Acid-suppression therapy early in life is associated with an increased risk of fracture in childhood, results of a retrospective study have shown.
“These findings, together with other research into negative sequelae of proton-pump inhibitor (PPI) use in young children, suggest that providers should be much more judicious in their prescribing of these medications to very young children,” Dr. Elizabeth Hisle-Gorman from Uniformed Services University of the Health Sciences, in Bethesda, MD, told Reuters Health by email.
The use of PPIs and histamine H2-receptor antagonists (H2RAs) in infants quadrupled from 1999 to 2003 and then doubled from 2004 to 2008, Dr. Hisle-Gorman and colleagues note in Pediatrics, online June 7.
“While acid-suppression medication is necessary in infants with GERD, these medications are often used to treat newborn reflux and crying, which are normal newborn behaviours,” Dr. Hisle-Gorman said. “Placebo-controlled trials have shown that infant crying and newborn reflux are not impacted by treatment with acid suppressants.”
Studies examining bone health in children on acid-suppression therapy have yielded inconsistent results. To investigate, Dr. Hisle-Gorman’s team used data on more than 850,000 infants who received continuous care in the Military Healthcare System for at least the first two years of life.
Eleven percent of these infants initiated acid-suppression therapy in the first year of life: 9% of these were prescribed a PPI, 73% an H2RA and 18% received both.
In unadjusted analyses, the hazard of fracture after one year of age was 23% higher among those prescribed a PPI, 13% higher among those prescribed an H2RA, and 32% higher among those prescribed both in the first year of life, all significant increases compared with unexposed children.
After adjustment for other factors, fracture hazard was 23% higher in children prescribed a PPI and 31% higher in children prescribed both a PDI and an H2RA in the first year of life, whereas H2RA initiation in the first year of life was not associated with significantly increased fracture risk.
The risk appeared to increase with increasing duration of acid-suppression therapy.
Compared with controls with no acid-suppression-therapy prescriptions before age 5, PPI initiation at 0 to 6 months of life was associated with a 23% increased fracture hazard, a 21% increase at 6 to 12 months, and no significant increase at 12 to 24 months.
Fracture hazard among children prescribed an H2RA was not increased regardless of when medication was initiated, whereas fracture hazard was significantly elevated in children prescribed both classes of medication.
“More research is needed to better understand how these medications are likely to affect bone on the cellular level,” Dr. Hisle-Gorman said. “We also need more research into whether there are critical developmental periods when children’s bone may be most susceptible to the effects of PPIs.”
“In the meantime, when the use of acid suppressants is necessary, use should be postponed as long as possible, and treatment should be for the shortest duration that meets clinical needs,” she said.
REFERENCE: Malchodi et al: Early Acid Suppression Therapy Exposure and Fracture in Young Children; https://pediatrics.aappublications.org/content/early/2019/06/05/peds.2018-2625..info