PURPOSE: Antacids, including proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) are frequently prescribed to treat gastro-esophageal reflux (GER) in healthy infants. PPI use has been associated with increased fracture risk in older adults. The purpose of this project is to examine the impact of antacid use during the first 6 months of life on the risk of fracture during infancy and early childhood. METHODS: We performed a retrospective cohort study of healthy children born within the Military Healthcare System (MHS) from 2001 to 2013 who received MHS care for two or more years. Outpatient pharmacy data was used to identify prescriptions for PPIs and H2RAs during the first 6 months of life. International Classification of Disease 9th edition (ICD-9) codes identified fractures after 6 months of age. Children with diagnosed osteogenesis imperfecta, pathologic fractures, and child maltreatment were excluded. Infants with NICU stays of 7+ days were also excluded as these infants often use inpatient antacids, and inpatient prescription data was not available. Groups were compared using Wilcoxon rank-sum test and ÷2 analysis. A Cox proportional hazard model was used to assess the relative hazard of fracture; adjusted analysis controlled for gender, prematurity, and low birth weight. RESULTS: 874,447 infants were born within the MHS between 2001 and 2013 and followed for two years or more (median 5.8, IQR 3.6-9.1 years). In the first 6 months of life 6,943 (0.8%) infants were prescribed PPIs, 67,096 (7.7%) H2RAs and 10,777 (1.2%) both. The median age at time of antacid prescription was 2.9 months, PPI 3.5 months, and H2RA 3.0 months. Infants who took antacids differed from controls on demographics and birth characteristics (Table 1). Fracture hazard was increased with male sex, PPI use, and use of both H2RAs and PPIs. Prior H2RA use alone was not associated with fracture, but interacted with time with fracture risk increasing with time. Fracture hazard was decreased with LBW and was not associated with preterm birth (Table 2). CONCLUSION: Use of H2RAs and PPIs in infancy is associated with an increased hazard of childhood fracture in healthy children. Use of antacid medications in infants should be weighed carefully against possible fracture.

Table 1

Descriptive statistics by antacid prescription

Table 1

Descriptive statistics by antacid prescription

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Table 2

Unadjusted and Adjusted Hazard Ratios of Fracture by Antacid use in early infancy

Table 2

Unadjusted and Adjusted Hazard Ratios of Fracture by Antacid use in early infancy

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