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French researchers are cautioning against excessive use of acid-suppressing drugs in infants due to the discovery of a connection between these medications and a heightened risk of serious infections later in life.
The study focuses on proton-pump inhibitors (PPIs) during infancy, as the utilization of these drugs is on the rise among young children in countries like France, New Zealand, Scandinavia, and the United States. Much of this usage is not for confirmed cases of gastroesophageal reflux but is aimed at easing parental concerns over discomfort in babies, as per the researchers who’ve examined national prescription trends. Alongside infection worries, inappropriate or prolonged application of acid suppressants is also linked to an increased chance of conditions such as hospital-acquired acute kidney injury and inflammatory bowel diseases in children.
While PPIs like omeprazole are effective for reducing gastric acid in infants with gastroesophageal reflux disease, the researchers caution against using these drugs for normal occurrences of spitting up and dribbling that would naturally resolve.
“In this study, the increased risk of severe infections was correlated with PPI usage in young children, both overall and across various sites and pathogens. In this demographic, PPIs should only be used when clearly indicated,” reported epidemiologist Marion Lassalle, PharmD, PhD, from EPI-PHARE in Saint-Denis, who led the research, along with her colleagues in JAMA Pediatrics.
Analyzing data from a national birth registry, Lassalle and her team compared infection rates among over 1.2 million infants who received a PPI at an average age of 88 days, to infection rates in children who were given a different type of acid suppressant (a histamine receptor blocker or antacid) at an average age of 82 days. Each group comprised more than 600,000 children.
Slightly over half of the participants were male, and the study followed these children up to a maximum age of 9 years. The results showed that children who used PPIs instead of other acid suppressants had an overall higher rate of serious infections necessitating hospitalization (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.32 – 1.36). Elevated infection rates were observed in the digestive tract, ear, nose, throat, kidneys or urinary tract, lower respiratory tract, and nervous system.
Instances of severe infections manifested around 9.7 (range, 3.9 – 21.3) months after discontinuing PPI use, a period determined by Lassalle’s group based on a delay of at least 90 days in refilling a PPI prescription.
Possible Variables “The study reveals an association, but not causation,” noted Rina Sanghavi, MD, a pediatric gastroenterologist at UT Southwestern Medical Center in Dallas, Texas. Sanghavi highlighted that the children who continued taking PPIs tended to be more ill in their first year, evident from higher rates of respiratory issues and corticosteroid usage. This suggests that the infections they eventually experienced might have had multiple causes, not solely the PPI.
Similarly, Sophia Patel, MD, a pediatric gastroenterologist at the Cleveland Clinic in Ohio, pointed out the nearly 10-month average gap between stopping PPI use and the onset of the first serious infection. This time frame is long enough to entertain the possibility that the infection was triggered by something other than PPIs, Patel indicated.
Despite the study’s limitations, Sanghavi and Patel emphasized that the findings underscore the importance for clinicians to prescribe PPIs only when necessary and to limit their duration of use. The general evidence for curtailing PPI use is compelling, both physicians remarked, even if this study does not establish direct causation between PPI application and infection rates.
“Ask: Does this child need a PPI?” Sanghavi recommended. If the answer is yes, she generally prescribes PPIs for a period of 2 weeks to a maximum of 2 months, and never approves automatic refills. This approach encourages frequent clinic visits for the child and parent, facilitating a quicker tapering off of the drugs.
Lassalle, Sanghavi, and Patel disclosed no relevant financial conflicts of interest.
Published online in JAMA Pediatrics on August 14, 2023.
