Prenatal use of medications for gastroesophageal reflux disease and early childhood fracture risk

Background: Gastroesophageal reflux disease is a common condition in pregnancy and is often managed with medications. Specific medications have been linked to osteoporosis and fragility fracture in older adults. This study assessed whether maternal use of antireflux medications is associated with early childhood fracture. Methods: TRICARE beneficiaries during pregnancy were retrospectively identified using the Military Health System Data Repository and pharmacy data. Mother and infant data were linked; children with continuous enrollment for the first 5 years of life were included. Differences in the children’s fracture risk were analyzed through multivariate analysis, adjusting for region, rank, and military branch of service. Results: A total of 378 150 patients comprised the final cohort with 3.3% (n = 12 479) prescribed antireflux medications during pregnancy. A significant decrease in fracture rate was found among children of women who were prescribed antireflux medications during pregnancy compared with those who were not (0.8% vs 1.2%, RR = 0.70, 95% CI 0.58-0.85). There was no difference in fracture risk between histamine type 2 receptor antagonists and proton pump inhibitors. A significantly increased fracture incidence was seen in pregnancies with multiple gestations (RR = 1.38, 95% CI 1.04-1.85). There was no identified difference in fracture risk for women with gestational diabetes, preeclampsia, preterm or low birthweight, chronic hypertension, induction, or breech presentation when compared to women without these conditions. Conclusions: We found no increase in early childhood fracture risk with maternal antireflux medication use. This suggests that prenatal exposure to antireflux medications does not affect fetal bones to a clinically significant extent.