Early Exposure to Acid Suppression Therapy: What Is the Harm?

Author:
Jordan N. Watson, MD
Thomas Jefferson University
Nemours/Alfred I. duPont Hospital for Children

Citation:
Watson JN. Early exposure to acid suppression therapy: What is the harm? [published online August 5, 2019]. Gastroenterology Consultant.

Malchodi L, Wagner K, Susi A, Gorman G, Hisle-Gorman E. Early acid suppression therapy exposure and fracture in young children. Pediatrics. 2019;144(1):e20182625. https://doi.org/10.1542/peds.2018-2625.

Acid suppression therapy is a hot topic in both adult and pediatric health care. In pediatrics, prescribing of these medications to young infants has increased,¹ while data supporting their efficacy in the treatment of gastroesophageal reflux (GER) symptoms in otherwise healthy infants have been weak.^2,3 In adults, studies have shown that acid suppression therapy is associated with an increased risk of fracture. A new study in Pediatrics⁴ indicates that acid suppression therapy initiated in the first year of life can have detrimental effects on bone health that can be long-lasting.

This large, retrospective cohort study included 851,631 children born between October 1, 2001, and September 30, 2013, who were in the US Military Healthcare System. Malchodi and colleagues used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes to exclude children with conditions that predisposed them to fractures—including osteogenesis imperfecta, cholestasis, and child maltreatment—as well as infants with prolonged birth hospitalizations of greater than 1 week.

Children were included in the study if they were prescribed an acid suppression medication, defined as a proton-pump inhibitor (PPI), histamine H2-receptor antagonist, (H2RA), or both, before 1 year of age. The final analysis also included children who initiated therapy before 2 years of age.

Data from outpatient pharmacy records were subsequently collected for 5 years, and data from these children were compared with those of children who were not prescribed any acid suppression therapy during the first 5 years of life. ICD-9-CM codes were used to identify children who had fractures before and after 1 year of life. Demographics that were considered in the final analysis were sex, obesity, preterm birth, low birth weight, antiepileptic prescription medication use, and history of fracture before 1 year of age. Adherence was not evaluated in this retrospective study.

Using a Cox proportional hazard model to assess the hazard ratio of fracture with acid suppression therapy use, the researchers found that acid suppression therapy with combination PPI and H2RA use or PPI alone before the first year of life was associated with an increased fracture hazard in the first 5 years of life. The adjusted hazard ratio for PPI use alone was 1.23, while the hazard ratio for PPI and H2RA combination use was 1.31. An increased risk of fracture was associated with male sex, overweight or obesity, and a previous fracture. H2RA use alone was not associated with a significant fracture risk. The risk of fracture increased with combination PPI and H2RA use, earlier onset of acid suppression medication (before 6 months of age), and duration of use, suggesting a dose-dependent relationship.

The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition 2018 clinical guidelines recommend not using H2RAs or PPIs for treating crying/distress or visible regurgitation in otherwise healthy infants and advise “the regular assessment of the ongoing need of long-term acid suppression therapy in infants and children with GERD.”³

Pediatric providers should continue to use acid suppression medications cautiously, being mindful to use the lowest effective dose and shortest duration indicated.

Jordan N. Watson, MD, is a clinical assistant professor of pediatrics at the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia, Pennsylvania. She is also a general pediatrician and the medical director of the Dermatology Access Clinic in the Division of General Pediatrics at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Delaware.

References:

1. Barron JJ, Tan H, Spalding J, Bakst AW, Singer J. Proton pump inhibitor utilization patterns in infants. J Pediatr Gastroenterol Nutr. 2007;45(4):421-427. https://doi.org/10.1097/MPG.0b013e31812e0149. 
2. Safe M, Chan WH, Leach ST, Sutton L, Lui K, Krishnan U. Widespread use of gastric acid inhibitors in infants: are they needed? Are they safe? World J Gastrointest Pharmacol Ther. 2016;7(4):531-539. https://doi.org/10.4292/wjgpt.v7.i4.531.
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.  https://dx.doi.org/10.1097%2FMPG.0000000000001889.
4. Malchodi L, Wagner K, Susi A, Gorman G, Hisle-Gorman E. Early acid suppression therapy exposure and fracture in young children. Pediatrics. 2019;144(1):e20182625. https://doi.org/10.1542/peds.2018-2625.