Over-Prescription of Acid-Suppressing Medications in Infants: How It Came About, Why It’s Wrong, and What to Do About It

Abstract

It has been almost 20 years since proton pump inhibitors (PPIs) were initially shown to be effective, safe, and well-tolerated for the short-term treatment of gastroesophageal reflux disease (GERD) in children over 1 year of age 1 ; GERD diagnosed on the basis of symptoms and hard diagnostic evidence of erosive esophagitis seen at endoscopy. 2 In these studies, mostly performed in children 2 to 17 years of age, 1-3 PPIs were shown to effectively treat symptoms and erosive esophagitis that were refractory to histamine-2receptor antagonists (H2RA), buffering agents, prokinetics, and in some subjects, antireflux surgery. Subsequent to those studies with omeprazole, other PPIs were found to be similarly effective. 4-8 Efficacy and safety were also shown for maintenance of remission of chronic, relapsing erosive esophagitis in prospective studies as long as 2 years, 9 and retrospective studies as long as 11 years of use. 10 Approximately 80% 10 of children who require long-term treatment for GERD have underlying disorders that predispose them to GERD, such as neurologic impairment, repaired congenital esophageal anomalies (eg, esophageal atresia), chronic lung disease, hiatal hernia, a strong family history of GERD, Barrett’s esophagus, or esophageal adenocarcinoma, or obesity. 11 In children without these underlying disorders, GERDisusuallynotchronicorsevere, 12 andmostcommonly follows a presumed upper gastrointestinal infection with post-infectious dysmotility and delayed gastric emptying, which resolves with time. In other words, in most otherwise healthy children, GERD is not chronic. In children in whom it is, the use of PPIs has revolutionized the long-term treatment of GERD, much for the better, including allowing for significantly decreased rates of antireflux surgery in some centers. 13 In this overall context, the topic of reflux in infants (ie, 7-fold increase in PPI prescription. One of the PPIs, available in a child-friendly liquid formulation, saw a 16-fold increase in use during that 6-year period. 14 Overall, approximately 0.5% of the approximately one million infants in the study database received a PPI during their first year of life. Approximately 50% of the infants started taking a PPI before 4 months of age. 15 These data would imply that somehow the diagnosis of GERD has been missed over the past several decades or has recently become a major scourge of infants in the developed world, with acid suppressing drugs becoming a new essential food group in their own right. This change in practice has come about for several reasons, none based in medical science. There is, however, data to show that this practice does not serve our patients. Two phenomena have long been observed in otherwise healthy, thriving infants. First, many of them spit up on a daily basis—some 40% to 70%. 16,17 The developing, rapidly-growing infant takes in feeding volumes that on a per-kg basis are huge compared with older children or adults. Infants have relatively poor gastric compliance and a short esophagus; therefore, some of the large volume intake simply overflows upward, or sometimes ‘‘spills’’ (lingua Australiana) out through the mouth. This has long been recognized as physiologic reflux not reflux disease [ie, not GERD]), and it is self-resolving in approximately 95% of