Advertisement
Previous article
Stable COPD and the Role of Inhaled Corticosteroids
Dec 2023
Next article
Preexposure Prophylaxis to Prevent Acquisition of HIV
Lown Right Care
Reducing Overuse and Underuse

Overuse of Antireflux Medications in Infants

Elizabeth R. Wolf, MD, MPH,
Naren Vadlamudi, MD,
Matthew Schefft, DO, MSHA,
Children’s Hospital of Richmond at Virginia Commonwealth University, Richmond, Virginia
Patient Perspective by Helen Haskell
John James

American Family Physician. 2023;108(6):614-616.

Author disclosure: No relevant financial relationships.

Case Scenario

A two-month-old full-term, formula-fed infant presents for the first well-child examination since the newborn period. The child’s parents are concerned because the infant spits up at least four times per day. The contents resemble curdled milk (nonbloody, nonbilious), and the spit-up is non-projectile. The infant is gaining weight and following the 75% weight curve for age. The parents report that the infant gets fussy every day around 5:00 p.m. The mother has a 10-year-old child who was prescribed antireflux medications around this age and is wondering if these medications should be prescribed for her infant.

Clinical Commentary

Gastroesophageal reflux, or the regurgitation of gastric contents, occurs in up to two-thirds of healthy infants.1 Gastroesophageal reflux begins approximately two to three weeks after birth and peaks between four and five months of age. Physiologic reasons for increased reflux in infants include an underdeveloped angle of His (the angle between the greater curvature of the stomach and esophagus), inadequate gastric accommodation, prolonged supine positioning, and a liquid diet. Symptoms usually resolve completely by one year of age.2 By one year of age, muscles in the lower esophagus strengthen, the esophagus lengthens, and esophageal and intestinal motility coordination improves. Normal developmental milestones, such as head control, sitting up, and the introduction of solid food, help improve gastroesophageal reflux symptoms. Infants who experience reflux without discomfort or other problems are sometimes referred to as “happy spitters.”

The North American Society for Pediatric Gastroenterology, Hepatology & Nutrition has developed guidelines to help clinicians differentiate gastroesophageal reflux from gastroesophageal reflux disease (GERD).3 The guidelines define GERD as reflux that involves pain, poor weight gain, or mucosal injury on upper endoscopy.3,4 Although changes in weight and endoscopy findings can be evaluated objectively, the assessment of pain (e.g., crying, grimacing, arching) is subject to parent and clinician interpretation. It can be challenging for parents and clinicians to distinguish manifestations of GERD-related pain from other conditions, such as dyschezia or colic.5 Clinicians can feel pressure to treat gastroesophageal reflux with medications even though it is a benign condition. One-fourth of parents of infants with gastroesophageal reflux perceive the symptoms as troublesome.1 Clinicians are subject to commission bias, which is the tendency to act even when inaction leads to an identical or better outcome.6

ANTIREFLUX MEDICATIONS

Clinicians may prescribe histamine H2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) to reduce the perceived discomfort associated with gastroesophageal reflux. These medications decrease the acidity in gastric contents but do not improve regurgitation in the absence of GERD.3,7,8 In many cases, treatments have not been proven more effective than placebo.8–10

Although the medical community once viewed H2RAs and PPIs as benign medications, there are now concerns about the short- and long-term effects.11,12 In the short term, these medications have been linked to necrotizing enterocolitis and sepsis in preterm and low-birth-weight infants.13–20 Full-term and normal-birth-weight infants are at increased risk of lower respiratory tract and gastrointestinal infections.8,21 In the long term, there is a link between acid suppression and alteration in the microbiome and higher rates of allergies, asthma, and obesity.22–25 PPI and combination H2RA/PPI therapy have been linked to a higher risk of fractures in children, with earlier initiation and longer duration of treatment associated with the highest risk.26 Patients treated with acid-suppressing medication incur more than $2,300 in additional health care costs compared with healthy patients.27

Address correspondence to Elizabeth R. Wolf, MD, MPH, at elizabeth.wolf@vcuhealth.org. Reprints are not available from the authors.

Author disclosure: No relevant financial relationships.

