Editor's Note: This article was originally written by Eric Hassall, M.D.
Proton pump inhibitors (PPIs) are the most potent acid suppressing medications currently available. These acid-suppressing drugs have revolutionized the treatment of GE reflux disease, and we and others have shown the enormous value of their use in children over last 15 years.1-3
However, there is no question but that PPIs are frequently prescribed inappropriately in infants.4, 5 This practice is not without potential harm. These are facts on which experts agree. In discussing this issue, it's important first to clarify the terminology.
Definitions: Newborns and _infants _ are those of ages 0-12 months (hereinafter 'infants').6, 7
Gastroesophageal reflux or GER or _GE reflux _ refers to the passage of gastric contents into the esophagus with or without regurgitation and vomiting.6, 7 GER is a normal physiologic process occurring several times per day in healthy infants, children, and adults. Most episodes of GER in healthy individuals last <3 minutes, occur during or immediately following meals, and cause few or no symptoms. Up to 70% of otherwise happy, healthy, thriving infants spit up at least once daily; they have reflux, not reflux disease. By the age of 12-15 months, less than 5% are spitting up. GE reflux does not warrant pharmacologic treatment.
Gastroesophageal reflux disease or GERD is present when the reflux of gastric contents causes troublesome symptoms and/or complications.6, 7 Complications include esophagitis, esophageal stricture (narrowing), Barrett's esophagus (not under the age of 5 years), sometimes chronic cough or pneumonias, occasionally failure to gain weight and grow, and other conditions. 'Troublesome' is a subjective term that can be reported reliably only by older children, adolescents or adults - not by infants. We as parents are often 'troubled' when our child is crying or unhappy; but the fact that we are troubled does not make the diagnosis of reflux disease. In making the diagnosis of reflux disease, we are looking for a condition that requires treatment, which can alleviate the symptoms.
The problem: a) Many (the majority) of otherwise healthy infants spit up - this is** true**;
b) Many infants are unhappy/irritable/have unexplained crying - this is also true.
This does not mean that the 'spitting up' or 'reflux' is the cause of the unexplained crying. It's more often than not a case of 'true-true-unrelated'.
The evidence for overprescription. Recently, 162 infants with symptoms said to be those of GERD (eg spitting up, arching, unexplained crying) were randomized, in double-blind fashion, to a PPI vs a placebo.8 After 2 weeks, an identical number - 54% - of infants in each group, responded. In other words, active drug - in this case PPI - was no better than placebo. This is the largest such study in the literature. The likeliest explanation is that the great majority of these infants did not have GERD. GE reflux disease (esophagitis and the like) does not respond to placebo. Other studies have shown this.
A recent study which included 1 million infants in US healthplan databases, showed the extent of prescription of PPIs.5 From 2000 through 2003 there was at least a 4-fold increase, and in the six years 1999 through 2004, there was more than a 7-fold increase. One of the PPIs, available in a child-friendly liquid formulation, saw a 16-fold increase in use during that six-year period.
What has happened is this: Studies in older children and adolescents have shown PPIs to be highly effective for treating the symptoms of GERD and severe esophagitis.1-3
The use has been extrapolated to infants, in whom there are no such studies. GERD is in fact, very very uncommon in infants who do not have a major underlying medical disorder. In most infants who are unhappy, or have 'unexplained crying' ("colic"), there is no clear cause. Since the use of PPIs in older children and adolescents has been popularized, parents and physicians alike have sprung to prescribe a reflux disease drug, where reflux disease is very very seldom the cause of symptoms.
Bottom line: Colic or unexplained crying is a problem, but GERD is very seldom the cause, and therefore acid suppressive agents are only very very seldom the answer.
In future Shareposts:
- Why it's difficult to diagnose GERD in infants
- Unexplained crying in infants who spit up, and what to do about it
- Why we should be concerned about the overuse of acid-suppressing medications
- The different types of acid-suppressing medications: how they work, how to use them
- Other reflux topics...
- Gunasekaran TS, Hassall EG. Efficacy and safety of omeprazole for severe gastroesophageal reflux in children. J Pediatr 1993;123:148-54.
- Hassall E, Israel D, Shepherd R, Radke M, Dalvag A, Skold B, Junghard O, Lundborg P. Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group. J Pediatr 2000;137:800-7.
- Tolia V, Ferry G, Gunasekaran T, Huang B, Keith R, Book L. Efficacy of lansoprazole in the treatment of gastroesophageal reflux disease in children. J Pediatr Gastroenterol Nutr 2002;35 Suppl 4:S308-18.
- Khoshoo V, Edell D, Thompson A, Rubin M. Are we overprescribing antireflux medications for infants with regurgitation? Pediatrics 2007;120:946-9.
- Orenstein SR, Hassall E. Infants and proton pump inhibitors: tribulations, no trials. J Pediatr Gastroenterol Nutr 2007;45:395-398.
- Sherman P, Hassall E, Fagundes-Neto U, Gold BD, Kato S, Koletzko S, Orenstein S, Rudolph C, Vakil N, Vandenplas Y. A global evidence-based consensus on the definition of gastroesophageal reflux disease in children. Am J Gastroenterol 2009;104:1278-95.
- Vandenplas Y, Rudolph CD, Di Lorenzo C, Hassall E, Liptak G, Mazur L, Sondheimer J, Staiano A, Thomson M, Veereman-Wauters G, Wenzl TG. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2009;49:498-547.
- Orenstein SR, Hassall E, Furmaga-Jablonska W, Atkinson S, Raanan M. Multicenter, double-blind, randomized, placebo-controlled trial assessing efficacy & safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. J Pediatr 2009;154:514-520 e4.