Early Antacid Exposure Increases Fracture Risk in Young Children

Abstract:

Background Antacids, including proton pump inhibitors (PPIs) and histamine H₂-receptor antagonists (H₂RAs) are frequently prescribed to treat gastro-esophageal reflux (GER) in healthy infants.[o1] PPI use [HE2] has been associated with increased fracture risk in older adults, the impact of PPI on fracture in children is unknown.

Objective To examine the impact of antacid use during the first 6 months of life on infant and early childhood fracture

Design/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 identified prescriptions for PPIs and H₂RAs during the first 6 months of life. International Classification of Disease 9^th edition (ICD-9) codes identified fractures after 6 months of age. Children with diagnosed osteogenesis imperfecta, pathologic fractures, child maltreatment and a NICU stay of 7+ days were excluded; infants admitted to the NICU often use inpatient antacids, and inpatient prescription data was not available. Groups were compared using Wilcoxon rank-sum test and Dz analysis. A Cox proportional hazard model assessed the relative hazard of fracture; adjusted analysis controlled for gender, prematurity, and low birth weight.

Results 874,447[KW1] 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 first antacid prescription was 2.9 months, PPI 3.5 months, and H₂RA 3.0 months. Infants [LM2] who took antacids differed from controls on demographic 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, Figure 1).

Conclusion(s) 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.