Neonatal Histamine-2 Receptor Antagonist and Proton Pump Inhibitor Treatment at United States Children's Hospitals

J Pediatr. 2016 Jul:174:63-70.e3. doi: 10.1016/j.jpeds.2016.03.059. Epub 2016 Apr 27.


Objective: To determine treatment frequency and duration of histamine-2 receptor antagonist (H2RA)/proton pump inhibitor (PPI) use among infants hospitalized within US children's hospital neonatal intensive care units and evaluate diagnoses/demographic factors associated with use.

Study design: We retrospectively analyzed a cohort of neonatal intensive care unit infants admitted to 43 US children's hospitals within the Pediatric Health Information System database between January 2006 and March 2013 to determine H2RA/PPI treatment frequency, timing/duration of treatment, factors associated with use, percent of infants remaining on treatment at discharge, and interhospital prescribing variation. We used a modified Poisson regression to calculate the adjusted probability of infants ever receiving H2RAs/PPIs in relation to diagnosis, gestation, and sex.

Results: Of the 122 002 infants evaluated, 23.8% (n = 28 989) ever received an H2RA or PPI; 19.0% received H2RAs (n = 23 187), and 10.5% (n = 12 823) received PPIs. Extremely preterm infants and term infants were the most likely to receive H2RA and PPI treatment. Infants with gastroesophageal reflux disease (relative risk [RR] = 3.13) and congenital heart disease (RR = 2.41) had the highest H2RA/PPI treatment probabilities followed by those with an ear, nose, and throat diagnosis (RR = 2.34; P < .05). The majority of treated infants remained treated at discharge.

Conclusions: Despite limited evidence and increasing safety concerns, H2RAs/PPIs are frequently prescribed to extremely preterm neonates and those with congenital anomalies and continued through discharge. Our findings support the need for innovative studies to examine the comparative effectiveness and safety of H2RA/PPIs vs no treatment in these high-risk neonatal populations.

Keywords: H2-receptor antagonist; comparative effectiveness; drug utilization; gastroesophageal reflux disease; neonatal; patient-centered outcomes; pharmacoepidemiology; practice variation; proton pump inhibitor; stress ulcer prophylaxis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Drug Utilization
  • Female
  • Histamine H2 Antagonists / therapeutic use*
  • Hospitalization
  • Hospitals, Pediatric*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / drug therapy*
  • Intensive Care, Neonatal*
  • Male
  • Proton Pump Inhibitors / therapeutic use*
  • Retrospective Studies
  • Sex Factors
  • United States


  • Histamine H2 Antagonists
  • Proton Pump Inhibitors