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Over-prescription Of Acid-suppressing Medications In Infants: How It Came About, Why It's Wrong, And What To Do About It.

Eric Hassall
Published 2012 · Medicine
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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
This paper references
10.1542/peds.2005-0147
Effect of a Low-Allergen Maternal Diet on Colic Among Breastfed Infants: A Randomized, Controlled Trial
David J Hill (2005)
10.1053/j.gastro.2009.03.058
Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy.
Christina Reimer (2009)
10.1016/S0022-3476(84)80541-7
Breath hydrogen excretion in normal newborn infants in response to usual feeding patterns: evidence for "functional lactase insufficiency" beyond the first month of life.
Ronald G. Barr (1984)
10.1001/archpedi.1997.02170430035007
Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group.
Steven P Nelson (1997)
10.1111/j.1365-2036.2006.02707.x
Review article: proton pump inhibitors and bacterial overgrowth.
C. Williams (2006)
Encyclopedia on Early Childhood Development
Yuko Munakata (2013)
10.1038/ajg.2009.46
Proton Pump Inhibitor Use and Enteric Infections
M Sandra Dial (2009)
10.1067/mpd.2000.104774
Role of food protein intolerance in infants with persistent distress attributed to reflux esophagitis.
David J Hill (2000)
10.1016/0016-5085(95)23148-X
Gastric polyps in children receiving omeprazole
D Israel (1995)
Prolonged and Unsoothable Crying Bouts in Infants with and without Colic
R. G. Barr (2005)
10.1007/S11894-008-0063-2
Step-up and step-down approaches to treatment of gastroesophageal reflux disease in children
E. Hassall (2008)
10.1542/peds.2005-1543
Association of H2-Blocker Therapy and Higher Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants
Ronnie Guillet (2006)
10.1053/j.gastro.2010.08.023
Safety of proton pump inhibitor exposure.
Y. Yang (2010)
A global evidence-based consensus on the definition of Hassall February 2012 COMMENTARY gastroesophageal reflux disease in children
P Sherman (2009)
10.1016/S0889-8553(05)70099-6
Gastroesophageal reflux disease in children.
Susan R. Orenstein (1999)
10.1016/S0016-5085(00)70135-1
Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa.
E. Klinkenberg-Knol (2000)
10.1038/ajg.2009.129
A Global, Evidence-Based Consensus on the Definition of Gastroesophageal Reflux Disease in the Pediatric Population
Philip M. Sherman (2009)
10.1097/MPG.0b013e318148c17c
Safety and Symptom Improvement With Esomeprazole in Adolescents With Gastroesophageal Reflux Disease
V. Tolia (2007)
10.1097/MPG.0b013e31812e0149
Proton Pump Inhibitor Utilization Patterns in Infants
J. Barron (2007)
10.1056/NEJMsa070502
A decade of direct-to-consumer advertising of prescription drugs.
J. Donohue (2007)
10.1067/S0022-3476(03)00207-5
Double-blind placebo-controlled trial of omeprazole in irritable infants with gastroesophageal reflux.
D. Moore (2003)
10.1111/j.1572-0241.2007.01324_7.x
Treatment Interruptus: The Need for Withdrawal
E. Hassall (2007)
10.1016/J.CGH.2007.09.010
Use of acid-suppressing drugs and the risk of bacterial gastroenteritis.
L. Garcia Rodriguez (2007)
Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs)
FDA Communication (2011)
10.1067/mpd.2000.109607
Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy, safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group.
E. Hassall (2000)
10.1016/j.jpeds.2007.09.009
Efficacy of conservative therapy as taught in the primary care setting for symptoms suggesting infant gastroesophageal reflux.
S. Orenstein (2008)
10.1007/S11894-008-0080-1
Crying in infant GERD: Acid or volume? Heartburn or dyspepsia?
Susan R. Orenstein (2008)
10.1097/MPG.0B013E31812E011D
Infants and proton pump inhibitors: tribulations, no trials.
Susan R. Orenstein (2007)
10.1111/j.1365-2036.2011.04592.x
Gastric histology in children treated with proton pump inhibitors long term, with emphasis on enterochromaffin cell-like hyperplasia.
