data from a national birth registry, Lassalle and her colleagues compared infection rates among more than 1.2 million infants who received a PPI at an average age of 88 days to infection rates among children who received another kind of acid suppressant (a histamine receptor blocker or antacid) at an average age of 82 days. More than 600,000 children made up each group.

Slightly over half of the participants were boys, and the study followed children to a maximum age of 9 years. Among children who used PPIs rather than another acid suppressant, there was an overall higher rate of serious infections that required hospitalization (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.32 – 1.36). There were higher rates of infections in the digestive tract; the ear, nose, and throat; the kidneys or urinary tract; the lower respiratory tract; and the nervous system.

Serious infections first appeared 9.7 (range, 3.9 – 21.3) months after a child stopped using a PPI ― a date that Lassalle's group determined on the basis of there being a delay of at least 90 days in filling a PPI prescription.

Possible Confounders

"The study shows an association, it does not show causation," Rina Sanghavi, MD, a pediatric gastroenterologist at UT Southwestern Medical Center in Dallas, Texas, said. Sanghavi noted that the children who continued taking PPIs generally were sicker in their first year of life, as shown by the higher rates of respiratory ailments and corticosteroid use. This could mean that the infections they eventually experienced had many causes and not necessarily the PPI.

Similarly, pediatric gastroenterologist Sophia Patel, MD, of the Cleveland Clinic in Ohio, pointed to the almost 10-month average lag time between stopping a PPI and developing a first serious infection. That interval is long enough that it is possible that the infection was caused by something else, Patel said.

Despite the limitations of the study, Sanghavi and Patel said the findings serve as a good reminder to clinicians to use PPIs only when needed and to limit their use once begun. The overall evidence base for limiting use of PPIs is strong, both physicians noted, even if this study does not show direct causation between PPI use and infection rates.

"Ask: Does this child need a PPI?" Sanghavi said. If so, she said, she generally prescribes PPIs for a period of 2 weeks to a maximum of 2 months and that she never authorizes automatic refills. Through this approach, a parent and child will come back to the clinic frequently, which in most cases allows faster tapering of the drugs.

Lassalle, Sanghavi, and Patel reported no relevant financial conflicts of interest.

JAMA Peds. Published online August 14, 2023. Full text

Marcus A. Banks, MA, is a journalist based in New York City who covers health news with a focus on new cancer research. His work appears in Medscape, Cancer Today, The Scientist, Gastroenterology and Endoscopy News, Slate, TCTMD, and Spectrum.

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