  1. 1.Nelson SP, Chen EH, Syniar GM, et al.; Pediatric Practice Research Group. Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Arch Pediatr Adolesc Med. 1997;151(6):569-572.
  2. 2.Campanozzi A, Boccia G, Pensabene L, et al. Prevalence and natural history of gastroesophageal reflux: pediatric prospective survey. Pediatrics. 2009;123(3):779-783.
  3. 3.Rosen R, Vandenplas Y, Singendonk M, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2018;66(3):516-554.
  4. 4.Quitadamo P, Urbonas V, Papadopoulou A, et al. Do pediatricians apply the 2009 NASPGHAN-ESPGHAN guidelines for the diagnosis and management of gastroesophageal reflux after being trained?. J Pediatr Gastroenterol Nutr. 2014;59(3):356-359.
  5. 5.Barr RG, Rajabali F, Aragon M, et al. Education about crying in normal infants is associated with a reduction in pediatric emergency room visits for crying complaints. J Dev Behav Pediatr. 2015;36(4):252-257.
  6. 6.Musiienko A. Commission bias. In: Raz M, Pouryahya P, eds. Decision Making in Emergency Medicine. Biases, Errors and Solutions. Springer Singapore; 2021: 77–82.
  7. 7.Simeone D, Caria MC, Miele E, et al. Treatment of childhood peptic esophagitis: a double-blind placebo-controlled trial of nizatidine. J Pediatr Gastroenterol Nutr. 1997;25(1):61-55.
  8. 8.Orenstein SR, Hassall E, Furmaga-Jablonska W, et al. 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. J Pediatr. 2009;154(4):514-520.e4.
  9. 9.van der Pol RJ, Smits MJ, van Wijk MP, et al. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127(5):925-935.
  10. 10.Higginbotham TW. Effectiveness and safety of proton pump inhibitors in infantile gastroesophageal reflux disease. Ann Pharmacother. 2010;44(3):572-576.
  11. 11.Boruta M, Boruta R, Li J. Acid suppression therapy and symptom improvement (or lack thereof) in children. Pediatrics. 2019;144(1):e20190909.
  12. 12.Quinonez RA, Garber MD, Schroeder AR, et al. Choosing wisely in pediatric hospital medicine: five opportunities for improved healthcare value. J Hosp Med. 2013;8(9):479-485.
  13. 13.Santana RNS, Santos VS, Ribeiro-Júnior RF, et al. Use of ranitidine is associated with infections in newborns hospitalized in a neonatal intensive care unit: a cohort study. BMC Infect Dis. 2017;17(1):375.
  14. 14.Terrin G, Passariello A, De Curtis M, et al. Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics. 2012;129(1):e40-e45.
  15. 15.Chung EY, Yardley J. Are there risks associated with empiric acid suppression treatment of infants and children suspected of having gastroesophageal reflux disease?. Hosp Pediatr. 2013;3(1):16-23.
  16. 16.Guillet R, Stoll BJ, Cotten CM, et al.; National Institute of Child Health and Human Development Neonatal Research Network. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2006;117(2):e137-e142.
  17. 17.Beck-Sague CM, Azimi P, Fonseca SN, et al. Bloodstream infections in neonatal intensive care unit patients: results of a multicenter study. Pediatr Infect Dis J. 1994;13(12):1110-1116.
  18. 18.Rojas MA, Efird MM, Lozano JM, et al. Risk factors for nosocomial infections in selected neonatal intensive care units in Colombia, South America. J Perinatol. 2005;25(8):537-541.
  19. 19.Graham PL, Begg MD, Larson E, et al. Risk factors for late onset gram-negative sepsis in low birth weight infants hospitalized in the neonatal intensive care unit. Pediatr Infect Dis J. 2006;25(2):113-117.
  20. 20.Bianconi S, Gudavalli M, Sutija VG, et al. Ranitidine and late-onset sepsis in the neonatal intensive care unit. J Perinat Med. 2007;35(2):147-150.
  21. 21.Canani RB, Cirillo P, Roggero P, et al.; Working Group on Intestinal Infections of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics. 2006;117(5):e817-e820.
  22. 22.Jackson MA, Goodrich JK, Maxan M-E, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016;65(5):749-756.
  23. 23.Mitre E, Susi A, Kropp LE, et al. Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood. JAMA Pediatr. 2018;172(6):e180315.
  24. 24.Wang Y-H, Wintzell V, Ludvigsson JF, et al. Association between proton pump inhibitor use and risk of asthma in children. JAMA Pediatr. 2021;175(4):394-403.
  25. 25.Stark CM, Susi A, Emerick J, et al. Antibiotic and acid-suppression medications during early childhood are associated with obesity. Gut. 2019;68(1):62-69.
  26. 26.Malchodi L, Wagner K, Susi A, et al. Early acid suppression therapy exposure and fracture in young children. Pediatrics. 2019;144(1):e20182625.
  27. 27.Kothari S, Nelson SP, Wu EQ, et al. Healthcare costs of GERD and acid-related conditions in pediatric patients, with comparison between histamine-2 receptor antagonists and proton pump inhibitors. Curr Med Res Opin. 2009;25(11):2703-2709.
  28. 28.Ho T, Dukhovny D, Zupancic JAF, et al. Choosing Wisely in newborn medicine: five opportunities to increase value. Pediatrics. 2015;136(2):e482-e489.
  29. 29.Karagas MR, Punshon T, Sayarath V, et al. Association of rice and rice-product consumption with arsenic exposure early in life. JAMA Pediatr. 2016;170(6):609-616.
  30. 30.Kwok TC, Ojha S, Dorling J. Feed thickener for infants up to six months of age with gastro-oesophageal reflux. Cochrane Database Syst Rev. 2017(12):CD003211.
  31. 31.Beal J, Silverman B, Bellant J, et al. Late onset necrotizing enterocolitis in infants following use of a xanthan gum-containing thickening agent. J Pediatr. 2012;161(2):354-356.

Lown Institute Right Care Alliance is a grassroots coalition of clinicians, patients, and community members organizing to make health care institutions accountable to communities and to put patients, not profits, at the heart of health care.

This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

A collection of Lown Right Care published in AFP is available at https://www.aafp.org/afp/rightcare.

Previous article
Stable COPD and the Role of Inhaled Corticosteroids
Dec 2023
Next article
Preexposure Prophylaxis to Prevent Acquisition of HIV

Current issue

September 2026

September 2026

Copyright © 2026 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. See permissions for copyright questions and/or permission requests.