Eric Hassall (2011)
10.1177/0009922810369253
Clinical Results From a Randomized, Double-Blind, Dose-Ranging Study of Pantoprazole in Children Aged 1 Through 5 Years With Symptomatic Histologic or Erosive Esophagitis
Robert Scott Dandridge Baker (2010)
10.1136/adc.2004.069674
Outcomes of fundoplication: causes for concern, newer options
E. Hassall (2005)
Parietal cell hyperplasia in children receiving omeprazole
E Hassall (1995)
10.1001/archpedi.154.2.150
Prevalence of symptoms of gastroesophageal reflux during childhood: a pediatric practice-based survey. Pediatric Practice Research Group.
Steven P Nelson (2000)
10.1097/MPG.0b013e3181b7f563
Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)
Yvan Vandenplas (2009)
10.1542/peds.2005-1655
Therapy With Gastric Acidity Inhibitors Increases the Risk of Acute Gastroenteritis and Community-Acquired Pneumonia in Children
R. B. Canani (2006)
Prospective long-termmaintenance treatment with proton pump inhibitors in children with erosive esophagitis
E Hassall (2011)
10.1542/peds.109.6.1061
Natural history and familial relationships of infant spilling to 9 years of age.
A. Martin (2002)
10.1016/S0022-3476(05)81561-6
Efficacy and safety of omeprazole for severe gastroesophageal reflux in children.
T. Gunasekaran (1993)
10.1111/j.1365-2036.2004.02271.x
Rebound acid hypersecretion after long-term inhibition of gastric acid secretion.
R. Fossmark (2005)
10.1016/j.jaci.2008.04.025
The role of protein digestibility and antacids on food allergy outcomes.
Eva Untersmayr (2008)
10.1111/j.1572-0241.2007.01152.x
Maintenance Therapy for Erosive Esophagitis in Children After Healing by Omeprazole: Is It Advisable?
G. Boccia (2007)
10.1097/00006454-200004000-00011
Risk factors for candidemia in Neonatal Intensive Care Unit patients
L. Saiman (2000)
10.1016/j.jpeds.2008.09.054
Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease.
Susan R. Orenstein (2009)
10.1186/1471-2431-10-41
Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study
Vasundhara Tolia (2010)
Crying Behaviour and Its Importance for Psychosocial Development in Children
R. G. Barr (2006)
How does direct-to-consumer advertising (DTCA) affect prescribing? A survey in primary care environments with and without legal DTCA.
B. Mintzes (2003)
10.1016/j.jpeds.2006.08.078
Characteristics of children receiving proton pump inhibitors continuously for up to 11 years duration.
E. Hassall (2007)
10.1001/archpedi.156.12.1172
Changing our understanding of infant colic.
Ronald G. Barr (2002)
10.1097/01.MPG.0000155369.54464.41
Efficacy and Safety of Lansoprazole in Adolescents with Symptomatic Erosive and Non-erosive Gastroesophageal Reflux Disease
Stephen C. Fiedorek (2005)
10.1001/jama.296.24.2947
Long-term proton pump inhibitor therapy and risk of hip fracture.
Yu-Xiao Yang (2006)
10.1053/j.gastro.2005.11.065
Childhood functional gastrointestinal disorders: neonate/toddler.
Paul E. Hyman (2006)
10.1097/01.mpg.0000188008.66752.72
Evaluation of Infantile Acid and Nonacid Gastroesophageal Reflux Using Combined pH Monitoring and Impedance Measurement
Adria A. Condino (2006)
10.1111/j.1365-2036.2011.04950.x
Long-term maintenance treatment with omeprazole in children with healed erosive oesophagitis: a prospective study.
Eric Hassall (2012)
10.1097/00005176-200211004-00003
Efficacy of Lansoprazole in the Treatment of Gastroesophageal Reflux Disease in Children
V. Tolia (2002)
10.1016/j.jclinepi.2003.08.015
A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults.
R. Valuck (2004)
10.1001/jama.292.16.1955
Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs.
R. Laheij (2004)



This paper is referenced by
10.1016/j.bpg.2015.06.008
Environmental and infectious factors in eosinophilic esophagitis.
Elizabeth T Jensen (2015)
10.1542/peds.2012-3070
Influence of “GERD” Label on Parents’ Decision to Medicate Infants
Laura D. Scherer (2013)
10.1016/j.jped.2013.05.009
Gastroesophageal reflux disease: exaggerations, evidence and clinical practice.
Cristina Ferreira (2014)
10.1007/s11894-013-0351-3
New Insights in Gastroesophageal Reflux, Esophageal Function and Gastric Emptying in Relation to Dysphagia Before and After Anti-Reflux Surgery in Children
Marije J. Smits (2013)
Gastroesophageal re fl ux disease : exaggerations , evidence and clinical practice ☆
Cristina Ferreira (2019)
10.1080/02646838.2017.1354360
Antenatal mother–infant bonding scores are related to maternal reports of infant crying behaviour
Deedee R Kommers (2017)
10.1097/01.mpg.0000441934.92221.ca
Gastrointestinal Food Allergy and Intolerance in Infants and Young Children
Ralf G Heine (2013)
10.1542/hpeds.2013-0036
Practice Variance, Prevalence, and Economic Burden of Premature Infants Diagnosed With GERD.
Sudarshan R Jadcherla (2013)
10.1111/jpc.14287
Non-indicated acid-suppression prescribing in a tertiary paediatric hospital: An audit and costing study.
Suzi Riess (2018)
10.1080/07315724.2013.828578
Milk Protein–Based Infant Formula Containing Rice Starch and Low Lactose Reduces Common Regurgitation in Healthy Term Infants: A Randomized, Blinded, and Prospective Trial
John B. Lasekan (2014)
10.1097/MPG.0000000000000790
Exposure to Gastric Acid–Suppression Therapy Is Associated With Health Care– and Community-Associated Clostridium difficile Infection in Children
Jennifer Jiménez (2015)
Studying use and risks of medicines in children: a European approach
Sandra de Bie (2013)
Effects of musculoskeletal dysfunction in excessive crying syndromes of infancy
Joyce Elaine Miller (2014)
Pediatric esophageal motility disorders: studies on (patho)physiology, diagnosis and management
Marije J. Smits (2015)
Paediatric drug development : an opportunity for academia to close the gap
Pauline De Bruyne (2016)
10.1371/journal.pone.0187081
The comparative analyses of different diagnostic approaches in detection of gastroesophageal reflux disease in children
Nina Ristić (2017)
10.1097/MPG.0000000000001264
Clostridium Difficile Infection in Children: A Review
Elena Borali (2016)
10.5937/MP69-16224
The significance of different methods for detection of gastroesophageal reflux in children
Nina Ristić (2018)
10.1111/jpc.12153
Diagnosing gastro-oesophageal reflux disease or lactose intolerance in babies who cry a lot in the first few months overlooks feeding problems.
Pamela S Douglas (2013)
10.1016/j.jpeds.2014.06.062
Association of Clostridium difficile infections with acid suppression medications in children.
Cade M. Nylund (2014)
10.1310/hpj4703-245
Recent Publications on Medications and Pharmacy
Flint Russett (2012)
10.1016/j.jpeds.2015.08.064
Side Effects and Complications of Proton Pump Inhibitors: A Pediatric Perspective.
Christopher M Stark (2016)
10.1093/pch/pxx010
Pharmacological treatment of children with gastro-oesophageal reflux.
Sanjay Mahant (2017)
10.1111/jpc.13946_16
Recognition and Management of Suspected Paediatric Sepsis in the Emergency Department
Caldwell Phy (2018)
10.1111/nmo.12922
Reflux monitoring in children.
Maartje M J Singendonk (2016)
10.12968/JOHV.2013.1.7.384
How health visitors can offer advice on calming a crying baby
Sara Patience (2013)
10.5223/pghn.2019.22.6.511
Is the Diagnostic Trial with Proton Pump Inhibitors Reasonable for School Age Children with Gastroesophageal Reflux Symptoms?
J. Yang (2019)
10.1097/MOP.0b013e328355a3e1
Clostridium difficile infection and proton pump inhibitors
John F. Pohl (2012)
10.1186/s12887-020-02047-3
Natural history of gastroesophageal reflux in infancy: new data from a prospective cohort
Marlène Curien-Chotard (2020)
10.1016/j.gtc.2014.02.002
Epidemiology of eosinophilic esophagitis.
Evan S. Dellon (2014)
10.1097/MPG.0b013e31823cadc6
Fifth European Paediatric Motility Meeting
M. Benninga (2011)
10.1016/j.dld.2018.03.031
Combined multichannel intraluminal impedance and pH monitoring is helpful in managing children with suspected gastro-oesophageal reflux disease.
P. Rossi (2018)
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